Arrhythmogenic right ventricular cardiomyopathies: Diagnostic challenges from imaging to genetics

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary cardiomyopathy, predominantly affecting young males, regardless of their ethnicity. Due to its variable penetrance, females usually have milder and less malignant phenotypes, and it may be diagnosed in older individuals. Accordingly, some affected individuals may remain asymptomatic while in others sudden cardiac death represents the inaugural symptom. Exercise-related palpitations and syncope are red-flag symptoms in otherwise healthy adolescents and young adults and should be fully investigated, with ARVC as a potential diagnosis. Clinicians should adopt a cardiomyopathy-oriented mindset that is focused on recognizing suspicious electrocardiograms, structural abnormalities, and family history of sudden cardiac death. Complete baseline investigations should be performed in all individuals with a clinical suspicion of ARVC, regardless of their symptoms. These include multi-modality imaging (echocardiogram, cardiac magnetic resonance imaging), electrocardiogram monitors, and maximal exercise tolerance tests. Genetic testing should be regarded as the final piece of the puzzle and offered in individuals with a high pre-test probability. A clinically actionable result allows for predictive family testing and pre-implantation diagnosis. Importantly, it should be offered only with appropriate pre and post-test counseling. Both clinicians and patients should understand that not identifying a disease-causing variant causing the disease does not exclude ARVC. Finally, three clinical cases illustrating the potential caveats in diagnosing ARVC are discussed.