Family Screening in Dilated Cardiomyopathy Prevalence, Incidence, and Potential for Limiting Follow-Up

BACKGROUND According to patterns of inheritance and incomplete penetrance, fewer than half of relatives to dilated cardiomyopathy probands will develop disease. OBJECTIVES The purpose of this study was to investigate the prevalence and incidence, and to identify predictors of developing familial dilated cardiomyopathy (FDC) in relatives participating in family screening. RESULTS In total, 211 families (563 relatives, 50% women) were included. At baseline, 124 relatives (22%) were diagnosed with FDC. Genetic sequencing identified the etiology in 37% of screened families and classified 101 (18%) relatives as unaffected carriers (n = 43) or noncarriers (ie, not at risk of FDC [n = 58]). The combined clinical and genetic baseline yield was 30%. During follow-up (2,313 person-years, median 5.0 years), 45 developed FDC (incidence rate of 2.0% per person-year; 95% CI: 1.4%-2.8%), increasing the overall yield to 34%. The incidence rate of FDC was high in relatives with baseline abnormalities on electrocardiogram or echocardiography compared with relatives with normal findings (4.7% vs 0.4% per person-year; HR: 12.9; P < 0.001). In total, baseline screening identified 326 (58%) relatives to be at low risk of FDC. CONCLUSIONS Family screening identified a genetic predisposition to or overt FDC in 1 of 3 relatives at baseline. Genetic and clinical screening was normal in more than half of relatives, and these relatives had a low risk of developing FDC during follow-up. Thus, baseline screening identified a large proportion, in whom follow-up may safely be reduced, allowing focused follow-up of relatives at risk. (J Am Coll Cardiol HF 2022;10:792-803) (c) 2022 by the American College of Cardiology Foundation.