Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a complex cardiomyopathy with autosomal dominant inheritance and age-related incomplete penetrance, characterized by a high risk of sudden cardiac death. Recent professional consensus guidelines recommend clinical cardiac lifelong serial screening for at-risk family members refined only by age, but family genotype might influence necessary screening. Although numerous studies report prevalence of disease and arrhythmia in family members and explore predictors of penetrance and arrhythmic risk, a systematic review consolidating this evidence is lacking.
Methods: We searched Medline (PubMed), Embase, The Cochrane Library, and Web of Science for studies that reported prevalence of (1) diagnosis of ARVC per 2010 Task Force Criteria and/or (2) sustained ventricular arrhythmias (VA) in at least 10 family members of definite patients with ARVC.
Results: We identified 41 studies, including 36 that reported diagnosis by Task Force Criteria and 22 VA. Meta-analysis of 1359 family members, from 13 unique cohorts showed an average prevalence estimate of 25% for diagnosis as per Task Force Criteria (95% CI, 0.15-0.35, I2=96.44%). Overall prevalence of VA among gene-positive family members was 18% (95% CI, 0.13-0.23, I2=33.25%) in 7 independent studies (n=597). Family genotype was a significant risk factor for diagnosis of both ARVC (odds ratio, 6.91 [95% CI, 1.27-37.70]; P=0.0005) and VA (odds ratio, 13.62 [95% CI, 0.91-204.13]; P=0.06). Male gender was not associated with disease prevalence (odds ratio, 1.18 [95% CI, 0.72-1.95]; P=0.42) or VA (odds ratio, 0.81 [95% CI, 0.51-1.29]; P=0.91).
Conclusions: The prevalence of ARVC and VA in at-risk family members differs significantly based on family genotype. Although recent recommendations provide a guideline based only on age, we propose screening every 1 to 2 years for gene-positive family members and every 3 to 5 years for first-degree relatives of gene-elusive cases, as long as they are asymptomatic and not athletes.
Keywords: cardiomyopathy; diagnosis; family; genotype; prevalence.