What are the non-ischemic causes of elevated troponin (cardiac biomarker) levels?

From the Guidelines

Elevated troponin levels can occur in numerous conditions beyond myocardial ischemia, including heart conditions like myocarditis, pericarditis, heart failure, and cardiomyopathies, as well as systemic conditions such as sepsis, pulmonary embolism, and severe respiratory infections, emphasizing the need for a comprehensive differential diagnosis. Non-ischemic causes of elevated troponin levels are diverse and can include:

• Heart conditions: myocarditis, pericarditis, heart failure, cardiac contusion from trauma, and cardiomyopathies 1
• Systemic conditions: sepsis, pulmonary embolism, severe respiratory infections, and critical illness 1
• Renal failure, which reduces troponin clearance 1
• Other causes: strenuous exercise, tachyarrhythmias, cardiac procedures or surgeries, certain medications (like chemotherapy drugs), and stroke or subarachnoid hemorrhage through neurogenic mechanisms 1

When evaluating elevated troponin levels, it is crucial to consider the clinical context, as the pattern of elevation often differs from the typical rise and fall seen in acute coronary syndromes. Management should focus on treating the underlying condition rather than assuming coronary artery disease is present, though cardiac ischemia should always be considered in the differential diagnosis. The most recent guidelines, such as the 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation, highlight the importance of considering non-ischemic causes of troponin elevation, including tachyarrhythmias, heart failure, hypertensive emergencies, critical illness, myocarditis, and valvular heart disease 1.

From the Research

Causes of Elevated Troponin

• Cardiac conditions:
  • Heart failure 2, 3, 4
  • Dysrhythmia 2
  • Dissection 2
  • Myocarditis 5, 4, 6
  • Pericarditis 5
• Non-cardiac conditions:
  • Pulmonary embolism 2, 3, 4, 6
  • Sepsis 2, 3, 4, 6
  • Stroke 2
  • Renal failure 3, 4, 6
  • Physical exertion 6
  • Inflammatory heart disease 6
  • Chronic renal failure 6
  • Systemic inflammatory response 6

Mechanisms of Troponin Elevation

• Myocyte injury and necrosis 2
• Myocyte apoptosis and cell turnover 2
• Oxygen supply demand mismatch 2
• Reversible or irreversible cardiomyocyte injury 6

Clinical Considerations

• Clinicians should consider the clinical context, patient symptoms, electrocardiogram, and ultrasound in their assessment of the patient with troponin elevation 2
• Elevated troponin is a marker for poor outcomes, including increased rates of mortality 2
• Troponin elevation in the absence of thrombotic acute coronary syndromes still retains prognostic value 4