Academic Editor: Takatoshi Kasai
Background: Transcatheter edge-to-edge repair of mitral valve (M-TEER) is reasonable consideration in symptomatic patients with severe degenerative mitral regurgitation (MR) who are at high or prohibitive risk of surgical repair or replacement. In symptomatic patients on maximally tolerated medical therapy with severe secondary MR from left ventricular systolic dysfunction, M-TEER is reasonable therapeutic option. Methods: In this review, we present a comprehensive overview of the most recent literature and considerations for M-TEER in patients excluded from key trials. These include patients with cardiogenic shock, acute ischemic MR, atrial functional MR, failed surgical mitral valve prosthesis and pulmonary hypertension. Conclusions: M-TEER is feasible and a reasonable alternative option for these patient populations with a significant clinical benefit. However, randomized clinical trials are needed to ascertain findings from these observational studies.
Mitral regurgitation (MR) can occur either due to primary degenerative pathology
of the mitral valve (degenerative MR) or secondary to other cardiac pathology
(functional MR) such as annular dilation, ventricular dilation (e.g., dilated
cardiomyopathy), atrial dilation (e.g., atrial fibrillation), or papillary muscle
dysfunction (e.g., coronary artery disease). If untreated, significant MR leads
to progressive left ventricular systolic dysfunction which results in higher than
5% annual mortality among symptomatic individuals [1]. While medical management
can help with symptom relief, it is unlikely to halt the progression of the
underlying pathology. Open surgical repair remains the definitive treatment for
degenerative mitral valve disease. However, a significant number of patients do
not undergo surgery due to profound left ventricular systolic dysfunction,
advanced age, or multiple co-morbidities which increase the risk of
peri-operative morbidity and mortality [2]. Transcatheter edge-to-edge repair
(M-TEER) with the MitraClip
M-TEER was developed based on the concept of surgical Alfieri stitch. This
surgical procedure aims to reduce MR by sewing together the anterior and
posterior leaflets where the valve is incompetent. The patent for the
MitraClip
The first RCT to examine the role of M-TEER was the Endovascular Valve
Edge-to-Edge Repair Trial (EVEREST II). A total of 279 patients eligible for
mitral valve repair or replacement with chronic 3+ or 4+ degenerative MR were
randomly assigned to M-TEER or surgical mitral valve repair or replacement in a
2:1 fashion. Amongst participants, symptomatic patients had left ventricular
ejection fraction of
In patients with functional MR, the role of M-TEER was evaluated in 2 RCTs with
conflicting results. Percutaneous Repair with the MitraClip
The discrepancy in outcomes between the two trials was attributed to the
difference in characteristics of respective cohorts. In the MITRA-FR trial,
participants had a higher degree of left ventricular dilatation and more
“proportionate” degree of MR compared to the COAPT trial which had more
patients with “disproportionate MR”, i.e., effective orifice area of 0.3 to 0.4
cm
Initial real-world data from the STS/TVT registry on 564 patients who underwent
M-TEER showed promising results. The predicted 30-day mortality for either
surgical mitral valve repair or replacement was 7.9% and 10.0% respectively,
for patients treated with M-TEER. Most of these patients had degenerative mitral
valve disease, and M-TEER was successful (defined as final MR grade
Even though technical success for this procedure is high, appropriate selection of patients is of paramount importance to achieve clinical benefits. Over the last decade, there has been a significant increase in the number of M-TEER procedures with improved clinical outcomes even in relatively complex patient populations [10]. This significant increase in M-TEER volume has been driven by patients with degenerative MR [11]. While the landmark trials have included patients with both degenerative and functional MR, M-TEER has also been successfully performed in patients who otherwise would be excluded from these trials.
In trials of M-TEER, patients with cardiogenic shock were excluded. However,
recent reports support the feasibility and potential benefit of the therapy in
this complex patient population. Most recently, the largest data on the efficacy
of M-TEER in patients with severe MR and cardiogenic shock (CS) was presented at
TCT as a late-breaking study from STS/TVT/ACC registry [12]. CS was defined by
hypotension and severe reduction in cardiac index (
A multicenter registry data of acute myocardial infarction (AMI) patients was used to examine the impact of M-TEER in patients with and without CS during index hospitalization [13]. A total of 93 patients were included, 50 of whom were diagnosed with CS. Technical success was similar between groups (90% vs. 93%, p = 0.79) with no significant difference in all-cause mortality at 30-days (10% vs. 2.3%, p = 0.21) and 7-months (16% vs. 9.3%, p = 0.38). There was also no difference in combined death/hospitalization due to heart failure at 7 months (28% vs. 25.6%, p = 0.79). M-TEER was performed approximately 24 days after AMI in patients with CS with the goal to achieve hemodynamic stability from shock before consideration for M-TEER. These studies suggest that M-TEER can serve as a safe and effective alternative for treating MR in patients who are not deemed to be candidates for open surgical repair or replacement.
A patient-level multicenter analysis of patients with CS (n = 141) and moderate to severe or severe mitral regurgitation further supported the feasibility of M-TEER in this patient population [14]. The majority of patients were in Society for Cardiovascular Angiography and Interventions (SCAI) shock stage C (50.4%) or D (29.8%) and half of the patients were on mechanical circulatory support. Procedural success was achieved in 88.7% of the patients. In-hospital, 90-day, and 1-year mortality occurred in 15.6%, 29.5%, and 42.6%, respectively. In patients who had procedural success, M-TEER reduced in-hospital (hazard ratio [HR] 0.36; 95% CI 0.13 to 0.98; p = 0.04) and 90-day (HR 0.36; 95% CI 0.13 to 0.78, p = 0.01) mortality, and the composite of 90-day mortality and HF hospitalization (HR 0.41; 95% CI 0.19 to 0.90, p = 0.03) compared to patients in whom procedural success could not be achieved [14].
MITRA-SHOCK is a retrospective multicenter study that reported the outcomes of
M-TEER in 31 patients with refractory CS treated with inotropes and diuretics
with or without mechanical circulatory support. These patients were deemed
inoperable by a heart team per site protocol, with an STS risk score for mitral
valve surgical repair of 37.9 (Inter Quartile Range 30.4–42.4). M-TEER was
pursued for compassionate care without any specific study protocol. Among the 31
patients, 24 had dilated cardiomyopathy and 17 had STEMI. Procedural success was
achieved in 87% of patients with significantly higher survival in patients with
procedural success when compared with those without procedural success (87.2%;
95% CI 73–99% vs. 25%; 95% CI 4.6–96%, p
Data from these observational studies suggest reasonably high procedural success in this critically ill population with CS with significant improvement in short- and mid-term outcomes. The Transcatheter Mitral Valve Repair for Inotrope Dependent Cardiogenic Shock (CAPITAL-MINOS) trial is enrolling patients to assess the efficacy of M-TEER in patients with inotrope-dependent cardiogenic shock (SCAI Stage C & D) with at least 3+ MR [16]. The study will evaluate a composite endpoint of in-hospital all-cause mortality, cardiac transplantation, left ventricular assist device implantation, or discharge on palliative inotropes. Results from this trial would further guide our decision-making in this select patient population.
Acute severe MR after myocardial infarction in patients treated with primary percutaneous intervention is associated with poor clinical outcomes when compared with patients who do not develop mitral regurgitation [17, 18]. Emergent surgical repair or replacement remains the gold standard therapy, however, most of these patients are at high or prohibitive risk for surgical intervention due to acute myocardial infarction and hemodynamic instability [19]. Those treated medically have the worst outcomes [20]. Pharmacologic afterload reduction and mechanical circulatory support are supportive options until definitive treatment can be provided. The availability of M-TEER offers an additional treatment option, but the landmark trials (MITRA-FR and COAPT) excluded this subset of patients.
Single- and multi-center case series have reported successful reduction of MR
with M-TEER, which translated into short-term clinical benefits [21, 22]. The
International Registry of MitraClip
Functional MR from atrial dilation (e.g., in patients with atrial fibrillation)
is secondary to annular dilatation which differs from functional MR from
ventricular dilatation in patients with HF. In the prospective, observational,
multicenter EXPAND (A Contemporary, Prospective, Multi-Center Study Evaluating
Real-World Experience of Performance and Safety for the Next Generation of
MitraClip Devices) study patients with atrial functional MR were identified by an
echocardiography core laboratory. Device success was achieved in 100% patients
at 1-year with significant improvement in functional class and Kansas City
Cardiomyopathy Questionnaire score. These results were similar to patients with
functional MR of ventricular dysfunction [24]. A recent study of 1044 patients
compared 2-year outcomes in patients with degenerative (48%), atrial functional
(11%), and ventricular functional (48%) MR with a mean STS Score of 8.6
Recently, a few studies from Europe have reported outcomes after M-TEER in
patients with atrial functional severe MR and compared outcomes with ventricular
functional severe MR [28, 29]. There was improvement in NYHA functional class
Similarly, a Belgian registry reported outcomes of 52 patients with atrial
functional MR compared with ventricular functional MR (n = 307) [28]. Reduction
in MR was greater when compared with ventricular functional MR (94% vs. 82%,
p
Surgical mitral valve repair is the preferred treatment for degenerative severe
MR in patients at acceptable surgical risk. Patients with prior surgical mitral
repair were excluded from all RCTs due to the change in the anatomy of the mitral
apparatus and concerns about the technical feasibility to achieve success with
M-TEER. The presence of a mitral ring can obscure posterior leaflet visualization
during the grasp and limit orifice dimensions for passage of the MitraClip
Development of pulmonary hypertension (PH) in patients with severe mitral
regurgitation is an indication for mitral valve repair or replacement [5]. Worse
clinical outcomes have been reported in patients with PH who undergo surgical
mitral valve repair or replacement [32]. Different studies have reported effect
of M-TEER on PH and effect of pre-existing PH on clinical outcomes after M-TEER.
In an initial study of 91 patients with functional MR, procedural success and
30-day mortality were similar in PH group (pulmonary artery systolic pressure
(PASP)
Among the concerns of surgical mitral valve repair is the impact of reduced
mitral valve area and elevated gradient on clinical outcomes after repair. This
is more of a concern with M-TEER compared with surgery as many cases require more
than 1 clip to achieve procedural success and clinical benefit, especially in
those with small pre-procedural valve area (
A recent post-hoc analysis of patients in the COAPT trial based on post-procedural mitral valve gradients of 2.1, 3.0, 4.2, and 7.2 mmHg showed no difference in a composite clinical end point of all-cause mortality, HF hospitalization and health status at the end of 2-year follow-up [42]. Another recent study analyzed outcomes after M-TEER amongst patients with primary mitral regurgitation. There was no difference in the composite outcome of all-cause mortality and HF hospitalization in patients with a post-procedural mitral valve gradient of 6.0 mmHg vs. 1.9, 3.0, or 4.0 mmHg (n = 419) [43].
Although initial data was concerning for worse clinical outcomes if
post-procedural mitral valve gradients were
Even though, M-TEER has been performed in both degenerative and functional MR
patients, significant challenges exist in certain populations. There is increased
risk of mitral stenosis following M-TEER in patients with severe mitral annular
calcification, calcified leaflets and multiple regurgitant jets. Adequate
reduction in MR may not be achieved in patients with cleft mitral leaflet, short
posterior leaflet (
Since the reporting of landmark trials, M-TEER has emerged as a reasonable
alternative to surgical mitral valve intervention in both degenerative and
functional MR. Even though these trials excluded critically and acutely ill
patients, observational data from single- and multi-center registries are
encouraging, especially when significant reduction of MR is achieved (see Fig. 1). Randomized controlled trials are needed to verify the promising results of
these observational studies. Significant challenges still exist in patients with
small valve area, calcified leaflets, multiple regurgitant jets, cleft leaflets,
short posterior leaflet (length
Feasibility of transcatheter mitral edge-to-edge repair in different patient populations.
HI and MS designed the research study and drafted initial manuscript. All authors contributed to editorial changes in the manuscript. KA, MB, IE, NI, AE, BS and PG contributed to editorial changes, read and approved the manuscript.
Not applicable.
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This research received no external funding.
The authors declare no conflict of interest.