What are the differential diagnoses and management strategies for myocardial infarction (MI)?

Differential Diagnosis of Myocardial Infarction

When a patient presents with suspected myocardial infarction, the differential diagnosis must include acute aortic dissection, pulmonary embolism, pericarditis, myocarditis, Takotsubo cardiomyopathy, and non-cardiac causes of chest pain—each requiring immediate recognition to prevent catastrophic outcomes. 1

Life-Threatening Conditions Requiring Immediate Exclusion

Acute Aortic Dissection

• Pericardiocentesis is absolutely contraindicated in aortic dissection due to risk of intensified bleeding and extension of dissection 1
• Suspect when ST-depression >0.1 mV in eight or more surface leads coupled with ST elevation in aVR and/or V1, particularly with hemodynamic compromise 1
• Pericardial effusion found in 17-45% of patients with ascending aortic dissection 1
• Requires immediate surgical intervention, not reperfusion therapy 1
• CT scan plays a critical role in differential diagnosis of acute aortic dissection 1

Massive Pulmonary Embolism

• Two-dimensional echocardiography is particularly valuable for diagnosing massive pulmonary embolism 1
• Consider D-dimer testing, BNP, and/or CT pulmonary angiography when suspected 1
• Can present with elevated cardiac troponin due to myocardial injury from right ventricular strain 1

Cardiac Conditions Mimicking MI

Takotsubo (Stress-Induced) Cardiomyopathy

• Often triggered by physical or emotional stress with transient apical or mid-left ventricular dilation and dysfunction 1
• ECG changes at presentation are usually modest and do not correlate with severity of ventricular dysfunction 1
• Emergency angiography should not be delayed and will show neither significant culprit coronary artery stenosis nor intracoronary thrombi 1
• Diagnosis confirmed by transient apical- to mid-ventricular ballooning with compensatory basal hyperkinesis and disproportionately low plasma cardiac biomarkers relative to ventricular dysfunction severity 1
• CMR is a key diagnostic tool for differentiating Takotsubo syndrome from true MI 1, 2

Acute Pericarditis

• Diagnosis requires at least 2 of 4 criteria: pericardial chest pain, pericardial friction rub, diffuse ST-segment elevation or PR-segment depression on ECG, and new or worsening pericardial effusion 1
• Two-dimensional echocardiography is of particular value for diagnosing pericardial effusion 1
• Stage I ECG changes with diffuse ST elevation distinguish pericarditis from MI 1

Myocarditis

• Suspect in patients with chest pain, ECG changes, elevated cardiac biomarkers, and/or ventricular dysfunction without obstructive coronary disease 1
• CMR with T1 and T2 mapping, T2-weighted short tau inversion recovery (T2STIR), and late gadolinium enhancement is fundamental for non-invasive diagnosis 1
• Patients require hospitalization with continuous ECG monitoring due to risk of malignant arrhythmias 1

Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA)

• Accounts for 5-15% of all acute MI presentations 2
• Defined as elevated cardiac troponin with at least one value above 99th percentile plus corroborative clinical evidence of infarction, but no coronary artery stenosis ≥50% on angiography 1
• CMR is recommended in all MINOCA patients without an obvious underlying cause (Class I, Level B recommendation) 1
• CMR can identify the underlying cause in up to 87% of MINOCA patients 1
• Intracoronary imaging with IVUS or OCT valuable for detecting unrecognized thrombus, plaque rupture/erosion, or spontaneous coronary artery dissection 1

Atypical MI Presentations Requiring Prompt Recognition

Isolated Posterior MI

• Presents with isolated ST-depression ≥0.05 mV in leads V1-V3 as the dominant finding 1
• Should be treated as STEMI 1
• Use additional posterior chest wall leads V7-V9 (≥0.05 mV elevation, or ≥0.1 mV in men >40 years old) to detect ST elevation 1

Left Main Coronary Obstruction

• ST elevation in lead aVR with infero-lateral ST depression suggests multivessel or left main coronary artery obstruction 1
• Particularly suspect when patient presents with hemodynamic compromise 1

Left Bundle Branch Block (LBBB)

• New or presumed new LBBB with ongoing ischemic symptoms warrants immediate reperfusion therapy 1
• Finding of elevated markers of necrosis may be helpful in deciding to give reperfusion therapy in patients with LBBB 1

Ventricular Paced Rhythm

• Deserves prompt management in patients with signs and symptoms of ongoing myocardial ischemia 1

Type 2 MI: Supply-Demand Mismatch

Type 2 MI occurs when conditions other than coronary artery disease create an imbalance between myocardial oxygen supply and demand 3, 4

Causes Include:

• Hypotension, hypertension, tachyarrhythmias, bradyarrhythmias 3
• Severe anemia, hypoxemia 3, 1
• Coronary artery spasm, spontaneous coronary artery dissection 3
• Coronary embolism, coronary microvascular dysfunction 3
• Sepsis, cardiac contusion 1

Management Strategy:

• Treat the underlying cause of oxygen supply-demand imbalance 4
• Oxygen supplementation for hypoxemia 4
• Rate control or cardioversion for tachyarrhythmias 4

Non-Cardiac Causes of Chest Pain

Conditions to Consider:

• Hyperventilation syndrome and functional complaints present with atypical symptoms more often than MI: palpitations, tingling of fingers, "numb feelings" in arms and legs 5
• Duration of prodromal pain attacks: non-cardiac chest pain typically lasts from a few minutes to several hours (median >30 minutes), while MI prodromal pain is shorter (median 10 minutes) 5
• Esophageal spasm and other gastrointestinal causes 1

Diagnostic Algorithm for Suspected MI

Immediate Actions (Within 10 Minutes):

• Obtain 12-lead ECG and evaluate for STEMI, LBBB, or other high-risk patterns 1
• Place patient on cardiac monitor with defibrillation capability nearby 1
• Consider additional ECG leads (V7-V9 for posterior MI, V4R for right ventricular infarction) 1

Risk Stratification:

• Measure cardiac troponin (but do not wait for results to initiate reperfusion treatment) 1
• Assess for high-risk features: hemodynamic compromise, ongoing ischemic symptoms despite medical therapy, elevated biomarkers 1

Advanced Imaging When Diagnosis Unclear:

• Two-dimensional echocardiography to assess regional wall motion abnormalities (occur within seconds-minutes of coronary occlusion) and exclude other causes 1
• Emergency coronary angiography indicated for ongoing suspicion of myocardial ischemia despite medical therapy, even without diagnostic ST-segment elevation 1
• CMR for definitive diagnosis when MINOCA suspected or to differentiate Takotsubo syndrome, myocarditis, or true MI 1, 2

Critical Pitfalls to Avoid

• Never perform pericardiocentesis in suspected aortic dissection—this is absolutely contraindicated 1
• Do not delay emergency angiography in Takotsubo cardiomyopathy because there is no specific test to rule out MI in this setting 1
• Regional wall motion abnormalities on echocardiography are not specific for acute MI and may be due to ischemia, old infarction, or ventricular conduction defects 1
• Absence of wall-motion abnormalities on echocardiography excludes major MI 1
• In elderly patients, presentations such as fatigue, dyspnea, faintness, or syncope are common instead of typical chest pain 1
• Postinfarction pericarditis (epistenocardiac or Dressler's syndrome) can complicate the clinical picture, with ECG changes often overshadowed by MI changes 1