Abstract: Background. Percutaneous mitral valve repair is an alternative treatment for high-risk patients with symptomatic mitral regurgitation (MR). Proper patient selection is crucial to ensure that patients will benefit from the procedure while avoiding futile and potentially harmful medical interventions. Objectives. To assess the reasons for and outcomes of patients who were declined MitraClip (Abbott Vascular) implantation and compare them with patients who underwent the procedure at our medical center. Methods. We screened 182 patients for percutaneous mitral valve repair with the MitraClip device. Of these, 84 were referred for MitraClip implantation and 75 underwent the procedure. Results. Procedural success was achieved in 64 patients (85%) and was associated with superior survival at 30 months (73%) compared with implanted patients who did not achieve procedural success (41%; P=.02). Ninety-eight patients were turned down for the procedure due to anatomical incompatibility (72%), lack of indication (“too well”) (16%), and clinical incompatibility (“too sick”) (12%). Among turned down patients, those who were deemed too well had the highest survival rate (85%) at 30 months, patients with anatomical incompatibility had intermediate survival rates (63%), and patients deemed “too sick” had a dismal survival rate of only 25% (P<.01). In fact, the patients who were too well had outcomes that were equivalent to patients who underwent successful MitraClip implantation. Conclusions. We identified a number of reasons for not performing MitraClip implantation that impact patient survival. The best outcomes were seen in patients who underwent successful MitraClip implantation and in patients who were deemed too well.
J INVASIVE CARDIOL 2020 July 10 (Epub Ahead of Print).
Key words: heart failure, MitraClip, mitral regurgitation, MR, percutaneous edge-to-edge repair
Mitral regurgitation (MR) is a common valvular disorder. Current guidelines recommend surgical repair or replacement of the mitral valve in patients with severe MR and symptoms of heart failure or left ventricular dysfunction.1,2 However, a large proportion of patients with MR are elderly and are at high risk for surgery. Until recently, these patients were relegated to medical therapy. Percutaneous mitral valve repair (PMVR) is a promising alternative for the treatment of high-risk patients with symptomatic MR.3-5 Numerous reports have described the experience with MitraClip (Abbott Vascular) implantation in patients with high surgical risk, predominantly in patients with functional MR secondary to ventricular remodeling.6-10 These data have suggested improved outcomes in patients undergoing MitraClip implantation compared with outcomes of similar patients treated medically.11-13 However, 1-year mortality in most of these series has been significant, at around 8%-22%.4,11-13 Therefore, proper patient selection is crucial to ensure that patients will benefit from the procedure while avoiding futile and potentially harmful medical interventions. The aim of this study was to assess the reasons for and outcomes of patients who were declined MitraClip implantation and compare them with patients who underwent the procedure at our medical center.
All patients who were assessed for MitraClip implantation from January 1, 2010 to December 31, 2017 were included in the study. All patients had a diagnostic work-up that included physical examination, functional capacity assessment according to the New York Heart Association (NYHA) class,14 medical background, electrocardiogram, blood tests, transthoracic and transesophageal echocardiography, and coronary angiography (if indicated). MR was assessed according to current guidelines15,16 and was classified as mild (1+), moderate (2+), moderate-severe (3+), or severe (4+). Echocardiographic evidence of suitability for MitraClip implantation was initially based on the EVEREST II study17 criteria and included: MR originating from the central two-thirds of the line of leaflet coaptation; flail segment width of 15 mm or a flail gap of 10 mm; mitral valve orifice area >4 cm2; coaptation length >2 mm and coaptation depth <11 mm; mobile leaflet length >1 cm; and absence of leaflet or excessive annular calcification. However, as operator experience improved, we tended to rely less on the EVEREST II criteria and more on technical factors related to anticipated procedural success, especially the height of the fossa ovalis (at least 3.5 cm), presence of at least minimal leaflet coaptation, lack of a significant transmitral valvular gradient, and lack of calcification on the grasping area of the leaflets.
Patients were evaluated by an interventional cardiologist, a cardiac surgeon, and a cardiologist specializing in echocardiography and valvular disease. The decision to refer patients for implantation or decline them was based on a multidisciplinary heart team discussion and was based on echocardiographic suitability (as described previously) and clinical suitability, especially whether the team anticipated clinical improvement following clip implantation.
Transthoracic echocardiography was performed on the day following implantation and during the first year in most patients. Clinical follow-up was performed during annual clinic visits and included an assessment of heart failure symptoms, NYHA class, a physical examination, and echocardiographic assessment.
The primary endpoint for efficacy was freedom from death. Mortality data were obtained from the national death registry for all patients censored at March 31, 2018.
Statistical analysis. Continuous variables are expressed as mean ± standard deviation, while categorical variables are presented as absolute numbers and percentages. Long-term event-free survival was estimated using Kaplan-Meier curves and the log-rank test to assess the significance of differences between the groups. A P-value <.05 was considered to indicate a statistically significant difference. We conducted statistical analyses with SPSS, version 20.0 (SPSS).
During the period from 2010-2017, a total of 182 patients were screened for PMVR with the MitraClip device. Of these, 84 were referred for MitraClip implantation and 75 underwent the procedure. Among patients referred for the procedure, reasons for not implanting a clip included: inability to grasp both leaflets (n = 3); inability to adequately reduce MR (n = 3); and other anatomical considerations (n = 3). MitraClip procedural success (defined as a reduction of at least 2 MR grades to MR grade ≤2) was achieved in 64 patients (85%). Baseline characteristics of patients who did and did not achieve procedural success were similar (Table 1).
Ninety-eight patients were turned down for the procedure due to one of three reasons: (1) anatomical incompatibility (70 patients, 72% of all rejected patients); (2) lack of indication for performing the procedure, defined as asymptomatic or MR grade ≤2 (16 patients, 16% of all rejected patients); and (3) clinical incompatibility, defined as patients deemed too sick to benefit from the procedure (12 patients, 12% of all rejected patients). Baseline characteristics of these three groups are shown in Table 2. Patients turned down due to lack of clinical indication had significantly lower incidence of grade 3-4 MR and of NYHA functional class III-IV compared with the other two groups. They also had a numerically higher level of serum albumin. Patients turned down due to clinical incompatibility were more likely to be in NYHA class IV. No differences in MR grade were noted between patients with anatomical and clinical incompatibility. Patients with anatomical incompatibility had a significantly higher left ventricular ejection fraction compared with the other two groups.
Among patients who underwent MitraClip implantation, procedural success was associated with superior survival at 30 months (73%) compared with implanted patients who did not achieve procedural success (41%; P=.02), as shown in Figure 1. Thirty-month survival rates among the three groups turned down for the procedure differed (Figure 2); patients without indication for MitraClip implantation had the highest survival rate (85%), whereas patients with anatomical incompatibility had an intermediate survival rate (63%). Patients deemed clinically unsuitable due to anticipated futility had the lowest survival rate, with only 25% still alive at 30 months (P<.01). In fact, when comparing patients turned down due to lack of clinical indication, their survival rate was excellent and similar to patients who achieved procedural success after MitraClip implantation (P=.32) (Figure 3). Baseline characteristics of these patients were similar except for MR and NYHA functional class (Supplemental Table S1). Conversely, patients turned down due to anatomical incompatibility had an unfavorable prognosis similar to patients who did not achieve procedural success following MitraClip implantation (P=.73) (Figure 4). Baseline characteristics of these patients were similar except for MR degree (Supplemental Table S2).
The two major findings in our study are: (1) successful MitraClip implantation is associated with superior outcomes compared with patients who had suboptimal implantation results; and (2) the prognosis of patients turned down for MitraClip implantation differed according to the reason for refusal.
Among patients who underwent MitraClip implantation at our center, the procedural success rate was 85%, similar to the reported success rate in contemporary literature (83%-96%).5,8,11,12,18 Importantly, patients who had a successful result after implantation (MR grade ≤2) had significantly better outcomes compared with patients who remained with residual MR grade ≥3. This finding is consistent with other published studies.3,11-13 Indeed, in the TRAMI registry, of all adverse prognostic indicators, procedural failure was associated with the highest hazard ratio for the prediction of 1-year mortality.19
The Sheba Medical Center MitraClip program was initiated in 2011.20 With increasing experience since 2011 and improvements in the MitraClip device, there has been an extensive shift in the willingness to attempt implantation in valvular anatomies that would have been seen as completely unsuitable at the beginning of our experience. This has allowed us to compare patients who are clinically and anatomically similar, but who were declined the procedure during the early phase of our experience. In addition, two other groups were declined the procedure: patients that we considered “too well” based on lack of symptoms and/or lack of significant MR (grade >2) and patients that we deemed “too sick” based on extensive comorbidities and/or very severe heart failure (NYHA class IV).
In fact, patients who were deemed too well had excellent outcomes that were equivalent to those who underwent successful MitraClip implantation. On the other hand, patients who were deemed too sick had a dismal prognosis. Patients who were deemed clinically suitable for the procedure but did not undergo implantation due to anatomical unsuitability had outcomes that were equivalent to patients who underwent MitraClip implantation, but remained with significant residual MR. Similar findings have been reported by the TRAMI registry, which showed considerably increased 30-day mortality in patients with NYHA class IV.18
To the best of our knowledge, this is the first study to report long-term follow-up of patients turned down for a MitraClip procedure and compare them with patients who were chosen for intervention. A number of non-randomized studies have attempted to compare patients undergoing MitraClip implantation with historical controls.11,12 An additional study compared 60 propensity-matched patients who underwent MitraClip implantation with 60 patients who were treated with optimal medical management due to anatomical unsuitability.13 These studies have consistently suggested better functional class and better survival in patients who underwent MitraClip implantation compared with the non-randomized controls chosen. Our data are consistent with these previous studies and add to these data by showing the graded outcomes associated with the reason for not performing a MitraClip implantation in a real-world setting.
Our data emphasize the importance of thorough preprocedural patient evaluation and selection to be performed by a multidisciplinary team with extensive experience in the assessment of high-risk valvular patients.
Study limitations. The major limitation of this study lies in its retrospective, non-randomized design, with a relatively small sample size derived from a single center. It is unique in that it followed patients turned down for the procedure and stratified them into three different groups based on the reason for refusal and reflects real-world decision making in a busy MitraClip center.
Successful MR reduction after MitraClip implantation is associated with improved outcomes compared with patients who remain with residual MR. The outcomes of patients turned down for the procedure depend on the reason for refusal, with excellent outcomes in patients deemed too well and dismal outcomes for patients deemed too sick. Patients who remain with residual MR after MitraClip implantation have outcomes similar to those who were refused based on anatomical unsuitability. Further studies are needed to elucidate which patients are most likely to benefit from the procedure.
From the Leviev Heart Center, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted November 28, 2019, provisional acceptance given December 3, 2019, final version accepted December 6, 2019.
Address for correspondence: Paul Fefer, MD, Leviev Heart Center, Sheba Medical Center, Tel Hashomer 5265601, Tel Aviv, Israel. Email: firstname.lastname@example.org.
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