Author + information
- Jason H. Rogers, MD∗ ()
- ↵∗Address for correspondence:
Dr. Jason H. Rogers, Division of Cardiovascular Medicine, 4860 Y Street, Suite 2820, Sacramento, California 95817.
Enthusiasm for the transcatheter treatment of functional mitral regurgitation (FMR) has continued to intensify with an increasing number of reports describing novel nonsurgical methods to favorably modify the mitral apparatus. This enthusiasm is based on the significant prevalence of MR in the setting of heart failure and the projected clinical need for nonsurgical solutions. Chronic systolic heart failure results in structural changes in cardiac geometry that can result in functional (also called secondary) MR. Specifically, left ventricular (LV) enlargement causes outward displacement of the papillary muscles, which pulls the chordae tendineae and mitral leaflets toward the apex of the heart, impairing leaflet coaptation. Enlargement of the mitral annulus and left atrium over time causes the mitral leaflets to be pulled away from one another, resulting in worsening MR. Associated clinical factors such as volume status of the patient, degree of afterload, presence of atrial fibrillation, and myocardial ischemia can also lead to dynamic worsening or improvement in FMR severity. Because FMR often complicates the management of patients with chronic systolic congestive heart failure, and because surgical correction is often perceived to be high risk or of questionable benefit, many patients are not referred for surgical correction. Consequently, many investigators are developing minimally invasive or transcatheter approaches to the correction of FMR, with the hope (yet to be proven) that these therapies will result in lasting and clinically meaningful improvements in patient outcomes as compared with current standard treatments.
In the paper by Park et al. (1) in this issue of JACC: Cardiovascular Interventions, the authors describe the first-in-human results at a single center of a mitral loop cerclage catheter annuloplasty system to treat FMR. The term cerclage is from French meaning literally “encirclement,” but has been used in the medical literature to describe a ring or loop used to bind together the ends of an obliquely fractured bone, or to encircle the opening of an incompetent cervix. There are no prior cardiac-related uses of this term. Five patients with FMR were enrolled. All were symptomatic New York Heart Association functional class III/IV, on stable guideline-directed medical therapy (GDMT), with significant MR based on an effective regurgitant orifice area of ≥0.20 cm2, regurgitant volume ≥30 ml, or a regurgitant fraction ≥50%.
In the mitral cerclage procedure, the mitral annulus is encircled with a loop (named the “cerclage tension element”) that can be tightened, resulting in compression of the mitral annulus and improved mitral leaflet coaptation. The step-by-step description of the procedure is quite detailed in the paper (1). Both the femoral vein and left subclavian vein (through a pacemaker-type pocket) access are required. The cerclage is accomplished by entering the coronary sinus and great cardiac vein, crossing the interventricular septum from the anterior interventricular vein into the right ventricle, snaring this wire with a uniquely designed snare, and forming a loop that can be tightened to compress the mitral annulus. Compression of the coronary arteries (usually branches of the circumflex) is prevented by a small curved tube that forms a “bridge” over the coronary artery. The procedure is performed either under general anesthesia or moderate sedation.
The primary efficacy endpoint was measured at 1 month as change in FMR from baseline. The primary safety endpoint was freedom from MACE or other adverse events at 1 month. Patients were followed up to 6 months in this report. The procedure was acutely successful, and the mitral loop cerclage was implanted in 4 of 5 patients; in 1 patient, the procedure was aborted due to unsuitable coronary venous anatomy. All treated patients had significant reduction in FMR severity at 1 month, and 3 patients had sustained reduction at up to 6 months. One patient died at 6 weeks from refractory heart failure. There were a few other events, including 1 patient who had a focal myocardial infarction related to entrapment of a small obtuse marginal branch. One subject developed a new right bundle branch block, and 1 patient required device repositioning by reopening the subclavicular pocket on post-procedure day 2.
This paper is of interest because transcatheter therapies for FMR are desirable, and intense research is focused in this intersecting area of structural heart disease and heart failure. The authors show that this clever technique can be accomplished with favorable outcomes. Despite these encouraging early results, there are numerous issues to consider in evaluating this new technology. First, this is a very small series of patients performed at a single center. The procedure appears to be somewhat complex (particularly in terms of navigating the interventricular crossing step), and may require a fair amount of adaptation to individual anatomies. It is not entirely clear how the operator decides how much tension to apply to the cerclage system. Presumably, the system could be tightened to a degree to essentially close off the mitral orifice. Finding the balance between adequate and inadequate tension may be challenging. For instance if the system is too loose initially, there may be a higher rate of recurrent FMR over time. Overtightening may increase the risk of device migration, erosion, or coronary compression. That said, the degree of reduction of the mitral septal-lateral (SL) dimension at 1 month in this series was moderate at 15%, and the final SL diameter in all treated patients at 1 month was ≥35 mm. Given that the goal of surgical ring annuloplasty is to reduce the SL dimension at least 25% and achieve a final diameter 26 to 28 mm (<30 mm), it remains to be seen what the durability of this approach will be over time. The mean regurgitant volumes at 1 month were also approximately 30 ml, which would still be considered moderate to severe for patients with FMR. Three of 5 patients enrolled had preserved LV ejection fraction, yet the authors describe this as a series of patients with secondary MR: these patients had LV enlargement but had varying degrees of systolic function and mitral annular dilation. This highlights the heterogeneity of the FMR population.
As an increasing number of reports demonstrate the feasibility of treating FMR by transcatheter means, we need an answer to the following question more than ever: Does transcatheter correction of FMR improve upon current standard-of-care therapy, which generally consists of GDMT, coronary revascularization, and cardiac resynchronization therapy? The ongoing COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial is the most robust trial investigating this question at the present time. This randomized trial examines the safety and effectiveness of the MitraClip system (Abbott, Santa Clara, California) with GDMT as compared with GDMT alone for the treatment of moderate-to-severe or severe FMR in symptomatic heart failure subjects deemed not appropriate for mitral valve surgery. It is certain that other devices will eventually need similar randomized or comparator trials to establish the efficacy of transcatheter FMR correction. Device correction of FMR is unlikely to become a “commodity” because there are so many highly varied devices targeted to FMR correction, each with unique features that could impact safety and efficacy. Finally, surgical guidelines for the correction of FMR remain lukewarm with a Class IIb, Level of Evidence: B recommendation for surgical MV repair in patients with ischemic MR (2).
In summary, the authors demonstrated early clinical feasibility of the mitral cerclage technique in humans, with promising early results related to safety and efficacy. Further data are certainly needed to bolster our understanding of the performance and safety of this procedure. There is a cornucopia of competing transcatheter devices for the treatment of FMR. To succeed, devices will need to demonstrate procedural adoptability (the complexity of the procedure cannot be too high), acceptable safety and efficacy, and that the proposed catheter-based therapy is additive in a clinically meaningful way to current management standards.
↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
Dr. Rogers is a consultant to MVRx and Millipede.
- 2017 American College of Cardiology Foundation
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