Diagnosis of Acute Coronary Syndrome
Geneviève Dufresne PGY-2, Montfort Unit
Acute Coronary Syndrome
Life-threatening event
Encompass a continuum that ranges from
unstable angina to the most severe MI (irreversible necrosis of heart muscle)
Acute Coronary Syndrome
Vast majority of MI’s (over 90%) result from
disruption of an atherosclerotic plaque with subsequent platelet aggregation and formation on an intracoronary thrombus which causes obstruction of the vessel lumen Formation of either complete or partial occlusion Incomplete occlusion of the vessel lumen is typically the cause of unstable angina and NSTEMI (no myocardial necrosis) where complete occlusion causes STEMI
Consequences of Coronary Thrombus
Coronary thrombus Small thrombus (nonflow-limiting) Partially occlusive thrombus Transient ischemia ST segment depression and/or T wave inversion Occlusive thrombus Prolonged ischemia
No ECG changes
ST elevation (Q waves later)
- Serum biomarkers Healing and plaque enlargement
+ Serum biomarkers
+ Serum biomarkers
Unstable angina
Non-ST-segment elevation MI
ST segment elevation MI
Adapted from Lilly, LS. Pathophysiology of Heart Disease, 3rd Edition.
Diagnosis of ACS – Hx & PE
Chest pain with or without radiation
Diaphoresis Nausea, vomiting Weakness Pain response to nitrates S4 (atrial contraction into a noncompliant ventricule) S3 if CHF present (failing LV systolic function) Systolic murmur if MR or VSD Pulmonary rales if CHF present Jugular venous distension if RV MI
Differential diagnosis of chest pain
Pericarditis
– Pleuritic pain varying with position, friction rub on auscultation, diffuse ST elevations
Aortic Dissection
– Tearing pain that migrates, asymmetry of arm BP, widened mediastinum
Pulmonary Embolism
– Localized pleuritic pain, dyspnea, possible pleural rub, predisposing factors for thrombosis
Differential diagnosis of chest pain
Pneumonia
– Pleuritic pain, cough, sputum, abnormal auscultation and chest percussion, CXR findings
Pneumothorax
– Sudden sharp unilateral pleuritic pain, decreased breath sounds and hyperresonance, CXR findings
Esophageal spasm
– RSP worse with swallowing, hx of dysphagia
Acute cholecystitis
– RUQ pain, nausea, hx of fatty food intolerance
Diagnosis of ACS
Prompt evaluation is the key (increased survival if transfer for urgent PCI within 90 minutes of infarct) Cardiac monitor to determine rhythm STAT 12-lead ECG – ST depressions or elevation, T wave inversion, presence of Q waves 15-lead ECG if inferior findings (r/o right heart MI) STAT Cardiology consult
STAT CXR CBC, Chem7, CKMB, urinalysis, possibly liver enzymes TnT – peaks at ~8 hours after onset of pain Serial TnT (q 8 hours x 2-3 after initial) If uncertain of time of onset of pain, get baseline TnT and then serials x 24h Transfer to tertiary cardiac center for urgent PCI prn Echocardiogram if not transferred
Management strategies in ACS
Chest pain consistent with ACS
ECG
No ST elevation (UA/NSTEMI)
ST elevation (STEMI)
Anti-thrombotic approach 1.Aspirin 2.IV Heparin or LMWH 3.Clopidogrel 4.High-risk patients: - GPIIb/IIIa inhibitor - Proceed to cardiac cath
1.Anti-ischemic medications - Beta-blockers - Nitrates - CCB prn 2.General measures - Bed rest in ICU - Oxygen - Pain control (morphine) 3.Additional therapy - ACE Inhibitor - Statin
Reperfusion approach 1.Aspirin 2.PCI or thrombolytic therapy 3.IV Heparin (tPA, rPA, TNK-tPA)
Adapted from Lilly, LS. Pathophysiology of Heart Disease, 3rd Edition.
Diagnosis of ACS - CKMB
CK reversibly transfers phosphate group from
creatine phosphate to ADP, producing ATP 3 isoenzymes – CK-MM (muscles), CK-BB (brain), CK-MB (predominantly heart and also uterus, prostate, gut, diaphragm and tongue) 1-3% of CK-MB in musculoskeletal tissue Level rises 3-8h post infarct, peaks at 24h and returns to normal within 48-72h Other non-cardiac conditions that raise CK-MB do not usually show delayed peaking pattern
Diagnosis of ACS – TnT
Regulatory protein in muscle cells that control
interactions between myosin and actin Virtually absent in healthy people therefore increased sensitivity Much more sensitive marker than CK-MB Preferred cardiac marker Start rising 3-4h following MI, peak between 1836h, slowly decline but persist for up to 10-14d
TnT for Evaluation and Management of ACS
Advantages
• • • • • Risk Stratificaton Sens/Spec > CKMB Sens/Spec Detect Recent MI Selection of Rx Detect Reperfusion
Disadvantages
• Low sens. early (< 6h) sens. • Repeat at 8-12 h if neg. 8• Limited ability to detect late minor reinfarction
Recommendation • Useful as single test to efficiently Dx NSTEMI • Clinicians should familiarize themselves with Dx “cutoffs” in local lab
Antman et al JAMA 284 : 835, 2000
Evolution of Cardiac Markers during acute MI
Evolution of Cardiac Markers
50
Multiples of MI threshold
20 10 5 2 1 0 1 2
Cardiac troponin CK-MB CK-
MI threshold
3 4 5 6 7 8 Days After Onset of AMI
9
10
Adapted from Lilly,LS. Pathophysiology of Heart Disease, 3rd Edition.
Differential diagnosis of elevated TnT and normal CK
False +, not due to myocardial necrosis
– – – – – – – – – Myocarditis Toxic CMP Severe CHF Pulmonary embolism RV microinfarctions (acute resp distress) Cardiac trauma Sepsis SAH Renal failure
Determination of risk - TIMI Score
What is the TIMI Score?
– « Thrombolysis in Myocardial Infarction » risk score – Simple prognostic tool to categorize a patient’s risk of death and ischemic events , and provides a basis for therapeutic decision- making – Stratifies patients as « low », « intermediate » or « high » risk of death or future events – Event rates increased significantly as the TIMI risk score increased (JAMA. 2000;284:835-842) – www.timi.org – www.mdcalc.com
TIMI Score
Score of 0 – 2: low risk Score of 3 – 4: intermediate risk Score of 5 – 7: high risk Risk scores of 5 to 7 - more likely to have a severe
culprit stenosis (81% vs 58%, P < .001) and multivessel disease (80% vs 43%, P < .001) compared to those with scores of 0 to 2 The probability of left main disease, visible thrombus, and impaired flow in the culprit lesion also increased progressively with rising risk scores
Am Heart J. 2005 May;149(5):846-50
TIMI Score
The TIMI risk score identifies patients who
are more likely to have intracoronary thrombus, impaired flow, and increased burden of coronary atherosclerosis. These findings likely explain in part the particular benefit of potent antithrombin and antiplatelet agents among patients with higher risk scores.
Am Heart J. 2005 May;149(5):846-50
TIMI Score for UA/NSTEMI
Age ≥ 65 years? Yes +1 ≥ 3 CAD risk factors (FHx, HTN, chol, DM, active
smoker)? Yes +1 Known CAD (stenosis ≥ 50%)? Yes +1 ASA use in the past 7 days? Yes +1 Recent (less than 24h) severe angina? Yes +1 Positive cardiac markers? Yes +1 ST deviation ≥ 0.5 mm Yes +1
Risk Score = Total points (0-7)
TIMI Score for UA/NSTEMI (2)
Evaluates risk of cardiac events 14 days post ACS
Risk Score Death or MI Death (all causes), (%) MI or urgent revascularization (%) 3 5 3 5 7 12 19 8 13 20 26 41
0/1 2 3 4 5 6/7
TIMI Score for STEMI
Age ≥ 65 years?
– < 65 +0 – 65-74 +2 – ≥ 75 +3 DM or HTN or Angina? Yes +1 SBP < 100 mmHg? Yes +3 HR > 100 bpm? Yes +2 Killip Class II-IV (rales + S3, pulm. edema, shock)? Yes +2 Weight < 67 kg (147.7 lbs)? Yes +1 Anterior ST Elevation or LBBB? Yes +1 Time to Treatment > 4 hrs? Yes +1
TIMI Score for STEMI (2)
Evaluates % of mortality 30-days post event Risk score = Total points (0-14)
Risk Score 0 1 2 3 4 5 6 7 8 >8 30-Day Mortality (%) 0.8 1.6 2.2 4.4 7.3 12 16 23 27 36
Other biomarkers of ACS - Myoglobin
Heme protein released into the circulation
after myocardial injury Can be detected 1 – 4 hours post MI, earlier than CK-MB and TnT Rapid clearance of this molecule and low specificity for myocardial damage limit its diagnostic value
Other biomarkers of ACS - LDH
Lactate dehydrogenase – enzyme catalyzes
the reversible formation of lactate from pyruvate Non specific marker for myocardial necrosis Peak levels 3-5 days after MI
Other Biomarkers of ACS - BNP
B-type Natriuretic Peptide is a circulating cardiac
hormone released mainly from the ventricules in response to increased wall stretch Measurement of N-terminal-proBNP Sensitive marker of LV dysfunction Improves early risk stratification of patients with ACS as strongly predictive of short-term mortality in patients with ACS No targeted therapeutic strategies developed yet
Circulation. 2004;110:128-134
Circulation. 2002;106:2913-2918.
Other biomarkers of ACS – Cystatin C
Cysteine protease inhibitor involved in the
catabolism of proteins Shown to be a better marker of GFR than creatinine Significantly improved the early stratification of patients with suspected of confirmed ACS (NSTEMI) Higher levels of Cystatin C increased the risk of death post event
Circulation. 2004;110:2342-2348.
Other references
Circulation. 2005;112:812-818.
– “Serum Soluble Lectin-like Oxidized LDL Receptor-1 Levels are Elevated in Acute Coronary Syndrome” Circulation. 2004;110:1586-1591 – “Circulating Endothelial Cell Count as a Diagnostic Marker for Non-ST-Elevation Acute Coronary Syndromes” Circulation. 2006;114:2251-2260. – “Coronary Multidetector Computed Tomography in the Assessment of Patients With Acute Chest Pain“