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Archives of cardiovascular diseases
Volume 106, n° 5
pages 287-294 (mai 2013)
Doi : 10.1016/j.acvd.2013.03.059
Received : 7 December 2012 ;  accepted : 18 Mars 2013
Initial French experience of percutaneous mitral valve repair with the MitraClip: A multicentre national registry
Registre multicentrique national sur l’expérience française initiale dans la réparation percutanée de la valve mitrale par le système MITRACLIP
 

Xavier Armoiry a, b, c, Éric Brochet d, Thierry Lefevre e, Patrice Guerin f, Nicolas Dumonteil g, Dominique Himbert d, Bertrand Cormier e, Nicolas Piriou h, Mathieu Gautier g, David Messika-Zeitoun d, Mauro Romano e, Gilles Rioufol i, Karine Warin Fresse j, Nicolas Boudou g, Florence Leclercq k, Marc Bedossa l, Jean-François Obadia m, n,
a Hospices Civils de Lyon, Délégation à la Recherche Clinique et à l’Innovation, Cellule Innovation, quai des Célestins, 69000 Lyon, France 
b Hospices Civils de Lyon, Hôpital Cardiothoracique Louis Pradel, Service pharmaceutique, 28, avenue du Doyen-Lépine, 69677 Lyon-Bron cedex, France 
c Université Claude Bernard Lyon 1, UMR-CNRS 5510/MATEIS, Lyon, France 
d Département de Cardiologie, Hôpital Xavier Bichat, 46, rue Henri-Huchard, 75018 Paris, France 
e Service de cardiologie interventionnelle, Institut hospitalier Jacques Cartier, 6, avenue du Noyer-Lambert, 91300 Massy, France 
f L’Institut du thorax, Clinique Cardiologique, Unité Hémodynamique et Cardiovasculaire Interventionnel, Hôpital Guillaume et René Laennec, CHU de Nantes, boulevard Jacques-Monod, 44093 Nantes, France 
g Pôle cardiovasculaire et métabolique, CHU de Rangueil, 1, avenue du Pr-Jean-Poulhès, TSA 50032, 31059 Toulouse cedex 9, France 
h L’Institut du thorax, Clinique Cardiologique, Unité d’échocardiographie, Hôpital Guillaume et René Laennec, CHU de Nantes, boulevard Jacques-Monod, 44093 Nantes, France 
i Service d’hémodynamique, Hôpital Cardiothoracique Louis Pradel, 28, avenue du Doyen-Lépine, 69677 Lyon-Bron cedex, France 
j Service d’imagerie cardiovasculaire non invasive, Hôpital Guillaume et René Laennec, CHU de Nantes, boulevard Jacques-Monod, 44093 Nantes, France 
k Service de cardiologie, Hôpital Arnaud de Villeneuve, 371, avenue du Doyen-Gaston-Giraud, 34295 Montpellier cedex 5, France 
l Service de cardiologie, CHU de Rennes, 2, rue Henri-Guilloux, 35000 Rennes, France 
m Service de Chirurgie Cardiothoracique et Transplantation, Hôpital Cardiothoracique Louis Pradel, 28, avenue du Doyen-Lépine, 69677 Lyon-Bron cedex, France 
n INSERM, U 886 « Cardioprotection », Laboratoire de Physiologie Lyon Nord, UCBL1, Lyon, France 

Corresponding author. Service de Chirurgie Cardiothoracique et Transplantation, Hôpital Cardiothoracique Louis-Pradel, 28, avenue du Doyen-Lépine, 69677 Lyon-Bron, France. Fax: +33 4 72 35 73 83.
Summary
Background

Percutaneous mitral valve repair (MVR) using the MitraClip® is a new option for severe mitral regurgitation (MR).

Aim

To describe initial French experience regarding short-term and mid-term safety and efficacy.

Methods

A multicentre cohort reported experience of percutaneous MVR using the MitraClip® in French centres from December 2010 to September 2012. All patients were judged inoperable or at high surgical risk. Short-term and mid-term safety and efficacy results are presented.

Results

Sixty-two patients (72.7±11.4years; 71.7% men; 81.0% New York Heart Association [NYHA] class III or IV; logistic Euroscore 18.7±13.1%; 93.3% MRgrade 3; 73.8% secondary MR) underwent percutaneous MVR using the MitraClip® under general anaesthesia. Procedural success was 95.2% (83.1% of patients received one clip; 16.9% received two clips). At discharge, 88.2% of implanted patients had a residual MRgrade 2. Transthoracic echocardiography showed a significant decrease in ejection fraction (39.9±14.8% pre vs. 36.2±14.3% post), end-diastolic diameter (63.8±10.6mm vs. 61.4±12.3mm, respectively) and systolic pulmonary pressure (52.1±13.9mmHg vs. 44.7±10.9mmHg, respectively). The in-hospital mortality rate was 3.2%. The survival rate at 6-month follow-up was estimated at 83.1%, with 90.9% of patients in NYHA class I or II and residual MRgrade 2 in 80% of cases.

Conclusion

This initial French experience, despite being in its learning phase, showed promising results in patients considered ineligible for surgery, as observed in more experienced centres. Randomized studies are mandatory to confirm these preliminary data.

The full text of this article is available in PDF format.
Résumé
Contexte

La réparation percutanée de la valve mitrale par le système MITRACLIP est une nouvelle option thérapeutique dans la prise en charge de la régurgitation mitrale sévère.

Objectifs

Cet article décrit l’expérience initiale du traitement percutané des IM sévères par le système « MitraClip » en France en termes d’efficacité et de tolérance.

Méthodes

Cette étude multicentrique rapporte l’expérience des centres français sur l’ensemble des procédures MitraClip® de décembre 2010 à septembre 2012. Tous les patients étaient jugés non éligibles ou à haut risque pour la chirurgie.

Résultats

Soixante-deux patients (72,7±11,4ans ; 71,7 % de sexe masculin ; 81,0 % de classe NYHA III ou IV ; logistic Euroscore : 18,7±13,1 % ; 93,3 % d’IM de grade 3 ou plus ; 73,8 % d’IM secondaire) ont bénéficié d’une procédure MitraClip sous-anesthésie générale. Le taux de succès de procédure était de 95,2 % (83,1 % des patients recevaient un clip et 16,9 % en recevaient deux). À la sortie de l’hôpital, 88,2 % des patients implantés avaient une IM résiduelle inférieure ou égale à 2. Les données d’échographie transthoracique ont rapporté une diminution significative de la fraction d’éjection (39,9±14,8 % pre vs 36,2±14,3 % post), du diamètre télédiastolique (63,8±10,6mm vs 61,4±12,3mm, respectivement) et de la pression pulmonaire systolique (52,1±13,9mmHg vs 44,7±10,9mmHg, respectivement). La mortalité intra-hospitalière était de 3,2 %. La survie à six mois post-procédure était estimée à 83,1 % avec 90,9 % des patients en classe NYHA de I ou II et 80 % avec une IM résiduelle inférieure ou égale à 2.

Conclusion

Cette expérience initiale, bien que dans sa phase d’apprentissage, rapporte, à l’instar de centres expérimentés, des résultats prometteurs chez des patients non éligibles à la chirurgie. Des essais randomisés contrôlés sont nécessaires pour confirmer ces résultats préliminaires.

The full text of this article is available in PDF format.

Keywords : Mitral regurgitation, Percutaneous intervention, French registry

Mots clés : Insuffisance mitrale, Intervention percutanée, Registre français

Abbreviations : MR, MVR, NYHA, PAPs, TAVI, VTI LVOT


Introduction

The recent revolution with transcatheter aortic valve implantation (TAVI) procedures has opened and stimulated the road to using the percutaneous approach for other valves. Different devices for the mitral valve have been tested in patients [1]. Most were stopped after disappointing initial experiences, some are in the early phase of development and only one – the MitraClip® system (Abbott Vascular, Santa Clara, CA, USA) – is in current commercial development (more than 6000 patients implanted worldwide), with encouraging results [2, 3, 4].

The objective of this paper is to describe initial French experience (seven centres) of feasibility, safety and efficacy and to discuss perspectives from growing worldwide experience.

Materials and methods
Study design and patient selection

This multicentre cohort study selected all patients who underwent a MitraClip procedure in France from December 2010 to September 2012.

All patients were judged inoperable or at high surgical risk by a heart team that included an interventional cardiologist, a cardiac surgeon, an echocardiographer and an anaesthesiologist. Procedure outcomes for all patients from seven French centres (Lyon, Montpellier, Nantes, Paris-Bichat, Paris-Massy, Rennes and Toulouse) were reported to a database. All centres had long-term experience of trans-septal catheterization and were authorized to perform TAVI according to French legislation. Data were collected anonymously from medical charts in each centre using a specific case report form and were recorded in a registry. The site reported events and changes in left ventricle function and mitral regurgitation (MR).

Description of procedure

All procedures were performed with proctoring from Abbott Vascular, including help in the selection of the patients (based on echocardiographic criteria as mentioned in the EVEREST programme), and the presence of two technician specialists during all the procedures. All implantations were performed in a catheterization laboratory or hybrid rooms under general anaesthesia. The medical team involved two interventional cardiologists or one interventional cardiologist plus one cardiac surgeon, one echocardiographer trained for the procedure and one anaesthesiologist. Fluoroscopy and three-dimensional transoesophageal echocardiography were systematically used throughout the procedure as previously described in the EVEREST II trial [2].

Endpoints

The feasibility of the MitraClip procedure was assessed by the proportion of successful clip implantations, corresponding to patients in whom a clip implantation was achieved.

Procedures were also described by the number of clips implanted per patient as well as by the mean duration of the procedure, corresponding to the duration from venous puncture to complete ablation of the implantation material.

Safety was evaluated and described by the occurrence of in-hospital deaths, in-hospital surgical mitral valve repairs (MVR) and other non-fatal adverse events, as well as by the proportion of per procedural blood transfusions. In-hospital events corresponded to events occurring during the hospital stay for the MitraClip procedure. The 6-month survival rate was also estimated.

Efficacy was assessed by the proportion of implanted patients with a residual MRgrade 2 at discharge and at 6months, as well as by the distribution of patients according to New York Heart Association (NYHA) class before procedure and at 6months. Furthermore, the impact of the MitraClip on echocardiographic variables was evaluated, taking into account systolic pulmonary artery pressure (PAPs), left ventricular end-diastolic diameter, left ventricular end-systolic diameter, ejection fraction, mean mitral gradient, velocity time-integral left ventricular outflow tract (VTI LVOT) and VTI mitral inflow. MR severity was quantified according to the American Society of Echocardiography guidelines [5]. Interpretation of echocardiographic examinations from each patient in the registry was not centralized.

Statistical analysis

Quantitative variables are presented as mean±standard deviation and were compared by using the paired Student's t test or the Wilcoxon signed rank test, depending on their normality, which was assessed by the Kolmogorov-Smirnov test. Ordinal variables are presented as counts and percentages and were compared by using the Wilcoxon signed rank test. For each variable, analysis was only performed on cases with matched data (i.e. excluding cases with missing data). A level of 0.05 was used to test for significance. Survival was calculated with the use of Kaplan-Meier analysis. Statistical analysis was performed using SPSS software, version 19.0 (IBM Corp., Armonk, NY, USA).

Results
Patient characteristics

From December 2010 to September 2012, 62 patients (71.7% men; 73.8% with secondary MR) underwent a percutaneous MVR using the MitraClip device; their demographic characteristics are presented in Table 1.

The number of MitraClip procedures performed in each centre varied between two and 18 (Paris-Bichat: n =18; Lyon: n =13; Nantes: n =9; Toulouse: n =9; Paris-Massy: n =7; Montpellier: n =4; Rennes: n =2). The mean logistic Euroscore was 18.7±13.1%. The mean number of hospitalizations for congestive heart failure in the 12months before the procedure was 2.5±2.6 per patient (range, 0–12) despite optimal medical treatment.

Procedural characteristics

The implantation started with a venous femoral access and a trans-septal puncture under fluoroscopy, plus two- and three-dimensional transoesophageal echocardiography. The clip delivery system was then introduced into the left atrium and the clip was positioned in the middle of the regurgitant jet where the two leaflets were grasped. After assessment of the regurgitation decrease, the decision to deliver or reposition the clip was taken. A second clip implantation was possible in case of unsatisfactory control of regurgitation.

Successful clip implantation was obtained in 95.2% of cases (95.5% for secondary MR; 92.8% for primary MR). One clip was implanted in 83.1% of cases and two clips in 16.9% of cases. The MR aetiologies in the patients who had two clips implanted were mainly functional (90% secondary MR vs. 10% primary MR). The three failed clip implantations, which occurred in two patients with primary MR (67%) and one with secondary MR (33%), corresponded to a challenging anatomy.

The mean duration of the procedure was 192±87min (range, 72–510min). Inotropic agents were used during the procedure in 28.6% of cases.

Postimplantation thromboprophylaxis included clopidogrel for 3–6months and low dose aspirin indefinitely. When vitamin K antagonists were needed (mainly for concomitant atrial fibrillation), the anticoagulation regimen combined a vitamin K antagonist with aspirin.

The mean duration of hospital stay was 10.9±8.8days (range, 4–43days; median, 8days).

Safety variables

In-hospital death occurred in two patients with secondary MR (3.2%): one on day 11 secondary to oesophagus complication and one on day 4 in a patient who required conversion to surgery, indicated for severe increased MR due to multiple grasping attempts during the MitraClip procedure.

Two other surgical MVRs were required after the MitraClip procedure (patients with secondary MR): one secondary to a clip partial detachment and one on day 11 because of a secondary mitral valve tear beside the clip. No further complications occurred in these two patients.

Other non-fatal adverse events were observed in seven patients (11.3%). One clip was implanted in the wrong position in the subvalvular apparatus, where it had been trapped during the intraventricular manoeuvres. No additional clip was implanted and this patient had an uneventful follow-up despite the persistence of non-modified MR. Other in-hospital events were: one deep venous thrombosis; one bleeding at puncture site; one new-onset atrial arrhythmia; one acute febrile respiratory illness; one false aneurysm at venous puncture site; and one tamponade on day 6 treated by percutaneous drainage.

Per procedural blood transfusion was necessary in five patients (8.1%); in these cases, the mean number of packed red blood cells received per patient was 3.0±2.2.

No cases of stroke or myocardial infarction were reported.

Efficacy variables at discharge and at 6-month follow-up

At discharge, the proportion of implanted patients with residual MRgrade 2 was 88.2%.

Echocardiographic data showed that MR severity grade, PAPs and left ventricular end-diastolic diameter were reduced before and after clip implantation (Table 2). VTI mitral inflow and mitral gradient were increased before and after the procedure. There was no significant change in left ventricular end-systolic diameter. Consequently, ejection fraction decreased from 39.9±14.8% to 36.2±14.3% (P =0.0004).

Short-term safety and efficacy outcomes depending on MR aetiology are summarized in Table 3.

Mean and median follow-up durations were 195 and 141days, respectively (range, 8–706days).

A Kaplan-Meier survival curve is shown on Figure 1. At 6-month follow-up, estimated survival was 83.1%, with 90.9% of patients in NYHA class I or II vs. 22.7% before MitraClip implantation (Figure 2). MR correction was maintained over time, with 12/15 patients (80%) with residual MRgrade 2 (Figure 3). Interestingly, PAPs was significantly reduced from 57.1±19.2mmHg to 45.8±9.5mmHg. Other variables were not modified because the number of observations was limited (Table 4).



Figure 1


Figure 1. 

Kaplan–Meier survival curve for the MitraClip French cohort.

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Figure 2


Figure 2. 

New York Heart Association (NYHA) class before mitral valve repair and at 6-month follow-up. Cases with matched data: n =22.

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Figure 3


Figure 3. 

Mitral regurgitation grade severity before mitral valve repair, at discharge and at 6-month follow-up. Cases with matched data: n =15.

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In implanted patients for whom 6-month follow-up visit was documented (n =24), no further surgery had been performed.

Discussion

The French centres that participated in this registry were already involved in the TAVI programme, with a structured heart team already used to performing accurate and multidisciplinary patient selection.

Encouraging results were seen in primary MR (Table 3) when the mitral valve prolapse was localized, ideally on P2, in a place where there are no chordae disturbing the clip implantation. This indication might be a good option when surgery is contraindicated or carries a very high risk.

One of the major evolutions with the MitraClip experience since the EVEREST II study publication [2] has been the shift in the indications, which were originally mainly organic (73% of primary MR vs. 23% of secondary MR in EVEREST II) and are now mainly functional (80% of secondary MR in the Euroaccess Registry). In this series, the ratio of 74% secondary MR corresponds to the current indications in Europe.

The MitraClip procedure is demanding, so the French experience reported here is still within the learning curve [6]. Thanks to an efficient proctoring support, the results of this initial experience are similar to those reported by more experienced teams in terms of proportions of successful clip implantation (95% in the French cohort vs. 98% in the German TRAMI registry [7]).

Procedure safety has been confirmed in this cohort, as previously described, and our results are similar to those reported in other recent publications [8, 9], despite the limited experience of the centres.

The efficacy of the MitraClip procedure in reducing MR severity grade has also been observed, with the limitations of quantification of MR after clip implantation. Indeed, quantification of severity of MR after MitraClip implantation may be challenging due to the presence of a double mitral orifice and multiple jets. However, previous studies have shown that the use of a combination of qualitative and quantitative variables (colour flow grade, vena contracta width, regurgitant orifice area, regurgitant volume and pulmonary vein flow pattern) in a systematic protocol may allow treatment efficacy after clip repair [10].

Finally, clinical benefit was achieved in patients in whom MR severity was corrected, as illustrated by the proportion of patients with NYHA functional class I or II at 6-month follow-up.

The main limitation of our study was the significant amount of missing data corresponding to variables not reported from each centre; this is the reason why our tables indicate the number of cases with matched data for greater clarity. Mid-term follow-up data (at 6months) on efficacy and tolerance were only available for a limited number of patients. Finally, a long-term view is needed to accurately determine the benefit of the MitraClip procedure on functional status.

It is too early to define who would be the best candidates for this technique, although the recent recommendations of the European Society of Cardiology/European Association for Cardio-Thoracic Surgery have mentioned this option for the first time. Percutaneous MVR may be considered in patients with symptomatic severe primary MR who fulfil the echo criteria of eligibility, are judged inoperable or at high surgical risk by a heart team and have a life expectancy>1year (recommendation class IIb, level of evidence C) [11]. This option may also be considered in patients with symptomatic severe secondary MR despite optimal medical therapy (including cardiac resynchronization therapy if indicated), with the same criteria as for primary MR (recommendation class IIb, level of evidence C) [11, 12].

As the level of evidence supporting its routine use in patients with secondary MR is limited to cohort studies, prospective comparative studies are now mandatory in order to assess the impact of percutaneous MVR in terms of cardiovascular mortality and morbidity, as well as quality of life. The COAPT and RESHAPE trials have recently started in well-defined populations of patients with secondary MR [13, 14]. Furthermore, the cost of this new therapeutic approach is currently not reimbursed in France, limiting its diffusion on a larger scale. Therefore, considering the potential impact of the percutaneous correction of severe MR in terms of reducing the rate of unplanned hospitalizations, evaluation should include both clinical and economical endpoints, i.e. the ‘cost-effectiveness ratio’ of this technique vs. optimal medical treatment. A French multicentre randomized trial – the MITRA-FR study – has just been approved by the ‘Programme Hospitalier de Recherche Clinique’ (French Health Ministry) and will soon be underway in patients with severe symptomatic secondary MR.

Conclusions

In conclusion, due to promising results, the success of the MitraClip is growing, with more than 6000 patients implanted worldwide, particularly in Northern Europe and Italy. The preliminary data of our registry are encouraging in terms of both efficacy and safety and may solve an unmet need in patients who are ineligible for conventional surgery. A randomized trial has been approved by the French Health Ministry in patients with cardiac failure and secondary MR in order to confirm these results with a higher level of evidence, leading to the possibility of reimbursement and more widespread use in our country.

Disclosure of interest

Nicolas Dumonteil: speaker honoraria from Abbott Vascular; Nicolas Piriou: speaker honoraria from Abbott Vascular; David Messika-Zeitoun: lecture fees from Abbott Vascular; Nicolas Boudou: speaker honoraria from Abbott Vascular; Jean-François Obadia: Landanger, Saint-Jude Medical, Edwards; other authors: none.


Acknowledgements

The authors would like to thank each institution (Drugs and Medical Devices Committees, Innovation Committees and others) for their support and approval of the use of the MitraClip® system, allowing this initial experience despite the absence of reimbursement.

References

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