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Slide 1 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010
Slide 2 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments
Slide 3 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193
Slide 4 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193
Slide 5 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2.
Slide 6 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention
Slide 7 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7%
Slide 8 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171.
Slide 9 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----]
Slide 10 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS
Slide 11 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis
Slide 12 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms
Slide 13 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI
Slide 14 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm
Slide 15 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization.
Slide 16 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management
Slide 17 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology
Slide 18 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS
Slide 19 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1)
Slide 20 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4
Slide 21 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes
Slide 22 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256.
Slide 23 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.
Slide 24 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.
Slide 25 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40.
Slide 26 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone?
Slide 27 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response?
Slide 28 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5.
Slide 29 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin
Slide 30 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986.
Slide 31 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS
Slide 32 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative
Slide 33 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High
Slide 34 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days
Slide 35 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours
Slide 36 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40%
Slide 37 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40%
Slide 38 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy
Slide 39 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins
Slide 40 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors
Slide 41 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm
Slide 42 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk
Slide 43 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours
Slide 44 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718.
Slide 45 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24
Slide 46 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial
Slide 47 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups
Slide 48 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies
Slide 49 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence
Slide 50 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early?
Slide 51 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management
Slide 52 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge
Slide 53 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid
Slide 54 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid New and Controversial Drug Therapies
Slide 55 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid New and Controversial Drug Therapies Early Treatment with Clopidogrel
Slide 56 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid New and Controversial Drug Therapies Early Treatment with Clopidogrel Shortcomings of the CURE Trial Conducted primarily at centers without routine use of early invasive strategy Only 462 (3.7%) patients enrolled from the U.S. 44% had catheterization during index hospitalization Adverse event reduced only in nonfatal MI set Major Bleeding rate of 9.6% among patients who were administered clopidogrel within 5 days of CABG
Slide 57 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid New and Controversial Drug Therapies Early Treatment with Clopidogrel Shortcomings of the CURE Trial Conducted primarily at centers without routine use of early invasive strategy Only 462 (3.7%) patients enrolled from the U.S. 44% had catheterization during index hospitalization Adverse event reduced only in nonfatal MI set Major Bleeding rate of 9.6% among patients who were administered clopidogrel within 5 days of CABG Clopidogrel Bleeding Risk and CABG “In hospitals in which patients with UA/NSTEMI undergo rapid diagnostic catheterization within 24 hours of admission, clopidogrel is not started until it is clear that CABG will not be scheduled within the next several days. However, unstable patients should receive clopidogrel or be take for immediate angiography.”
Slide 58 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid New and Controversial Drug Therapies Early Treatment with Clopidogrel Shortcomings of the CURE Trial Conducted primarily at centers without routine use of early invasive strategy Only 462 (3.7%) patients enrolled from the U.S. 44% had catheterization during index hospitalization Adverse event reduced only in nonfatal MI set Major Bleeding rate of 9.6% among patients who were administered clopidogrel within 5 days of CABG Clopidogrel Bleeding Risk and CABG “In hospitals in which patients with UA/NSTEMI undergo rapid diagnostic catheterization within 24 hours of admission, clopidogrel is not started until it is clear that CABG will not be scheduled within the next several days. However, unstable patients should receive clopidogrel or be take for immediate angiography.” Clopidogrel vs. Prasugrel
Slide 59 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid New and Controversial Drug Therapies Early Treatment with Clopidogrel Shortcomings of the CURE Trial Conducted primarily at centers without routine use of early invasive strategy Only 462 (3.7%) patients enrolled from the U.S. 44% had catheterization during index hospitalization Adverse event reduced only in nonfatal MI set Major Bleeding rate of 9.6% among patients who were administered clopidogrel within 5 days of CABG Clopidogrel Bleeding Risk and CABG “In hospitals in which patients with UA/NSTEMI undergo rapid diagnostic catheterization within 24 hours of admission, clopidogrel is not started until it is clear that CABG will not be scheduled within the next several days. However, unstable patients should receive clopidogrel or be take for immediate angiography.” Clopidogrel vs. Prasugrel
Slide 60 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid New and Controversial Drug Therapies Early Treatment with Clopidogrel Shortcomings of the CURE Trial Conducted primarily at centers without routine use of early invasive strategy Only 462 (3.7%) patients enrolled from the U.S. 44% had catheterization during index hospitalization Adverse event reduced only in nonfatal MI set Major Bleeding rate of 9.6% among patients who were administered clopidogrel within 5 days of CABG Clopidogrel Bleeding Risk and CABG “In hospitals in which patients with UA/NSTEMI undergo rapid diagnostic catheterization within 24 hours of admission, clopidogrel is not started until it is clear that CABG will not be scheduled within the next several days. However, unstable patients should receive clopidogrel or be take for immediate angiography.” Clopidogrel vs. Prasugrel
Slide 61 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid New and Controversial Drug Therapies Early Treatment with Clopidogrel Shortcomings of the CURE Trial Conducted primarily at centers without routine use of early invasive strategy Only 462 (3.7%) patients enrolled from the U.S. 44% had catheterization during index hospitalization Adverse event reduced only in nonfatal MI set Major Bleeding rate of 9.6% among patients who were administered clopidogrel within 5 days of CABG Clopidogrel Bleeding Risk and CABG “In hospitals in which patients with UA/NSTEMI undergo rapid diagnostic catheterization within 24 hours of admission, clopidogrel is not started until it is clear that CABG will not be scheduled within the next several days. However, unstable patients should receive clopidogrel or be take for immediate angiography.” Clopidogrel vs. Prasugrel
Slide 62 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid New and Controversial Drug Therapies Early Treatment with Clopidogrel Shortcomings of the CURE Trial Conducted primarily at centers without routine use of early invasive strategy Only 462 (3.7%) patients enrolled from the U.S. 44% had catheterization during index hospitalization Adverse event reduced only in nonfatal MI set Major Bleeding rate of 9.6% among patients who were administered clopidogrel within 5 days of CABG Clopidogrel Bleeding Risk and CABG “In hospitals in which patients with UA/NSTEMI undergo rapid diagnostic catheterization within 24 hours of admission, clopidogrel is not started until it is clear that CABG will not be scheduled within the next several days. However, unstable patients should receive clopidogrel or be take for immediate angiography.” Clopidogrel vs. Prasugrel
Slide 63 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid New and Controversial Drug Therapies Early Treatment with Clopidogrel Shortcomings of the CURE Trial Conducted primarily at centers without routine use of early invasive strategy Only 462 (3.7%) patients enrolled from the U.S. 44% had catheterization during index hospitalization Adverse event reduced only in nonfatal MI set Major Bleeding rate of 9.6% among patients who were administered clopidogrel within 5 days of CABG Clopidogrel Bleeding Risk and CABG “In hospitals in which patients with UA/NSTEMI undergo rapid diagnostic catheterization within 24 hours of admission, clopidogrel is not started until it is clear that CABG will not be scheduled within the next several days. However, unstable patients should receive clopidogrel or be take for immediate angiography.” Clopidogrel vs. Prasugrel
Slide 64 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid New and Controversial Drug Therapies Early Treatment with Clopidogrel Shortcomings of the CURE Trial Conducted primarily at centers without routine use of early invasive strategy Only 462 (3.7%) patients enrolled from the U.S. 44% had catheterization during index hospitalization Adverse event reduced only in nonfatal MI set Major Bleeding rate of 9.6% among patients who were administered clopidogrel within 5 days of CABG Clopidogrel Bleeding Risk and CABG “In hospitals in which patients with UA/NSTEMI undergo rapid diagnostic catheterization within 24 hours of admission, clopidogrel is not started until it is clear that CABG will not be scheduled within the next several days. However, unstable patients should receive clopidogrel or be take for immediate angiography.” Clopidogrel vs. Prasugrel Prasugrel-Key Facts Contraindicated in pts with prior TIA/Stroke Not recommended for patients >75 years 5 mg maintenance dose suggested in patients <60 Kg, though this dose has not been studied
Slide 65 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid New and Controversial Drug Therapies Early Treatment with Clopidogrel Shortcomings of the CURE Trial Conducted primarily at centers without routine use of early invasive strategy Only 462 (3.7%) patients enrolled from the U.S. 44% had catheterization during index hospitalization Adverse event reduced only in nonfatal MI set Major Bleeding rate of 9.6% among patients who were administered clopidogrel within 5 days of CABG Clopidogrel Bleeding Risk and CABG “In hospitals in which patients with UA/NSTEMI undergo rapid diagnostic catheterization within 24 hours of admission, clopidogrel is not started until it is clear that CABG will not be scheduled within the next several days. However, unstable patients should receive clopidogrel or be take for immediate angiography.” Clopidogrel vs. Prasugrel Prasugrel-Key Facts Contraindicated in pts with prior TIA/Stroke Not recommended for patients >75 years 5 mg maintenance dose suggested in patients <60 Kg, though this dose has not been studied Summary ACS includes UA, NSTEMI, and STEMI Management guideline focus Immediate assessment/intervention (MONA+BAH) Risk stratification (UA/NSTEMI vs. STEMI) RAPID reperfusion for STEMI (PCI vs. Thrombolytics) Conservative vs Invasive therapy for UA/NSTEMI Aggressive attention to secondary prevention initiatives for ACS patients Beta blocker, ASA, ACE-I, Statin
Slide 66 - Acute Coronary Syndrome Steven R. Bruhl MD, MS 3rd Year Cardiology Fellow Internal Medicine Didactics July 14, 2010 Goals and Objectives Discuss the definition & pathophysiology of ACS Recognize the clinical features of low, intermediate and high risk ACS Be able to identify and treat patients appropriate for a conservative or invasive strategy Discuss new and controversial pharmacological treatments Gold Standard for Treatment of ACS ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction http://circ.ahajournals.org/cgi/content/full/102/10/1193 Algorithm for evaluation and management of patients suspected of having ACS. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 2. ACS Overview Overview of ACS Assessment of “Likelihood of ACS” Early Risk Stratification Invasive vs Conservative Strategy Pharmacotherapy Long-term Therapy/Secondary Prevention Scope of the Problem 5 million ER visits nationwide for CP 800,000 experience an MI each year 213,000 die from their event ½ of those die before reaching the ER Pre-CCU, mortality for MI was >30% Fell to 15% with CCU With current interventions, in hospital mortality of STEMI is 6-7% Overview of ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million Admissions per year 0.33 million Admissions per year *Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA. Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171. Acute Coronary Syndrome (ACS) Definition: The spectrum of acute ischemia related syndromes ranging from UA to MI with or without ST elevation that are secondary to acute plaque rupture or plaque erosion. [----UA---------NSTEMI----------STEMI----] Decreased O2 Supply Flow- limiting stenosis Anemia Plaque rupture/clot Increased O2 Demand O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis Pathophysiology ACS Asymptomatic Angina Myocardial Infarction Pathophysiology of Stable Angina and ACS Pathophysiology of ACS Evolution of Coronary Thrombosis Unstable Angina STEMI NSTEMI Non occlusive thrombus Non specific ECG Normal cardiac enzymes Non-occlusive thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion on ECG Elevated cardiac enzymes Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms STEMI Name 3 situations in which you cannot diagnose STEMI STEMI Name 3 situations in which you cannot diagnose STEMI Left Ventricular Hypertrophy Chronic or Rate Dependent LBBB Paced Rhythm Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. Cardiac Catheterization Name the only 3 situations that demand emergent cardiac catheterization. STEMI or new LBBB ACS with hemodynamic or electrical instability despite optimal medical management Uncontrolled CP despite optimal medical management Diagnosis of ACS At least 2 of the following History ( angina or angina equivalent) Acute ischemic ECG changes Typical rise and fall of cardiac markers Absence of another identifiable etiology Initial Evaluation and management of Non ST-elevation ACS Likelihood of ACS by Hx/PE History/Examination Pain in Chest or Left Arm CP Radiation Right Shoulder Left Arm Both Left & Right Arm Diaphoresis 3rd Heart Sound SBP < 80 mm Hg Pulmonary Crackles Panju AA. JAMA. 1998;280:1256. Suggesting AMI LR 2.7 LR 2.9 (1.4-6.0) LR 2.3 (1.7-3.1) LR 7.1 (3.6-14.2) LR 2.0 (1.9-2.2) LR 3.2 (1.6-6.5) LR 3.1 (1.8-5.2) LR 2.1 (1.4-3.1) Likelihood of ACS by Hx/PE Clinical Examination – Pleuritic Chest Pain Sharp or Stabbing Pain Positional Chest Pain Reproducible Chest Pain Panju AA. JAMA. 1998;280:1256. Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR 0.3 (0.2-0.4) LR 0.2-0.4 Risk Stratification by ECG Simple, quick, noninvasive tool Universally available, cheap Correlates with risk and prognosis Guides treatment decisions Can identify alternative causes Risk Stratification by ECG ECG Findings and Associated LR for AMI New ST-E > 1mm LR 5.7-53.9 New Q waves LR 5.3-24.8 Any ST-E LR 11.2 (7.1-17.8) New Conduction Defect LR 6.3 ( 2.5-15.7) New ST-D LR 3.0-5.2 NORMAL ECG LR 0.1-0.4 Panju AA. JAMA. 1998;280:1256. Risk Stratification by ECG CAVEATS 1-8% AMI have a normal ECG Only Approx 50% of AMI patients have diagnostic changes on their initial ECG Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. Risk Stratification by ECG CAVEATS cont. 1 ECG cannot exclude AMI Brief sample of a dynamic process Small regions of ischemia or infarction may be missed Peter J. Zimetbaum, M.D., N Engl J Med 2003;348:933-40. How Sensitive is the ECG Alone? How Predictive is NTG response? Timing of Release of Various Biomarkers After Acute Myocardial Infarction Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5. Mortality at 42 Days 831 174 148 134 50 67  % % % % % % Risk Stratification by Troponin Non ACS causes of Troponin Elevation Trauma (including contusion; ablation; pacing; ICD firings,, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially with diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hypertension Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion Modified from Apple FS, et al Heart J. 2002;144:981-986. Combined Sensitivities for ACS Early Invasive Conservative Unstable angina/NSTEMI cardiac care Evaluate for conservative vs. invasive strategy based upon: Likelihood of actual ACS Risk stratification by TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High TIMI Risk Score Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days TIMI Risk Score T: Troponin elevation (or CK-MB elevation) H: History or CAD (>50% Stenosis) R: Risk Factors: > 3 (HTN, Hyperlipidemia, Family Hx, DM II, Active Smoker) E: EKG changes: ST elevation or depression 0.5 mm concordant leads A2:Aspirin use within the past 7 days; Age over 65 T: Two or more episodes of CP within 2 hours Deciding between Early Invasive vs a Conservative Strategies Hemodynamic instability Elecrical instability Refractory angina PCI in past 6 months CABG EF <40% Specifics of Early Hospital Care Anti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy Early Hospital Care Anti-Ischemic Therapy Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation >90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no contraindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF<40% (Class IIa for all other pts) (ARBs for those intolerant) Statins Early Hospital Care Anti-Ischemic Therapy Class III Nitrates if BP<90 mmHg or RV infarction Nitrates within 24-hrs of Sildenafil or 48 hrs of Tadalafil Immediate release dihydropyradine Ca-blockers in the absence of B-Blocker therapy IV ACE-inhibitors IV B-blockers in patients with acute HF, Low output state or cardiogenic shock, PR interval >0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors Early Hospital Care Anti-Platelet Therapy Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for those with Aspirin allergy/intolerance (300-600 mg load and 75 mg/d) GI prophylaxis if a Hx of GI bleed GP IIb/IIIa inhibitors should be evaluated based on whether an invasive or conservative strategy is used GP IIb/IIIa inhibitors recommended for all diabetics and all patient in early invasive arm Early Hospital Care Anticoagulant Therapy Class I Unfractionated Heparin Enoxaparin Bivalarudin Fondaparinux Relative choice depends on invasive vs conservative strategy and bleeding risk Early Hospital Care Statin Therapy MIRACL Trial Inclusion Criteria 3086 patients with Non ST ACS Total cholesterol <270 mg/dl No planned PCI Randomized to Atorvastatin vs Placebo Drug started at 24-96 hours Statin Evidence: MIRACL Study Relative risk = 0.84 P = .048 95% CI 0.701-0.999 Atorvastatin Placebo 0 5 10 15 0 4 8 12 16 Time Since Randomization (weeks) Cumulative Incidence (%) Time to first occurrence of: Death (any cause) Nonfatal MI Resuscitated cardiac arrest Worsening angina with new objective evidence and urgent rehospitalization 17.4% 14.8% Primary Efficacy Measure Schwartz GG, et al. JAMA. 2001;285:1711-1718. Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24 All-Cause Death or Major CV Events in All Randomized Subjects 0 3 18 21 24 27 30 6 9 12 15 % with Event Months of Follow-up Pravastatin 40mg (26.3%) Atorvastatin 80mg (22.4%) 16% RR (P = 0.005) 30 25 20 15 10 5 0 PROVE-IT Trial Summary of PROVE-IT Results In patients recently hospitalized within 10 days for an acute coronary syndrome: “Intensive” high-dose LDL-C lowering (median LDL-C 62 mg/dL) compared to “moderate” standard-dose lipid-lowering therapy (median LDL-C 95 mg/dL) reduced the risk of all cause mortality or major cardiac events by 16% (p=0.005) Benefits emerged within 30 days post ACS with continued benefit observed throughout the 2.5 years of follow-up Benefits were consistent across all cardiovascular endpoints, except stroke, and most clinical subgroups Invasive vs Conservative Strategies Invasive vs Conservative Strategy Clinical Trials TIMI IIIB (94) Conservative Strategy Favored N=920 Invasive Strategy Favored N=7,018 VANQWISH (98) MATE FRISC II (99) TACTICS- TIMI 18 (01) VINO RITA-3 (02) TRUCS ISAR- COOL ICTUS (05) No difference N=2,874 Weight of the evidence How Early is Early? Secondary Prevention Class I Indications Aspirin Beta-blockers: (all pts, slow titration with moderate to severe failure ACE-Inhibitors: CHF, EF<40%, HTN, DM (All pts-Class IIa) ARB when intolerant to ACE. (Class IIa as alternative to ACEI) Aldosterone blockade: An ACEI, CHF with either EF<40% or DM and if CrCl>30 ml/min and K<5.0 mEq/L Statins Standard Risk Factor Management Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group ASA 162 to 325 mg/d for at least 1 month, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 month and up to 1 year (Class I, LOE:B) Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Yes No Indication for Anticoagulation? ASA 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d at least 1 month (Class I, LOE: A) and up to 1 year (Class I, LOE: B) ASA 162 to 325 mg/d for at least 3 to 6 months, then 75 to 162 mg/d indefinitely (Class I, LOE: A) & Clopidogrel 75 mg/d for at least 1 year (Class I, LOE: B) Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence. UA/NSTEMI Patient Groups at Discharge Secondary Prevention Class III Hormone Replacement Therapy Antioxidants (Vit C, Vit E) Folic Acid New and Controversial Drug Therapies Early Treatment with Clopidogrel Shortcomings of the CURE Trial Conducted primarily at centers without routine use of early invasive strategy Only 462 (3.7%) patients enrolled from the U.S. 44% had catheterization during index hospitalization Adverse event reduced only in nonfatal MI set Major Bleeding rate of 9.6% among patients who were administered clopidogrel within 5 days of CABG Clopidogrel Bleeding Risk and CABG “In hospitals in which patients with UA/NSTEMI undergo rapid diagnostic catheterization within 24 hours of admission, clopidogrel is not started until it is clear that CABG will not be scheduled within the next several days. However, unstable patients should receive clopidogrel or be take for immediate angiography.” Clopidogrel vs. Prasugrel Prasugrel-Key Facts Contraindicated in pts with prior TIA/Stroke Not recommended for patients >75 years 5 mg maintenance dose suggested in patients <60 Kg, though this dose has not been studied Summary ACS includes UA, NSTEMI, and STEMI Management guideline focus Immediate assessment/intervention (MONA+BAH) Risk stratification (UA/NSTEMI vs. STEMI) RAPID reperfusion for STEMI (PCI vs. Thrombolytics) Conservative vs Invasive therapy for UA/NSTEMI Aggressive attention to secondary prevention initiatives for ACS patients Beta blocker, ASA, ACE-I, Statin Questions?