Now that transcatheter aortic valve replacement (TAVR) is rapidly becoming an established treatment option, cardiology has shifted focus toward the next major frontier in interventional structural heart technology — transcatheter mitral valve repair (TMVR). It was very obvious at the 2014 Transcatheter Cardiovascular Therapeutics (TCT) meeting that mitral valve technology will become the next major trend, as sessions on this topic were packed to capacity.
“Everything is now focused on the mitral valve,” said Chad Kliger, M.D., M.S., who attended these sessions. Kliger is assistant professor of cardiology at the Hofstra University School of Medicine within the Division of Structural and Congenital Heart Disease, Lenox Hill Heart and Vascular Institute/North Shore LIJ Health. “All the key people at TCT involved in cardiac surgery and structural heart interventions were either presenters on new mitral valve technologies or they were sitting in the audience.”
Mitral regurgitation is common, affecting more than 4 million Americans — nearly one in 10 people aged 75 and older.  Due to the success of TAVR in attracting many new patients with aortic disease to hospitals’ TAVR programs, many are now looking to do the same with that large pool of mitral valve patients. From a practical standpoint, TAVR currently is only indicated for high-risk and non-surgical replacement patients, so its use is limited. However, hospitals with TAVR programs have attracted many new patients despite the fact that most will be turned down for not meeting the U.S. Food and Drug Administration (FDA) indication criteria. But, from a business standpoint, hospitals have been very successful at retaining these patients for their surgical valve replacement programs, boosting surgical procedural volume. TMVR will likely follow a similar path, starting with the sickest patients and a narrow indication, but likely attracting less sick patients who would rather have this minimally invasive procedure over surgery.
The FDA cleared the first transcatheter mitral repair device, Abbott’s MitraClip, in October 2013. The device only mimics one type of open surgical repair for a specific type of mitral regurgitation (MR). It cannot replace a worn-out or heavily stenosed valve, so several vendors are now developing transcatheter mitral valves and new types of delivery systems.
Watch the video “Transcatheter Mitral Valve Therapies in Development.” An interview with Juan Granada, M.D., executive director and chief scientific officer of the Cardiovascular Research Foundation's Skirball Center for Innovation.
Watch the video “Transcatheter Mitral Valve Repair Technologies.” An interview with Ted Feldman, M.D., FACC, MSCAI, FESC, cardiac cath lab director, Evanston Hospital, North Shore Health System, and principle investigator, Everest II MitraClip U.S. pivotal trial.
The Complex Mitral Anatomy
Mitral valve anatomy is much more complex than the aortic valve, which is why it has taken more time to develop a transcatheter valve and deployment system, said Neil Moat, MB, BSMS, FRCS, Royal Bromton Hospital, U.K., at the TCT mitral valve session. He explained there are frequently issues with left ventricular outflow tract (LVOT) obstruction due to the close proximity of the aortic and mitral valves and the steep angle of the LVOT, so new valves will have to find ways to mitigate this issue. Additionally, the mitral valve is part of the left ventricular wall and its leaflets are tethered with chordae tendineae, which may entrap a transcatheter valve. Calculating annular area and length to also is more challenging than the aortic valve and a system will have to be standardized to allow for accurate valve sizing, he explained. This, combined with a much larger angular range as opposed to the TAVR and more variable and complex biomechanical behavior, makes dislodgment of a mitral valve more likely than with aortic valves.
Transesophageal echo (TEE) is used in the cath lab to help guide TAVR procedures and it is mandatory to perform MitraClip procedures. With TMVR, 4-D TEE will likely be required to visualize the implant to clearly hit the narrow landing zone and to help avoid complications.
Mitral Valves in Development
Several medical device companies are now in competition to bring first-generation transcatheter mitral valves to market. The leaders so far appear to be Edwards Lifesciences’ Fortis mitral transcatheter heart valve, and Neovasc Inc.’s Tiara transcatheter mitral valve. Both companies reported first-in-human implants in 2014.
The Fortis transcatheter mitral valve features treated bovine pericardial tissue leaflets, a cloth-covered self-expanding frame designed to minimize paravalvular leak, and an anatomical anchoring system. It is delivered using a transapical approach with a sheathless delivery system. The valve has paddles that fold out at the base and clip the native mitral valve leaflets to help anchor it. The first human trial began in August 2014 with centers in the United Kingdom, Canada and Switzerland.
Edwards also has experience with its Sapien TAVR device being implanted in the mitral valve position in many patients in Europe since 2011. Henry Ford Hospital in Detroit recently implanted a Sapien device in a non-operable mitral valve patient and said it is working on an FDA-approved trial to further investigate the use of the Sapien valve in the mitral position. In addition, the next-generation Edwards Lifesciences Sapien XT TAVR system is already cleared in Europe with an additional indication for use in the mitral valve. Last February, the Sapien XT received an additional European market clearance for use in valve-in-valve procedures for both the aortic and mitral valves. Edwards may have an advantage over potential competitors because it already has established relationships and a distribution network with many hospitals using its surgical and Sapien valves.
Neovasc’s Tiara device uses a self-expanding frame, uses bovine pericardial tissue leaflets, has a fabric-covered skirt to prevent paravalvular leak, and deploys two tabs to help engage the native valve for anchoring. It is delivered transapically using a 32 French sheathless system under rapid pacing.
The Tiara is the first transcatheter mitral valve to receive an FDA conditional investigational device exemption (IDE) approval to initiate the U.S. arm of its Tiara-I Early Feasibility Trial. The study will enroll up to 30 patients globally and is being overseen by a multidisciplinary committee co-chaired by Martin Leon, M.D., director of center for interventional vascular therapy Columbia University Medical Center/New York-Presbyterian Hospital, and Anson Cheung, M.D., professor of surgery and director of cardiac transplant at St. Paul's Hospital, Vancouver Canada. It will enroll patients at three U.S. centers: Columbia University Medical Center/New York-Presbyterian, Lenox Hill Hospital and Cedars-Sinai Medical Center. The first U.S. patients should be enrolled by early 2015.
Another potential player is CardiAQ Valve Technologies, which announced a successful implantation of its valve in June 2012 in Europe. In 2014, the company implanted its first patient using a transapical delivery system. The CardiAQ device is self-conforming, self-anchoring and uses a self-expanding structure with barbs that deploy on both sides of the native valve to engage the mitral annulus. Its design uses a foreshortening frame to address the specific challenges of the mitral anatomy, and includes numerous proximal and distal anchors connected to the frame. Radial expansion of the frame causes the ends of the anchors on both ends to draw closer together. It is slated to begin a CE mark trial in Europe in early 2015 that will include 100 patients at 10 centers. It was already implanted in four patients in Denmark who were turned down for MitraClip repairs and were offered the Cardiaq valve on compassionate grounds.
In November, the Tendyne Transcatheter Mitral Valve Implantation system (TMVI) was successfully implanted in the first patient involved in the Tendyne Feasibility Study. This three-continent, multicenter trial is examining the safety and performance of the device in inoperable patients suffering from mitral regurgitation. Tendyne recently secured $25 million in financing from investors for the clinical trial.
“The device was implanted transapically without cardiopulmonary bypass and performed as intended by completely eliminating mitral regurgitation,” said Dr. David Muller in a statement, who performed the implantation at St. Vincent’s Hospital in Sydney, Australia. “The patient recovered quickly and was released from the hospital on day five. We believe the device has the potential to offer a very effective solution for patients at high risk for conventional mitral valve surgery.”
Medtronic is developing a self-expanding covered stent valve that has a large crown to cover the atrial portion of the valve and arms on the ventricular side to engage both sides of the native valve. It is designed to be recapturable and retrievable.
Cephea Valve Technologies is developing a valve that recreates the annual plane, mimicking the surgical approach for valve replacement, according to Juan Grenada, executive director and chief scientific officer of the Skirball Center for Cardiovascular Research at the Cardiovascular Research Foundation. He explained the valve uses a transseptal delivery system in a two-step deployment process. Once deployed it self-orientates and conforms to the native valve.
Heading Into the Future
“Two years from now we will be well on our way in clinical trials with some of these devices,” said Afredo Trento, M.D., director, division of cardiothoracic surgery Cedars-Sinai Medical Center.
He said good candidates for TMVR will be patients with failed mitral valve prosthesis and failed mitral valve repairs. For patients with high-risk degenerative pathology with good ventricular function, the question will be whether they should get a MitraClip or a new valve. He said this might lead to future trials that examine the use of the clip verses TMVR.
Trento raised the question of which access route will become dominant as new mitral valve technologies become available. Both transapical and transseptal approaches are currently used or being proposed for various devices. He believes transseptal access will likely become the more commonly used method, because it will be safer and less invasive.
Advancements in TAVR and TMVR Technologies at TCT 2016
Watch the video VIDEO “Transcatheter Valve Technology Advancements at TCT 2016.” This is an interview Torsten Vahl, M.D., about advancements in transcatheter valve repair technology, including new devices for the aortic, mitral and tricuspid valves. Vahl is director of experimental and translational research and assistant professor of medicine, Columbia University Medical Center, Center for Interventional Vascular Therapy.
Watch the video “VIDEO: Transcatheter Mitral Valve Technology, Anatomical Challenges.” A discussion with Juan Granada, M.D., about transcatheter mitral valve advancements and device challenges at the Transcatheter Cardiovascular Therapeutics (TCT) 2016 annual meeting. Granada is executive director and chief scientific officer of the Cardiovascular Research Foundation's Skirball Center for Innovation.