Transcatheter Mitral Valve Interventions: An Introduction for the FIT For patients at elevated surgical risk, there has been rapid advancement in catheter-based technologies to treat valvular heart disease in the past five years. As compared with aortic valve disease, there are numerous challenges to repair or replace the mitral valve through dedicated transcatheter technology. The mitral apparatus is complex, changes geometrically during a single cardiac cycle and is subject to higher closing pressures. There is also a lack of a reliable native annular ‘anchor’ to hold a non-surgical mitral valve in place. The etiologies for mitral pathology can be at the level of the leaflet, the annulus or chordae. Given these anatomical and pathophysiologic considerations, it is important for the fellow in training to consider the current commercially available devices in the context of the emerging challenges ahead. First off, it is important to recognize that the MitraClip system (for mitral valve repair) is only approved by the U. S. Food and Drug Administration (FDA) for primary (degenerative) mitral regurgitation (MR) in prohibitive-risk surgical candidates. This includes patients with flail scallops/leaflets, calcific degeneration or restricted leaflets. It is true that the EVEREST II trial included patients with functional MR (normal mitral valve with regurgitation due to dilatation of the left ventricle). However, ‘functional’ was not included in the FDA approval as uncertainty remained about the long-term benefit of the procedure, especially as it does not address the underlying left ventricular pathology, which is a more frequent cause of future morbidity than MR.1 As a result, patients who have functional MR who are being considered for MitraClip would need to be enrolled in the COAPT study, a 1:1 randomized study evaluating the MitraClip versus medical therapy.2 To date, enrollment has been slow for COAPT. The inclusion criteria for COAPT require optimal medical therapy with no medication changes for 30 days. While patients with mixed MR, with both functional and degenerative components, might be considered for on-label use outside of a clinical trial, this indication is often controversial. The Edwards Sapien 3 valve, designed for aortic use, has been successfully used off-label for transcatheter mitral valve replacement (TMVR), often using a transeptal antegrade technique or transapical retrograde approach. This technique has been used most commonly in degenerated mitral bioprostheses (valve-in-valve) and degenerated valve repairs (valvein- ring).3 Less commonly, a Sapien 3 valve can be used to replace a native mitral valve.4 These cases rely on circumferential mitral annular calcification (MAC) to anchor the valve in place. As an important corollary to TMVR, the potential for left ventricular outflow tract (LVOT) obstruction with a new valve is a paramount consideration.5 Valve-in-valve, valve-in-ring and valve-in-MAC procedures are at increasing degrees of LVOT obstruction from a new valve. The general pathophysiology involves the shifting of redundant native anterior leaflet of the mitral valve obstructing outflow from the left ventricle.6 Valve-in-valve cases are certainly at the lower risk of LVOT obstruction from TMVR as compared with valve-in-ring and valve-in-MAC procedures. However, valve-in-valve procedures with hypertrophied ventricles can still pose a risk of LVOT obstruction from prosthetic leaflet tissue. Several institutions have created 3D modeling software to assess this risk and model the ‘neo-LVOT’ area post valve replacement.7 This modeling has been instrumental to the safety of TMVR. In cases where there is predicted LVOT obstruction with TMVR, several techniques have been reported to modify this risk. Emergent alcohol septal ablation has been reported as a bail-out technique in the setting of severe rise in LVOT gradient post TMVR.8,9 An emerging area of investigation is pre-emptive alcohol septal ablation and waiting four to six weeks for myocardial remodeling. These patients can then be re-imaged to again model the ‘neo-LVOT’ area prior to TMVR. This may be a preferred approach for valve-in-valve TMVR in patients at high risk for LVOT obstruction. Another novel technique is called the LAMPOON (Intentional Laceration of the Anterior Mitral Valve Leaflet to Prevent Left Ventricular Outflow tract ObstructioN). This is a percutaneous method to longitudinally lacerate the anterior mitral leaflet at A2 during TMVR. Particularly in valve-in-ring and valve-in-MAC, this procedure has been technically successful in an animal model and in humans to reduce LVOT obstruction risk.10,11 A study directed by the National Heart, Lung, and Blood Institute will start enrollment soon to evaluate the safety of the LAMPOON technique in transcatheter MVR.12 At this time, MitraClip and off-label Edwards Sapien 3 valves are the only commercially available therapies to treat either primary degenerative MR or degenerative surgical prostheses. For those with mitral valve pathologies outside of the above, such as functional etiologies or even degenerative valves that may be poor MitraClip anatomical substrates, there are several investigational studies ongoing for the Tendyne (acquired by Abbott) and Tiara (Neovasc Inc) valves. Tendyne and Tiara are both transapical valves with large delivery sheaths. Both valves are self-expanding with D-shaped configurations. Given the large delivery systems, there may be similar concerns for morbidity with transapical access as there has been for transcatheter aortic valve replacement.13,14 In summary, transcatheter mitral valve interventions are in their infancy. Our understanding of the physiology of the mitral apparatus is evolving through our experiences with current technology. There are multiple anatomic, pathophysiologic and patient considerations that are necessary to match the right patient to the appropriate therapeutic approach that will serve as the most durable option to treat their mitral valve disease. References 1. Feldman T, Foster E, Glower DD, et al. N Engl J Med 2011;364:1395-406. 2. Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial). Available at: https://clinicaltrials.gov/ct2/show/NCT01626079. Accessed May 12, 2017. 3. Webb JG, Wood DA, Ye J, et al. Circulation 2010;121:1848-57. 4. Guerrero M, Dvir D, Himbert D, et al. JACC Cardiovasc Interv 2016;9:1361-71. 5. Blanke P, Naoum C, Dvir D, et al. JACC Cardiovasc Imaging 2017;10:482-5. 6. Greenbaum AB, Condado JF, Eng M, et al. Catheter Cardiovasc Interv 2017;May 4:[Epub ahead of print]. 7. Wang DD, Eng M, Greenbaum A, et al. JACC Cardiovasc Imaging 2016;9:1349-52. 8. Deharo P, Urena M, Himbert D, et al. JACC Cardiovasc Interv 2016;9:e73-e6. 9. Guerrero M, Wang DD, Himbert D, et al. Catheter Cardiovasc Interv 2017;Mar 7:[Epub ahead of print]. 10. Khan JM, Rogers T, Schenke WH, et al. JACC Cardiovasc Interv 2016;9:1835-43. 11. Babaliaros VC, Greenbaum AB, Khan JM, et al. JACC Cardiovasc Interv 2017;10:798-809. 12. NHLBI DIR LAMPOON Study: Intentional Laceration of the Anterior Mitral Leaflet to Prevent Left Ventricular Outflow Tract Obstruction During Transcatheter Mitral Valve Implantation. Available at: https://clinicaltrials.gov/ct2/show/NCT03015194?term=LAMPOON+Study&rank=1. Accessed May 12, 2017. 13. Reynolds MR, Magnuson EA, Lei Y, et al. J Am Coll Cardiol 2012;60:2683-92. 14. Leon MB, Smith CR, Mack MJ, et al. N Engl J Med 2016;374:1609-20. Neil Gheewala, MD, MPH, is a Structural Heart Fellow at the Center for Structural Heart Diseases at Henry Ford Hospital. He is a member of the Leadership Academy for the American College of Cardiology and has interests in healthcare management. The Quest For a Fellowship in Structural Heart Disease As an internal medicine resident, I stood in the back corner of the cardiac catheterization laboratory, behind thirty cardiologists, witnessing our hospital’s first transcatheter aortic valve replacement (TAVR). For my senior resident lecture, I spoke about self-expanding versus balloonexpandable TAVR devices. As a general cardiology fellow, I stood twice more in the back corner of the laboratory during the hospital’s first MitraClip and Lariat procedures. I attended every structural procedure I could, wrote case reports and undertook a data registry analysis. During my third year of general cardiology fellowship, I began to seek a fifth-year structural heart disease (SHD) training position to follow my fourth year, dedicated to coronary and peripheral intervention. Three notable challenges complicated this process. The first challenge was finding fellowship programs for which to apply. I scoured the internet for programs willing to offer SHD training. More recently, the ACC compiled an online list of many SHD fellowship programs. This list, though not complete, is a great starting point for applicants. Since this list was not available at the time of my application, I phoned interventional cardiology fellowship programs at more than 75 institutions. Fifteen institutions were willing to accept my curriculum vitae and cover letter. The second challenge was the application schedule: program timelines varied by 18 months, some beginning as early as July of the third year and some as late as December of the fourth year of fellowship. Over this 18-month period, I received interview invitations from 12 programs. The third challenge was that, for the first time in my life, I was not applying within the framework of a match system. Interviews one through seven were discouraging for me: other candidates were selected for the positions immediately. Despite spending time and money traveling, and constantly requesting call coverage from my colleagues, I was no closer to my goal. Interviews eight and nine occurred back-to-back on a Monday and Tuesday in November of my fourth year. Both program directors called me on Wednesday to offer me a position. Although each seemed to expect me to accept immediately on the phone, I negotiated giving a reply by Friday, giving me 48 hours to decide. Interview number 10, scheduled for Saturday, was now out of the question, as were numbers 11 and 12: I could not turn down two actual offers for the sake of interviews. Forty-eight hours is not much time, which is another challenge in this process. I considered the programs carefully, and although cardiology fellows are not supposed to care about anything except cardiology, I dared to consider personal issues as well. Would my wife, also a medical subspecialist, find a job? Could we sell our home? Where would our children attend school? Where would we live? Late Friday afternoon, with answers to none of these questions, I chose my fellowship. Everything has turned out splendidly. In four months, I have served as primary operator for 41 TAVRs and nine MitraClips. I have performed more than 30 coronary interventions as the attending cardiologist and I spend one day each week participating in peripheral vascular interventions. My wife is a successful assistant professor at our institution with external grant support for her research. In fact, there’s only one problem with this happy ending to my fellowship quest: as my excellent fellowship unfolds, the more difficult search has begun for a permanent SHD job! This article was authored by Andrew M. Goldsweig, MD, FACC, RPVI, structural heart disease fellow at the Warren Alpert Medical School of Brown University.
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