Although the initial results of the COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation; ClinicalTrials.gov identifier NCT01626079) provided “unequivocal evidence” of clinical improvement in patients with heart failure (HF) and mitral regurgitation, the results of the similar MITRA-FR trial (Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation; ClinicalTrials.gov identifier NCT01920698) were negative, according to a published in the Journal of the American College of Cardiology. According to researchers for the current study, these differences were possibly due “in large part to differences in the echocardiographic severity” of both mitral regurgitation and left ventricular dysfunction present in both patient populations.
Based on challenges identified in the MITRA-FR study, investigators for the COAPT study chose to employ a specific echocardiographic mitral regurgitation assessment algorithm to accurately identify patients for the COAPT trial. In the study, researchers described the novel algorithm used in the COAPT trial, as well as the echocardiographic characteristics that predict favorable outcomes following transcatheter mitral valve replacement (TMVR) in patients with HF and severe secondary mitral regurgitation.
COAPT was a multicenter, randomized, controlled, open-label trial of TMVR with the MitraClip device (Abbott; Chicago, IL). Study participants had HF and either moderate-to-severe or severe mitral regurgitation and remained symptomatic despite “maximally tolerated guideline-directed medical therapies.”
The applied novel algorithm consisted of 3 evaluation tiers, applied in a hierarchal manner; patients who qualified for COAPT inclusion met at least 1 of these criteria.
In total, 1576 patients were screened at 78 centers across the United States and Canada between December 2012 and June 2017. Of these patients, 57.8% were ineligible for COAPT inclusion. Principal exclusion criteria included <3+ mitral regurgitation severity, primary or mixed mitral regurgitation etiology, left ventricle end-systolic diameter (LVESD) >70 mm and left ventricle ejection fraction (LVEF) <20% or >50%. From the screening, 665 patients were enrolled, and 85.7% of these patients met the ≥3+ mitral regurgitation severity criteria based on the first tier of the algorithm.
Overall, the feasibility of obtaining most baseline echocardiographic measures was high, with LV volumes, LVEF by Simpson’s rule, proximal isovelocity surface area (PISA)-derived effective regurgitant orifice area (EROA), and vena contracta and color Doppler mitral regurgitation were obtained in >93% of cases.
Pulmonary vein flow and right ventricular systolic pressure were assessable in 77.2% and 86% of cases as well. Investigators were able to grade mitral regurgitation severity using the American Society of Echocardiography-derived integrative approach in all patients, although significant limitations were noted in assessing regurgitant volume and flow by the combined 2D volumes Simpson’s rule/Doppler hemodynamics method; calculations were feasible in only 42.3% of patients at baseline, and were available for paired baseline follow-up analysis in only 11.4% of patients.
Unadjusted analysis of baseline echocardiographic parameters was performed on all patients to identify potential predictors of first HF hospitalization or death. In all echocardiographic subgroups, the salutary effect of TMVR were comparable to guideline-directed medical therapies alone in reducing HF hospitalization or time to death over 12 and 24 months. Independent predictors of death and HF hospitalization included reduced LVEF, greater EROA and right ventricular systolic pressure, and TR severity in patients treated with guideline-directed medical therapy alone.
In contrast, only higher right ventricular systolic pressure and STS score were predictors of death and HF hospitalization in TMVR-treated patients.
Over the 30-day follow-up period, only 7.4% of patients treated via TMVR had ≥3+ mitral regurgitation, which investigators noted was “durable through the 24-month follow-up period.” In the control group, some patients also had improved mitral regurgitation severity during follow-up, but this number was much less than after TMVR at all timepoints. Mitral regurgitation improved by ≥2 grades at 12 months in 84.1% of still-living patients in the device group and in 15.9% in the control group.
Both LVESV and LVEDV increased over time in both groups but did so less after TMVR. LVEF also decreased in both groups, initially more in the TMVR group compared with the guideline-directed treatment group alone. By 12 months, LVEF reduction from baseline was less in patients in the TMVR group.
“The potential implications of effectively applying the COAPT results to clinical practice are substantial,” the researchers wrote. “The COAPT trial demonstrates that such patients who remain symptomatic despite maximally-tolerated [guideline-directed medical therapy] may benefit from [mitral regurgitation reduction] with TMVR, in terms of improved quality of life and exercise capacity, reduced HF hospitalizations, and prolonged survival.”
“The present analysis, representing the formal COAPT trial echocardiographic sub-study, is thus of direct clinical relevance in identifying those patients likely to benefit (and not benefit) by TMVR,” they added.
Limitations to the study included inconsistencies between 2D-derived LV volumes and total stroke volume as well as Doppler-derived forward stroke volume and RV and PISA-derived mitral regurgitation severity. Additionally, the current study focused on subgroup analyses prespecified at study inception, and further exploratory analyses are required. Longer-term follow-up is necessary.
“Echocardiography is of critical importance in determining the etiology and severity of [mitral regurgitation] and LV dimension and function to identify those patients most likely to benefit from percutaneous leaflet approximation, while avoiding treatment of patients less likely to benefit,” the researchers concluded. “Advanced echocardiographic expertise specific to this technology and population is imperative to ensure that the results of COAPT (and MITRA-FR) are translated to ‘real-world’ clinical practice to provide clinical benefit to a population that is at extremely high-risk of death and HF hospitalization.”
Disclosure: This clinical trial was supported by Abbott. Please see the original reference for a full list of authors’ disclosures.
Asch FM, Grayburn PA, Siegel RJ, et al; on behalf of the COAPT Investigators. Transcatheter mitral valve replacement in patients with heart failure and secondary mitral regurgitation: From COAPT Trial [published online September 19, 2019]. J Am Coll Cardiol. doi:10.1016/j.jacc.2019.09.017