What are the possible cardiac and non‑cardiac causes of T‑wave inversion on a 12‑lead ECG?

Causes of T-Wave Inversion on 12-Lead ECG

Cardiac Causes

Acute Coronary Syndromes and Ischemic Heart Disease

Deep symmetrical T-wave inversions ≥2 mm in precordial leads (especially V2-V4) strongly suggest critical stenosis of the proximal left anterior descending coronary artery and mandate urgent coronary evaluation. 1

• Critical LAD stenosis often presents with anterior wall hypokinesis on echocardiography and carries high risk with medical therapy alone—revascularization can reverse both the ECG changes and wall motion abnormalities 1
• Coronary angiography typically reveals severe stenosis with collateral circulation in patients with this pattern 1
• Inferior/lateral T-wave inversions raise suspicion for right coronary artery or left circumflex stenosis 2
• Dynamic T-wave inversions (developing during symptoms and resolving when asymptomatic) strongly indicate acute ischemia and high likelihood of severe coronary disease 1

Cardiomyopathies

• Hypertrophic cardiomyopathy is the primary concern when lateral territory T-wave inversions (V5-V6, I, aVL) are present, with 30% of athletes showing this pattern having underlying cardiomyopathy 2
• Arrhythmogenic right ventricular cardiomyopathy (ARVC) should be suspected when T-wave inversion extends beyond V3, especially if accompanied by epsilon waves or ventricular arrhythmias 1, 2
• Dilated cardiomyopathy can manifest with diffuse T-wave inversions 2
• Left ventricular non-compaction may present with inferior and/or lateral T-wave inversions 1, 2
• T-wave inversion may represent the initial phenotypic expression of cardiomyopathy even before structural changes become detectable on imaging 1

Structural Heart Disease

• Aortic valve disease (particularly aortic stenosis) can cause T-wave inversions 1
• Congenital heart disease leading to right ventricular volume or pressure overload may manifest as T-wave inversion beyond V1 in post-pubertal individuals 2
• Left ventricular aneurysm can produce persistent T-wave inversions 1

Other Cardiac Conditions

• Pericarditis and myocarditis are capable of generating T-wave abnormalities 1, 3
• Takotsubo cardiomyopathy can present with diffuse T-wave inversions 1
• Systemic hypertension with left ventricular hypertrophy may cause T-wave inversions 1, 2
• Inherited ion-channel diseases (e.g., long QT syndrome) should be considered, particularly with post-pubertal persistence of T-wave inversion beyond V1 1, 2

Non-Cardiac Causes

Central Nervous System Events

Intracranial hemorrhage and subarachnoid hemorrhage can produce deep T-wave inversions with QT prolongation that mimic critical LAD stenosis—this "CVA pattern" requires systematic neurological evaluation. 1

• Deep symmetrical T-wave inversions in V2-V4 with significant QT prolongation (QTc ≥470 ms in men, ≥480 ms in women) suggest either severe proximal LAD stenosis or acute intracranial hemorrhage 1

Medications

• Tricyclic antidepressants may cause deep T-wave inversions 1, 2
• Phenothiazine antipsychotics can produce T-wave abnormalities 1, 2
• Quinidine-like drugs may alter T-wave morphology 2

Electrolyte Abnormalities

• Hypokalemia can cause T-wave flattening or inversion 2

Pulmonary Conditions

• Pulmonary embolism may present with T-wave inversions, particularly in right precordial leads 1

Normal Variants and Physiological Patterns

Age-Related Patterns

• Juvenile pattern: T-wave inversions in V1-V3 may be normal in individuals younger than 16 years, but only after comprehensive clinical assessment excludes cardiac disease 1
• Anterior T-wave inversion becomes positive in 94% of children by age 14 years 4

Race-Specific Patterns

• Black/African-Caribbean individuals: T-wave inversions in V2-V4 preceded by J-point elevation and convex ST-segment elevation represent adaptive early repolarization changes in up to 25% of cases 5, 1, 2
• This pattern is considered normal when confined to V2-V4 and not extending to lateral leads 2

Lead-Specific Normal Variants

• T-wave inversion in lead aVR is normal in adults over 20 years 1
• T-wave inversion in V1 alone can be a normal finding in adults 1
• T-wave inversion confined to V1-V2 only occurs in up to 4.3% of healthy young females and is considered a normal variant 5

Distribution-Based Risk Stratification

High-Risk Patterns Requiring Urgent Evaluation

• Lateral/inferolateral involvement (I, aVL, V5-V6, II, III, aVF) carries highest concern for cardiomyopathy and ischemic disease 1, 2
• Deep inversions ≥2 mm in ≥2 contiguous leads are rarely seen in healthy individuals and denote high-risk pathology 1, 2
• Extension beyond V3 raises suspicion for ARVC 1, 2

Intermediate-Risk Patterns

• Anterior T-wave inversion (V1-V4) requires comprehensive evaluation but may be normal in specific populations (young Black individuals with J-point elevation, children <16 years) 5, 1
• Inferior T-wave inversions warrant thorough evaluation for ischemic disease, cardiomyopathy, and structural abnormalities 1, 2

Lower-Risk Patterns

• Isolated V1 or V1-V2 inversion in young females without other features is likely benign but still requires echocardiography 5
• Right precordial T-wave inversions (V1-V3) in middle-aged adults are relatively rare (0.5%) and not associated with adverse outcomes 6

Critical Pitfalls to Avoid

• Never dismiss T-wave inversions as normal variants without proper evaluation, especially when depth ≥2 mm or extension beyond V1 in non-Black individuals 1, 2
• A single normal echocardiogram does not exclude future cardiomyopathy—T-wave inversion may precede structural heart disease by months or years, mandating serial monitoring 5, 1, 2
• Do not overlook non-cardiac causes such as CNS events or medications when evaluating global T-wave inversions 1
• Ensure proper ECG lead placement, as misplacement can create pseudo-pathological patterns 1
• In athletes, do not interpret T-wave inversion as exercise-induced remodeling without comprehensive exclusion of inherited cardiovascular disease 2, 7
• Infero-lateral T-wave inversion in children should never be interpreted as physiologically related to age or training—it is rare, persistent, and may indicate structural heart disease requiring strict surveillance 4