Prevalence and Cumulative Risk of Familial Idiopathic Dilated Cardiomyopathy
Authors: Gordon S. Huggins, Daniel D. Kinnamon, Garrie J. Haas, Elizabeth Jordan, Mark Hofmeyer, Evan Kransdorf, Gregory A. Ewald, Alanna A. Morris, Anjali Owens, Brian Lowes, Douglas Stoller, W. H. Wilson Tang, Sonia Garg, Barry H. Trachtenberg, Palak Shah, Salpy V. Pamboukian, Nancy K. Sweitzer, Matthew T. Wheeler, Jane E. Wilcox, Stuart Katz, Stephen Pan, Javier Jimenez, Keith D. Aaronson, Daniel P. Fishbein, Frank Smart, Jessica Wang, Stephen S. Gottlieb, Daniel P. Judge, Charles K. Moore, Jonathan O. Mead, Hanyu Ni, Wylie Burke, Ray E. Hershberger
Journal: JAMA (2022)

<h3>Importance</h3> Idiopathic dilated cardiomyopathy (DCM) aggregates in families, and early detection in at-risk family members can provide opportunity to initiate treatment prior to late-phase disease. Most studies have included only White patients, yet Black patients with DCM have higher risk of heart failure–related hospitalization and death. <h3>Objective</h3> To estimate the prevalence of familial DCM among DCM probands and the age-specific cumulative risk of DCM in first-degree relatives across race and ethnicity groups. <h3>Design, Setting, and Participants</h3> A family-based, cross-sectional study conducted by a multisite consortium of 25 US heart failure programs. Participants included patients with DCM (probands), defined as left ventricular systolic dysfunction and left ventricular enlargement after excluding usual clinical causes, and their first-degree relatives. Enrollment commenced June 7, 2016; proband and family member enrollment concluded March 15, 2020, and April 1, 2021, respectively. <h3>Exposures</h3> The presence of DCM in a proband. <h3>Main Outcomes and Measures</h3> Familial DCM defined by DCM in at least 1 first-degree relative; expanded familial DCM defined by the presence of DCM or either left ventricular enlargement or left ventricular systolic dysfunction without known cause in at least 1 first-degree relative. <h3>Results</h3> The study enrolled 1220 probands (median age, 52.8 years [IQR, 42.4-61.8]; 43.8% female; 43.1% Black and 8.3% Hispanic) and screened 1693 first-degree relatives for DCM. A median of 28% (IQR, 0%-60%) of living first-degree relatives were screened per family. The crude prevalence of familial DCM among probands was 11.6% overall. The model-based estimate of the prevalence of familial DCM among probands at a typical US advanced heart failure program if all living first-degree relatives were screened was 29.7% (95% CI, 23.5% to 36.0%) overall. The estimated prevalence of familial DCM was higher in Black probands than in White probands (difference, 11.3% [95% CI, 1.9% to 20.8%]) but did not differ significantly between Hispanic probands and non-Hispanic probands (difference, −1.4% [95% CI, −15.9% to 13.1%]). The estimated prevalence of expanded familial DCM was 56.9% (95% CI, 50.8% to 63.0%) overall. Based on age-specific disease status at enrollment, estimated cumulative risks in first-degree relatives at a typical US advanced heart failure program reached 19% (95% CI, 13% to 24%) by age 80 years for DCM and 33% (95% CI, 27% to 40%) for expanded DCM inclusive of partial phenotypes. The DCM hazard was higher in first-degree relatives of non-Hispanic Black probands than non-Hispanic White probands (hazard ratio, 1.89 [95% CI, 1.26 to 2.83]). <h3>Conclusions and Relevance</h3> In a US cross-sectional study, there was substantial estimated prevalence of familial DCM among probands and modeled cumulative risk of DCM among their first-degree relatives. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03037632