Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies

Abstract

To the Editor: Ware et al. report a striking similarity of the presumed genetic causes of peripartum and idiopathic dilated cardiomyopathies in a large series of women. In our recent analysis of data from a large administrative U.S. database (the Healthcare Cost and Utilization Project National Inpatient Sample), we found remarkable similarity between patients with dilated cardiomyopathy and those with peripartum cardiomyopathy in terms of demographic and clinical characteristics and patient outcomes in pregnancy during the hospitalization for delivery. 1 Approximately 30% of the women in each cohort were black, and the two cohorts had similarly elevated rates of death, heart failure, arrhythmias, and preeclampsia spectrum disorders. Perhaps some of the patients (mis)classified as having peripartum cardiomyopathy were women with an asymptomatic dilated cardiomyopathy before pregnancy, and the hemodynamic demands of pregnancy worsened the degree of left ventricular dysfunction, leading to clinical heart failure. Have the authors considered whether the overlap in the reported genetic variants is consequent to the same disease presenting differently owing to pregnancy? Kathleen Stergiopoulos, M.D., Ph.D. DOI: 10.1056/NEJMc1602671The authors reply: In response to Biteker: we agree that there is an important need for prognostic indicators for women with peripartum cardiomyopathy. Our study was not powered to test whether genetic variants correlate with clinical outcomes, nor did we have information on clinical outcomes for all patients. We did, however, have information for 1 year after enrollment on the 83 women in the Investigations in Pregnancy Associated Cardiomyopathy (IPAC) study. We noted that women enrolled in that study whoThe New England Journal of Medicine Downloaded from nejm.org at IMPERIAL COLLEGE LONDON on August 4, 2016. For personal use only. No other uses without permission.

Association of Variants in BAG3 With Cardiomyopathy Outcomes in African American Individuals

“…13 Truncating variants in TTN, the gene most commonly associated with DCM, 14 are more prevalent in women of African ancestry with postpartum cardiomyopathy than in women of European ancestry with postpartum cardiomyopathy. 15 Genetic variants in more than 40 genes have been linked with DCM. One such gene encodes Bcl-2-associated athanogene 3 (BAG3), an evolutionarily conserved protein that is expressed predominantly in the heart and skeletal muscle and in many cancers.…”

Titin mutations and muscle disease

“…TTNtv have also been linked to peripartum cardiomyopathy (PPCM) where the distribution of truncating variants in PPCM is similar to that found in DCM [108,112]. PPCM can also be a manifestation of familial DCM and TTNtv in PPCM patients is a possible prognostic factor for low recovery rate [108,112].…”

Making sense of missense variants in TTN-related congenital myopathies

“…TTN-related myopathies show considerable clinico-pathological overlap as a group but also with other neuromuscular disorders, in particular the congenital myopathies (CMs), limb girdle muscular dystrophies (LGMDs) and distal myopathies. TTN mutations, whether recessive or dominant, are also emerging as major causes of dilated cardiomyopathy [3,18,43,59,60] and have been implicated in hypertrophic cardiomyopathy (HCM) [35], however no families with co-segregation of TTN missense variants with HCM or DCM have been identified to date [1,56].…”