Role of Cardiac Troponin Testing in COVID-19

Introduction

• High-sensitive cardiac troponin (hs-cTn) is a marker of myocardial injury, regardless of cause.
• Elevated hs-cTn does not confirm acute myocardial infarction (MI) on its own.
• Causes of increased hs-cTn include:
  • Ischaemic: myocardial infarction
  • Non-ischaemic: myocarditis
• A rise and/or fall of hs-cTn levels must be interpreted with:
  • Clinical judgment
  • Signs and symptoms
  • ECG findings

In patients with COVID-19:

• Elevated hs-cTnI/T was found in 12–28% of hospitalised patients.
• These patients were typically older and had more comorbidities (e.g. hypertension, coronary artery disease, diabetes).
• Higher troponin levels were associated with:
  • Increased ICU admissions
  • Increased in-hospital mortality

Mechanisms of Troponin Elevation in COVID-19

Proposed causes of myocardial injury:

• Direct myocardial damage via:
  • SARS-CoV-2 binding to ACE2 receptors
  • Downregulation of ACE2 expression
• Resulting physiological changes:
  • Angiotensin II upregulation
  • Imbalance between Angiotensin II and Angiotensin 1-7
• These changes contribute to:
  • Endothelial dysfunction
  • Cytokine storm
  • Oxidative stress
  • Coagulopathy
  • Indirect myocardial damage

These mechanisms are inferred from experience with the original SARS virus.

Clinical Use of Cardiac Troponins in COVID-19

Risk Factors and Diagnostic Utility:

• Patients with pre-existing CAD and cardiovascular risk factors are at increased risk for acute coronary syndromes during COVID-19.
• Type 2 MI may occur due to an imbalance in oxygen supply and demand, triggered by:
  • Hypoxia
  • Fever
  • Tachycardia
  • Endocrine disturbances
• COVID-19 may also precipitate Type 1 MI through:
  • Plaque rupture
  • Thrombus formation

Insights from Clinical Studies:

• Although early guidance recommended hs-cTn testing only in patients with known CAD, later studies suggest broader use can:
  • Detect myocardial injury
  • Aid in risk stratification

Wuhan University Study (n=461):

• Patients with cardiac injury required:
  • Non-invasive ventilation: 46.3% vs 3.9%
  • Invasive ventilation: 22.0% vs 4.2%
• More complications seen in patients with elevated hs-cTn:
  • ARDS
  • Acute kidney injury
  • Coagulation disorders

Zhou et al. Cohort (n=191):

• Univariable odds ratio for death with elevated hs-cTnI: 80.1
  • 95% CI: 10.3–620.4
• For comparison:
  • D-dimer >1 mg/L → odds ratio: 20.04
• hs-cTnI was not included in multivariable analysis

Clinical Recommendations

• Cardiac troponins, especially hs-cTnI or hs-cTnT, are considered:
  • Key diagnostic and prognostic tools during the COVID-19 pandemic
• Elevated hs-cTn should prompt:
  • Careful consideration before ordering further investigations
  • Interpretation in clinical context, alongside ECG and symptom evaluation

References

1. Chapman AR, Bularga A, Mills NL. Circulation, 2020; 141: 1733–1735.
2. Januzzi JL. American College of Cardiology Magazine, 2020.
3. Tersalvi G et al. Journal of Cardiac Failure, 2020; 26(6): 470–475.
4. Shi S et al. JAMA Cardiology, published online March 25, 2020.
5. Zhou F et al. Lancet, 2020; 395: 1054–62.