Functional Mitral Regurgitation – EMPOWERed by The Carillon Device – Perspectives From Dr. Samir Kapadia

Dr. Samir Kapadia is the Chief of the Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at the Cleveland Clinic. He is a Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. He is a pioneer of structural interventional cardiology with special interests in aortic, mitral and tricuspid valve interventions.

Functional/secondary mitral regurgitation (FMR) is a common finding in patients with heart failure and/or atrial fibrillation due to an imbalance of closing versus tethering forces as well as annular dilation.¹ FMR is associated with increased morbidity and mortality. Development of transcatheter mitral valve (MV) interventions has been challenging due to the mitral valve’s accessibility, anatomic complexity, and co-morbid myocardial disease. But innovation in this space has been extraordinary with proliferation of several devices either approved or being tested. Transcatheter edge to edge repair (TEER) now has a Class 2a indication in the American guidelines for patients with chronic severe secondary MR related to LV systolic dysfunction who have persistent symptoms while on optimal guideline directed medical therapy for HF with appropriate anatomy, LVEF 20-50%, LVESD ≤70mm, and pulmonary artery systolic pressure ≤70mmHg.²

CardioNerds: Dr. Kapadia, the advent of TEER has revolutionized the care of appropriately selected patients with FMR. What gaps remain? In which patients is TEER not an option?

Dr. Kapadia: FMR is a complex problem. There are several interesting areas with limited information:

1. Moderate MR – a. Implications for clinical outcomes (death, hospitalizations, AF), b. Contribution to worsening MR (tertiary MR), unfavorable remodeling, EF decline, ect.

2. Annual dilation and FMR – a. Contribution from atrial versus ventricular dilation, b. Importance of preserving annular function with reduction in annular size, c. Effects of FMR on annular morphology and function.

Although our understanding of FMR has improved considerably over the years, treatment options for moderate MR remain understudied. Since most of the MR studies are not addressing specific mechanisms of MR, it is hard to tease out clinical and management implications for different stages as well as different etiologies of FMR from current literature.

More recently, FMR is broadly classified as atrial or ventricular FMR. Atrial FMR (A-FMR) is typically defined as patients with large atrium but normal size and function of LV. Ventricular FMR (V-FMR) is typically defined as MR resulting from ventricular dilatation and reduced EF. It is clear that many patients with “ventricular MR” have atrial dilatation and so most V-FMR patients have V+A FMR with variable contribution from each (A or V). It will be interesting to study these different forms and stages of MR to be able to “personalize treatment” – a concept commonly referred to as precision medicine.

TEER is not studied for patients with moderate symptomatic MR. TEER is also suboptimal for patients with very wide jet of MR or tethered anterior leaflet where significant MS can result from further restriction with TEER.

 CardioNerds: The Carillon device (CardiacDimensions, Inc.) is a constricting band which is placed in the coronary sinus. The REDUCE FMR trial showed that it reduced regurgitant volume and improved LV dimensions 1-year after annuloplasty.³ How does this device work and how does it add to your toolkit beyond TEER?

Dr. Kapadia: The Carillon Device reduces the annular dimension by mechanically pulling the tissue surrounding annulus. Most commonly the CS is on the atrial side of the annulus and the device exerts constant pull from antero-lateral part of the sinus (distal anchor) to the more postero-medial part of the sinus (proximal anchor).  This force is transmitted to the annulus to remodel the annulus while preserving annular function, a distinguishing effect compared to direct annuloplasty where annulus is directly reduced with a ring that may also immobilize the annulus.

The Carillon device is simple to deploy via 10F venous access from right internal jugular vein. The procedure can be performed with conscious sedation without TEE. Overall safety profile is excellent. Further, future treatment options for the MR are preserved. These characteristics make the device ideal for moderate MR treatment.

CardioNerds: What are the downsides or noted complications associated with Carillon device implantation? Would use of Carillon impact a patient’s candidacy for a coronary sinus pacing lead for cardiac resynchronization?

Dr. Kapadia: The Carillon device procedure is overall very safe. Constriction of the left circumflex coronary artery or its branches can occur but typically this is seen at the time of the procedure. Repositioning of the device can help alleviate this. Infrequently, the device has to be retrieved completely but this is achieved easily. Future lead in the CS is also possible after Carillon device implantation.

CardioNerds: You are the lead principal investigator for the EMPOWER Trial which is an international randomized sham-controlled trial of Carillon implantation in patients with symptomatic heart failure with LVEF ≤50% and at least mild MR. How did you come up with this design and specifically the decision to include patients with mild-moderate MR?

Dr. Kapadia: The REDUCE MR trial was conducted outside of US with an idea to enroll patients with severe MR but this was investigator reported MR. When we analyzed the echo studies blindly at the Cleveland Clinic corelab, we found some patients with moderate MR enrolled in the trial. On post hoc analysis, these patients benefited with positive remodeling of the ventricle with Carillon device placement. This led to the interesting modification of the EMPOWER study to include moderate MR. Since there is no corrective treatment for moderate FMR, comparator can be standard of care (medical management). We included need for corrective mitral valve procedure or surgery as an endpoint. This innovative trial design will allow us to treat patients at an earlier stage of their disease process while preserving future options.

CardioNerds: What are you most excited about in anticipation of this trial?

Dr. Kapadia: An ability to treat moderate and severe MR, staged treatment strategy by preserving future treatment options, and a simple procedure!

References

1. Goyal A, Krishnaswamy A. Percutaneous Valve Interventions in Heart Failure. Curr Treat Options Cardiovasc Med 2020 2211 [Internet]. 2020 [cited 2022 Feb 19];22:1–23. Available from: https://link.springer.com/article/10.1007/s11936-020-00841-x
2. Otto CM, Nishimura RA, Bonow RO, Carabello BA, rwin JP, Gentile F, Jneid H, Krieger ric V., Mack M, McLeod C, O’Gara PT, Rigolin VH, Sundt TM, Thompson A, Toly C. 2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2021;143:E72–E227.
3. Witte KK, Lipiecki J, Siminiak T, Meredith IT, Malkin CJ, Goldberg SL, Stark MA, von Bardeleben RS, Cremer PC, Jaber WA, Celermajer DS, Kaye DM, Sievert H. The REDUCE FMR Trial: A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation. JACC Hear Fail. 2019;