Acute coronary syndrome : Risk stratification – markers of myocardial necrosis

1. Acute coronary syndrome : Risk stratification – markers of myocardial necrosis Paul Calle Emergency Department Ghent University Hospital Belgium

2. Introduction • ACS in ED is frequent, often difficult to recognize, a major cause of morbidity and mortality with prognosis related to early treatment high risk of suboptimal care with poor outcome high need for management strategy

3. ACS classification (focus on ECG and troponin) • ST-elevation myocardial infarction (STEMI) • non-STEMI(includes "micro-infarctions", i.e. no ECG changes, no CK-MB , only troponin ) • unstable angina (no troponin )

4. New criteria for acute, evolving or recent MI Either one of the following criteria satisfies the diagnosis for an acute, evolving or recent MI : 1. Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB) of biochemical markers of myocardial necrosis with at least one of the following: a) ischemic symptoms; b) development of pathologic Q waves on the ECG; c) ECG changes indicative of ischemia (ST segment elevation or depression); or d) coronary artery intervention (e.g. coronary angioplasty). 2. Pathologic findings of an acute MI

5. Illustrative figures (USA) • ACS accounts for only 20% among 6 million chest pain patients in ED • costs to rule out ACS : 500 to 5,000 S • missed ACS diagnosis in ED : 2 to 5%, with 30 day mortality rate of 10% • missed MI diagnosis in ED : 40% of mal-practice awards against emergency physicians • at least 20% of non-ACS patients with chest pain suffer from (potentially) life threatening diseases : aortic dissection, pulmonary embolism, stable angina, pneumothorax, ...

6. Risk stratification Patient presents with chest pain or potential chest pain equivalent (e.g. jaw, shoulder, arm, back, or epigastric pain, unexplained dyspnea, syncope, palpitations) Chest pain triage and ECG (< 10 min) Physician's history Physician's physical examination Prompt 12- or 15-lead ECG Prompt differentiation ST-segment elevation meeting fibrinolytic criteria or new/presumably new LBBB or evidence of acute posterior MI ST-segment depression > 0.5 mm or transient ST-segment elevation not meeting fibrinolytic criteria (ECG or clinical evidence of unstable angina) ECG is nondiagnostic or normalClinical suspicionof ACS Very low suspicion of ACS (modified from Pollack et al,2003)

7. Nature of presenting episode and time course Cardiac risk factors (previous MI, hypertension, lipids, smoking, diabetes, family history) and related past medical (atherosclerotic cardio-vascular disease, CVA, peripheral vascular disease) and surgical history (percutaneous coronary intervention, CABG) Comorbidities and quick review of systems (to suggest alternative diagnoses, such as lung infection or infarction, chest wall or gastro-intestinal pain) Physician's history (Pollack et al,2003)

8. Physician's physical examination • Evaluate hemodynamic status and perfusion • Lung auscultation for rales, ronchi, ... • Evaluate for possible alternative diagnoses (e.g. chest wall pain, pneumonia, pulmonary embolism, [evidence of DVT]) • Cardiac examination (Pollack et al,2003)

9. ECG for acute chest pain • Not a perfect diagnostic tool (specificity-sensitivity) • 10% of new ST-elevations are not caused by MI • Up to 50% of MI patients present with normal or inconclusive ECG (e.g. previous MI, LV hypertrophy) • 2% of patients with normal ECG will develop MI • 15-lead ECG for right ventricular or posterior MI • Request previous ECG for comparison • Serial ECGs (and continuous ST-monitoring?) improve sensitivity

10. Risk stratification Patient presents with chest pain or potential chest pain equivalent (e.g. jaw, shoulder, arm, back, or epigastric pain, unexplained dyspnea, syncope, palpitations) Chest pain triage and ECG (< 10 min) Physician's history Physician's physical examination Prompt 12- or 15-lead ECG Prompt differentiation ST-segment elevation meeting fibrinolytic criteria or new/presumably new LBBB or evidence of acute posterior MI ST-segment depression > 0.5 mm or transient ST-segment elevation not meeting fibrinolytic criteria (ECG or clinical evidence of unstable angina) ECG is nondiagnostic or normalClinical suspicionof ACS Very low suspicion of ACS Markers and ECG to confirm MI and to determine prognosis Markers and/or ECG to rule out ACS or to guide strategy therapy (modified from Pollack et al,2003)

11. The perfect marker • Marker for myocardial necrosis, and also for cardiac ischemia • Linear relationship between blood levels and extent of myocardial injury (and prognosis) • 100% sensitive • 100% specific • Immediate increase (+ constant blood level for hours to days) • Test kits : reliable, rapid, universally available and inexpensive

12. What about troponin T and I ? • Very high sensitivity for myocardial necrosis • Related to prognosis • Not 100% specific for atherosclerotic coronary artery disease • myocarditis, cardiomyopathy, myocardial contusion, ... • renal failure, auto-immune diseases, ...) • Up to 6 hours before raised blood levels no early MI diagnosis possible • Raised blood levels for many days troublesome diagnosis of re-infarction BUT

13. Role for myoglobin ? • Initial elevation : 1 to 4h after onset better early marker than troponins BUT : early myoglobin is less sensitive and less specific (due to skeletal muscle trauma) than late troponin decisions mainly based on clinical skills, ECG and late troponin (except rarely for reperfusion therapy) • Duration of elevation : 24 – 48h useful for re-infarction diagnosis

14. Role for CK-MB ? • Initial elevation comparable with troponins • Less sensitive than troponins • High specificity (comparable with troponins) • Rapid rise and fall (instead of gradual fall for troponins) allowing more accurate estimation of MI extent

15. ED strategy in chest pain patients Patient presents with chest pain or potential chest pain equivalent (e.g. jaw, shoulder, arm, back, or epigastric pain, unexplained dyspnea, syncope, palpitations) Chest pain triage and ECG (< 10 min) Physician's history Physician's physical examination Prompt 12- or 15-lead ECG Prompt differentiation STEMI Non-STEMIunstable angina Suspicion of ACS Other causes of chest pain Continuous risk-oriented ACS evaluation and treatment in ED Diagnostic workup and treatment as indicated in ICU, ward, ED or asoutpatient Start appropriate treatment and send patient to CCU or cath lab (modified from Pollack et al,2003)

16. TIMI risk score 1 point each for presence of : • Age > 65 years • Documented prior coronary artery stenosis > 50% • Three or more conventional cardiac risk factors (e.g. age, sex, family history, hyperlipidemia, diabetes, smoking, obesity) • Use of aspirin in the preceding 7 days • Two or more anginal events in the preceding 24h • ST-segment deviation (transient elevation or persistent depression) • Increased cardiac biomarkers Score 5 – 7 :high risk Score 3 – 4 :intermediate risk Score 0 – 2 :low risk (Pollack et al, 2003)

17. Conclusions • The diagnosis of ACS during the first few hours of evolution is a difficult task that challenges the best of (emergency) physicians. • Critical decisions should be based on much more elements than biomarkers. • For emergency physicians, the most difficult and medicolegally risky decisions center on how to minimize the costs to the healthcare system without jeopardizing the quality of care provided to patients with atypical symptoms and/or inconclusive ECG.Chest pain center