Genetic Predisposition and Peripartum Cardiomyopathy

Study Questions:

Do peripartum and dilated cardiomyopathies share similar genetic predisposition?


A total of 172 women with peripartum cardiomyopathy (PPCM) were recruited from six independent groups, including the IMAC-2 (Intervention in Myocarditis and Acute Cardiomyopathy 2) study and the IPAC (Investigations in Pregnancy Associated Cardiomyopathy) trial. Reference groups were provided from the Exome Aggregation Consortium. In the 172 women, next-generation sequencing was performed on 43 genes with variants that have been associated with dilated cardiomyopathy (DCM). The prevalence of specific variant types was compared between PPCM, DCM, and population controls.


Approximately 30% of the women with PPCM were of African descent; 26 of the 172 carried 26 distinct rare heterozygous truncating variants in eight different genes. While the prevalence of truncating variants did not differ between cohorts, the prevalence in the women with PPCM (15%) was significantly higher than that in the reference population (4.7%) and similar to that in a cohort of DCM (17%). The majority of the truncating variants (65%) affected TTN. Of the 17 truncating variants that affected TTN, 14 were located in a region that encodes the A-band, the portion of the sarcomere that contains the myosin thick filament. The prevalence of this finding was significantly higher than in the reference populations (p = 0.002) and similar to the pattern in DCM. In the IPAC cohort, the prevalence of TTN truncating variants was significantly greater among patients without hypertension than among those with hypertension. In addition, the presence of this variant was associated with a lower ejection fraction at 1 year compared to patients without the variant.


PPCM shares a genetic predisposition with DCM, as demonstrated by a higher prevalence of TTN truncating variants. PPCM in patients with hypertension may represent a different pathophysiologic process than PPCM in the absence of hypertension.


The etiology of PPCM remains unclear; however, the identification of shared genetic determinants between PPCM and familial and sporadic idiopathic DCM is a step forward in potentially determining who may be at risk for PPCM.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Hypertension

Keywords: Cardiomyopathies, Cardiomyopathy, Dilated, Genetic Predisposition to Disease, Heart Failure, Heterozygote, Hypertension, Myocarditis, Myosins, Peripartum Period, Pregnancy, Sarcomeres

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