Original Contribution

Characteristics and Outcomes of Patients Who Are Denied From a Percutaneous Edge-to-Edge Mitral Valve Repair After Being Referred to a Transcatheter Mitral Valve Program: Impact of a Dedicated Multidisciplinary Mitral Heart Team Approach

Anthony Poulin, MD1*; Frédéric Beaupré, MD1*; Caroline Gravel, RN1; Sandra Hadjadj, MSc1; Mathieu Bernier, MD1; Jonathan Beaudoin, MD1; Kim O’Connor, MD1; Alfredo Nunes Ferreira-Neto, MD1; Jérôme Wintzer, MD1; Eric Dumont, MD2; François Dagenais, MD2; Josep Rodés-Cabau, MD1; Jean-Michel Paradis, MD1

Anthony Poulin, MD1*; Frédéric Beaupré, MD1*; Caroline Gravel, RN1; Sandra Hadjadj, MSc1; Mathieu Bernier, MD1; Jonathan Beaudoin, MD1; Kim O’Connor, MD1; Alfredo Nunes Ferreira-Neto, MD1; Jérôme Wintzer, MD1; Eric Dumont, MD2; François Dagenais, MD2; Josep Rodés-Cabau, MD1; Jean-Michel Paradis, MD1

Abstract: Background. Many patients referred for a MitraClip intervention are finally refused for this intervention, and data are very scarce on their outcomes. Our study sought to determine the characteristics and outcomes of patients who are referred to a mitral valve clinic and are finally denied from a percutaneous mitral edge-to-edge repair. Methods. A total of 210 patients referred to our clinic for severe mitral regurgitation were retrospectively analyzed. Fifty-seven patients underwent a MitraClip procedure. For exploratory purposes, a propensity-matched cohort comparing the patients accepted for a MitraClip procedure and those refused for any mitral intervention was analyzed. Results. Among the 153 patients who were refused for MitraClip, 46% had functional MR, 42% had degenerative MR, and 11% had mixed disease. Reasons for denial included unfavorable anatomy, patient refusal, mitral valve surgery referral, cardiac resynchronization therapy, other advanced heart failure therapies, and palliative care. After a mean follow-up of 13 months, 50% were in New York Heart Association class I or II, 63% had less than severe MR, and mortality rate was 29%. In the propensity-matched cohort, there was no difference in symptoms improvement, but there was less overall mortality (P=.01), cardiovascular mortality (P<.01) and severe MR (P<.01) in the MitraClip group. Conclusions. A multidisciplinary heart team evaluation for complex MR patients can be useful not solely for selecting the ideal MitraClip eligible patients, but also to select the best treatment strategy in each individualized context. 

J INVASIVE CARDIOL 2020;32(6):E151-E157.

Key words: edge-to-edge, heart team, MitraClip, mitral regurgitation, percutaneous 

Mitral regurgitation (MR) is the most common heart valve disease in the global population.1 In individuals older than 65 years of age, the prevalence is 6% and this number is expected to increase with the aging population. Severe MR, particularly in the setting of left ventricular dysfunction, portends a poor prognosis, with annual hospitalization and mortality rates >15% and >10%, respectively.2 Mitral valve surgery remains the standard of care for symptomatic patients or those with left ventricular dysfunction. However, in clinical practice, many patients are considered inoperable due to high periprocedural risk and comorbidities. Therefore, numerous patients do not undergo surgery and stay untreated. In this context, transcatheter mitral valve therapies have been developed and there is growing evidence showing their feasibility, safety, and efficacy.3-6 Percutaneous mitral edge-to-edge repair with the MitraClip system (Abbott Vascular) has been used in more than 70,000 patients thus far, and has demonstrated superior safety at 30 days (15% vs 48%, respectively; P<.001) and similar improvement in clinical outcomes compared with mitral valve surgery in highly selected patients with primary MR in the EVEREST II trial.4 However, there was a 10-fold increase in reoperation for mitral valve surgery in patients receiving the MitraClip device (20% vs 2% in the surgical group; P<.001). In another high-risk surgical cohort, a MitraClip procedure significantly reduced MR, improved clinical symptoms, and decreased left ventricular dimensions at 1 year.5 

At present, the 2017 American College of Cardiology/American Heart Association practice guidelines recommend the use of MitraClip (class 2b indication) for treatment of high-risk patients with significant primary MR.7 The 2017 European Society of Cardiology/European Association for Cardiothoracic Surgery extends its indication to also include secondary MR as a class 2b recommendation.8 Recently, for patients with functional MR, this procedure showed significant reduction in heart failure hospitalization and mortality at 24 months for inoperable patients with reduced ejection fraction in the randomized COAPT trial.6 

In real-world practice, a substantial proportion of patients referred for transcatheter mitral valve therapies will not receive any percutaneous treatments, even if they are less invasive than conventional surgery. Oftentimes, after a thorough assessment, alternative therapeutic options (mostly medical treatment) will be offered to those patients who were initially referred for a transcatheter therapy. However, the current evidence is very heterogeneous and data are very scarce regarding the characteristics and outcomes of patients with severe mitral insufficiency who are not offered any percutaneous edge-to-edge repair. The aim of this study was to describe the characteristics and the outcomes of patients who were initially referred for a MitraClip therapy, but who were eventually offered another treatment option. We also sought to understand the impact of a dedicated mitral heart team in the decision-making process of these complex comorbid patients. 


Study design. This study retrospectively analyzed the data of all patients who were referred to our transcatheter mitral valve program. Each patient was encountered by our nurse coordinator and at least one of our heart team physicians (three interventional echocardiographers, two heart failure specialists, two cardiothoracic surgeons, and two interventional cardiologists). When necessary, electrophysiologists were consulted, especially for their opinion on the potential benefits of cardiac resynchronization therapy. The first step was to evaluate their symptoms and comorbidities, as well as their surgical risk using a standard validated risk score (Society of Thoracic Surgeons Predicted Risk of Mortality [STS-PROM]). All patients had local transthoracic and transesophageal echocardiograms. Further functional or anatomical evaluations were requested if needed. For all patients, an invasive or non-invasive ischemic stratification was done. When appropriate, imaging was sent to the Abbott Vascular team to confirm the technical feasibility of a MitraClip procedure. Once the patient clinical evaluation was completed, every case was discussed during our bi-monthly mitral heart team meeting. After review of all clinical characteristics and imaging modalities, the patient’s final therapeutic orientation was determined. 

Baseline characteristics, clinical endpoints, and echocardiographic follow-up data were collected according to Mitral Valve Academic Research Consortium (MVARC) criteria,9 from time of referral to last follow-up. Reasons for refusal of percutaneous mitral edge-to-edge repair and final treatment allocation were documented for each patient. 

Statistical analysis. Continuous variables are presented as mean ± standard deviation or median (interquartile range) according to the data distribution and compared using the Student’s t-test or Wilcoxon rank-sum test. Categorical variables are presented as count (percentage) and compared using the Fisher’s exact test. For exploratory purposes, a propensity-score analysis representing the likelihood of having a percutaneous mitral edge-to-edge valve procedure was calculated for each patient by use of a logistic regression analysis. Variables closely related to both treatment effect and the choice of treatment were involved. These variables included in the logistic regression analysis were age, sex, creatinine, hemoglobin, right ventricular systolic pressure, STS-PROM score, New York Heart Association (NYHA) classification, MR severity and mechanism, history of coronary artery disease, myocardial infarction, and atrial fibrillation. Continuous variables were checked for the assumption of linearity in the logic and the graphical representations suggested linear relationships. Interactions between variables were allowed only if it was supported clinically. After model building, the Hosmer-Lemeshow test was performed to assess the goodness-of-fit of the model, resulting in the statistic of Chi-Square=8.5 with df=8 and P=.39, indicating that the final model fitted quite well. On estimation of the propensity score, subjects having a MitraClip procedure were matched 1:1 to subjects denied from any mitral intervention. The 1:1 propensity-score matching using the greedy algorithm was performed. A caliper width of 0.1 of the pooled standard deviation of the logit of the propensity score was used. The balance in baseline variables was assessed by standardized difference. Statistical significance was present when the two-tailed P-value was <.05. Analyses were performed using SAS, version 9.4 (SAS Institute).


Study population and baseline characteristics. Between November 2014 and August 2018, a total of 210 patients with moderate to severe MR were referred to our transcatheter mitral valve program to evaluate the possibility of a percutaneous mitral valve repair procedure. Of those, only 57 were deemed to be good candidates for a MitraClip procedure. Therefore, a total of 153 patients were included in the main analysis cohort of our study and follow-up data were available for 150 patients (98%). 

Baseline characteristics of patients who were denied a percutaneous mitral edge-to-edge repair (Table 1) revealed a cohort of predominantly male patients (60%) with a mean age of 75 years. There was a history of previous myocardial infarction in 80 patients (52%) and 59 patients (39%) had undergone a coronary artery bypass graft surgery. Atrial fibrillation was present in 79 of those patients (52%) and 96 (63%) had clinically significant renal dysfunction, defined by an estimated glomerular filtration rate of <60 mL/min. A majority of patients who were denied from a percutaneous edge-to-edge repair were in NYHA functional class III or IV (107 patients; 70%). The median left ventricular ejection fraction (LVEF) was 40% and mean N-terminal pro-B-type natriuretic peptide level was 5224 pg/mL. MR was finally deemed mild to moderate in 35 patients (23%) and severe in 118 patients (77%). In our cohort of patients excluded from a MitraClip procedure, 46% of patients had functional MR, 42% had degenerative MR, and 11% had mixed mitral disease.

Reasons for denial of percutaneous therapies are described in Table 1 and the trajectory of patients referred to our mitral clinic is illustrated in Figure 1. About one-third of the patients (46 patients; 30%) were finally treated with optimal guideline-directed medical therapy alone. Palliative care was offered to 11 patients (7%). Fifteen patients (10%) decided to finally refuse the intervention and 13 patients (8%) were judged ineligible due to technical issues (mainly unfavorable anatomy for the MitraClip procedure). Of note, a total of 26 patients (17%) were referred for mitral valve surgery, 11 (7%) for transcatheter mitral valve replacement, and 18 patients (12%) to cardiac resynchronization therapy (CRT). One patient was referred to heart transplantation, and another to experimental left-to-right interatrial shunt implantation with the V-Wave device (V-Wave Ltd). In 11 patients (7%), the heart team deemed that MR was not an issue and that they would not derive any benefit from a mitral valve intervention.

Compared to patients refused for a MitraClip intervention, those who underwent a percutaneous edge-to-edge repair procedure had similar characteristics except for a higher incidence of chronic kidney disease. However, patients were more symptomatic, with 89% in NYHA functional class III or IV at baseline and MR evaluated as severe in almost all patients (96%). In the MitraClip group, 3 patients had been initially referred for CRT and 1 patient had been oriented for transcatheter aortic valve replacement. Because of persistent severe MR, those 4 patients finally underwent a MitraClip procedure after a second mitral heart team assessment. In addition, 2 patients needed a redo MitraClip intervention (1 single leaflet device attachment and 1 residual severe MR lateral to the clip implanted during the index procedure). 

Follow-up evaluation. Excluded patients were nonetheless followed in our institution through regular clinical visits and echocardiograms (Table 2). In this cohort, after a mean follow-up of 13 months, we observed a mortality rate of 29% and a hospitalization rate of 50%. At last follow-up, a total of 52 patients (50%) were in NYHA functional class I or II and 57 patients (63%) had less than severe MR. Median LVEF was stable over time, varying between 40%-42% throughout follow-up. In patients with severe MR, the mortality rate was 32% and the hospitalization rate was 54%. When considering only patients for whom medical treatment was decided and excluding those oriented to palliative care, the overall mortality rate slightly increased to 37% (heart failure was the cause of death in 72% of those patients). In the group of patients who underwent MitraClip implantation, the mortality rate was 24% (heart failure was the cause of death in 31% of those patients). Periprocedural complications were also relatively infrequent during our initial experience with MitraClip. Major bleeding occurred in 3 patients (5.4%) and 1 patient (1.8%) died of cardiogenic shock after the procedure. One patient had to undergo surgical mitral valve replacement within the same hospitalization and 1 patient needed a surgical femoral vein repair. No stroke or new-onset atrial fibrillation was noted in our MitraClip cohort.

Five of the 18 patients (28%) in the cohort oriented to CRT died within 1 year of follow-up. However, 62% of survivors maintained or improved their NYHA functional class and 69% presented less than severe MR at follow-up. Selected patients referred for mitral valve surgery had a low 1-year mortality rate (2 of 26 patients; 8%). MR improved in nearly all those patients at last follow-up (21 of 22 patients; 95%). Indeed, 20 patients (90%) showed none to mild MR, 1 patient (5%) showed moderate MR, and only 1 patient (5%) retained severe MR. A majority of patients were in NYHA functional class I or II (15 of 22 patients; 68%). In comparison, the patients chosen for transcatheter mitral valve replacement had a higher mortality rate (4 of 11 patients; 36%) and remained more symptomatic, with 3 of 11 patients (27%) in NYHA functional class I or II, despite having 72% of the group with none to mild MR at last follow-up. This discrepancy is certainly due to the fact that transcatheter mitral valve replacement patients were sicker independent of their MR severity.

Propensity-matched analysis. The propensity-matched cohort comparing patients refused for any mitral intervention and those who underwent a MitraClip procedure (Table 3) matched 50 patients in each group. Between the two groups, there was no difference in NYHA functional class at last follow-up, despite a lower rate of severe MR after the MitraClip procedure (10% vs 46% in those refused for mitral intervention; P<.01). Cardiovascular mortality was significantly less prevalent in the MitraClip group (33% vs 88% in those refused for mitral intervention; P<.01) and overall mortality was significantly lower in the MitraClip group (24% vs 48% in those refused for mitral intervention; P=.01). There was also a higher hospitalization rate in the MitraClip group (P<.001). 


The impact of our dedicated mitral heart team and our patient-centered approach on patient therapeutic trajectory is well described in this study. Indeed, at our institution, most patients (153 of 210; 73%) with significant MR who were initially referred for a MitraClip procedure were finally oriented toward a different treatment strategy. Mortality rate in patients denied from a MitraClip intervention averaged 29% after a mean follow-up of 13 months. The vast majority of them (82%) died of cardiovascular causes. Late referral from physicians — and most importantly, the very elevated comorbidity burden of those complex patients — can explain the sizable excess mortality rate observed in this cohort. This mortality rate can compare with recent pivotal trials like MITRA-FR10 and COAPT,6 which had 12-month mortality rates in their control groups of 22.4% and 23.2%, respectively.

Interestingly, in  a recent review of 1294 patients with newly diagnosed isolated moderate to severe MR from Olmsted county,2 mortality was 2.3 times higher in patients with significant MR compared with a matched control population. Only 18% of this cohort underwent mitral valve surgery and 47% of patients died within 5 years. Of note, in the COAPT trial,6 58% of patients referred for enrollment were considered ineligible for the study. Device intervention was not attempted in an additional 3% in the randomized MitraClip group. In our mitral heart team cohort, only 27% received a MitraClip and 46% ended up without any invasive intervention after a thorough evaluation, mostly because of comorbidity burden or technical issues. This clearly illustrates the fact that MR still does not have an all-comer transcatheter solution. It also shows the importance of early referral to a specialized heart team along with close follow-up to ensure that potential patients do not get past their optimal interventional therapeutic window. Furthermore, the statistically significant difference in overall and cardiovascular mortality rates in our propensity-matched cohort illustrates the fact that this is a highly diseased population, and targeting the MR could effectively have an impact on hard outcomes. 

When considering treatment for patients with complex mitral valve disease, determining the mechanism of MR and potential repairability, either percutaneously or surgically, is crucial. Thereafter, many therapies have to be considered based on anatomical factors, physiologic state, and comorbidities, ie, optimal medical therapy, CRT, advanced heart failure therapies (including left ventricular assist devices, heart transplantation, and unidirectional interatrial shunt), percutaneous mitral edge-to-edge repair, surgical mitral valve repair or replacement and, more recently, transcatheter mitral valve replacement. In our cohort of patients, it is important to mention that we were very assertive with CRT. After 12 months, more than one-half of the patients treated with biventricular pacing improved their MR grade as well as their NYHA functional class, suggesting clear benefits of this treatment in our cohort. CRT should therefore be considered prior to percutaneous mitral valve intervention for all patients with significant MR and high surgical risk who meet the criteria for this technology. Indeed, several small studies have shown advantages of CRT on left ventricular positive remodeling and eventually on reducing MR.11 

We found that up to 57% of our study population had some degree of functional MR. The best therapy for functional MR remains uncertain, and before the COAPT trial, no study had shown any clinical superiority of the MitraClip device in a randomized trial.6,10 Nowadays, the conflicting results between the COAPT and MITRA-FR studies, along with the emerging concept of proportionate and disproportionate MR, clearly illustrate the importance of optimizing medical therapy and wisely choosing the patients who could benefit from a percutaneous mitral edge-to-edge repair.12 Therefore, as demonstrated in our study (despite the fact that the decision-making process depicted in this manuscript was applied before the publication of COAPT and MITRA-FR), a heart team evaluation is crucial to establish a personalized treatment strategy for these complex patients. 

The statistical difference in hospitalization rate between the two groups needs to be interpreted with caution. Every hospitalization, including for the index procedure, was included in the analysis, which highly dis-favored the MitraClip group. Also, a substantial proportion of the preoperative investigations was performed on an inpatient basis because of geographical referral location. However, the percentage of patients who were hospitalized for heart failure at follow-up was still numerically lower in the group without MitraClip (31.5% vs 20.9%). Longer mean follow-up in the MitraClip group can certainly explain this finding as well as more robust data collection in this group that was systematically followed at our institution. For these reasons, it is very difficult to draw any strong conclusion for this particular outcome. 

Based on our findings, we believe that in a tertiary-care cardiology institution, a multidisciplinary heart team must be implemented to select the best treatment options for these challenging mitral valve patients. In fact, they represent a much older and sicker population than the patients encountered in regular clinical practice and initial MitraClip studies.4 Thus, we are convinced that the trajectory of care must be patient centered. Figure 2 suggests a structure for the heart team and a patient healthcare trajectory to minimize adverse outcomes in this particular cohort. It is also essential to mention that if a MitraClip procedure is finally considered the most appropriate treatment, it remains a relatively safe option with low periprocedural complications even in low- to moderate-volume centers.13

Study limitations. Our study, although very informative, has some limitations, ie, its retrospective and single-center design, its small number of patients, and its relatively short follow-up. There is also a risk of selection bias caused by the fact that patients referred to an academic institution might have particularly severe disease and then fare poorly. Besides, follow-up data were more limited for patients who did not receive any invasive therapy, thus possibly underestimating the outcomes in this group of patients. Another limitation is the lack of core-laboratory adjudication of echocardiographic parameters. Nevertheless, the study certainly provides a thorough evaluation of the prognosis of patients referred to a mitral valve disease clinic who are denied from a MitraClip procedure in a real-world setting.

Despite reducing the impact of multiple covariates, the strength of our propensity-matched analysis is still limited. Indeed, many confounding variables, such as frailty or autonomy loss, as well as various echocardiographic attributes, were not included in the analysis and probably drove some treatment decisions for our patients.


We describe the outcomes of patients who were referred to our mitral valve clinic and were ultimately denied a percutaneous edge-to-edge repair. In those patients, 30% were oriented toward a medical therapy approach, 17% to a mitral valve surgery, and 12% to CRT. Overall mortality rate was 29% at a mean follow-up of 13 months. In a propensity-matched analysis comparing patients who received a MitraClip procedure and those who did not receive any mitral intervention, there was no statistical difference in NYHA functional class improvement, but there was statistically less overall mortality and cardiovascular mortality, and better improvement in MR severity in the MitraClip group. 

Transcatheter approaches have immense potential to reshape the field of MR therapy. Numerous technologies are becoming available, and the landscape of opportunities is vast. Enormous scientific and financial investments have already been made to overcome the difficulties associated with MR and the technical challenges for its transcatheter treatment. As demonstrated in our study, the availability of numerous therapeutic strategies, on top of an already puzzling valve disease, mandates the implementation of a multidisciplinary mitral heart team to lead to the best decision-making process and patient-centered care.

Acknowledgments. The authors would like to acknowledge the work of Serge Simard, statistician.

*Joint first authors.

From the 1Department of Cardiology, Quebec Heart and Lung Institute, Quebec, Canada; and the 2Department of Cardiothoracic Surgery, Quebec Heart and Lung Institute, Quebec, Canada.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Rodés-Cabau holds the Canadian Research Chair “Fondation Famille Jacques Larivière” for the Development of Structural Heart Disease Interventions; and reports research grants from Edwards Lifesciences, Heartleaflet Technologies, and Medtronic. Dr Paradis reports consulting fees from Abbott Vascular and Medtronic. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted December 9, 2019, provisional acceptance given December 14, 2019, final version February 5, 2020.

Address for correspondence: Jean-Michel Paradis, MD, Quebec Heart and Lung Institute, 2725 Chemin Sainte-Foy, Québec, Quebec, Canada G1V 4G5. Email: jean-michel.paradis@criucpq.ulaval.ca

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