How to differentiate Acute Coronary Syndrome (ACS) from infection?

Differentiating Acute Coronary Syndrome from Infection

The key to differentiating ACS from infection lies in the pattern of troponin elevation, ECG findings, and clinical context: ACS typically shows a rising/falling troponin pattern with ischemic ECG changes and chest pain, while infection-related troponin elevation is usually mild (<2-3 times upper limit of normal), stable, and accompanied by fever, respiratory symptoms, and inflammatory markers without ischemic ECG changes. 1

Clinical Presentation Patterns

ACS Presentation

• Chest discomfort described as pressure, tightness, or burning, typically lasting >10 minutes at rest or with minimal exertion, often radiating to arms, neck, or jaw 2
• Approximately 79% of men and 74% of women present with chest discomfort, though 40% of men and 48% of women have nonspecific symptoms like dyspnea 3
• Associated symptoms include diaphoresis, nausea, and syncope 2

Infection Presentation

• Fever and respiratory symptoms predominate, with chest discomfort being atypical or pleuritic in nature 1
• Systemic signs of infection including elevated white blood cell count, fever, and inflammatory markers 1
• In COVID-19,5-25% of hospitalized patients show troponin elevation, higher in ICU patients 1

ECG Differentiation

ACS ECG Findings

• Persistent ST-segment elevation (>20 minutes) indicates STEMI requiring immediate reperfusion 2
• Ischemic ST-segment depression ≥0.5 mm or dynamic T-wave inversion with symptoms indicates NSTE-ACS 2
• New pathological Q waves suggest myocardial necrosis 2

Infection-Related ECG

• Typically shows non-specific changes or sinus tachycardia without ischemic patterns 1
• May show diffuse ST changes in myocarditis, but lacks the regional pattern of coronary occlusion 1

Troponin Pattern Analysis

ACS Troponin Pattern

• Rising and/or falling pattern with serial measurements at 1-2 hour intervals using high-sensitivity assays 2, 1
• At least one value above the 99th percentile with ≥20% change between measurements indicates acute myocardial necrosis 1
• Troponin rises within 3-4 hours of symptom onset and may remain elevated for up to 2 weeks 1
• Marked elevations >5 times upper limit of normal have >90% positive predictive value for acute type 1 MI 1

Infection-Related Troponin Pattern

• Mild elevations (<2-3 times upper limit of normal) are typical and generally do not require workup for type 1 MI unless strongly suggested by clinical symptoms or ECG changes 1
• Stable elevations rather than dynamic rising/falling pattern 1
• Marked elevations (>5 times ULN) may indicate severe respiratory failure, tachycardia, systemic hypoxemia, shock, or myocarditis requiring further cardiac evaluation 1

Diagnostic Algorithm

Step 1: Immediate Assessment (Within 10 Minutes)

• Obtain 12-lead ECG immediately 2, 3
• Assess for persistent ST-elevation (STEMI) versus non-ST-elevation presentation 2
• Check vital signs including fever, oxygen saturation, and hemodynamic stability 1

Step 2: Clinical Context Evaluation

• If chest pain with ischemic ECG changes: Proceed with ACS protocol regardless of infection presence 1
• If fever, respiratory symptoms, and mild troponin elevation without ischemic ECG: Focus on treating underlying infection 1
• If hemodynamically unstable with either presentation: Obtain troponin and consider type 2 MI from supply-demand mismatch 1

Step 3: Serial Troponin Measurements

• Obtain baseline troponin immediately, then repeat at 1-2 hours (high-sensitivity assay) or 3-6 hours (standard assay) 2, 1
• Rising/falling pattern with ischemic symptoms/ECG: Diagnose ACS and initiate intensive management 1
• Stable mild elevation with infection: Continue infection treatment without invasive cardiac workup 1

Step 4: Risk Stratification

• High-risk features requiring coronary angiography include: recurrent chest pain, dynamic ST-segment changes, elevated troponin, hemodynamic instability, major arrhythmias, or diabetes 2
• Low-risk features include: stable mild troponin elevation, no ischemic ECG changes, clear infectious etiology, and appropriate response to infection treatment 1

Mechanisms of Troponin Elevation in Infection

Type 2 MI Mechanisms

• Severe respiratory distress and hypoxemia cause oxygen supply-demand mismatch without coronary occlusion 1
• Tachycardia from fever and systemic illness increases cardiac demand leading to myocardial stress 1
• Systemic inflammatory response triggers cytokine release potentially causing microinfarction 1

Direct Myocardial Injury

• Direct viral cytopathic effects particularly in COVID-19 infections 1, 4
• Myocarditis from inflammatory damage to cardiac myocytes 1

Common Pitfalls to Avoid

Pitfall 1: Dismissing Troponin Elevation as "Just Infection"

• Even mild troponin elevations carry prognostic significance and require serial monitoring 1
• Infection can trigger type 1 MI through plaque destabilization in patients with underlying coronary disease 5, 4

Pitfall 2: Pursuing Invasive Testing for All Troponin Elevations

• Coronary angiography should be restricted to patients with symptoms/ECG changes suggestive of type 1 MI 1
• Mild elevations (<2-3 times ULN) in clear infectious context do not warrant invasive evaluation 1

Pitfall 3: Single Troponin Measurement

• A single elevated troponin is insufficient for diagnosis—serial measurements are essential 1
• In 10-15% of patients, initial troponin may be normal despite ongoing ACS 1

Pitfall 4: Ignoring Clinical Context

• Troponin elevation indicates myocardial injury but does not specify the cause 1
• Interpret troponin in context of chest pain characteristics, ECG changes, risk factors, and presence of infection 1

Management Based on Differentiation

If ACS Confirmed

• Immediate aspirin 75-150 mg, clopidogrel, low-molecular-weight heparin, beta-blocker, and nitrates 2
• Coronary angiography within 24-48 hours for high-risk NSTE-ACS reduces mortality from 6.5% to 4.9% 3
• Primary PCI within 120 minutes for STEMI reduces mortality from 9% to 7% 3

If Infection-Related Troponin Elevation

• Focus on treating underlying infection without invasive cardiac workup 1
• Consider echocardiography if marked troponin elevation without clear type 1 MI features 1
• Monitor serial troponins and ECGs during infection treatment 1

If Uncertain or Mixed Picture

• Admit for observation with continuous ECG monitoring 1
• Serial troponins at 3-6 hour intervals 1
• Echocardiography to assess for wall motion abnormalities suggesting ischemia versus global dysfunction from sepsis 1