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Acute Coronary Syndrome Muhammad Asim Rana MRCP(UK) Worldwide Statistics Each year: > 4 million patients are admitted with unstable angina and acute MI > 900,000 patients undergo PTCA with or without stent Myocardial Ischemia Spectrum of presentation silent ischemia exertion-induced angina unstable angina acute myocardial infarction STEMI NSTEMI Cumulative 6-month mortality from ischemic heart disease Deaths / 100 pts / month 25 N = 21,761; 1985-1992 Diagnosis on adm to hosp 20 15 Acute MI Unstable angina Stable angina 10 5 0 0 1 2 3 4 5 Months after hospital admission Duke Cardiovascular Database 6 Percentage of deaths from heart disease others 23% ACS 48% Hypertension 5% CHF 5% Atherosclerosis 2% 0.5% 0.5% Stroke Myocardial infarction remains a major cause of death despite contemporary therapeutic strategies. Diagnosis in the intensive care unit is challenging, but is essential to target therapy accurately. In patients admitted to the intensive care unit, myocardial infarction is observed to occur frequently, often without being clinically apparent, with a high associated mortality. Myocardial infarction (MI) in the critically ill presents a diagnostic challenge to the physician and is associated with a particularly adverse outcome for the patient. Such patients have high metabolic demands and are often subject to sustained adverse physiology. Typical signs and symptoms can be difficult to elicit and surrogate physiological markers of impaired coronary perfusion masked or misinterpreted in the context of the index pathology. Cardiac troponin measurements and the 12lead echocardiogram (ECG) remain sensitive in this setting, but specificity decreases, resulting in diagnostic uncertainty. Recent consensus guidelines from the European Society of Cardiology, American College of Cardiology Foundation, American Heart Association and World Heart Federation emphasise the role of cardiac biomarkers in defining MI. Diagnosis requires a rise and/or fall in serum levels (preferably troponin) together with evidence of myocardial ischaemia defined: clinically by patient history; electrocardiographically (new ST-T wave changes, new left bundle branch block or evolving pathological Q waves); or by imaging evidence of new regional wall motion abnormality. Acute Coronary Syndrome Definition The term ACS refers to a spectrum of presentations caused by myocardial ischemia that includes Unstable Angina Non ST elevation myocardial infarction ST elevation myocardial infarction Ischemic Heart Disease Evaluation Based on the patient’s History / Physical exam Electrocardiogram Biochemical markers Patients are categorized into 3 groups Non-cardiac chest pain Unstable angina Myocardial infarction (STEMI,NSTEMI) Acute Coronary Syndrome The embracing term reflects the common pathophysiology of plaque disruption Intravascular thrombosis and Impaired myocardial blood supply STEMI is the result of complete epicardial occlusion following plaque disruption & leads to propagation of thrombus & epicardial vasoconstriction NSTEMI is incomplete & transient epicardial occlusion with platelet-rich & phasic distal embolisation Pathophysiology Pathophysiology (cont’d) Pathophysiology (cont’d) Formation of haemostatic plaque Patients withClinical an ACS mayFeatures complain of a new onset of Exertional chest pain Chest pain at rest or A deterioration of pre-existing angina. However, some patients present with atypical features including Indigestion Pleuritic chest pain or Dyspnoea Diagnosis ECG Biochemical Markers The Cardiac Troponin Complex Myoglobin Creatinine-Kinase MB ECG Biochemical markers Unstable Angina Anti-platelet Therapy Abciximab (Abciximab is a monoclonal antibody that binds tightly to GP (glycoprotein) IIb/IIIa receptors and has a long half-life) EPIC Trial effective in preventing death, MI, and abrupt closure associated with coronary angioplasty Unstable Angina Anti-platelet Therapy Abciximab CAPTURE At 30 days, there was a 29% reduction in the primary composite endpoint of death, MI, or urgent revascularization in the abciximab group Lancet 1997;349:1429-1435 Unstable Angina Anti-platelet Therapy Tirofiban (Tirofiban is a small non-peptide that rapidly blocks the GPIIb/IIIa receptors and is reversible in 4–6 hours) PRISM (Platelet Receptor Inhibition for Ischemic Syndrome Management) 3,200 patients with unstable angina were treated with either heparin or tirofiban At 48 hours, there was significant risk reduction (5.9% to 3.6%) in the rate of death, MI, or refractory ischemia. N Engl J Med 1998;338:1498-505 Unstable Angina Anti-platelet Therapy Tirofiban PRISM -PLUS (Platelet Receptor Inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms) randomized 1,915 patients with UA and non-QMI to tirofiban alone, heparin alone, or a combination of the two (all received aspirin) N Engl J Med 1998;338:1488-97 Unstable Angina Anti-platelet Therapy Eptifibatide (Eptifibatide is a cyclic peptide that selectively inhibits GPIIb/IIIa receptors, but has a short half-life and wears off in 2–4 hours.) PURSUIT (Platelet IIb/IIIa Underpinning the Receptor for Suppression of Unstable Ischemia Trial) ~11,000 patients admitted with unstable angina or nonQ-wave myocardial infarction a broad-based trial encompassing a variety of clinical practices and practice styles NEJM 1998;339:436-443 10/98 MedSlides.com 36 Unstable Angina Anti-platelet Therapy Eptifibatide PURSUIT randomized to eptifibatide or placebo; all patients received aspirin and heparin significantly reduced the risk of death and MI at 30 days from 15.7% to 14.2%, a 9% risk reduction NEJM 1998;339:436-443 10/98 MedSlides.com 37 Unstable Angina Anti-platelet Therapy Summary the four “P trials” (PRISM, PRISM-PLUS, PARAGON, PURSUIT) all show reduction of death rate between 1.3% and 3.4% - in addition to the benefit of aspirin useful in the management of patients with unstable angina and MI without ST elevation Unstable Angina Anti-coagulant Therapy Heparin recommendation is based on documented efficacy in many trials of moderate size meta-analyses of six trials showed a 33% risk reduction in MI and death, but with a two fold increase in major bleeding Titrate PTT to 2x the upper limits of normal 1. Circulation 1994;89:81-88 2. JAMA 1996;276:811-815 Unstable Angina Anti-coagulant Therapy Low-molecular-weight heparin advantages over heparin: better bio-availability higher ratio (3:1) of anti-Xa to anti-IIa activity longer anti-Xa activity, avoid rebound induces less platelet activation ease of use (subcutaneous - qd or bid) no need for monitoring ESSENCE Trial incidence of death, MI, or recurrent angina 25 Day 14 Day 30 25 20 20 15 23.3% 19.8% 19.8% 16.6% P=0.016 15 P=0.019 10 10 5 5 n=1564 n=1607 n=1564 n=1607 0 0 heparin Lovenox heparin Lovenox N Eng J Med 1997;337:447-452 ACS Clinical Diagnosis MONA: Morphine + antiemetic Oxygen Nitrates Aspirin 300 mg stat About 33% of patients with ACS and normal CK (and no ECG changes of infarction) have elevated cTn. Such patients with elevated cTn are, however, four times more likely to suffer further infarction or death in the next 30 days. Blood Tests: Troponin at 12 hours after onset of pain, U&E, cholesterol, FBC, coagulation Admission or subsequent ECG Relationship between cardiac troponin I levels and risk of death in patients with the acute coronary syndrome (ACS). High Risk ECG changes: (2 or more contiguous leads) ST depression > 1mm T inversion > 1mm Transient BBB Minor/ transient ST elevation High Risk Clinical features: Ongoing rest pain. Haemodynamic instability. Arrythmias NO Troponin Elevated? Inconclusive NO ZO Consider further investigations: Perfusion scan Angiography Cardiology Referral Able to exercise ? YES Exercise Tolerance Test Normal Low Risk (Discharge) Positive High Risk TIMI Score One point is scored for each variable 0- 2 : Low risk 3- 4 : Intermediate risk 5-7 : High risk High Risk ECG changes: (2 or more contiguous leads) ST depression > 1mm T inversion > 1mm Transient BBB Minor/ transient ST elevation High Risk Unstable Ongoing pain Dynamic high risk ECG changes GPIIbIIIa inhibitors. Consider urgent cardiac cath. Consider pre-morbid state and suitability for revascularisation. High Risk Clinical features: Ongoing rest pain. Haemodynamic instability. Arrythmias Troponin Elevated High Risk 1. 2. 3. 4. LMWH Clopidogrel 300 mg stat, 75mg OD Aspirin 75 mg OD Beta Blockers: metoprolol 25 mg tds 5. Hyperglycaemic control DIGAMI protocol, if RBS > 10 mmol 6. Morphine and / or IV nitrates if continuing pain, titrate to pain and blood pressure. High Risk Stable Cardiac Cath. consider premorbid state and suitability for revascularisation Acute STEMI ECG criteria 1 mm ST elevation in at least 2 limb leads 2 mm ST elevation in at least 2 precordial leads LBBB with typical clinical presentation Immediate Triage 12 Lead ECG Showing thrombolyseable criteria Definite STEMI Extra ECG requirements Inferior ST elevation Do Rt. ECG Posterior changes Posterior ECG Primary PCI Thrombolysis (if PCI unavailable immediately) Target < 20 min Door-needle time in > 75% patients MONA: Morphine + antiemetic Oxygen Nitrates Aspirin 300 mg stat Ix on admission U&E, FBC, Cholest, coagulation Repeat 12 hrs Troponin, ECG Control RBS Tenectoplase (TKN-tPA) Drug of choice with LMWH for pts <75 yrs independent of site of infarct Streptokinase (SK) Consider for pts > 75 yrs due to lower incidence of ICH Repaeat ECG 90 min from comencement of lytic Aim: > 50% reduction in peak ST segment elevation REASSESS Risk assessment & secondary prevention Aspirin Statin Early beta blokade Ace- inhibitors ETT or angiogram pre discharge Rehablitation Consider patient’s pre morbid state & suitability for revascularisation Failed Reperfusion Haemodynamics compromise Continuing pain Disscuss suitability for rescue PCI There is no evidence of benefit from readministration of thrombolysis Contraindications to thrombolysis ABSOLUTE RELATIVE Active GI Bleed Aortic Dissection Previous ICH Stroke<2 months Intracranial aneurysm/ neoplasm Head injury<2 months Pericarditis Pancreatitis Warfarin/INR>3 Traumatic CPR Surgery<10 days Arterial Puncture<24 hrs SBP>180 Bleeding Tendency Trauma Pregnancy Bacterial Endocarditis Contraindications vary slightly between thrombolytics Thrombolysis not suitable Thrombolysis Contraindicated or Cardiogenic shock Patient presented >12 hrs LMWH Nitrates & Morphine Admit in ICCU Risk assessment & secondary prevention Aspirin Statin Early beta blokade Ace- inhibitors ETT or angiogram pre discharge Rehablitation Thank you very much