Anterior T Wave inversion as a marker of cardiomyopathy: distinguishing benign from pathological patterns in young individuals

Background Anterior T-wave inversion (ATWI) is a relatively common finding in young individuals. While ATWI may reflect a benign juvenile pattern or physiological adaptation to exercise, it may also be an early marker of cardiomyopathy, particularly arrhythmogenic cardiomyopathy (ACM). Distinguishing benign from pathological ATWI remains an unmet clinical need in cardiovascular screening. Purpose This study sought to differentiate benign ATWI from ATWI suggestive of underlying cardiomyopathy by evaluating final clinical diagnoses, alongside demographic characteristics and ECG features, in a large cohort of young individuals undergoing cardiac screening. Methods Between 2008 and 2018, a cohort of 23,276 individuals aged 14–35 years underwent voluntary cardiac screening (ECG and health questionnaire) in the UK and had complete follow-up data available through a follow-up questionnaire. Final diagnoses were obtained through clinical evaluation and national digital follow-up using linkage to centralised health data, ensuring complete ascertainment of diagnoses. Individuals with ATWI were referred for comprehensive evaluation. For the analysis, we focused on isolated ATWI, defined as inversion restricted to the anterior leads without TWI in other leads, in the absence of RBBB. Results Out of the 15,454 individuals aged 16 and above, 440 (2.85%) had ATWI and 301 (1.94%) had isolated ATWI (70.4% females and 85.3% white). A total of 12/301 (4%) individuals were diagnosed with a cardiomyopathy: 8 with ACM, 2 with dilated cardiomyopathy and 2 with hypertrophic cardiomyopathy. Six individuals were diagnosed with other cardiac conditions: 2 with long-QT syndrome, one with Brugada syndrome, two with atrial septal defect and one with ventricular septal defect. Two individuals suffered an out-of-hospital cardiac arrest during follow-up: one was prior diagnosed with ACM, while the other was labelled as idiopathic ventricular fibrillation. Individuals who were eventually diagnosed with a cardiomyopathy were more commonly males (67% vs 28%, p=0.008), exhibited more frequently left axis deviation (LAD) (25% vs 4%, p=0.001), TWI to V4 (33% vs 12%, p=0.05), at least 1 one premature ventricular contraction (PVC) (17% vs 0.4%, p=0.004), S-wave terminal activation delay >55ms (TAD) (17% vs 0%, p=0.001) and deep TWI (at least 2mm, 58% vs 29%, p=0.048). The variable that was more strongly associated with cardiomyopathy was LAD (OR 8.2, 95% CI 1.95-34.63, p=0.015). When TWI was limited to V1-V2, none of these individuals had isolated TWI, but also showed other features, such as LAD and PVCs. Conclusion In a large cohort of young individuals undergoing cardiac screening, isolated ATWI was infrequently associated with an underlying cardiomyopathy, but when present, it most commonly signalled ACM. Male sex, deeper T-wave inversion, left axis deviation, TAD >55ms, and at least 1 PVC were key features distinguishing pathological from benign ATWI.Central figure