Cardiac Biomarkers

1. Mechanism of Release

• Intracellular location (cytoplasmic vs. bound to structural complexes)
• Molecular weight
• Local blood and lymphatic flow

2. Cardiac Troponins (cTnI and cTnT) — Gold Standard

• Cardiac troponin I (cTnI) and troponin T (cTnT) have amino-acid sequences distinct from skeletal muscle isoforms, enabling highly specific monoclonal antibody assays.
• Neither is released with skeletal muscle injury alone.

• A rising and/or falling pattern with ≥1 value above the 99th percentile upper reference limit (URL) of a normal reference population.

• Preferred over conventional assays — greater negative predictive value.
• Rapid rule-out protocols using serial testing over 1–2 hours perform well for ACS diagnosis.
• At presentation >2–3 h after symptoms: a very low hs-cTn (single sample) can exclude MI with NPV >99%.
• In STEMI: less immediately impactful since reperfusion decisions are made before lab results return.

3. Non-Ischemic Causes of Troponin Elevation ("Troponin Leak")

Key principle: Rising and falling kinetics (delta troponin) distinguish acute myocardial injury from chronic elevation. A stable, modestly elevated troponin suggests chronic structural disease rather than AMI.

4. Creatine Kinase-MB (CK-MB)

• Historically the standard for AMI diagnosis; now largely superseded by troponin.
• CK-MB relative index (CK-MB mass / total CK activity ≥2.5%) suggests myocardial rather than skeletal source — but not diagnostic alone.
• Remains useful for detecting early re-infarction: because CK-MB clears more rapidly than troponin (returns to baseline in ~48–72 h), a new rise in CK-MB during a period of still-elevated troponin suggests reinfarction.
• Limitation: Elevated in severe skeletal muscle injury, liver, diaphragm, or intestinal trauma — unreliable in multi-trauma patients.
• Not cost-effective to measure CK-MB alongside troponin routinely.

5. Myoglobin

• Earliest marker: rises within 1–2 hours of AMI onset.
• Highly sensitive but not specific — also released from skeletal muscle.
• Serum half-life: 1–3 hours; absent after ~24 hours.
• No longer recommended as a standalone diagnostic tool; largely replaced by hs-cTn.

6. B-type Natriuretic Peptide (BNP) and NT-proBNP

• Diagnosis of heart failure: BNP/NT-proBNP is the preferred biomarker; elevated levels support HF diagnosis when assessed alongside history and exam.
• Risk stratification in ACS: BNP provides incremental prognostic information in acute MI.
• Pulmonary embolism: BNP is a prognostic (not diagnostic) marker for PE — reflects RV wall stress.
• Preoperative cardiac risk: Canadian Cardiovascular Society (CCS) 2017 guidelines recommend BNP/NT-proBNP for further risk stratification before non-cardiac surgery.

• BNP: EDTA-anticoagulated whole blood or plasma (plastic tubes only).
• NT-proBNP: serum, heparin plasma, or EDTA plasma acceptable; more assays available globally.

• BNP <100 pg/mL: HF unlikely
• BNP >400 pg/mL: HF probable
• NT-proBNP age-adjusted cut-offs apply (>450 pg/mL for <50 yrs; >900 for 50–75 yrs; >1800 for >75 yrs)

7. Summary Comparison Table

8. Sampling Protocol

• Conventional troponin: measure at presentation and repeat at 3–6 hours; additional measurements if clinical suspicion persists.
• High-sensitivity troponin: measure at presentation and repeat at 1–3 hours (0h/1h or 0h/2h algorithms validated).
• Serial delta-troponin (the change between samples) is as important as absolute values — a significant rise or fall defines acute injury.

Key Clinical Pearls

1. Troponin is the preferred biomarker for AMI; hs-cTn assays are preferred over conventional where available.
2. Context matters: always interpret troponin in light of clinical probability, ECG, and serial kinetics — an elevated troponin does not equal MI.
3. CK-MB retains a niche role for diagnosing reinfarction during the troponin-elevated window.
4. BNP/NT-proBNP are not for diagnosing AMI — they assess myocardial wall stress and are used for HF and risk stratification.
5. In renal failure, cTnT is chronically elevated — use cTnI and serial delta values.
6. In trauma, troponin I is preferred over CK/CK-MB (EAST guideline Level 2: normal troponin + normal ECG rules out significant blunt cardiac injury).