In the new trial, moderate or severe paravalvular leaks, a complication that has previously been linked with worse outcomes and increased mortality, occurred in 17% of the patients who received the approved valve and in 24% of patients who received the XT valve at 30-day follow-up, a difference that did not reach significance.
"Is there a difference in paravalvular leaks between Sapien XT and Sapien? We’re not entirely sure. There was a nonsignificant trend" that will be the subject of further analysis, Dr. Leon said. He stressed that the leak rate is confounded because significantly more patients who received the approved valve underwent a second valve placement, which often occurs because a leak occurred with the first valve. "Putting in a second valve is a big thing and is not good," he said. "No matter how you look at it, there still was a significant leak rate that is not as good as it needs to be." Dr. Leon said that he hopes the issue of paravalvular leaks will be addressed by a third-generation valve system that will enter clinical trials later this year.
Dr. Michael J. Mack
But some surgeons and interventionalists involved in the PARTNER II trial noted that the incidence of paravalvular leaks has already begun to come down in the past year or so.
"We are [now] much better at sizing the valve with CT scans, and that is reducing the number of paravalvular leaks, at least anecdotally at our center," said Dr. Michael J. Mack, a cardiothoracic surgeon at the Heart Hospital in Plano, Texas, and a PARTNER II investigator. "We also underfill or overfill our [valve expansion] balloons based on the CT scans, and we’re getting better results with that. We’re fitting the valve better into the space," he said in an interview.
Dr. Jeffrey J. Popma
"We do everything we can to minimize patients leaving with a moderate or severe leak by balloon dilatation or putting in a second valve," said Dr. Jeffrey J. Popma, an interventional cardiologist and professor of medicine at Harvard University in Boston and a PARTNER II investigator. He also noted that use of the XT device reduces the number of patients who need transapical valve placement, because the smaller catheter can be more easily manipulated through a patient’s ileofemoral anatomy.
A further advantage of the XT valve for minimizing paravalvular leaks is that it is available in a 29-mm diameter, although the 29-mm valve was not included in the PARTNER II trial. The widest valve available in the original Sapien design was 26 mm.
Dr. Joseph E. Bavaria
"The 29-mm valve is a huge advance because we know that [until now] TAVR success is greater in women, probably because about 20% of American men need a larger valve, and their leak rate was higher," said Dr. Joseph E. Bavaria, a professor of surgery at the University of Pennsylvania in Philadelphia and a PARTNER II investigator. "Having the 29-mm valve available will be a big difference," he said in an interview.
The PARTNER II trial has a second cohort, cohort A, that is comparing the Sapien XT valve system against open surgical valve replacement in patients who are deemed eligible by cardiac surgeons for surgical aortic valve replacement and are at "intermediate" risk for undergoing surgery. Enrollment of the roughly 2,000 patients who will enter this study should be complete by this summer, and with a 2-year primary endpoint the results should be available sometime in 2015, Dr. Leon said.
The PARTNER II trial is sponsored by Edwards Lifesciences, which markets the XT transcatheter aortic valve system. The company has not filed an application for approval of the Sapien XT device. Dr. Leon, Dr. Mack, Dr. Popma, and Dr. Bavaria all participated in the trial. Dr. Mintz said that he has been a consultant to Boston Scientific.