Identification of Early HFpEF after Preeclampsia by Exercise Stress Testing

ABSTRACT Pregnancy is a unique, early moment of cardiovascular stress in young women that may “unmask” cardiovascular disease (CVD) propensity. Preeclampsia (PreE)—characterized by new-onset hypertension and proteinuria—has been linked to left ventricular diastolic dysfunction that may persist for years post-partum, and an increased risk of developing heart failure with preserved ejection fraction (HFpEF) over the decade following pregnancy. It is unclear if PreE simply represents a failed stress test or directly contributes to the pathophysiology of future CVD. Women and minorities are traditionally understudied in HFpEF, despite their disproportionate risk. This is the first large prospective study to investigate the hypothesis that PreE leads to persistent functional, hemodynamic, structural and biochemical cardiovascular changes that mirror early HFpEF. By defining the echo, proteomic and hemodynamic risk profile for early HFpEF, this will afford the opportunity for future studies to mitigate disease through pharmacologic/lifestyle interventions in a targeted population. We hypothesize that persistent structural-functional myocardial alterations in women with PreE are linked to pre- and post-gravid cardiometabolic risk factors and functional capacity and select pathways of vascular and inflammatory stress central to HF risk. We will use perturbational hemodynamic studies to elaborate myocardial phentoypes defining of HFpEF in women with PreE. We address our central hypothesis in 3 Specific Aims (SA): SA1: To measure relation between post-partum subclinical LVDD and pregnancy-specific risk factors in 250 women with PreE and 250 normotensive women (25% Black) through rest and provocation echocardiographic imaging, SA2: To quantify the hemodynamic consequences of early persistent LVDD in women with PreE, SA3: To identify differences in cardiovascular pathways of vascular remodeling and inflammation and their association with subclinical myocardial dysfunction in women with PreE. For this study, we will leverage the infrastructure of our NIH funded multidisciplinary cardio-obstetrics clinical research team for recruitment, retention, and risk factor modification (U01HG013189, R21NR020857). A fundamental strength of this proposal is the ESI PI’s experience in recruiting and retaining women at this critical stage in CV development. Our targeted enrollment of Black women addresses clinical and investigative gaps in this population at high short and long-term CV risk following a preeclamptic pregnancy. Successful completion of these studies in a large group of women across race will define high-risk PreE-linked structural/functional changes to support risk stratification and future interventional studies at this critical moment in CVD development in women.