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SAN DIEGO -- A novel transcatheter device for mitral valve repair in heart failure reduced regurgitation, the REDUCE FMR sham-controlled trial showed.

The Carillon device for indirect annuloplasty cut regurgitant volume by a relative 22% compared with an increase of 8% at 1 year with the sham procedure (-7.1 vs +3.3 mL, P=0.03) as assessed by the blinded echo core lab.

The per-protocol analysis excluding 14 patients not implanted out of the 45 in the intervention arm as well as those who didn't meet anatomical or regurgitation severity criteria increased the effect to a 12.5-mL reduction in regurgitant volume, albeit not significant versus sham due to small numbers.

There was some evidence of positive remodeling, with improvements in left ventricular end diastolic and end systolic volume at 1 year, as well as as well a numerically lower rate of first heart failure hospitalizations and half as many readmissions for it.

However, the trial was too underpowered to say much about the impact on clinical outcomes, cautioned Horst Sievert, MD, of the CardioVascular Center Frankfurt, Germany, in presenting the results here at the Transcatheter Cardiovascular Therapeutics meeting.

This "relatively safe device" appeared "promising" in the preliminary data, commented Ori Ben-Yehuda, MD, executive director of the Cardiovascular Research Foundation clinical trial center. "I think it sets them on the path to a larger study that is underway in the United States."

The study drew comparison to the landmark COAPT trial presented at the same late-breaking trial session, which also used a percutaneous mitral valve repair device -- MitraClip -- but for moderate to severe functional mitral regurgitation in heart failure. It showed substantial outcome improvements over medical therapy alone.

One of the differences was the patient population, with much milder regurgitation in REDUCE FMR.

Another difference was that there appeared to be both positive remodeling along with prevention of continued deterioration with Carillon in REDUCE FMR, whereas in COAPT with MitraClip there was only stabilization of the disease, commented Michael Mack, MD, of The Heart Hospital Baylor Plano in Texas and a primary investigator of the latter trial.

Sievert again cautioned about lack of power to draw conclusions about outcomes. But, he added: "The advantage of this technique is that all other options are still open. You can do whatever you want -- MitraClip, surgery, mitral valve implantation, even direct annuloplasty. It doesn't prevent from CRT [cardiac synchronization therapy]."

Not only would that allow for treating nonresponders (this device is known to improve but not completely eliminate mitral regurgitation) but also deterioration of disease and even initial combination of strategies, he noted.

"I think this device may have a nice part in between medial therapy and MitraClip implantation," he said at a press conference.

The surprisingly positive results despite the small size and less severe than expected mitral regurgitation supported a sham-controlled pivotal trial, which is now underway, Sievert noted.

And it proved that sham could be done in valve device procedures, he added.

"As part of the randomization they had to do anyway a coronary sinus angiogram, so that allowed them to do a sham-controlled [procedure]," said Ben-Yehuda, noting it "gives their data a lot of robustness."

The trial included 120 patients in Europe, Australia, and New Zealand randomized three-to-one to the device, which is implanted transvenous and pushes the mitral valve leaflets closer together from inside the adjacent coronary sinus, or to sham.

While moderate to severe mitral regurgitation in dilated ischemic or non-ischemic cardiomyopathy was required for trial inclusion, MR grade 1 ended up in the trial because the timing of imaging was blinded so trialists didn't know how severe the MR was at baseline.

The 1-year rate of adverse events was similar between groups overall. One death and two procedural MIs were adjudicated as "possibly" related to device, and one MI was deemed clearly device related. There were two procedure-related deaths and three procedure-related MIs compared with none in the control arm. But Sievert pointed out the lack of any coronary artery compression in these.

Asked if such a device could have a role in the armamentarium, Scott Lim, MD, of the University of Virginia in Charlottesville, called it "too premature. One of the interesting things is that each site thought they were enrolling patients with severe functional MR."

Session moderator Martin Leon, MD, of New York-Presbyterian/Columbia University Medical Center in New York City, agreed: "If you want to do a study on quantitative MR, good luck," he said, calling it difficult to discern and measure MR quantitatively.

"Certainly it's not expected that 30% of the patients by the core lab are told they have 1+ MR when the sites felt that they definitely had more than mild MR," he added. "It tells you where the state of imaging is in terms of analyzing this complex entity."

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