Medical Policies - Surgery


Transcatheter Mitral Valve Repair

Number:SUR707.025

Effective Date:10-15-2017

Coverage:

*CAREFULLY CHECK STATE REGULATIONS AND/OR THE MEMBER CONTRACT*

Transcatheter mitral valve repair with a device cleared by the United States (U.S.) Food and Drug Administration (FDA) for use in mitral valve repair may be considered medically necessary for patients with symptomatic, degenerative mitral regurgitation who are considered at prohibitive risk (see NOTE 1 below) for open surgery.

NOTE 1: Prohibitive risk for open surgery may be determined based on the following indications:

Presence of a Society for Thoracic Surgeons predicted mortality risk of 12% or greater; and/or

Presence of a logistic EuroSCORE of 20% or greater.

Transcatheter mitral valve repair is considered experimental, investigational and/or unproven in all other situations.

Transcatheter mitral valve repair using percutaneous annuloplasty is considered experimental, investigational, and/or unproven for the treatment of mitral valve regurgitation (insufficiency).

Description:

Mitral Regurgitation (MR): Epidemiology and Classification

MR is the second most common valvular heart disease, occurring in 7% of people older than age 75 years and accounting for 24% of all patients with valvular heart disease. (1) MR can result from a heterogeneous set of disease processes that may affect 1 or more parts of the mitral valve (MV) complex. The functional anatomy of the MV complex includes the left ventricular (LV) myocardium, the subvalvular apparatus including the papillary muscles and chordae tendineae, the mitral annulus, the MV leaflets, and the left atrium. (2) The underlying cause of MR and the portion of the MV complex involved determine the underlying treatment strategy.

MR is classified into degenerative and functional MV disease. In degenerative mitral regurgitation (DMR), disease results from a primary structural abnormality of the MV complex. Common causes of DMR include MV prolapse syndrome with subsequent myxomatous degeneration, rheumatic heart disease, coronary artery disease, infective endocarditis, and collagen vascular disease. (3) In contrast, in functional mitral regurgitation (FMR), the primary abnormality is a dilated LV due to ischemic or dilated cardiomyopathy, which leads to secondary dilatation of an anatomically normal MV. (4) MR severity is classified into mild, moderate, and severe disease on the basis of echocardiographic and/or angiographic findings (1+, 2+, and 3-4+ angiographic grade, respectively).

MR with accompanying valvular incompetence leads to LV volume overload with secondary ventricular remodeling, myocardial dysfunction, and left heart failure. Clinical signs and symptoms of dyspnea and orthopnea may also present in patients with valvular dysfunction. (4) MR can be acute or chronic. (3) Acute MR can result from conditions such as ruptured chordae tendineae or infectious endocarditis; and when severe, it can present with simultaneous shock and pulmonary congestion. Chronic MR may remain asymptomatic over a long period of time due to compensatory LV hypertrophy secondary to the LV overload. This leads to increased LV end-diastolic volume and, in turn, increased stroke volume (to restore forward cardiac output) and increased LV and left atrial size (to accommodate the regurgitant volume at lower filling pressure). Eventually, prolonged volume overload leads to contractile dysfunction, with increased end-systolic volume, further LV dilatation, and increased LV filling pressure. These changes ultimately lead to reduced forward cardiac output and signs and symptoms of pulmonary congestion. (3)

MR: Standard Management

Medical Management

Medical management has role in a subset of MR cases. Among patients with chronic DMR, there is no generally accepted medical management. In FMR, medical management plays a much greater role because the underlying pathophysiology is related to LV dysfunction and dilatation. Primary treatment of the LV systolic dysfunction with angiotensin-converting enzyme inhibitors, β-blockers, and biventricular pacing can reduce LV pressures, decrease LV dilatation, improve cardiac output, and thus ameliorate clinical symptoms. (3,4)

Surgical Management

In patients with symptoms of MR with preserved LV function (DMR), surgery is the main therapy. In most cases, repair of the MV is preferred over replacement, as long as the valve is suitable for repair and personnel with appropriate surgical expertise are available. The American College of Cardiology (ACC) and the American Heart Association (AHA) have issued joint guidelines for the surgical management of MV, which are outlined as follows (3):

MV surgery is recommended for the symptomatic patient with acute severe MR.

MV surgery is beneficial for patients with chronic severe MR and New York Heart Association (NYHA) functional class II, III, or IV symptoms in the absence of severe LV dysfunction (severe LV dysfunction is defined as ejection fraction <0.30) and/or end-systolic dimension >55 mm.

MV surgery is beneficial for asymptomatic patients with chronic severe MR and mild-to-moderate LV dysfunction, ejection fraction 0.30 to 0.60, and/or end systolic dimension ≥40 mm.

MV repair is recommended over MV replacement in the majority of patients with severe chronic MR who require surgery, and patients should be referred to surgical centers experienced in MV repair.

MV repair is also reasonable for asymptomatic patients with chronic severe MR with preserved LV function who have a high likelihood of successful MV repair, who have new-onset atrial fibrillation, or who have pulmonary hypertension, and in patients with chronic severe MR with NYHA functional class III-IV symptoms and severe LV dysfunction who have chronic severe MR due to a primary abnormality of the mitral apparatus and have a high likelihood of successful MV repair.

Standard open MV repair includes quadrangular leaf resection (if MV prolapse is present), transposition of normal valve chords to other areas of prolapsing leaflet, and a remodeling annuloplasty with ring prosthesis. Multiple types of annuloplasty rings and bands specific to the underlying cause of the MR are commercially available. (2) In the 1990s, the edge-to-edge approximation technique (Alfieri repair) was introduced. Typically combined with an annuloplasty, the Alfieri repair involves suturing the anterior and posterior MV leaflets together at their midpoint, creating a double-orifice MV. (2,5)

However, there are limitations to the standard approaches for MV surgery. While surgical MV repair is durable, its use is limited by the requirement for thoracotomy and cardiopulmonary bypass, which is a concern among patients who are elderly or debilitated due to their underlying cardiac disease or other conditions. In a 2007 study of 396 patients in Europe with severe, symptomatic MR, Mirabel et al found that about half of patients did not undergo surgical repair. (6) Fifty-six percent and 32% of patients with DMR and FMR, respectively, did not undergo surgery. Older age, impaired LV ejection fraction, and presence of comorbidities were all associated with the decision not to operate. In a single-center evaluation of 5737 patients with severe MR in the U.S., Goel et al. found that 53% of patients did not have MV surgery performed. (7) Compared with those who received surgery, patients who did not receive surgery had lower ejection fractions (27% vs 42%, p<0.001) and were of higher surgical risk, as judged by a higher Society of Thoracic Surgeons score (median, 5.8 vs 4.0, p<0.001). These findings suggest that there is an unmet need for less invasive procedures for MV repair.

Transcatheter MV Repair

Transcatheter approaches have been investigated to address the unmet need for less invasive MV repair, particularly among patients who face prohibitively high surgical risks due to their ages or comorbidities. MV repair devices under development address various components of the MV complex and generally are performed on the beating heart without the need for cardiopulmonary bypass. (1,8) Approaches to MV repair include direct leaflet repair, repair of the mitral annulus via direct annuloplasty, or indirect repair based on the annulus’s proximity to the coronary sinus. There are also devices in development to counteract ventricular remodeling, and systems designed for complete MV replacement via catheter.

Direct Leaflet Approximation

One device that undertakes direct leaflet repair, the MitraClip® Clip Delivery System (Abbott Vascular, Menlo Park, CA), has approval through the U.S. FDA premarket approval (PMA) process for use in certain patients with symptomatic MR (see Regulatory Status section below). Of the transcatheter MV repair devices under investigation, MitraClip has the largest body of evidence evaluating its use and has been in use in Europe since 2008. (9) The MitraClip system is a percutaneously deployed device that approximates the open Alfieri edge-to-edge repair approach to treating MR. The delivery system consists of a delivery catheter, a steerable sleeve, and the MitraClip device, which is a 4- mm wide clip fabricated from a cobalt-chromium alloy and polypropylene fabric. MitraClip is deployed via a transfemoral approach, with transseptal puncture used to access the left side of the heart and the MV. Placement of MitraClip leads to coapting of the mitral leaflets, thus creating a double-orifice valve.

Other MV Repair Devices

Additional devices for transcatheter MV repair that use various approaches are in development.

Techniques to repair the mitral annulus include those that target the annulus itself (direct annuloplasty) and those that tighten the mitral annulus via manipulation of the adjacent coronary sinus (indirect annuloplasty). Indirect annuloplasty devices include the Carillon® Mitral Contour System™ (Cardiac Dimension, Kirkland, WA) and the Monarc™ device (Edwards Lifesciences, Irvine, CA). The CE-marked Carillon Mitral Contour System is comprised of self-expanding proximal and distal anchors connected with a nitinol bridge, with the proximal end coronary sinus ostium and the distal anchor in the great cardiac vein. The size of the connection is controlled by manual pullback on the catheter (CE marked). The Carillon system was evaluated in the AMADEUS (Carillon Mitral Annuloplasty Device European Union Study) and the follow-up TITAN (Tighten the Annulus Now) study, with further studies planned. (10) The Monarc system also involves 2 self-expanding stents connected by a nitinol bridge, with one end implanted in the coronary sinus via internal jugular vein and the other end in the great cardiac vein. Several weeks following implantation, a biologically degradable coating over the nitinol bridge degrades, allowing the bridge to shrink and the system to shorten. It has been evaluated in the EVOLUTION I (Clinical Evaluation of the Edwards Lifesciences Percutaneous Mitral Annuloplasty System for the Treatment of Mitral Regurgitation) trial. (11)

Direct annuloplasty devices include the Mitralign Percutaneous Annuloplasty System (Mitralign, Tewksbury, MA.) and the AccuCinch® System (Guided Delivery Systems, Santa Clara, CA.), both of which involve transcatheter placement of anchors in the MV, which are cinched or connected to narrow the mitral annulus. Other transcutaneous direct annuloplasty devices under investigation include the enCorTC™ device (MiCardia, Irvine, CA.), which involves a percutaneously insertable annuloplasty ring that is adjustable using radiofrequency energy, a variation on its CE-marked enCorSQ™ Mitral Valve Repair System, and the Cardioband™ Annuloplasty System (Valtech Cardio, Or-Yehuda, Israel), an implantable annuloplasty band with a transfemoral venous delivery system.

Transcatheter MV Replacement

Several devices are under development for transcatheter MV replacement, including the Endovalve™ (MicroInterventional Devices, Langhorne, PA.), the CardiAQ™ (CardiAQ Valve Technologies, Irvine, CA.) valve, the Cardiovalve (Valtech Cardio, Or-Yehuda, Israel), and the Fortis Transcatheter Mitral Valve (Edwards Lifesciences, Irvine, CA.).

Regulatory Status

In October 2013, the MitraClip® Clip Delivery System (Abbott Vascular, Menlo Park, CA.) was approved by the U.S. FDA through the PMA process for treatment of “significant symptomatic mitral regurgitation (MR ≥3+) due to primary abnormality of the mitral apparatus (degenerative MR) in patients who have been determined to be at a prohibitive risk for MV surgery by a heart team.” (12) FDA product code: NKM.

The FDA’s approval of MitraClip was based on data from 1 randomized controlled trial (RCT) and 2 patient registry databases. (9,12) These studies are described further in the Rationale section.

Carillon® Mitral Contour System™ for percutaneous annuloplasty, Portico™ (St. Jude Medical) and SAPIEN pulmonary valve (Edwards Lifesciences) are not FDA approved in the U.S.

Rationale:

This evidence review was created in June 2014 based, in part, on a 2014 Blue Cross Blue Shield Association (BCBSA) Technology Evaluation Criteria (TEC) Assessment that evaluated the use of transcatheter mitral valve (MV) repair in patients with symptomatic degenerative mitral regurgitation (DMR) who are at prohibitive risk for mortality during open surgery and determined that the procedure did not meet TEC. (13) The evidence review has been updated periodically with literature reviews through searches of the Medline database. The most recent update covered the period through November 30, 2015.

The literature search for this evidence review focused primarily on studies evaluating MitraClip, but evidence related to other devices is discussed. Assessment of efficacy for therapeutic interventions such as MitraClip involves a determination of whether the intervention improves health outcomes. The optimal study design for this purpose is a randomized controlled trial (RCT) that includes clinically relevant measures of health outcomes. Intermediate outcome measures, also known as surrogate outcome measures, may be adequate if there is an established link between the intermediate outcome and true health outcomes. Nonrandomized comparative studies and uncontrolled studies can sometimes provide useful information on health outcomes, but are prone to biases. For MitraClip, the appropriate comparison group could be either open surgical repair (for surgical candidates) or best medical therapy (among persons at prohibitive surgical risk).

There are 2 major categories of patients with mitral regurgitation (MR) who are potential candidates for transcatheter MV repair: those who are considered to be at prohibitively high risk for cardiac surgery and those considered surgical candidates. Studies addressing these 2 subsets of patients are outlined separately. Although outcomes and etiology differ for functional mitral regurgitation (FMR) and DMR, studies on MitraClip most often evaluate the device in mixed populations.

MitraClip in Prohibitive Surgical Risk Candidates

The MitraClip device delivery system was approved by the U.S. Food and Drug Administration (FDA) for use in patients with DMR who are not candidates for open surgery. There are no controlled trials of MitraClip in this population. Available studies include multiple cohort studies and case series, the largest of which are the EVEREST II High Risk Registry (HRR) and the EVEREST II Real World Expanded Multicenter Study of the MitraClip System (REALISM) studies. Systematic reviews of these uncontrolled studies have also been published.

Systematic Reviews and Meta-Analyses

A 2014 BCBSA TEC Assessment evaluated the evidence on the use of MitraClip for FDA-approved indication. (13) The assessment included 5 case series reporting outcomes of patients with DMR considered at high risk of surgical mortality who underwent MitraClip placement. In the 2 studies the Assessment considered higher quality, 30-day mortality rates were 6.0% and 6.3%, and 12- to 25-month mortality rates were 17.1% and 23.6%, respectively. In evaluable patients at 12 months, the percentage of patients who had an MR grade of 2 or less was 83.3% and 74.6% in the 2 studies; the percentage of patients with New York Heart Association (NYHA) class I/II functional status was 81% and 87%; and improvement of at least 1 NYHA class was present in 68% and 88% of patients, respectively. Table 1 (adapted from the BCBSA TEC Assessment) summarizes health outcomes for the 5 studies that the Assessment reviewed.

Table 1: Health Outcomes at 12 Months of Case Series of Studies of MitraClip for Patients with Degenerative Mitral Valve Disease

Study

Original N

MR Grade at 12 Months, % (n/N)

NYHA Class at 12 Months, % (n/N)

Other Pertinent Outcomes Assessed at 12 Months

Lim et al. (2014)14

127

MR ≤2+, 83.3%

(70/84)

o NYHA I/II, 86.9% (73/84)

o Improved ≥1 class, 86.9% (73/84)

o SF-36 PCS score change, 6.0 (95% CI, 4.0 to 8.0), n=76

o SF-36 MCS score change, 5.6 (95% CI, 2.3 to 8.9), n=76

Reichenspurner et al.

(2013)15

117

MR ≤2+, 74.6%

(53/71)

o NYHA I/II, 81% (63/78)

o Improved ≥1 class, 68% (53/78)

o Change in MLHFQ from baseline, 13.3 points (p=0.03), n=44

o Change in 6MWT from baseline, 77.4 m (p<0.001), n=52

Estévez-Loureiro et al.

(2013)16

79

NR

NR

Grasso et al. (2013)17

28

NR

NR

Kaplan-Meier estimate of freedom from death, surgery, or ≥3+ MR, 70% (visual estimate from graph).

Chan et al. (2012)18

15

MR severity, 1.9a

NYHA class, 2.1a

Adapted from the BCBSA TEC Assessment.

CI: confidence interval; MCS: Mental Component Summary; MLHFQ: Minnesota Living with Heart Failure 10 Questionnaire; MR: mitral regurgitation; NR: not reported; NYHA: New York Heart Association; PCS: Physical Component Summary; 6MWT: Six-Minute Walk Test; SF-36: 36-Item Short-Form Health Survey. a Values are mean. Sample sizes unknown.

The Assessment reviewed the evidence on the natural history of patients with MR who were considered at high risk for surgery in an attempt to determine an appropriate comparison group for the uncontrolled case series of MitraClip in high surgical risk patients. The evidence included 1 published study by Whitlow et al. (19) and data presented to the FDA as part of the device’s premarket approval application. The TEC Assessment concluded that these control groups may not provide unbiased or precise estimates of the natural history of patients who are eligible to receive MitraClip because most patients were either not evaluated for anatomic eligibility for MitraClip or were ineligible. As such, the control groups are likely to have higher mortality rates than patients eligible to receive MitraClip.

Due to the lack of an appropriate control group or clear evidence about the natural history of patients with DMR considered at high risk for surgery, the Assessment concluded that it cannot be determined whether the mortality rate associated with MitraClip use is improved, equivalent, or worse than medical treatment.

Also in 2014, Philip et al. reported results of a systematic review of studies evaluating MitraClip or surgical MV repair or replacement for severe symptomatic MR in patients at high surgical risk (logistic EuroSCORE >18 or Society for Thoracic Surgeons [STS] score >10). (20) The review included 21 studies that used MitraClip (n=3198 patients) and surgical MV repair (n=490) or MV replacement (n=2775). MitraClip patients had a mean STS score of 14 and a mean EuroSCORE of 23. Acute procedural success did not differ significantly between groups. However, the 30-day pooled technical failure rate was 3.2% (95% confidence interval [CI], 1.5% to 7%) for MitraClip patients, compared with 0.6% (95% CI, 0.2% to 1.8%) for surgical repair/replacement patients (p=0.002). In pooled analysis, the 30-day mortality rate was 3% (95% CI, 2.6% to 4.2%) among MitraClip patients and 16% (95% CI, 13% to 20%) in surgical repair/replacement patients. Of the total sample, 1-year data were available for 1064 MitraClip patients (1-year data for surgical repair patients was limited to 47 patients and was not reported). Overall, among MitraClip patients, the 1-year mortality rate was 13.0% (95% CI, 9% to 18.3%), the 1-year stroke rate was 1.6% (95% CI, 0.8 to 3.2), and the need for repeat MV surgery was 1.3% (95% CI, 0.7 to 2.6).

A systematic review by Munkholm-Larsen et al. published in 2014 summarized safety and efficacy results from 12 publications evaluating the efficacy of MitraClip in surgically high-risk patients. (21) The authors included studies that evaluated high-risk surgical patients with significant MR who underwent transcatheter MR repair with the MitraClip device, and excluded studies with surgical candidates. All studies were prospective, observational studies from specialized tertiary centers, with 3 multicenter studies and 9 single-institution studies. The 3 largest studies included 202, 117, and 100 patients, respectively, while the rest included fewer than 100 patients. Follow-up duration ranged from 1 month to 14 months. Across the studies, 30-day mortality rates ranged from 0% to 7.8%. Most of the high surgical risk patients had successful reduction of MR of grade 2+ or less (73%-100% across studies). In studies that reported follow-up at 6 to 12 months, 61% to 99% of patients demonstrated continued MR reduction of grade 2+ or less, and 50% to 89% of patients demonstrated improvements in NYHA functional class to I to II. This systematic review suggests that MitraClip is associated with short-term improvements in echocardiographic parameters among high surgical risk patients, but does not provide evidence on clinical outcomes. Longer term follow-up studies are limited. In addition, most studies included both FMR and DMR, which limits the ability to assess outcomes stratified by etiology.

Nonrandomized Studies Evaluating MitraClip in Prohibitive Surgical Risk Populations

Evidence on the use of MitraClip in high surgical risk patients in practice is available through a number of single-arm cohort studies, including the pivotal EVEREST II HRR study and the EVEREST II REALISM study, which included non-high-risk and high-risk arms in the United States. In addition, several cohort studies have reported experience with MitraClip in European centers, because the device has been CE marked for use in Europe since 2008.

EVEREST High-Risk Registries

The EVEREST II RCT, described below, was a pivotal multicenter trial designed to evaluate the efficacy of transcatheter MV repair with MitraClip compared with open MV repair. (22,23) Concurrent with the EVEREST II RCT, investigators enrolled patients into the EVEREST II HRR study who were deemed ineligible for surgery due to prohibitively high surgical risks. In addition, a continued access study (EVEREST II REALISM), which included a high-risk and a non-high-risk arm, was conducted. For inclusion in the EVEREST II HRR, patients were considered high surgical risk if either their STS predicted operative mortality risk was 12% or higher or the surgeon investigator determined the patient to be high risk (≥12% predicted operative mortality risk) due to the presence of 1 of several prespecified risk factors. (9) Patients were excluded from the registry if they had left ventricular ejection fraction (LVEF) less than 20%, left ventricular end-systolic diameter (LVESD) greater than 60 mm, MV orifice area less than 4 cm (2), or leaflet anatomy that might preclude MitraClip device implantation and/or proper MitraClip device positioning and/or sufficient reduction in MR. The REALISM registry high-risk arm had the same inclusion criteria as the EVEREST II HRR.

In 2014, Lim et al. published outcomes from transcatheter MV repair with MitraClip among high surgical risk patients with DMR who were included in the EVEREST II HRR and REALISM registries. (14) For this analysis, prohibitive risk for surgical repair of DMR was defined as the presence of 1 or more of the following documented surgical risk factors: STS Risk Calculator predicted risk of 30-day mortality for MV replacement of 8% or greater, porcelain aorta or extensively calcified ascending aorta, frailty (assessed by ≥2 indices), hostile chest, severe liver disease or cirrhosis, severe pulmonary hypertension, severe pulmonary hypertension, or an “unusual extenuating circumstance” (e.g., RV dysfunction with severe tricuspid regurgitation, chemotherapy for malignancy, major bleeding diathesis, AIDS, severe dementia). One hundred forty-one patients with severe (≥3+) DMR who met the definition of prohibitive surgical risk were identified, 127 of whom had follow-up data available at 1 year. Of these, 25 patients were from the EVEREST II HRR, 98 were from the high-risk arm of the EVEREST REALISM study, and 4 were treated under compassionate use and met the definition of prohibitive risk and all MV anatomic criteria for entry. At baseline, patients had poor functional status, with 87% in NYHA functional status class III/IV.

MitraClip was successfully placed in 95.3% of patients. Thirty-day and 12-month mortality rates were 6.3% and 23.6%, respectively. MitraClip reduced MR to grade 2+ or less in 86.1% of patients with baseline MR of 3+ and in 68.4% of patients with baseline MR of 4+. Fifty-eight percent of patients with 3+ MR at baseline and 36.8% of patients with 4+ MR at baseline had MR reduced to 1+. Of 91 patients who had procedural reduction of MR to grade 2+ or less, 64 patients (70.3%) had sustained MR 2+ or less at 1 year, 10 (11.0%) experienced worsening MR to 3+ or 4+, and 17 (18.7%) died. Of 59 patients who had a procedural reduction of MR to grade 1 or less, 21 patients (35.6%) had sustained MR of 1+ or less at 1 year, 20 (33.9%) had an increase in MR grade to 2+, 8 (13.6%) had an increase in MR grade to 3+ or 4+, and 10 (16.9%) died. There were no significant differences in 12-month survival between those who were discharged with an MR grade of 1+ or less compared with those with an MR grade of 2+. At 1 year, 30.6% of the 98 patients with baseline NYHA functional class III or IV had an improvement of at least 2 classes. In this high surgical risk population, MitraClip use was associated with a relatively low rate of procedural complications and a high rate of short-term improvements in MR grade to 2+ or less, along with improvements in functional status. However, a major limitation of this trial is the lack of a control group. In addition, the cohort of high-risk patients with DMR was retrospectively identified, so all analyses were post hoc. There are questions about the validity of combining registry data from 2 separate registries that were collected over different time periods, along with the consistency of the inclusion criteria measures, because the STS Risk Calculator changed over time.

In 2014, Glower et al. reported 12-month results for MitraClip use in the first 351 patients enrolled in either the Everest HRR (N=78) or high-risk patients in the REALISM study (n=273), which had previously been presented to FDA. (24) Seventy percent of patients had FMR. Following MitraClip implantation, 325 patients (86%) had MR reduced 2+ or less. At 12 months, 225 patients (84%) had MR of 2+ or less. By Kaplan- Meier analysis, survival at 12 months was 77.2%. Patients had improvements in quality of life scores and NYHA functional class. An earlier (2012) analysis of 78 EVEREST II HRR study subjects with high surgical risk, who were compared with a historical cohort of high surgical risk patients who did not receive MitraClip, was published Whitlow et al.19 MitraClip was successfully placed in 76 patients, of whom 62 (79.5%) achieved at least a 1-grade reduction in MR and 56 (71.8%) had reduction in MR grade to 2+ or less.

Other Nonrandomized Comparative Studies

Swaans et al. reported results of a study comparing survival for MR patients considered at high surgical risk who underwent MitraClip placement with high-risk patients who had conservative management and with patients who had surgical repair. (25) MitraClip-treated patients (n=139) included those treated at a single institution with MitraClip for symptomatic MR whose high surgical risk was based on a logistic EuroSCORE of at least 20, or who were denied surgery based on additional factors associated with increased mortality, as judged by the heart team. These patients were compared with a retrospectively defined cohort of patients with MR and indications for MV repair treated at the same institution in the 2 years prior to MitraClip availability who were treated with either conservative management (n=59) or open surgery (n=38). At baseline, patients treated with MitraClip had a higher logistic EuroSCORE than the other 2 groups (23.9 with MitraClip verses (vs) 14.2 with surgical repair vs 18.7 with conservative treatment; p<0.001). Rates of coronary artery disease and previous coronary artery bypass grafting were higher in the MitraClip group as well. At 1-year follow-up, survival rates were 85.8%, 82.2%, and 67.75% in the MitraClip, open surgery, and conservatively treated groups, respectively. Survival rates for the transcatheter MV repair group were 75.5% and 62.3% after 2 and 3 years, respectively.

Noncomparative Cohort Studies

Since the publication of the Munkholm-Larsen meta-analysis, several non-comparative studies of the use of MitraClip in high surgical risk patients have been published. Most studies included a mix of patients with DMR and FMR, but 1 study Reichenspurner et al. (15) included only patients with DMR and reported outcomes for patients at high risk for surgery. Taramasso et al. (26) included only patients with DMR and reported outcomes for inoperable patients and those considered high risk for surgery. Another cohort study, Estévez-Loureiro et al., (16) reported results separately for patients with DMR considered to be at high surgical risk. Some of the representative non-comparative cohort studies with a focus on patients at high or prohibitive risk are described below.

In 2014, Taramasso et al. retrospectively reported midterm outcomes for 48 patients with DMR who were either elderly or considered high risk who underwent transcatheter MV repair at a single center. (26) The mean logistic EuroSCORE at baseline was 15.7; the mean STS score was 12%. Of all patients, 40% had a baseline logistic EuroSCORE of 20% or greater and 45.5% had an STS score of 10% or greater. Implantation was successful in 98% of patients. Thirty-day mortality was 2% (n=1). There was no incidence of acute MI, stroke, major vascular complication, or cardiac tamponade at 30 days. With a median follow-up of 16 months, the overall actuarial survival was 89% and 70.2% at 1 and 2 years, respectively. One patient required open MV surgery and 1 patient underwent repeat transcatheter MV repair. Freedom from 3+ or greater MR was 80% and 76.6% at 1 and 2 years, respectively.

Reichenspurner et al. reported procedural and acute safety results at 30 days and survival results at 12 months for patients with DMR enrolled in the ACCESS-EU study, a European prospective nonrandomized postapproval study of MitraClip therapy. (15) The authors included 117 patients with DMR (20.6% of the ACCESS-EU cohort at the time of analysis), all of whom had either symptomatic MR or, if asymptomatic, 3+ or 4+ MR, and underwent transcatheter MV repair with MitraClip from October 2008 to April 2011. Outcomes were analyzed for the entire DMR cohort and stratified for low-risk and high-risk surgical patients (logistic EuroSCORE l <20% or >20%, respectively). Of the 106 patients successfully implanted with a MitraClip device and with information on baseline MR severity and hospital discharge, 88.7% (94/106) had an MR reduction to grade 2+ or lower. Fifty-six percent had reduction to grade 1+ or lower. Thirty-day mortality was 6.0% (7/117) for the entire DMR cohort; 30-day mortality was 9.1% (3/33) for high-risk subgroup patients and 4.8% (4/84) for low-risk subgroup patients. Echocardiographic follow-up data were available for 71 patients at 12 months. The rate of freedom of recurrent/persistent MR greater than grade 3+ was 74.6%, with no statistically significant differences between high- and low-risk subgroups. Most patients (68%) improved by at least 1 NYHA functional class. By 12 months, 13 patients required repeat MV interventions, including MV surgery in 9 cases and a repeat MitraClip placement in 4 cases.

In 2013, Estévez-Loureiro et al. reported outcomes for 173 patients who received MitraClip, 79 of whom had DMR and were judged to be high surgical risk. (16) Procedural success occurred in 76 patients (96.2% of those with DMR), and most patients had improvement in MR severity. Six-month follow-up data were available for 60 patients, in whom all-cause mortality was 8.3%.

Other cohort and registry studies report high rates of reduction in MR to grade 2+ or lower. These studies include Baldus et al. (2012), (27) which included 486 patients with DMR or FMR, Divchev et al (2012), (28) which included 33 patients with DMR or FMR who were not surgical candidates, and Armoiry et al. (2013), (29) which included 62 patients who were inoperable or at high surgical risk.

Section Summary: MitraClip in Prohibitive Surgical Risk Candidates

The evidence for the use of MitraClip among patients who are not considered surgical candidates consists primarily of non-comparative cohort studies. In general, these studies demonstrate that MitraClip implantation is feasible and reasonably safe and associated with high rates (on the order of at least 70% to 90%) of short-term reductions in MR grade to 2+ or lower. In addition, heart failure-related symptoms and quality of life have been shown to improve. Without intervention, symptomatic MR is likely to worsen. However, the natural history of DMR and FMR in patients with characteristics similar to those who underwent MitraClip placement are not clearly defined, which limits conclusions drawn about the net health outcomes of MitraClip in patients who are not surgical candidates.

MitraClip in Surgical Candidates

Percutaneous repair of MR with MitraClip has been compared with open surgical repair in patients who are considered surgical candidates. Studies pertaining to this indication include 1 RCT, multiple nonrandomized comparative studies, and multiple non-comparative studies. Similar to studies of nonsurgical candidates, many evaluations of MitraClip among surgical candidates include mixed populations of FMR and DMR patients.

EVEREST II RCT

The EVEREST II RCT was a pivotal multicenter trial designed to evaluate the efficacy of transcatheter MV repair with MitraClip compared with open MV repair. (22,23) Eligible patients had grade 3+ or 4+ MR and were all candidates for MV repair surgery. Symptomatic patients were required to have LVEF of more than 25% and a LVESD of 55 mm or less; asymptomatic patients were required to have at least 1 of the following: LVEF of 25% to 60%; LVESD of 40 to 55 mm; new atrial fibrillation; or pulmonary hypertension. Patients were excluded if they had an MV orifice area less than 4.0 cm or leaflet anatomy that precluded MitraClip device implantation, proper MitraClip positioning, or sufficient reduction in MR. Two hundred seventy-nine patients were randomized 2:1 to transcatheter repair (184 patients) or standard MV surgery (95 patients). The composite primary safety end point was major adverse events at 30 days, defined as freedom from death, myocardial infarction, nonelective cardiac surgery for adverse events, renal failure, transfusion of 2 or more units of blood, reoperation for failed surgery, stroke, gastrointestinal complications requiring surgery, ventilation for 48 or more hours, deep wound infection, septicemia, and new onset of permanent atrial fibrillation. The composite primary efficacy end point was freedom from MR at 2+ or higher, freedom from cardiac surgery for valve dysfunction, and survival beyond 12 months.

MitraClip was considered to have acute procedural success if the clip deployed and MR was reduced to less than 3+. The protocol’s safety and efficacy analyses were reported on both an intention-to-treat (ITT) and a per-protocol basis. In the ITT analyses presented in the main article, crossover to surgery in the immediate postprocedure period if MitraClip failed to adequately reduce MR was considered a successful treatment strategy. Thus, in the ITT analysis, for patients who did not have acute procedural success (and may have undergone open MV repair), the efficacy end point was considered met for MitraClip group subjects if they were free from death, reoperation for MR, and MR greater than 2+ at 12 months. For patients who did have acute procedural success, the efficacy end point was considered met for MitraClip group subjects if they were free from death, any MV surgery for MR, and MR greater than 2+ at 12 months. The study had a predetermined efficacy end point of noninferiority of the MitraClip strategy, with a margin of 25% for the ITT analysis and 31% for prespecified per-protocol analyses. This implies that the MitraClip strategy is non-inferior to surgery at 12 months if the rate of the primary efficacy end point for the MitraClip group is not more than 25 percentage points less than that in the surgery group (for the ITT analysis).

The treatment groups were generally similar, except that a higher proportion of those in the MitraClip group had congestive heart failure (91% [167/184] vs 78% [74/95], p=0.005). Of 178 patients who were randomized to the MitraClip group and who did not withdraw from the study, 41 (23%) had grade 3+ or 4+ MR before hospital discharge and were referred for immediate surgery, which was performed in 28. On an ITT basis, the study’s primary combined efficacy end point (rates of freedom from death, MV surgery, and grade 3+/4+ MR at 12 months), was 55% in the MitraClip group and 73% in the surgery group (noninferiority, p=0.007). Rates of death and grade 3+ or 4+ MR at 12 months postprocedure were similar between groups; however, MitraClip group subjects were more likely to require surgery for MV dysfunction, either immediately post-MitraClip implantation or in the 12 months following. Twenty percent (37/181) of the MitraClip group and 2% (2/89) of the surgery group required reoperation for MV dysfunction (p<0.001). Although in the ITT analysis rates of grade 3+ or 4+ MR at 12 months were similar between groups, in the study’s per-protocol analysis patients in the MitraClip group were more likely to have grade 3+ or 4+ MR (17.2% [23/134] vs 4.1% [3/74], p=0.01), which suggests that a larger proportion of patients with grade 1+ or 2+ MR in the MitraClip group had had surgical repair.

Rates of major adverse events at 30 days were lower in the MitraClip group than in the surgery group (15% [27/181] vs 48% [45/89], p<0.001). Rates of transfusion of more than 2 units of blood were the largest component of major adverse events in both groups, occurring in 13% (24/181) of the MitraClip group and 45% (42/89, p<0.001) of the surgery group. In subgroup analysis, there was significant subgroup interaction between those with FMR and those with DMR (p=0.02), in which patients with DMR had more favorable rates of the primary efficacy end point with surgery.

In 2013, Mauri et al. reported 4-year follow-up results for patients enrolled in the EVEREST II trial. (30) Of patients randomized to the percutaneous repair group, 161 (88%) were included in the 4-year efficacy analysis; of those in the surgery group, 73 (77%) were included in the 4-year efficacy analysis. The study evaluated several end points, including freedom from death, surgery for MV dysfunction, and 3+ and 4+ MR at 4 years; freedom from surgery for MV dysfunction; and freedom from death. The authors also evaluated interactions between treatment groups and 2 additional variables: age 70 years or older and FMR (vs DMR). At 4 years, 39.8% of those in the MitraClip group (64/161) achieved the primary efficacy end point of freedom from death, freedom from surgery for MV dysfunction, and freedom from 3+ or 4+ MR, compared with 53.4% (39/73) of the surgical group (p=0.070). However, significantly more MitraClip patients required surgery for MV dysfunction during the follow-up period (24.85 [40/161] in the MitraClip group vs 5.5% [4/73], p<0.001); in the MitraClip group, most of the MV surgery occurred before 12 months. Tests of interaction between age and MR etiology were significant. Among those younger than 70, the difference between rates of the primary efficacy end point between the MitraClip and surgery groups was -28.5% (favoring surgery; 95% confidence interval [CI], -46% to -10.5%). Among those 70 or older, this difference was 3.3% (favoring MitraClip; 95% CI, -16.4 to 23.0). Among those with DMR, the difference in rates of the primary efficacy end point between the MitraClip and surgery groups was -24.85 (favoring surgery; 95% CI, -40.5 to -9.1). Among those with FMR, this difference was 11.4% (favoring MitraClip; 95% CI, -11.1% to 33.8%). These results suggest that outcomes following MitraClip and surgical repair for MR are similar at 4-year follow-up as they are at 1-year follow-up.

In 2012, Glower et al., in a follow-up analysis of the EVEREST II study population, evaluated differences in subsequent surgical MV replacement between the MitraClip and the open surgery groups. (31) In the year following enrollment, 37 of 178 (21%) of MitraClip patients underwent MV surgery, of whom 54% underwent MV repair (vs replacement). The number of MitraClip devices implanted (17 with no clip, 7 with 1 clip, 13 with 2 clips) was not associated with the likelihood of MV replacement (p=0.12). In the group randomized to surgery, 67 of 80 patients (84%) underwent MV repair surgery during the year following enrollment. The authors assessed characteristics predictive of MR repair versus replacement, and demonstrated that baseline characteristics, including age, etiology of the MR, prior cardiac surgery, and anterior/bilateral leaflet pathology, were not significantly associated with MR correction method (p=0.47). Of the 37 cases of MV surgery after MitraClip placement, 11 cases (30%) reported valve injury by the surgeon, although the surgical repair rate in patients who were noted to have MV injury did not significantly differ from the remaining patients who had MV surgery after MitraClip placement (54% in the valve injury group vs 58% in the remainder, p=0.95). This study suggests that MitraClip therapy is not associated with subsequent surgical MV replacement (vs repair).

Nonrandomized Comparative Studies: MitraClip versus Surgical Repair

A number of retrospective cohort studies have compared outcomes for MR treated with either surgical or transcatheter MV repair using the MitraClip device (Conradi et al. [2013], [32] Taramasso et al. [2012], [33] Paranskaya et al. [2013], [34]). Two studies (Conradi et al, [32] Taramasso et al. [33]) included patients with only FMR, while Paranskaya et al. (34) reported results for a mixed DMR and FMR cohort.

The 4 studies comparing MitraClip with surgery outlined earlier (Feldman et al, Conradi et al., Taramasso et al., Paranskaya et al.) were summarized in a systematic review and meta-analysis by Wan et al. in 2013. (35) Across all studies, age was significantly higher in groups receiving MitraClip than those receiving surgery (weighted mean difference [WMD], 7.22; 95% CI, 1.75 to 12.70; p=0.01). In the 3 studies that reported logistic EuroSCORE, scores were significantly higher in the MitraClip group (WMD=14.25; 95% CI, 7.72 to 20.79; p<0.001). The proportion of patients with residual MR greater than grade 2 was significantly higher in the MitraClip group (17.2% vs 0.45%; odds radio [OR], 20.72; 95% CI, 4.91 to 87.44; p<0.001). Thirty-day mortality, rates of NYHA functional class III or IV at 12 months, and 12-month mortality did not differ significantly between the MitraClip and the surgical groups. Overall, this study suggested that, despite baseline higher age and surgical risk, patients receiving MitraClip for MR have mortality and functional outcomes comparable to those receiving open surgery, but have higher rates of persistent MR. However, as the authors noted, the conclusions were limited by lack of subgroup analyses comparing outcomes for those with DMR and FMR and lack of consistent definitions of success across studies.

Non-comparative Studies Evaluating MitraClip in Surgical Candidates

There have been numerous non-comparative studies of surgical candidates for MitraClip. (17,36-40) In addition, a number of non-comparative studies have reported on use of MitraClip in unselected patients, including those with DMR and FMR without surgical risk criteria. (41,42) However, these studies offer little relevant evidence on the comparative efficacy of MitraClip versus surgery and, therefore, will not be reviewed further here.

Section Summary: MitraClip in Surgical Candidates

The evidence related to use of MitraClip among patients who are surgical candidates consists of 1 RCT (EVEREST II), along with multiple nonrandomized comparative studies and non-comparative cohort studies and case series. The most direct evidence related to the efficacy of MitraClip comes from the EVEREST II trial, which demonstrated noninferiority of MitraClip to open surgery for safety and effectiveness among patients who are surgical candidates for MR repair. Major strengths of this study include its multicenter, randomized design. Limitations include higher dropout rates in the surgery group, the use of a relatively wide definition of successful reduction (≤2+, rather than to 1+), and a broad margin for noninferiority (25 percentage points). About 20% of patients who received MitraClip required reoperation for persistent MV dysfunction, and the study’s per-protocol subanalysis suggests that a larger proportion of patients with grade 1+ or 2+ MR at 12-month follow-up who were analyzed in the MitraClip group had undergone surgical repair. Overall, the RCT and cohort study evidence suggests that patients who have persistent MV dysfunction after MitraClip typically develop it within the first year postprocedure.

Outcomes for MitraClip for Degenerative Versus Functional MR

MitraClip currently has FDA approval for patients with DMR. Limited evidence exists on differences in outcomes between FMR and DMR patients. Subanalyses from EVEREST II suggest that DMR patients may demonstrate greater benefit from surgical repair.

Braun et al prospectively compared MitraClip placement outcomes for DMR and FMR in a cohort of 117 patients with symptomatic MR. (43) Patients were at high risk for open surgery or declined open surgery. At baseline, the 72 patients with DMR differed from the 47 with FMR. The DMR group had a higher proportion of NYHA functional class greater than II, higher end-diastolic and end-systolic volumes, lower ejection fraction, and a higher incidence of comorbidities. Successful MR reduction by at least 1 grade occurred in 83.3% (60/72) of DMR patients and 89.4% (42/47) of FMR patients (p=0.42). For the study’s primary composite efficacy end point (freedom from MR grade 3+ or 4+, reintervention for MV dysfunction, and death 12 months after implantation), rates occurred in 59.7% of the DMR group and 63.8% of the FMR group (p=0.73)

MitraClip Safety

In 2015, Bail et al. reported results of a systematic review and meta-analysis of the safety and efficacy of MitraClip placement, which included 26 studies (3821 patients). (44) Within the first 30 days postprocedure, 3.5% (95% CI, 2.9% to 4.2%) required open MV repair, 18.3% (95% CI 17.0% to 19.6%) experienced an adverse event, and 2.8% (95% CI, 2.3% to 4.4%) died. At 6 months, 4.5% (95% CI, 15.1% to 24.1%) required open MV repair, 18.9% (95% CI, 15.1% to 24.1%) experienced an adverse event, and the all-cause mortality rate was 11.9% (95% CI, 10.3 to 14.2%). By 12 months, 11.4% (95% CI, 9.6% to 13.5%) required open repair, and the all-cause mortality rate was 17.4% (95% CI, 15.1% to 18.9%).

In 2014, Vakil et al. reported results of a systematic review of the safety and efficacy of the MitraClip system for moderate-to-severe or severe FMR or DMR; it included 16 studies (2980 patients). (45) Based on calculated STS score, EuroSCORE, or the surgeon’s discretion, 2689 patients in 14 studies were considered high risk for surgery and 291 patients in 2 studies were considered low risk for surgery. The pooled 30-day mortality rate (primary safety outcome) was 4.2%. During a mean follow-up of 310 days (range, 80 days to 4 years), 387 of 2457 (15.8%) deaths occurred. In the 8 studies reporting the cause of death, the pooled incidence of cardiac mortality was 3.7%.

In 2015, Eggebrecht et al. (46) summarized complication rates after transcatheter MV repair using data from the German TRAMI registry (initially described above by Baldus et al.). (27) At the time of publication, 828 patients were included in the registry, 70% of whom had FMR. During the in-hospital period, major adverse cardiac and cerebrovascular events (including in-hospital death, stroke, or MI) occurred in 21 of 780 (2.7%). Severe in-hospital complications occurred in 106 of 828 (12.8%), most commonly major bleeding requiring transfusion (7.4%) and respiratory failure requiring reintubation (2.0%). Compared with patients who had no complications, patients with procedural complications were more likely to have DMR (36.3% vs 24.8%; p<0.01) and were less likely to have FMR (64.5% vs 72.3%; p<0.05).

Iatrogenic atrial septal defect, related to the required route to access the left heart, has been noted with MitraClip. (47)

Other Transcatheter MV Repair Devices

Several devices other than MitraClip are being investigated for transcatheter MV repair, although none is FDA approved for use in the U.S.

Several indirect annuloplasty devices, the Carillon® Mitral Contour System™ (Cardiac Dimension, Kirkland, WA) and the Monarc device (Edwards Lifesciences, Irvine, CA), have been evaluated. A case series evaluating use of the Carillon device in 53 patients with 2+ FMR at 7 European centers was reported in 2012. (10) Of the 53 patients who underwent attempted device implantation, 36 underwent permanent implantation and 17 had the device recaptured due to transient coronary compromise in 8 patients and less than 1 grade of FMR reduction in 9 patients. Echocardiographic measures of FMR improved in the implanted groups up through 12-month follow-up, along with improvements in 6-minute walk distance. An earlier feasibility study of the Carillon device in 48 patients with moderate-to-severe FMR demonstrated successful device placement in 30 patients, with 18 patients unable to be implanted due to access issues, insufficient acute FMR reduction, or coronary artery compromise. (48) The Monarc device has been evaluated in a phase 1 safety trial at 8 European centers. (11) Among 72 patients enrolled, the device was successfully implanted in 59 patients (82%). The primary safety end point (freedom from death, tamponade, or myocardial infarction at 30 days) was met in 91% of patients at 30 days and in 82% at 1 year.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this review are listed in Table 2.

Table 2. Summary of Key Trials

NCT No.

Trial Name

Planned Enrollment

Completion Date

Ongoing

NCT01920698

Multicentre Randomized Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR).

288

Oct 2017

NCT01626079a

Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation.

420

Aug 2020

Unpublished

NCT01772108a

A Randomized Study of the MitraClip Device in Heart Failure Patients With Clinically Significant Functional Mitral Regurgitation.

42

Terminated (enrollment)

NCT: national clinical trial.

a Denotes industry-sponsored or cosponsored trial.

Summary of Evidence

The evidence for the use of MitraClip in patients with severe symptomatic DMR or FMR who are considered at prohibitive risk for open surgery includes single-arm cohort studies. Relevant outcomes are overall survival, morbid events, functional outcomes, and treatment related morbidity. The available single-arm cohort studies include the pivotal EVEREST II High Risk Registry (HRR) study and the EVEREST II Real World Expanded Multi-center Study of the MitraClip System (REALISM). These studies demonstrate that MitraClip implantation is feasible, with high rates (on the order of at least 70% to 90%) of short-term reductions in MR grade to 2+ or less, and has a reasonable safety profile. However, the lack of concurrent control groups makes it difficult to draw conclusions about whether there is a net health benefit compared with alternative therapies in this population. The body of evidence consists of single-arm studies, even though there are no strong barriers to controlled trials that compare MitraClip with continued medical management. The evidence is insufficient to determine the effects of the technology on health outcomes.

The evidence for the use of MitraClip in patients with DMR or FMR who are considered candidates for open MV repair surgery includes 1 RCT (EVEREST II) and multiple comparative and non-comparative cohort studies. Relevant outcomes are overall survival, morbid events, functional outcomes, and treatment-related morbidity. The most rigorous evidence related to MitraClip’s efficacy is from the EVEREST II RCT, which demonstrated noninferiority to open surgery for safety and effectiveness. About 20% of patients who received MitraClip required reoperation for persistent MV dysfunction, and the study’s per-protocol subanalysis suggests that a larger proportion of patients with grade 1+ or 2+ MR at 12-month follow-up in the MitraClip group had undergone surgical repair. Overall, the RCT and cohort study evidence suggests that the device is associated with lower rates of major complications than open repair and that results are durable for patients who remain free of recurrent or persistent MR after the first year. However, this trial has some methodologic limitations. The noninferiority margin of 25% was large, indicating that MitraClip could be somewhat inferior to surgery and the noninferiority margin still met. Crossover to surgery was allowed for patients who had 3+ or more MR prior to discharge, and 23% of patients assigned to MitraClip met this criterion. This large rate of crossover would bias results toward the null on intention-to-treat analysis, thus increasing the likelihood of meeting the noninferiority margin. In an analysis by treatment received, this crossover would result in a less severely ill population in the MitraClip group and bias the results in favor of MitraClip. A high proportion of patients required open MV replacement or repair during the first year postprocedure, thus limiting the number of patients who had long-term success without surgical intervention. As a result of these factors, this single trial is not definitive in demonstrating improved clinical outcomes with MitraClip compared with surgery and further RCTs are needed to corroborate these results. In addition, the most appropriate population of patients in terms of MR etiology for MitraClip therapy (FMR vs DMR) has not been well-established. The evidence is insufficient to determine the effects of the technology on health outcomes.

The evidence for the use of transcatheter mitral valve repair devices other than the MitraClip for patients with MR includes primarily non-comparative feasibility studies. Relevant outcomes are overall survival, morbid events, functional outcomes, and treatment-related morbidity. The body of evidence consists only of very small case series and case reports. The evidence is insufficient to determine the effects of the technology on health outcomes. There is insufficient evidence in the clinical literature demonstrating the long-term efficacy of coronary sinus annuloplasty devices for treating MR. Further results from prospective, randomized controlled trials are needed to determine the safety and efficacy for the procedure.

In 2015, Blue Cross Blue Shield Association received input from 4 academic medical centers, one of which provided 4 responses, for a total of 7 responses. The input supported the use of transcatheter MV repair in patients with DMR at prohibitive risk of open surgery. The greatest consensus for selection criteria to determine “prohibitive risk” was for the use of the Society of Thoracic Surgeons predictive operative risk of 12% or higher, or a logistic EuroSCORE of 20% or higher.

Practice Guidelines and Position Statements

American College of Cardiology and American Heart Association

The American College of Cardiology (ACC) and American Heart Association released guidelines on the management of valvular heart disease in 2014. (49) The guidelines include the following class IIB recommendation related to the use of transcatheter MV repair for MR:

Transcatheter mitral valve repair may be considered for severely symptomatic patients (NYHA [New York Heart Association] class III to IV) with chronic severe primary MR (stage D) who have favorable anatomy for the repair procedure and a reasonable life expectancy but who have a prohibitive surgical risk because of severe comorbidities and remain severely symptomatic despite optimal guideline-directed medical therapy for heart failure. (Level of Evidence: B.)

American College of Cardiology, American Association for Thoracic Surgery, et al.

The ACC, American Association for Thoracic Surgery, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons released a position statement on transcatheter therapies for MR in 2014. (50) This statement outlines critical components for successful transcatheter MR therapies and recommends ongoing research and inclusion of all patients treated with transcatheter MR therapies in a disease registry.

European Society of Cardiology and European Association for Cardio-Thoracic Surgery

In 2012, the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery released guidelines on the management of valvular heart disease. (51) These guidelines do not address transcatheter MV repair.

National Institute for Health and Care Excellence (NICE)

The 2010 NICE guidance document states that current evidence on the safety and efficacy of percutaneous mitral valve annuloplasty is inadequate in quality and quantity. Therefore, this procedure should only be used in the context of research, which should clearly describe patient selection, concomitant medical therapies and safety outcomes. Both objective measurements and clinical outcomes should be reported. (52)

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

33418, 33419, 0345T

HCPCS Codes

None

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does have a national Medicare coverage position.

A national coverage position for Medicare may have been changed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1. Chiam PT, Ruiz CE. Percutaneous transcatheter mitral valve repair: a classification of the technology. JACC Cardiovasc Interv. Jan 2011; 4(1):1-13. PMID 21251623.

2. Fedak PWM, McCarthy PM, Bonow RO. Evolving concepts and technologies in mitral valve repair. Circulation. February 19, 2008 2008; 117(7):963-974.

3. Bonow RO, Carabello BA, Chatterjee K, et al. 2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients with valvular heart disease). Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. Sep 23 2008; 52(13):e1-142. PMID 18848134.

4. Carabello BA. The current therapy for mitral regurgitation. J Am Coll Cardiol. Jul 29 2008; 52(5):319-326. PMID 18652937.

5. De Bonis M, Lapenna E, Alfieri O. Edge-to-edge Alfieri technique for mitral valve repair: which indications? Curr Opin Cardiol. Mar 2013; 28(2):152-157. PMID 23147777.

6. Mirabel M, Iung B, Baron G, et al. What are the characteristics of patients with severe, symptomatic, mitral regurgitation who are denied surgery? Eur Heart J. Jun 2007; 28(11):1358-1365. PMID 17350971.

7. Goel SS, Bajaj N, Aggarwal B, et al. Prevalence and outcomes of unoperated patients with severe symptomatic mitral regurgitation and heart failure: comprehensive analysis to determine the potential role of MitraClip for this unmet need. J Am Coll Cardiol. Jan 21 2014; 63(2):185-186. PMID 24036029.

8. Young A, Feldman T. Percutaneous mitral valve repair. Curr Cardiol Rep. Jan 2014; 16(1):443. PMID 24281977.

9. Minha S, Torguson R, Waksman R. Overview of the 2013 Food and Drug Administration Circulatory System Devices Panel meeting on the MitraClip Delivery System. Circulation. Aug 20 2013; 128(8):864-868. PMID 23960257.

10. Siminiak T, Wu JC, Haude M, et al. Treatment of functional mitral regurgitation by percutaneous annuloplasty: results of the TITAN Trial. Eur J Heart Fail. Aug 012; 14(8):931-938. PMID 22613584.

11. Harnek J, Webb JG, Kuck KH, et al. Transcatheter implantation of the MONARC coronary sinus device for mitral regurgitation: 1-year results from the EVOLUTION phase I study (Clinical Evaluation of the Edwards Lifesciences Percutaneous Mitral Annuloplasty System for the Treatment of Mitral Regurgitation). JACC Cardiovasc Interv. Jan 2011; 4(1):115-122. PMID 21251638.

12. U.S.Food and Drug Administration (FDA). Summary of Safety and Effectiveness Data: Mitral Valve Repair Device. 2013; <http://www.accessdata.fda.gov> Accessed October 26, 2015.

13. Percutaneous mitral valve repair. Chicago, Illinois Blue Cross Blue Shield Association Technology Evaluation Criteria Assessments 2014; 29(Tab TBA).

14. Lim DS, Reynolds MR, Feldman T, et al. Improved functional status and quality of life in prohibitive surgical risk patients with degenerative mitral regurgitation after transcatheter mitral valve repair. J Am Coll Cardiol. Jul 15 2014; 64(2):182-192. PMID 24184254

15. Reichenspurner H, Schillinger W, Baldus S, et al. Clinical outcomes through 12 months in patients with degenerative mitral regurgitation treated with the MitraClip(R) device in the ACCESS-EUrope Phase I trial. Eur J Cardiothorac Surg. Oct 2013; 44(4):e280-288. PMID 23864216.

16. Estévez-Loureiro R, Franzen O, Winter R, et al. Echocardiographic and clinical outcomes of central versus noncentral percutaneous edge-to-edge repair of degenerative mitral regurgitation. J Am Coll Cardiol. Dec 24 2013; 62(25):2370-2377. PMID 24013059.

17. Grasso C, Capodanno D, Scandura S, et al. One- and twelve-month safety and efficacy outcomes of patients undergoing edge-to-edge percutaneous mitral valve repair (from the GRASP Registry). Am J Cardiol. May 15 2013; 111(10):1482-1487. PMID 23433761.

18. Chan PH, She HL, Alegria-Barrero E, et al. Real-world experience of MitraClip for treatment of severe mitral regurgitation. Circ J. 2012; 76(10):2488-2493. PMID 22785461.

19. Whitlow PL, Feldman T, Pedersen WR, et al. Acute and 12-month results with catheter-based mitral valve leaflet repair: the EVEREST II (Endovascular Valve Edge-to-Edge Repair) High Risk Study. J Am Coll Cardiol. Jan 10 2012; 59(2):130-139. PMID 22222076.

20. Philip F, Athappan G, Tuzcu EM, et al. MitraClip for severe symptomatic mitral regurgitation in patients at high surgical risk: a comprehensive systematic review. Catheter Cardiovasc Interv. Oct 1 2014; 84(4):581-590. PMID 24905665.

21. Munkholm-Larsen S, Wan B, Tian DH, et al. A systematic review on the safety and efficacy of percutaneous edge-to-edge mitral valve repair with the MitraClip system for high surgical risk candidates. Heart. Mar 2014; 100(6):473-478. PMID 23813844.

22. Feldman T, Foster E, Glower DD, et al. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med.Apr 14 2011; 364(15):1395-1406. PMID 21463154.

23. Mauri L, Garg P, Massaro JM, et al. The EVEREST II Trial: design and rationale for a randomized study of the evalve mitraclip system compared with mitral valve surgery for mitral regurgitation. Am Heart J. Jul 2010; 60(1):23-29. PMID 20598968.

24. Glower DD, Kar S, Trento A, et al. Percutaneous mitral valve repair for mitral regurgitation in high-risk patients: results of the EVEREST II study. J Am Coll Cardiol. Jul 15 2014; 64(2):172-181. PMID 25011722.

25. Swaans MJ, Bakker AL, Alipour A, et al. Survival of transcatheter mitral valve repair compared with surgical and conservative treatment in high-surgical-risk patients. JACC Cardiovasc Interv. Aug 2014; 7(8):875-881. PMID 25147032.

26. Taramasso M, Maisano F, Denti P, et al. Percutaneous edge-to-edge repair in high-risk and elderly patients with degenerative mitral regurgitation: midterm outcomes in a single-center experience. J Thorac Cardiovasc Surg. Dec 2014; 148(6):2743-2750. PMID 24768099.

27. Baldus S, Schillinger W, Franzen O, et al. MitraClip therapy in daily clinical practice: initial results from the German transcatheter mitral valve interventions (TRAMI) registry. Eur J Heart Fail. Sep 2012; 14(9):1050-1055.PMID 22685268.

28. Divchev D, Kische S, Paranskaya L, et al. In-hospital outcome of patients with severe mitral valve regurgitation classified as inoperable and treated with the MitraClip(R) device. J Interv Cardiol. Apr 2012; 25(2):180-189. PMID 22188385.

29. Armoiry X, Brochet E, Lefevre T, et al. Initial French experience of percutaneous mitral valve repair with the MitraClip: a multicentre national registry. Arch Cardiovasc Dis. May 2013; 106(5):287-294. PMID 23769403.

30. Mauri L, Foster E, Glower DD, et al. 4-year results of a randomized controlled trial of percutaneous repair versus surgery for mitral regurgitation. J Am Coll Cardiol. Jul 23 2013;62(4):317-328. PMID 23665364

31. Glower D, Ailawadi G, Argenziano M, et al. EVEREST II randomized clinical trial: predictors of mitral valve replacement in de novo surgery or after the MitraClip procedure. J Thorac Cardiovasc Surg. Apr 2012; 143(4 Suppl):S60-63. PMID 22423604.

32. Conradi L, Treede H, Rudolph V, et al. Surgical or percutaneous mitral valve repair for secondary mitral regurgitation: comparison of patient characteristics and clinical outcomes. Eur J Cardiothorac Surg. Sep 2013; 44(3):490-496; discussion 496. PMID 23401496.

33. Taramasso M, Denti P, Buzzatti N, et al. Mitraclip therapy and surgical mitral repair in patients with moderate to severe left ventricular failure causing functional mitral regurgitation: a single-centre experience. Eur J Cardiothorac Surg. Dec 2012; 42(6):920-926. PMID 22961958.

34. Paranskaya L, D'Ancona G, Bozdag-Turan I, et al. Percutaneous vs surgical repair of mitral valve regurgitation: single institution early and midterm outcomes. Can J Cardiol. Apr 2013; 29(4):452-459. PMID 22926038.

35. Wan B, Rahnavardi M, Tian DH, et al. A meta-analysis of MitraClip system versus surgery for treatment of severe mitral regurgitation. Ann Cardiothorac Surg. Nov 2013; 2(6):683-692. PMID 24349969.

36. Maisano F, Franzen O, Baldus S, et al. Percutaneous mitral valve interventions in the real world: early and 1- year results from the ACCESS-EU, a prospective, multicenter, nonrandomized post-approval study of the MitraClip therapy in Europe. J Am Coll Cardiol. Sep 17 2013; 62(12):1052-1061. PMID 23747789.

37. Franzen O, Baldus S, Rudolph V, et al. Acute outcomes of MitraClip therapy for mitral regurgitation in highsurgical- risk patients: emphasis on adverse valve morphology and severe left ventricular dysfunction. Eur Heart J. Jun 2010; 31(11):1373-1381. PMID 20219746.

38. Foster E, Kwan D, Feldman T, et al. Percutaneous mitral valve repair in the initial EVEREST cohort: evidence of reverse left ventricular remodeling. Circ Cardiovasc Imaging. Jul 2013; 6(4):522-530. PMID 23633132.

39. Geidel S, Schmoeckel M. Impact of failed mitral clipping on subsequent mitral valve operations. Ann Thorac Surg. Jan 2014; 97(1):56-63. PMID 24075487.

40. Feldman T, Wasserman HS, Herrmann HC, et al. Percutaneous mitral valve repair using the edge-to-edge technique: six-month results of the EVEREST Phase I Clinical Trial. J Am Coll Cardiol. Dec 6 2005; 46(11):2134- 2140. PMID 16325053.

41. Nickenig G, Estevez-Loureiro R, Franzen O, et al. Percutaneous mitral valve edge-to-edge repair: in-hospital results and 1-year follow-up of 628 patients of the 2011-2012 Pilot European Sentinel Registry. J Am Coll Cardiol. Sep 2 2014; 64(9):875-884. PMID 25169171.

42. Yeo KK, Yap J, Yamen E, et al. Percutaneous mitral valve repair with the MitraClip: early results from the MitraClip Asia-Pacific Registry (MARS). EuroIntervention. Sep 2014; 10(5):620-625. PMID 24425362.

43. Braun D, Lesevic H, Orban M, et al. Percutaneous edge-to-edge repair of the mitral valve in patients with degenerative vs. functional mitral regurgitation. Catheter Cardiovasc Interv. Dec 10 2013. PMID 24323541.

44. Bail DH. (Meta)-analysis of safety and efficacy following edge-to-edge mitral valve repair using the MitraClip system. J Interv Cardiol. Feb 2015; 28(1):69-75. PMID 25689550.

45. Vakil K, Roukoz H, Sarraf M, et al. Safety and efficacy of the MitraClip(R) system for severe mitral regurgitation: a systematic review. Catheter Cardiovasc Interv. Jul 1 2014; 84(1):129-136. PMID 24323764.

46. Eggebrecht H, Schelle S, Puls M, et al. Risk and outcomes of complications during and after MitraClip implantation: Experience in 828 patients from the German TRAnscatheter mitral valve interventions (TRAMI) registry. Catheter Cardiovasc Interv. Oct 2015; 86(4):728-735. PMID 25601532.

47. Schueler R, Ozturk C, Wedekind JA, et al. Persistence of iatrogenic atrial septal defect after interventional mitral valve repair with the MitraClip system: a note of caution. JACC Cardiovasc Interv. Mar 2015; 8(3):450-459. PMID 25703879.

48. Schofer J, Siminiak T, Haude M, et al. Percutaneous mitral annuloplasty for functional mitral regurgitation: results of the CARILLON Mitral Annuloplasty Device European Union Study. Circulation. Jul 28 2009; 120(4):326-333. PMID 19597051.

49. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. Jun 10 2014; 129(23):2440-2492. PMID 24589852.

50. O'Gara PT, Calhoon JH, Moon MR, et al. Transcatheter therapies for mitral regurgitation: a professional society overview from the American College of Cardiology, The American Association for Thoracic Surgery, Society for Cardiovascular Angiography and Interventions Foundation, and The Society of Thoracic Surgeons. J Thorac Cardiovasc Surg. Mar 2014; 147(3):837-849. PMID 24529172.

51. Authors/Task Force Members, Vahanian A, Alfieri O, et al. Guidelines on the management of valvular heart disease (version 2012): The Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. October 1, 2012 2012; 33(19):2451-2496.

52. National Institute for Health and Care Excellence (NICE). IPG352. Percutaneous mitral valve annuloplasty. July 2010. Available at: <http://www.nice.org.uk> Accessed December 22, 2015.

53. ECRI Institute. Transcatheter mitral valve repair (MitraClip) for treating degenerative mitral regurgitation in patients at high/prohibitive surgical risk. Emerging Technology Evidence Report. 2015 November.

54. Centers for Medicare and Medicaid Services. National Coverage Determination (NCD) for Transcatheter MITRAL Valve Repair (TMVR) (20.33). 2015; <http://www.cms.gov> Accessed June 24, 2015.

55. Transcatheter Mitral Valve Repair. Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual (Oct 2015). Cardiology 2.02.30.

Policy History:

Date Reason
10/15/2017 Reviewed. No changes.
2/15/2016 Document updated with literature review. Coverage changed to: 1) Transcatheter mitral valve repair with a device cleared by the U.S. Food and Drug Administration (FDA) for use in mitral valve repair may be considered medically necessary for patients with symptomatic, degenerative mitral regurgitation who are considered at prohibitive risk (see NOTE 1 below) for open surgery. 2) Transcatheter mitral valve repair is considered experimental, investigational and/or unproven in all other situations.3) added NOTE 1: Prohibitive risk for open surgery may be determined based on the presence of a Society for Thoracic Surgeons predicted mortality risk of 12% or greater; and/or the presence of a logistic EuroSCORE of 20% or greater. 4) Transcatheter mitral valve repair using percutaneous annuloplasty is considered experimental, investigational, and/or unproven for the treatment of mitral valve regurgitation (insufficiency).
9/15/2014 Document updated with literature review. Coverage unchanged. Document title changed from “Percutaneous Endovascular Mitral Valve Repair” to “Transcatheter Mitral Valve Repair.”
4/1/2013 Document updated with literature review. Coverage unchanged.
5/15/2011 Document updated with literature review. Coverage unchanged.
11/1/2009 Updated document with literature search. References added. No change to Coverage statement.
7/1/2007 Revised/Updated Entire Document.
1/1/2005 New Medical Document. Percutaneous endovascular mitral valve repair using leaflet clips and/or annuloplasty is considered experimental, investigational and unproven for treatment of mitral valve regurgitation (insufficiency).

Archived Document(s):

Back to Top