University of Pittsburgh Medical Center
Presentation Abstract
Peripartum Cardiomyopathy
Peripartum cardiomyopathy (PPCM) is a rare complication of pregnancy that remains a major cause of maternal morbidity and mortality. PPCM presents as a nonischemic cardiomyopathy late in pregnancy or in the first few months postpartum, and while most women recover, a subset are left with chronic cardiomyopathy and chronic heart failure. Women can frequently present severely ill in cardiogenic shock and 5 to 10% of women will die or require cardiac transplantation or mechanical support during the first year postpartum. Black women are at greater risk for the disorder, present with more severe disease, and demonstrate less myocardial recovery. Genetic background may increase the risk of this disorder as 15% of women presenting with PPCM have truncation mutations of sarcomere proteins including 10% with mutations in the gene titin. While these mutations of sarcomere proteins demonstrate the importance of cardiac myocyte biology in its pathogenesis, investigations in preclinical models and small clinical studies also suggest a vascular component to the etiology of PPCM. This work has focused on the role of vasoinhibins, in particular a 16 kDa N-terminal fragment of prolactin. In murine models, this fragment has an adverse impact on vascular endothelium and plays a clear role in the pathogenesis of the disorder. These models also suggest bromocriptine, a dopaminergic agonist which inhibits prolactin secretion, can improve myocardial recovery in PPCM. Clinical studies have also suggested benefits of bromocriptine but are not definitive, and REBIRTH, a National Heart, Lung, and Blood Institute-sponsored multicenter investigation has been initiated to evaluate the role of bromocriptine as a potential therapy for PPCM. Future investigations are needed to identify the genetic and socioeconomic factors that influence outcomes, and to determine the factors that increase the risk in Black women. Further investigation of the vascular etiology of PPCM will hopefully lead to more targeted therapies for this disorder.
Roundtable on Cardiovascular Risks and Interventions
Cardiovascular disease comprises the leading cause of maternal death in the peripartum and postpartum first year period. Within these events, Black women and other minorities are at higher risk than White women for cardiovascular events. Cardiovascular risk factors alone contribute to increased risk of a complicated pregnancy, delivery, and postpartum period. However, there is an intersection between the traditional cardiovascular risk factors and social determinants of health that exponentially increases this risk. The session will spotlight advances in the understanding and treatment of peripartum cardiomyopathy and will include a patient sharing her personal experience with maternal cardiovascular complications. The subsequent cardiovascular roundtable will address pre-pregnancy and pregnancy risk factors, the intersection and interplay between cardiovascular risk and social determinants of health, and the cardiovascular events that may occur in the pre, peri, and postpartum period. The session will conclude with an open dialogue among the expert discussants.
About Dr. McNamara
Dr. Dennis M. McNamara is a Professor of Medicine and the Director of the Center for Heart Failure Research at the University of Pittsburgh Medical Center (UPMC). Dr. McNamara, a graduate of Yale University and Harvard Medical School, completed his research and clinical training at Massachusetts General Hospital in Boston before joining the University of Pittsburgh faculty in 1994. A cardiologist specializing in advanced heart failure, he directed the Heart Failure/Transplantation Program at UPMC for a decade prior to being named the Director of the Center for Heart Failure research in 2014. His research has focused on understanding myocardial recovery in non-ischemic dilated cardiomyopathy and the impact of genetic heterogeneity on clinical outcomes. More recently his work has centered on understanding the pathogenesis and therapy of peripartum cardiomyopathy. He directed the IPAC study (Investigation of Pregnancy Associated Cardiomyopathy), a 30-center National Institutes of Health-funded investigation of myocardial recovery for women with peripartum cardiomyopathy. He is currently the Principal Investigator for the REBIRTH trial, a 50-center investigation funded by the National Heart, Lung, and Blood Institute of the use of bromocriptine therapy to improve outcomes in peripartum cardiomyopathy.
Dr. McNamara did not disclose any conflicts of interest for this workshop.