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EROA to LVEDV Ratio and Transcatheter Mitral Valve Repair Outcomes
Quick Takes
- This study used the COAPT trial database to test whether differences in secondary mitral regurgitation (SMR) severity relative to LVEDVi can explain the divergent findings from the MITRA-FR and COAPT trials.
- In this post hoc analysis of MITRA-FR resembling patients in the COAPT trial, TMVr in addition to GDMT was not associated with improvement in the composite endpoint of all-cause mortality or heart failure hospitalizations, but was associated with statistically significant or nonsignificant trends toward improvement in QOL and 6MWD.
- This study does not fully support the hypothesis that proportionate vs. disproportionate SMR can explain the differences in outcomes between MITRA-FR and COAPT.
Study Questions:
Among patients with heart failure (HF) and secondary mitral regurgitation (SMR) treated with guideline-directed medical therapy (GDMT) plus transcatheter edge-to-edge mitral valve repair (TMVr) vs. GDMT alone, can differences in the severity of SMR relative to left ventricular end-diastolic volume index (LVEDVi) explain differences in study outcomes between the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) and MITRA-FR (Multicenter Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation) trials?
Methods:
Data from the COAPT trial (performed December 2012–June 2017) were subjected to post hoc analysis. A subgroup of COAPT patients with characteristics similar to patients enrolled in the MITRA-FR trial (SMR effective regurgitant orifice area [EROA] ≤0.30 cm2, LVEDVi >96 ml/m2; n = 56; group 1) was compared to the remaining COAPT patients (EROA >0.30 cm2, LVEDVi ≤96 ml/m2; n = 492; group 2). The composite endpoint of all-cause mortality (ACM) or heart failure hospitalizations (HFHs), quality of life (QOL) from the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, and 6-minute walk distance (6MWD) were evaluated in six subgroups of COAPT patients based on the ratios of SMR EROA or regurgitant volume to LVEDVi.
Results:
A total of 548 participants (71.9 ± 11.2 years, 351 [64%] male) were included. No significant difference was found at 24 months in the composite rate of ACM or HFH between TMVr plus GDMT versus GDMT alone in group 1 patients (27.8% vs. 33.1%, p = 0.83), compared to a significant difference at 24 months in group 2 patients (31.5% vs. 50.2%, p < 0.001). However, patients randomized to undergo TMVr versus those treated with GDMT alone had significantly greater improvement in QOL at 12 months in both groups (mean KCCQ summary scores 18.36 ± 5.38 vs. 0.43 ± 4.00 points [group 1], p = 0.01; and 16.54 ± 1.57 vs. 5.78 ± 1.82 points [group 2]; p < 0.001). TMVr-randomized patients versus those treated with GDMT alone had significantly greater improvement in 6MWD at 12 months in group 1 (mean paired improvement 39.0 ± 28.6 vs. −48.0 ± 18.6 min, p = 0.02), with a statistically nonsignificant trend toward improvement in group 2 (mean paired improvement 35.0 ± 7.7 vs. 16.0 ± 9.1 min, p = 0.11).
Conclusions:
In a small subgroup of MITRA-FR-resembling patients enrolled in the COAPT trial, TMVr was not associated with improvement in the combined endpoint of ACM or HFH at 24 months, but was associated with benefit in the patient-centered outcomes of QOL and 6MWD. The authors concluded that this subgroup analysis suggests that the benefit of TMVr is not fully supported by the hypothesis of proportionate versus disproportionate SMR.
Perspective:
Two prospective, randomized trials testing the impact of TMVr in addition to GDMT among patients with HF and SMR, both published in 2018, had dramatically different findings. Whereas MITRA-FR found no difference in the primary endpoint of ACM or HFH at 12 months (N Engl J Med 2018;379:2297-306), COAPT found that TMVr added to GDMT was associated with significant reductions in the annualized rate at 24 months of HFH and ACM. Based on the observation that patients enrolled in MITRA-FR in general had less severe SMR and larger LVEDVi compared to patients enrolled in COAPT, one hypothesis proposed to explain the different outcomes related to the concept of proportionate (where SMR severity is proportionate to the degree of LV enlargement) versus disproportionate SMR (where SMR is out of proportion to the degree of LV enlargement).
The present study reanalyzed patients enrolled in the COAPT trial in an attempt to test this hypothesis, creating a MITRA-FR-like subgroup of 56 patients (with lower SMR EROA and larger LVEDVi) extracted from the COAPT cohort. The findings are mixed, with a demonstrated difference between groups in ACM or HFH supporting the proportionate/disproportionate SMR hypothesis, but with KCCQ score and 6MWD outcomes not supporting the hypothesis. Limited by post hoc analysis and uneven group sizes, this study is not fully supportive of the proportionate/disproportionate SMR hypothesis. Additional work is required to explain the dramatically different findings of the MITRA-FR and COAPT trials, and ultimately to inform decisions regarding TMVr among patients with HF and SMR.
Clinical Topics: Cardiac Surgery, Cardiovascular Care Team, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Acute Heart Failure, Interventions and Imaging, Interventions and Structural Heart Disease, Mitral Regurgitation
Keywords: Cardiac Surgical Procedures, Cardiomyopathies, Diagnostic Imaging, Geriatrics, Heart Failure, Heart Valve Diseases, Mitral Valve Insufficiency, Outcome Assessment, Health Care, Quality of Life, Stroke Volume
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