BACKGROUND Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. METHODS In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. RESULTS We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P = 1.3×10−7) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P = 0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P = 2.7×10−10); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P = 0.005). CONCLUSIONS The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder.

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1695T he incidence of coronary artery disease (CAD) in women of child-bearing age is low, and acute myocardial infarction (AMI) is uncommon.1,2 Pregnancy, however, has been shown to increase the risk of AMI ≈3-fold compared with the risk in nonpregnant women of similar age. [2][3][4][5] Although previous studies have provided some data related to the incidence of pregnancyassociated MI (PAMI), clinical characteristics, risk factors, and outcome 1,2,4 more information is needed on the mechanisms of AMI, the efficacy and safety of standard therapy, and the applicability of guideline recommendations designed for the general AMI population, to women with PAMI.The aim of this study was therefore to review contemporary data on PAMI in an attempt to provide recommendations for the management of this condition. MethodsA literature search for cases with AMI related to pregnancy was performed using PubMed and Google Scholar. References from these studies were cross-checked to obtain additional studies that may have been missed by the original search.All original articles were obtained online or by interlibrary communication. Articles published in languages other than English were translated by medical translators. A total of 134 cases published in the literature from 2006 to 2011 not included in a previous review 4 were included in this study. In addition, 7 cases presented at the First International Congress on Cardiac Problems in Pregnancy in 2010 (Valencia, Spain) and 9 patients treated or consulted by the authors were also included in the analysis. Recommendations were made on the basis of available clinical information, with the understanding that the cases published in the literature and reviewed by us do not represent all the patients who developed PAMI during the period of the study and that reporting may therefore be incomplete and biased. ResultsOne hundred fifty patients with PAMI were included in the study (Table 1). The age ranged from 17 to 52 years; the mean age was 34±6 years; 75% of the patients were >30 years of age; and 43% were >35 years. Reported risk factors for CAD included smoking in 25% of the patients, dyslipidemia in 20%, hypertension in 15%, and diabetes mellitus and a family history of CAD in 9% each.The type and timing of AMI are shown in Figure 1. Data on the type of AMI were available in 139 of the patients. Of these, 105 (75%) presented with ST-segment-elevation MI (STEMI) and the rest with non-STEMI (NSTEMI). The majority of the patients developed AMI during either the third trimester of pregnancy (STEMI, 25%; NSTEMI, 32%) or the postpartum period (STEMI, 45%; NSTEMI, 55%). The myocardial infarct involved the anterior wall of the left ventricle (LV) in 69% of the patients, the inferior wall in 27%, and the lateral wall in 4%. Table 2 shows the mechanisms of AMI. Coronary angiography was performed in 129 patients and demonstrated coronary dissection (CD) in 56 patients (43%), atherosclerotic disease in 27%, a clot without angiographic evidence for atherosclerotic disease in 22 patients (1...

(N Engl J Med. 2016;374:233–241) It is possible that peripartum cardiomyopathy is influenced by genetic factors, though this remains unclear. Similar to idiopathic dilated cardiomyopathy, this disease is associated with decreased systolic function, enlarged cardiac dimensions, and nonspecific histologic findings. These similarities are significant in that idiopathic dilated cardiomyopathy has been shown to be caused by a number of gene mutations. The authors of this study sequenced the DNA of 172 women suffering from peripartum cardiomyopathy to investigate whether there was a contribution from variants in the 43 genes known to be associated with dilated cardiomyopathy.

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