TCT 2018: Sham-controlled trial indicates indirect annuloplasty reduces mitral regurgitation

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Horst Sievert

REDUCE-FMR indicates that indirect annuloplasty with the Carillon device (Cardiac Dimensions) is associated with a significant reduction in mitral regurgitation in patients with secondary mitral regurgitation. The trial was unique in that it was sham controlled and, therefore, suggests that sham-controlled trials in valve therapy can be performed. Horst Sievert (CardioVascular Center Frankfurt, Frankfurt, Germany), who presented REDUCE-FMR at the 2018 Transcatheter Cardiovascular Therapeutics (TCT) meeting (21–25 September, San Diego, USA), spoke to Cardiovascular News about the study and the Carillon device.

How does the Carillon device reduce mitral regurgitation?

The Carillon device works by cinching the posterior annulus of the mitral valve. The device is placed in the coronary sinus, which wraps around the posterior annulus of the mitral valve; however, the device is placed a bit higher in the level of the left atrium.

What do you think are the potential benefits of this system compared with more well-known devices such as MitraClip (Abbott)?

There are many possible answers to this question. One advantage is that it does not prevent any other therapies, such as percutaneous mitral valve replacement, from being used whereas a MitraClip does preclude further treatment. Furthermore, the Carillon device does not cause any mitral stenosis or atrial septal defect—which MitraClip can do—and the procedure is shorter and less technically demanding, so probably can be done by more doctors at more centres.

Why did you decide to make REDUCE-FMR a sham-controlled study?

Some have criticised that the clinical benefits seen in prior Carillon studies might have been due to a placebo effect (lots of doubters out there!). Due to the simplicity of the procedure, and the need for a coronary sinus venogram to know if the vein is suitable for Carillon (which could be used as a legitimate sham procedure), it seemed interesting to see how feasible was a sham-controlled study.

How was the “sham” procedure performed?

As alluded to above, patients have to undergo a coronary sinus venogram, with quantitative measurements to see if the vein is suitable sized for a Carillon device. In about 5–10% of cases, the vein is not suitably sized. The technical challenge of the procedure is coronary sinus venous access.   In REDUCE-FMR, once the measurements were taken, the patient was randomised and it only took another 10–15 minutes to implant a Carillon device; so, that process facilitated blinding. The patients were either under general anaesthesia during the case or wore blindfolds and headphones.

What were the key findings of your study?

The Carillon device was successful in reducing mitral regurgitation compared to the sham-controlled population, at one-year follow-up. Additionally, there was a reduction in left ventricular size, which almost met statistical significance, and was consistent with findings from earlier studies.   Interestingly, these findings are despite the fact that the baseline mitral regurgitation was actually milder than planned and much milder than had been studied with MitraClip.

How does the data from REDUCE-FMR relate to the data from MITRA-FR and COAPT? (i.e. collectively what do they indicate about reducing mitral regurgitation in heart failure patients?)

There is quite a lot that could be said about the dramatic differences between MITRA-FR and COAPT, one being dramatically negative and the other dramatically positive. The positive impact of reducing secondary mitral regurgitation seen in the COAPT study truly opens up the field by demonstrating that reducing mitral regurgitation can have important clinical benefits. It is interesting that some have tried to explain the negative findings of MITRA-FR based upon possibly lesser degrees of mitral regurgitation than what was seen in COAPT. However, the mitral regurgitation in REDUCE FMR was if anything even less, yet benefits were seen. Also, the inexperience of the operators has been suggested as a possible reason for the negative impact of MitraClip in MITA-FR, but many of the operators in REDUCE FMR were first-time Carillon operators.

As REDUCE FMR was powered as a mechanistic study, rather than a clinical one, the clinical impact of reducing mitral regurgitation with Carillon will be better addressed with the newly initiated CARILLON trial.

What further data are needed in this area?

As noted, the clinical impact of reducing mitral regurgitation with Carillon needs to be studied with a larger, pivotal trial with clinical endpoints. That is being done with the CARILLON trial, which has recently started. An interesting component of that trial, based upon the favourable findings in REDUCE FMR, is the inclusion of patients with less severe mitral regurgitation. Such patients were not studied in either of the MitraClip studies, which enrolled patients with 3+ and 4+ MR; the CARILLON study includes patients with 2+ patients as well—a subgroup that would still benefit from being studied.

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