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Acute Coronary Syndrome. Steven R. Bruhl MD, MS 3 rd 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
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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 millionAdmissions per year 0.33 millionAdmissions 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----]
Pathophysiology of Stable Angina and ACS Pathophysiology ACS • Decreased O2 Supply • Flow- limiting stenosis • Anemia • Plaque rupture/clot • Increased O2 Demand Asymptomatic Angina Myocardial Infarction O2 supply/demand mismatch→Ischemia Myocardial ischemia→necrosis
Unstable Angina STEMI NSTEMI • Non-occlusive thrombus • sufficient to cause • tissue damage & mild • myocardial necrosis • ST depression +/- • T wave inversion on • ECG • Elevated cardiac • enzymes • Non occlusive • thrombus • Non specific • ECG • Normal 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
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 Diagnosis of ACS
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
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.
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-interventionalclosure 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.
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 High Intermediate
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 CareAnti-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 CareAnti-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 CareAnti-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 CareAnticoagulant Therapy • Class I • Unfractionated Heparin • Enoxaparin • Bivalarudin • Fondaparinux • Relative choice depends on invasive vs conservative strategy and bleeding risk
Early Hospital CareStatin Therapy • MIRACL TrialInclusion 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 Primary Efficacy Measure Placebo 17.4% 15 14.8% Atorvastatin 10 • Time to first occurrence of: • Death (any cause) • Nonfatal MI • Resuscitated cardiac arrest • Worsening angina with new objective evidence and urgent rehospitalization Cumulative Incidence (%) 5 Relative risk = 0.84P = .048 95% CI 0.701-0.999 0 0 4 8 12 16 Time Since Randomization (weeks) Schwartz GG, et al. JAMA. 2001;285:1711-1718.
2 Placebo 1.5 Cumulative Incidence (%) 1 Atorvastatin 0.5 Relative risk = 0.49 P = .04 95% CI 0.24-0.98 0 0 4 8 12 16 Time Since Randomization (weeks) Statin Evidence: MIRACL Study Fatal and Nonfatal Stroke Waters DD, et al. Circulation. 2002;106:1690-1695. S24
0 30 3 6 9 12 15 18 21 24 27 PROVE-IT Trial All-Cause Death or Major CV Events in All Randomized Subjects 30 Pravastatin 40mg (26.3%) 25 20 % with Event Atorvastatin 80mg (22.4%) 15 10 16% RR (P = 0.005) 5 0 Months of Follow-up
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 Strategy Clinical Trials ISAR-COOL ICTUS (05) RITA-3 (02) VANQWISH (98) VINO MATE TRUCS TIMI IIIB (94) TACTICS-TIMI 18 (01) FRISC II (99) Weight of the evidence ConservativeStrategy Favored N=920 InvasiveStrategy Favored N=7,018 No difference N=2,874