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Review
. 2022 Dec 13;80(24):2331-2347.
doi: 10.1016/j.jacc.2022.09.044.

Research Opportunities in the Treatment of Mitral Valve Prolapse: JACC Expert Panel

Francesca N Delling  1 , Peter A Noseworthy  2 , David H Adams  3 , Cristina Basso  4 , Michael Borger  5 , Nabila Bouatia-Naji  6 , Sammy Elmariah  7 , Frank Evans  8 , Edward Gerstenfeld  9 , Judy Hung  10 , Thierry Le Tourneau  11 , John Lewis  12 , Marc A Miller  13 , Russell A Norris  14 , Muralidhar Padala  15 , Martina Perazzolo-Marra  16 , Dipan J Shah  17 , Jonathan W Weinsaft  18 , Maurice Enriquez-Sarano  19 , Robert A Levine  20
Affiliations
Review

Research Opportunities in the Treatment of Mitral Valve Prolapse: JACC Expert Panel

Francesca N Delling et al. J Am Coll Cardiol. .

Abstract

In light of the adverse prognosis related to severe mitral regurgitation, heart failure, or sudden cardiac death in a subset of patients with mitral valve prolapse (MVP), identifying those at higher risk is key. For the first time in decades, researchers have the means to rapidly advance discovery in the field of MVP thanks to state-of-the-art imaging techniques, novel omics methodologies, and the potential for large-scale collaborations using web-based platforms. The National Heart, Lung, and Blood Institute recently initiated a webinar-based workshop to identify contemporary research opportunities in the treatment of MVP. This report summarizes 3 specific areas in the treatment of MVP that were the focus of the workshop: 1) improving management of degenerative mitral regurgitation and associated left ventricular systolic dysfunction; 2) preventing sudden cardiac death in MVP; and 3) understanding the mechanisms and progression of MVP through genetic studies and small and large animal models, with the potential of developing medical therapies.

Keywords: cardiac magnetic resonance imaging; echocardiography; mitral regurgitation; mitral valve prolapse; sudden cardiac death.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Delling is supported by the UCSF Resource Allocation Program 7501268 and by National Institutes of Health (NIH) research grant R01HL153447. Dr Noseworthy has received research funding from the NIH, including the National Heart, Lung, and Blood Institute (R21AG 62580-1, R01HL 131535-4, R01HL 143070-2), the National Institute on Aging (R01AG 062436-1), Agency for Healthcare Research and Quality (R01HS 25402-3), Food and Drug Administration (FD 06292), and the American Heart Association (18SFRN34230146; has filed patents related to the application of artificial intelligence to the ECG for diagnosis and risk stratification and has licensed several A-ECG algorithms to Anumana; is involved in potential equity/royalty relationship with AliveCor; is a study investigator in an ablation trial sponsored by Medtronic; and has served on an expert advisory panel for OptumLabs. Dr Adams’s institution, the Icahn School of Medicine at Mount Sinai, receives royalties for mitral and tricuspid valve repair prostheses related to his intellectual property from Edwards Lifesciences and Medtronic. Dr Borger’s institution receives speakers’ honoraria and/or consulting fees on his behalf from Edwards Lifesciences, Medtronic, Abbott, and CryoLife. Dr Elmariah has received research funding from the NIH (R01HL 151838) and the American Heart Association (19TPA34910170); has received research grants from Edwards Lifesciences, Medtronic, and Abbott Vascular; and is a consultant for Edwards Lifesciences. Dr Gerstenfeld has received lecture honoraria from Medtronic, Boston Scientific, and Abbott; has received research funding from, is on the scientific advisory board, and has received compensation from Biosense Webster; is on the scientific advisory board for and is PI of a clinical ablation trial sponsored by Farapulse; and is on the Data and Safety Monitoring Board for trials sponsored by Thermedical Inc and Abbott. Dr Norris has received research funding from the NIH (HL131546, GM103444, HL149696, HL122906), and the American Heart Association (19TPA34850095, 20SRG35540029, 19TPA34900016, 17CSA33590067). Dr Padala is supported by the National Heart, Lung, and Blood Institute (R01HL135145, R01HL140325, R01HL133667, R01HL144714, R01HL135505) and by the National Institute of Biomedical Imaging and Bioengineering (R01EB031101); has significant stock ownership and a role as a director in Nyra Medical; and has received consulting fees from Heart Repair Technologies Inc in the last 12 months. Dr Weinsaft is supported by NIH research grants R01HL128278 and R01HL151686. Dr Enriquez-Sarano has served as a consultant for Edwards, Cryolife, ChemImage, and HighLife. Dr Levine is supported by NIH research grants R01HL128099 and R01HL141917, American Heart Association 963793/Levine/2022, and funding of the Ellison Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

FIGURE 1
FIGURE 1. Research Opportunities in DMR
Preventing heart failure through identification of earlier triggers for intervention in degenerative mitral regurgitation (DMR). CMR = cardiac magnetic resonance; MR = magnetic resonance; MVP = mitral valve prolapse.
FIGURE 2
FIGURE 2. Research Opportunities in DMR
Preventing recurrent MR postintervention through development of large databases and centers of excellence. SMR = surgical mitral valve repair; TEER = transcatheter edge-to-edge repair; other abbreviations as in Figure 1.
FIGUER 3
FIGUER 3. Research Opportunities in the Genetics of MVP
The importance of comprehensive genetic maps and understanding of gene regulation and expression in the mitral valve. CRISPRi = clustered regularly interspaced short palindromic repeats interference; eQTLs = expression quantitative trait loci; MVP = mitral valve prolapse; scRNA-Seq = single-cell RNA sequencing.
FIGURE 4
FIGURE 4. Understanding the Developmental Basis of MVP
Demonstration of the altered interactions between valve endothelial (yellow)/interstitial (orange)/inflammatory cells (blue) using mouse models. MVP = mitral valve prolapse.
CENTRAL ILLUSTRATION
CENTRAL ILLUSTRATION. Research Opportunities: Degenerative Mitral Regurgitation and Arrhythmic Mitral Valve Prolapse
Valvular-ventricular interactions and potential fibrotic stimuli and arrhythmogenic triggers in mitral valve prolapse (MVP) include (right): papillary muscle (PM) traction, associated curling motion (black arrows in opposite directions), and increased systolic annular expansion augmented by mitral annular disjunction (MAD). MV schematics adapted with permission from Nagata et al. AO = aorta; CMR = cardiac magnetic resonance; DMR = degenerative mitral regurgitation; ECG = electrocardiography; EP = electrophysiology; ICD = implantable cardioverter-defibrillator; ILR = implantable loop recorder; LA = left atrium; LV = left ventricular; PET = positron emission tomography; PVC = premature ventricular contraction; SCA = sudden cardiac arrest; SCD = sudden cardiac death; TEER = transcatheter edge-to-edge repair.
See this image and copyright information in PMC

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