Transapical Transcatheter Mitral Valve Replacement Trial Raises Questions

PHOENIX -- Global experience with the novel Intrepid transapical transcatheter mitral valve replacement (TMVR) device through 2 years showed high risks of mortality and complications, raising concerns that might not be alleviated by the planned shift to a transfemoral approach.

In the analysis pooling data from a pilot study and the APOLLO trial, the high-risk patient population studied with at least moderate-severe symptomatic mitral regurgitation (MR) not considered candidates for surgical treatment had "reduced but continued primary endpoint events after 30 days, largely due to underlying myocardial dysfunction," reported Martin B. Leon, MD, of Columbia University/NewYork-Presbyterian Hospital and the Cardiovascular Research Foundation in New York City.

The combined rate of all-cause mortality and heart failure hospitalization rose from 41.3% at 1 year to 52.8% at 2 years, he noted at the annual TVT conference hosted by the Cardiovascular Research Foundation.

The rate of all-cause mortality increased from 13.1% in the first 30 days to 16.3% in year 1 to 12.4% in year 2. For heart failure hospitalization, those rates were 9.6%, 21.2%, and 17.9%, respectively.

The APOLLO trial also included Kansas City Cardiomyopathy Questionnaire (KCCQ) quality-of-life score improvement as part of the composite primary endpoint. At 2 years, the proportion of patients alive and well with a KCCQ score at least 10 points better than baseline declined to 39.3% from 47.9% at 1 year.

The high mortality risk in these patients was notable, said session panelist Gorav Ailawadi, MD, of the University of Michigan in Ann Arbor.

Also concerning was the decline in left ventricular ejection fraction (LVEF) seen over time, he said. In the primary MR patients, it declined from 56% at baseline to 48% at 1 month and 1 year to 47% at 2 years. In the secondary MR patients, LVEF fell from 40% at baseline to 34% at 1 month before stabilizing to 36.5% at 1 year then falling again to 31.5% at 2 years.

While Leon said this reduction was "as you would expect with mitral valve replacement started at a lower baseline, with about the same level of reduction over time for both primary and secondary MR," he also acknowledged that the platform is moving to a transfemoral approach to reduce risks.

Session panelist Tsuyoshi Kaneko, MD, a cardiothoracic surgeon at Barnes Jewish Hospital in St. Louis, agreed, pointing to the nine cases out of 252 that required emergency surgery (four each due to apical access and to malposition, migration, or embolization) and the 11.4% rate of 30-day reoperation or reintervention, and the 22.3% major or worse bleeding complication rate.

"It also shows the risk of transapical procedure on dysfunctional MR patients with bad ventricles," he said. "Those patients do not tolerate surgical invasiveness, and I think your comment about [transfemoral] is right on. I think that's going to be the future."

However, the data raise concern that the transfemoral approach might not be enough to resolve these problems, Ailawadi suggested.

"What's interesting is there's ongoing worsening of ejection fraction in patients that have a transapical mitral replacement," Ailawadi told MedPage Today. "That's probably going to be true for transfemoral as well. So why do you see the ejection fraction [drop] from a year to 2 years? Even now that you've fixed the mitral regurgitation, it's still getting worse."

"The ventricles are sick, that's probably one part of it," he added. "Is there something going on physiologically where you have a big valve sitting in the heart that's having a detrimental effect? Those are the questions we don't know."

The international APOLLO trial included 157 patients and the pilot trial included 95, both with symptomatic moderate-severe MR deemed unsuitable for mitral valve surgery. Patients had to have anatomy suitable for the Intrepid device delivery based on annular size, LV outflow tract, and LV function. Excluded were patients with less than 24 months of life expectancy, severe/prohibitive mitral annular calcification, severe tricuspid regurgitation, or right ventricular dysfunction.

Of the 244 patients with a device implanted, 144 had 2-year follow-up available. Seventy percent of the patients had secondary MR, while the remainder had primary MR. LVEF was less than 30% for 10% of patients; the majority (56%) fell into the 30-50% range.

The APOLLO trial has a roll-in design with a planned 1,350-patient final enrollment, with evolution to the transfemoral Intrepid system. A randomized trial is also planned to compare mitral transcatheter edge-to-edge repair against transfemoral mitral valve replacement, Leon noted.

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