INTRODUCTION — Transcatheter mitral valve repair (TMVR) is a minimally invasive technique for treatment of selected patients with symptomatic chronic moderate-severe or severe (3+ or 4+) mitral regurgitation (MR).
Mitral regurgitation (MR) can be caused by a primary disease of the valve leaflets (so-called primary MR, which is most commonly caused by "degenerative" or myxomatous mitral valve disease in developed countries), or by secondary (functional) causes such as by adverse left ventricular remodeling from cardiomyopathy or coronary artery disease.
This topic reviews TMVR, with a focus on the indications for use in chronic primary MR, patient selection, outcomes, and complications using the MitraClip device. Overviews of management of chronic primary and secondary MR, use of TMVR in secondary MR, and surgical treatment of chronic MR are presented elsewhere. (See "Management of chronic primary mitral regurgitation" and "Management and prognosis of chronic secondary mitral regurgitation" and "Surgical procedures for severe chronic mitral regurgitation".)
AVAILABLE TECHNOLOGY — While a number of technologies are in clinical development, an edge-to-edge leaflet repair device (the MitraClip) is currently the only US Food and Drug Administration (FDA) approved device for TMVR. The MitraClip, as well as the CARILLON mitral annuloplasty device, has CE Mark approval. (See 'Investigational technologies' below.)
The MitraClip is a transcatheter technology based on the surgical Alfieri edge-to-edge repair, which involves suturing together the middle segments of the anterior and posterior mitral valve leaflets, thereby creating a "double orifice" mitral regurgitant area [1]. The MitraClip system utilizes a cobalt chromium clip covered with a polypropylene fabric that grasps both the anterior and posterior mitral valve leaflets, thereby reducing mitral regurgitation (MR) by increasing the coaptation between the regurgitant valve leaflets. In some cases, a second clip may be required to adequately reduce the MR severity toward a goal of final regurgitant severity ≤2+ [2].
Investigational approaches to transcatheter mitral valve repair are discussed below. (See 'Investigational technologies' below.)
CLINICAL USE — A multidisciplinary dedicated heart team approach (including primary [general] cardiologists, interventional cardiologists, cardiac surgeons, imaging specialists, valve and heart failure specialists, and cardiac anesthesiologists) is recommended for the evaluation and care of potential candidates for transcatheter mitral valve repair (TMVR) [3].
Indications — For patients with primary mitral regurgitation (MR) who meet all of the following criteria, we suggest referral to a Heart Valve Team for evaluation of the feasibility and potential benefit and risk of TMVR:
•Chronic moderate to severe or severe (3 to 4+) MR
•Severely symptomatic (New York Heart Association Class III or IV) heart failure despite medical therapy
•Favorable anatomy for the repair procedure
•Reasonable life expectancy (eg, ≥2 years)
•Prohibitive surgical risk due to comorbidities
The above criteria are similar to those included as weak recommendations (effectiveness is less well established) in the 2017 focused update of the 2014 American Heart Association/American College of Cardiology valve guidelines and 2017 European Society of Cardiology valve guidelines, except the guidelines require severe (4+) primary MR [4,5].
Use of TMVR in selected patients with secondary MR is discussed separately. (See "Management and prognosis of chronic secondary mitral regurgitation", section on 'Indications'.)
Contraindications — Contraindications to MitraClip placement include:
●Patients who cannot tolerate procedural anticoagulation or antiplatelet agents post-procedure
●Active endocarditis of the mitral valve
●Rheumatic mitral valve disease or other causes of mitral stenosis
●Thrombus of the femoral vein, inferior vena cava, or intracardiac thrombus
Echocardiographic criteria — Transthoracic echocardiography and transesophageal echocardiography (the latter with adjunctive real-time three-dimensional imaging) are critical to pre-procedural planning.
The determination of MR severity and etiology should be based on careful, quantitative echocardiographic or cardiac magnetic resonance imaging assessment. (See "Clinical manifestations and diagnosis of chronic mitral regurgitation" and "Echocardiographic evaluation of the mitral valve" and "Transesophageal echocardiography in the evaluation of mitral valve disease".)
We use the following criteria for moderate-severe (3+) or severe (4+) MR as specified in the EVEREST II trial [6]. At least three of the following criteria should be met:
●Color flow jet may be central and large (>6 cm2 or >30 percent of left atrial area) or smaller if eccentric, encircling the left atrium
●Pulmonary vein flow may show systolic blunting or systolic flow reversal
●Vena contracta width ≥0.5 cm measured in the parasternal long axis view
●Regurgitant volume of ≥45 mL/beat
●Regurgitant fraction ≥40 percent
●Regurgitant orifice area ≥0.30 cm2
In addition to measuring severity, several anatomic features of the mitral valve must be examined to assess the feasibility of TMVR. These anatomic criteria include:
●Planimetered mitral valve area (in parasternal short axis view at tips of the mitral valve) ≥4.0 cm2.
●Minimal leaflet calcification in the grasping area.
●If leaflet flail is present, width of the flail segment <15 mm and flail gap of <10 mm. Flail gap was defined as the greatest distance between the ventricular side of the flail segment and the atrial side of the opposing leaflet (measured in the four-chamber long axis and left ventricular outflow tract views).
Transesophageal echocardiography is important in the pre-procedural evaluation of the valve as well as for procedural guidance in ensuring adequate clip placement. Transesophageal echocardiography demonstrates the location of the major leaflet pathology, the size and extent of a flail segment, and the demonstration that there is adequate leaflet support for clip implantation. Three-dimensional transesophageal echocardiography enhances the visualization of the valve with improved localization of the leaflet pathology and demonstration of anatomic features unsuitable for treatment with the clip such as a cleft leaflet, vegetations, and perforations [7-10]. It is important that the transesophageal examination be performed at the valve center where the procedure will be performed to ensure adequacy of the examination.
Determination of surgical risk — All patients undergoing evaluation for TMVR should be seen by a multidisciplinary heart team that includes a cardiologist and a cardiac surgeon. Prohibitive surgical risk is based on a 30-day Society of Thoracic Surgeons (STS)-predicted operative mortality of ≥8 percent for mitral valve replacement [11,12]. However, STS estimated risk does not capture all relevant risk factors, so the STS risk estimate should be combined with other risk assessment [4] (see "Estimating the risk of valvular procedures"). Other specific factors that may classify a patient as prohibitive risk include:
●Porcelain or highly calcified aorta
●Patient frailty
●Severe pulmonary hypertension
●Severe liver disease
PROCEDURE — Transcatheter mitral valve repair with the MitraClip device is performed in the cardiac catheterization laboratory using a combination of fluoroscopic and transesophageal echocardiographic (TEE) guidance. Because of the need for TEE guidance and careful device manipulation, the procedure is usually performed under general anesthesia. Antithrombotic therapy is discussed below. (See 'Antithrombotic therapy' below.)
Access is obtained via the femoral vein, and a transseptal puncture is performed to cross the interatrial septum into the left atrium. The MitraClip steerable catheter is then advanced into the left atrium, and echocardiographic guidance is utilized to align the MitraClip device with the regurgitant valve leaflets and into the left ventricle. The MitraClip is then drawn back with the clip arms open in order to grasp the leaflets at the site of regurgitation. The arms are then closed, and Doppler echocardiography is used to determine the consequent reduction in MR. If the reduction in MR is not adequate, the clip arms can be reopened and the placement adjusted prior to final device deployment. In approximately 40 percent of cases, an additional MitraClip may be implanted in order to adequately reduce MR [2].
During the procedure, real-time two- and three-dimensional transesophageal echocardiography guides the positioning of the trans-septal puncture, placement of the mitral clip, and assessment of the mitral valve morphology and regurgitation severity following the clip placement [7,13].
ANTITHROMBOTIC THERAPY — Antithrombotic therapy in patients undergoing TMVR includes management of anticoagulation prior to the procedure, anticoagulation during the procedure, and anticoagulation or antiplatelet therapy after the procedure.
Management prior to transcatheter mitral valve repair — For patients receiving anticoagulation prior to TMVR, anticoagulants should be discontinued prior to the procedure to allow sufficient time for restoration of normal coagulation. For example, vitamin K antagonist (warfarin) should generally be discontinued at least three days prior to the procedure and an international normalized ratio ≤1.7 verified prior to the procedure. Similarly, direct oral anticoagulants (such as dabigatran) should be discontinued prior to the procedure.
During the time that long-term anticoagulation is subtherapeutic prior to TMVR, heparin may be used if deemed appropriate based on an individualized assessment of the risk of thrombosis and bleeding. If subcutaneous low molecular heparin is used, it should be discontinued 12 hours prior to the procedure (ie, the last dose administered 24 hours prior to the procedure). If intravenous unfractionated heparin is used, it should be discontinued at least four hours prior to the procedure.
During the procedure — During the procedure, heparin is administered to maintain an activated clotting time >250 seconds; a therapeutic level is especially important after transseptal puncture.
Post-procedural management — Following the procedure, patients are treated with anticoagulation or antiplatelet therapy; patients should receive anticoagulant or antiplatelet therapy for at least six months following the procedure:
●For patients with an indication for anticoagulation, vitamin K antagonist or direct oral anticoagulant is reinitiated.
●For patients who do not have an indication for anticoagulation, antiplatelet therapy consisting of aspirin and/or clopidogrel is used [6,14,15]. If aspirin is used, a loading dose of 325 mg aspirin can be followed by 81 mg daily. If clopidogrel is used, a loading dose of 300 mg of clopidogrel is recommended (within 24 hours prior to the procedure or immediately following the procedure) followed by 75 mg daily. At least one of these antiplatelet agents should be continued for six months or longer. These recommendations are based on extrapolation from prior studies of device endothelialization.
OUTCOMES OF TRANSCATHETER MITRAL VALVE REPAIR — The outcomes of transcatheter mitral valve repair (TMVR) for primary MR have been investigated in a number of cohort studies as well as one large randomized trial comparing transcatheter repair with surgical repair (the EVEREST II trial).
Early results — Studies of commercial use of TMVR in Europe and the United States (US) have shown rates of procedural success (including postimplantation mitral regurgitation [MR] grade ≤2) generally over 90 percent and in-hospital mortality rates of 0 to 4 percent [16,17]. As an example, a study of the initial commercial experience with TMVR in the US included data on 564 high surgical-risk patients (median Society of Thoracic Surgeons Predicted Risk of Mortality score 7.9 percent for surgical repair and 10 percent for MV replacement) with symptomatic, predominantly primary (degenerative) MR [17]. Procedural success (defined as MR ≤2 without conversion to open surgery or in-hospital death) was achieved in 90.6 percent with an in-hospital mortality rate of 2.3 percent. Thirty-day complication rates included death in 5.8 percent, stroke in 1.8 percent, bleeding in 2.6 percent, and device-related complications in 1.4 percent. Further study is required to determine the long-term efficacy of TMVR in various patient populations. (See 'Reduction in mitral regurgitation' below.)
Comparison with surgical mitral valve repair — Both TMVR and surgical repair of the mitral valve reduce or eliminate MR in properly selected patients. The EVEREST II randomized trial compared the outcomes of TMVR with surgical mitral repair or replacement among 279 patients with moderate-to-severe or severe (grade 3+ or 4+) MR who were candidates for either procedure [6]. Most of the patients had heart failure at baseline (91 percent in the TMVR group and 78 percent in the surgical group). A primary regurgitant jet originating from malcoaptation of the middle scallops of the anterior and posterior leaflets was required. Most of the patients (73 percent) had primary (degenerative) MR. Among the patients undergoing mitral valve surgery, 14 percent underwent mitral valve replacement and 86 percent underwent repair. The following results were obtained:
●The primary composite end point for efficacy was freedom from death, from surgery for mitral valve dysfunction, and from grade 3+ or 4+ mitral regurgitation at 12 months. This end point was more frequent in the surgery group (73 versus 55 percent) due to the higher rate of subsequent surgery for mitral valve dysfunction in the TMVR group (20 versus 2 percent).
●TMVR and mitral valve surgery were associated with similar rates of overall mortality at one year (6 percent for both).
●Grade 3+ or 4+ MR was similar in the two groups (21 versus 20 percent).
●Major adverse event rates at 30 days were significantly lower in the TMVR group compared with the surgical group (15 versus 48 percent). This was largely due to the higher rate of transfusion of at least 2 units of blood in the surgical group (13 versus 45 percent).
●At four-year follow-up, the overall rates of mortality (17.4 versus 17.8 percent) and of 3+ or 4+ MR (21.9 versus 24.7) remained similar in the TMVR and surgical groups [18]. However, surgery for mitral valve dysfunction was significantly higher in the TMVR group (24.8 versus 5.5 percent).
Reduction in mitral regurgitation — Successful TMVR leads to a reduction in MR severity to ≤2+ as assessed by echocardiography. Several studies have reported the long-term efficacy of transcatheter repair in reducing MR severity:
●In the EVEREST II trial, the prevalence of 3 to 4+ MR at four years was 21 percent [6,18], although 24.8 percent required surgery for mitral valve dysfunction.
●In the high-risk and continued access registry of the EVEREST II trial, 16.4 percent of patients had an MR grade of 3+ to 4+ at 12 months [19]; no subsequent mitral valve surgery was performed.
●In a European-based registry of 567 patients with 3+ to 4+ MR, 21.1 percent of patients had 3+ to 4+ MR at 12 months [20].
These results suggest that successful TMVR in selected patients with secondary or degenerative MR is associated with sustained reduction in MR severity in the majority of patients at one-year follow-up. A limitation of some of these studies is lack of a core lab for adjudication of MR severity during follow-up.
Left ventricular reverse remodeling — MR causes a chronic volume overload that leads to dilation of the left atrium and left ventricle. Correction of MR is associated with left ventricular remodeling with a reduction in LV chamber size. Even though transcatheter repair often does not completely eliminate MR, reduction in MR to 2+ or less is associated with some degree of left ventricular reverse remodeling:
●In a study of 801 patients undergoing MitraClip implantation, reduction in MR at 12 months was associated with a reduction in both left ventricular end-diastolic volume and left atrial volume [21].
●In the EVEREST II trial, surgical repair was associated with a greater reduction in left ventricular volumes, likely due to less residual MR [6].
Functional and quality of life improvement — Patients with severe MR have a significant impairment in exercise capacity and quality of life. Reduction in MR by TMVR using the MitraClip is associated with improvement in both functional and quality-of-life metrics:
●In the EVEREST II study, the proportion of patients with New York Heart Association (NYHA) Class III/IV symptoms was 45.7 percent at baseline and 5.7 percent at four years among patients who underwent TMVR [18].
●In patients with degenerative MR at high surgical risk, reduction of MR by TMVR was associated with improved quality-of-life scores and a reduced rate of hospitalizations for heart failure [11].
Use for secondary MR — The use of TMVR in patients with secondary MR is discussed separately. (See "Management and prognosis of chronic secondary mitral regurgitation", section on 'Transcatheter edge-to-edge repair'.)
COMPLICATIONS OF TRANSCATHETER MITRAL VALVE REPAIR — Transcatheter mitral valve repair (TMVR) is associated with an overall complication rate of 15 to 19 percent at 30 days [6,19]. Early (30-day) complication rates are primarily due to need for periprocedural blood transfusion, while late events are primarily related to underlying heart failure or patient comorbidities [19].
Complications include access site bleeding, partial clip detachment, and rarely device embolization or development of mitral stenosis.
Bleeding — Due to the large sheath size, TMVR poses a risk of access site bleeding. However, the rate of significant bleeding is lower for TMVR than for surgery:
●In the EVEREST II trial, 13 percent of patients randomized to TMVR required transfusion of ≥2 units of blood, compared with 45 percent of patients who underwent surgical mitral valve repair [6].
●In the EVEREST II high-risk study, 17.9 percent of patients required transfusion of ≥2 units of blood [22].
●In registries of TMVR, the percentage of patients who required ≥2 units of blood transfusion has been significantly lower, ranging from 0.9 to 3.9 percent [20,23].
Device embolization or partial clip detachment — Device embolization is an exceedingly rare complication of MitraClip placement. More commonly, the clip may partially detach; this complication can usually be treated with surgery. Low rates of clip detachment have been reported in studies. As an example, in the EVEREST II study, nine patients were noted in the first 12 months to have partial clip detachment; one additional patient developed partial clip detachment from years one to four. All of these patients were treated with subsequent mitral valve surgery [6].
An ongoing post-approval study will include device embolization as an end point in order to identify any signal of device complication during clinical use.
Mitral stenosis — TMVR creates an increase in diastolic pressure gradient across the mitral valve, and the development of clinically significant mitral stenosis is a potential but rare complication of MitraClip implantation:
●Hemodynamic studies of mitral valve area before and after MitraClip implantation have not shown clinically significant increases in mean diastolic mitral valve gradients or reduction in mitral valve area acutely or at 12-month follow-up [24]. There were also no differences in mitral valve hemodynamics between patients who had one versus two clips placed [25].
●Individual cases of mitral stenosis after MitraClip implantation have been reported in one patient with borderline pre-procedure mitral valve area and in another patient on dialysis who developed late calcific changes resulting in mitral stenosis [26,27].
Infective endocarditis — Limited information is available on the risk of infective endocarditis following MitraClip implantation since published data are limited to sporadic case reports [28]. Patients who have undergone TMVR should be instructed regarding the importance of careful dental hygiene and prompt medical care for fever or other signs of infection.
The role of antibiotic prophylaxis for infective endocarditis for patients with prosthetic material used for valve repair is controversial. For patients with prosthetic material used for valve repair, we suggest antibiotic prophylaxis when undergoing a relevant procedure, particularly dental procedures that involve manipulation of gingival tissue or the periapical region of the teeth or perforation of the oral mucosa. However, there is lack of consensus among experts on the role of antibiotic prophylaxis for infective endocarditis for patients with prosthetic material used for valve repair. The 2015 European Society of Cardiology infective endocarditis guidelines included prosthetic material used for valve repair as an indication for antibiotic prophylaxis [29]. In contrast, the 2014 American Heart Association/American College of Cardiology valve guidelines did not include presence of prosthetic material used for valve repair, such as a MitraClip, as an indication for infective endocarditis prophylaxis [4]. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)
INVESTIGATIONAL TECHNOLOGIES — Although the MitraClip is currently the only US Food and Drug Administration approved device for transcatheter mitral valve repair (TMVR), a number of other devices are in various stages of development.
Investigational devices for mitral valve repair work by a number of mechanisms include the following [30,31]:
●Altering the geometry of the mitral valve annulus via direct or indirect annuloplasty to reduce the severity of MR. The CARILLON Mitral Contour system implants a nitinol device in the coronary sinus that indirectly cinches the mitral annulus [32,33].
●Chordal replacement.
●Remodeling the ventricle, thereby reducing the severity of secondary mitral regurgitation (MR).
●Attaching (simultaneously or serially) the mid-anterior and posterior mitral valve leaflets to each side of a small spacer via the PASCAL TMVR system [34].
Many patients with severe MR do not meet anatomic criteria for MitraClip repair [35]. The PASCAL transcatheter mitral valve repair system was developed to reduce the anatomical requirements for transcatheter valve repair. The feasibility of PASCAL mitral valve repair was evaluated in 23 patients with symptomatic severe mitral regurgitation (22 with New York Heart Association [NYHA] functional class III or IV), most of whom were not considered candidates for MitraClip repair due to anatomical complexity or lack of an approved indication for use [34]. During 30-day follow-up, three patients (13 percent) died. Among the 20 patients alive at 30-day follow-up, 19 were NYHA functional class I or II. Further study is needed to evaluate the effect on clinical outcomes of this device.
Transcatheter mitral valve replacement (with a bioprosthetic valve) is an investigational alternative to TMVR [36,37].
Each of these technologies will require rigorous evaluation of risk/benefit and long-term durability in the treatment of MR.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiac valve disease".)
SUMMARY AND RECOMMENDATIONS
●A transcatheter edge-to-edge mitral leaflet repair device (the MitraClip) reduces mitral regurgitation (MR) by improving the coaptation of the anterior and posterior mitral leaflets. (See 'Available technology' above.)
●For patients with chronic primary MR who meet all of the following criteria, we suggest referral to a heart valve team to evaluate the feasibility and potential benefit and risk of transcatheter mitral valve repair (TMVR) (Grade 2C):
•Chronic moderate-severe to severe (3+ to 4+) MR
•Severely symptomatic (New York Heart Association Class III or IV) heart failure despite medical therapy
•Favorable anatomy for the repair procedure
•Reasonable life expectancy
•Prohibitive surgical risk due to comorbidities
Use of TMVR in selected patients with secondary MR is discussed separately. (See "Management and prognosis of chronic secondary mitral regurgitation", section on 'Indications'.)
●Based on evidence in patients with primary MR, TMVR using the MitraClip device is less effective at reducing MR than mitral surgery, with subsequent surgery for mitral valve dysfunction at one year more common after TMVR. On the other hand, major postprocedural adverse events are less frequent with TMVR. (See 'Comparison with surgical mitral valve repair' above.)
●Clinical studies have demonstrated reduction in the severity of primary MR, reduced left ventricular and left atrial volumes, and improved exercise capacity and quality of life in patients treated with the MitraClip device. (See 'Outcomes of transcatheter mitral valve repair' above.)
●Transthoracic echocardiography and transesophageal echocardiography (the latter with adjunctive real-time three-dimensional imaging) are critical to pre-procedural planning. (See 'Echocardiographic criteria' above.)
●Fluoroscopy and transesophageal echocardiography (two- and three-dimensional) are used to guide the implantation procedure. (See 'Procedure' above.)
●Complications of TMVR using the MitraClip include bleeding (particularly at the access site) and partial clip detachment. Although the diastolic pressure gradient across the mitral valve increases following MitraClip insertion, development of clinically significant mitral stenosis is rare. (See 'Complications of transcatheter mitral valve repair' above.)
