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CHEST PAIN/ACUTE MI Sati Adlakha Cardiovascular Disease Fellow July 22nd, 2009 Disclosures • None Objectives • Review the pathophysiology of angina • Review the differential diagnosis of chest pain • Review current medical strategies at reducing morbidity and mortality in ACS • Review current invasive techniques for reducing morbidity and mortality in ACS CHEST PAIN • • • • • • • • Musculoskeletal pain Coronary heart disease Aortic dissection Valvular heart disease Pericarditis Myocarditis Stress-induced cardiomyopathy Cardiac syndrome X CHEST PAIN • Gastroesophageal reflux disease • Esophageal rupture, mediastinitis, and foreign bodies • Medication-induced esophagitis • Acute pulmonary thromboembolism • Pneumonia • Psychogenic • Coronary inflammation MECHANISM OF ANGINA Ischemia Acidemia, Loss of the normal ATP sodiumpotassium pump, Loss of myocardial membrane integrity, and the release of chemical substances lactate, serotonin, bradykinin, histamine, reactive oxygen species, and adenosine Platelets (serotonin, thromboxane A2, and 5hydroxytyrptamine) Angina A1 adenosine receptor sympathetic afferent sympathetic ganglia (C7-T4) Ascending spinothoracic pathways to the medial and lateral thalamus Cortex ANGINA PATHOPHYSIOLOGY OF ANGINA Heart rate Preload Myocardial oxygen demand Afterload Contractility ANGINA Oxygen carrying capacity of the blood Myocardial oxygen supply oxygen unloading from hemoglobin coronary artery blood flow Coronary Blood Flow Coronary artery diameter and tone Collateral blood flow Coronary Perfusion pressure Heart rate (Diastolic filling period) Conditions provoking or exacerbating ischemia Increased oxygen demand Decreased oxygen supply Non-cardiac Anemia Hyperthermia Non-cardiac Hypoxemia Pneumonia Hyperthyroidism Asthma Sympathomimetic toxicity (eg, cocaine use) Chronic obstructive pulmonary disease Hypertension Interstitial pulmonary fibrosis Anxiety Obstructive sleep apnea Arteriovenous fistulae Sickle cell disease Pulmonary hypertension Sympathomimetic toxicity (eg, cocaine use) Cardiac Hypertrophic cardiomyopathy Aortic stenosis Dilated cardiomyopathy Hyperviscosity Polycythemia Leukemia Thrombocytosis Hypergammaglobulinemia Tachycardia Cardiac Ventricular Aortic stenosis Supraventricular Hypertrophic cardiomyopathy Reproduced with permission from: ACC/AHA/ACP Guidelines for the Management of Patients with Chronic Stable Angina. J Am Coll Cardiol 1999; 33:2092. Copyright ©1999 American College of Cardiology. The Normal Artery • Composed of three layers: – Adventitia – Media – Intima Hospitalizations in the U.S. Due to ACS Acute Coronary Syndromes* 1.57 Million Hospital Admissions - ACS UA/NSTEMI† STEMI 1.24 million 0.33 million Admissions per year 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 Thrombus occluding Lumen Plaque: Lipid core Pathophysiology of STEMI vs. NSTEMI/UA • STEMI: – Complete coronary occlusion – So-called “red clot” – erythrocyte- and fibrinrich • NSTEMI/UA: – Incomplete coronary occlusion – So-called “white clot” – platelet-rich Ischemic Discomfort Acute Coronary Syndrome Presentation Working Dx ECG Cardiac Biomarker Final Dx No ST Elevation ST Elevation Non-ST ACS UA NSTEMI Unstable Angina Myocardial Infarction NQMI Qw MI Libby P. Circulation 2001;104:365, Hamm CW, Bertrand M, Braunwald E, Lancet 2001; 358:1533-1538; Davies MJ. Heart 2000; 83:361-366. Anderson JL, et al. J Am Coll Cardiol. 2007;50:e1-e157, Figure 1. Reprinted with permission. Classifications • Characterization of chest pain symptoms: Canadian Cardiovascular Society (CCS) Angina Classification Stable vs. Unstable Angina Characteristics of Unstable Angina: 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. 3 rd 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. UA/NSTEMI STEMI Oxygen/Nitrates • Given to patients with O2 levels less than 90% • Nitrates are contraindicated in hypotension, RV infarct, Severe AS and after erectile dysfunction meds. BETA BLOCKERS Chadda, K, Goldstein, S, Byington, R, et al, Circulation 1986;73:503. ASA • Research on Instability in Coronary Artery Disease (RISC) • Lancet. 1990;336:827-30 • Oral aspirin (75 mg/day) reduced the risk of MI and death (57-69%) at 1 year • Same data supported in 3 more randomized trials Antiplatelet Trialists’ Collaboration •Meta-analysis of randomized trials of antiplatelet therapy for prevention of death, MI, and stroke in high-risk patients •195 trials and > 143,000 pts •22% ↓ in odds of vascular death, MI, or stroke with antiplatelet therapy across broad spectrum of clinical presentations that included UA/NSTEMI •Similar ↓ in odds of vascular events with ASA doses of 75-1500 mg daily; < 75 mg benefit ↓; dose-dependent ↑ bleeding* * Yusuf S, et al. N Engl J Med 2001;345:494–502 (bleeding analysis from CURE trial). Antiplatelet Trialists’ Collaboration. BMJ 1994;308:81–106. Antithrombotics Trialists’ Collaboration. BMJ 2002; 324:71– 86. ISIS - 2 Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group Lancet 1988 Aug 13;2(8607):349-60 ASA ISIS-2 • 804 deaths (9.4%) with aspirin vs. 1016 (11.8%) with placebo (23% odds reduction; SD = 4; 2p <0.00001) • Aspirin significantly reduced nonfatal reinfarction (1.0% vs. 2.0% in the placebo group) and nonfatal stroke (0.3% vs. 0.6%) Clopidogrel SYNERGY Primary Outcomes 1.0 14.5 14 14 12 10 UFH Enoxaparin 8 6 Freedom from Death/MI 16 0.95 0.9 0.85 Enoxaparin UFH 4 0.8 0 2 5 10 15 20 25 30 Days from Randomization 0 Death or MI at 30 d Absolute Risk Reduction Hazard Ratio 95% CI p Kaplan Meier Curve 0.5 0.96 0.86–1.06 0.40 Reprinted with permission from Ferguson JJ, et al. JAMA 2004;292:45–54. Primary End Point (ITT) Death or Nonfatal MI Primary End Point (%) 15 UFH 12 12.0% 17% RRR 9 9.9% ENOX Relative Risk 0.83 (0.77 to 0.90) P<0.0001 6 3 Lost to follow up = 3 0 0 5 10 15 Days 20 25 30 Glycoprotein IIb/IIIa Inhibitors • Consider in high risk patients • (eptifibatide) • Those undergoing an early invasive therapy • No benefit of starting prior to revascularization in STEMI or with thrombolytics Variables Used in the TIMI Risk Score •Age ≥ 65 years •At least 3 risk factors for CAD •Prior coronary stenosis of ≥ 50% •ST-segment deviation on ECG presentation •At least 2 anginal events in prior 24 hours •Use of aspirin in prior 7 days •Elevated serum cardiac biomarkers The TIMI risk score is determined by the sum of the presence of the above 7 variables at admission. 1 point is given for each variable. Primary coronary stenosis of 50% or more remained relatively insensitive to missing information and remained a significant predictor of events. Antman EM, et al. JAMA 2000;284:835–42. TIMI = Thrombolysis in Myocardial Infarction. TIMI Risk Score TIMI 11B and ESSENCE TIMI Risk Score All-Cause Mortality, New or Recurrent MI, or Severe Recurrent Ischemia Requiring Urgent Revascularization Through 14 Days After Randomization % 0-1 4.7 2 8.3 3 13.2 4 19.9 5 26.2 6-7 40.9 Reprinted with permission from Antman EM, et al. JAMA 2000;284:835–42. Copyright © 2000, American Medical Association. All Rights reserved. The TIMI risk calculator is available at www.timi.org. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Table 8. TIMI = Thrombolysis in Myocardial Infarction. GRACE Risk Score Variable Odds ratio Older age 1.7 per 10 y Killip class 2.0 per class Systolic BP 1.4 per 20 mm Hg ↑ ST-segment deviation 2.4 Cardiac arrest during presentation 4.3 Serum creatinine level 1.2 per 1-mg/dL ↑ Positive initial cardiac biomarkers 1.6 Heart rate 1.3 per 30-beat/min ↑ The sum of scores is applied to a reference monogram to determine the corresponding all-cause mortality from hospital discharge to 6 months. Eagle KA, et al. JAMA 2004;291:2727–33. The GRACE clinical application tool can be found at www.outcomes-umassmed.org/grace. Also see Figure 4 in Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157. GRACE = Global Registry of Acute Coronary Events. Selection of Initial Treatment Strategy: Initial Invasive Versus Conservative Strategy Invasive Recurrent angina/ischemia at rest with low-level activities despite intensive medical therapy Elevated cardiac biomarkers (TnT or TnI) New/presumably new ST-segment depression Signs/symptoms of heart failure or new/worsening mitral regurgitation High-risk findings from noninvasive testing Hemodynamic instability Sustained ventricular tachycardia PCI within 6 months Prior CABG High risk score (e.g., TIMI, GRACE) Reduced left ventricular function (LVEF < 40%) Conservative Low risk score (e.g., TIMI, GRACE) Patient/physician presence in the absence of high-risk features STEMI • Thrombolytics vs PCI • PCI has been found to be superior to lytics in multiple trials • PAMI • Cadillac • DANAMI-2 • STOPAMI • STAT Thrombolytics Mortality Benefit