Genetic similarities in cardiomyopathies

The incidence of peripartum cardiomyopathy is 1 in 4000 pregnant women in Western Europe, but is as high as 1 in 100 in Haiti and Nigeria.  Although peripartum cardiomyopathy can resolve, it can also be devastating as evidenced by a 5 to 10% mortality rate and the condition accounting for 4% of all U.S. women receiving heart transplantation.  Although risk factors such as pre-eclampsia, twin pregnancies, and advanced maternal age have been identified, little is known about the pathophysiology of peripartum cardiomyopathy and an individual’s susceptibility to this condition.  In comparison, the genetic underpinnings of what was previously considered idiopathic dilated cardiomyopathy are increasingly understood.  Given phenotypic similarities between peripartum cardiomyopathy and dilated cardiomyopathy, the authors sought to evaluate the contribution of genetic variants previously described in dilated cardiomyopathy among women with peripartum cardiomyopathy.  In this study, 172 women with peripartum cardiomyopathy underwent genetic sequencing of 43 genes associated with dilated cardiomyopathy.  The prevalence of variants was compared both with a population of patients with dilated cardiomyopathy and healthy controls.  A total of 26 distinct truncating variants were identified in eight genes among the women with peripartum cardiomyopathy.  The prevalence of these variants in women with peripartum cardiomyopathy (15%) were similar to that of patients with dilated cardiomyopathy (17%, P=0.81) and more common than a healthy population (4.7%, P = 1.3×10−7). Two-thirds of these variants were in the gene TTN which encodes for the very large structural cardiac sarcomeric protein titin.  Seven of these TTN variants had been previously described in patients with dilated cardiomyopathy.  Furthermore, TTN truncating variants in women with peripartum cardiomyopathy were correlated with a lower ejection fraction at 1-year follow-up (P = 0.005).


In this study of a well-characterized cohort of women with peripartum cardiomyopathy, genetic variants of the structural protein titin, which have previously been described in dilated cardiomyopathy, were implicated in development of the peripartum cardiomyopathy.  Further characterization of the pathophysiology and genetics of this condition will afford better risk prediction and may eventually lead to more targeted therapeutics.

Summarized by Hussain Contractor and Steven M. Bradley

Ware JS, Li J, Mazaika E, Yasso CM, DeSouza T, Cappola TP, Tsai EJ, Hilfiker-Kleiner D, Kamiya CA, Mazzarotto F, Cook SA, Halder I, Prasad SK, Pisarcik J, Hanley-Yanez K, Alharethi R, Damp J, Hsich E, Elkayam U, Sheppard R, Kealey A, Alexis J, Ramani G, Safirstein J, Boehmer J, Pauly DF, Wittstein IS, Thohan V, Zucker MJ, Liu P, Gorcsan J 3rd, McNamara DM, Seidman CE, Seidman JG and Arany Z. Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies. N Engl J Med. 2016 Jan 6. [Epub ahead of print]

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