A prospective, multi-center, single-arm study of a novel double-disc left atrial appendage closure system: The periprocedural and mid-term outcomes (english version)

Shuang Li; Wei Chen; Mengyun Zhu; Junbo Ge; Daxin Zhou; Xiaochun Zhang; Jianan Wang; Youqi Fan; Yan Wang; Dong Chang; Yihan Chen; Fadong Chen; Hua Fu; Hongde Hu; Heng Cai; Yushun Zhang; Jing Zhou; Wei Ma; Zhongyuan Ren; Dongdong Zhao; Kai Tang; Yifan Zhao; Xiaoxin Chang; Weijing Liu; Yawei Xu

doi:10.4103/ijhr.ijhr_5_21

ORIGINAL ARTICLE

Year : 2021 | Volume : 6 | Issue : 1 | Page : 60-66

A prospective, multi-center, single-arm study of a novel double-disc left atrial appendage closure system: The periprocedural and mid-term outcomes (english version)

Shuang Li¹, Wei Chen¹, Mengyun Zhu¹, Junbo Ge², Daxin Zhou², Xiaochun Zhang², Jianan Wang³, Youqi Fan³, Yan Wang⁴, Dong Chang⁴, Yihan Chen⁵, Fadong Chen⁵, Hua Fu⁶, Hongde Hu⁶, Heng Cai⁷, Yushun Zhang⁸, Jing Zhou⁹, Wei Ma⁹, Zhongyuan Ren¹, Dongdong Zhao¹, Kai Tang¹, Yifan Zhao¹, Xiaoxin Chang¹, Weijing Liu¹, Yawei Xu¹
¹ Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
² Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China
³ Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
⁴ Department of Cardiology, Xiamen Cardiovascular Hospital of Xiamen University, Xiamen, Fujian Province, China
⁵ Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
⁶ Department of Cardiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
⁷ Department of Cardiology, General Hospital of Tianjin Medical University, Tianjin, China
⁸ Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
⁹ Department of Cardiology, The First Hospital of Peking University, Beijing, China

Date of Submission	24-Feb-2021
Date of Decision	12-May-2021
Date of Acceptance	20-May-2021
Date of Web Publication	30-Jun-2021

Correspondence Address:
Dr. Junbo Ge
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai
China
Dr, Wei Chen
Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai
China
Dr. Yawei Xu
Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai
China

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ijhr.ijhr_5_21

Abstract

Background: Percutaneous left atrial appendage (LAA) closure has been demonstrated to be an alternative to oral anticoagulation for the prevention of ischemic stroke in nonvalvar atrial fibrillation (NVAF) patients. However, there were some designed limitations of current widely-used devices. This study was designed to evaluate the efficacy and safety of a novel double-disc LAA closure (LAAC) device, the LEFTEAR, in patients with NVAF who had contraindications of long-term oral anticoagulation or still high risks of stroke with anticoagulation treatment. Subjects and Methods: A total of 200 NVAF patients who underwent LAAC were prospectively recruited in nine participating centers in China between April 2014 and March 2019 in this prospective, multi-center, single-arm study. The study was approved by the institutional review board of each clinical center. The enrolled cases had ages ranged from 38 to 89 years (mean 68.3 ± 8.7) years. There were 112 males (56%). CHA₂DS₂-VASc scores were 3.5 ± 1.44, and HAS-BLED scores 2.5 ± 1.18. LAAC was conducted with the LEFTEAR occluder. Successful closure of LAA was defined as there was no or a small amount of peri-device leak (PDL ≤3 mm) of residual shunt, evaluated by transesophageal echocardiography. The composite end-point events (hemorrhagic/ischemic stroke, systemic embolism, and cardiogenic/unexplained death) within 12 months after the procedure were the main efficacy indicators. Severe adverse events (SAEs) within 12 months were safety indicators. Results: Totally 196 were implanted with an occluder, and the remaining 4 were not (1 case found with an large LAA which the ostium was great than 35 mm, the upper limit of the clinical program, 1 case gave up after failed attempt of LAAC procedure, 2 cases showed “pericardial tamponade” after AF ablation and no attempts were made to continue LAAC). Among them, the “Hybrid procedures” (LAAC combined with AF ablation) reached up to 133 cases (66.5%). Up to December 31, 2019, the mean follow-up was 6 months. There were none major composite endpoint events occurred during the perioperative and follow-up periods (0%). SAEs were recorded in 10 cases, of which 7 were “pericardial tamponades” and 3 of “occluder detachment or displacements.” All SAEs occurred in “Hybrid procedures” cases, of which 9 occurred in the perioperative period (90%). Six cases of “pericardial tamponade” were recorded in the perioperative period, but only two required emergency surgeries. The successful rate of immediate LAAC was 100%, among which 178 cases (90.8%, 178/196) had no residual shunt (PDL = 0 mm). A total of 153 cases (79.7%, 153/192) had completed at least one follow-up transoesophageal echocardiography examination, and the success of mid-term LAAC was 98.7% (151/153), with no events of device-related thrombosis. Conclusions: LAAC with a novel disc-like occlude, named LEFTEAR was generally effective and safe. The “Hybrid procedures” increased the incidence of adverse events to some extent. This study was the first-in-human trial of LEFTEAR, thus further larger sample studies are still needed to verify.

Keywords: Atrial fibrillation, complications, efficacy, left atrial appendage closure, mid-term, perioperative period, safety

How to cite this article:
Li S, Chen W, Zhu M, Ge J, Zhou D, Zhang X, Wang J, Fan Y, Wang Y, Chang D, Chen Y, Chen F, Fu H, Hu H, Cai H, Zhang Y, Zhou J, Ma W, Ren Z, Zhao D, Tang K, Zhao Y, Chang X, Liu W, Xu Y. A prospective, multi-center, single-arm study of a novel double-disc left atrial appendage closure system: The periprocedural and mid-term outcomes (english version). Int J Heart Rhythm 2021;6:60-6

How to cite this URL:
Li S, Chen W, Zhu M, Ge J, Zhou D, Zhang X, Wang J, Fan Y, Wang Y, Chang D, Chen Y, Chen F, Fu H, Hu H, Cai H, Zhang Y, Zhou J, Ma W, Ren Z, Zhao D, Tang K, Zhao Y, Chang X, Liu W, Xu Y. A prospective, multi-center, single-arm study of a novel double-disc left atrial appendage closure system: The periprocedural and mid-term outcomes (english version). Int J Heart Rhythm [serial online] 2021 [cited 2023 Jun 3];6:60-6. Available from: https://www.ijhronline.org/text.asp?2021/6/1/60/319972

This manuscript is an English version based on Li S, Zhu M, Ge J, Zhou D, Zhang X, Wang J, et al. A multi.center clinical study of a novel disc.like left atrial appendage closure system: the periprocedural and mid.term outcomes. Chin J Cardiac Arrhyth 2020;24(3):270.5. The second publication of this manuscript has obtained the permission from Chinese Journal of Cardiac Arrhythmias.

Introduction

Atrial fibrillation (AF) is one of the most common arrhythmia with the incidence of about 0.4–1.2%. The incidence of AF increases with age, which increases to 8% in the age of 79 or older.^[1] AF is closely associated with stroke. Compared to the same age group with sinus rhythm, patients with AF have a 5–17-fold increased risk of stroke.^[2] Warfarin, an anticoagulant commonly used clinically, has been shown to reduce the incidence older.^[1] AF is closely associated with stroke. Compared to the same age group with sinus rhythm, patients with AF have a 5–17-fold increased risk of stroke.^[2] Warfarin, an anticoagulant commonly used clinically, has been shown to reduce the incidence of stroke by more than 60%. However, it has a relatively narrow therapeutic window, with varying dose-response fluctuations between patients. Even within the same patient, its effect is influenced by genetic variability, food, and other drugs. Thus, <10% of Chinese patients with AF need long-term warfarin anticoagulant therapy according to the guidelines.

Studies have found that in patients with AF, thromboembolism mainly formed in the left atrial appendage (LAA) of the heart. For patients with nonvalvar AF (NVAF), 91% of the thrombus was of origin and isolated within the LAA.^[3] Percutaneous LAA closure (LAAC) is a new technique developed in recent years to prevent stroke in patients with AF by occlusion of the LAA in a minimally invasive way, which is noninferior to warfarin in effectiveness and superior to warfarin in safety.^[4],[5] Currently, LAAC has been approved for clinical use in nearly 100 countries and regions, including China, the United States, and Europe. More than 200,000 human implants have been performed worldwide. LAAC was first performed in China in 2013, and more than 30,000 have been performed to date.

However, some problems and potential problems caused by the rapid development of LAAC still need to be solved. One of the most important items is the problem with the existing occluders. Currently-used occluders could be generally classified into two types:^[6] “Plug-like” types (such as WATCHMAN, Lefort,^[7]) and “disc-like” types (such as Amplatzer Cardiac Plug (ACP),^[8] Amulet,^[9] LAmbre,^[10],[11]). There are some design defects in these two types of plugs. “Plug-like” occluder is actually more suitable for the single lobe of the LAA, which occupied not a very high percentage.^[12] Furthermore, it had the common problem of residual cavity after occlusion, which may become the potential sites of thrombosis. In addition, the risk of perforation is increased because the push sheath must be “deep” into the bottom of LAA before the occluder can be released. “Disc-like” occluder always has two discs, one for fixation in the LAA and one for sealing the LAA's ostium. However, the disc for sealing the LAA's ostium is almost larger than LAA's widest length, which not only could affect potentially peripheral structures (such as the left upper pulmonary vein and mitral valve), but also take a long time to endothelialize,^[13] suggesting longer anticoagulant and antiplatelet time clinically.

The LEFTEAR^@ system (Guangdong Pulse Medical Technology Co., Ltd., China) is a novel double-disc occluder that theoretically has better fixation and closure performance and accelerates endothelialization after operation. This multi-center clinical study was designed to evaluate the effectiveness and safety of the LEFTEAR system for LAAC in patients with NVAF.

Subjects and Methods

Subjects

Ge JB and Xu YW were co-investigators of this study. Nine top medical facilities participated in this prospective, multi-center, single-arm study, including Zhongshan Hospital, Fudan University (n = 15), Shanghai Tenth People's Hospital, Tongji University School of Medicine (n = 61), Shanghai Dongfang Hospital (n = 11), the First Hospital of Peking University (n = 5), the Second Affiliated Hospital of School of Medicine of Zhejiang University (n = 35), the Xiamen Cardiovascular Hospital of Xiamen University (n = 33), the West China Hospital of Sichuan University (n = 12), the First Affiliated Hospital of Xi'an Jiaotong University (n = 9), and General Hospital of Tianjin Medical University (n = 19). The study was performed in accordance with the principles of the Declaration of Helsinki and approved by the institutional review board of each clinical center with approval Nos. 2018-068R, SHSY IFC4.0/1824/01, EC.D(BG).020.03.0, 2018 (23), 2018-123/I2018001313, 2018 (3), 2019 (7), XJTU1AF2019-LSY-75, and IRB2019-073-01, respectively. Each patient signed the informed consent form before the study. The chief operator at each facility had ≥2 years of hands-on experience LAAC.^[14] A total of 200 participants were prospectively recruited in nine participating centers in China between April 2014 and March 2019. Inclusion criteria:^[10],[15] (a) ≥18 years of age with NVAF; (b) CHA₂DS₂-VASc (congestive heart failure, hypertension, age ≥75 (doubled), diabetes mellitus, previous stroke or transient ischemic attack (doubled), vascular disease, age 65–74 years, female) score ≥2 for men or ≥3 for women; (c) any of the following criteria: Contraindicated for long-term standard anticoagulation therapy; cerebral infarction or thromboembolic events despite on-target international normalized ratio after warfarin treatment; HAS-BLED score ≥3; and unwillingness or inability to tolerate long-term oral anticoagulation therapy. Exclusion criteria: (a) only one episode of AF; (b) myocardial infarction in the last 3 months or the presence of severe coronary lesions that required intervention per coronary imaging; (c) new stroke in the last 30 days; (d) radiofrequency ablation within 30 days of LAAC or planned cardioversion; (e) previous heart operations, such as LAA resection (without apparent residual cavity), valve replacement with a mechanical prosthesis, atrial septal defect closure, or heart transplantation, with contraindications for LAAC; (f) contraindications for anticoagulation and antiplatelet therapy due to bleeding disorders, unhealed gastrointestinal ulcers, or similar conditions; (g) anteroposterior diameter of left atrial >65 mm, LAA thrombus and/or dense spontaneous echo contrast on transesophageal echocardiography (TEE), unexplained pericardial effusion with a depth of >3 mm, heart tumor, or intracardiac vegetation; (h) LAA ostium <10.5 mm or >35 mm, or depth <10 mm on echocardiography; (i) left ventricular ejection fraction <35%; (j) ineligibility to participate in the opinion of the investigators.

LEFTEAR occluder system

The LEFTEAR occluder system [Guangdong Pulse Medical Technology Co., Ltd., Zhuhai, Guangdong Province, China; [Figure 1]] includes a fixed disc, a sealing disc, and a shaft. The fixed disc looks like an umbrella, with a 1-mm barb on each of the eight frames for repeated withdrawal and positioning. The frames are covered with resistor film. The sealing disc is an isosceles trapezoid-shaped three-dimensional network structure [Figure 1]a. LEFTEAR occluders are available in two models, the conventional model (the disc occluder is 4 mm larger than the fixation disc) and the “small-umbrella large-disc” model (the disc occluder is 12 mm larger than the fixation disc). The delivery system [Figure 1]b includes a delivery sheath, a dilator, a delivery cable, and a loader. The delivery catheter is 10 F (outer diameter: 4 mm, inner diameter: 3.5 mm).

Figure 1: The LEFTEAR^@ system including a novel double-lumen occluder and a delivery system. (a) LEFTEAR occluder (25 mm × 37 mm). (b) Delivery systems of LEFTEAR occluder (10F)

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Outcomes

Effectiveness outcomes

(1) Primary outcomes: The 12-month incidence of composite endpoint events. Endpoint events included hemorrhagic/ischemic stroke, systemic embolism, and cardiogenic or unexplained death.^[10],[16] (2) Secondary outcomes: a. the rate of successful surgical closure: successful occluder delivery and release in LAA, with successful closure;^[17] no forward or reverse blood flow through the occluder and peri-device leak (PDL) ≤3 mm on TEE. b. Postoperative closure: TEE was performed 3 months after operation to evaluate PDL. c. Other outcomes: Postoperative complications, the incidence of late ischemic events (including ischaemic stroke and systemic embolism), the incidence of bleeding events, and all-cause mortality (including cardiogenic, noncardiogenic, and unexplained death).

Safety outcomes

Primary outcomes included serious adverse events (SAEs), including but not limited to pericardial effusion, cardiac tamponade, closure-related stroke (gas embolism, cerebral hemorrhage), occluder dislodgement and embolism, thrombosis on the surface of the occluder, bleeding, hematoma at the puncture site, arteriovenous fistula, severe arrhythmia, and pseudoaneurysm. Cardiac tamponade was defined as pericardial effusion that required percutaneous drainage or surgical drainage.

Operation procedure

The usable LAA depth (H_LAA) was defined as the perpendicular distance from the inner wall of distal LAA to the diameter of fixation area (D_LAA). H_LAA had to be > 10 mm. For single-lobe LAA, D_LAA was defined as the mostly perpendicular distance from the ridge formed between the mitral annulus and the LAA to the inner wall of the LAA on the side of the left superior pulmonary vein. For bi/multi-lobe LAA, D_LAA was defined as the mostly perpendicular distance from the fold formed between the top of the mitral valve and the LAA to the main branch of the two/multiple lobes of the LAA. For bi/multi-lobe LAA, the distance from the ridge formed between the top of the mitral valve and LAA to the main branch of the two lobes (Hmv) was also measured, which had to be <10 mm. For general “single-lobed” LAA, the “conventional” occluder was preferred, and the diameter of fixation disc (Dl) had to be 3–5 mm larger than D_LAA. For bi/multi-lobe LAA, the “small umbrella-large disc” occluder was preferred, and Dl had to be 3–5 mm larger than D_LAA [Figure 2].

Figure 2: Measurements of LAA with single lobe or double/more lobes.(a) Measurements of LAA with single lobe. (b) Measurements of LAA with double or more lobes. Dlaa = Landing zone diameter of LAA, Hlaa = Height of LAA (>10 mm), Hmv = Distance from the ridge formed between the top of the mitral valve and LAA to the main branch of the two lobes (<10 mm), LAA = Left atrial appendage

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After a proper occluder was selected, an outer sheath was advanced and positioned in the fixation area, which was 5–10 mm from the LAA ostium. The occluder was manually deflated and then connected to a delivery steel cable. Any air or liquid was completely excluded. The outer sheath was secured, the inner sheath was advanced, and the fixation disc was slowly unfolded and secured in the anchoring area. Next, the outer sheath was withdrawn, and the occlusion disc was deployed while keeping the inner sheath in place. The readiness for release, including the anchoring location and fixation effect of the fixation disc and the occlusion effect of the occlusion disc on the LAA ostium, was evaluated according to the CODIS criteria^[6] [Figure 3], which was described in detail in the previous literature. The occluder was released if the criteria were met. If not, the occluder was withdrawn and repositioned and then released when the CODIS criteria were met.

Figure 3: CODIS criteria of LEFTEAR occluder

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Postoperative management and follow-up

An independent organization (Guangzhou Jiutai Medical Device Technology Co., Ltd., China) was contracted to monitor this clinical study. After the operation, patients were instructed to take warfarin or novel anticoagulants for 3 months ± 15 days. Based on TEE at 3 months after operation, patients were switched to dual antiplatelet therapy (aspirin 100 mg + clopidogrel 75 mg, once daily) or single-drug antiplatelet therapy (aspirin 100 mg or clopidogrel 75 mg, once daily) through 12 months after operation if no thrombosis was observed on the surface of the occluder, or they continued to take warfarin or novel anticoagulants if thrombosis was present. The latter patients, based on TEE at 6 months after operation, were switched to dual antiplatelet therapy through 12 months after operation if TEE showed no thrombosis, or they continued to take warfarin or novel anticoagulants through 12 months after operation if TEE showed thrombosis.

The incidence of composite endpoint events, postoperative complications, postoperative LAAC effect, the incidence of ischemic events, the incidence of bleeding events, all-cause mortality, and the pass rate of the investigated product were analyzed at discharge and at 3, 6, and 12 months after operation. In this study, endpoint events were followed up and reported through December 30, 2019.

Sample size calculation

Based on the sample estimation, the assurance of 80% (β =0.2) was used, and α =0.025 was used as the test level. The confidence interval (CI) method was used to conduct the unilateral noninferiority test. According to domestic and foreign literature reports,^[15] a single-group target value design was used in this trial. The 12-month incidence of composite endpoint events after LAAC in patients with NVAF was 1.22–3%. The annual incidence of ischemic stroke with aspirin alone was 7.3%.^[5] Data from the clinical investigation literature on Chinese patients with AF^[18] showed that the incidence of stroke (no data including systemic embolism, cardiogenic/unexplained death cases) was 6–13%. By integrating the above data and suggestions from clinical experts and statistics experts, it could suppose that in patients with NVAF who received the LAAC, the incidence of composite end point events can be controlled at about 3%, expected not to exceed 8%. Therefore, the target of this test was set as 3%, the noninferiority boundary values of the δ =5%. When the level of statistical significance was set as one-sided test α =0.025 and the test efficiency was not < 80% (1–β), a hypothesis was established that: The upper 95% CI of the difference between the composite end point incidence and the target value was greater than (or equal to) the noninferiority boundary values of the (δ =5%). At least 177 subjects were required to participate in this study. Considering that samples may fall off during the trial, the sample size was expanded to 200 cases.

Statistical analysis

SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) or above was used for statistical analysis. Measurement data were expressed as mean ± standard deviation, maximum, minimum, and median. Count data were expressed as frequency (percentage). The investigated product was considered noninferior to the target value if the upper limit of the 95% CI of the difference between the incidence of composite endpoint events and the target value was less than the given noninferiority threshold (δ =5%). Otherwise, the product was considered inferior.

Results

Clinical data

A total of 200 patients were enrolled into this study between August 2018 and October 2019. The patients were aged 68.3 ± 8.71 (38–89). Among them, 44 patients (22%, 44/200) were 75 years or older. Moreover, 112 patients (56%, 112/200) were men, and 88 were women. The preoperative CHA₂DS₂-VASc score was 2–8 (3.5 ± 1.44), indicating a high risk of stroke. The HAS-BLED score was 2–6 (2.5 ± 1.18).

Peri-operative period

Operation protocol

A total of 133 patients (67%, 133/200) underwent combined operations (AF ablation combined with LAAC), 63 underwent LAAC alone, 3 underwent LAAC combined with atrial septum defect closure, and 1 underwent LAAC combined with percutaneous coronary intervention. Eight facilities (88.9%, 8/9) performed the combined operations [Figure 4].

Figure 4: The proportions of different operation protocols totally and in each center. (a) The proportions of different operation protocols. (b) Different operation protocols in each clinical center. 1: Zhongshan Hospital, Fudan University, 2: Shanghai Tenth People's Hospital, Tongji University School of Medicine, 3: Shanghai Dongfang Hospital, 4: The First Hospital of Peking University, 5: The Second Affiliated Hospital of School of Medicine of Zhejiang University, 6: The Xiamen Cardiovascular Hospital of Xiamen University, 7: The West China Hospital of Sichuan University, 8: The First Affiliated Hospital of Xi'an Jiaotong University, 9: General Hospital of Tianjin Medical University

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Immediate occlusion effectiveness

A total of 196 patients (98%, 196/200) received a single LEFTEAR occluder. Four patients did not receive any occluder because the LAA ostium was >35 mm (the upper limit stated in the protocol) on imaging (n = 1), we were unable to deploy the occluder due to partial segmentation of the LAA on imaging (n = 1), and cardiac tamponade during LAAC after AF ablation (n = 2). TEE showed immediate success, and the overall success rate was 100%. Moreover, PDL was 0 mm in 178 patients (90.8%, 178/196) and ≤3 mm in 18 patients. In 148 cases (75.5%, 148/196) we succeeded in the first attempt with an occluder (one occluder), and in 48 we succeeded in the second or later attempt with two or more types of occluder (i.e., replacing one or more occluders). The occluder was removed from four patients before discharge. Specifically, occluder displacement or dislodgement occurred in three patients (one of whom did not undergo any further implantation and one of whom received a WATCHMAN occluder [Boston Scientific, USA]). For one patient, intraoperative exploration showed LAA ostium >37 mm (one of the exclusion criteria). Nevertheless, a LEFTEAR occluder was implanted for LAAC because little to no pulmonary vein potential was noted during AF ablation, indicating a high risk of recurrence of AF. The patient developed severe pericardial effusion by day 2 after operation, and his vital signs were unstable despite pericardiocentesis. The patient underwent emergency operation, which showed that the occluder had damaged the pulmonary artery. The occluder was removed, followed by LAA ligation and pulmonary hemostasis.

Peri-operative adverse events

No primary endpoint events occurred during the perioperative period. Nine SAEs occurred across four facilities. All six cases of cardiac tamponade occurred in patients undergoing combined operations. All six of these patients underwent percutaneous drainage, two of whom underwent emergency operation for tamponade relief and LAA ligation. Moreover, two cases occurred during LAAC after AF ablation; three cases occurred after LAAC (and in the ward); and one case occurred on the day after discharge (which patient was readmitted for pericardiocentesis). Occluder dislodgment/displacement occurred in three patients. Two were acute cases that occurred in the ward, and trans-thoracic echocardiography (TTE) showed that the occluder was dislodged and was hanging on the mitral annulus. One patient underwent emergency operation for occluder removal and LAA ligation, and one patient underwent occluder removal without any further implantation. The remaining patient was asymptomatic, but TTE performed before discharge indicated occluder displacement. For safety, the occluder was removed, following by implantation of a WATCHMAN occluder.

Follow-up

Endpoint events

The patients were followed up for 2–14 (7 ± 4) months through December 31, 2019. One patient was lost to follow-up, and 199 completed follow-up. A total of 51 patients (25.5%, 51/200) completed the scheduled 12-month follow-up, 109 (54.5%, 109/200) completed the scheduled 6-month follow-up, and 9 patients had yet to enter the initial 3-month follow-up period. No endpoint events occurred. All the patients had completed at least one follow-up and TTE/TEE, and three patients were found to have pericardial effusion. Among these, one patient had severe pericardial effusion without cardiac tamponade 1 month after operation and underwent pericardial drainage; one patient had moderate pericardial effusion 1.5 months after operation and received conservative treatment without percutaneous drainage; and the last one had moderate to severe pericardial effusion 3.5 months after operation and received conservative treatment without percutaneous drainage.

Left atrial appendage closure rate

At discharge, 192 patients kept their occluders, and 153 patients (79.7%, 153/192) had completed at least one TEE follow-up. PDL was 0 mm in 128 patients (83.6%, 128/153) and ≤3 mm in 23 patients, indicating successful closure.

Discussion

This prospective multi-center study was designed to evaluate the effectiveness and safety of the LEFTEAR occluder for LAAC in patients with NVAF. A total of 200 patients were enrolled in the study. Among them, 133 patients (67%) underwent combined operations (ablation combined with LAAC), and 63 patients underwent LAAC alone. The patients were followed up for 7 ± 4 months. No primary composite endpoint events occurred during the perioperative and follow-up periods. A total of 10 SAEs were recorded, all of which occurred in patients undergoing combined operations for AF. The immediate LAAC rate was 100%, and the success rate was 98.7% (151/153) as per TEE follow-up.

In this study, 200 eligible patients were scheduled for LAAC. An occluder was implanted in 196 patients (98%). The immediate closure rate was 100%, and the success rate was 98.7% during postoperative follow-up. Previous studies reported that the implantation success rate was 92% (55/60, PDL <5 mm),^[19] 99.3% (152/153, PDL ≤3 mm),^[10] 100% (30, PDL ≤3 mm),^[20] or 100% (17, intraoperative X-ray).^[21] We previously conducted a retrospective study^[6] of 328 cases of disc occluder implantation (including ACP, LAmbre, Lacbes, and LEFTEAR [the first 48 cases in our hospital]) over 5 years. The results showed that the overall implantation rate was 99.6% (222/223), and the overall success rate was 98.2% (219/223).

LAA anatomy to some extent restricts the implantation of the LAA occluder. WATCHMAN and ACP/Amulet occluders are not suitable if the LAA ostium or anchoring area is >31 mm. In addition to LAA ostium diameter, certain LAA anatomies are contraindicated for implantation. In the PREVAIL study,^[22] two patients did not undergo WATCHMAN implantation for the same reason. In the EWOLUTION registration study, some patients did not undergo WATCHMAN implantation due to LAA anatomy, and 15 (1.5%) operations in the implantation group did not succeed due to LAA anatomy. So et al.^[11] retrospectively analyzed 964 cases of LAAC performed at three hospitals in China between 2009 and 2018 and found that 27 patients (2.8%) were contraindicated for WATCHMAN or ACP implantation due to a large LAA (defined as LAA ostium diameter >31 mm). These patients were implanted with LAmbre occluders, and 24 of them (88.9%) achieved successful occlusion (PDL ≤3 mm). In this study, we attempted occlusion in 197 of 200 patients and failed in only one patient due to significant segmentation of the LAA that affected occluder deployment. The other 196 implantations were successful despite sub-optimal LAA anatomy in some patients (multi-lobed LAA, shallow LAA, and other anatomies), suggesting that LEFTEAR occluders have broader clinical indications for LAAC.

In this study, 196 patients underwent implantation: 62 (31.8%, 62/195) underwent LAAC alone, and 133 (67.8%, 133/196) underwent combined operations of LAAC combined with AF ablation across eight facilities (88.9%), which enrolled a total of 195 patients (97.5%, 195/200). This is level of coverage is unprecedented in previous premarket studies of the LAA occluders.^{[8],[10],[20],[22],[23]}

In this study, 7/200 (3.5%) patients had cardiac tamponade, and all of them underwent combined operations (5.3%, 7/133). Five patients underwent pericardiocentesis, and two patients required emergency operation. Previous small studies on combined operations reported different incidences of cardiac tamponade, such as 2.4% (2/82)^[23] and 8.6% (3/35), but other studies did not show any significant increase in the incidence of cardiac tamponade after combined operations.^{[24],[25],[26]} Moreover, in this study, occluder dislodgment occurred in two patients, and occluder displacement occurred in one patient. All three of them underwent combined operations. This was likely because combined operations were associated with more adverse events as well as a lack of experience with LEFTEAR occluders among most of our facilities and surgeons, since this was a premarket clinical study, suggesting that special training and a learning curve are required for novel occluders, even among experienced LAAC specialists from specialized hospitals.

Study limitations

This was a multi-center, small-scale, premarket, single-arm study with a target-value design. It was also a first-in-human study. Some patients are still in the follow-up period, which may affect our conclusions. Most surgeons are unfamiliar with LEFTEAR occluders, which may contribute to LAAC difficulty and adverse events. Only approximately 30% of the patients underwent LAAC alone, and “one-stop” operation may contribute to confounding factors and adverse events. Large, long-term follow-up studies are needed to evaluate LEFTEAR occluders versus commercially available occluders or drugs.

Conclusion

This study shows that the novel LEFTEAR occluder is effective and safe for LAAC. However, the “Hybrid procedures” increase the incidence of adverse events to some extent.

Financial support and sponsorship

This study was supported by the Key Research and Development Program of Ministry of Science and Technology (No. 2017YFC0111800, to YX); National Natural Science Foundation of China (No. 81800441, to SL); Shanghai Science and Technology Commission (No. 16411965700, to WC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflicts of interest

There are no conflicts of interest.

Institutional review board statement

The protocol was approved by the ethics committee at each of the 9 participating centers.

Declaration of patient consent

The authors certify that they have obtained all appropriate consent from patients. In the forms, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity forms.

References

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