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 ± 11.4 years; 71.7% men; 81.0% New York Heart Association [NYHA] class III or IV; logistic Euroscore 18.7 ± 13.1%; 93.3% MR ≥ grade 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 MR ≤ grade 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 ± 10.6 mm vs. 61.4 ± 12.3 mm, respectively) and systolic pulmonary pressure (52.1 ± 13.9 mmHg vs. 44.7 ± 10.9 mmHg, 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 MR ≤ grade 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.
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 ± 11,4 ans ; 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 ± 10,6 mm vs 61,4 ± 12,3 mm, respectivement) et de la pression pulmonaire systolique (52,1 ± 13,9 mmHg vs 44,7 ± 10,9 mmHg, 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.
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 . 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 .
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 .
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 MR ≤ grade 2 at discharge and at 6 months, as well as by the distribution of patients according to New York Heart Association (NYHA) class before procedure and at 6 months. 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 . 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 .
| Variable | |
|---|---|
| Age (years) | 72.7 ± 11.4 |
| Age > 65 years | 79 |
| Men | 71.7 |
| Permanent pacemaker or implantable automatic defibrillator | 41.9 |
| Previous cardiovascular surgery | 30.6 |
| Previous percutaneous coronary intervention | 27.4 |
| History of coronary artery disease | 57.4 |
| Number of hospitalizations for CHF (< 12 months) | 2.5 ± 2.6 |
| Logistic Euroscore (%) | 18.7 ± 13.1 |
| NYHA class III or IV | 81.0 |
| MR severity at rest ≥ grade 3 | 93.3 |
| MR etiology | |
| Primary | 23.0 |
| Secondary | 73.8 |
| Mixed | 3.2 |
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 12 months 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 ± 87 min (range, 72–510 min). Inotropic agents were used during the procedure in 28.6% of cases.
Postimplantation thromboprophylaxis included clopidogrel for 3–6 months 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 ± 8.8 days (range, 4–43 days; median, 8 days).
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 MR ≤ grade 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).
