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

Hanyu Ni; Elizabeth Jordan; Daniel D Kinnamon; Jinwen Cao; Garrie J Haas; 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; Daniel P Fishbein; Frank Smart; Jessica Wang; Stephen S Gottlieb; Daniel P Judge; Charles K Moore; Gordon S Huggins; Ray E Hershberger; DCM Precision Medicine Study of the DCM Consortium

doi:10.1016/j.jacc.2023.03.419

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

J Am Coll Cardiol. 2023 May 30;81(21):2059-2071. doi: 10.1016/j.jacc.2023.03.419.

Authors

Hanyu Ni¹, Elizabeth Jordan¹, Daniel D Kinnamon¹, Jinwen Cao¹, Garrie J Haas², Mark Hofmeyer³, Evan Kransdorf⁴, Gregory A Ewald⁵, Alanna A Morris⁶, Anjali Owens⁷, Brian Lowes⁸, Douglas Stoller⁸, W H Wilson Tang⁹, Sonia Garg¹⁰, Barry H Trachtenberg¹¹, Palak Shah¹², Salpy V Pamboukian¹³, Nancy K Sweitzer¹⁴, Matthew T Wheeler¹⁵, Jane E Wilcox¹⁶, Stuart Katz¹⁷, Stephen Pan¹⁸, Javier Jimenez¹⁹, Daniel P Fishbein²⁰, Frank Smart²¹, Jessica Wang²², Stephen S Gottlieb²³, Daniel P Judge²⁴, Charles K Moore²⁵, Gordon S Huggins²⁶, Ray E Hershberger²⁷; DCM Precision Medicine Study of the DCM Consortium

Affiliations

¹ Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; The Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
² The Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA; Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA.
³ Medstar Research Institute, Washington Hospital Center, Washington, DC, USA.
⁴ Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁵ Washington University, St Louis, Missouri, USA.
⁶ Emory University School of Medicine, Atlanta, Georgia, USA.
⁷ Center for Inherited Cardiovascular Disease, Division of Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁸ University of Nebraska Medical Center, Omaha, Nebraska, USA.
⁹ Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio, USA.
¹⁰ University of Texas Southwestern Medical Center, Dallas, Texas, USA.
¹¹ Houston Methodist DeBakey Heart and Vascular Center, J.C. Walter Jr Transplant Center, Houston Texas, USA.
¹² Inova Heart and Vascular Institute, Falls Church, Virginia, USA.
¹³ University of Alabama, Birmingham, Alabama, USA.
¹⁴ Sarver Heart Center, University of Arizona, Tucson, Arizona, USA (current address Division of Cardiology, Washington University, St Louis, Missouri, USA).
¹⁵ Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA.
¹⁶ Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁷ New York University Langone Medical Center, New York, New York, USA.
¹⁸ Department of Cardiology, Westchester Medical Center and New York Medical College, Valhalla, New York, USA.
¹⁹ Miami Cardiac and Vascular Institute, Baptist Health South, Miami, Florida, USA.
²⁰ University of Washington, Seattle, Washington, USA.
²¹ Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
²² University of California Los Angeles Medical Center, Los Angeles, California, USA.
²³ University of Maryland School of Medicine, Baltimore, Maryland, USA.
²⁴ Medical University of South Carolina, Charleston, South Carolina, USA.
²⁵ University of Mississippi Medical Center, Jackson, Mississippi, USA.
²⁶ Cardiology Division, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts, USA.
²⁷ Division of Human Genetics, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA; The Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA; Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio, USA. Electronic address: Ray.Hershberger@osumc.edu.

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.

Keywords: dilated cardiomyopathy; family members; screening.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adult
Black People
Cardiomyopathy, Dilated* / diagnosis
Cardiomyopathy, Dilated* / genetics
Echocardiography
Ethnicity
Female
Hispanic or Latino
Humans
Hypertrophy, Left Ventricular
Male
Middle Aged

Abstract

Publication types

MeSH terms

Grants and funding