Fourth Universal Definition of Myocardial Infarction (2018)

Major Updates

• Explicit differentiation of MI from myocardial injury: Elevated troponin alone is insufficient for MI diagnosis; clinical evidence of acute myocardial ischemia is mandatory.
• Peri-procedural MI: Type 4a (PCI-related) and Type 5 (CABG-related) MI have specific cTn thresholds (>5× and >10× URL respectively) PLUS new ischemic evidence required for diagnosis.
• Revised Type 2 MI: Focus on oxygen supply/demand imbalance with detailed decision framework to distinguish Type 2 MI from myocardial injury.
• Enhanced imaging role: Cardiac magnetic resonance (CMR) now recommended for diagnosis of MI when troponin/ECG findings are inconclusive or MINOCA suspected.
• High-sensitivity troponin (hs-cTn): New recommendations for rapid rule-out protocols (0/1-hour, 0/3-hour algorithms) and rise/fall pattern interpretation.
• Takotsubo syndrome: Recognized as distinct entity from acute atherosclerotic MI; requires different diagnostic and therapeutic approach.

Detection of elevated cardiac troponin (cTn) with ≥1 value above the 99th percentile upper reference limit (URL).

Injury is considered acute if there is a rise and/or fall pattern of cTn values (≥20% absolute change or ≥3× assay coefficient of variation).

Acute myocardial injury WITH clinical evidence of acute myocardial ischemia from ≥1 of:

• Symptoms of myocardial ischemia (chest pain, dyspnea, ischemic equivalent)
• New ischemic ECG changes (ST elevation, ST depression, T inversions, new LBBB)
• Development of pathological Q waves
• Imaging evidence of new loss of viable myocardium in ischemic distribution
• Identification of coronary thrombus on angiography or autopsy

MI caused by atherothrombotic coronary artery disease (CAD). Plaque rupture/erosion → acute coronary thrombus → myocyte necrosis. Accounts for ~85% of all MI cases.

Acute myocardial injury due to mismatch between oxygen supply and demand, unrelated to acute atherosclerotic CAD rupture. Type 2 MI occurs in the setting of acute illness or physiologic stress.

MI presenting as sudden cardiac death with symptoms suggestive of myocardial ischemia and presumed new ischemic ECG changes or new ventricular fibrillation, before cardiac biomarker levels can be obtained or are not available.

Baseline cTn normal (≤99th percentile, stable). Post-procedure: cTn >5× 99th percentile URL within 48 hours, PLUS evidence of:

• New ischemic ECG changes (ST elevation, ST depression, new LBBB, Q waves), OR
• Imaging evidence of new loss of viable myocardium (echo wall motion, CMR), OR
• Angiographic findings (dissection, major epicardial closure, side-branch occlusion, slow flow, distal embolization)

Acute stent thrombosis (angiography or autopsy confirmed) with cTn >10× 99th percentile URL. Can occur at any time post-PCI (acute <24h, subacute <30d, or late >30d). Requires urgent re-PCI and DAPT optimization.

In-stent or focal restenosis (angiography documented) with cTn elevation >99th percentile URL and rise/fall pattern. Can occur anytime post-PCI. Less common with modern drug-eluting stents.

Baseline cTn normal. Post-CABG: cTn >10× 99th percentile URL (higher threshold due to surgical trauma) within 48 hours, PLUS evidence of:

• New pathological Q waves or new ischemic ECG changes, OR
• Imaging evidence of new loss of viable myocardium, OR
• Angiographic documentation of new graft occlusion or native coronary artery occlusion

Cardiac troponin I (cTnI) and T (cTnT) are components of the myocardial contractile apparatus, expressed almost exclusively in the heart. KEY PRINCIPLE: Elevated cTn indicates myocardial injury; it does NOT diagnose MI without clinical ischemia evidence.

The 99th percentile URL is the decision level for myocardial injury and MI diagnosis. Every troponin assay has a manufacturer-validated 99th percentile URL. Know your institution's cutoff.

A rise and/or fall pattern is essential for diagnosing ACUTE myocardial injury. Rise/fall defined as:

• ≥20% absolute change in serial cTn values, OR
• ≥3× assay coefficient of variation (CV) if initial value is below 99th percentile URL

Rationale: Rising/falling pattern distinguishes acute injury from chronic myocardial damage. Stable troponin suggests chronic myocardial injury (CKD, HF, cardiomyopathy), NOT acute MI.

hs-cTn assays detect myocardial injury earlier (within 1–2h) and enable rapid rule-out protocols (0/1-hour, 0/3-hour algorithms).

Advantages: Earlier detection, faster risk stratification, improved negative predictive value.

Limitations: Higher prevalence of detectable cTn in healthy population (~50%); risk of MI overdiagnosis if kinetics not carefully evaluated; many non-MI conditions cause cTn elevation (HF, sepsis, PE, renal failure, stroke).

RV infarction occurs in ~40% of inferior STEMI (usually RCA). Diagnosis: ST elevation in right-sided leads V3R–V5R (especially V4R ≥1 mm).

Clinical significance: RV afterload-dependent; IV fluids may improve hemodynamics; avoid nitrates/diuretics (cause hypotension and shock).

MINOCA = acute MI (elevated troponin + ischemia evidence) WITHOUT angiographically significant CAD (≥50% stenosis). Accounts for 6–8% of MI cases; more common in women and younger patients.

Takotsubo syndrome (TTS) = transient LV dysfunction mimicking acute MI, triggered by intense emotional or physical stress. Found in ~1–2% of suspected STEMI presentations; >95% female; predominantly postmenopausal women.

Elevated baseline cTn is common in CKD (present in 20–50% of dialysis patients without acute MI).

Diagnostic approach:

• Use rise/fall pattern as primary criterion (more reliable than absolute cTn value)
• Obtain serial troponin at 0, 3, 6 hours to establish kinetics
• Integrate with clinical presentation, ECG, imaging
• High-sensitivity troponin assays help discriminate chronic from acute elevation

Elevated baseline cTn common in decompensated HF. Type 2 MI is the most common MI subtype in HF patients (tachycardia, increased afterload, reduced perfusion).

Approach: Distinguish acute decompensation (stable troponin) from Type 2 MI (rising troponin with new ischemia evidence). Search for precipitant (infection, arrhythmia, anemia, renal dysfunction).

Elevated cTn is very common in sepsis (up to 50%) without atherosclerotic MI. Mechanisms: Type 2 MI (tachycardia, shock), myocarditis, or myocardial toxin exposure.

Approach: Obtain serial troponin kinetics. Assess for ischemia evidence. Echo for wall motion abnormality. Angiography often deferred unless strong clinical suspicion for acute MI.

New AF with RVR can precipitate Type 2 MI via increased oxygen demand and reduced diastolic filling. ST changes and T-wave inversions common but may improve with rate control. Serial ECGs help distinguish rate-related changes from coronary occlusion.

Women have higher prevalence of Type 2 MI and MINOCA. Atypical presentation (dyspnea, fatigue, epigastric discomfort) more common in women. Spontaneous coronary artery dissection (SCAD) more common in young women and peripartum women.

CMR provides the most accurate assessment of myocardial viability and scar location.

Role in MI: Acute edema imaging (T2) shows myocardial edema within hours; late gadolinium enhancement (LGE) shows scar in ischemic vs. non-ischemic patterns. Useful for MINOCA, myocarditis, Takotsubo diagnosis.

Readily available; assesses regional wall motion abnormality and LV function. Identifies mechanical complications (VSD, free wall rupture, papillary muscle rupture, RV infarction, thrombus). Cannot differentiate acute from chronic wall motion abnormality alone.

Less commonly used acutely but useful for viability assessment and ischemia detection. Gated SPECT, PET for myocardial perfusion and metabolism.

NOT recommended for acute STEMI diagnosis (time constraints). May be useful for MINOCA to detect SCAD; helpful for rule-out of other acute thoracic pathology (PE, aortic dissection).