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.

Relaxin is a 6 kDa protein hormone produced by the corpus luteum and secreted into the blood during pregnancy in rodents and humans. Growing evidence indicates that circulating relaxin causes vasodilatation and increases in arterial compliance, which may be among its most important actions during pregnancy. Here we investigated whether there is local expression and function of relaxin and relaxin receptor in arteries of nonpregnant females and males. Relaxin-1 and its major receptor, Lgr7, mRNA are expressed in thoracic aortas, small renal and mesenteric arteries from mice and rats of both sexes, as well as in small renal arteries from female tammar wallabies (an Australian marsupial). Using available antibodies for rat and mouse Lgr7 receptor and rat relaxin, we also identified protein expression in arteries. Small renal arteries isolated from relaxin-1 gene-deficient mice demonstrate enhanced myogenic reactivity and decreased passive compliance relative to wild-type (WT) and heterozygous mice. Taken together, these findings reveal an arterial-derived, relaxin ligand-receptor system that acts locally to regulate arterial function.

(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.

BACKGROUND Among various cardiac autoantibodies (AAb), those recognizing the β1 adrenergic receptor (β1AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption. OBJECTIVES We investigated the role of β1AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. METHODS Peripheral blood was drawn at enrollment in subjects with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; <6 months). Presence of IgG and IgG3-β1AR-AAb was determined and echocardiograms assessed at baseline and 6 months. Subjects were followed for up to 4 years. RESULTS Among the 353 enrolled subjects, 62 (18%) were positive for IgG3-β1AR-AAb (IgG3), 58 (16%) were positive for IgG but not IgG3 (non-IgG3), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. LV end-diastolic and end-systolic (LVEDD and LVESD, respectively) diameters were significantly larger in the non-IgG3 group compared to the other groups (LVEDD: p < 0.01; LVESD: p = 0.03). At 6 months, LVEF was significantly higher in the IgG3 group (p = 0.007). Multiple regression analysis demonstrated IgG3-β1AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In the subjects with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. CONCLUSIONS IgG3-β1AR-AAb was associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.