TY - JOUR
AU - Speziale,, Giuseppe
AB - Abstract Mitral regurgitation (MR) is the second most common valvular heart disease after aortic valve stenosis. With increased understanding of the heterogenic pathophysiology of MR, cardiac surgeons have developed various techniques that increase the likelihood of successful mitral valve repair (MVR). Nowadays, a rate of repair >90% may be reached in some mitral valve reference centres. In recent years, the introduction of transcatheter mitral valve intervention techniques has opened up new frontiers in mitral therapy, specifically in patients at high risk for standard surgery. Current percutaneous technologies for MVR have been developed on the basis of some of the surgical principles. Based on current evidence, surgery remains the standard treatment for MR according to very long-term survival and durability of MVR using Carpentier's technique. Today, in clinical practice, only the MitraClip device may be considered as a real and effective alternative in selected patients with high or prohibitive risk for surgery. Mitral valve repair, Transcatheter mitral valve therapy, New devices, Clinical outcomes, Long-term repair results Introduction Mitral regurgitation (MR) is the second most common valvular heart disease after aortic valve stenosis, being present in 24% of adults with valvular heart disease and in 7% of the elderly population ≥75 years of age. The mitral valve apparatus is a complex structure that incorporates the leaflets, chordae tendineae, papillary muscles, annulus, and left ventricle (LV) in its function. As a result, diseases that affect any of these structures can result in severe MR. More than 30 years ago, Carpentier described the mitral valve as a complex functional structure. He also developed a functional classification to reflect the underlying dysfunction contributing to MR.1 Although mitral valve repairs (MVRs) have been applied for several set lesions, degenerative (myxomatous) and functional disease (chronic ischaemic MR and dilated cardiomyopathy) are most frequently the motivation for valve repair. In myxomatous degeneration, the leaflets and chordae become thickened, elongated, and redundant, which results in leaflet prolapse beyond the plane of the annulus and MR. Secondary MR is caused by ventricular remodelling without primary valve leaflet pathology. This condition is secondary to ventricular dilatation and is typically seen in idiopathic-dilated cardiomyopathy and in post-infarction ventricular remodelling. Indications for surgical treatment are found in the ESC/EACTS and AHA/ACC guidelines.2,3 Treatment options With increased understanding of the heterogenic pathophysiology underlying MR, cardiac surgeons have developed various techniques that increase the likelihood of successful repair. The natural history of severe MR is now well known. Medically treated patients have a 10-year survival rate between 27 and 60%, which represents excess mortality compared with the expected survival rate. A historical comparison of prognoses in medically and surgically treated patients shows a trend in favour of surgical treatment especially for early surgery. Through preservation of the normal valvular tissue and the subvalvular apparatus, valve repair is preferable to valve replacement. Compared with prosthetic replacement, MVR has a lower surgical mortality rate and provides both better survival rates and better LV function. Therefore, valve repair is the gold standard for surgical correction of MR. For patients with non-rheumatic heart disease, valve repair is almost always possible with more than a 90% success rate in different centres. According to Carpentier and colleagues,4 MVR, using the French correction in patients with non-rheumatic MR, provides excellent long-term results with a mortality rate similar to that of the general population and a very low incidence of reoperation at 10 and 20 years, 94% (95% confidence interval [CI] 90–98) and 92% (95% CI 87–97), respectively. Thanks to advances in video-assisted general and thoracic surgery, minimally invasive cardiac surgery has successfully been performed. Recently, described techniques of less invasive mitral valve surgery include limited right thoracotomy, parasternal incision, and partial sternotomy. These methods have been coupled with video-assisted thoracoscopy to further decrease the skin incision length. From the Euro Heart Survey on Valvular Heart Disease database, it emerged that as many as 49% of patients with MR and in need of repair or replacement are considered at high risk for surgical intervention, and are therefore not amenable to surgery. Such patients are relegated to medical management, which alleviates symptoms but does not alter the progression of disease. In recent years, the introduction of transcatheter mitral valve intervention (TMVI) techniques has opened up new frontiers in MR therapy, eliminating the need for surgical intervention and extracorporeal circulation.5 Transcatheter mitral valve intervention techniques can correct MR by means of the direct or indirect reduction in mitral annular dilatation, or through intervention on the primary or secondary abnormalities of the mitral apparatus. The efficacy and feasibility of TMVI depends on patient selection, and on an accurate evaluation of the mechanism and severity of MR using integrated Doppler echocardiography. Various transcatheter techniques have been developed to treat MR with less invasive approaches to minimize surgical trauma. Currently, the device with the widest clinical use is the MitraClip system. Surgical therapies and results The goal of MVR procedure for degenerative disease follows two fundamental principles: to restore a good surface of leaflet coaptation and to reshape annuloplasty to correct annular dilatation.1 A leaflet coaptation line of 8 mm is considered essential to provide a durable long-term repair result. In terms of valve repair procedures, Carpentier's techniques remain the most commonly performed world wide, and are associated with excellent long-term outcomes. Posterior leaflet prolapse is treated by quadrangular or triangular resection. When excessive posterior leaflet tissue is present, such as in Barlow's disease, it is important to reduce the height of the posterior leaflet to <15 mm to prevent postoperative systolic anterior motion. A sliding leaflet technique is performed after quadrangular resection (Figure 1). An emerging paradigm of ‘respect rather than resect tissue’ has become popular in recent years, and is based on the use of polytetrafluoroethylene (PTFE) neochordae. Early and long-term results have been encouraging and no, or limited, leaflet resection in combination with PTFE chordae is now a preferred technique in many centres. Figure 1 Open in new tabDownload slide Patients with Barlow syndrome underwent mitral valve repair in right mini-thoracotomy access. (A) Preoperative transthoracic parasternal view shows a bileaflet prolapse and billowing. (B) Postoperative echocardiogram shows a good leaflet coaptation without regurgitation. (C) Intraoperative surgical view shows several segment prolapse. (D) Valve repair performed by P2 segment resection, sliding of P1 and P3 and Gore-Tex chordae implantation on A2–A3 segments, and annuloplasty using a semi-rigid Memo 3D prosthetic ring (Sorin). Figure 1 Open in new tabDownload slide Patients with Barlow syndrome underwent mitral valve repair in right mini-thoracotomy access. (A) Preoperative transthoracic parasternal view shows a bileaflet prolapse and billowing. (B) Postoperative echocardiogram shows a good leaflet coaptation without regurgitation. (C) Intraoperative surgical view shows several segment prolapse. (D) Valve repair performed by P2 segment resection, sliding of P1 and P3 and Gore-Tex chordae implantation on A2–A3 segments, and annuloplasty using a semi-rigid Memo 3D prosthetic ring (Sorin). Calcification of the chordae, papillary muscles, leaflets, and annulus may occur in the setting of degenerative valve disease. In general, debridement of calcified tissue is required to restore a good mobility to leaflet tissue. Mitral annular calcification can pose a special challenge to valve reconstruction, particularly when it is diffuse. Regardless of the leaflet and chordal techniques employed, a prosthetic ring or band annuloplasty that restores the normal circumference and shape of the mitral valve to match the available leaflet tissue is a mainstay of all repair procedures. The fibrous skeleton of the heart is not contiguous around the posterior aspect of the mitral annulus (MA), so long-standing regurgitation associated with ventricular and atrial enlargement leads to pathological dilatation of the MA and flatness, particularly along the posterior aspect of the valve. Regardless of the type of annular prosthesis (complete ring, partial posterior band; rigid, semi-rigid, or flexible), annuloplasty is a fundamental step in MVR. Failure to perform an annuloplasty at the time of MVR is one of the strongest predictors of failure, resulting in recurrent moderate or severe mitral valve regurgitation. Papillary muscle elongation or chordae elongation involving a group of chordae can also be treated by papillary muscle shortening. This not only corrects the leaflet prolapse but also reduces considerably the billowing of the leaflet body. This procedure is typically indicated in Barlow's disease. Although freedom from reoperation is very high in degenerative mitral valve surgery (15-year freedom from reoperation is ∼95%),4 recent studies have documented the potential for recurrence of significant mitral valve regurgitation. Studies by Flameng et al.6 and David7 suggest that a return of moderate-to-severe MR occurs in 1–2% of patients per year during mid-term follow-up. This observation places renewed emphasis on the need for expert mitral surgical repair initially (not only mitigating MR procedurally, but ensuring a long surface of leaflet coaptation to minimize the risks of late failure), and also on the necessity that surgical expertise continues to evolve so as to optimize long-term MVR results. Between January 2009 and September 2013, 6182 patients underwent mitral valve surgery in our centres (GVM Care and Research Hospitals). Mitral valve regurgitation was found present in 60.8%, valve stenosis in 4%, mixed lesions in 13.2%, and other causes in 22%. Mitral valve repair was performed in 2970 patients (with valve regurgitation and mixed lesions), with a 2.9% rate of in-hospital death. Data are illustrated in Table 1. Table 1 Mitral valve procedures performed in GVM Hospitals between January 2009 and September 2014 Variables No. of patients (%) In-hospital mortality (%) Mitral valve procedures (total) 6182 273 (4.4)  Isolated mitral 2938 (47.5) 60 (2.0)  Mitral + tricuspid 812 (13.1) 36 (4.4)  Mitral combined 2432 (39.3) 177 (7.3) Valve dysfunction  Regurgitation 3759 (60.8) 128 (3.4)  Stenosis 245 (4.0) 16 (6.5)  Mixed 819 (13.2) 47 (5.7)  Others 1359 (22.0) 82 (6.0) Regurgitation + mixed dysfunction group 4578 175 (3.8)  Repair 2970 (64.9) 85 (2.9)  Replacement 1608 (35.1) 90 (5.6)  Full sternotomy 3447 (78.9) 151 (4.4)  Right mini-thoracotomy 924 (21.1) 17 (1.8) Variables No. of patients (%) In-hospital mortality (%) Mitral valve procedures (total) 6182 273 (4.4)  Isolated mitral 2938 (47.5) 60 (2.0)  Mitral + tricuspid 812 (13.1) 36 (4.4)  Mitral combined 2432 (39.3) 177 (7.3) Valve dysfunction  Regurgitation 3759 (60.8) 128 (3.4)  Stenosis 245 (4.0) 16 (6.5)  Mixed 819 (13.2) 47 (5.7)  Others 1359 (22.0) 82 (6.0) Regurgitation + mixed dysfunction group 4578 175 (3.8)  Repair 2970 (64.9) 85 (2.9)  Replacement 1608 (35.1) 90 (5.6)  Full sternotomy 3447 (78.9) 151 (4.4)  Right mini-thoracotomy 924 (21.1) 17 (1.8) Data regarding the rate of in-hospital mortality according to valve procedures. Open in new tab Table 1 Mitral valve procedures performed in GVM Hospitals between January 2009 and September 2014 Variables No. of patients (%) In-hospital mortality (%) Mitral valve procedures (total) 6182 273 (4.4)  Isolated mitral 2938 (47.5) 60 (2.0)  Mitral + tricuspid 812 (13.1) 36 (4.4)  Mitral combined 2432 (39.3) 177 (7.3) Valve dysfunction  Regurgitation 3759 (60.8) 128 (3.4)  Stenosis 245 (4.0) 16 (6.5)  Mixed 819 (13.2) 47 (5.7)  Others 1359 (22.0) 82 (6.0) Regurgitation + mixed dysfunction group 4578 175 (3.8)  Repair 2970 (64.9) 85 (2.9)  Replacement 1608 (35.1) 90 (5.6)  Full sternotomy 3447 (78.9) 151 (4.4)  Right mini-thoracotomy 924 (21.1) 17 (1.8) Variables No. of patients (%) In-hospital mortality (%) Mitral valve procedures (total) 6182 273 (4.4)  Isolated mitral 2938 (47.5) 60 (2.0)  Mitral + tricuspid 812 (13.1) 36 (4.4)  Mitral combined 2432 (39.3) 177 (7.3) Valve dysfunction  Regurgitation 3759 (60.8) 128 (3.4)  Stenosis 245 (4.0) 16 (6.5)  Mixed 819 (13.2) 47 (5.7)  Others 1359 (22.0) 82 (6.0) Regurgitation + mixed dysfunction group 4578 175 (3.8)  Repair 2970 (64.9) 85 (2.9)  Replacement 1608 (35.1) 90 (5.6)  Full sternotomy 3447 (78.9) 151 (4.4)  Right mini-thoracotomy 924 (21.1) 17 (1.8) Data regarding the rate of in-hospital mortality according to valve procedures. Open in new tab Transcatheter approaches to mitral valve therapies When considering the complexity of the mitral valve apparatus, it is useful to classify the transcatheter approaches according to the major structural abnormality that they address. Therefore, the proposed classification can be broadly classified into those aimed at the leaflets/chordal repair, at the annulus (indirect annuloplasty: coronary sinus (CS) approach or asymmetrical approach, direct or LV annuloplasty), and those aimed at mitral valve replacement. Leaflet/chordal repair: MitraClip The concept that underlies the MitraClip system is derived from the edge-to-edge surgical stitch operation (Alfieri technique), in which the middle scallops of the posterior and anterior mitral leaflets (P2 and A2, respectively) are sutured together to create a double orifice mitral valve. At present, the MitraClip system is the only percutaneous therapeutic approach that can be considered as clinically validated.8 The other techniques are still in the experimental phase. The MitraClip (Abbott Vascular, Santa Clara, CA, USA) system uses a steerable catheter to deliver a clip to the anterior leaflet and the posterior leaflet: the clip is introduced through a 24-F sheath from the right femoral vein into the left atrium via a transseptal puncture. It is then guided using a series of turning knobs and transoesophageal echocardiographic (TEE) imaging through the mitral valve into the LV and then placed on the P2 and A2 leaflet segments to create leaflet apposition before release. Repositioning before detachment is feasible and a second clip, or more, can be positioned as needed for optimal MR reduction (Figure 2). Figure 2 Open in new tabDownload slide Percutaneous Mitral Valve repair using MitraClip Device after surgical annuloplasty. Severe eccentric mitral regurgitation is confirmed by 2D-transoesophageal echocardiographic colour doppler in the 2 chamber intercommissural view (A); 3D-transoesophageal echocardiographic en-face view (B) shows the annuloplasty ‘C-shape’ ring in place (white arrow) and the wide prolapse of the posterior leaflet (red arrow); transgastric short-axis view (C) confirms presence of posterior flail in the lateral portion of P2 scallop (flail width 11.07 mm). The first MitraClip device is going to be implanted in the 2 chamber intercommissural view and his orthogonal LVOT view (D); in the fluoroscopic image the second MitraClip device has just been deployed medial to the first clip (E). The location of each Clip is indicated by the number 1 and 2. The two MitraClip devices have successfully reduced the mitral regurgitation to a trivial residual grade confirmed at 2D-transoesophageal echocardiographic colour doppler in the 2 chamber intercommissural view (F). Figure 2 Open in new tabDownload slide Percutaneous Mitral Valve repair using MitraClip Device after surgical annuloplasty. Severe eccentric mitral regurgitation is confirmed by 2D-transoesophageal echocardiographic colour doppler in the 2 chamber intercommissural view (A); 3D-transoesophageal echocardiographic en-face view (B) shows the annuloplasty ‘C-shape’ ring in place (white arrow) and the wide prolapse of the posterior leaflet (red arrow); transgastric short-axis view (C) confirms presence of posterior flail in the lateral portion of P2 scallop (flail width 11.07 mm). The first MitraClip device is going to be implanted in the 2 chamber intercommissural view and his orthogonal LVOT view (D); in the fluoroscopic image the second MitraClip device has just been deployed medial to the first clip (E). The location of each Clip is indicated by the number 1 and 2. The two MitraClip devices have successfully reduced the mitral regurgitation to a trivial residual grade confirmed at 2D-transoesophageal echocardiographic colour doppler in the 2 chamber intercommissural view (F). The safety and feasibility trial, Endovascular Valve Edge-to-edge REpair STudy (EVEREST I), showed that, in 107 patients, procedural success (post-procedure MR ≤2+) was achieved in 74% with <1% in-hospital mortality.8 At 1 year, freedom from death, MV surgery, or MR >2+ was 66%. Freedom from death and freedom from surgery were 90.1 and 76.3% at 3 years, respectively. No clip embolized, although partial clip detachment occurred in 10 (9%) patients. Subsequently, 32 patients required surgery for MR; repair—when planned—was possible in 84%, demonstrating that surgical options were preserved.8 The 5-year data from the EVEREST II study, randomizing MitraClip vs. surgical repair or replacement, were recently presented. Patients (n = 279) with symptomatic or asymptomatic severe MR were randomized in a 2 : 1 fashion to the device (n = 184) or surgery (n = 95). Freedom from the combined end point of death, MV surgery or reoperation >90 days after the index procedure, and MR >2+ at 1 year was 72.4 and 87.8% in the device and surgical groups, respectively, meeting the non-inferiority hypothesis. The safety end point (all predefined adverse events plus blood transfusions ≥2 units) was superior in the device group (9.6 vs. 57% for surgery). At 5 years, overall mortality was similar in the two groups (81.2 vs. 79.0% for surgery) as well as Kaplan–Meier freedom from MV surgery or reoperation (91.4 vs. 93.7% for surgery) beyond the first 6 months. Clinical benefits provided by MitraClip are durable through 5 years in terms of reduction in MR severity, improvement in LV volumes and dimensions, and improvement in NYHA functional class. A randomized study is underway to compare the MitraClip device with medical therapy in heart failure patients with functional MR (RESHAPE-HF), and is powered for a primary end point of all-cause mortality and recurrent heart failure hospitalizations with 800 patients. Other leaflet and chordal repair approaches The NeoChord DS1000 system (CE Mark) is a transapically inserted device that can capture a flail leaflet, pierce it with a semi-dull needle, attach a standard PTFE artificial chord, and then anchor the chord to the apical entry site with a pledgeted suture without cardiopulmonary bypass. Early experience with this device was obtained in 30 patients at seven centres in the Transapical Artificial Chordae Tendinae (TACT) trial. At 30 days, 17 (59%) patients achieved MR grade ≤2+.9 V-Chordal (Pre-clinical; Valtech Cardio, Inc., or Yehuda, Israel) is being developed as a similar adjustable sutureless neochordal implant. This device, which is in preclinical evaluation, is implanted transseptally in the head of the papillary muscle. It has the potential advantages of avoiding the more invasive transapical approach as well as tension and wear on the implant due to apical tethering. Other devices are in early phase 1 evaluation or preclinical testing for MR repair at the chordal and leaflet level.10 Indirect annuloplasty This approach mimics surgical annuloplasty rings, which are commonly used for repair of both degenerative and functional MR. Coronary sinus approaches The Monarc (previously Viking) system (Edwards Lifesciences, Irving, CA, USA) consists of an outer guide catheter, a smaller delivery catheter, and a nitinol implant. The implant has three sections: distal and proximal self-expanding anchors, and a spring-like ‘bridge’ that has shortening forces. This draws the proximal CSs and distal great cardiac vein closer, indirectly displacing the posterior annulus anteriorly. The Viking device produced an initial favourable effect on MR, although device fracture and recurrence of MR occurred, and the feasibility study was stopped.10 The re-engineered device (Monarc) has a reinforced bridge segment. The phase 1 trial (Evolution) of functional MR with the Monarc device demonstrated11 an implantation success rate of 82% (59 of 72 patients), with 13 failures (18%) due to tortuous anatomy or inappropriate CS dimensions. Three myocardial infarctions occurred due to coronary artery compression (1 received coronary stenting, 1 was treated medically, and 1 was fatal). Event-free survival rates were 81, 72, and 64% at 1, 2 and 3 years, respectively. A larger Evolution II study is ongoing. The Carillon Mitral Contour System (Cardiac Dimension, Inc., Kirkland, WA, USA) consists of self-expandable nitinol distal and proximal anchors connected by a nitinol bridge that are placed in the great cardiac vein and proximal CS via a catheter-based system. The device received the CE Mark in 2011. Tension applied on the system results in cinching of the posterior peri-annular tissue and deflection of the posterior MA anteriorly. A feasibility study showed modestly reduced septal–lateral dimension and MR when placed temporarily. Data from the CARILLON Mitral Annuloplasty Device European Union Study (AMADEUS trial)12 using the modified CARILLON XE device (Cardiac Dimension, Inc.) in functional MR due to dilated cardiomyopathy demonstrated implantation success in 62% (30 of 48 patients), with a mean 1 grade reduction of MR (although it is uncertain, whether this would be clinically meaningful). Implantation could not be achieved in 18 (38%) patients due to access issues (CS dissection/perforation), insufficient MR reduction, and coronary artery compression. Coronary arteries were crossed frequently (36 of 43 implant attempts), although the device was recaptured in only 17% where compromise was significant. There are major limitations to the use of CS reshaping. The technique exploits the proximity of the CS to the MA. However, surgical anatomy suggests that the CS is located behind the left appendage (LA) wall, at a significant distance from the MA. Direct annuloplasty This technology reshapes the MA directly without using the CS, approaching the MA from the LV or the LA side. The Cardioband Annuloplasty System (Valtech Medical, Inc., or Yehuda, Israel) combines an implantable annuloplasty band, similar to the surgical band, with a transfemoral venous delivery system. Connection of the band to the MA is sutureless, using specially designed anchors. Size tuning of the implant is done under beating heart conditions and echocardiographic guidance for optimal results. A multicentre study is currently ongoing in leading European centres to study the safety and efficacy of the Cardioband transfemoral system in patients suffering from functional MR who are at high risk to undergo surgery.13 Mitral valve replacement Following the feasibility of transcatheter aortic valve implantation (TAVI), different devices especially for MR are developing. The main differences when compared with TAVI are the need for a larger prosthesis, the absence of calcium to fix the device in non-circular annulus, and the risk to interfere with the LV outflow tract. Facing all these difficulties, several companies have developed a transcatheter implantable mitral valve. Initial preclinical and first in-human experiences with the transapical valve implantation system have been performed recently in patients with a prohibitive surgical risk using different devices: CardiAQ (self-expanding stent-based bovine pericardial bioprothesis), Tiara (Neovasc self-expanding bovine pericardial bioprothesis), Forti (Edwards self-expanding stent-based bovine pericardial bioprothesis), and Medtronic (self-expanding bioprothesis with a trileaflet pericardial valve).14–16 Conclusion Based on the current evidence, surgery remains the standard treatment for MR in patients with degenerative disease according to very long-term survival and durability of MVR using Carpentier's technique. Surgical repair provides excellent long-term results with a mortality rate similar to that of the general population and a very low incidence rate of reoperation at 10 and 20 years, 94% (95% CI 90–98) and 92% (87–97), respectively. Percutaneous MVR therapy is in the evolutionary phase with good future prospects, but today only the MitraClip device may be considered as a valid alternative to surgery in selected and high-risk patients. Conflict of interest: none declared. References 1 Carpentier A . Cardiac valve surgery: the ‘French correction , J Thorac Cardiovasc Surg , 1983 , vol. 86 (pg. 323 - 337 ) Google Scholar PubMed WorldCat 2 Vahanian A , Alfieri O , Andreotti F , Antunes MJ , Baron-Esquivias G , Baumgartner H , Borger MA , Carrel TP , De Bonis M , Evangelista A , Falk V , Iung B , Lancellotti P , Pierard L , Price S , Schafers HJ , Schuler G , Stepinska J , Swedberg K , Takkenberg J , Von Oppell UO , Windecker S , Zamorano JL , Zembala M . 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A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Developed in Collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons , J Am Coll Cardiol , 2014 , vol. 22 (pg. e57 - 185 ) Google Scholar Crossref Search ADS WorldCat 4 Braunberger E , Deloche A , Carpentier A . Very long-term results (more than 20 years) of valve repair with Carpentier's techniques in nonrheumatic mitral valve insufficiency , Circulation , 2001 , vol. 104 Suppl I (pg. I-8 - I-11 ) Google Scholar Crossref Search ADS WorldCat 5 Feldman T , Young A . Percutaneous approaches to valve repair for mitral regurgitation , J Am Coll Cardiol , 2014 , vol. 63 pg. 2057 Google Scholar Crossref Search ADS PubMed WorldCat 6 Flameng W , Herijgers P , Bogaerts K . 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U120 - U128 ) Google Scholar Crossref Search ADS PubMed WorldCat 16 Cheung A , Stub D , Moss R , Boone RH , Leipsic J , Verheye S , Banai S , Webb J . Transcatheter mitral valve implantation with Tiara bioprosthesis , EuroIntervention , 2014 , vol. 10 Suppl (pg. U115 - U119 ) Google Scholar Crossref Search ADS PubMed WorldCat Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com
TI - Mitral valve therapy still surgical?
JF - European Heart Journal Supplements
DO - 10.1093/eurheartj/suv009
DA - 2015-03-01
UR - https://www.deepdyve.com/lp/oxford-university-press/mitral-valve-therapy-still-surgical-4psVFs0m3h
SP - A43
VL - 17
IS - suppl_A
DP - DeepDyve
ER -