Acute Coronary Syndromedr. Isbandiyah, SpPD

World Health OrganizationDiagnosis of Myocardial Infarction(MI) Requires 2 of the Following:

1) Prolonged ischemic-type chestdiscomfort2) Serial electrocardiogram (ECG)changes3) Rise and fall of serum cardiac markers

Acute MI

Serum Markers of MI:Creatine Kinase (CK)

Also known as CPK First detectable in 3-4 hours, peaks in 8-24hours, lasts for 3-4 days Not very specific abnormal in skeletal andsmooth muscle injury as well as severe CNSinjury Peak value commonly used as a index of MIsize (e.g. a 1,400 peak CK infarct)

Serum Markers of MI: CKMB

More specific for cardiac muscle thantotal CK (though not perfect) Rises and falls slightly earlier than totalCK Should be considered the currentstandard for diagnosing MI

Serum Markers of MI:Troponins T and I

Very sensitive and specific Similar early rise in serum levels as CK-MB(2-4 hours) but stays elevated longer (10-14days) Good for patients presenting late after MI May be mildly elevated in unstable angina Worse prognosis

Serum Markers of MI: LactateDehydrogenase (LDH)

Very nonspecific (in liver, red cells, etc.) High LDH1 isoenzyme somewhat morespecific Rises late and stays elevated 4-5 days Should be replaced by troponin T

Serum Markers of MI:Myoglobin

First detectable in 1-4 hours, peaks in 6hours, lasts for24 hours Non-specific also present in skeletalmuscle Not (yet) widely used, but may be usefulfor early detection of MI

Acute Coronary SyndromeIschemic Discomfort Unstable SymptomsNo ST-segment elevation ST-segment elevationUnstable Non-QQ-Wave angina AMI AMIECGAcute ReperfusionHistory Physical Exam

Pathogenesis OF AMI/ACS

Long-Term Management After MI

1) Aspirin 13% mortality, 31% nonfatal MI Ticlid unproven alternative2) Beta-blocker metoprolol, timolol, propranolol all shown toreduce mortality 1 to 6 years in more than35,000 patients mortality 30%

Long-Term Management After MI

3) ACE Inhibitor Best if started early (25% mortality) Probably should be stopped in 4-6 weeksfor patients with preserved left ventricular(LV) function and no CHF symptoms Continue indefinitely if LVdysfunction/CHF is present

Long-Term Management After MI

4) Lipid Lowering Agents Prognosis improved even in post-MI withnormal cholesterol level CARE trial mean cholesterol 209, LDL139 at entry showed 24% mortality/nonfatal MI at 5 years withpravastatin Aggressive approach to lipid control (goalLDL

Long-Term Management After MI

5) Estrogen in post-menopausalwomen improves lipid profile andlowers fibrinogen6) Vitamin E and other antioxidants theHATS trial suggests antioxidants mayinhibit HDL

Long-Term Management After MI

7) Warfarin (Coumadin) 13% mortality (most patients not on ASA) CARS trial ASA 180mg worked as well as ASA80mg+1-3mg Warfarin Definitely indicated for post-MI patients withlarge anterior MIs with/without thrombus orpatients with atrial fibrillation (to preventsystemic embolism from LV thrombus) Use for 3 months for LV thrombus or largeanterior MI Use indefinitely for atrial fibrillation

Long-Term Management After MI

8) Homocysteine Significant risk factor for CAD at serum levels Homocysteine levels can be with folate and B6 No randomized data to date on whether vitaminsupplementation to reduce homocysteine risk,9) Lifestyle modification Smoking Diet Exercise

************Note: Plavix (clopidogrel bisulfate) is not indicated for all the conditions listed on this slide.Vascular disease is the common underlying disease process for MI, ischemia and vascular death.Acute coronary syndrome (ACS) is a classic example of the progression of vascular disease to an ischemic event.ACS (in common with ischemic stroke and critical leg ischemia) is typically caused by rupture or erosion of an atherosclerotic plaque followed by formation of a platelet-rich thrombus.Atherosclerosis is an ongoing process affecting mainly large and medium-sized arteries, which can begin in childhood and progress throughout a persons lifetime.Stable atherosclerotic plaques may encroach on the lumen of the artery and cause chronic ischemia, resulting in (stable) angina pectoris or intermittent claudication, depending on the vascular bed affected.Unstable atherosclerotic plaques may rupture, leading to the formation of a platelet-rich thrombus that partially or completely occludes the artery and causes acute ischemic symptoms.

*Platelets play a central role in the development of thrombi and subsequent ischemic events. The process of platelet-mediated thrombus formation involves adhesion, activation, and aggregation.Within seconds of injury, platelets adhere to collagen fibrils through glycoprotein (GP) Ia/IIa receptors. An adhesive glycoprotein, von Willebrand factor (vWF) allows platelets to stay attached to the subendothelial vessel wall (via GP Ib) despite high shear forces. Following adhesion, platelets are activated to secrete a variety of agonists including thrombin, serotonin, adenosine diphosphate (ADP), and thromboxane A2 (TXA2). These agonists, which further augment the platelet activation process, bind to specific receptor sites on the platelets to activate the GP IIb/IIIa receptor complex, the final common pathway to platelet aggregation. Once activated, the GP IIb/IIIa receptor undergoes a conformational change that enables it to bind with fibrinogen.[1,2]

Handin RI. Bleeding and thrombosis. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrisons Principles of Internal Medicine. Vol 1. 14th ed. New York, NY: McGraw-Hill; 1998:339-345. Schafer AI. Antiplatelet therapy. Am J Med. 1996;101:199-209.

**Treatment of acute coronary syndrome (ACS) should be directed by patient presentation.[1] The algorithm shown here shows the different treatment approaches (early invasive vs delayed invasive) that can be used in patients with unstable angina (UA) or nonST-segment elevation myocardial infarction (NSTEMI; also known as nonQ-wave MI).

Bowen WE, Mckay RG. Optimal treatment of acute coronary syndromesan evolving strategy. N Engl J Med. 2001;344:1939-1942. Editorial.Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guidelines for the management of patients with unstable angina and nonST-segment elevation myocardial infarction. Available at: www.acc.org. Accessed March 19, 2002.

*Acute medical management of patients with acute coronary syndrome should include supplemental oxygen and bed rest with continuous ECG monitoring; nitroglycerin (and morphine sulfate if nitroglycerin does not relieve symptoms); beta blockers (or nonhydropyridine calcium antagonists if beta blockers are contraindicated); and ACE inhibitors (in patients with continuing hypertension and left-ventricular dysfunction, chronic heart failure, or diabetes); and antiplatelet and anticoagulation therapy. Maintenance therapy in patients discharged following acute coronary syndrome should include antiplatelet therapy (aspirin or clopidogrel), beta blockers (in the absence of contraindications), calcium channel blockers, lipid-lowering agents (in patients with low-density lipoprotein [LDL] cholesterol of >130 mg/dL), and ACE inhibitors (in patients with congestive heart failure, left-ventricular dysfunction, hypertension, or diabetes).

Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guidelines for the management of patients with unstable angina and nonST-segment elevation myocardial infarction. Available at: www.acc.org. Accessed March 19, 2002.******