Internal Medicine Board Review: Cardiology Acute Coronary Syndrome

1. Internal Medicine Board Review: CardiologyAcute Coronary Syndrome Christine Nardi May 20, 2009

2. Hospitalizations in the U.S. Due to ACS Incidence rate of MI has not changed but survival has 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.

3. Acute Coronary Syndrome • Clinical syndromes caused by acute myocardial ischemia • Unstable angina • Angina at rest or new onset angina, accelerating symptoms • No detectable increase of biomarkers • Non-ST-elevation MI • Angina at rest or new onset angina, accelerating symptoms • Detectable release of biomarkers • ST-elevation MI • Clinical presentation of acute myocardial infarction with EKG evidence of ST-segment elevation

4. 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.

5. Pathophysiology: unstable angina and NSTEMI • Spontaneous rupture of lipid-laden, macrophage rich atherosclerotic plaques leading to platelet activation and thrombosis • Leads to episodic cessation of coronary blood flow, ischemia and pain • Rarely, caused by vasospasm (Prinzmetal’s or cocaine)

6. Causes of UA/NSTEMI* • Thrombus or thromboembolism, usually arising on disrupted or eroded plaque • Occlusive thrombus, usually with collateral vessels† • Subtotally occlusive thrombus on pre-existing plaque • Distal microvascular thromboembolism from plaque-associated thrombus • Thromboembolism from plaque erosion • Non–plaque-associated coronary thromboembolism • Dynamic obstruction (coronary spasm‡ or vascoconstriction) of epicardial and/or microvascular vessels • Progressive mechanical obstruction to coronary flow • Coronary arterial inflammation • Secondary UA • Coronary artery dissection§ *These causes are not mutually exclusive; some patients have 2 or more causes. †DeWood MA, et al. N Engl J Med 1986;315:417–23. ‡May occur on top of an atherosclerotic plaque, producing missed-etiology angina or UA/NSTEMI. §Rare. Modified with permission from Braunwald E. Circulation 1998;98:2219–22. Anderson JL, et al. J Am Coll Cardiol. 2007;50:e1-e157, Table 3.

7. Pathophysiology of STEMI • Occlusive thrombus that develops on a dissected or ulcerative atherosclerotic plaque, resulting in complete epicardial coronary artery occlusion • Moderately sized plaques are more common than those causing severe stenosis

8. Evaluation • History • Physical exam • EKG • Cardiac biomarkers

9. Variables Used in the TIMI Risk Score 0-2 low risk (5%) 3-4 intermediate risk 5-7 high risk (40%) 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.

10. Selection of Initial Treatment Strategy: Initial Invasive Versus Conservative Strategy angiography Stress testing

11. UA/NSTEMI Statin ASA and/or clopidogrel B-blocker Nitrate Heparin/LMWH TIMI 1-2 TIMI 5-7 TIMI 3-4 Recurrent angina Elevated trop New ST depression CHF Prior CABG PCI within 6 mo Sustained VT Hemodynamic instability yes no GP IIb/IIIa inhibitor Stress imaging study Positive Or EF<40 normal cath Medical therapy

12. Short-Term Risk of Death/Nonfatal MI in Patients With UA/NSTEMI

13. Short-Term Risk of Death/Nonfatal MI in Patients With UA/NSTEMI, Continued Estimation of the short-term risk of death and nonfatal cardiac ischemic events in UA/NSTEMI is a complex multivariable problem that cannot be fully specified in a table such as this; this table is mean to offer general guidance & illustration rather than rigid algorithms. Braunwald E, et al. AHCPR Publication No. 94-0602:1–154. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Table 7.

14. Long-Term Antithrombotic Therapy at Hospital Discharge after UA/NSTEMI UA/NSTEMI Patient Groups at Discharge Medical Therapy without Stent Bare Metal Stent Group Drug Eluting Stent Group 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) 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 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) Indication for Anticoagulation? Yes No Add: Warfarin (INR 2.0 to 2.5) (Class IIb, LOE: B) Continue with dual antiplatelet therapy as above Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 11. INR = international normalized ratio; LOE = level of evidence.

15. PCI Higher vessel patency, lower reinfarction and stroke rates, immediate risk stratification Should be performed if presenting within 12 hours of symptom onset if a skilled PCI lab is available Fibrinolytic therapy Highly available, ease of use If no contraindications and no PCI available, fibrinolytics should be administered within 30 minutes from arrival to ED (if symptoms started within the last 12 hours) Management of STEMI

16. Absolute Contraindications to Fibrinolytics • Prior intracranial hemorrhage • Known structural cerebral vascular lesion (AVM) • Known malignant intracranial neoplasm • Ischemic stroke without 3 months • Suspected aortic dissection • Active bleeding (excluding menses) • Significant closed-head injury or facial trauma within 3 months

17. Mortality Predictors in STEMI • Age > 65 years • Clinically evident heart failure • Diabetes • Renal failure • Previous myocardial infarction • Time of presentation (reperfusion less successful 12 hours after symptom onset)

18. Complications during STEMI • Hypotension • Hypovolemia, increased vagal tone, low CO, hypoxia, rhythm disturbances • Pulmonary congestion • O2, nitrates, morphine, diuretics when appropriate • RV infarction • Hypotension, elevated JVP, inferior STEMI, bradcardia • ST-elevation in V4R • Treatment: fluids, temporary pacemaker

19. Complications after STEMI • Occur in 0.1% of STEMI patients 2-7 days after infarction • Ventricular septal defect • Papillary muscle rupture (acute MR) • Left ventricular free wall rupture (tamponade) • pericarditis • New systolic murmur (VSD or MR) • Diagnosed with echo or Swan-Ganz catheter • VSD: O2 saturation step-up • Tamponade: equalization of diastolic pressures in all heart chambers

20. Key Points • Intermediate and high risk patients with UA or NSTEMI benefit from an early invasive strategy with angiography • Early management of UA or NSTEMI includes ASA, heparin, nitrates, b-blocker, GP IIb/IIIa inhibitor, clopidogrel and statin • LMWH (enoxaparin) is a suitable alternative to unfractionated heparin for patients with acute coronary syndrome or STEMI and those undergoing early PCI

21. Key Points • Clinical predictors of mortality in patients with acute STEMI are time to presentation after symptom onset, age>65, heart failure, DM, renal failure and previous MI • Immediate reperfusion, preferable with PCI, should be performed for any STEMI • Most patients with STEMI should be started early on oral b-blocker • STEMI patients with anterior infarction, pulmonary congestion, or a LVEF<40% should be started on an ACE inhibitor

22. Differential Diagnosis • Aortic dissection • Pulmonary embolus • Perforating ulcer • Tension pneumothorax • Esophageal rupture (Boerhaave’s syndrome)

23. Key Points • In patients with STEMI, successful fibrinolysis is suggested by resolution of chest pain and ST-segment elevation and/or transient ventricular arrhythmias early after reperfusion. • In patients with STEMI, reperfusion arrhythmias usually do not require therapy. • Immediate coronary angiography is not indicated unless recurrent ischemia, persistent ST elevation or hemodynamic instability (including CHF) occurs.

24. Key Points • Patients with STEMI should undergo coronary reperfusion in the most expeditious manner • STEMI patients who cannot be reperfused by direct coronary intervention within 90 to 120 minutes should receive fibrinolytic therapy if there are no contraindications

25. Key Points • Ascending aortic dissection may involve the coronary arteries, most commonly the RCA • Ascending aortic dissection may lead to disruption of the aortic valve, leading to aortic regurgitation

26. Key Points • Glycoprotein receptor blockade is indicated for patients with acute coronary syndrome who will undergo coronary angiography and intervention

27. Key Points • Medical therapy for acute, recent myocardial infarction includes B-blocker, aspirin, ACE-inhibitor and statins • This is an uncomplicated (based on the absence of further symptoms and EKG changes) anterior STEMI • Late fibrinolysis is not beneficial for most patients and may be associated with an increase of transformation to a hemorrhagic zone of infarction • A glycoprotein IIb/IIIa blocker in addition to aspirin and heparin is indicated for patients with continuing ischemia, elevated troponin level or other high-risk features including angina at rest with ST changes and CHF

28. Key Points • In patients with chest pan and intermediate risk of CAD, non-invasive testing is indicated • Patients with chest pain and low coronary artery disease risk with a normal EKG and a normal exercise EKG can be discharged without coronary angiography • Immediate coronary angiography would be appropriate if there were high risk markers: • Elevated enzymes • Hypotension • Decreased LVEF • New EKG changes in a patient with unstable angina or NSTEMI

29. Key Points • Right ventricular infarction is a cause of hypotension following inferior infarction and typically requires appropriate volume infusion • Right ventricular infarction should be suspected as a cause of hypotension when findings of right heart failure coincides with an absence of evidence of pulmonary congestion

30. Key Points • Papillary muscle rupture and ventricular septal defect are recognized mechanical complications that occur early after myocardial infarction • Both papillary muscle rupture and ventricular septal defect present with hypotension and acute dyspnea