Author + information
- Received March 14, 2017
- Revision received June 8, 2017
- Accepted June 29, 2017
- Published online November 6, 2017.
- He Huang, MDa,b,c,
- Yu Liu, MDa,b,c,
- Yawei Xu, MDd,
- Zulu Wang, MDe,
- Yigang Li, MDf,
- Kejiang Cao, MDg,
- Shu Zhang, MDh,
- Yanzong Yang, MDi,
- Xinchun Yang, MDj,
- Dejia Huang, MDk,
- Bo Yu, MDl,
- Xi Su, MDm,
- Liqun Wu, MDn and
- Congxin Huang, MDa,b,c,∗ ()
- aDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China
- bCardiovascular Research Institute of Wuhan University, Wuhan, People's Republic of China
- cHubei Key Laboratory of Cardiology, Wuhan, People's Republic of China
- dDepartment of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
- eDepartment of Cardiology, General Hospital of Shenyang Military Region, Shenyang, People's Republic of China
- fDepartment of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
- gDepartment of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China
- hState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- iDepartment of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China
- jDepartment of Cardiology, Chaoyang Hospital, Capital Medical University, Beijing, People's Republic of China
- kDepartment of Cardiology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
- lDepartment of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China
- mDepartment of Cardiology, Wuhan Asian Heart Hospital, Wuhan, People's Republic of China
- nDepartment of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
- ↵∗Address for correspondence:
Dr. Congxin Huang, Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, No.238 Jiefang Road, Wuhan 430060, People's Republic of China.
Objectives The authors sought to assess the clinical outcomes of left atrial appendage (LAA) closure with the LAmbre closure system in patients with nonvalvular atrial fibrillation (NVAF).
Background Over 90% of thrombi are located in the LAA in NVAF patients.
Methods A prospective, multicenter study was conducted in 153 NVAF patients with CHADS2 score ≥1.
Results The LAA was successfully occluded in 152 patients. Serious complications occurred in 5 patients. During the 12-month follow-up, ischemic stroke occurred in 2 patients, 1 patient had incomplete LAA sealing, and there was no device embolization.
Conclusions LAA closure with the LAmbre device shows encouraging results for stroke prevention.
Atrial fibrillation (AF) is the most common sustained arrhythmia observed in clinical practice and is a major cause of morbidity and mortality due to cardioembolic stroke, which is responsible for 15% to 20% of all ischemic strokes (1). The incidence of ischemic stroke among patients with nonvalvular AF (NVAF) is approximately 5% per year, a 5.6-fold increase when compared with an age-matched population in sinus rhythm (2). There is a great deal of published reports on stroke prevention demonstrating that oral anticoagulation with warfarin is the current most common and effective therapy to prevent stroke associated with AF (3–5). Unfortunately, this treatment is generally underused due to its several limitations, including the narrow therapeutic window, the drug and food interactions, the need for repeated monitoring, and the poor patient tolerance.
Autopsy and echocardiography studies have shown that more than 90% of atrial thrombi in patients with NVAF locate in the left atrial appendage (LAA) (6,7). Therefore, percutaneous LAA closure has been developed as an alternative strategy to warfarin for stroke prophylaxis in AF patients. Many studies demonstrated the effectiveness of percutaneous LAA closure in stroke prevention in patients with AF (8–16). The PROTECT-AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) study showed that percutaneous LAA closure with WATCHMAN device (Boston Scientific, Natick, Massachusetts) was superior to warfarin in patients with NVAF for the prevention of stroke, systemic embolization, cardiovascular death, and all-cause mortality after 3.8 years of follow-up (13). In addition, another LAA-occluding device, the Amplatzer Cardiac Plug (St. Jude Medical, Saint Paul, Minnesota), has shown favorable efficacy for the prevention of AF-related thromboembolism (16). LAmbre (Lifetech Scientific, Shenzhen, China) is a new, self-expanding LAA occluder, specifically designed for LAA closure. Preliminary study suggested the percutaneous LAA closure with LAmbre device is feasible with a high success rate in canines (17). However, there are no data available on the clinical safety and efficacy of this device. This prospective, multicenter clinical study reported the initial experience of LAmbre implantation for NVAF patients in China.
This was an open-label, nonrandomized pilot trial designed to assess the safety, feasibility, and efficacy of deploying the LAmbre LAA occlusion device. One hundred fifty-three consecutive patients who underwent percutaneous LAA closure with the LAmbre device at 12 hospitals in China between March 2014 and January 2015 were prospectively studied. All patients had a diagnosis of NVAF, over 18 years of age, scored at least 1 point according to the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack (CHADS2) score, and were not suitable for long-term anticoagulation with warfarin (presence of a cerebrovascular or gastrointestinal bleeding history, increased bleeding tendency, poor compliance, or warfarin allergy). All patients received transthoracic and transesophageal echocardiography (TEE) before the LAmbre implantation procedure. Patients found to have thrombus formation in the left atrium, a left ventricular ejection fraction <30%, or a LAA orifice diameter ≤12 mm were excluded from the study. Other exclusion criteria included symptomatic carotid disease, acute myocardial infarction or unstable angina, New York Heart Association functional class IV, prior stroke or transient ischemic attack within 30 days, acute infective endocarditis, hemorrhagic disease, pregnancy, life expectancy <2 years, presence of a prosthetic valve, or presence of an atrial septal repair or closure history. Informed consent was obtained from all studied patients, and the study was approved by the institutional review board.
The LAmbre LAA closure system comprises an implant and a delivery system, and is designed for device implantation via the transseptal route into the LAA. The LAmbre implant is a self-expanding, nitinol-based device consisting of an umbrella and a cover connected by a short central waist. The distal umbrella comprises 8 claws with individual stabilizing hooks with a polyethylene terephthalate membrane on the distal face. The proximal cover is filled with sewn-in polyethylene terephthalate fabric (Figure 1). The LAmbre implant is available in 15 diameter sizes referring to the umbrella, that is, 16 to 36 mm. The delivery system consists of a double-curve configuration delivery sheath (8-F to 10-F in size) and a delivery cable, allowing for contrast injection and device positioning. The implantation was performed under general anesthesia by the femoral vein approach under fluoroscopic, angiographic, and continuous TEE guidance. After transseptal puncture, intravenous heparin was immediately administered to patients to achieve activated clotting time of at least 250 s. The delivery sheath was then placed in the proximal part of LAA. The diameters of the orifice and length of LAA are measured from LAA angiography in right anterior oblique cranial projection. The size of the implant would be 4 to 8 mm larger than the measured LAA orifice, based on the clinical judgment of the physician. The distal umbrella was released into the LAA by stepwise pushing out the device from the delivery sheath. Subsequently, the sheath was withdrawn to expose the proximal cover, allowing it to expand in the left atrium and seal the LAA ostium. Once the implant was placed in the LAA, angiography and echocardiography were performed to check device positioning, LAA sealing and impingement on surrounding structures (Figure 2). A gentle tug test is performed to ensure device stability. If the implant location or stability is deemed unsatisfactory, the implant would be completely retrieved and redeployed unless proper device position is achieved.
All patients were prescribed aspirin 100 mg per day indefinitely, and clopidogrel 75 mg per day for 3 months after the procedure. TTE was performed at day 1 post-implantation to exclude device embolization and pericardial effusion. Clinical follow-up was arranged at 1, 3, 6, and 12 months after LAmbre device implantation to assess the clinical outcomes. TEE was scheduled at 3 and 12 months to assess device position, peridevice LAA flow, and device-related thrombus.
Major adverse events
Major adverse events were defined as death, stroke, systemic embolism, device embolization, pericardial bleeding requiring an intervention (cardiac tamponade), or other major bleeding requiring invasive treatment or blood transfusion.
The occurrence of events is expressed as absolute numbers and percentage. Continuous variables are summarized by mean ± SD, and minimum and maximum values.
There were 153 patients treated at 12 centers in China who met all inclusion and exclusion criteria and were enrolled in the study. Mean patient age was 69 years (range 42 to 86 years), and 56% were male. A history of paroxysmal AF was noted in 25 of 153 (16%) patients, persistent AF in 85 of 153 (56%) patients, and permanent AF in 43 of 152 (28%) patients. The most common risk factor for stroke was hypertension (73%), and 65% of patients previously had an ischemic stroke/transient ischemic attack. The average CHADS2 score was 2.5, representing a 6.4% annual risk for stroke (Figure 3) (18,19). The mean congestive heart failure, hypertension, age≥75 years (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled)-. vascular disease, age 65 to 74 years, and sex category (female) (CHA2DS2-VASc) score was 4.0. On the basis of the CHA2DS2-VASc score, the expected annual risk for thromboembolism was 5.2% (20). Table 1 showed the baseline characteristics of the study participants.
The LAA was successfully occluded by the LAmbre device in 152 patients (99.4%). In 87% of the successful cases, device implantation was managed with the first device selected, and in 9% or 3%, a second or third device, respectively, was needed. The implant was completely retrieved and redeployed in 43% patients. The average angiographic maximal LAA diameter was 24 mm, and the mean LAA landing zone diameter was 23 mm (Table 2). The distribution of successfully deployed devices is shown in Figure 4. The mean procedure duration was 66 min, and the average contrast volume was 84 ml.
There were serious complications in 5 (3.3%) of the patients (Table 3). Clinically serious pericardial effusion (defined as the need for pericardiocentesis or surgical intervention) was documented in 3 patients. Two of these patients were treated with pericardiocentesis, and 1 underwent surgical LAA excision. One patient experienced an ischemic stroke probably because of embolism of cardiac thrombus. Her condition improved with conservative treatment. A major bleeding event was observed in 1 patient. She was transfused with 2 U of packed red blood cells. No acute device embolization was observed before discharge. Minor complications were hematoma at puncture site of femoral vein in 2, femoral arteriovenous fistula in 1, and pseudoaneurysm in 1 of the cases. There were no procedure-related deaths.
During the 12-month clinical follow-up period, ischemic stroke occurred in 2 patients. Both patients had a prior history of stroke. Hemorrhagic stroke occurred in 1 patient. TEE revealed no pulmonary venous obstruction or delayed device embolization. Thrombus formation on the atrial surface of the device was documented in 2 patients during surveillance TEEs at a follow-up of 3 months. Both patients had no neurological symptoms and were conservatively managed, and 1 patient was noncompliant with anticoagulation treatment starting early after device implantation. One patient suddenly died of unknown cause at day 7 post-discharge. The death was deemed unrelated to the LAA closure device. One hundred twenty-one patients came for 12-month TEE follow-up. Ninety-nine percent (120 of 121) of the LAA were completely sealed with absence of flow or with minimal flow around the device (jet of <3 mm). Table 4 summarizes the clinical outcomes during follow-up.
This is the first study to our knowledge to report the clinical outcomes among patients with NVAF having the new LAmbre LAA occluder device implanted. We have shown that LAA closure with the LAmbre device is feasible and has a high short-term procedural success rate. Moreover, follow-up results suggest that the LAmbre device could be associated with encouraging clinical outcomes in the prevention of stroke.
The structure of the LAmbre device is different compared with the WATCHMAN and the Amplatzer Cardiac Plug devices. The WATCHMAN device is a relatively long, mesh-like umbrella device and therefore not suitable for patients with shallow LAA or multiple-lobe LAA. However, with the continuous improvements in implant techniques, the implant procedure success reached 98.5% in the EWOLUTION (Registry on Watchman Outcomes in Real-Life Utilization) registry (21). The Amplatzer Cardiac Plug device consists of a distal lobe and proximal disk connected by an articulating waist. The multicenter experience with the Amplatzer Cardiac Plug reported a favorable procedural success (97.3%) (16). The LAmbre device is a short device to be placed within 2 cm of the LAA ostium and is delivered by a relatively small sheath (8-F to 10-F). The implant can be intentionally recaptured, completely retrieved, and then redeployed. More importantly, the LAmbre device has more sizes and is more suitable for special morphological LAA. In this study, we achieved 99.4% short-term procedural success, and there was no problem encountered during recapture and repositioning.
Significant pericardial effusion (defined as the need for percutaneous or surgical interventions) is a severe complication that plagued the LAA closure procedure. In the PROTECT AF trial, this complication was related to the experience of the operator because it occurred in 7.1% of the first 3 patients at each site and in 4.4% of subsequent patients (22). The initial European Amplatzer Cardiac Plug series (N = 143) reported 3.6% of serious pericardial effusion after Amplatzer Cardiac Plug implants (23). A major difference between the LAmbre and the WATCHMAN devices or the Amplatzer Cardiac Plug device is the deployment sequence. During deployment of the LAmbre device, the delivery catheter is positioned at the very proximal portion of the LAA, and the umbrella is released to the landing zone by gently pushing forward “en bloc.” LAA perforation is less likely to occur by avoiding both deep location of the delivery sheath and device manipulation at the distal LAA. In our series, serious pericardial effusion occurred only in 3 patients (2.0%).
Device embolization is a rare, but tough, complication of the LAA closure procedure. Although our small series reported that no device embolization occurred, device embolization occurred in 3 patients (0.6%) in the PROTECT AF trial: 1 was noted during the procedure and 2 were discovered by TEE on day 45 (9). The initial European experience of LAA closure with the Amplatzer Cardiac Plug also reported 2 cases of device embolization (1.5%) (23). Three possible mechanisms may contribute to improve the stability of the LAmbre device. First, claws and hooks of the distal umbrella facilitate the anchoring to the LAA wall. Second, an oversized umbrella provides a stenting effect against the LAA wall. Last, the pectinate muscles located at the mid-to-distal portion of LAA may trap the individual claws of the umbrella.
The expected annual risk of stroke based on the CHADS2 score and CHA2DS2-VASc score in this study cohort was calculated to be 6.4% and 5.2%, respectively (18–20). However, the observed ischemic stroke rate was only 1.3%, representing significantly fewer events than expected. Although this result does not provide sufficient power to demonstrate equivalence or superiority to anticoagulation, the results appear generally comparable to those reported for the PLAATO system, the WATCHMAN system, and the Amplatzer Cardiac Plug system, which have also been demonstrated to have a lower event rate of stroke compared with the expected stroke rate predicted by the CHADS2 score or CHA2DS2-VASc score (8,10,16). Two patients had thrombus seen on the device at 3-month follow-up, 1 of which was noncompliant with anticoagulation treatment starting early after device implantation. Therefore, adequate antithrombotic therapy with aspirin and clopidogrel is important to prevent thrombus formation before the endothelialization process finished. However, given the known occurrence of later thrombus formation on the atrial surface of the device, even after complete endothelialization of the device (24,25), the optimal therapeutic regimen or therapeutic time needs to be further investigated.
The present study included NVAF patients with a CHADS2 score of 1 or greater; from these, 10 (6.5%) were moderate stroke risk (CHA2DS2-VASc score = 1) (Table 1). However, current guidelines would recommend aspirin or antithrombotic therapy in this risk cohort. In addition, there was no control group, and the use of CHADS2 and CHA2DS2-VASc scores for comparisons is methodologically imperfect. A recent systematic review showed that substantial variation exists across cohort studies and randomized controlled trials in overall stroke rates and rates corresponding to CHA2DS2-VASc point scores (26). Finally, this is a small sample study with a medium-term follow-up, and therefore, it is not sufficient to conclude the long-term efficacy and safety of the LAmbre device in stroke prevention in AF patients. Thus, prospective, multicenter, randomized, controlled (LAmbre vs. oral anticoagulant agents) clinical trials are needed to further confirm the efficacy and safety of LAmbre device in NVAF patients with high risk of stroke.
LAA closure with the LAmbre device shows encouraging results for stroke prevention in patients with NVAF. Further large-scale trials are needed to confirm the long-term safety and efficacy of this novel device.
WHAT IS KNOWN? Preliminary study suggested the percutaneous LAA closure with the LAmbre device is feasible.
WHAT IS NEW? This prospective, multicenter, clinical study showed a low ischemic stroke rate with a small number of complications.
WHAT IS NEXT? Prospective, multicenter, randomized, controlled clinical trials are needed to further confirm the long-term efficacy and safety of the LAmbre device.
This work was supported by grants from the National Natural Science Foundation of China (No. 81570306 and No. 81570459), and the Science and Technology Support Program of Hubei Province (No. 2013BCB013). The authors have reported that they have no relationships relevant to the contents of this paper to disclose. The first two authors contributed equally to this work.
- Abbreviations and Acronyms
- atrial fibrillation
- congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack
- congestive heart failure, hypertension, age ≥75 years (doubled), diabetes mellitus prior stroke or transient ischemic attack (doubled). vascular disease, age 65 to 74 years, and sex category (female)
- left atrial appendage
- nonvalvular atrial fibrillation
- transesophageal echocardiography
- Received March 14, 2017.
- Revision received June 8, 2017.
- Accepted June 29, 2017.
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