Transcatheter Trials Break New Ground
Clinical Trials Take on Mitral and Tricuspid Valve Disease
Mitral valve regurgitation is a complex disease to treat as it is a condition of the muscles more than the actual valve. The tricuspid valve was once considered the forgotten valve until older patients began presenting with degenerative heart disease. With successful minimally invasive solutions now readily available for the treatment of aortic valve disease, treating disorders of the mitral valve and the tricuspid valve with transcatheter approaches has captured the attention of interventional cardiologists. Perhaps nowhere is this more apparent than at NewYork-Presbyterian Hospital, where collaborative heart teams at Columbia University Irving Medical Center and Weill Cornell Medicine are confronting the challenges of these two valves with the same intensity they applied to developing transcatheter aortic valve replacement procedures.
Transcatheter Mitral Valve Replacement
Columbia faculty have been serving as lead investigators of the international, multicenter APOLLO trial, beginning with the initial pilot study of the Intrepid™ valve prosthesis in 50 patients from 13 sites. The feasibility study, reported in the January 2, 2018, issue of the Journal of the American College of Cardiology, demonstrated that transcatheter mitral valve replacement is a viable minimally invasive alternative to surgery in patients with symptomatic primary or secondary mitral regurgitation.
The Intrepid valve is a self-expanding stent with an integrated tissue valve designed to facilitate a catheter-based implantation. It is expanded directly into the mitral valve to address the backflow of blood from the left ventricle into the left atrium. The inner stent houses the valve for maintaining blood flow while the outer stent secures the implant within the diseased mitral valve without the need for additional sutures or tethers.
The pilot study showed that it is easy to implant in the challenging mitral anatomy due to its conformable, dual stent design. The study paved the way for the first-ever pivotal trial of transcatheter therapy for the mitral valve and is now enrolling patients with severe, symptomatic mitral valve regurgitation from more than 50 sites nationwide.
Currently the device is inserted from an incision in the chest wall from the apex. Interventional cardiologists at Columbia are now involved in the development of a transseptal delivery system that would allow transcatheter delivery of the Intrepid valve from the femoral vein with a fully percutaneous approach. It is anticipated that the transseptal version will be rolled into the main trial.
Weill Cornell faculty have begun enrolling patients in a pivotal study – the SUMMIT trial – of the Tendyne™ transcatheter mitral valve implantation (TMVI) system for the treatment of severe mitral regurgitation in patients, replacing their native mitral valve without open heart surgery to reduce their heart failure symptoms.
The Tendyne device is a dual frame bioprosthetic valve that has been designed to conform to a broad range of anatomies and, therefore, may allow for better outcomes and procedural ease-of-use. A pad and tether mechanism stabilizes the pad in place inside the native valve. The device is the first and only mitral valve replacement that can be repositioned and fully retrieved, allowing the surgeon to precisely place the device during implantation, which also could improve outcomes.
The SUMMIT trial, which focuses on patients with symptomatic, moderate-to-severe or severe mitral regurgitation or mitral annular calcification, is expected to recruit approximately 1,000 patients at up to 80 sites worldwide. The study will compare outcomes of the Tendyne mitral valve system to MitraClip™ transcatheter mitral valve repair, the current standard of care for patients not suitable for mitral valve surgery. Results of the first 100 patients treated in the global study showed that, at 30 days, patients treated with Tendyne had a significant reduction in symptoms of MR and low mortality rates.
Transcatheter Tricuspid Valve Repair
Columbia cardiologists have worked extensively on developing and refining less invasive therapeutic options to treat tricuspid valve disease, and were among the first investigators to explore transcatheter devices for treatment of tricuspid regurgitation.
They are now major participants in the TRILUMINATE trial, which is evaluating the investigational clip-based percutaneous edge-to-edge repair device – TriClip™ – for the reduction of symptomatic tricuspid regurgitation.
An early feasibility study leading to this pivotal trial was based on strict guidelines developed by an eligibility committee of interventionalists, which identified anatomically those patients who would benefit from the edge-to-edge repair device. Results from the feasibility study presented at the EuroPCR 2019 conference showed that at 30 days, “the clip-based transcatheter tricuspid valve repair significantly reduced tricuspid regurgitation by at least one grade in the vast majority of patients and led to significant improvements in quality of life and NYHA functional class.” At one-year follow-up , patients had sustained improvement in symptoms and quality of life.
Based on these promising results, the TRILUMINATE trial has since been enrolling patients with severe-or-greater tricuspid regurgitation for a prospective, multicenter study, with a planned enrollment of approximately 700 patients. Patients will be randomized to treatment with either medical therapy or TriClip and followed for five years.
Transcatheter edge-to-edge repair for reduction of tricuspid regurgitation: 6-month outcomes of the TRILUMINATE single-arm study. Nickenig G, Weber M, Lurz P, von Bardeleben RS, Sitges M, Sorajja P, Hausleiter J, Denti P, Trochu JN, Näbauer M, Dahou A, Hahn RT. Lancet. 2019 Nov 30;394(10213:2002-2011.