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

BACKGROUND

Rare variant genetics have been associated with peripartum cardiomyopathy (PPCM) but the role of genetics remains unsettled.

OBJECTIVE

The study sought to compare dilated cardiomyopathy (DCM) genetic risk in first-degree relatives (FDRs) of female patients with DCM or PPCM (probands), 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 pDCM was defined as left ventricular (LV) enlargement or a LV ejection fraction of <50%, was estimated in 665 FDRs from 452 female probands, all of whom had been pregnant, of which 67 had PPCM and 385 had DCM; prevalence of pathogenic, likely pathogenic or uncertain significance variants (P/LP/VUS) was estimated among probands.

RESULTS

The risk of DCM/pDCM for FDRs of PPCM probands was similar to that for FDRs of DCM probands (HR, 0.77; 95% CI, 0.47 - 1.28). 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) exceeded population estimates from a UK Biobank study (0.30% females, 0.63% males). Estimated prevalences of a P/LP/VUS among AA and EA 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 P/LP variants among EA PPCM probands (26.6%; 95% CI, 12.6%-40.6%) exceeded a population estimate from a UK Biobank study (0.6%).

CONCLUSION

The risk of DCM/pDCM 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 shared genetic basis for PPCM and DCM. These findings underscore the need for genetic evaluations in all PPCM patients.