Identification of Early HFpEF After Preeclampsia by Exercise Stress Testing
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 500
- Locations
- 1
- Primary Endpoint
- To measure relation between postpartum subclinical LV diastolic dysfunction and pregnancy-specific risk factors in 250 women with PreE and 250 normotensive women through echocardiographic imaging.
Study Overview
Brief Summary
Though cardiovascular disease (CVD) is the leading cause of mortality in women, traditional epidemiology in this area has focused on later life, when cardiometabolic risk has already exacted a cumulative toll on the vascular system. Recent data from the investigators and others has highlighted pregnancy as a unique, early moment of cardiovascular stress in young women that may "unmask" CVD propensity. It is unclear if PreE simply represents a "failed stress test" or directly contributes to the pathophysiology of future CVD. While mechanistic studies have largely been the purview of model-based studies, endothelial dysfunction has emerged as central to the pathogenesis of both PreE and peripartum cardiac dysfunction. Indeed, biomarkers of endothelial dysfunction and angiogenic imbalance during pregnancy have been shown to remain elevated at least 6 months post-partum. Moreover, peri-partum endothelial dysfunction can persist for years post-delivery and remains a significant risk factor for CVD (even after adjustment for other traditional risk factors). While these findings suggest that PreE-associated endothelial dysfunction and inflammation may contribute to early myocardial dysfunction that presages HF risk decades before its onset, the modifiable epidemiology of PreE-associated LVDD, including potential mechanisms of risk, remains unclear, limited by lack of precision molecular phenotypes accessible in a large number of American women across race. Ultimately, understanding the epidemiology and pathobiology of PreE-associated myocardial dysfunction affords a unique opportunity to identify women at risk with a longer lead-time for risk factor modification to interrupt CVD.
The investigators hypothesize that persistent structural-functional myocardial alterations after PreE are linked to pre- and post-gravid cardiometabolic risk factors (SA1), functional and hemodynamic impairment (SA2) and select pathways of vascular and inflammatory stress relevant to HF risk (SA3). Despite extensive study on the role of inflammation/ischemia in PreE, there have been no large studies connecting these phenotypes with early PP functional response and biochemical alterations, a key barrier to designing studies for improving CVD/HF in women.
SA1: To identify pregnancy-specific clinical factors related to postpartum HFpEF phenotypes Clinical Implication: Improve identification of women at highest risk for developing post-PreE LV diastolic dysfunction (a harbinger of HFpEF).
SA2: To define functional and hemodynamic signatures of early HFpEF due to preeclampsia
Clinical Implication: Identify women at highest risk for developing early HFpEF.
SA3: To identify shared pathophysiologic mechanistic pathways for PreE-associated HFpEF Clinical Implication: Identify targetable pathways for post-PreE cardiac dysfunction that may prevent/ delay HFpEF development.
Detailed Description
Participants will be identified by daily electronic health record (EHR) search with American College of Obstetricians and Gynecologists (ACOG) criteria for PreE. The investigators will begin recruitment of participants in both their third trimester, as well as at admission to the Labor and Delivery Service. The investigators may consent and enroll patients in the study prior to being admitted, to allow ample time to consider participation. Patients admitted to the Labor and Delivery service will be identified as being diagnosed with PreE using a checklist, with supervision of a board-certified obstetrician with NIH- funded experience in obstetric research.
Participants will be recruited and enrolled until the investigators reach the goal of 250 cases and 250 controls. The subject will first be prescreened for eligibility. The study team will then approach the care team of the subject and request permission to approach the subject about participation in the study. Once permission has been granted the study team will then approach the subject.
Once the study team is in contact with the potential participant (and it has been assessed that they meet study eligibility), they will receive a complete explanation of the protocol, and the informed consent will be reviewed with them. The consent form will clearly state that participants may end participation at any time without prejudice, and this is emphasized to the subject. In particular, participants who receive their health care at Vanderbilt University Medical Center will be reassured that their decision to decline participation will in no way affect their medical treatment.
In order to assess the capacity to consent in critically ill patients, a member of the study team will ask the participants about their understanding/awareness of their condition and their perceived reason for their hospitalization. If the study team suspect impaired competence based on subject's responses, the subject will be excluded from the study.
Enrollment. For this study, the investigators will leverage the multidisciplinary cardio-obstetrics clinical research team, a collaboration between the Cardiology Division, Dept of Medicine and Maternal Fetal Medicine, Dept of Obstetrics and Gynecology established and led by PI Lindley. The team is designed to deploy high-success methods to recruit, schedule, follow-up and retain participants. At Vanderbilt University Hospital, there are >5000 deliveries per year; of these, 22% women develop hypertensive disorders of pregnancy. The investigators have previously been very successful in recruiting patients with PreE from both the Women's Health Clinic, and the inpatient Labor and Delivery service, and anticipate no difficulties with recruitment. PI Lindley has previously successfully recruited over 350 postpartum women with hypertensive disorders of pregnancy for prospective clinical studies and has previously successfully completed a pilot study of postpartum exercise stress testing at 12-16 weeks after delivery in 53 women with PreE, with 49% racial/ethnic minority women recruited and retained. For this study, the goal is that ~25% of enrolled participants would self-identify as black.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Women age > 18 years
- •Give birth at VUMC
- •Have a diagnosis of PreE based on accepted American College of Obstetricians and Gynecologists criteria
Exclusion Criteria
- •Age <18 years old
- •Unable to provide informed consent
- •Does not speak English
- •Active COVID-19 infection
- •Residual symptoms related to prior COVID-19 infection
- •HIV infection
- •Hepatitis B or C infection
- •Pulmonary arterial hypertension
- •Sickle cell disease
- •Pulmonary embolism
- •Pre-existing cardiomyopathy
- •Coronary artery disease
- •Active substance abuse (other than tobacco or marijuana)
- •Unable to attend postpartum visits
- •1. Enrolling controls who meet the same inclusion/exclusion criteria, except they do not have preeclampsia and do not have pre-existing diabetes or chronic hypertension.
Arms & Interventions
Control
Controls who meet the same inclusion/exclusion criteria, except they do not have preeclampsia and do not have pre-existing diabetes or chronic hypertension.
PreE Px
Preeclamptic participants who meet the inclusion/exclusion criteria
Outcomes
Primary Outcomes
To measure relation between postpartum subclinical LV diastolic dysfunction and pregnancy-specific risk factors in 250 women with PreE and 250 normotensive women through echocardiographic imaging.
Time Frame: 12 months
Pre-pregnancy risk factors (HTN, DM, delivery body mass index \[BMI\], age), pregnancy-specific risk factors (PreE severity, gestational age at delivery, gravidity, GDM, SGA) and PP risk factors (weight change, median systolic BP 0-2 weeks PP, resting BP at study visit) will be measured. Ordinary least squares (OLS) regressions will be used to estimate the relationship between Lateral E/e' at 52 weeks and the above risk factors, adjusting for baseline values, to determine if the diastolic function parameters are affected by the risk factors of interest.
Secondary Outcomes
No secondary outcomes reported
Investigators
Kathryn Lindley
Dr. Kathryn Lindley, MD, FACC
Vanderbilt University Medical Center