Can a patient have a myocardial infarction (MI) without a significant troponin leak?

Myocardial Infarction Without Troponin Elevation

By definition, a myocardial infarction cannot occur without troponin elevation according to current guidelines, as elevated cardiac troponin above the 99th percentile is a fundamental diagnostic criterion for MI.

Understanding MI Diagnosis

The Fourth Universal Definition of Myocardial Infarction clearly establishes that MI diagnosis requires:

1. Detection of a rise and/or fall of cardiac troponin with at least one value above the 99th percentile upper reference limit 1
2. Clinical evidence of myocardial ischemia as shown by at least one of the following:
   • Symptoms of ischemia
   • New ischemic ECG changes
   • Development of pathological Q waves
   • Imaging evidence of new loss of viable myocardium
   • Identification of coronary thrombus 1

Unstable Angina vs. NSTEMI

What might be confused with "MI without troponin leak" is actually unstable angina:

• Unstable angina: Myocardial ischemia without cardiomyocyte necrosis (and thus no troponin elevation) 1
• NSTEMI: Myocardial ischemia with cardiomyocyte necrosis (evidenced by troponin elevation) 1

With the introduction of high-sensitivity troponin assays, many cases previously classified as unstable angina are now recognized as NSTEMI, resulting in:

• ~4% absolute and ~20% relative increase in detection of type 1 MI
• Corresponding decrease in unstable angina diagnoses 1

Troponin Sensitivity and Timing

Several factors may lead to initially negative troponin results in MI:

1. Early presentation: Patients presenting very early after symptom onset may have troponin levels that haven't yet risen above the 99th percentile 1, 2

   • Serial measurements at 3-6 hours are mandatory for this reason 1
   • For patients presenting within 3 hours of chest pain onset, sensitive assays significantly improve diagnostic accuracy 2

2. Assay sensitivity: Standard (older) troponin assays may miss smaller MIs that high-sensitivity assays can detect 1, 2

   • High-sensitivity assays reduce the "troponin-blind" interval 1

Clinical Implications

• If clinical suspicion for ACS remains high despite initial negative troponin:

  • Obtain additional troponin levels beyond 6 hours in patients with normal initial troponins who have ECG changes or intermediate/high-risk clinical features 1
  • Consider time of presentation as time of symptom onset when symptom timing is ambiguous 1

• For patients with symptoms consistent with ACS but without objective evidence of myocardial ischemia (normal ECG and troponin), observation in a chest pain unit with serial ECGs and troponin measurements at 3-6 hour intervals is recommended 1

Pitfalls to Avoid

1. Don't rely on a single troponin measurement, especially if obtained early after symptom onset
2. Don't dismiss clinical symptoms when initial troponin is negative
3. Don't confuse myocardial injury with MI - elevated troponin can occur in many non-MI conditions 1
4. Don't use outdated biomarkers - CK-MB and myoglobin are no longer recommended for ACS diagnosis 1

In conclusion, while unstable angina represents myocardial ischemia without troponin elevation, true myocardial infarction by current definition requires troponin elevation as evidence of myocardial necrosis.