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

BACKGROUND

Peripartum cardiomyopathy (PPCM) presents substantial risk of maternal mortality, but underlying cause remains unsettled.

METHODS

We compared the prevalence of dilated cardiomyopathy (DCM)-relevant genetic variants in 452 female patients (probands) of African and European ancestry (AA, EA) with PPCM or DCM who had been pregnant at least once. Pathogenic and likely pathogenic (P/LP) variants were identified in DCM-associated genes. Risk of DCM or partial DCM, defined as left ventricular enlargement or a left ventricular ejection fraction of <50%, were compared in 665 FDRs of PPCM and DCM probands.

RESULTS

The estimated prevalences of P/LP findings among 67 probands with PPCM compared to 385 probands with DCM were comparable within ancestry (for AA, 7.8% [95% CI: 0.0%-15.7%] vs. 7.8% [95% CI: 1.1%-14.4%]; for EA, 29.5% [12.5%-46.5%] vs. 29.8% [15.5%-44.2%]). The risk of DCM/partial DCM was not lower for FDRs of PPCM probands relative to FDRs of DCM probands (HR, 0.77; 95% CI, 0.47 - 1.28). For an FDR of a non-Hispanic EA proband with PPCM, the lowest estimated DCM/partial DCM risk by age 80 was 26.8% (95% CI, 15.0%-45.0%) compared to 33.2% (95% CI, 21.2%-49.5%) for an FDR of a proband with DCM. Further validating PPCM genetic risk by using a set of genes common between studies, the estimated prevalence of P/LP variants among EA PPCM probands (26.6%; 95% CI, 12.6%-40.6%) was higher than the general population estimate from a UK Biobank study (0.6%), Also, the estimated DCM prevalence among the lowest-risk FDRs of non-Hispanic EA probands with PPCM (7.0% [95% CI, 0%-14.1%] females, 9.0% [95% CI, 1.6%-16.3%] males) was higher than general population estimates from another UK Biobank study (0.30% females, 0.63% males).

CONCLUSIONS

Comparing women with PPCM to those with DCM, a similar prevalence of DCM-relevant genetic variants and similar risk of DCM or partial DCM among their first-degree relatives were observed. These findings, along with comparisons to the general population showing higher prevalence of DCM-relevant genetic variants in women with PPCM and higher DCM prevalence in their FDRs, strengthen evidence for the genetic basis of PPCM and underscore the need for clinical genetic evaluations for PPCM patients.

CLINICAL TRIAL

clinicaltrials.gov, NCT03037632.