What is the differential diagnosis for a patient with diffuse ST wave inversion on an electrocardiogram (ECG), considering potential underlying conditions such as acute myocardial infarction, pericarditis, or cardiomyopathy?

Differential Diagnosis for Diffuse ST Wave Inversion

Diffuse ST-segment and T-wave inversions on ECG represent a critical finding that demands immediate consideration of life-threatening cardiac and non-cardiac conditions, with acute coronary syndrome, stress cardiomyopathy, pulmonary embolism, and intracranial pathology being the most urgent diagnoses to exclude.

Cardiac Causes

Acute Coronary Syndromes

• Acute myocardial ischemia/infarction is the most critical diagnosis to exclude, as more profound ST-segment shift or T-wave inversion involving multiple leads/territories is associated with greater degree of myocardial ischemia and worse prognosis 1
• Diffuse T-wave inversions may indicate Wellens' syndrome (critical LAD stenosis) or evolving non-ST elevation MI, requiring urgent cardiac biomarkers and serial ECGs 1
• Circumflex artery occlusion is frequently overlooked and may present with diffuse changes rather than localized ST elevation, warranting posterior leads (V7-V9) 1

Cardiomyopathies

• Stress cardiomyopathy (Takotsubo) presents with ST-T changes mimicking acute coronary syndrome, often with diffuse deep T-wave inversions and prolonged QT interval 1, 2
• Hypertrophic cardiomyopathy causes ST-T abnormalities that can mimic ischemic patterns, particularly with left ventricular hypertrophy 1, 2
• Myocarditis/myopericarditis may show focal or diffuse ST-T changes with elevated cardiac biomarkers, making differentiation from MI challenging 3, 4

Pericardial Disease

• Acute pericarditis typically shows diffuse ST elevation initially, but can present with ST-T changes that may be confused with ischemia, particularly when associated with myocarditis 1, 2, 3
• Unlike MI, pericarditis classically shows PR depression and lacks reciprocal changes, though focal presentations can mimic transmural infarction 3, 4

Other Cardiac Conditions

• Left ventricular hypertrophy produces ST-T abnormalities that may mimic ischemic patterns 1, 2
• Left bundle branch block causes secondary ST-T changes that can obscure or mimic acute MI 1
• Brugada syndrome has distinctive ECG patterns that could be confused with anterior ischemia 1, 2

Non-Cardiac Causes

Pulmonary

• Pulmonary embolism may result in ST-T abnormalities, often with right ventricular strain pattern and diffuse T-wave inversions 1

Neurological

• Intracranial processes (subarachnoid hemorrhage, stroke) produce characteristic diffuse, deep, symmetric T-wave inversions with prolonged QT interval due to catecholamine surge 1, 5
• These "cerebral T waves" are typically splayed and wider than ischemic T waves, though differentiation can be challenging 5

Metabolic/Other

• Electrolyte abnormalities (particularly hypokalemia, hypocalcemia) may result in ST-T abnormalities 1
• Hypothermia can produce ST-T changes 1

Critical Diagnostic Algorithm

Immediate Actions

• Obtain serial ECGs at 15-30 minute intervals if initial ECG is non-diagnostic, as dynamic changes help differentiate acute ischemia from other causes 1
• Compare with prior ECGs when available—this dramatically improves diagnostic accuracy for distinguishing new from old findings 1, 2
• Measure cardiac biomarkers (troponin, CK-MB) immediately, but do not wait for results if clinical suspicion for acute MI is high 1

Key Differentiating Features

• Assess distribution: Diffuse changes across multiple territories suggest non-ischemic causes (Takotsubo, intracranial pathology, pericarditis), while territory-specific changes favor coronary occlusion 1
• Evaluate T-wave morphology: Narrow, symmetric inversions suggest ischemia; wide, splayed inversions suggest cerebral pathology 5
• Look for reciprocal changes: Present in MI, absent in pericarditis and most non-ischemic causes 1
• Check for PR depression: Suggests pericarditis rather than ischemia 3, 4

Advanced Diagnostic Tools

• Bedside echocardiography is invaluable—regional wall motion abnormalities support ischemia, while apical ballooning suggests Takotsubo; absence of wall motion abnormalities excludes major MI 1
• Consider posterior leads (V7-V9) if circumflex occlusion suspected, using 0.05 mV ST elevation as cutpoint 1

Common Pitfalls to Avoid

• Do not dismiss diffuse T-wave inversions as "non-specific"—they may represent critical LAD disease (Wellens'), Takotsubo, or intracranial catastrophe 1, 5
• Avoid anchoring on normal initial biomarkers—troponins may not rise for 3-6 hours after symptom onset; serial measurements are essential 1
• Do not overlook clinical context: Young patients without risk factors presenting with diffuse changes are more likely to have myopericarditis or Takotsubo than acute MI 3, 4
• Beware of pseudo-normalization: Previously inverted T waves becoming upright during chest pain indicates acute ischemia 1
• Remember that 5-40% of patients with normal initial ECG develop acute MI—serial ECGs and biomarkers are mandatory 1