COAPT: Transcatheter mitral valve replacement brings health status improvements
NEW ORLEANS —Two substudies from the COAPT trial presented at the American College of Cardiology Scientific Session found that patients with moderate-to-severe or severe mitral regurgitation who had transcatheter mitral valve repair and guideline-directed medical therapy had improvements in health status as soon as 1 month.
Moreover, an echocardiographic substudy determined that all subgroups analyzed based on their echocardiographic characteristics at baseline obtained a benefit from the MitraClip (MitraClip, Abbott) implantation.
As Cardiology Today’s Intervention previously reported, in the main results of COAPT, patients with HF with moderate-to-severe or severe functional mitral regurgitation who underwent transcatheter mitral valve repair and received optimal medical therapy had reduced risk for HF hospitalization and mortality compared with patients treated with optimal medical therapy alone.
In the echocardiographic substudy, those assigned guideline-directed medical therapy alone had four independent baseline echocardiographic predictors of poor outcomes (LV ejection fraction, mitral and tricuspid regurgitation severity and right ventricular systolic pressure), while only right ventricular systolic pressure predicted a poor outcome in those who had device therapy. But even among those with higher right ventricular systolic pressures, patients that received the device did better than those in optimal medical treatment alone.
“To duplicate the COAPT results in our daily clinical practice, specific COAPT screening echo criteria and expert echo analysis should be applied to identify proper candidates for the MitraClip,” Federico M. Asch, MD, director of the Echocardiography Core Lab at MedStar Health Research Institute in Washington, D.C., and associate professor of medicine at Georgetown University, said during the presentation.
In this substudy of 614 patients, all underwent transthoracic echocardiograms at baseline, 1 month, 6 months, 12 months, 18 months and 24 months, which would continue to 5 years. At baseline, both groups of patients that were assigned treatment in the COAPT trial had similar echocardiographic characteristics, although the only difference was seen in pulmonary vein flow, as 56.7% of the device group and 44% of the control group had a severe case of it.
Both groups of patients had increases in left ventricular end diastolic volume up to 24 months (P < .05), although there was less of an increase in the device group. This was also seen for changes in LV end systolic volume up to 24 months (P < .05).
LV ejection fraction decreased over time in the device and control groups up to 24 months of follow-up (P < .05).
Mitral regurgitation improved more in the MitraClip at all times of follow-up. Compared with the control group, more patients in the device group had a mitral regurgitation severity of 2+ or less at 30 days (92.7% vs. 34.2%), 6 months (93.8% vs. 38.1%), 12 months (94.8% vs. 46.9%), 18 months (95% vs. 40.4%) and 24 months (99.1% vs. 43.4%; P for all < .001).
From baseline to 12 months, 84.1% of patients assigned the device had improved their mitral regurgitation severity by at least two grades compared with 15.9% in those assigned medical therapy alone (P < .0001). Both groups had similar rates of changed to 12 months in tricuspid regurgitation severity (P = .34) and RV systolic pressure (P = .13).
When the top half and bottom half of each echocardiographic subgroup was compared with each other, those assigned to the device therapy always had better outcomes, Asch said.
Predictors of mortality or first HF hospitalization at 24 months for patients in the control group included a tricuspid regurgitation grade equal or greater than 2+, those with lower LVEF and those with higher right ventricular systolic pressure and mitral regurgitant effective regurgitant orifice area. The only predictor of poor outcomes in the device group was a higher RV systolic pressure.
“It is important to understand that the high pulmonary pressures in this population are not necessarily because of the mitral regurgitation by itself, but also because of the cardiomyopathy,” Asch said during the discussion portion of the presentation. “These patients have a dual disease, and we are taking care [of them] with the MitraClip for the mitral regurgitation aspect of that. Is there any other threshold we should be using for this? I really don’t know. I don’t think we can get the answers at least from the data that we have so far, but it is a very interesting observation.”
Suzanne V. Arnold, MD, cardiologist at St. Luke’s Mid America Heart Institute in Kansas City, associate professor of medicine at University of Missouri-Kansas City and a Cardiology Today Next Gen Innovator, and colleagues analyzed health status as reported by patients in the COAPT trial who were assigned the device (n = 302) or standard care (n = 309). Three patients from the COAPT trial were excluded for not completing health status assessments at baseline.
Health status was assessed at baseline, 1 month, 6 months, 12 months and 24 months using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and SF-36 Physical and Mental Summary Scores.
The primary outcome was the KCCQ summary score over a 24-month period.
At baseline, the overall KCCQ summary score was 53.2 in the treatment group and 51.6 in the control group, with the quality of life domain being most impacted.
“This roughly correlates to NYHA class III,” Arnold said during the presentation.
The SF-36 physical summary score was 33 in the treatment group and 32.6 in the control group, which was nearly 2 standard deviations below the mean of the general population.
At 1 month, the mean between-group difference in KCCQ score was 15.9 points (95% CI, 12.3-19.5) in favor of the device-therapy group, which was maintained with minimal attenuation at 24 months (12.8 points; 95% CI, 7.5-18.2).
“This represents a moderately large clinical change over three times the minimal clinically important difference for the KCCQ,” Arnold said.
Similar patterns were seen in individual KCCQ domains including quality of life, physical limitations, social limitations and total symptoms.
At 24 months, the mean difference in Short Form-36 scores was 3.6 for both the physical and mental summary scores, with a greater improvement in patients assigned the device.
In subgroup analyses, researchers found consistent benefit in the treatment group across several demographic and clinical factors, including frailty measures. In addition, patients in the treatment group who had ischemic cardiomyopathy had a greater health status benefit (mean difference = 18.3; 95% CI, 13.6-22.9) compared with those with non-ischemic cardiomyopathy (mean difference = 8.4; 95% CI, 2.7-14.1; P for interaction = .02). There were substantial and significant benefits of the treatment compared with standard care in both of these groups with cardiomyopathy, according to the researchers.
“Furthermore, this result should be considered exploratory given the number of secondary outcomes that were tested,” Arnold said during the presentation.
Although there were observed improvements in health status as per this analysis, there are challenges in performing these kinds of studies, especially in studies with a high mortality rate.
“Health status can only be assessed amongst survivors, and yet we know that patients with worse health status are more likely to die,” Arnold said during the presentation. “When we look at the COAPT population, we see that not only is the mortality rate high, but it also differs between groups. When we ignore these deaths, it biases our results, as the sickest patients are systematically removed from the analysis due to death. This makes health status appear to be better than it otherwise would had these patients survived.”
Given this, researchers in this analysis employed several strategies to address this challenge, including categorical analyses and to jointly model health status and mortality.
“Considering the previously reported benefits of [transcatheter mitral valve repair] on survival and heart failure hospitalization, these health status results further support the use of MitraClip for patients with heart failure and 3+ or 4+ secondary MR who remain symptomatic despite maximally tolerated guideline-derived medical therapy,” Arnold said during the presentation.
The findings of the quality-of-life study were also simultaneously published in JACC: Cardiovascular Interventions. – by Darlene Dobkowski with additional reporting by Katie Kalvaitis
Arnold SV, et al.
Asch FM, et al. Joint American College of Cardiology/New England Journal of Medicine Late-Breaking Clinical Trials. Both presented at: American College of Cardiology Scientific Session; March 16-18, 2019; New Orleans.
Disclosures: The COAPT trial was funded by Abbott. Arnold and Asch report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Editor’s Note: This article was updated on March 22, 2019 to clarify the conclusions of the COAPT echocardiographic study.