Author + information
- Received March 14, 2016
- Accepted April 18, 2016
- Published online July 11, 2016.
- Mayra Guerrero, MDa,∗ (, )
- Danny Dvir, MDb,
- Dominique Himbert, MDc,
- Marina Urena, MDc,
- Mackram Eleid, MDd,
- Dee Dee Wang, MDe,
- Adam Greenbaum, MDe,
- Vaikom S. Mahadevan, MBBS, MDf,
- David Holzhey, MD, PhDg,
- Daniel O’Hair, MDh,
- Nicolas Dumonteil, MDi,
- Josep Rodés-Cabau, MDj,
- Nicolo Piazza, MDk,
- Jose H. Palma, MD, PhDl,
- Augustin DeLago, MDm,
- Enrico Ferrari, MDn,
- Adam Witkowski, MD, PhDo,
- Olaf Wendler, MD, PhDp,
- Ran Kornowski, MDq,
- Pedro Martinez-Clark, MDr,
- Daniel Ciaburri, MDs,
- Richard Shemin, MDt,
- Sami Alnasser, MDu,
- David McAllister, DOv,
- Martin Bena, MDw,
- Faraz Kerendi, MDx,
- Gregory Pavlides, MDy,
- Jose J. Sobrinho, MDz,
- Guilherme F. Attizzani, MDaa,
- Isaac George, MDbb,
- George Nickenig, MDcc,
- Amir-Ali Fassa, MDdd,
- Alain Cribier, MDee,
- Vinnie Bapat, MDff,
- Ted Feldman, MDa,
- Charanjit Rihal, MDd,
- Alec Vahanian, MDc,
- John Webb, MDb and
- William O’Neill, MDe
- aDepartment of Medicine, Division of Cardiology, Evanston Hospital, Evanston, Illinois
- bCenter for Heart Valve Innovation, St. Paul's Hospital, Vancouver, British Columbia, Canada
- cCardiology Department, Bichat-Claude Bernard Hospital, Paris, France
- dDepartment of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
- eDepartment of Medicine, Division of Cardiology, Henry Ford Hospital, Detroit, Michigan
- fDepartment of Medicine, Division of Cardiology, University of California San Francisco, San Francisco, California
- gDepartment of Cardiac Surgery, Leipzig Heart Center, Leipzig, Germany
- hDepartment of Surgery, Aurora St. Luke's Medical Center, Milwaukee, Wisconsin
- iDepartment of Cardiology, Rangueil University Hospital, Toulouse, France
- jQuebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada
- kDepartment of Interventional Cardiology, McGill University Health Centre, Montreal, Quebec, Canada
- lDepartment of Cardiovascular Surgery, Escola Paulista de Medicina, São Paolo, Brazil
- mDepartment of Medicine, Division of Cardiology, Albany Medical Center Hospital, Albany, New York
- nCardiac Surgery Unit, Cardiocentro Ticino Foundation, Lugano, Switzerland
- oDepartment of Interventional Cardiology & Angiology, Institute of Cardiology, Warsaw, Poland
- pDepartment of Surgery, King's College Hospital, London, United Kingdom
- qDepartment of Medicine, Division of Cardiology, Rabin Medical Center, Petah Tikva, Israel
- rDepartment of Medicine, Division of Cardiology, Angiografía de Occidente, Cali, Colombia
- sDepartment of Surgery, Saint Francis Medical Center, Peoria, Illinois
- tDepartment of Surgery, UCLA Medical Center, Los Angeles, California
- uDepartment of Medicine, Division of Cardiology, St. Michael’s Hospital, Toronto, Canada
- vDepartment of Medicine, Division of Cardiology, The Iowa Heart Center, Des Moines, Iowa
- wDepartment of Cardiac Surgery, National Institute of Cardiovascular Diseases, Bratislava, Slovakia
- xDepartment of Surgery, Heart Hospital of Austin, Austin, Texas
- yDepartment of Medicine, Division of Cardiology, The Nebraska Medical Center, Omaha, Nebraska
- zDepartment of Surgery, Complexo Hospitalar de Niteroi, Niteroi, Brasil
- aaThe Valve and Structural Heart Interventional Center, University Hospitals Case Medical Center, Cleveland, Ohio
- bbColumbia Heart Valve Center, New York Presbyterian Hospital-Columbia University Medical Center, New York, New York
- ccHeart Center, University of Bonn, Bonn, Germany
- ddDepartment of Medicine, Division of Cardiology, Hôpital de La Tour, Geneva, Switzerland
- eeDepartment of Cardiology, University of Rouen’s Charles Nicolle Hospital, Rouen, France
- ffDepartment of Cardiology and Cardiac Surgery, St. Thomas’ Hospital, London, United Kingdom
- ↵∗Reprint requests and correspondence:
Dr. Mayra Guerrero, Director of Cardiac Structural Interventions, Evanston Hospital/NorthShore University Health System, 2650 Ridge Avenue, Walgreen Building, 3rd Floor, Evanston, Illinois 60201.
Objectives This study sought to evaluate the outcomes of the early experience of transcatheter mitral valve replacement (TMVR) with balloon-expandable valves in patients with severe mitral annular calcification (MAC) and reports the first large series from a multicenter global registry.
Background The risk of surgical mitral valve replacement in patients with severe MAC is high. There are isolated reports of successful TMVR with balloon-expandable valves in this patient population.
Methods We performed a multicenter retrospective review of clinical outcomes of patients with severe MAC undergoing TMVR.
Results From September 2012 to July of 2015, 64 patients in 32 centers underwent TMVR with compassionate use of balloon-expandable valves. Mean age was 73 ± 13 years, 66% were female, and mean Society of Thoracic Surgeons score was 14.4 ± 9.5%. The mean mitral gradient was 11.45 ± 4.4 mm Hg and the mean mitral area was 1.18 ± 0.5 cm2. SAPIEN valves (Edwards Lifesciences, Irvine, California) were used in 7.8%, SAPIEN XT in 59.4%, SAPIEN 3 in 28.1%, and Inovare (Braile Biomedica, Brazil) in 4.7%. Access was transatrial in 15.6%, transapical in 43.8%, and transseptal in 40.6%. Technical success according to Mitral Valve Academic Research Consortium criteria was achieved in 46 (72%) patients, primarily limited by the need for a second valve in 11 (17.2%). Six (9.3%) had left ventricular tract obstruction with hemodynamic compromise. Mean mitral gradient post-procedure was 4 ± 2.2 mm Hg, paravalvular regurgitation was mild or absent in all. Thirty-day all-cause mortality was 29.7% (cardiovascular = 12.5% and noncardiac = 17.2%); 84% of the survivors with follow-up data available were in New York Heart Association functional class I or II at 30 days (n = 25).
Conclusions TMVR with balloon-expandable valves in patients with severe MAC is feasible but may be associated with significant adverse events. This strategy might be an alternative for selected high-risk patients with limited treatment options.
- calcific mitral stenosis
- mitral annular calcification
- mitral valve disease
- mitral valve replacement
- transcatheter valve replacement
Patients with mitral annular calcification (MAC) are an elderly high-risk patient population with multiple comorbidities even before they develop valvular dysfunction. They have higher risk of cardiovascular disease, cardiovascular death, and all-cause mortality (1–3). The risk of surgical mitral valve (MV) replacement in this population is high due to comorbidities and technical challenges related to calcium burden (4) precluding successful surgery in many. Rupture of the posterior wall of the left ventricle has been reported as a potential complication (5). There is currently an unmet clinical need for many who are not treated due to their high surgical risk. There have been isolated reports of successful transcatheter MV replacement (TMVR) with the compassionate use of balloon-expandable transcatheter aortic valves in this patient population (Edwards Lifesciences, Irvine, California). The first few procedures were performed utilizing a surgical transapical (6,7) or an open transatrial approach (8), but subsequent reports described successful implantation with a completely percutaneous transfemoral approach (9–11). Although these case reports are encouraging, the safety and efficacy of this procedure are unknown. We hypothesized that TMVR with balloon-expandable valves is a feasible alternative therapeutic option in selected patients with severe MAC who cannot have surgery. We established the TMVR in MAC Global Registry to collect outcomes data of similar procedures performed worldwide to better understand its safety and efficacy in a larger patient population.
The TMVR in MAC Global Registry was initiated in October of 2013. Centers around the world with experience of TMVR using balloon-expandable valves in patients with MAC were invited to participate (Online Appendix). Sixty-four patients from 32 centers in North America, Europe, and South America who underwent TMVR with compassionate use of balloon-expandable transcatheter heart valve (THV) between September of 2012 and July of 2015 were included. The study was approved by the Institutional Review Board of the NorthShore University HealthSystem Research Institute. The inclusion criteria were the presence of symptomatic severe mitral valvular disease with severe MAC in patients not eligible for standard MV surgery due to comorbidities or technical reasons related to calcium burden. A quantitative definition of severe MAC was not specified. However, most operators considered severe MAC the presence of diffuse almost circumferential heavy calcification of the MV ring as seen by cardiac computed tomography (CT) (Figure 1). Data were collected retrospectively for the procedures performed before the registry was initiated and prospectively thereafter in the majority of the patients, using a standardized case report form and included: 1) Baseline clinical characteristics, baseline echocardiographic characteristics, and CT-based MV annulus diameter and area measurements when available; 2) procedural characteristics including type and size of THV implanted, valve delivery approach, and technical success; early post-implantation echocardiographic evaluation including ejection fraction, mean MV gradient (MVG), MV area (MVA), and left ventricular outflow tract (LVOT) gradient; and 3) procedural complications and major adverse events were collected at discharge, 30 days, and 1 year, and New York Heart Association (NYHA) functional class at 30 days and 1 year. The follow-up data were reported according to the lapse of time between the index procedure and data lock for this analysis (September 2, 2015).
Technical success (measured at exit from the cardiac catheterization/operating room) was defined according to the Mitral Valve Academic Research Consortium (MVARC) criteria (12) as a procedure meeting all of the following: absence of procedural mortality; successful access, delivery, and retrieval of the device delivery system; and successful deployment and correct positioning of the first intended device; and freedom from emergent surgery or reintervention related to the device or access. Periprocedural death was defined as death occurring within 30 days on the intervention or beyond 30 days for patients not yet discharged. All clinical endpoints were also defined according to MVARC criteria.
Continuous variables were summarized as mean ± SD or median (range). Categorical variables were summarized as frequency and percentage. Repeated measures analysis of variance was used to compare clinical parameters among different time points. Mean difference, standard error, and adjusted p values were reported. Percentages were on the basis of all known values if the missing items were <5%. Missing data items resulted in reduced denominators for many variables. If 5% or more of the values are missing for a particular variable, the number of known values was indicated and included in the denominator. Statistical analysis was performed using SAS 9.3 platform (SAS Institute, Cary, North Carolina). A p value <0.05 was considered statistically significant.
Baseline patient characteristics are listed in Table 1. Mean age was 73 ± 13 years (range 39 to 96 years), and 66% were female. Multiple comorbidities were present. Thirty-four of 62 (54.8%) patients had a prior aortic valve replacement of which 9 (26.5%) were THV, 8 were Edwards, 1 was CoreValve (Medtronic, Minneapolis, Minnesota), and 25 (73.5%) were surgical aortic valves (10 mechanical and 15 bioprosthetic). The mean Society of Thoracic Surgeons score was 14.4 ± 9.5 (range 1 to 41.5). The reason for inoperability was deemed to be technical in 18.5%, due to comorbidities in 25.5% and both in 55%. Left ventricular ejection fraction was preserved in most patients (59.5 ± 11.3%). The primary MV pathology was stenosis in 93.5% and 6.5% had primarily mitral regurgitation (MR). The mean MVG in patients with stenosis was 11.4 ± 4.4 mm Hg and the mean MVA was 1.18 ± 0.51 cm2. The mean pre-existing LVOT gradient was 6.4 ± 18.2 mm Hg (range 0 to 60 mm Hg). Most patients were in NYHA functional class III or IV (91.9%).
The procedural results are summarized in Table 2. The transatrial delivery under direct visualization through an open surgical approach was utilized in a minority of cases (10 of 64 [15.6%]). Two to 3 sutures were used to help secure the stent frame to the annulus, and in some cases the anterior mitral leaflet was resected to reduce risk of LVOT obstruction. In 1 case, the annulus was too large (area 703 mm2), for which a 32 mm Physio ring (Edwards Lifesciences) was sutured to provide a landing zone prior to deployment of a 29 mm SAPIEN XT (Edwards Lifesciences) valve. Transapical and transseptal approaches were used in most cases, 28 of 64 (43.8%) and 26 of 64 (40.6%), respectively. In 4 of the 26 transseptal procedures (15.4%), a modified technique was used externalizing the guidewire through a sheath percutaneously placed into the left ventricular apex (Figure 2). This was done with the intention of providing coaxiality and support during THV deployment in cases where the extreme valve leaflet calcification was thought could prevent coaxial position. To decrease the risk of embolization, most operators made efforts to deploy the valve in a conical shape and flare it in the left ventricle (Figure 3).
Technical success according to MVARC criteria was achieved in 46 of 64 patients (72%), primarily limited by the need for a second THV in 11 (17.2%) due to migration in 5 and regurgitation in 6. After a second valve, a stable position was achieved in 57 (89%) patients. At the end of the procedure, the mean MV gradient was 4 ± 2.2 mm Hg, while the MV orifice area was 2.2 ± 0.95 cm2. In the 6 patients who required a second valve due to MR, the mechanism was malposition in 5 patients, either too atrial or too ventricular, preventing adequate seal by the stent frame skirt, and the sixth case (1.5%) was thought to have a malfunctioning leaflet causing severe central MR 3 h after the implant requiring reintervention with a valve in valve. By the end of the procedure, paravalvular regurgitation was mild or absent in all. There were 4 valve embolizations to the left atrium (6.25%), all of them during the index procedure. Three were treated with surgical extraction and 1 was stabilized/trapped in the intra-atrial septum percutaneously with a 30 mm Amplatzer Septal Occluder device (St. Jude Medical, St. Paul, Minnesota) in a patient who was not a candidate for surgical rescue.
Six patients (9.3%) had LVOT obstruction with hemodynamic compromise after valve deployment. The average peak LVOT gradient in these patients was 72 mm Hg (range 39 to 100 mm Hg). One died while on the catheterization laboratory table, 1 was stabilized medically but died of pneumonia 9 days later, 1 was converted to open surgery for valve retrieval and died hours later, 1 was treated with simultaneous kissing aortic and MV balloon valvuloplasty with significant improvement in LVOT gradient but died 48 h later due to multiorgan failure, and 1 was treated with emergent percutaneous alcohol septal ablation with resolution of the gradient and hemodynamic recovery although the patient died 4 days later of complete heart block secondary to alcohol septal ablation. Subsequently, 1 patient was treated successfully with emergent alcohol septal ablation, improved clinically, and was discharged home in stable condition (Figure 4).
There were no cases of annular rupture or perforation reported. The mean length of stay was 17.7 ± 18 days. Most patients (68.2%) in whom discharge medication information was available were discharged on anticoagulation with warfarin plus single or dual antiplatelet drug.
Clinical outcomes are shown in Table 3. The mean follow-up was 4 months (range 1 to 34 months). Periprocedural death occurred in 29.7% (19 of 64). A cardiovascular cause was identified in 12.5% (8 of 64) and noncardiac in 17.2% (11 of 64). Of the 8 cardiovascular deaths, 2 were due to LVOT obstruction, 2 were secondary to left ventricular perforation, 2 were related to ischemic stroke, 1 was due to complete atrioventricular block, and 1 was due to acute myocardial infarction secondary to massive air embolism in the setting of guidewire-induced pulmonary vein perforation during a transapical procedure. Of the 11 noncardiac deaths, 5 were attributed to multiorgan failure, 3 were secondary to pneumonia, 2 were due to infection, and 1 was due to bleeding.
Thirty-day follow-up echocardiographic data were available in 22 patients at the time of present analysis. Mean MVG was 5.9 ± 2.1 mm Hg (p < 0.0001) with a MVA of 2.3 ± 0.8 cm2 (p < 0.0001). Eighteen patients (81.8%) had zero to trace MR and 4 (18.2%) had mild MR; moderate to severe MR was absent in all (p < 0.0001). The average peak LVOT gradient was 15 ± 17.8 mm Hg (p = 0.13).
Most survivors reported significant improvement of symptoms. At 30 days, 21 of the 25 patients (84%) with 30-day clinical follow-up data were in NYHA functional class I or II, and 4 (16%) in NYHA functional class III (p < 0.0001) (Figure 5).
Simultaneous TMVR and aortic valve replacement
Twelve patients (18.7%) underwent concomitant surgical (5 of 12) or transcatheter (7 of 12) aortic valve replacement at the index procedure. In the 5 patients who underwent surgical aortic valve replacement, the SAPIEN XT (3) and SAPIEN 3 (2) were implanted in the native MV via open transatrial approach. When transcatheter aortic valve replacement was performed, a transapical approach with Edwards valves was selected for all. Thirty-day mortality or complication rate was similar in this small subcohort; 2 of the 12 patients died within 30 days (25%), 1 treated with surgical aortic valve replacement (1 of 3 [30%]) and 1 with transcatheter aortic valve replacement (1 of 5 [20%]).
Complication rate by access type
The complication rate and 30-day mortality were similar among delivery approaches. However, the highest technical success of 88.9% was achieved with the surgical transatrial approach but the sample size is small with only 10 patients in this group. Technical success with the transapical approach was 71.4% and 65.4% with transseptal approach. Thirty-day mortality was 20% with transatrial approach, 32.1% with transapical and 30.7% with antegrade transseptal approach. Valve embolization was seen in 2 transapical cases, 1 transseptal and 1 transatrial. LVOT obstruction was observed in 3 transapical and 3 transseptal cases. A second valve was needed in 11 cases (5 transapical, 5 transseptal, and 1 transatrial). There was 1 pulmonary vein perforation in a transapical case and 2 left ventricular perforations in the transseptal cases. Conversion to open heart surgery was needed in 3 transapical cases and 1 transseptal procedure.
This study is the first large multicenter evaluation of TMVR with balloon-expandable valves in patients with severe native MV disease due to severe MAC who were considered poor candidates for traditional surgical MV replacement. We found that TMVR with balloon-expandable valves designed for aortic position is feasible in this extremely high-risk patient population. Technical success was achieved in most patients. Although there were important complications and a high 30-day mortality, these results are encouraging considering this represents the first human experience with a THV not designed for the mitral position and used in an extremely high-risk patient population with a mean Society of Thoracic Surgeons risk score higher than in the PARTNER I (Placement of AoRtic TraNscathetER Valves) trial (13).
The results we report are similar to the complications and mortality reported in the initial experience with transcatheter valves designed for the MV to treat patients with MR. In the early experience with the CardiAQ valve (CardiAQ Valve Technologies, Inc., Edwards Lifesciences), the FORTIS valve (Edwards Lifesciences) and Tiara valve (Neovasc Inc., Richmond, British Columbia, Canada), there were complications and several patients died after a seemingly successful procedure (14–18). This might have been related to patient selection as some had severe left ventricular dysfunction and died of progression of heart failure. It is encouraging that technical success was achieved in the majority of patients despite the multiple challenges of the MV anatomy including its saddle oval shape, a subvalvular apparatus, interaction with the LVOT and aortic valve, and a large size requiring a larger prosthesis, as well as considering that the balloon-expandable technology was not designed for the MV and has no anchoring mechanism. It is possible that newer repositionable and retrievable valve designs might be more beneficial in this patient population. The use of the Lotus valve (Boston Scientific, Marlborough, Massachusetts) and Direct Flow (Direct Flow Medical Inc. Santa Rosa, California) has been reported with success in patients with severe MAC (19,20). The option of repositioning or retrieving the valve in the setting of TMVR-induced LVOT obstruction is an important advantage over the balloon-expandable valve technology. One disadvantage is that both technologies have the transapical route as the only delivery option at this time.
The learning curve
The learning curve for TMVR in patients with severe MAC has been very steep. There were many unknowns and uncertainties during the initial experience of this registry including the best method for mitral annulus sizing, the amount of calcium needed for valve anchoring, the percent of prosthesis frame oversizing needed for a stable valve position, and the depth of valve implantation in relation to the annular plane (how much ventricular and how much atrial). Additional questions included: Can the round-shaped balloon-expandable valve provide adequate seal when implanted in an oval-shaped valve? Or will it leave a large uncovered space resulting in significant paravalvular leak? Can embolization be predicted or prevented? How to prevent and treat significant LVOT obstruction post-deployment? What is the optimal valve delivery method? Which patients are the best candidates for this technology? This registry provided some answers.
Mitral annulus sizing and the role of imaging
In the absence of a validated standard method for mitral annulus sizing, operators have extrapolated from TAVR experience and used a variety of sizing approaches including echocardiography, 3D transesophageal echocardiography, cardiac CT, and balloon sizing techniques. Only few patients treated in the early experience were not evaluated with cardiac CT. However, this imaging modality rapidly became the most accepted method for annulus sizing. It was soon recognized that CT may also provide essential information for pre-procedural planning. It helps evaluate the amount and distribution of calcium in an attempt to predict valve anchoring and features that may assist in predicting LVOT obstruction including the aortomitral angle, the anterior leaflet length, the size of the left ventricular cavity, the presence of septal hypertrophy, and the change in the residual LVOT space in relation with the depth of valve implantation. It can also be helpful in planning the site and trajectory of transapical or transseptal access (Figure 1).
Most of the procedural deaths were noncardiac. The registry’s patient population had an extremely high-risk profile and some were perhaps treated too late in their disease process, similar to the so-called “cohort C” patients in the transcatheter aortic valve replacement experience. As the operators learned about annulus sizing, LVOT obstruction risk assessment, anchorage prediction assessment and better patient selection, there was a decreased rate of major cardiac complications and overall mortality.
This study has important limitations inherent to registries. The total number of patients analyzed is small and most centers included only 1 or 2 patients. Because this is real-world practice experience, the patient population is not homogeneous. Most of the data were collected retrospectively, and not all data were captured or reported in all centers, resulting in significant amount of missing data. The clinical outcomes were self-reported. Because the clinical events were not adjudicated, it is possible that the adverse events were underestimated. In addition, there were no core laboratories utilized. This is a new procedure and most patients were treated fairly recently. Therefore, 1-year or longer follow-up was available in a small number of patients and durability and long-term outcomes are yet unknown.
Need for a clinical trial
A prospective clinical trial may help overcome the important limitations of this registry. The MITRAL (Mitral Implantation of TRAnscatheter vaLves) trial (NCT02370511) is an Food and Drug Administration–approved physician-sponsored pilot Investigational Device Exemption trial that is currently ongoing in the United States to systematically evaluate the safety and feasibility of this technology in severe native MV disease with severe MAC. We anticipate that the MITRAL trial will help provide insights to further improve technical success, patient selection, and the overall clinical outcomes of this patient population.
This first multicenter registry report of TMVR with balloon-expandable valves in patients with severe MAC demonstrates that the procedure is feasible but may be associated with significant adverse events. This strategy might be an alternative for selected high-risk or inoperable patients with limited treatment options, but remains off-label at this time. Further studies are needed to refine the screening process to improve outcomes of this challenging procedure.
WHAT IS KNOWN? Patients with severe MAC have very high surgical risk for standard MV surgery. There is currently an unmet clinical need for many patients who are not treated due to their high surgical risk. There is limited data from few isolated reports of successful TMVR with balloon-expandable aortic THVs in patients with MAC who are not candidates for standard surgery.
WHAT IS NEW? This is the largest multicenter report to date of patients with severe MAC undergoing TMVR. We found that TMVR is feasible in patients with severe MAC who are not candidates for standard MV surgery but is associated with significant adverse events.
WHAT IS NEXT? Further studies are needed to refine the screening process to improve outcomes. The MITRAL trial is prospectively evaluating the safety and feasibility of this procedure and may provide further insights to improve the technical success, patient selection, and overall clinical outcomes.
The authors wish to thank Ying Zhou for the statistical analysis support provided in the preparation of this manuscript.
For an expanded Methods section, please see the online version of this article.
Dr. Guerrero has served as a proctor and consultant for and received research grant support from Edwards Lifesciences. Dr. Dvir has served as a consultant to Edwards Lifesciences. Dr. Himbert has served as a proctor for Edwards Lifesciences and Medtronic; and a consultant for Edwards Lifesciences. Dr. Greenbaum has served as a proctor for Edwards Lifesciences. Dr. Mahadevan has served as a proctor for Edwards Lifesciences. Dr. Holzhey has served as a proctor for Symetis; and on the advisory board for Edwards Lifesciences and Medtronic. Dr. O'Hair is a consultant to Medtronic. Dr. Dumonteil has served as a proctor for Edwards Lifesciences, Medtronic, and Boston Scientific; and consultant to Biotronik. Dr. Rodes-Cabau has served as a consultant to St. Jude Medical. Dr. Piazza has served as a consultant to Medtronic and HighLife; and received research grant support from Medtronic. Dr. Ferrari has served as a proctor and consultant for Edwards Lifesciences. Dr. Witkowski has received speakers fees from Edwards Lifesciences. Dr. Wendler has served as a consultant to Edwards Lifesciences, St. Jude Medical, and JenaValve; on the Speakers Bureau for Edwards Lifesciences; and as a proctor for the Edwards Lifesciences THV Program. Dr. Shemin has served as a consultant for Edwards Lifesciences and Sorin. Dr. McAllister has served as a proctor for Medtronic. Dr. Attizzani has served as a proctor for Edwards Lifesciences and Medtronic; on the Speakers Bureau for Medtronic and Abbott Vascular; and as a consultant to St. Jude Medical. Dr. George is a consultant to Edwards Lifesciences and Medtronic. Dr. Cribier has served as a consultant to Edwards Lifesciences. Dr. Bapat has served as a consultant to Edwards Lifesciences, Medtronic, Sorin, Boston Scientific, and Sorin; and as a proctor for Edwards Lifesciences. Dr. Feldman has served as a consultant and received research grant support from Abbott, Boston Scientific, and Edwards Lifesciences. Dr. Vahanian has served as a consultant to Edwards Lifesciences, Medtronic, and Abbott Vascular; and has received research grant support from Valtech. Dr. Webb has served as a consultant to Edwards Lifesciences. Dr. O’Neill has served as a proctor and consultant for Edwards Lifesciences; has served as a consultant for St. Jude Medical and Medtronic; and is the director of Neovasc Inc. All other authors report that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- computed tomography
- left ventricular outflow tract
- mitral annular calcification
- mitral regurgitation
- mitral valve
- mitral valve area
- Mitral Valve Academic Research Consortium
- mitral valve gradient
- New York Heart Association
- transcatheter heart valve
- transcatheter mitral valve replacement
- Received March 14, 2016.
- Accepted April 18, 2016.
- American College of Cardiology Foundation
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