Initially designed as a treatment for inoperable patients with aortic stenosis, because of encouraging results in high- and intermediate-risk patients as well as in inoperable patients, transcatheter aortic valve implantation (TAVI) is now being evaluated in low-risk patients. This success has prompted interest in developing percutaneous options for other structural heart valves—as evidenced by the large number studies on novel therapies for the mitral valve presented at EuroPCR (17–20 May, Paris, France).
Carmelo Grasso (Cardiovascular Department and Division of Cardiology, Ferrarotto Hospital, University of Catania, Catania, Italy), who spoke about pipeline mitral valve therapies at EuroPCR, believes another reason for the current interest in the mitral valve is the complexity of the valve and that of the surrounding area. He says: “In the mitral apparatus, there are complex interactions between all the structures involved in the functions of the valve that can influence the development of mitral regurgitation. As a consequence, there are more opportunities to develop different devices to fix different problems. The percutaneous ‘mitral space’ is mostly unexplored and there is not a definitive device, but there are a lot of ongoing projects in this area.”
Adapting TAVI technology
One such project is to evaluate the use of currently available TAVI devices for mitral valve replacement. During a late-breaking trial session at EuroPCR, Mayra Guerrero (NorthShore University Health System, Evanston, USA) presented results from the first global registry of using TAVI to manage mitral annular calcification in patients who were unable to undergo surgery. She stated that, as part of the registry, 104 patients (from 47 centres from 11 countries) underwent transcatheter mitral valve implantation (TMVI) with “compassionate use of an aortic transcatheter heart valve”. The majority of the patients underwent TMVI with Sapien XT (Edwards Lifesciences) and the transapical approach was the most common approach used. Guerrero reported that the procedural success rate improved with experience (the overall technical success rate was 75%) as did the 30-day mortality rate (overall, 10.6%). “TMVI is feasible in patients with mitral valve disease and severe mitral annular calcification. It may be an option in carefully selected patients and there is an important learning curve, with difficulties seen with the early experiences. Studies are needed to determine the best sizing and delivery methods, left ventricular outflow tract obstruction prevention strategies and to improve patient selection,” she concluded—adding that the MITRAL (Mitral implantation of transcatheter valves) would further explore the use of TAVI devices to manage mitral annular calcification.
Maurice Buchbinder (Foundation of Cardiovascular Medicine, San Diego, USA) also spoke at EuroPCR about the use of TMVI with a TAVI device, discussing the combined use of a proprietary valve support/dock device (deployed in native mitral annulus) with a TAVI device. He said: “The MValve dock is designed as a universal device that is fully compatible with a variety of commercially available as well as proprietary, transcatheter valves. The docking system enables accurate and optimal positioning of transcatheter valve prosthesis given its excellent fluoroscopic visibility and sealing skirt allowing for minimal or no paravalvular leak.” Describing the first human experience of TMVI with the MValve dock (in a 75-year-old male with both aortic and mitral valve diease), Buchbinder noted that “follow up transoesophageal echocardiogram/transthoracic echocardiogram confirmed excellent valve position and function with no residual mitral regurgitation.” However, he added that the patient developed severe bilateral pneumonia with respiratory failure, on day 20 after the operation, and his family refused further extended medical care. “In extensive preclinical and very limited clinical experience, the MValve system appears to be a safe, effective, and relatively simple procedure for TMVI,” Buchbinder concluded.
Specific replacement devices
The majority of TMVI innovations involve specifically designed bioprosthetic devices for the mitral valve. Speaking at EuroPCR, David Muller (St Vincent’s Hospital, Sydney, Australia) discussed the 30-day outcomes from the Tendyne global feasibility trial. This study is evaluating the use of Tendyne transcatheter mitral valve—a self-expanding double frame device with a symmetrical trileaflet porcine pericardial valve. Muller reported that, based on the 30 day outcomes of 23 patients who received the device, the valve is associated with a low rate of mortality. He added that there were “no procedural deaths, strokes or device dislodgements” during the first 30 days and that the expanded trial was currently enrolling more patients.
Another specific TMVI device discussed at EuroPCR was Medtronic’s Intrepid device, which has a dual stent design (a conformable outer stent and a circular inner stent). Vinayak Bapat (Guy’s and St Thomas’ Hospital, London, UK) reported that, at present, the device has been implanted in 15 patients. He commented that based on the latest follow-up data, 14 patients had mitral regurgitation grade 0. Furthermore, six-month data for one patient (an 85-year-old man) showed good valve function (according to TTE) with no paravalvular leak. Bapat concluded that the device was “adaptable to multiple approaches”.
Noting that there are several specific mitral bioprosthetic valves in development, Grasso comments that there “many promising projects”. He adds: “One of the best is the Tendyne valve. Compared with data for the other mitral valves, it is associated with the best performance and a very low rate of adverse events. If the company succeeds in developing a trans-septal approach, this valve could become a reference for other valves.”
As well as innovations that are designed to replace the mitral valve, there are several therapies in the pipeline that seek to repair the mitral valve. Ganesh Manoharan (Royal Victoria Hospital, Belfast, Northern Ireland, UK) presented data at EuroPCR for a novel percutaneous septal sinus shortening device. He explained that the Arto system (Myrx) uses direct anterior to posterior diameter shortening to treat functional mitral regurgitation, was “acutely reversible or removable”, and had “little impact to potential future therapy”. “Long-term data suggest clinical efficacy and safety are maintained up to one year and early phase II results support feasibility conclusions,” Manoharan commented.
Hendrik Treede (Mid-German Heart Center, University Hospital Halle, Germany) outlined data for a device that could be used to treat both tricuspid and mitral regurgitation. He said the “semi-rigid” ring (Millipede IRIS) was associated with “positive clinical results” with mitral regurgitation and tricuspid regurgitation “significantly reduced” in the patients it had been used in. He added that the device enabled preservation of future options.
Transition to clinical practice
Only time, and further studies, will tell if the novel devices discussed in this article will make the transition from investigational to clinical practice. The path to approval may be more difficult than it was for the TAVI devices. Grasso notes that the aortic valve is “much simpler” than the mitral valve because it is “just a hole in a tube” and that it is treated in a similar way to a coronary stenosis “by dilating and implanting a big stent”. “The mitral valve is a complex apparatus made by leaflets, annulus, chordae, papillary muscle and left ventricle. This complexity makes the development of transcatheter device much more difficult. Devices to repair or replace the mitral valve have to take into account all the structures and their interactions,” he adds.
At present, only a few percutaneous options for the mitral valve are approved for use in Europe—including the two recently approved transcatheter direct annuloplasty systems (Valtech’s Cardioband and Mitralign’s MPAS). Of these CE-marked devices, Abbott Vascular’s percutaneous edge-to-edge repair system (MitraClip) is the most well-known. Grasso comments that the device, which is the only percutaneous mitral valve system to be approved in the USA, has been implanted in more than 30,000 patients worldwide. He notes that the system represents the “gold standard of percutaneous repair” because it “leads to an improvement in New York Heart Association (NYHA) class, mitral regurgitation, the six-minute walk test, re-hospitalisation rate, and improves left ventricular volume and diameter.”
However, Grasso states that the long-term term duration of the system “could be affected by the lack of a combined annuloplasty” and notes “the availability of other devices to perform percutaneous direct and indirect annuloplasty, chordae implantation and left ventricle reshaping could permit to deliver more appropriate therapies even with a combination of multiple devices.”