Patient presents with chest pain and a normal 12‑lead electrocardiogram; what is the appropriate acute coronary syndrome management?

Management of Chest Pain with Normal 12-Lead ECG

A normal initial ECG does not exclude acute coronary syndrome—you must obtain serial high-sensitivity troponin measurements at 0 and 1–2 hours using validated algorithms, repeat ECGs if symptoms recur, and pursue non-invasive stress testing or coronary CT angiography before discharge if troponins remain negative but clinical suspicion persists. 1

Immediate Diagnostic Protocol

ECG Strategy

• Obtain a 12-lead ECG within 10 minutes of first medical contact and have it interpreted immediately by an experienced physician 1, 2
• The initial ECG is normal or nondiagnostic in >33% of patients with non-ST-elevation ACS, making it insufficient to rule out myocardial infarction 1, 3
• Perform serial ECGs at 15–30 minute intervals during the first hour if the initial ECG is nondiagnostic and symptoms persist or recur 1
• Consider additional ECG leads (V3R, V4R, V7–V9) if ongoing ischemia is suspected when standard leads remain inconclusive 1

High-Sensitivity Troponin Testing

• Measure high-sensitivity cardiac troponin immediately at presentation (0 hour) with results available within 60 minutes of blood sampling 1
• Use the ESC 0h/1h algorithm with repeat troponin at 1 hour if a validated high-sensitivity assay is available (Class I, Level B recommendation) 1
• Alternatively, use the 0h/2h algorithm with sampling at 0 and 2 hours if a validated protocol exists 1
• Serial troponin measurements are mandatory—a single normal troponin is insufficient because 10–15% of patients may not show elevation initially 1, 4, 3

The 0h/1h protocol achieves a negative predictive value approaching 100% for ruling out myocardial infarction when both values fall in the "very low" range using assay-specific cutoffs 4, 3

Risk Stratification During Observation

When to Extend Monitoring Beyond Initial Testing

• Obtain additional troponin testing at 3 hours if the first two measurements (0h/1h or 0h/2h) are not conclusive and clinical suspicion remains high 1
• Continue rhythm monitoring until NSTEMI has been established or ruled out 1
• Repeat ECG immediately if chest pain recurs or diagnostic uncertainty persists 1

Identifying High-Risk Features That Mandate Admission

Even with normal ECG and initial troponin, admit patients with:

• Recurrent or ongoing chest pain despite initial negative workup 1
• Hemodynamic instability (hypotension, pulmonary edema) 1
• Known coronary artery disease or multiple cardiovascular risk factors 2, 5
• Age ≥65 years with typical anginal symptoms 5

Pre-Discharge Evaluation for Low-Risk Patients

In patients with no recurrence of chest pain, normal ECG findings, and normal cardiac troponin levels (preferably high-sensitivity), but still with suspected ACS, perform non-invasive stress testing (preferably with imaging) or coronary CT angiography before deciding on discharge (Class I recommendation) 1

Stress Testing Indications

• Non-invasive stress test with imaging is recommended to evaluate for inducible ischemia in patients with negative serial troponins and ECGs but persistent clinical concern 1
• Coronary CT angiography (CCTA) is recommended as an alternative to invasive coronary angiography to exclude ACS when there is low-to-intermediate likelihood of coronary artery disease and cardiac biomarkers/ECG are normal or inconclusive 1

Echocardiography Role

• Perform echocardiography to evaluate regional and global left ventricular function and rule in or rule out differential diagnoses 1
• In patients with cardiac arrest or hemodynamic instability of presumed cardiovascular origin, echocardiography should be performed immediately following the 12-lead ECG 1

Critical Pitfalls to Avoid

Common Diagnostic Errors

• Never dismiss chest pain based solely on a normal initial ECG—up to 55% of patients with acute MI can have a normal or nondiagnostic initial ECG 1
• ST-segment changes are frequently unstable in early ACS, representing a dynamic process that a single ECG may miss 1
• Serial 12-lead ECG monitoring detected injury in an additional 16.2% of AMI patients, representing a 34% relative increase in patients eligible for emergency reperfusion therapy 1

Troponin Interpretation Errors

• Do not use point-of-care troponin assays for rule-out—they have substantially lower sensitivity than central laboratory high-sensitivity methods 4, 3
• A rising/falling pattern (≥20% change) is required to distinguish acute myocardial injury from chronic elevation when baseline troponin is elevated 4, 3
• Troponin remains elevated for up to 14 days after myocardial injury, complicating detection of reinfarction 4

Differential Diagnosis Considerations

Non-ACS Causes of Chest Pain with Normal ECG

When troponin is elevated despite normal ECG, consider:

• Type 2 myocardial infarction from supply-demand mismatch (tachyarrhythmias, severe hypertension, anemia, hypotension) 1, 4
• Myocarditis with inflammatory cardiac injury 1, 4
• Takotsubo syndrome mimicking ACS 4, 6
• Pulmonary embolism causing right ventricular strain 4, 6
• Aortic dissection with coronary involvement 4

Interpret troponin elevation in clinical context—the presence of ischemic chest pain, risk factors, and serial troponin dynamics guide whether this represents Type 1 MI requiring invasive management versus alternative diagnoses 4, 3

Management Algorithm Summary

1. Immediate (0–10 minutes): 12-lead ECG, clinical assessment, high-sensitivity troponin 1, 2
2. 1–2 hours: Repeat high-sensitivity troponin using validated 0h/1h or 0h/2h algorithm 1, 3
3. 3 hours: Additional troponin if first two measurements inconclusive 1
4. Before discharge: Non-invasive stress testing or CCTA if troponins negative but clinical suspicion persists 1
5. Continuous: Serial ECGs with any symptom recurrence, rhythm monitoring until ACS ruled out 1

Patients with diagnostic changes on serial ECG monitoring had 2.5 times greater risk of ACS, 9.6 times greater risk of life-threatening complications, and 12.3 times greater risk of death compared to those without changes 1