Mitral Valve Prolapse Researchers Receive $8.7 Million NIH Grant to Study Life-Threatening Arrhythmias

The National Institutes of Health has awarded the Houston Methodist DeBakey Heart & Vascular Institute an $8.7 million grant to advance research into life-threatening arrhythmias associated with mitral valve prolapse (MVP).

The research will address gaps in understanding the pathogenesis of MVP and developing better risk assessment tools for potentially life-threatening complications of the condition, which affects 2%-3% of the population — roughly 200 million people globally.

"This project has the potential to revolutionize the way we identify and manage mitral valve prolapse patients at risk for sudden cardiac death," said Dr. Dipan Shah, chief of Cardiovascular Imaging at Houston Methodist and the leader of the research. "By combining advanced imaging techniques with biomarker analysis, we aim to provide clinicians with reliable tools to intervene early and improve patient outcomes."

The funding is part of the NIH's initiative under the CAROL Act, a legislative effort aimed at bolstering research on valvular heart disease.

The NIH grant will fund a multi-year study on SCD risk assessment and mechanistic insights in arrhythmic MVP using cardiac MRI and circulating proteomic biomarkers. Additional, related research efforts from Dr. Shah and team include a prospective SCD risk stratification study using cardiac MRI and echocardiography machine learning, analysis of circulating proteomics to phenotype the development and reversal of myocardial remodeling in aortic stenosis, and mechanistic insights on arrhythmic MVP using cardiac MRI and circulating proteomic biomarkers.

Study aims and rationale

The researchers are trying to understand what factors lead to mitral valve prolapse patients developing arrhythmias, including identifying early markers of risk through imaging, cardiac monitoring and blood biomarker analysis.

"The goal is to eventually be able to look at an imaging scan and predict which patients are at highest risk, allowing for earlier interventions," explained Dr. Shah, who is also the Daniel C. Arnold Distinguished Centennial Chair, Department of Cardiology at Weill Cornell Medical College.

Typically benign, MVP causes some patients to develop ventricular arrhythmias that can lead to sudden cardiac death (SCD). Studies suggest the annual incidence of SCD in MVP patients may range from 0.4% to 1.9%.

Although MVP has long been associated with risk of SCD in a subset of patients, tools for identifying that subset and assessing an individual's risk remain limited. The researchers aim to change that by establishing new guidelines and developing a validated risk prediction model for MVP-associated SCD.

Specifically, Houston Methodist's ongoing research efforts will include:

• Deep Phenotyping of MVP Patients: Researchers will conduct comprehensive analyses of MVP patients to identify clinical, imaging and mechanistic factors associated with ventricular arrhythmias.
• Biomarker Development: The team will investigate a panel of blood biomarkers, including FDA-approved and novel proteomic markers, to develop a cost-effective screening strategy for identifying MVP patients with myocardial fibrosis — a key risk factor for SCD.
• Risk Prediction Model: The researchers will assemble a multicenter cohort of over 2,000 MVP patients with contrast-enhanced cardiac magnetic resonance imaging (CMR) and perform longitudinal follow-up to create and validate a novel risk prediction model for SCD and life-threatening arrhythmias.

A growing concern

Houston Methodist's ongoing research efforts underscore the growing recognition of MVP's potential for severe outcomes, particularly among otherwise healthy young women. The CAROL Act was inspired by Kentucky U.S. Rep. Andy Barr's wife, Carol, who died of sudden cardiac arrest at the age of 39.

The researchers recently presented findings at the American Heart Association's Annual Scientific Sessions showing that women had a threefold higher risk of arrhythmias compared to men. Myocardial fibrosis was another significant marker, with affected patients also experiencing a threefold increased risk.

Current treatment options for high-risk MVP patients include beta blockers, catheter ablation, and implantable defibrillators. However, researchers are also investigating whether mitral valve surgery could reduce arrhythmic risk.

"Right now, we don't have a standardized set of guidelines on who should receive early intervention," Dr. Shah said. "A key part of this study is determining which patients would benefit from proactive treatment."

Lasting impact

The study has already begun enrolling patients scheduled for cardiac MRI scans at Houston Methodist. Eligible patients are invited to participate in longitudinal monitoring, which includes Holter monitoring, additional echocardiography and blood sample collection.

The research is also part of the larger MVP-Scar registry involving several other institutions, including Duke University, Cornell University, the University of Minnesota, the University of California-San Francisco, Piedmont Heart Institute and Atrium Health.

"This is one of the largest grants of its kind offered by the NIH, as we're one of the key groups in the country studying this," Dr. Shah said. "Our hope is that it will lead to much-needed insights and targeted interventions to help prevent unexpected and tragic deaths like the one that inspired this grant."