Evaluation of Women With Peripartum or Dilated Cardiomyopathy and Their First-Degree Relatives: The DCM Precision Medicine Study

Authors

• Evan P. Kransdorf, Cedars-Sinai Medical Center, Los Angeles, CA
• Rashmi Jain, Cedars-Sinai Medical Center, Los Angeles, CA
• Jonathan O. Mead, Ohio State University, Columbus, OH
• Garrie Haas, Ohio State University, Columbus, OH
• Mark Hofmeyer, Washington Hospital Center, Washington, DC
• Gregory A. Ewald, Washington University in St. Louis, St. Louis, MO
• Jamie Diamond, Emory University, Atlanta, GA
• Anjali Owens, University of Pennsylvania, Philadelphia, PA
• Brian Lowes, University of Nebraska Medical Center, Omaha, NE
• Douglas Stoller, University of Nebraska Medical Center, Omaha, NE
• W. H.Wilson Tang, Cleveland Clinic Foundation, Clveland, OH
• Mark H. Drazner, University of Texas Southwestern Medical Center, Dallas, TX
• Cindy M. Martin, Houston Methodist Hospital, Houston, TX
• Palak Shah, Houston Methodist Hospital, Houston, TX
• Jose Tallaj, University of Alabama at Birmingham, Birmingham, AL
• Stuart Katz, NYU Langone Medical Center, New York, NY
• Javier Jimenez, Baptist Health South, Miami, FL
• Supriya Shore, University of Michigan Medical Center, Ann Arbor, MI
• Frank Smart, LSU Health Sciences Center - New OrleansFollow
• Jessica Wang, University of California Los Angeles Medical Center, Los Angeles, CA
• Stephen S. Gottlieb, University of Maryland, Baltimore, MD
• Daniel P. Judge, Medical University of South Carolina, Charleston, SC
• Gordon S. Huggins, Tufts University, Boston, MA
• Jason Cowan, Ohio State University, Columbus, OH
• Patricia Parker, Ohio State University, Columbus, OH
• Jinwen Cao, Ohio State University, Columbus, OH
• Natalie S. Hurst, Ohio State University, Columbus, OH
• Elizabeth Jordan, Ohio State University, Columbus, OH
• Hanyu Ni, Ohio State University, Columbus, OH
• et al

Document Type

Article

Publication Date

3-25-2026

Publication Title

Circulation: Genomic and Precision Medicine

Abstract

BACKGROUND: – Rare variant genetics have been associated with peripartum cardiomyopathy (PPCM), but the role of genetics remains unsettled. The study sought to compare dilated cardiomyopathy (DCM) genetic risk in first-degree relatives (FDRs) of female patients (probands) with DCM or PPCM to gain causal inference, and to assess DCM-relevant rare variant prevalence in DCM/PPCM probands and population controls. METHODS: – Clinical and genetic data were analyzed from the DCM Precision Medicine Study. Risk of DCM or partial DCM, where partial DCM was defined as left ventricular enlargement or a left ventricular ejection fraction of < 50%, was estimated in 665 FDRs from 452 female probands, all of whom had been pregnant; 67 had PPCM and 385 had DCM; prevalence of pathogenic, likely pathogenic, or uncertain significance variants was estimated among probands. RESULTS: – The risk of DCM/partial DCM for FDRs of PPCM probands was similar to that for FDRs of DCM probands (hazard ratio, 0.77 [95% CI, 0.47–1.28]). Estimated DCM prevalence among the lowest-risk FDRs of non-Hispanic European ancestry probands with PPCM (7.0% [95% CI, 0%–14.1%] females, 9.0% [95% CI, 1.6%–16.3%] males) exceeded population estimates from a UK Biobank study (0.30% females, 0.63% males). Estimated prevalences of a pathogenic, likely pathogenic, or uncertain significance variant among African ancestry and European ancestry probands with PPCM were 55.4% (95% CI, 33.1%–77.7%) and 66.0% (95% CI, 38.6%–93.3%), respectively. The estimated prevalence of pathogenic/likely pathogenic variants among European ancestry PPCM probands (26.6% [95% CI, 12.6%–40.6%]) exceeded a population estimate from a UK Biobank study (0.6%). CONCLUSIONS: – The risk of DCM/partial DCM among FDRs was similar regardless of whether their probands had PPCM or DCM. Also, DCM-relevant rare variant findings for females with PPCM or DCM were similar and greater than in population controls, suggesting a similar causal basis for PPCM and DCM. These findings underscore the need for genetic evaluations in all patients with PPCM. REGISTRATION: – URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037632.

PubMed ID

41878807

Volume

19

Issue

2

Comments

See article for full author list.

Recommended Citation

Kransdorf, Evan P.; Jain, Rashmi; Mead, Jonathan O.; Haas, Garrie; Hofmeyer, Mark; Ewald, Gregory A.; Diamond, Jamie; Owens, Anjali; Lowes, Brian; Stoller, Douglas; Tang, W. H.Wilson; Drazner, Mark H.; Martin, Cindy M.; Shah, Palak; Tallaj, Jose; Katz, Stuart; Jimenez, Javier; Shore, Supriya; Smart, Frank; Wang, Jessica; Gottlieb, Stephen S.; Judge, Daniel P.; Huggins, Gordon S.; Cowan, Jason; Parker, Patricia; Cao, Jinwen; Hurst, Natalie S.; Jordan, Elizabeth; Ni, Hanyu; and al, et, "Evaluation of Women With Peripartum or Dilated Cardiomyopathy and Their First-Degree Relatives: The DCM Precision Medicine Study" (2026). School of Medicine Faculty Publications. 4701.
https://digitalscholar.lsuhsc.edu/som_facpubs/4701
10.1161/CIRCGEN.125.005541