Showing papers by "John P. Boehmer published in 2016"
Brigham and Women's Hospital1, University of Pittsburgh2, National Institute for Health Research3, University of Rochester4, Hannover Medical School5, National University of Singapore6, Intermountain Medical Center7, University of Southern California8, Jewish General Hospital9, University of Maryland, College Park10, Newark Beth Israel Medical Center11, University of Missouri–Kansas City12, Primary Children's Hospital13, Vanderbilt University14, Cleveland Clinic15, McGill University16, University of Calgary17, Pennsylvania State University18, Truman Medical Center19, Johns Hopkins University20, Wake Forest University21, Saint Barnabas Medical Center22, University of Toronto23, Harvard University24, University of Pennsylvania25
TL;DR: TTN truncating variants were the most prevalent genetic predisposition in each disorder and were significantly correlated with a lower ejection fraction at 1-year follow-up.
Abstract: 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.
360 citations
Vanderbilt University1, Brigham and Women's Hospital2, Harvard University3, Intermountain Medical Center4, Washington University in St. Louis5, Duke University6, Baylor College of Medicine7, Penn State Milton S. Hershey Medical Center8, Columbia University9, Stony Brook University10, University of Pittsburgh11, University of Chicago12, University of Pennsylvania13
TL;DR: In women with newly diagnosed PPCM, higher relaxin-2 levels soon after delivery were associated with myocardial recovery at 2 months, and higher sFlt1 levels correlated with more severe symptoms and major adverse clinical events.
Abstract: Objectives This study explored the association of vascular hormones with myocardial recovery and clinical outcomes in peripartum cardiomyopathy (PPCM). Background PPCM is an uncommon disorder with unknown etiology. Angiogenic imbalance may contribute to its pathophysiology. Methods In 98 women with newly diagnosed PPCM enrolled in the Investigation in Pregnancy Associated Cardiomyopathy study, serum was obtained at baseline for analysis of relaxin-2, prolactin, soluble fms-like tyrosine kinase 1 (sFlt1), and vascular endothelial growth factor (VEGF). Left ventricular ejection fraction (LVEF) was assessed by echocardiography at baseline and 2, 6, and 12 months. Results Mean age was 30 ± 6 years, with a baseline of LVEF 0.35 ± 0.09. Relaxin-2, prolactin, and sFlt1 were elevated in women presenting early post-partum, but decreased rapidly and were correlated inversely with time from delivery to presentation. In tertile analysis, higher relaxin-2 was associated with smaller left ventricular systolic diameter (p = 0.006) and higher LVEF at 2 months (p = 0.01). This was particularly evident in women presenting soon after delivery (p = 0.02). No relationship was evident for myocardial recovery and prolactin, sFlt1 or VEGF levels. sFlt1 levels were higher in women with higher New York Heart Association functional class (p = 0.01) and adverse clinical events (p = 0.004). Conclusions In women with newly diagnosed PPCM, higher relaxin-2 levels soon after delivery were associated with myocardial recovery at 2 months. In contrast, higher sFlt1 levels correlated with more severe symptoms and major adverse clinical events. Vascular mediators may contribute to the development of PPCM and influence subsequent myocardial recovery. (Investigation in Pregnancy Associate Cardiomyopathy [IPAC]; NCT01085955 )
68 citations
TL;DR: In this article, the authors compared the prevalence of different variant types (nonsense, frameshift, and splicing) in women with peripartum cardiomyopathy and with population controls, and found that truncating variants were the most prevalent genetic predisposition in each disorder.
Abstract: 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.
32 citations
TL;DR: This pilot study aimed to explore how patients with exacerbation-prone disease trajectories such as advanced heart failure or chronic obstructive pulmonary disease experience advance care planning using an online decision aid and to compare whether patients with different types of exacerbations had varied experiences using the tool.
Abstract: ObjectiveMany patients with chronic illnesses report a desire for increased involvement in medical decision-making. This pilot study aimed to explore how patients with exacerbation-prone disease tr...
19 citations
2 citations