What are the causes of non-contiguous T wave inversion?

Causes of Non-Contiguous T Wave Inversion

Non-contiguous T wave inversions—where inverted T waves appear in non-adjacent leads scattered across different anatomical territories—most commonly indicate either a systemic/non-cardiac process (central nervous system events, pulmonary embolism, medications) or a diffuse cardiomyopathy rather than focal coronary ischemia, which typically produces contiguous patterns. 1, 2

Primary Causes by Category

Systemic and Non-Cardiac Causes

• Central nervous system events (intracranial hemorrhage, subarachnoid hemorrhage, stroke) produce diffuse, deeply inverted T waves with QT prolongation through catecholamine surge and autonomic dysregulation 1, 3, 2
• Pulmonary embolism can cause scattered T wave inversions, sometimes giant inversions, particularly when moderate to severe 4, 2
• Medications including tricyclic antidepressants, phenothiazines, and quinidine-like drugs produce non-contiguous T wave changes 1, 5, 2
• Electrolyte abnormalities, particularly hypokalemia, cause diffuse T wave flattening or inversion across multiple non-contiguous leads 5

Cardiomyopathies

• Hypertrophic cardiomyopathy produces T wave inversions that may appear non-contiguous when involving both anterior and lateral territories, particularly with apical variant (Yamaguchi syndrome) showing giant inversions 6, 1, 4, 7
• Left ventricular non-compaction causes scattered T wave inversions across multiple territories 1
• Arrhythmogenic right ventricular cardiomyopathy (ARVC) produces T wave inversions that may extend beyond typical contiguous patterns 1, 5
• Cardiac amyloidosis can cause diffuse repolarization abnormalities with low voltage, creating non-contiguous T wave patterns 6

Inflammatory and Infiltrative Conditions

• Myocarditis produces diffuse, non-contiguous T wave inversions with elevated troponin, often without chest pain 8, 2
• Late-stage pericarditis causes widely splayed T wave inversions that may appear non-contiguous 2

Genetic and Metabolic Disorders

• Mitochondrial disorders (MELAS, MERFF) produce diffuse conduction and repolarization abnormalities with scattered T wave inversions 6
• Storage diseases (Pompe, Danon, Anderson-Fabry, PRKAG2) cause non-contiguous patterns due to diffuse myocardial infiltration 6
• Noonan/LEOPARD syndrome produces scattered repolarization abnormalities 6

Critical Distinguishing Features

Morphology Matters

• Narrow, symmetric inversions with isoelectric ST segments suggest coronary ischemia (typically contiguous) 2
• Wide, splayed inversions scattered across leads indicate non-cardiac causes (CNS events, pulmonary embolism) or cardiomyopathy 3, 2
• Giant inversions (>10 mm) in non-contiguous leads suggest apical hypertrophic cardiomyopathy, raised intracranial pressure, or pulmonary embolism 6, 4

Distribution Patterns

• Anterior + lateral involvement (non-contiguous) raises suspicion for hypertrophic cardiomyopathy or left ventricular non-compaction 1, 8
• Diffuse/global pattern suggests CNS event, medication effect, or myocarditis 1, 3
• Inferior lead inversions alone are often benign and not associated with increased mortality 9

Diagnostic Algorithm

Immediate Evaluation

• Obtain detailed history focusing on neurological symptoms (headache, altered mental status), chest pain character, medication list, and family history of sudden cardiac death or cardiomyopathy 1, 5
• Serial ECGs comparing with prior tracings to assess for dynamic changes versus chronic pattern 6, 5
• Cardiac troponin at 0,1-2, and 3 hours to exclude acute myocardial injury or myocarditis 1, 8
• Electrolytes particularly potassium and calcium 5

Imaging Strategy

• Transthoracic echocardiography is mandatory for all patients with non-contiguous T wave inversions ≥1 mm depth to assess for cardiomyopathy, wall motion abnormalities, and structural disease 1, 8, 5
• Cardiac MRI with gadolinium when echocardiography is non-diagnostic but suspicion remains high, looking specifically for late gadolinium enhancement indicating fibrosis 1, 8
• Head CT/MRI if any neurological symptoms or signs present, as CNS events are a critical mimic 1, 3
• CT pulmonary angiography if clinical suspicion for pulmonary embolism exists 4

Risk Stratification

• Anterior and lateral T wave inversions (even if non-contiguous) independently predict increased CHD risk (HR 2.37 and 1.65 respectively) 9
• Lateral T wave inversions specifically associate with increased mortality (HR 1.51) even in patients without baseline CHD 9
• Inferior T wave inversions are generally benign and not associated with adverse outcomes 9

Common Pitfalls to Avoid

• Do not assume coronary ischemia based solely on T wave inversions—non-contiguous patterns argue against focal coronary disease and demand evaluation for systemic causes 1, 2
• Do not dismiss as "non-specific changes" without proper evaluation—non-contiguous inversions ≥1 mm depth in ≥2 leads require comprehensive workup 1, 8
• Do not overlook CNS events—deeply inverted T waves with QT prolongation may be the presenting sign of intracranial hemorrhage before neurological symptoms develop 1, 3
• Do not stop at normal initial echocardiogram—T wave inversions may precede structural changes in cardiomyopathy by months to years, requiring serial surveillance 1, 5
• Do not misinterpret secondary T wave changes—T wave abnormalities secondary to bundle branch block or ventricular hypertrophy should be labeled as such, not as primary ischemic changes 6, 5

Follow-Up Strategy

• Serial ECGs and echocardiography every 6-12 months even when initial evaluation is normal, as T wave inversions may represent initial phenotypic expression before structural changes become detectable 1, 8, 5
• Cardiology consultation for ongoing management, particularly with lateral lead involvement or concerning family history 1, 8
• Genetic counseling and family screening when cardiomyopathy is diagnosed 8