Exercise Testing After Preeclampsia

NCT06741436 | Recruiting

• 1 other identifier: U13728
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

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.

Conditions

Preeclampsia; Hypertension; Heart Failure Preserved Ejection Fraction

Keywords

CPET; Placental vascular dysfunction; echo

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  12 months

Study Arms (2)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The population will include women who can biologically bear children. Traditionally, women (especially minorities) have been under-represented in studies to characterize HFpEF predisposition, despite their disproportionate risk. VUMC is located in the Southeast and cares for a disproportionate number of Black pregnant women with Preeclampsia. Given the increased risk of PreE in Black populations, we strive to maximize enrollment of Black women in our study, with a target of at least 25% of the enrolled subjects self-identifying as Black. 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.

You may qualify if:

• Women age \> 18 years
• Give birth at VUMC
• Have a diagnosis of PreE based on accepted American College of Obstetricians and Gynecologists criteria

You may not qualify if:

• 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
• Controls

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37203, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Samples of cord blood, placenta, urine, and venous blood will be collected and stored.

MeSH Terms

Conditions

Pre-Eclampsia; Heart Failure, Diastolic; Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Heart Failure; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• Kathryn Lindley, MD, FACC

  VUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olivia H Patridge, BS

CONTACT

615-875-2942; olivia.h.patridge@vumc.org

Cassandra F Reynolds, BS, CCRC

CONTACT

615-875-9854; cassandra.f.reynolds@vumc.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Kathryn Lindley, MD, FACC

Study Record Dates

• First Submitted: December 9, 2024
• First Posted: December 19, 2024
• Study Start: February 18, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)