What are the causes of elevated troponin levels?

Causes of Elevated Troponin

Elevated troponin levels can result from numerous cardiac and non-cardiac conditions, with the most frequent causes being tachyarrhythmias, heart failure, hypertensive emergencies, critical illness, myocarditis, Takotsubo syndrome, and valvular heart disease. 1

Primary Cardiac Causes

Acute Coronary Syndromes

• Type 1 myocardial infarction (thrombotic occlusion)
  • Elevations beyond 5-fold the upper reference limit have high (>90%) positive predictive value for acute type 1 MI 1
  • Rising and/or falling pattern (dynamic change) is characteristic of acute MI 1

Other Cardiac Causes

• Heart failure (acute and chronic) 1
• Tachyarrhythmias and bradyarrhythmias 1
• Myocarditis 1
• Takotsubo syndrome (stress cardiomyopathy) 1
• Valvular heart disease (especially aortic stenosis) 1
• Hypertensive emergencies/crisis 1
• Cardiac procedures:
  • Cardiac contusion
  • Ablation
  • Pacing
  • Cardioversion
  • Endomyocardial biopsy
  • CABG and PCI 1
• Hypertrophic cardiomyopathy 1

Non-Cardiac Causes

Vascular Conditions

• Pulmonary embolism and pulmonary hypertension 1
• Aortic dissection 1

Systemic Conditions

• Critical illness (shock/sepsis/burns) 1, 2
• Renal dysfunction and associated cardiac disease 1
  • Troponin elevation is frequently found when serum creatinine >2.5 mg/dL 1
  • Should not be primarily attributed to impaired clearance 1
• Acute neurological events:
  • Stroke
  • Subarachnoid hemorrhage 1
• Endocrine disorders:
  • Hypothyroidism
  • Hyperthyroidism 1
• Infiltrative diseases:
  • Amyloidosis
  • Haemochromatosis
  • Sarcoidosis
  • Scleroderma 1
• Drug toxicity or poisoning:
  • Doxorubicin (Adriamycin)
  • 5-fluorouracil
  • Herceptin (trastuzumab)
  • Snake venoms 1
• Extreme endurance effort 1
• Rhabdomyolysis 1
• Burns affecting >30% of body surface area 1

Interpretation of Troponin Elevation

Clinical Context is Critical

• Troponin elevation indicates myocardial injury but alone cannot establish MI diagnosis 3
• Elevations up to 3-fold the upper reference limit have limited (50-60%) PPV for AMI 1
• Rising and/or falling pattern helps differentiate acute from chronic damage 1

Prognostic Significance

• Elevated troponin is associated with increased mortality in many conditions, even non-ACS 3, 4
• In ICU patients with MI (defined by troponin elevation plus ischemic changes), mortality is significantly higher than those without MI 3

Common Pitfalls in Troponin Interpretation

1. Failing to consider non-ACS causes: Elevated troponin is not synonymous with coronary thrombosis 5

2. Inappropriate treatment: Patients with non-thrombotic troponin elevation should not receive antithrombotic and antiplatelet agents without evidence of ACS 5

3. Dismissing elevations in elderly or renal patients: These elevations often indicate underlying cardiac pathology and confer poor prognosis 2

4. Relying on single measurements: Serial testing is essential, looking for significant rise and/or fall pattern 2

5. Missing MI in critically ill patients: In the ICU setting, 47% of patients may have elevated troponin but only 26% meet criteria for MI 3

Diagnostic Approach

1. Serial measurements: Obtain troponin at presentation and 1-2 hours later (with high-sensitivity assays) or 6-12 hours later (with conventional assays) 2

2. Look for dynamic changes: A significant rise and/or fall pattern suggests acute myocardial injury 1, 2

3. Correlate with clinical presentation: Assess for ischemic symptoms, ECG changes, or new wall motion abnormalities 3

4. Consider the magnitude of elevation: Higher levels increase likelihood of ACS, but any elevation has prognostic significance 1, 2

5. Evaluate for non-ACS causes: Systematically consider other cardiac and non-cardiac conditions that may explain troponin elevation 6

By understanding the diverse causes of troponin elevation and applying a systematic approach to interpretation, clinicians can avoid misdiagnosis and ensure appropriate management of patients with elevated troponin levels.