Prospective evaluation of relatives for familial arrhythmogenic right ventricular cardiomyopathy/dysplasia reveals a need to broaden diagnostic criteria.

Objectives: We sought to ascertain the prevalence and mode of expression of familial disease in a consecutive series of patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D).

Background: Autosomal-dominant inheritance is recognized in ARVC. The prevalence and mode of expression of familial disease in consecutive, unselected families is uncertain.

Methods: First- and second-degree relatives of 67 ARVC index patients underwent cardiac evaluation with history and examination, 12-lead and signal-averaged electrocardiogram (ECG), two-dimensional and Doppler echocardiography, metabolic exercise testing and Holter monitoring. Diagnoses were made in accordance with published criteria.

Results: Of 298 relatives, 29 (10%; mean age 37.4 +/- 16.4 years) had ARVC. These were from 19 of the 67 families, representing familial involvement in 28%. Of these affected relatives, 72% were asymptomatic, 17% had ventricular tachycardia (sustained VT 10%, nonsustained VT 7%) and 21% had left ventricular involvement. A further 32 relatives (11%; 37.7 +/- 12.4 years) exhibited nondiagnostic ECG, echocardiographic or Holter abnormalities. Fifteen of these relatives were from families with only the proband affected, and inclusion of this subset of relatives would have resulted in familial ARVC in 48% of index cases. Four additional relatives (1% to 3%) fulfilled diagnostic criteria for dilated cardiomyopathy without any features of right ventricular disease.

Conclusions: By using current diagnostic criteria, familial disease was present in 28% of index patients. A further 11% of their relatives had minor cardiac abnormalities, which, in the context of a disease whose mode of inheritance is autosomal dominant, are likely to represent early or mild disease expression. We advocate that the current ARVC diagnostic criteria are modified to reflect the broader spectrum of disease that is observed in family members.