What are the causes of gross T wave inversion on an electrocardiogram (ECG)?

Causes of Gross T Wave Inversion on ECG

Gross T wave inversion (≥2 mm depth) most commonly indicates critical stenosis of the proximal left anterior descending coronary artery in symptomatic patients, but can also result from cardiomyopathies, central nervous system events, pulmonary embolism, or certain medications. 1

Cardiac Causes

Acute Coronary Syndromes

• Marked symmetrical precordial T wave inversion (≥2 mm) strongly suggests acute myocardial ischemia, particularly from critical stenosis of the proximal LAD, and is associated with anterior wall hypokinesis and high risk with medical treatment alone. 1, 2
• Deep symmetrical inversion of T waves in anterior chest leads is often related to significant stenosis of the proximal left anterior descending coronary artery. 3
• Revascularization will often reverse both the T wave inversion and wall-motion disorder in ischemic cases. 1
• ST-segment depression >1 mm in two or more contiguous leads, combined with inverted T waves (>1 mm) in leads with predominant R-waves, is highly suggestive of acute coronary syndrome. 3

Cardiomyopathies

• T wave inversion may be the only sign of an inherited heart muscle disease even before structural changes in the heart can be detected on imaging. 1, 2
• Hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy (ARVC), and left ventricular non-compaction can all present with gross T wave inversions. 2
• T wave inversion in lateral leads (V5-V6) is particularly concerning for cardiomyopathy and warrants comprehensive investigation. 1, 4
• Post-pubertal persistence of T wave inversion beyond V1 may reflect underlying congenital heart disease, ARVC, or inherited ion-channel disease. 2

Valvular and Structural Heart Disease

• Severe aortic regurgitation can cause giant T wave inversion, possibly related to myocardial ischemia from increased left ventricular wall stress and changes in phasic coronary blood flow. 5
• Aortic valve disease and systemic hypertension are potential causes of T wave inversion. 2

Non-Cardiac Causes

Central Nervous System Events

• Central nervous system events, particularly intracranial hemorrhage and subarachnoid hemorrhage, can cause deep T wave inversion with QT prolongation that mimics cardiac ischemia. 1, 2, 6
• The mechanism involves microvascular spasm and increased levels of circulating catecholamines. 6
• Diffuse splayed T wave inversions may occur in the context of acute cerebrovascular accident. 6

Medications

• Tricyclic antidepressants and phenothiazines can cause deep T wave inversion. 1

Pulmonary Embolism

• Pulmonary embolism can produce T wave inversions and should be considered in the differential diagnosis. 3, 4

Other Non-Cardiac Causes

• Myocarditis, particularly post-COVID-19, can present with T wave inversions. 1
• Pericarditis may cause T wave changes and should be excluded through physical examination and additional testing. 3, 7

Normal Variants (Not Gross Inversion)

• In adults 20+ years, normal T wave inversion occurs only in aVR; may be upright or inverted in leads aVL, III, and V1; and should be upright in leads I, II, and chest leads V3-V6. 1
• In children older than 1 month, T wave inversion is often normal in leads V1, V2, and V3. 1
• In Black/African-Caribbean athletes, T wave inversions in V2-V4 preceded by ST-segment elevation may represent a normal adaptive variant. 2, 4
• Respiratory variation in T wave morphology can occur and may suggest a non-cardiac cause of chest pain. 8

Distribution Patterns and Clinical Significance

High-Risk Patterns

• T wave inversion extending from V1 to V5 with depth ≥2 mm is highly concerning for critical proximal LAD stenosis and requires urgent evaluation. 2
• T wave inversion in inferior and/or lateral leads is uncommon even in Black athletes and warrants further investigation for systemic hypertension, left ventricular non-compaction, ARVC, or inherited ion-channel disease. 1, 2
• Multiple lead involvement (≥2 contiguous leads with T wave inversion ≥1 mm) indicates greater degree of myocardial ischemia and worse prognosis. 2

Dynamic Changes

• Dynamic T wave inversions (developing during symptoms and resolving when asymptomatic) strongly suggest acute ischemia and very high likelihood of severe coronary artery disease. 2
• Transient episodes of T wave changes may occur during ischemic attacks. 3

Common Pitfalls

• Misinterpreting normal variant T wave inversions as pathological, particularly in young patients and athletes of African/Caribbean descent, is a common error. 1, 4
• Failing to recognize that central nervous system events can mimic cardiac ischemia with deep T wave inversions and QT prolongation. 2, 6
• Dismissing T wave inversions beyond V1 as normal variants without proper evaluation, when they may represent early phenotypic expression of cardiomyopathy. 2
• Overlooking medication effects (tricyclic antidepressants, phenothiazines) as potential causes of deep T wave inversion. 1, 4