What are the differential diagnoses for a biphasic T wave in the presence of normal coronary (coronary arteries) arteries?

Differential Diagnoses for Biphasic T Waves with Normal Coronary Arteries

Biphasic T waves in the presence of normal coronary arteries most commonly represent either a normal age-related variant in adolescents (juvenile pattern), a benign athletic adaptation in young athletes (particularly Black athletes in anterior leads), or early manifestations of cardiomyopathy that precede structural changes detectable by standard imaging. 1, 2, 3

Normal Physiologic Variants

Age-Related (Juvenile Pattern)

• Biphasic T waves or T-wave inversion beyond V2 in adolescents under 16 years who have not reached physical maturity is considered normal and does not require further evaluation in the absence of symptoms, signs, or family history of cardiac disease 1
• This pattern is present in 10-15% of white adolescent athletes aged 12 years but only 2.5% of those aged 14-15 years 1
• Anterior T-wave inversion extending beyond V2 is rare (0.1%) in white athletes ≥16 years or those who have completed puberty 1

Athletic Heart Adaptation

• In Black athletes, J-point elevation with convex ST-segment elevation followed by biphasic T waves in V1-V4 is a normal variant and should not prompt further investigation when present in isolation 1
• This pattern occurs in 63-91% of Black athletes of African-Caribbean descent 1
• Early repolarization with J-point elevation, concave ST-segment elevation, and peaked T waves is present in up to 45% of Caucasian athletes and is considered benign 1

Pathologic Cardiac Causes (Despite Normal Coronaries)

Wellens Syndrome Type A (Critical LAD Stenosis)

• Biphasic T waves in V2-V3 with a negative component ≥1 mm require urgent evaluation to exclude critical proximal LAD stenosis, even if initial coronary imaging appears normal, as this may represent dynamic stenosis or vasospasm 3, 4, 5
• This pattern is associated with anterior wall hypokinesis and high risk with medical management alone 2
• The biphasic pattern (Type A) may progress to deeply inverted T waves (Type B) 3, 4
• Revascularization often reverses both the T-wave abnormality and wall-motion disorder 2

Early Cardiomyopathy

• T-wave abnormalities may represent the only sign of inherited heart muscle disease even before structural changes are detectable on echocardiography or standard cardiac MRI 2, 3
• Arrhythmogenic right ventricular cardiomyopathy (ARVC) characteristically shows anterior T-wave inversion in V1-V2/V3 3
• Absence of J-point elevation or presence of ST-segment depression makes ARVC more likely than athlete's heart 3
• T-wave abnormalities may precede structural changes by months to years 3

Myocarditis

• Post-viral myocarditis (including post-COVID-19) can present with biphasic T waves and normal coronaries 2
• May present with chest pain as the only symptom with preserved LV function 2

Non-Cardiac Causes

Central Nervous System Events

• Intracranial hemorrhage, subarachnoid hemorrhage, and other CNS events can produce deep biphasic or inverted T waves with QT prolongation 1, 2
• These changes occur in the absence of coronary disease 1, 2

Medications

• Tricyclic antidepressants and phenothiazines can cause deep T-wave abnormalities including biphasic patterns 1, 2
• Drug-induced changes are reversible with discontinuation 2

Electrolyte Abnormalities

• Hypokalemia causes T-wave flattening with ST depression and prominent U waves that reverse completely with potassium repletion 2
• Electrolyte abnormalities can affect repolarization and cause various T-wave changes 2

Conduction Abnormalities

• Right precordial biphasic or inverted T waves may result from recent left bundle branch block itself, even in the absence of coronary artery disease 6
• T-wave abnormalities during LBBB conduction occur in 48% of cases and are more common than in permanent LBBB 6

Other Cardiac Conditions with Normal Coronaries

Takotsubo Cardiomyopathy

• Stress cardiomyopathy can present with ST-T changes including biphasic T waves similar to ischemic patterns 1, 7
• Typically occurs in postmenopausal women with emotional or physical stress 1

Pericarditis

• Acute pericarditis may show ST-T changes that could include biphasic T waves 1, 7
• Distinguished by diffuse distribution, PR depression, and clinical features 1

Left Ventricular Hypertrophy

• LVH can cause ST-T changes including biphasic patterns that may mimic ischemia 7
• Voltage criteria and strain patterns help identify this cause 1

Diagnostic Algorithm for Biphasic T Waves with Normal Coronaries

Immediate Assessment

1. Obtain detailed history focusing on: recent chest pain episodes, syncope, family history of sudden cardiac death or cardiomyopathy, medication use, and recent CNS events 3
2. Assess age: <16 years suggests juvenile pattern; adult requires full workup 3
3. Determine ethnicity: Black athletes may have normal variant if limited to single lead with J-point elevation 3
4. Measure depth of negative component: ≥1 mm in ≥2 contiguous leads is pathological 3

ECG Analysis

• Assess for J-point elevation and ST-segment morphology: presence suggests benign athletic adaptation; absence or ST depression suggests ARVC or ischemia 3
• Compare with previous ECGs when available 7
• Obtain serial ECGs to detect evolution of pattern 7

Risk Stratification

• High-risk features requiring urgent action: biphasic T waves in V2-V3 with negative component ≥1 mm, recent chest pain, anterior wall motion abnormalities, or family history of sudden death 3, 8
• Intermediate concern: isolated biphasic T waves in single lead V3 in athletes, or in adolescents <16 years without other features 1, 3

Further Testing

• Serial cardiac biomarkers to exclude acute coronary syndrome 2
• Echocardiography to assess for structural heart disease and wall motion abnormalities 3
• Cardiac MRI for suspected cardiomyopathy, particularly if echocardiography is normal but clinical suspicion remains high 3
• Exercise stress testing or pharmacologic stress imaging if ischemia suspected despite normal resting coronaries 2
• Electrolyte panel including potassium and magnesium 2

Long-Term Surveillance

• Serial cardiac imaging (echocardiography or cardiac MRI) at 6-12 month intervals initially, even if initial evaluation is normal, for all patients with pathological biphasic T waves 3
• Continued clinical surveillance is essential as T-wave abnormalities may identify patients at risk for subsequent development of structural heart disease 2, 3

Critical Pitfalls to Avoid

• Do not dismiss biphasic T waves in V2-V3 as benign without excluding Wellens syndrome, even if initial coronary imaging is normal, as this represents dynamic stenosis that may not be apparent on resting angiography 3, 4, 5
• Do not assume all anterior T-wave changes in young athletes are benign; biphasic T waves in only V3 are acceptable in athletes, but extension beyond this or presence in lateral/inferior leads warrants investigation 1, 3
• Do not overlook medication history, particularly tricyclic antidepressants and phenothiazines, which can mimic cardiac pathology 1, 2
• Do not fail to consider CNS events in patients with dramatic T-wave changes and normal coronaries, especially with altered mental status or neurologic symptoms 2
• Do not rely solely on initial imaging; structural cardiomyopathy may not be evident for months to years after ECG changes appear 2, 3