Percutaneous Transcatheter Mitral Valve Replacement (2014)

HomeCirculation: Cardiovascular InterventionsVol. 7, No. 3Percutaneous Transcatheter Mitral Valve Replacement Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBPercutaneous Transcatheter Mitral Valve ReplacementAn Overview of Devices in Preclinical and Early Clinical Evaluation Ole De Backer, MD, PhD, Nicolo Piazza, MD, PhD, Shmuel Banai, MD, Georg Lutter, MD, PhD, Francesco Maisano, MD, Howard C. Herrmann, MD, Olaf W. Franzen, MD and Lars Søndergaard, MD, DMSc Ole De BackerOle De Backer From the Department of Interventional Cardiology, Rigshospitalet, Copenhagen, Denmark (O.D.B, O.W.F, L.S.); Department of Interventional Cardiology, McGill University Health Centre, Montreal, Quebec, Canada (N.P.); Department of Interventional Cardiology, Tel Aviv Medical Center, Tel Aviv, Israel (S.B.); Department for Experimental Cardiac Surgery and Heart Valve Replacement, University of Kiel, Kiel, Germany (G.L.); Department of Cardiology, University Hospital Zurich, Zurich, Switzerland (F.M.); and Department of Interventional Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (H.C.H.). , Nicolo PiazzaNicolo Piazza From the Department of Interventional Cardiology, Rigshospitalet, Copenhagen, Denmark (O.D.B, O.W.F, L.S.); Department of Interventional Cardiology, McGill University Health Centre, Montreal, Quebec, Canada (N.P.); Department of Interventional Cardiology, Tel Aviv Medical Center, Tel Aviv, Israel (S.B.); Department for Experimental Cardiac Surgery and Heart Valve Replacement, University of Kiel, Kiel, Germany (G.L.); Department of Cardiology, University Hospital Zurich, Zurich, Switzerland (F.M.); and Department of Interventional Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (H.C.H.). , Shmuel BanaiShmuel Banai From the Department of Interventional Cardiology, Rigshospitalet, Copenhagen, Denmark (O.D.B, O.W.F, L.S.); Department of Interventional Cardiology, McGill University Health Centre, Montreal, Quebec, Canada (N.P.); Department of Interventional Cardiology, Tel Aviv Medical Center, Tel Aviv, Israel (S.B.); Department for Experimental Cardiac Surgery and Heart Valve Replacement, University of Kiel, Kiel, Germany (G.L.); Department of Cardiology, University Hospital Zurich, Zurich, Switzerland (F.M.); and Department of Interventional Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (H.C.H.). , Georg LutterGeorg Lutter From the Department of Interventional Cardiology, Rigshospitalet, Copenhagen, Denmark (O.D.B, O.W.F, L.S.); Department of Interventional Cardiology, McGill University Health Centre, Montreal, Quebec, Canada (N.P.); Department of Interventional Cardiology, Tel Aviv Medical Center, Tel Aviv, Israel (S.B.); Department for Experimental Cardiac Surgery and Heart Valve Replacement, University of Kiel, Kiel, Germany (G.L.); Department of Cardiology, University Hospital Zurich, Zurich, Switzerland (F.M.); and Department of Interventional Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (H.C.H.). , Francesco MaisanoFrancesco Maisano From the Department of Interventional Cardiology, Rigshospitalet, Copenhagen, Denmark (O.D.B, O.W.F, L.S.); Department of Interventional Cardiology, McGill University Health Centre, Montreal, Quebec, Canada (N.P.); Department of Interventional Cardiology, Tel Aviv Medical Center, Tel Aviv, Israel (S.B.); Department for Experimental Cardiac Surgery and Heart Valve Replacement, University of Kiel, Kiel, Germany (G.L.); Department of Cardiology, University Hospital Zurich, Zurich, Switzerland (F.M.); and Department of Interventional Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (H.C.H.). , Howard C. HerrmannHoward C. Herrmann From the Department of Interventional Cardiology, Rigshospitalet, Copenhagen, Denmark (O.D.B, O.W.F, L.S.); Department of Interventional Cardiology, McGill University Health Centre, Montreal, Quebec, Canada (N.P.); Department of Interventional Cardiology, Tel Aviv Medical Center, Tel Aviv, Israel (S.B.); Department for Experimental Cardiac Surgery and Heart Valve Replacement, University of Kiel, Kiel, Germany (G.L.); Department of Cardiology, University Hospital Zurich, Zurich, Switzerland (F.M.); and Department of Interventional Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (H.C.H.). , Olaf W. FranzenOlaf W. Franzen From the Department of Interventional Cardiology, Rigshospitalet, Copenhagen, Denmark (O.D.B, O.W.F, L.S.); Department of Interventional Cardiology, McGill University Health Centre, Montreal, Quebec, Canada (N.P.); Department of Interventional Cardiology, Tel Aviv Medical Center, Tel Aviv, Israel (S.B.); Department for Experimental Cardiac Surgery and Heart Valve Replacement, University of Kiel, Kiel, Germany (G.L.); Department of Cardiology, University Hospital Zurich, Zurich, Switzerland (F.M.); and Department of Interventional Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (H.C.H.). and Lars SøndergaardLars Søndergaard From the Department of Interventional Cardiology, Rigshospitalet, Copenhagen, Denmark (O.D.B, O.W.F, L.S.); Department of Interventional Cardiology, McGill University Health Centre, Montreal, Quebec, Canada (N.P.); Department of Interventional Cardiology, Tel Aviv Medical Center, Tel Aviv, Israel (S.B.); Department for Experimental Cardiac Surgery and Heart Valve Replacement, University of Kiel, Kiel, Germany (G.L.); Department of Cardiology, University Hospital Zurich, Zurich, Switzerland (F.M.); and Department of Interventional Cardiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (H.C.H.). Originally published1 Jun 2014https://doi.org/10.1161/CIRCINTERVENTIONS.114.001607Circulation: Cardiovascular Interventions. 2014;7:400–409IntroductionMitral regurgitation (MR) is one of the most prevalent valvular heart diseases in Western countries. The current estimated prevalence of moderate and severe MR in the United States is 2 to 2.5 million, and it is expected that this number will rise to 5 million by 2030.1 Surgical intervention is recommended for symptomatic severe MR or asymptomatic severe MR with left ventricular (LV) dysfunction.2 Treatment of degenerative MR has evolved from mitral valve (MV) replacement to MV repair because of superior long-term outcomes after repair.2–4 For functional MR, however, the benefit over MV replacement is less certain.5 In addition, minimally invasive MV surgery has become a well-established and increasingly used option for managing patients with MV pathology.6Although surgery remains the gold standard treatment for significant MR, MV surgery is deferred in a large number of patients because of high surgical risk.7 The decrease in the prevalence of rheumatic valve disease, in combination with an increased life expectancy, has led to a high prevalence of degenerative MR. As a consequence, patients are older and present with comorbidities that increase operative mortality and morbidity risks.8 In octogenarians, there has been reported a mortality and morbidity rate of 17.0% and 35.5%, respectively, following MV surgery.9 This results in denial or nonreferral for surgery in a large group of patients with significant MR—the Euro Heart Survey revealed that up to 50% of patients hospitalized with symptomatic severe MR are not referred for MV surgery, mainly because of advanced age, comorbidities, and LV dysfunction. In patients aged ≥80 years, surgical treatment was performed in only 15% compared to 60% in patients aged ≤70 years.8,10The observation that a significant number of patients are not referred for MV surgery and the desire for less invasive approaches have led to the development of different percutaneous approaches aiming at treating MR.Transcatheter MV RepairDuring the past few years, several percutaneous transcatheter MV repair (TMVRe) technologies have emerged as possible alternatives to open surgery for high-risk patients, and these technologies are currently at different stages of investigation and clinical implementation. A classification of percutaneous TMVRe technologies on the basis of anatomic targets is proposed and groups the devices into those targeting the following: (1) leaflets: percutaneous leaflet plication (edge-to-edge MV repair), leaflet coaptation, leaflet ablation; (2) annulus: indirect annuloplasty through the coronary sinus or direct annuloplasty (true percutaneous or by hybrid approach); (3) chordae: percutaneous chordal implantation; or (4) LV: percutaneous LV remodeling.11The device with the largest clinical experience is the MitraClip system (Abbott Laboratories, IL) using the edge-to-edge clip technique for percutaneous MV repair. The EVEREST (Endovascular Valve Edge-to-Edge Repair Study) II study is the only randomized controlled trial with published data comparing MitraClip therapy with conventional surgery in degenerative MR. One-year results showed that percutaneous MV edge-to-edge repair was less effective than surgery in reducing MR but that it was associated with superior safety and similar improvements in clinical outcome.12 At 4-year follow-up, patients treated with the MitraClip system were reported to require more frequently MV surgery to treat residual MR compared with the surgical group, although no differences were observed after 1-year follow-up. In addition, there were no differences in the prevalence of (moderate)-severe MR or mortality at 4-year follow-up.13 As a result, the MitraClip system obtained approval from the US Food and Drug Administration in 2013 for patients with significant symptomatic degenerative MR who are at prohibitive risk for MV surgery. Trials studying the role of the MitraClip system in patients with symptomatic functional MR are still ongoing.The other percutaneous TMVRe technologies using the concepts of annuloplasty, chordal implantation, and LV remodeling are still under development, and although safety rates have generally been equal or superior to conventional surgery, efficacy has been suboptimal.11,14 In the future, multiple percutaneous repair techniques may be used in combination to increase overall efficacy.11 However, for many patients MV repair will not be possible, and MV replacement will be required. Further limitations of TMVRe are unequal tension on left atrium or mitral annulus (coronary sinus at a distance from annulus) when using coronary sinus reshaping devices, as well as the possibility of iatrogenic mitral stenosis.11Transcatheter MV ReplacementTranscatheter valve replacement for the treatment of diseased heart valves in selected patients is of increasing importance, with promising results after transcatheter aortic valve replacement.15–17 The performance of transcatheter aortic valve replacement has rapidly increased in the past few years—the number of procedures in Europe more than tripled in recent years, from 4500 in 2009 to >18 000 in 2011 (>50% of these were performed in ocotgenarians).18 In accordance, transcatheter MV replacement (TMVR) may have the potential to become an alternative to treat severe MR in patients who are at high surgical risk because of its theoretical possibility to reduce MR to a similar extent as surgery while reducing procedural risks. Furthermore, TMVR could offer a wider applicability across patient and disease variations compared with TMVRe and can be made into a rather simple and fast procedure.The feasibility of this approach has been reported for TMVR with the SAPIEN XT valve (Edwards, CA) and Melody valve (Medtronic, MN) in dysfunctional mitral bioprostheses and annuloplasty rings. These percutaneous valve-in-valve and valve-in-ring implantations of transcatheter heart valves have shown excellent hemodynamic performance with low transvalvular gradient and perivalvular regurgitation.19–24 In February 2014, Edwards received CE Mark approval for transcatheter mitral valve-in-valve procedures using the SAPIEN XT valve. Furthermore, 3 recent case reports described successful TMVR using balloon-expandable transcatheter heart valves in patients with a severely calcified native MV stenosis, indicating that MV disease with a calcified annulus may be treated with TMVR in selected high-risk patients.25–27The data showing that MV disease is undertreated worldwide coupled with the large number of patients not eligible for TMVRe has driven the field of percutaneous TMVR. However, many challenges need to be addressed in the design of a device that targets the most complex of the heart's 4 valves.28,29 These challenges for TMVR devices are discussed more extensively in Table 1. Ideally, TMV implants should restore unidirectional flow while minimizing the risks associated with the procedure, allowing high-risk and inoperable patients to receive definitive treatment.Table 1. Challenges for Percutaneous TMVR DevicesValve position To be deployed in the left AV position, making a truly percutaneous, transfemoral delivery a challenge—because of the requirement for transseptal (or transaortic retrograde) access to the LA or LV and the need for a multidimensional, highly curved catheter course (which is challenging with a large delivery system and limits the precision with which tension and traction are transmitted to the operating end of the system) Possible access routes: transapical, transseptal, transatrialValve anatomy Should fit an asymmetrical saddle-shaped mitral annulus There is no stable calcified structure for anchoring (unlike for TAVR) in most cases* The mitral valve is a complex structure composed of leaflets, annulus, chordae tendineae, and papillary muscles—preservation of the subvalvular apparatus is mandatory to preserve LV geometry There is an irregular geometry of the mitral valve leafletsDynamic environment There are dynamic changes in mitral annular geometry (shape/size) during the cardiac cycle, resulting in an overall reduction of annular area up to 30% and a reduction of annular circumference of up to 15%30 The device should be resistant to displacement or migration while enduring continuous cyclic movements of the annulus and LV base, as well as high transvalvular gradients (high dislodgment forces)Device requirements The device should have a balanced radial stiffness to resist the dynamic environment and avoid frame fracture, whereas at the same time its stiffness should not cause perforation of adjacent structures. Valve materials must be durable enough to withstand the loads generated The device should not obstruct the left ventricular outflow tract, occlude the circumflex coronary artery, compress the coronary sinus, or cause major conduction system disruption Because of the large annular size, there is a need for large delivery systemsHemodynamic performance Paravalvular leak (PVL) should be minimized because regurgitation is poorly tolerated in the mitral position as a result of the higher pressure gradient across the valve. Moreover, PVL may result in hemolysis. The TMVR should restore unidirectional flow while minimizing the risks associated with the procedureOther issues Thrombogenicity of a bulky device implanted in the left AV position Possibility of reoperation or TMVR-in-TMVR is still unclearAV indicates atrioventricular; LA, left atrium; LV, left ventricle; TAVR, transcatheter aortic valve replacement; and TMVR, transcatheter mitral valve replacement.*In some patients with mitral valve stenosis, it is possible to anchor the device in the severely calcified mitral annulus.25–27This review aims to give an overview of the different percutaneous TMVR technologies currently under development. We report a list that is complete to the best of our knowledge. All manufacturers were asked to provide information on valve design and (pre)clinical results—this information was integrated with data available in peer-reviewed journals as well as with information provided by the coauthors that was not published before. Many of the device specifications and image material are published here for the first time; still some information could not be provided because of confidentiality reasons.CardiAQ ValveDeviceThe CardiAQ valve (CardiAQ Valve Technologies, CA) consists of a self-expanding nitinol frame, which carries 3 leaflets of bovine pericardial tissue. The device is designed in such a way that it does not use radial force for fixation to the annulus. Two sets of anchors grasping the mitral leaflets from the left atrial and LV side are used for fixation of the valve prosthesis. In addition, foreshortening of the frame creates a clamping action that anchors the valve above and below the annulus. The chordae and papillary apparatus should normally be preserved (Figure 1A). The different steps of valve deployment should be well controllable, and the fact that the valve is designed to be repositionable before final deployment should help ensure accurate placement (Figure 1B–1F). The device can be inserted truly percutaneously through the femoral vein using a transseptal access to the left atrium (antegrade). Alternative access is a transapical approach (retrograde).Download figureDownload PowerPointFigure 1. CardiAQ valve. A, The valve consists of a self-expanding nitinol frame that carries 3 leaflets of bovine pericardial tissue. Implantation sequence of CardiAQ valve: (B) coaxial alignment, (C) opening of the ventricular anchors, (D) opening of the atrial anchors, and (E) final release of the CardiAQ valve before removal of the delivery system. F, Left ventriculogram showing good position of the transcatheter mitral valve prosthesis and absence of significant mitral regurgitation. A, Image was provided by and is the property of CardiAQ Valve Technologies, Inc. Printed with permission. B–F, Images courtesy of Dr Søndergaard. Printed with permission.Preclinical DevelopmentPreclinical assessment of safety and feasibility of the CardiAQ valve has been successful. Animal experiments were conducted in 20 swine. A correct implantation position was obtained in 14 of 19 animals, whereas an infra- and supra-annular implant was observed in 4 and 1 animal(s), respectively. One animal was lost before initiating the procedure. None of the valves migrated or embolized after implantation. Successful implantation resulted in an excellent TMV function and stable hemodynamics, with no LV outflow tract (LVOT) obstruction, coronary artery obstruction, or transvalvular gradient (unpublished data, presented at TCT 2012 by L. Søndergaard).First-In-HumanA milestone was achieved on June 12, 2012, when the first-in-human TMVR was conducted at Rigshospitalet, Copenhagen, Denmark. The patient, a 86-year-old man experiencing symptomatic severe MR grade IV+, was declined for MV surgery and MitraClip treatment. With the use of an antegrade transseptal approach, a CardiAQ valve was successfully implanted, resulting in an accurate and stable position. The first 24 hours, the patient made an uneventful recovery and was hemodynamically stable. However, despite a well-functioning TMV prosthesis, the patient died 3 days postprocedure because of multiorgan failure (unpublished data, provided by L. Søndergaard).Tiara ValveDeviceThe Tiara valve (Neovasc Inc, British Columbia, Canada) is a self-expanding bioprosthesis with cross-linked bovine pericardial tissue leaflets mounted inside a metal alloy frame. The atrial portion is designed specifically to fit the saddle-shaped mitral annulus; the D shape should match the natural shape of the mitral orifice and prevent impingement of the LVOT. The ventricular portion of the device comprises a covered skirt to prevent paravalvular leakage (PVL), as well as 3 anchoring structures. The 2 anterior anchoring structures are designed to capture the fibrous trigones at both sides of the anterior MV leaflet, whereas the posterior anchoring structure projects behind the posterior MV leaflet, thus creating a 3-point anchor on the ventricular side that works in conjunction with the atrial flange to secure the prosthetic valve within the mitral annulus. This securement should prevent retrograde dislodgment during systole (Figure 2).28,31 In all stages, until the final step of ventricular deployment, the Tiara valve should be fully retrievable and repositionable. Implantation is performed transapically by means of a 32F delivery catheter and should not require rapid pacing (Figure 2).Download figureDownload PowerPointFigure 2. Tiara valve. A, The D-shape of the valve, the atrial skirt that engages the atrial aspect of the mitral annulus, and the saddle-shaped valve are clearly seen. B, Transapical 32F delivery system. Implantation sequence of Tiara valve: (C) the coronary sinus wire outlines the mitral annulus; the pigtail catheter is anteriorly in the ascending aorta, and the delivery system is through the mitral annulus into the left atrium; (D) opening of the atrial skirt in the left atrium and the flat aspect of the D-shaped Tiara are facing anteriorly; (E) the atrial skirt is open and positioned on the atrial aspect of the mitral annulus, and the ventricular portion of the Tiara valve is delivered into position just before final release; (F) final release of the Tiara valve, before removal of the delivery system. Reprinted from Banai et al28 with permission of the publisher. Copyright ©2014, American College of Cardiology Foundation.Preclinical DevelopmentPreclinical assessment of safety and feasibility of the Tiara valve has been successful.28 This included both acute and chronic animal models, as well as human cadavers. In the acute animal model, Tiara valves were successfully implanted in 29 of 36 (81%) swine. Implantation was unsuccessful in 7 animals because of improper positioning of the valve (n=3), failure of the valve anchors (n=2), and ventricular fibrillation (n=2). None of the valves migrated or embolized after implantation. There was a steady increase in the rate of successful implantation as the series progressed, with the final 12 animals all undergoing successful and uneventful implantation. Both acute and chronic evaluation demonstrated excellent valve function and alignment, with no LVOT obstruction, coronary artery obstruction, or transvalvular gradient. Chronic evaluation of 7 sheep demonstrated clinically stable animals throughout a follow-up of 150 days. The investigators attribute a relatively high rate of PVL observed in the chronic animal model to the fact that only one size of the Tiara valve was available, making size mismatch between the native annulus and prosthetic device unavoidable in many hearts. In situ cardioscopy showed homogeneous coverage of the metal struts with a tissue both the atrial and ventricular and evaluation demonstrated that devices well and all valve showed good by a the atrial and ventricular with fibrous tissue for The pericardial leaflets were or The human model demonstrated that implantation resulted in positioning with coverage of the atrial aspect of the mitral annulus and good and of the ventricular anchoring first 2 of human Tiara valve implantation were performed in and February at British Columbia, Both patients severe functional MR, LV and were high-risk for conventional MV surgery. The transapical procedures resulted in of MR and LV the need for cardiac device and with no procedural (unpublished data, provided by The was ValveDeviceThe valve Inc, MN) is a pericardial valve a nitinol frame (Figure Because the valve is a of the Lutter valve, the valve several design with the Lutter valve: (1) an atrial fixation (2) a ventricular made of a nitinol self-expanding frame that a heart valve, and (3) a ventricular fixation system composed of to the The valve is designed to be fully and deployment and accurate of its position should be to the risk of The prosthetic valve is delivered transapically and is a the LV using a that on the figureDownload PowerPointFigure valve. A, The valve consists of a self-expanding metal alloy frame made of an a pericardial valve and an that the native mitral annular The device is in using a that through the left to an Implantation (B) access of left atrium with and (C) of valve within valve in left atrium; traction is used to position the valve in native annulus; (D) the the valve to be for or replacement with alternative valve size, and left ventriculogram showing of severe mitral regurgitation in human These were provided by and are the property of Inc. Printed with permission.Preclinical Lutter valve has been successfully implanted in several acute and chronic models, with follow-up of up to 2 first mitral implantation with follow-up of and 7 days. positioning was in all but 5 There were no issues of device or LVOT These the feasibility of deployment of the Lutter valve, prosthesis and valve function in acute and However, and were 2 of the throughout this a more recent valve deployment and function were obtained in all but 1 animal with a of the Lutter valve regurgitation after valve deployment in 1 animal just after 1 and in The gradients across the valve and LVOT were All animals hemodynamics, and was during follow-up. and PVL were not in the animals after 4 and evaluation revealed that 50% to of the atrial was covered by tissue at 4 to study on the evaluation of 2 different frame (1) the first design of a atrial to a ventricular and (2) in the this atrial was D-shaped to anatomic in showed less PVL in the in D-shaped design animal showed less with of all with D-shaped more severe PVL and these to more are to this first 2 of human valve implantation were performed in patients to surgical MV replacement at the The transapical resulted in of MR grade in one patient and reduction of MR grade to grade in the other patient (unpublished data, provided by The was TMV is a pericardial valve, for the mitral position. The valve a large atrial portion that is for and a outflow ventricular portion to avoid LVOT has that function to capture the anterior MV MV leaflet and the The device is designed in such way that it should not on radial for it the mitral apparatus for fixation (Figure The valve is designed to be fully retrievable and it should be possible to and the valve a catheter in case a is The current device is delivered similar to a minimally invasive MV with transseptal delivery under figureDownload PowerPointFigure transcatheter mitral valve. A, The valve is a pericardial has that function to capture the anterior and posterior mitral valve leaflet and the B, The of fixation using the mitral apparatus to secure the device in position. animal results showing good positioning with no or paravalvular of the apparatus and no left ventricular outflow tract Images courtesy of Dr Printed with permission.Preclinical acute animal TMV has been successfully implanted, resulting in accurate and stable valve were performed using a combination of and