July 2020
Dr Marita du Plessis – Chemical Pathologist
Ampath | ampath.co.za

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.

📌 For more information, please contact your local Ampath pathologist.

✅ Let me know when you're ready for the next Lab Update!

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Lab Update 18.2 – Role of Cardiac Troponin Testing in COVID-19

July 2020
Dr Marita du Plessis – Chemical Pathologist
Ampath | ampath.co.za

Introduction

• High-sensitive cardiac troponin (hs-cTn) is a marker of myocardial injury, regardless of the mechanism.
• Increased hs-cTn does not equal acute myocardial infarction (MI).
• Elevated hs-cTn can result from:
  • Ischaemic causes: e.g. myocardial infarction
  • Non-ischaemic causes: e.g. myocarditis
• Diagnosis of acute MI requires:
  • Rise/fall of hs-cTn
  • Clinical judgement
  • Symptoms and ECG changes

In COVID-19:

• 12–28% of hospitalised patients showed elevated hs-cTnI/T.
• These patients were generally:
  • Older
  • More likely to have comorbidities (hypertension, CAD, diabetes)
• Higher troponin levels correlated with:
  • Increased ICU admissions
  • Higher in-hospital mortality

Mechanisms of Troponin Elevation in COVID-19

These are based on experience with SARS-CoV-1 and not yet fully understood for SARS-CoV-2.

Direct myocardial injury (most likely mechanism):

• Viral binding to ACE2 receptors, allowing cell entry and causing direct myocyte injury
• Downregulation of ACE2 expression, resulting in:
  • Angiotensin II upregulation
  • Imbalance with Angiotensin 1-7

This leads to:

• Endothelial dysfunction
• Cytokine storm
• Oxidative stress
• Coagulopathy
• Indirect myocardial damage

Potential Use of Cardiac Troponins in COVID-19

Clinical context:

• Patients with pre-existing coronary artery disease (CAD) or cardiovascular risk factors are at increased risk for acute coronary syndrome during infection.
• Type 2 MI may result from:
  • Oxygen supply/demand mismatch due to:
    • Hypoxia
    • Fever
    • Tachycardia
    • Endocrine dysregulation
  • This may unmask underlying CAD.
• Type 1 MI may also occur via:
  • Plaque rupture
  • Thrombus formation

Troponin testing insights:

• The American College of Cardiology initially recommended troponin testing only in known CAD patients.
• Later evidence suggests hs-cTn testing helps:
  • Detect myocardial injury
  • Risk stratify patients at admission

Supporting Clinical Studies

Wuhan University Study (n = 461):

• Cardiac injury patients required:
  • Non-invasive ventilation: 46.3% vs 3.9%
  • Invasive ventilation: 22.0% vs 4.2%
• Also had more complications:
  • Acute respiratory distress syndrome (ARDS)
  • Acute kidney injury
  • Coagulation disorders

Zhou et al. Study (n = 191):

• Univariable odds ratio for death with hs-cTnI above the 99th percentile:
  • 80.1 (95% CI: 10.3–620.4)
• For comparison:
  • D-dimer >1 mg/L: odds ratio = 20.04 (95% CI: 6.52–61.56)
• Note: hs-cTnI was not included in multivariable analysis

Clinical Recommendations

• hs-cTn is a critical diagnostic and prognostic marker during COVID-19.
• Elevated levels should not automatically trigger further cardiac investigations.
• Results must be interpreted with:
  • Clinical signs and symptoms
  • ECG findings
  • The degree and trend of troponin elevation

UK cardiologists emphasise hs-cTn as an “ally and a crucial diagnostic and prognostic aid” during the pandemic.

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.

📌 For more information, contact your local Ampath pathologist.

✅ Let me know when you're ready to continue with the next Lab Update!

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