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February 3, 2021

Reconciling COAPT and Mitra-FR Results Based on Mitral Regurgitation Severity and Left Ventricular Size: It’s Not So Simple

Author Affiliations
  • 1Department of Cardiovascular Medicine, Morristown Medical Center/Atlantic Health System, Morristown, New Jersey
JAMA Cardiol. 2021;6(4):376-378. doi:10.1001/jamacardio.2020.7214

Since the simultaneous publication of the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) trial1 and Multicenter Study of Percutaneous Mitral Valve Repair with the MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (Mitra-FR) trial,2 there have been ongoing efforts to reconcile their widely divergent results, which persisted with the release of the Mitra-FR 2-year data.3 Briefly stated, COAPT demonstrated a clear benefit of edge-to-edge transcatheter mitral repair (TMVr) in symptomatic patients with secondary mitral regurgitation (MR) whereas Mitra-FR did not, despite similar trial design and end points. Proffered explanations have included the adequacy of guideline-directed medical therapy (GDMT), reportedly better in COAPT; MR reduction, reportedly better in COAPT; and differences in patient selection that resulted in patients with less MR, defined by 2-dimensional echocardiographic effective regurgitant orifice area (EROA), and more dilated left ventricles, defined by indexed left ventricular end-diastolic volume (LVEDVi), in the Mitra-FR trial. The differences in patient selection were captured in the concept of disproportionate vs proportionate MR,4 which somewhat intuitively concludes that patients who have more MR and less remodeling (disproportionate MR) are more likely to respond to TMVr, an intervention that directly reduces MR and only indirectly affects the left ventricle. Packer and Grayburn5 proposed a cutoff of 0.14 for the ratio of EROA to LVEDV to separate proportionate from disproportionate MR. They noted that there were more patients with proportionate MR in the Mitra-FR cohort, reflecting differences in trial inclusion criteria, and argued that this accounted for outcome differences. They supported their case by reporting that a small subgroup of patients in COAPT with proportionate MR (EROA of 30 cm2 or less and LVEDVi greater than 96 mL/m2) experienced no significant effect of TMVr on the composite end point of all-cause mortality (ACM) and heart failure hospitalizations (HFH) at 1 year, similar to the outcomes in Mitra-FR. All other subgroups with more MR and/or smaller left ventricular (LV) end-diastolic volumes were determined to have disproportionate MR and benefited from TMVr, as had been reported for the entire cohort. Taking a different approach based on the ratio of regurgitant volume (RV) to LVEDV,6 Gaasch et al7 argued that differences in trial results could not be explained on the basis of disproportionality because, based on an RV to LVEDV ratio with a cutoff of 0.20, there were comparably few patients with disproportionate MR in either study, as is generally the case with secondary MR.

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