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New Evidence Supporting a Novel Conceptual Framework for Distinguishing Proportionate and Disproportionate Functional Mitral Regurgitation

Educational Objective To review the pathophysiology and subtypes of severe mitral regurgitation in the setting of severe left ventricular systolic dysfunction.
1 Credit CME

Importance  Traditionally, physicians distinguished between mitral regurgitation (MR) as a determinant of outcomes and MR as a biomarker of left-ventricular (LV) dysfunction by designating the lesions as primary or secondary, respectively. In primary MR, leaflet abnormalities cause the MR, resulting in modest increases in LV end-diastolic volume over time, whereas in patients with classic secondary MR, LV dysfunction and dilatation lead to MR without structural leaflet abnormalities. However, certain patients with global LV disease (eg, those with left bundle branch block or regional wall motion abnormalities) have the features of primary MR and might respond favorably to interventions that aim to restore the proper functioning of the mitral valve apparatus.

Observations  A novel conceptual framework is proposed, which classifies patients with meaningful LV disease based on whether the severity of MR is proportionate or disproportionate to the LV end-diastolic volume. Treatments that reduce LV volumes (eg, neurohormonal antagonists) are effective in proportionate MR but not disproportionate MR. Conversely, procedures that restore mitral valve function (eg, cardiac resynchronization and mitral valve repair) are effective in patients with disproportionate MR but not in those with proportionate MR. The proposed framework explains the discordant findings in the Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR) and the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trials; differences in procedural success and medical therapy in the 2 studies cannot explain the different results. In addition, the small group of patients in the COAPT trial who had the features of proportionate MR and were similar to those enrolled in the MITRA-FR trial did not respond favorably to transcatheter mitral valve repair.

Conclusions and Relevance  The characterization of patients with functional MR into proportionate and disproportionate subtypes may explain the diverse range of responses to drug and device interventions that have been observed.

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Article Information

Accepted for Publication: November 28, 2019.

Corresponding Author: Milton Packer, MD, Baylor Scott & White Heart and Vascular Hospital, 621 N Hall St, Dallas, TX 75226 (milton.packer@baylorhealth.edu).

Published Online: February 19, 2020. doi:10.1001/jamacardio.2019.5971

Author Contributions: Dr Grayburn had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Both authors.

Acquisition, analysis, or interpretation of data: Both authors.

Drafting of the manuscript: Packer.

Critical revision of the manuscript for important intellectual content: Both authors.

Statistical analysis: Both authors.

Administrative, technical, or material support: Grayburn.

Conflict of Interest Disclosures: Dr Packer reported receiving personal fees from AbbVie, Akcea, AstraZeneca, Amgen, Actavis, Boehringer, Cardiorentis, Daiichi Sankyo, Johnson & Johnson, Novo Nordisk, Pfizer, Sanofi, Synthetic Biologics, and Theravance outside the submitted work. Dr Grayburn reported receiving grants and personal fees from Abbott Vascular, Edwards Lifesciences, and W. L. Gore; grants from Boston Scientific, Medtronic, NeoChord, and Cardiovalve; and personal fees from 4C Medical during the conduct of the study.

Additional Information: The analyses of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) subgroups have been publicly presented, have been included in regulatory submissions by the sponsor of the COAPT trial (Abbott), and were confirmed and expanded by Maria Alu, BA, of the Cardiovascular Research Foundation, New York, NY. No compensation outside of salary was provided.

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