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Acute Coronary Syndromes

ACS: Definition
• A spectrum of clinical diagnoses
comprising unstable angina, Non-STEMI,
and STEMI that share similar pathological
features involving intracoronary thrombosis

ACS: Definition

From: Braunwald’s Heart Disease

Pathophysiology • atherosclerosis with superimposed coronary thrombosis • Slowly growing high-grade stenoses can progress to complete occlusion but do not usually precipitate acute STEMI d/t collateral circulation • During development of plaques. resulting in • Platelet activation • Thrombin generation • Thrombus formation • Blood flow occlusion leads to imbalance between supply and demand and could lead to myocardial necrosis . abrupt transition can occur.

Stable Angina •Progressive narrowing of coronary lumen •Stable fibrous cap Unstable Angina •Progressive narrowing •Acute worsening of coronary lumen due to thrombus formation NSTEMI •Acute worsening of coronary lumen due to thrombus formation •Sub-occlusive/ transient coronary thrombus with myocardial necrosis Pathophysiology STEMI •Minimal prior narrowing of coronary lumen •Acute rupture of thin fibrous cap •Occlusive thrombus formation •Acute injury pattern •Myocardial necrosis .

ACS Evaluation .

teeth. relieved by rest and/or NTG Character Location Provoking Factors Favors Ischemic Origin Against Ischemic Origin Constricting Squeezing Burning Heaviness Dull ache Knife-like. meals. Interscapular Left submammary area Left hemithorax Exertion Excitement Cold.” that characteristically comes on with exertion.Angina • Definition: Discomfort in the chest/ “choking. sharp Jabs Pleuritic Substernal Anterior thorax Arms. shoulders Neck. stress Pain after completion of exercise Pain with movement .

05mV) or T wave inversion (≥0.Likelihood that signs & symptoms represent an ACS secondary to CAD Feature High Intermediate Low History Chest or left arm pain or discomfort as chief symptom reproducing prior documented angina Known history of CAD. including MI Chest or left arm pain or discomfort as chief symptom Age > 70 Male gender Diabetes mellitus Probable ischemic symptoms in absence of the intermediate likelihood characteristics Recent cocaine use Exam Transient MR. hypotension. diaphoresis. TnT or CK-MB Normal Normal Braundwald 1994 AHCPR Publication No.2mV) with symptoms Fixed Q waves Abnormal ST segments or T waves not documented to be new T wave flattening or inversion in leads with dominant R wave Normal EKG Cardiac Marker Elevated cardiac TnI. 94-0602 . pulmonary edema or rales Extracardiac vascular disease Chest discomfort reproduced by palpation or respiration EKG New or presumably new. transient ST segment deviation (≥0.

Chest Pain Classification • Substernal • Exertional • Relieved with rest • Interpretation – Typical Angina: 3 criteria from above – Atypical Angina: 2 criteria from above – Non-Anginal Chest Pain: 1 or less criteria from above .

climbing less than one flight of stairs – IV: Any physical activity brings on angina.Classification of Angina • STABLE vs UNSTABLE • CCS Classification for STABLE Angina – I: No symptoms. angina at rest . climbing more than one flight of stairs brings on angina – III: Marked limitation of ordinary physical activity • Walking less than two blocks. or angina with strenuous exertion – II: Slight limitation of ordinary physical activity • Walking more than two blocks.

. frequent. longer longer in in duration. severity. Braunwald Braunwald Circulation Circulation 80:410. rest. usually usually >> 20 20 minutes minutes New-onset New-onset Angina Angina New-onset New-onset angina angina of of at at least least CCS CCS Class Class III III severity severity Increasing Increasing Angina Angina Previously Previously diagnosed diagnosed angina angina that that has has become become distinctly distinctly more more frequent. increased increased by by >> 11 CCS) CCS) class class to to at at least least CCS CCS Class Class III III severity. 80:410.. ** Pts Pts with with NSTEMI NSTEMI usually usually present present with with angina angina at at rest.e. or or lower lower in in threshold threshold (i. (i.e. 1989 1989 . prolonged.UA/NSTEMI 9/00 UA/NSTEMI THREE PRINCIPAL PRESENTATIONS Rest Rest Angina* Angina* Angina Angina occurring occurring at at rest rest and and prolonged. duration.

) Nonanginal pain Men Women Atypical angina Men Women Typical angina Men Women 30-39 4 2 34 12 76 26 40-49 13 3 51 22 87 55 50-59 20 7 65 31 93 73 60-69 27 14 72 51 94 86 Diamond and Forrester.Pre-Test Likelihood of CAD Age (y. 1979 . NEJM.

Relationship of Rise in Biochemical Markers to Onset of AMI .

Troponin • cTnT (33 kDa) binds to tropomyosin to complex molecule to thin filament • cTnI (24kDa) inhibits actin-myosin interactions • cTnC binds Ca2+ • Generally not detectable in plasma of normal persons .

Troponin • TnT and TnI have different amino acid sequence in cardiac vs. skeletal muscle – Permits development of cardiac specific antibodies • More sensitive and specific than CKMB – Detects minimal amounts of cardiac necrosis (neg. with increased troponin: • • • • • CHF ICU Renal failure CVA Myocarditis/other myocardial injury . CKMB) – New guidelines suggest troponin is sufficient to dx MI • Other situations assoc. CKMB) • “minor myocardial damage/microinfarction” – Elevated in MI (pos.

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7 1.3 3.4 77 66 5.9 6. Trials 1057 1057 Pos Pos 6 RR RR 1641 1641 792 792 Neg Neg Pos Pos 7 RR RR .0 2.3 2.4 6.0 1. Neg Trop.7 11 00 PTS 1993 PTS 1993 Trop.0 55 44 33 22 3.TROPONINS T AND I AS PREDICTORS OF MORTALITY Cardiac Mortality 6. Neg No.9 Total Total Mortality 6.0 5.

337:1648-53 .Prognostic Significance of Cardiac Troponin N Engl J Med 1997.

Risk Stratification of Patients with ACS in ER .

US/NSTEMI Rx .

4 mg/hr x 12 hours daily – IV NTG • Beta-blocker – Metoprolol 25-50 mg PO BID • + Calcium channel blocker • ACEI for secondary prevention • Statin • Investigations: – Serial cardiac enzymes – Definitive in-hospital risk stratification. LMWH Nitrates for pain – Nitropatch 0.Management of UA/NSTEMI • • • • • 8 medication Oxygen ASA . clopidogrel Anticoagulant: UFH. .

102:1193-1209 . in addition to ASA and UFH. to patients with continuing ischemia or with other high risk features—” • “Level of the evidence: A” ACC/AHA Guideline Circulation 2000.Platelet Inhibitors in the ACS • “A platelet GpIIb/IIIa receptor antagonist should be administered.

1 9 10 5.DEATH OR MI AT 30 DAYS 18 Placebo 16.9 10.8 2 0 3.8 6 3.9 4.6 10.2 10.7 GP IIb-IIIa Inhibitor Percent of Patients 14.1 14 11.6 1.9 EPIC CAPTURE EPILOG EPISTENT PRISM-PLUS PURSUIT ACC Slide .

ANTIPLATELET Rx Class I Definite ACS with continuing Possible ACS Likely/Definite ACS Ischemia or Other High-Risk Features or planned PCI Aspirin ACC Slide Aspirin Aspirin + + Subcutaneous LMWH IV heparin + or IV heparin IV platelet GP IIb/IIIa antagonist .

Other Antiplatelet Agents: Clopidogrel Primary efficacy endpoints in the CURE trial Endpoint Clopidogrel Placebo Relative risk p value CV death/MI/stroke 9.001 The CURE Investigators.86 <0.3% 11. Role at this point in combination with 2b3a inhibitor unclear: a useful option in ASA allergic pt’ .4% 18. .4% 0.8% 0.80 <0.345: 494-502. N Engl J Med 2001.001 CV death/MI/stroke/ refractory ischemia 16.

Effect of Clopidogrel in ACS: the CURE trial .

etc.In Hospital Risk Stratification with ACS: Principles • Spectrum of risk • Features associated with poor prognosis (high probability of short term MI.) – EKG features: dynamic ST depression – Cardiac markers: increased troponin • Risk stratification refers to identifying patients at risk .

Strategies for Risk Stratification • Non-invasive – EST • Sensitivity 70% • Specificity 70% – MIBI scan • Sensitivity 86-90% • Specificity 90% • Invasive – Diagnostic coronary angiography .

Exercise Stress Testing – Positive response: horizontal 1mm ST depression and symptoms – High risk response: • Deep ST depression • Poor exercise tolerance: unable to exercise past stage 2 (<6 mins) • Exercise induced hypotension and dysrhythmias – Uninterpretable: • LBBB • Digoxin • LVH – Contra-indications: • • • • Severe Aortic stenosis Aortic dissection MI/ACS within 24 h PE .

ventricular arrhythmias Previous PCI. . 3VD. CABG or medical therapy • Indications – – – – – – UA/post MI with ongoing pain. CABG High risk non-invasive test Emerging as the strategy of choice for initial evaluation of most ACS with elevated troponins or EKG changes • Based on FRISC II. ST depresssion Hemodynamic instability CHF.Angiography • Gold standard – Defines anatomy: 1VD. TACTICS trials • Strategy needs to be individualized. 2VD. LM – Assesses LV function – Guides treatment: PCI.

Angiography .

Indications for Invasive Risk Stratification Strategy in UA/NSTEMI • Class I – – – – – – – – – Recurrent ischemia at rest despite medical Rx Elevated troponin I or T New ST depression High risk findings on non-invasive testing Depressed LV function Hemodynamic instability Sustained VT PCI within 6 months Prior CABG • In the absence of the above. either non-invasive or invasive strategy can be followed. ACC/AHA Guidelines for Management of UA/NSTEMI 2002 .

SUMMARY: ER Evaluation of Patient with Chest Pain NO Symptoms Suggestive of Cardiac Origin? YES Consider Alternative Diagnosis Stable Unstable Early Risk Stratification in ER .

RISK (4-8%) •No high risk features but >=1 of: •Ongoing chest pain •Crescendo angina •Borderline positive troponin I (0. (>5 leads) •Biochemical markers: •Troponin/CKMB abnormal •Recurrent ischemia •AMI in last 4 weeks •Hemodynamic compromise •ASA + heparin/LMWH •GP IIb/IIIa •Early cardiac cath INTERM. exertional •EKG: normal or nonspecific or unchanged •May include previous hx of CAD or risk factors •ASA •No heparin •Observe/outpt tests *30 day rate of death or MI HIGH RISK (12-30%)* . single episode.SUMMARY: Management of UA/NSTEMI •Prolonged CP (>20 minutes or ongoing). •Deep T wave inv.0) •Previous intervention: PCI or CABG •Increased baseline risk (DM. elderly) •ASA + clopidogrel •UFH or LMWH •Cardiac cath lab LOW RISK (<2%) •No high or intermediated features •Chest pain. plus: •EKG: •Transient ST changes •Sustained ST depr.4-2.

CK-MB) + one of • • • • ischemic symptoms development of pathological Q waves ECG changes suggestive of ischemia Coronary angiography .STEMI • WHO defn: 2 of – characteristic chest pain – ECG changes – ST elevation – Biochemical changes • ACC + ESC – Rise and fall of biochemical marker (Tn.

STEMI • More than 1 million MI’s per year in US • Fatal in 1/3 of pts. ½ of death occurs within 1 hr of symptoms (arrhythmias) .

upper extremity. interscapular region sometimes epigastric • pain usually implies ischemia • other sx – – – – – – nausea/vomiting more common in inferior MI weakness dizziness palpitation cold perspiration sense of impending doom . or compressing. heaviness or squeezing • can be choking. radiating to L>R side of chest. knife-like • retrosternal. shoulder. neck.Symptoms • prolonged pain > 30 min usually • constricting. ulnar sides of arms L>R. jaw. crushing. burning.

EMS ambulance AED to first responders Relief of pain to reduce sympathetic tone Rapid transfer to hospital – Prehosp fibrinolysis • Some evidence suggesting improved mortality . first response.STEMI • Pre-hospital care – EMS • • • • Dispatch.

STEMI • ER Management – Early recognition • Ischemic type chest pain • ECG signs – – – – ECG monitor rhythm IV access O2 Reperfusion strategy will depend on • • • • Time since symptoms Risk assoc with STEMI Risk of lytics Time required for PCI .

Time to Rx .

decrease preload by increasing venous capacitance • Avoid if suspect RV infarct – Beta blockers • • • • Reduce HR. decrease myocardial oxygen demand Reduce pain Reduce the need for analgesics Reduce infarct size – Oxygen .STEMI .Acute Rx • ASA – Block formation of thromboxane A2 in platelets by blocking cox – Chew 160-325 mg to allow for buccal absorption • Pain control – Try to decrease sympathetic activity – Analgesics – Nitrates • Coronary vasodilation.

STEMI .Reperfusion • “Time is muscle” • Increased mortality with delay in reperfusion regardless of strategy • Less time: – – – – Recovery of LV systolic fxn Improved diastolic dysfxn Reduced mortality Post ischemic contractile dysfxn can occur after reperfusion – Myocardial stunning .

STEMI .Lytics • Benefits – – – – – – Recanalize thrombotic occlusion Restores coronary flow Reduce infarct size Improves myocardial function Improves survival May result in microvascualr damage and reperfusion injury – STR strong predictor of reperfusion .

STEMI .lytics • GISSI first trial to demonstrate benefit of streptokinase • Other fibrinolytics – Alteplase (t-PA) • GUSTO I – Reteplace (rtPA) • GUSTO III (equivalence) – Tenecteplase (TNK) • ASSENT II (equiv with t-PA) .

000 ARR: 2% RRR: 18% Circ. 1998 .Evidence for Fibrinolysis: GISSI n >11.

000 ARR 0.9% RRR 12. 1993 .5% NEJM.Comparison of Thrombolytics: GUSTO n=>41.

ASSENT 2 • N= 16949 • Design: non-inferiority • Trend toward decrease in bleeding • Improve ease of use with Bolus infusion • Combination with heparin IV Lancet 1999. 354: 716-22 .

Time to Rx .

Lancet.Efficacy of Thrombolysis: Subgroups n=56.800 Fibrinolytic Therapy Trialists’ Group. 1988 .

Choosing a Fibrinolytic
• Patients in whom t-PA is proven superior to SK:
– Age < 75
– Anterior MI, presenting within 4 hours
– High risk/extensive MI at other site within 4 hours
– Cardiogenic shock
– Previous SK exposure
• TNK = rtPA > tPA
– Easy administration
– Lower chance of med error
– Less non-cerebral bleeds
• Patients in whom SK appears to be equivalent to t-PA:
– Inferior, posterior or lateral MI
– MI at any site after 6 hours
– Age > 75 years

Bleeding complications with Lytics
• Major bleeding 0.5-2%
• Minor bleeding: 10-20 %
• Intracranial hemorrhage: 0.5-2%
• Management:
– D/C thrombolytic
– Cryoprecipitate (fibrinogen enriched)
– If heparin, give protamine sulfate

Indications for Primary PCI
• Class I
– Alternative to thrombolytic if performed in a timely fashion by skilled
individuals
– Patients within 36 hours of AMI, with cardiogenic shock, <75 years
• Class IIa
– Contraindication to thrombolysis
• Class IIb
– NSTEMI within 12 hours, with less than TIMI II flow in infarct related
artery
• Class III
– Elective PCI of non-IRA at time of AMI
– Beyond 12 hours of symptoms, no evidence of ischemia
– Successful thrombolysis

From ACC/AHA Guidelines, 2000

STEMI -PCI • Meta analyis shows improved clinical endpoints favoring PCI – Factors to consider • • • • • • Time to treatment Risk of STEMI Cardiogenic shock Kilip class >= II Risk of bleeding Time to transport to skilled PCI center .

STEMI – Other Rx • ASA – ISIS-2 • Thienpyridines – Clopidogrel • CLARITY – Ticlopidine • Inhibit binding to adenosine diphosphate receptor • GPIIb/IIIa inhibitors – Abciximab – Tirofiban – Eptifibatide • GUSTO V – rtPA vs 1/2rtPA and abciximab – similar efficace endpoints but increased bleeds with IIb/IIIa .

000 Lancet.ASA: ISIS 2 n > 17. 1988 .

PE – reduces mortality in pts receiving lytic • LMWH – ASSENT III showed benefit over UFH in pts receiving TNK • Others – Bivalirudin (HITT) . stroke.STEMI – Other Rx • Heparin – reduces reinfarction.

STEMI Rx • BB • ACEi – – – – Prevents ventricular remodeling Improved hemodynamics Reduces CHF Selected population: (long-term. started day 3-16) • SAVE • AIRE • TRACE – Unselected pop (short term. started early) • • • • GISSI 3 SMILE ISIS-4 CCS-1 .Post.

LV dysfxn.Post. HF) – Reduction in mortality • Statins – PROVE-IT .STEMI Rx • ARB – OPTIMAAL (losartan) – VALIANT (valsartan) • Aldasterone antagonists – EPHESUS (acute MI.

Mechanical Complications of MI Variable VSD Free Wall Rupture Papillary Muscle Rupture Age 63 69 65 Days. post MI 3-5 3-6 3-5 Anterior MI 66% 50% 25% New Murmur 90% 25% 50% Thrill Yes No Rare Previous MI 25% 25% 30% Echo: VSD Pericardial Effusion Flail leaflet MR O2 step-up RA-RV Equalization of diastolic press. Prominent Vwave 90% 50% 90% ? 90% 40-90% PA catheter: Mortality: Medical Surgical .

Other Complications • Arrhythmias – Electrical instability • • • • VPB VT VF AIVR – Pump failure/inc symp drive • Sinus tachy • AFib/Flutter • SVT – Brady/conduction • Sinus brady • Junctional escape • AVB .

Other Complications • Recurrent chest pain – Distinguish reinfarction from recurrent ischemia from non-ischemic chest pain • Pericarditis • LV aneurysm .

PET – Residual potentially ischemic myocardium • Submaximal ETT – Susceptibility to vent arrhythmias .Risk Stratification • survival after STEMI depends on – LV fxn • Stress/pharma Echo.

Risk Stratification .

Discharge Planning • usually 5 days post STEMI • counseling – ambulation but avoid heavy lifting – graded activity (symptom limited) – Rehabilitation .

Questions .