Initial experience with the WATCHMAN™ left atrial appendage system for stroke prevention in atrial fibrillation: A single-centre registry

Initial experience with the WATCHMAN™ left atrial appendage system for stroke prevention in atrial fibrillation: A single-centre registry

+Model ARTICLE IN PRESS ACVD-928; No. of Pages 7 Archives of Cardiovascular Disease (2016) xxx, xxx—xxx Available online at ScienceDirect www.sci...

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ACVD-928; No. of Pages 7

Archives of Cardiovascular Disease (2016) xxx, xxx—xxx

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CLINICAL RESEARCH

Initial experience with the WATCHMANTM left atrial appendage system for stroke prevention in atrial fibrillation: A single-centre registry Expérience préliminaire de l’occlusion de l’auricule gauche par une prothèse de WATCHMANTM pour prévenir la survenue d’un accident vasculaire cérébral embolique dans la fibrillation auriculaire : registre monocentrique Guillaume Bonnet a, Erwan Salaun b, Mathieu Pankert a, Thomas Cuisset a, Jean-Louis Bonnet a,∗ a b

Service de cardiologie A, CHU Timone, 265, rue Saint-Pierre, Marseille cedex 05, France Service de cardiologie B, CHU Timone, Marseille, France

Received 7 May 2015; received in revised form 20 February 2016; accepted 3 March 2016

KEYWORDS Left atrial appendage closure; WATCHMANTM

Summary Background. — Left atrial appendage (LAA) closure using the WATCHMANTM device (WM) may be considered in patients with non-valvular atrial fibrillation (AF) and a high-risk of stroke who are ineligible for long-term oral anticoagulation (OAC). Aim. — To report our single-centre preliminary experience, focusing on feasibility, safety and short-term efficacy of this procedure. Methods. — Patients implanted from December 2013 to February 2014 were included. The procedure, performed under general anaesthesia, was guided by fluoroscopy and transoesophageal

Abbreviations: AF, atrial fibrillation; CHADS2 , Cardiac failure, Hypertension, Age, Diabetes, Stroke (Doubled); CHA2 DS2 -VASc, Cardiac failure, Hypertension, Age ≥ 75 years (Doubled), Diabetes, Stroke (Doubled), Vascular disease, Age 65—74 years and Sex category (Female); CI, confidence interval; HAS-BLED, Hypertension, Abnormal liver/renal function, Stroke, Bleeding, Labile international normalized ratio, Elderly (age > 65 years), Drugs/alcohol; LAA, left atrial appendage; NOAC, non-vitamin K antagonist oral anticoagulant; OAC, oral anticoagulant; TOE, transoesophageal echocardiography. ∗ Corresponding author. E-mail address: [email protected] (J.-L. Bonnet). http://dx.doi.org/10.1016/j.acvd.2016.03.003 1875-2136/© 2016 Elsevier Masson SAS. All rights reserved.

Please cite this article in press as: Bonnet G, et al. Initial experience with the WATCHMANTM left atrial appendage system for stroke prevention in atrial fibrillation: A single-centre registry. Arch Cardiovasc Dis (2016), http://dx.doi.org/10.1016/j.acvd.2016.03.003

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ARTICLE IN PRESS G. Bonnet et al. echocardiography (TOE). Efficacy was defined as the ability to implant the WM with no peridevice leak; safety was defined as the occurrence of in-hospital and 45-day events, including stroke, pericardial effusion and device migration. Results. — Twenty-three patients (mean age: 77.6 years; 16 men [69.6%]; mean CHA2 DS2 -VASc score: 5) underwent WM implantation. The indication was gastrointestinal bleeding in 14 (60.9%) patients, cerebral haemorrhage in eight (34.8%) and need for long-term ticagrelor after stent thrombosis on clopidgrel in one (4.3%). Procedural success was 95.7% (95% confidence interval: 77.3—100.0); efficacy was 90.9% (95% confidence interval: 71.0—98.7). The size of the implanted WATCHMANTM device was in agreement with the prespecified size, based on measurement of the LAA, in 56.5% of cases. In five cases, the criteria were not met, but the device was successfully implanted in four of these, with a good result (80.0%). Treatment at discharge was a reduced dose of anticoagulant plus aspirin in three cases (13.0%) or antiplatelet therapy alone in 20 cases (90.9%). No adverse event occurred during the index hospitalization or at 45 days. At 45 days, the LAA was sealed in 18/19 patients (94.7%) on TOE, with no difference between those who did or did not have an implanted device of the prespecified size. Conclusion. — When performed by an operator trained in the procedure, WM implantation appears to be safe and effective. This procedure may be considered in patients at high-risk of stroke who are ineligible for long-term OAC. © 2016 Elsevier Masson SAS. All rights reserved.

MOTS CLÉS Fibrillation auriculaire ; Occlusion de l’auricule gauche ; Prévention de l’accident vasculaire cérébral ischémique ; Prothèse de WATCHMANTM

Résumé Contexte. — L’occlusion de l’auricule gauche (AG), par une prothèse de WATCHMANTM , peut être proposée à certains patients présentant une fibrillation auriculaire (FA) non valvulaire, un risque élevé d’accident vasculaire cérébral embolique (AVC) et une contre-indication au traitement anticoagulant oral (ACO) de longue durée. Objectif. — Rapporter les résultats préliminaires de notre centre, en termes de faisabilité, sécurité et efficacité à court terme. Méthodes. — Les premiers patients implantés entre décembre 2013 et février 2015 ont été inclus. L’intervention était réalisée sous anesthésie générale, et la procédure guidée par radioscopie et échographie trans-œsophagien (ETO). L’efficacité de la procédure était définie par l’implantation d’une prothèse sans fuite péri-prothétique résiduelle et la sécurité par la proportion de patients ayant présenté un AVC, un épanchement péricardique ou une migration de prothèse durant l’hospitalisation ou à 45 jours. Résultats. — La procédure a été tentée chez 23 patients (77,6 ans ; 16 hommes [69,6 %] ; 12 FA permanent [52,2 %] ; CHA2 DS2 -VASc score moyen : 5 ; HAS-BLED score moyen : 4,8). L’indication était une hémorragie digestive dans 14 cas (60,9 %), cérébrale 8 fois (34,8 %) et la nécessité d’un traitement par ticagrelor justifié par une thrombose de stent survenue sous clopidogrel 1 fois (4,3 %). La prothèse était implantée avec succès dans 95,7 % des cas (intervalle de confiance de 95 % : 77,3—100,0) et de manière efficace dans 90,9 % (intervalle de confiance de 95 % : 71,0—98,7). La taille de la prothèse implantée était celle choisie à partir des mesures des diamètre et longueur maximaux de l’AG dans 56,5 % des cas. Bien que les critères d’implantation ne soient pas tous réunis chez 5 patients, la prothèse était implantée avec succès 4 fois (80,0 %). Le traitement de sortie était une dose réduite d’un anticoagulant 3 fois (13,6 %) et une antiagrégation plaquettaire seule chez 20 patients (90,9 %). Aucun événement n’a été déploré dans les suites de la procédure ou lors du contrôle. À 45 jours, l’AG était occlue chez 18 des 19 patients contrôlés par ETO (94,7 %) sans différence entre ceux pour lesquels la taille de la prothèse respectait les mesures ETO pré-implantation et les autres. Conclusion. — Réalisée par un opérateur expérimenté dans la ponction trans-septale et ayant bénéficié d’une formation spécifique, l’implantation d’un WM est une procédure sûre et efficace. Elle peut être envisagée chez les patients présentant un haut risque d’AVC et une contre-indication au traitement ACO au long cours. © 2016 Elsevier Masson SAS. Tous droits r´ eserv´ es.

Please cite this article in press as: Bonnet G, et al. Initial experience with the WATCHMANTM left atrial appendage system for stroke prevention in atrial fibrillation: A single-centre registry. Arch Cardiovasc Dis (2016), http://dx.doi.org/10.1016/j.acvd.2016.03.003

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Experience with the WATCHMANTM for stroke prevention in AF

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Background

WATCHMANTM LAA system

Atrial fibrillation (AF) is the most common sustained arrhythmia, with an estimated prevalence of 6 million among all Europeans [1]. As AF mainly affects elderly people, its prevalence is expected to increase in parallel with the increasing age of the population, with a projected doubling of the disease in the next 50 years [1,2]. Stroke is the most serious complication of AF, and occurs in 5% of non-anticoagulated patients every year, with an incidence that increases from 1—5% in individuals aged 50—59 years to 23.5% for those aged 80—89 years [3]. Randomized controlled trials have shown that the oral anticoagulant (OAC) warfarin is effective in preventing stroke — more so than aspirin or the combination of aspirin plus clopidogrel [4] — but is associated with a high-risk of bleeding complications [5]. Non-vitamin K antagonist oral anticoagulant anticoagulants (NOACs) have a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage and mortality compared with warfarin, but with similar major bleeding complications and an increase in gastrointestinal bleeding [6]. In autopsy and echocardiography studies, the left atrial appendage (LAA) was shown to be the source of thrombi in > 90% of patients with non-valvular atrial fibrillation and a recent embolic event [7,8]. Percutaneous catheter-based devices have been developed to close and thereby effectively exclude LAA from the systemic circulation. Pilot studies have shown acceptable risk-benefit ratios for these non-pharmacological alternatives to chronic warfarin therapy [9—13]. The PROTECT-AF study provided the first evidence from a randomized clinical trial that a strategy of LAA occlusion using the WATCHMANTM device (Boston Scientific, Natick, MA, USA) can be non-inferior to anticoagulation with warfarin for a combined endpoint of stroke, cardiovascular death and systemic embolism in patients with non-valvular atrial fibrillation [14,15]. The objective of this study was to describe our first year of experience with the WATCHMANTM LAA system in terms of feasibility and safety, and to discuss perspectives to improve patient and device selection.

The WATCHMANTM system is a three-part system consisting of a transseptal access sheath, a delivery catheter and an implantable nitinol device. The system is designed to facilitate device placement via femoral venous access via the transseptal route into the LAA. The 14 F transseptal access sheath is available in a double- or single-curve configuration. The access sheath is used to gain access to the LAA, and serves as a conduit for the delivery catheter. The WATCHMANTM device comprises a self-expanding nickel titanium (nitinol) frame structure, with fixation barbs and a permeable polyester fabric that covers the atrial facing surface of the device. The implant is constrained in a 12 F sheath (delivery system) until deployment in the LAA. The WATCHMANTM device is available in diameters of 21, 24, 27, 30 and 33 mm, to accommodate the unique anatomy of each patient’s LAA. The device is deployed by retracting the sheath covering the device; it can be partially recaptured and redeployed if the implant location is deemed unsatisfactory, or recaptured completely if a device of a different size is determined to be more suitable.

Methods Patient selection Patients with paroxysmal, persistent or permanent nonvalvular AF were eligible for LAA closure if they had a definite contraindication to long-term OACs and if the procedure was considered achievable based on images obtained from transoesophageal echocardiography (TOE). The final decision was taken by a medical team, including a gastroenterologist, a neurologist, a geriatrician and the cardiologists involved. The CHA2 DS2 -VASc (Cardiac failure, Hypertension, Age ≥ 75 years [Doubled], Diabetes, Stroke [Doubled], Vascular disease, Age 65—74 years and Sex category [Female]) and HAS-BLED (Hypertension, Abnormal liver/renal function, Stroke, Bleeding, Labile international normalized ratio, Elderly [age > 65 years], Drugs/alcohol) risk scores were calculated in all cases.

Device implantation All procedures were performed in a catheterization laboratory under general anaesthesia. The medical team involved two interventional cardiologists, one cardiologist specialized in echocardiography and trained for the procedure and one anaesthesiologist. TOE was used for preprocedural evaluation of the LAA and implantation guidance. The presence of a thrombus within the LAA was a contraindication for the procedure. The size of the LAA was determined by the measurement at the landing zone of the device, 10 or 20 mm distal to the orifice, beyond the left lateral ridge, adjacent to the circumflex artery. The diameter at the landing zone was evaluated in four views (0◦ , 45◦ , 90◦ and 135◦ ). The number of lobes was assessed, and the distance between the landing zone and the apex of the primary lobe was measured, as it represents the usable LAA length. If the appendage was particularly angulated, the length was measured before the angulation. The ratio of maximal to minimal diameter of the LAA defined the shape at its orifice as circular (1.0—1.1), semielliptical (1.2—1.3) or elliptical (≥ 1.4). The choice of the size of the device was based on the maximal diameter at the landing zone and the length of the LAA measured in the primary lobe from the landing zone to the tip, at a mid left atrium pressure level ≥ 10 mmHg. The device size was chosen to be 8—20% larger than the diameter of the LAA body, to have sufficient compression for stable positioning and anchoring of the device. Therefore, the diameter of the LAA had to be > 17 mm (20% compression of a 21 mm WATCHMANTM device) or < 30 mm (8% compression of a 33 mm WATCHMANTM device). Moreover, the length of the LAA had to be greater than or equal to the maximal landing zone diameter, because the sheath-constrained length of the WATCHMANTM device is very similar to its unconstrained diameter once deployed. Accordingly, a ratio of maximal diameter to maximal length ≤ 1 is required.

Please cite this article in press as: Bonnet G, et al. Initial experience with the WATCHMANTM left atrial appendage system for stroke prevention in atrial fibrillation: A single-centre registry. Arch Cardiovasc Dis (2016), http://dx.doi.org/10.1016/j.acvd.2016.03.003

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After transseptal puncture, the pigtail catheter was carefully advanced through the access sheath into the distal LAA under fluoroscopic guidance. The access sheath was then advanced over the pigtail catheter. Opacification of the LAA is usually done in two oblique views at 20◦ (cranial 30◦ and caudal 30◦ ). The access sheath was advanced until the access sheath marker band corresponding to the device size was at the level of the landing zone. Proper device positioning was confirmed by angiography and echocardiography. The pigtail catheter was slowly removed and the delivery system was advanced into the access sheath under fluoroscopic guidance, until the most distal marker band was aligned with the most distal marker band on the access sheath. The delivery system was stabilized, and the access sheath was retracted and snapped together to form the access sheath/delivery system assembly. The WATCHMANTM device was deployed by retracting the assembly. Proper positioning and stability were verified by TOE and angiography (tug test) before device release. After implantation, the size of the device at the landing zone was measured in the four index views, to assess the decompression percentage and to identify a protrusion in the LAA or a peridevice flow. Compression of the implanted device was optimal, suboptimal or inappropriate when it was between 8% and 20% in, respectively, 4, 2, 3 or < 2 views. Transthoracic echocardiography was performed 3 hours later and on day after implantation, to rule out pericardial effusion and device migration.

Medical treatment and follow-up Heparin was given during the procedure (60 IU/kg), immediately after the transseptal puncture, and was stopped after implantation. After a successful event-free procedure, patients were discharged with an individualized antithrombotic treatment depending on the characteristics of the bleeding: either aspirin alone (75 mg/day) or combined with clopidogrel (75 mg/day) or an anticoagulant at a low-dose. TOE imaging was planned at 45 days to assess residual peridevice flow and device stability and position, as well as at follow-up visits at 6 months, 12 months and then every year for neurological assessments.

Endpoints Feasibility was assessed as the proportion of successful device implantations. Efficacy was determined by the percentage of LAAs that were optimally sealed after the procedure and at 45 days, defined as an absence of or minimal flow around the device (jet ≤ 5 mm) evaluated by TOE. Compliance with the planned strategy was defined as the proportion of implanted devices with a size in agreement with the prespecified evaluation, based on TOE measurement of the maximal diameter and length of the LAA. The effect of agreement with or deviation from the prespecified evaluation on the immediate and mid-term results was assessed, focusing on compression, protrusion and leakage (jet > 5 mm) after implantation, and sealing or migration at 45 days. Safety was evaluated by the occurrence of in-hospital events, mainly pericardial effusion, device embolization,

procedure-related stroke and 45-day clinical outcome, focusing on stroke or transient ischaemic attack and device embolization.

Statistical analysis Continuous variables are presented as means, with standard deviations and minimum and maximum values. Estimates of the frequency of occurrence of events are expressed as percentages or rates. PASW Statistics 17.0 software (IBM, Armonk, NY, USA) was used to perform the statistical analysis.

Results Patient characteristics From 12 December 2013 to 26 February 2014, 23 patients where eligible for WATCHMANTM device implantation: 16 men (69.6%); 7 women (30.4%); mean age: 77.6 years (range: 57—93 years). Patients’ demographic characteristics are presented in Table 1. AF was permanent in 12 patients

Table 1

Patient characteristics at baseline (n = 23).

Variable Age (years) Men Atrial fibrillation pattern Permanent Paroxysmal or persistent CHA2 DS2 -VASc score 3 4 5 6 9 Congestive heart failure History of hypertension Age ≥ 75 years Diabetes mellitus History of ischaemic stroke or transient ischaemic attack Vascular disease Age 65—74 years Anticoagulation before implantation No anticoagulant Low-dose NOAC Low-dose low-molecular-weight heparin

77.6 (57—93) 16 (69.6) 12 (52.2) 11 (47.8) 3 6 7 5 2 13 21 16 9 6

(13.0) (26.1) (30.4) (21.7) (8.7) (56.5) (91.3) (69.6) (39.1) (26.1)

17 (73.9) 5 (21.7)

16 (69.6) 7 (30.4) 4 (17.4)

Data are expressed as mean (range) or number (%). CHA2 DS2 VASc: Cardiac failure, Hypertension, Age ≥ 75 years (Doubled), Diabetes, Stroke (Doubled), Vascular disease, Age 65—74 years and Sex category (Female); NOAC: non-vitamin K antagonist oral anticoagulant.

Please cite this article in press as: Bonnet G, et al. Initial experience with the WATCHMANTM left atrial appendage system for stroke prevention in atrial fibrillation: A single-centre registry. Arch Cardiovasc Dis (2016), http://dx.doi.org/10.1016/j.acvd.2016.03.003

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Experience with the WATCHMANTM for stroke prevention in AF (52.2%). The mean CHA2 DS2 -VASc score was 5 (range: 3—9), indicating a high stroke risk. The most frequently occurring CHA2 DS2 -VASc characteristic was hypertension in 21 patients (91.3%), followed by history of vascular disease in 17 (73.9%) patients, including 13 (56.5%) with coronary artery disease. Indications for long-term NOAC cessation are shown in Table 2; these were severe bleeding in 22 patients (95.7%), and the need for long-term treatment with ticagrelor and aspirin after a successful percutaneous coronary intervention for stent thrombosis in one patient (4.3%), who was receiving clopidogrel and aspirin at the time of the acute coronary event. The location of the bleeding was gastrointestinal in 14 patients (63.6%), all with a need for repeated blood transfusions, and cerebral in eight patients (36.4%). The mean HAS-BLED risk score was 4.8 (range: 3—6), indicating a high bleeding risk. The most frequently occurring HAS-BLED characteristic was age ≥ 65 years (21 patients; 91.3%), followed by long-term treatment with aspirin (16 patients; 69.6%); 10 patients (43.5%) were receiving an antiplatelet agent for vascular disease in 9 of 10 (90%). NOAC treatment had been withdrawn at the time of the procedure in 16 patients (69.6%); the dosage had been reduced in seven patients (30.4%) and it had been replaced by a low-dose heparin in 4 patients (17.4%).

Procedural details The average maximal and minimal LAA diameters were 23.3 mm (range: 16—31 mm) and 19.5 mm (range: 12—27 mm). The shape of the LAA at the landing zone was circular in eight patients (34.8%), semielliptical in 11 patients (47.8%) and elliptical in four patients (17.4%). The LAA was single lobed in nine patients (39.1%), with a severe bend in one patient (4.3%), double lobed in 10 patients (43.5%) and multilobed in four patients (17.4%). The average maximal length of the primary lobe was 32 mm (range: 20—44 mm).

Table 2 Reason for ineligibility for long-term anticoagulant and bleeding risk. Variable Acute gastrointestinal haemorrhage Recurrent gastrointestinal bleeding Cerebral haemorrhage Need for long-term ticagrelor HAS-BLED score 3 4 5 6 Abnormal renal function Abnormal liver function Age ≥ 65 years Long-term treatment with aspirin

6 8 8 1

(21.6) (34.8) (34.8) (4.3)

2 4 13 4 13 1 21 16

(8.7) (17.4) (56.5) (17.4) (56.5) (4.3) (91.3) (69.6)

Data are expressed as number (%). HAS-BLED: Hypertension, Abnormal liver/renal function, Stroke, Bleeding, Labile international normalized ratio, Elderly (age > 65 years), Drugs/alcohol.

5 Based on the maximal diameter, two WATCHMANTM sizes could fit the LAA in nine patients (39.1%), one size could fit the LAA in 12 patients (52.2%) and no size could fit the LAA in two patients (8.7%). Based on the maximal diameter and length, two WATCHMANTM sizes could fit the LAA in six patients (26.1%), one size could fit the LAA in 12 patients (52.2%) and no size could fit the LAA in five patients (21.7%). Nevertheless, implantation was attempted in 23 patients. A recapture of the device was necessary in seven patients (30.4%) because of a technical issue in two patients (8.7%) and for replacement with a larger size in two patients (8.7%). In one patient (4.3%), LAA occlusion followed the implantation of two MitraClips (Abbott Vascular, Abbott Park, IL, USA) to reduce severe mitral regurgitation. The procedure was successful in 22 patients (95.7%, 95% confidence interval [CI]: 77.3—100.0) and effective in 20 patients (90.9%, 95% CI: 71.0—98.7). The median WATCHMANTM size was 27 mm (range: 21—33 mm); two patients (8.7%) received the 21-mm size, nine (39.1%) received the 24-mm size, two (8.7%) received the 27-mm size, five (21.7%) received the 30-mm size and four (17.4%) received the 33-mm size. After implantation, the LAA orifice was circular in 17 patients (77.3%) and semielliptical in five patients (22.7%). In the patient with the most elliptical orifice (ratio: 1.7), it became circular (ratio: 1.0), but with a peridevice leak despite adequate compression. The compression of the device was evaluated in 22 patients (95.7%); it was considered optimal in 10 patients (45.5%), suboptimal in six patients (27.3%) and excessive in six patients (27.3%). The ratio of maximal diameter to maximal length of the LAA was optimal in 18 patients (81.8%), the length of the primary lobe being, in theory, too short to implant the optimal size in four patients (18.2%). A minor leak was identified in two patients (9.1%) with overcompression. A protrusion was noted in eight patients (36.4%): two (9.1%) were associated with excess compression; three (13.6%) had a lobe that was too short; and three (13.6%) were unexplained by the data derived from the sizing. The size of the implanted device was in agreement with the prespecified size in 12 patients (52.2%) and deviated from the prespecified size in 11 patients (47.8%) — larger in seven patients (30.4%) and smaller in three patients (13.0%). There was no difference between the agreement with or deviation from the prespecified size groups with regard to the rate of optimal, suboptimal or excessive WATCHMANTM compression (6 [50.0%], 2 [16.7%], 4 [33.3%] vs. 4 [36.4%], 4 [36.4%], 2 [16.7%], respectively) or protrusion (5 [41.7%] vs. 8 [66.7%]), the failed procedure being in the latter group.

Medical treatment and follow-up No adverse in-hospital event occurred during hospitalization. All patients were discharged on antiplatelet therapy: two received clopidogrel 75 mg alone (8.7%) and 21 received aspirin 75 mg (91.3%), which was combined with a lowdose anticoagulant until TOE at 45 days in three patients (13.0%), combined with clopidogrel in nine patients (39.1%), combined with ticagrelor in one patient (4.3%) or given as a single therapy in eight patients (34.8%). In the eight patients with a history of cerebral haemorrhage, treatment was limited to aspirin in five patients

Please cite this article in press as: Bonnet G, et al. Initial experience with the WATCHMANTM left atrial appendage system for stroke prevention in atrial fibrillation: A single-centre registry. Arch Cardiovasc Dis (2016), http://dx.doi.org/10.1016/j.acvd.2016.03.003

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(62.5%), combined with a low-dose of low-molecular-weight heparin in one patient (12.5%) and with clopidogrel in two patients (25%). In the 14 patients with a history of gastrointestinal bleeding, two received clopidogrel alone (14.3%), two received aspirin alone (14.3%), two received aspirin in combination with a low-dose anticoagulant (14.3%) and eight received aspirin plus clopidogrel (57.1%). One patient was discharged on ticagrelor and aspirin after percutaneous coronary intervention for stent occlusion. All successfully implanted patients were event-free at 45 days. TOE was performed in 19 patients (86.4%), showing an occlusion of the LAA in 18 patients (94.7%). The LAA remained patent in one of the two patients with a postprocedural leak.

Discussion The results of our preliminary study confirm the feasibility (95.7%), efficacy (90.9%) and safety (0% events) of the WATCHMANTM procedure, but underline the need for better analysis of the shape and measurements of the LAA before considering the procedure. In this study, the medical indication for LAA closure followed current European expert opinion [16]. The European Society of Cardiology published updated guidelines for the management of AF in 2012, and gave the WATCHMANTM technique a Class IIb with a level of evidence B indication for patients with a high stroke risk and contraindications for long-term OACs [17]. Nevertheless, on 13 June 2014, the Haute Autorité de Santé in France restricted the indication to patients with a CHA2 DS2 -VASc risk score ≥ 4 with a definite contraindication to long-term NOACs established by a multidisciplinary team. In our study, three patients had a score < 4; all had received repeated blood transfusions for gastrointestinal bleeding and one had a history of stroke, and the indication was discussed by the cardiologists and gastroenterologists in charge of these patients. Nevertheless, according to the European Society of Cardiology, efficacy and safety evidence is currently insufficient to recommend this approach for any patients other than those in whom long-term OACs are contraindicated [17]. No adverse event was observed during or after the procedure, despite the need for a recapture of the device in seven patients. In all patients, LAA occlusion was performed by a skilled operator acquainted with transseptal puncture techniques and pericardiocentesis, having long-term experience of mitral valvuloplasty and having been involved in a MitraClip registry. Before the first procedure, the primary and secondary operators, accompanied by an echocardiographer dedicated to the procedure, had attended theory courses, practical bench training and hands-on simulator training on virtual cases, and had obtained a certificate of completion. In the main PROTECT-AF study, which showed that the efficacy of percutaneous closure of the LAA with the WATCHMANTM device was non-inferior to that of warfarin therapy in patients with non-valvular AF, serious pericardial effusion (defined as the need for percutaneous or surgical drainage) occurred in 4.8% of patients, effusion rates declining with operator experience [14,15]. The PREVAIL trial demonstrated an improvement in the safety endpoint [18]. All 7-day procedure-related complications, defined

as a composite of cardiac perforation, pericardial effusion with tamponade, ischaemic stroke, device embolization and other vascular complications, decreased from 8.7% in PROTECT-AF to 4.2% in PREVAIL (P = 0.004). After implantation, none of the patients in our study received a NOAC. This strategy deviated from the protocol of systemic anticoagulation adopted in the landmark PROTECT-AF study [14]. In the prospective non-randomized ASAP study, including patients with non-valvular AF and a CHADS2 (Cardiac failure, Hypertension, Age, Diabetes, Stroke [Doubled]) score ≥ 1, who were considered ineligible for warfarin, 6 months of treatment with clopidogrel and aspirin was given [19]. All-cause stroke or systemic embolism occurred in four of 150 patients (2.3% per year) and ischaemic stroke in three (1.7% per year). This ischaemic stroke rate was less than expected (7.3% per year) based on the CHADS2 scores of the patient cohort. Kar et al. [20] observed complete neoendocardial coverage of the WATCHMANTM device 28 days after implantation in a canine model. At 45-day follow-up, patients with no significant peridevice leak were able to stop taking warfarin in the PROTECT-AF study [14]. The most surprising results of this preliminary study were related to the procedure itself. Based on measurement of the maximal diameter of the orifice of the LAA and the length of its primary lobe by TOE, the size of the device was inadequate in half of the patients, but with no effect on the final result or follow-up. Early peridevice leak was associated with overcompression, but the latter was noted even in patients who had a supposedly optimally sized device implanted. In addition, protrusion was noted, not only in patients with a too-long sheath-constrained device compared with the length of the lobe, but also in patients with an optimal WATCHMANTM device. No migration was detected at 45 days despite overcompression. This finding may be explained by a lack of sensitivity of TOE for measuring the structures of interest or, more importantly, by a lack of device capacity to adapt to the LAA. However, these hypotheses are to be confirmed, and there is a need to improve the results of the procedure.

Study limitations This study was designed to test the feasibility and safety of the WATCHMANTM procedure. The study size was not large enough to address efficacy, and the reported follow-up was limited to 45 days.

Conclusion Occlusion of the LAA with a WATCHMANTM implant is safe when carried out by trained operators with extensive experience in septal puncture. The procedure can be considered in patients ineligible for long-term anticoagulation and with a high-risk of embolic stroke. However, evaluation of the morphology and size of the LAA needs to be improved. Contemporary contrast-enhanced gated multidetector cardiovascular computed tomography could be an interesting modality for evaluating patients non-invasively before intervention.

Please cite this article in press as: Bonnet G, et al. Initial experience with the WATCHMANTM left atrial appendage system for stroke prevention in atrial fibrillation: A single-centre registry. Arch Cardiovasc Dis (2016), http://dx.doi.org/10.1016/j.acvd.2016.03.003

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Experience with the WATCHMANTM for stroke prevention in AF

Disclosure of interest The authors declare that they have consulting agreement with Boston Scientific International S.A.

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Please cite this article in press as: Bonnet G, et al. Initial experience with the WATCHMANTM left atrial appendage system for stroke prevention in atrial fibrillation: A single-centre registry. Arch Cardiovasc Dis (2016), http://dx.doi.org/10.1016/j.acvd.2016.03.003