Screening for Dilated Cardiomyopathy in At-Risk First-Degree Relatives

• Type of Material: Article
• Authors: Hanyu Ni, The Ohio State University, Columbus; Elizabeth Jordan, The Ohio State University, Columbus; Daniel D. Kinnamon, The Ohio State University, Columbus; Jinwen Cao, The Ohio State University, Columbus; Garrie J. Haas, The Ohio State University, Columbus; Mark Hofmeyer, Washington Hospital Center; Evan Kransdorf, Cedars-Sinai Medical Center; Gregory A. Ewald, Washington University, St Louis; Alanna Morris, Emory University; Anjali Owens, University of Pennsylvania; Brian Lowes, University of Nebraska, Omaha; Douglas Stoller, University of Nebraska, Omaha; W.H. Wilson Tang, Cleveland Clinic; Sonia Garg, University of Texas, Dallas; Barry H. Trachtenberg, J.C. Walter Jr Transplant Center; Palak Shah, Inova Heart Vascular Institute; Salpy V. Pamboukian, University of Alabama, Birmingham; Nancy K. Sweitzer, University of Arizona, Tucson; Matthew T. Wheeler, Stanford University; Jane E. Wilcox, Northwestern University; Stuart Katz, New York University; Stephen Pan, New York Medical College; Javier Jimenez, Baptist Health South; Daniel P. Fishbein, University of Washington, Seattle; Frank Smart, Louisiana State University; Jessica Wang, University of California, Los Angeles; Stephen S. Gottlieb, University of Maryland, Baltimore; Daniel P. Judge, University of South Carolina, Charleston; Charles K. Moore, University of Mississippi, Jackson; Gordon S. HUggins, Tufts University; Ray E. Hershberger, The Ohio State University, Columbus
• Language: English
• Date: 2023-05-30
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2023 by the American College of Cardiology Foundation. Published by Elsevier.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1016/j.jacc.2023.03.419
• Title of Journal or Parent Work: Journal of the American College of Cardiology
• Volume: 81
• Issue: 21
• Start Page: 2059
• End Page: 2071
• Grant/Funding Information: Research reported in this publication was supported by a parent award from the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number R01HL128857, which included a supplement from the National Human Genome Research Institute. The DCM Precision Medicine Study was supported by computational infrastructure provided by The Ohio State University Division of Human Genetics Data Management Platform and the Ohio Supercomputer Center.
• Keywords: screening; dilated cardiomyopathy; cardiology; family members
• Research Categories: Biology, Genetics; Health Sciences, Public Health; Health Sciences, Epidemiology

Abstract

BACKGROUND Cardiovascular screening is recommended for first-degree relatives (FDRs) of patients with dilated cardiomyopathy (DCM), but the yield of FDR screening is uncertain for DCM patients without known familial DCM, for non-White FDRs, or for DCM partial phenotypes of left ventricular enlargement (LVE) or left ventricular systolic dysfunction (LVSD). OBJECTIVES This study examined the yield of clinical screening among reportedly unaffected FDRs of DCM patients. METHODS Adult FDRs of DCM patients at 25 sites completed screening echocardiograms and ECGs. Mixed models accounting for site heterogeneity and intrafamilial correlation were used to compare screen-based percentages of DCM, LVSD, or LVE by FDR demographics, cardiovascular risk factors, and proband genetics results. RESULTS A total of 1,365 FDRs were included, with a mean age of 44.8 ± 16.9 years, 27.5% non-Hispanic Black, 9.8% Hispanic, and 61.7% women. Among screened FDRs, 14.1% had new diagnoses of DCM (2.1%), LVSD (3.6%), or LVE (8.4%). The percentage of FDRs with new diagnoses was higher for those aged 45 to 64 years than 18 to 44 years. The age-adjusted percentage of any finding was higher among FDRs with hypertension and obesity but did not differ statistically by race and ethnicity (16.2% for Hispanic, 15.2% for non-Hispanic Black, and 13.1% for non-Hispanic White) or sex (14.6% for women and 12.8% for men). FDRs whose probands carried clinically reportable variants were more likely to be identified with DCM. CONCLUSIONS Cardiovascular screening identified new DCM-related findings among 1 in 7 reportedly unaffected FDRs regardless of race and ethnicity, underscoring the value of clinical screening in all FDRs.