Generalizability is tricky
SAN DIEGO – In patients with heart failure and functional mitral regurgitation, implantation of an investigational device led to reduced MR and improved left ventricular remodeling at 1 year, compared with patients who received sham treatment in the REDUCE-FMR trial.
Jim Kling/MDedge News
Dr. Horst Sievert
The device showed promise in this trial, despite a small sample size, and its nature makes it possible to follow up with other procedures if the disease progresses. “The advantage of this technique is that all other options are still open,” Horst Sievert, MD, director of the CardioVascular Center in Frankfurt, said during a press conference at the Transcatheter Cardiovascular Therapeutics annual meeting.
The Carillon Mitral Counter System includes two anchors, one in the great cardiac vein and one in the coronary sinus, connected by a shaping ribbon. The tension of the ribbon bolsters the mitral annulus, which in turn reduces mitral regurgitation.
REDUCE-FMR recruited 120 patients from centers in eight countries and randomized 87 to the Carillon device (73 implanted) and 33 to a sham procedure. Sham patients were sedated and received a coronary sinus angiogram. Patients were included if they had dilated ischemic or nonischemic cardiomyopathy and moderate to severe functional MR, among other requirements. Exclusion criteria included existing coronary artery stents in the implant target zone, severe mitral annular calcification, and significant organic mitral valve pathology.
The primary endpoint was the mean reduction of regurgitant volume at 1 year. The treated patients had a 22% reduction of 7.1 mL, while the sham group on average had an 8% increase of 3.3 mL (P = .03). In the as-treated subpopulation, which comprised 45 patients in the treatment group and 13 controls, the values were –7.5 mL and +3.3 mL (P = .02). A per-protocol analysis, which excluded patients who did not meet protocol criteria, led to an amplification of the effect when the study design was adhered to (–12.5 mL vs. +1.3 mL), though this result did not achieve statistical significance owing to the small sample size.
For the safety endpoints, the researchers examined the frequency of major adverse events (MAE), including death, myocardial infarction, cardiac perforation, device embolism, and surgery or percutaneous coronary intervention related to the device at 1 year. In the treatment group, 16.1% experienced a MAE, compared with 18.2% of control patients, a statistically nonsignificant difference.
A secondary efficacy endpoint of change in left ventricular end-diastolic volume showed improvements in the treatment group at 6 months (–12.4 mL) and 12 months (–8.6 mL), compared with increases in the sham group at 6 months (+5.4 mL) and 12 months (+6.5 mL). A similar trend occurred in left ventricular end-systolic volume (–7.8 mL and –4.8 mL; +3.4 mL and +6.1 mL, respectively).
The study was conducted in a patient population similar to that of the COAPT trial, which examined implantation of Abbott’s MitraClip. That study, presented here at TCT 2018 and simultaneously published in the New England Journal of Medicine, also examined patients with heart failure and secondary MR.
However, in REDUCE-FMR, many of the patients had milder heart failure than the researchers had expected: 44.8% in the treatment group had NYHA class II, as did 48.5% in the sham group. That surprise may help identify an appropriate patient population. “I think this device may have a nice spot in between medical therapy and MitraClip implantation, because we have, by chance, a patient population with mild heart insufficiency and mild MR,” said Dr. Sievert.
Dr. Michael Mack
The two devices also showed different physiologic effects, Michael Mack, MD, said at a press conference. “One subtle difference is that, in this trial, the difference is due to both positive left ventricular remodeling in the treatment arm and continued progression in the sham control. In COAPT, the difference in improvement that we saw was totally due to prevention of progression of disease. We just stabilized the disease to where it was at. So that’s an intriguing difference here, that you actually were able to demonstrate positive left ventricular remodeling,” noted Dr. Mack, medical director for cardiovascular surgery at Baylor Scott & White Medical Center, Plano, Tex. He was a coinvestigator in the COAPT trial.
REDUCE-FMR was funded by Cardiac Dimensions. Dr. Sievert has received consulting fees, travel expenses, and study honoraria from Cardiac Dimensions, and 35 other companies. Dr. Mack has received grant support or had a research contract with Abbott Vascular, Medtronic, and Edwards Lifesciences.