Can infection cause elevated troponin levels in a patient with chest pain?

Can Infection Cause Elevated Troponin?

Yes, infection can definitively cause elevated troponin levels through multiple mechanisms including type 2 myocardial infarction from supply-demand mismatch, direct viral myocardial injury, systemic inflammatory response, and sepsis-induced myocardial stress. 1, 2

Mechanisms of Infection-Related Troponin Elevation

Infections trigger troponin release through several distinct pathways:

• Supply-demand mismatch (Type 2 MI) occurs when severe respiratory distress, hypoxemia, or tachycardia creates an oxygen imbalance in the myocardium without coronary artery occlusion 1, 3

• Direct viral cytopathic effects can cause myocardial injury, particularly observed in COVID-19 and influenza infections where the virus directly damages cardiac myocytes 1

• Systemic inflammatory response during infections triggers cytokine release syndrome that can lead to microinfarction and myocardial stress 3

• Sepsis is the strongest independent predictor of troponin elevation in non-coronary artery disease patients, causing inflammatory mediators and demand ischemia 3, 2

Clinical Prevalence and Significance

The frequency of infection-related troponin elevation varies by infection type and severity:

• COVID-19 infections show troponin elevations in 5-25% of hospitalized patients, with higher prevalence (up to 25%) in those admitted to intensive care units 3

• Influenza infection during the 2017-2018 season demonstrated troponin elevations >0.3 ng/mL in 2.9% of patients with laboratory-confirmed infection 4

• Sepsis was identified as the strongest independent cause of elevated troponin in non-CAD patients in a study of 586 patients 2

• Infective endocarditis shows troponin elevation in 65% of patients, with elevated levels strongly associated with worse outcomes including death, abscess formation, and CNS events 5, 6

• Overall non-ACS causes account for 79% of all elevated troponin cases in emergency settings, with infectious causes being one of the most frequent subgroups 7

Interpreting Troponin Levels in Infection

The magnitude of troponin elevation helps distinguish infection-related injury from acute coronary syndrome:

• Mild elevations (<2-3 times upper limit of normal) in older patients with pre-existing cardiac disease generally do not require workup for type 1 MI unless strongly suggested by angina chest pain and/or ECG changes 1

• Marked elevations (>5 times upper limit of normal) may indicate severe respiratory failure, tachycardia, systemic hypoxemia, shock as part of infection, myocarditis, Takotsubo syndrome, or type 1 MI triggered by the infection 1, 3

• Troponin levels correlate with disease severity and have prognostic value in infectious conditions, with higher levels predicting worse outcomes 1, 3

Clinical Approach Algorithm

When encountering elevated troponin in a patient with infection:

Step 1: Assess for Type 1 MI indicators

• Look for angina-type chest pain lasting >20 minutes 3
• Obtain 12-lead ECG immediately to assess for ST-segment elevation/depression, new T-wave inversions, or new conduction abnormalities 1, 3
• Check for known coronary artery disease or multiple cardiovascular risk factors 3

Step 2: Obtain serial troponin measurements

• Draw troponins at 3-6 hour intervals to establish rising/falling pattern characteristic of acute injury versus stable chronic elevation 1, 3
• A rising and/or falling pattern with at least one value above the 99th percentile indicates acute myocardial necrosis 3

Step 3: Risk stratify based on troponin magnitude and clinical context

For mild elevations (<2-3× ULN) without ischemic symptoms or ECG changes:

• Focus on treating the underlying infection 3
• These elevations are generally well explained by pre-existing cardiac disease and/or acute stress related to infection 1
• No invasive cardiac workup is needed unless clinical presentation changes 1

For marked elevations (>5× ULN) or any elevation with ischemic symptoms/ECG changes:

• Consider echocardiography to help diagnose underlying cause (myocarditis, Takotsubo, regional wall motion abnormalities suggesting MI) 1, 3
• Coronary angiography should be restricted to those in whom type 1 MI is strongly suspected based on clinical presentation 3
• Admit for intensive monitoring and management 3

Important Clinical Pitfalls

• Do not assume all troponin elevations in infected patients represent ACS - 79% of elevated troponins in emergency settings are from non-ACS causes, with infection being a major contributor 7

• Single troponin measurements are insufficient - 10-15% of patients may not have detectable elevations initially, requiring serial measurements 3

• Average troponin levels are significantly lower in non-ACS causes (median 0.14 ng/mL) compared to STEMI (10.2 ng/mL) or NSTEMI (0.4 ng/mL), helping differentiate etiology 7

• Avoid unnecessary invasive procedures in patients with infection-related troponin elevation without clear evidence of type 1 MI, as this exposes patients to procedural risks without benefit 1, 3

Prognostic Implications

Troponin elevation in the setting of infection carries independent prognostic significance:

• Any troponin elevation predicts increased mortality risk independent of the underlying cause 3

• In COVID-19, troponin levels correlate directly with disease severity and mortality 1, 3

• In infective endocarditis, 77.8% of patients with elevated troponin had adverse clinical outcomes compared to only 5.88% with normal levels 6

• The degree of elevation correlates with outcomes, with higher levels predicting worse prognosis across infectious etiologies 3, 5