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| GUIDELINE |
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| Year : 2016 | Volume
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| Issue : 1 | Page : 5-23 |
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Left Atrial Appendage Intervention for the Prevention of Thromboembolic Events in Patients with Atrial Fibrillation: A Joint Consensus Document of the Chinese Society of Pacing and Electrophysiology, Chinese Society of Cardiology, Chinese Society of Arrhythmias
Congxin Huang1, Yong Huo2, Shu Zhang3, Kejiang Cao4, Keping Chen3, Minglong Chen4, Hua Deng5, Yansheng Ding2, Jianzeng Dong6, Pihua Fang3, Xianhong Fang7, Lianjun Gao8, Wei Hua3, He Huang1, Dejia Huang9, Hong Jiang1, Jian Jiang9, Chenyang Jiang10, Li Li11, Yigang Li12, Qiming Liu13, Shaowen Liu14, Xingpeng Liu15, Xu Liu16, Yu Liu1, Changsheng Ma6, Jian Ma3, Ju Mei12, Xu Meng6, Feifan Ouyang17, Lihua Shang18, Xi Su19, Min Tang3, Fang Wang14, Huishan Wang20, Yutang Wang21, Zulu Wang20, Gang Wu1, Liqun Wu22, Shulin Wu7, Yunlong Xia8, Yawei Xu23, Jiefu Yang24, Xinchun Yang15, Yanzong Yang8, Yan Yao3, Kuijun Zhang3, Shulong Zhang8, Zhe Zheng3, Shenghua Zhou13
1 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
2 Department of Cardiology, Peking University First Hospital, Beijing 100034, China
3 State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases & Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037, China
4 Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China
5 Department of Cardiology, Peking Union Medical College Hospital, Beijing 100730, China
6 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
7 Guangdong Cardiovascular Institute, Guangzhou 510080, China
8 Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
9 Department of Cardiology, West Hospital, Sichuan University, Chengdu 610041, China
10 Department of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China
11 Department of Cardiology, Changhai Hospital of Shanghai, Shanghai 200433, China
12 Department of Cardiology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
13 Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, China
14 Department of Cardiology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200080, China
15 Department of Cardiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China
16 Shanghai Chest Hospital, Shanghai 200030, China
17 St. Georg Hospital, Hamburg, Germany
18 Department of Cardiology, The First Hospital of Tsinghua University, Beijing 100016, China
19 Wuhan Asia Heart Hospital, Wuhan 430022, China
20 Department of Cardiology, The General Hospital of Shenyang Military, Shenyang 110016, China
21 Department of Cardiology, Chinese People's Liberation Army General Hospital, Beijing 100853, ;, China
22 Department of Cardiology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
23 Department of Cardiology, Tenth People's Hospital of Tongji University, Shanghai 200072, China
24 Department of Cardiology, Beijing Hospital, Beijing 100730, China
| Date of Web Publication | 30-Sep-2016 |
Correspondence Address:
Congxin Huang
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060
China
Shu Zhang
State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases & Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100037
China
Yong Huo
Department of Cardiology, Peking University First Hospital, Beijing 100034
China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2352-4197.191475
How to cite this article:
Huang C, Huo Y, Zhang S, Cao K, Chen K, Chen M, Deng H, Ding Y, Dong J, Fang P, Fang X, Gao L, Hua W, Huang H, Huang D, Jiang H, Jiang J, Jiang C, Li L, Li Y, Liu Q, Liu S, Liu X, Liu X, Liu Y, Ma C, Ma J, Mei J, Meng X, Ouyang F, Shang L, Su X, Tang M, Wang F, Wang H, Wang Y, Wang Z, Wu G, Wu L, Wu S, Xia Y, Xu Y, Yang J, Yang X, Yang Y, Yao Y, Zhang K, Zhang S, Zheng Z, Zhou S. Left Atrial Appendage Intervention for the Prevention of Thromboembolic Events in Patients with Atrial Fibrillation: A Joint Consensus Document of the Chinese Society of Pacing and Electrophysiology, Chinese Society of Cardiology, Chinese Society of Arrhythmias. Int J Heart Rhythm 2016;1:5-23 |
How to cite this URL:
Huang C, Huo Y, Zhang S, Cao K, Chen K, Chen M, Deng H, Ding Y, Dong J, Fang P, Fang X, Gao L, Hua W, Huang H, Huang D, Jiang H, Jiang J, Jiang C, Li L, Li Y, Liu Q, Liu S, Liu X, Liu X, Liu Y, Ma C, Ma J, Mei J, Meng X, Ouyang F, Shang L, Su X, Tang M, Wang F, Wang H, Wang Y, Wang Z, Wu G, Wu L, Wu S, Xia Y, Xu Y, Yang J, Yang X, Yang Y, Yao Y, Zhang K, Zhang S, Zheng Z, Zhou S. Left Atrial Appendage Intervention for the Prevention of Thromboembolic Events in Patients with Atrial Fibrillation: A Joint Consensus Document of the Chinese Society of Pacing and Electrophysiology, Chinese Society of Cardiology, Chinese Society of Arrhythmias. Int J Heart Rhythm [serial online] 2016 [cited 2023 Jun 5];1:5-23. Available from: https://www.ijhronline.org/text.asp?2016/1/1/5/191475 |
∗On behalf of the Chinese Society of Pacing and Electrophysiology, the Chinese Society of Cardiology, the Chinese Society of Arrhythmias
| Preamble | |  |
Atrial fibrillation (AF) is one of the common arrhythmias and can lead to serious thromboembolic events that may affect the quality of life and even cause disability and death. For this reason, preventing the occurrence of thromboembolism events is the most important prevention and treatment strategy. Regular antithrombus treatment has acquired satisfied therapeutic effect in prevention of thromboembolic events. However, the patient compliance is poor due to long-term therapy and potential side effects caused by antithrombotic medication. It is estimated that <10;% of patients with AF have regular anti-thrombotic therapy in China. Therefore, it is necessary to explore new strategies for the prevention of thromboembolic events in patients with AF in China.
In recent years, there are many studies showing that left atrial appendage (LAA) intervention is useful in prevention of thromboembolic events clinically. Surgical LAA intervention and percutaneous LAA occlusion have been applied in clinical practice in many Chinese centers. Evidence-based research has initially confirmed that the effect of LAA intervention on prevention of thromboembolic events is non-inferior to warfarin therapy,[1] which provides a strong evidence to promote this strategic implementation in our country.
To standardize the clinical application of LAA intervention for preventing thromboembolic events, a writing group which is composed of domestic experts summarized the successful application experience of foreign studies and cardiologists in Chinese centers, and then offered this current opinion and consensus on LAA intervention for prevention of thromboembolic events in patients with AF to provide references for LAA intervention application.
| Background | | |
Left atrial appendage structure and function
LAA is the remnant of original embryonic left atrium that develops during the 4th week of gestation.[2] LAA is located between left superior pulmonary vein and left ventricular free wall, and the basal part is close to left circumflex coronary artery, and the post-superior part is adjacent to left superior pulmonary vein. The LAA is a long, tubular, hooked structure with variable morphology and size, and a length varying considerably from 16 to 51 mm and a diameter of 10–40 mm 3. The morphology of LAA can be assessed by computer tomography (CT), magnetic resonance imaging (MRI) and percutaneous selective angiography of LAA. Studies show that the morphologies of LAA are heterogeneous. Wang [4] divided LAA shapes of 622 patients into five types according to cardiac CT examination results: Oval (68.9%), foot-like (10%), triangular (7.7%), water drop-like (7.7%), and round (5.7%). An autopsy study demonstrated that 80% of normal LAAs had multiple lobes, and 54% were bilobular.[3] Differing from matured left atrial (LA), LAA composes rich pectinate muscles and trabecular muscles, which may easily make blood flow slowdown and form vortex. This anatomic basis of thrombosis, to certain extent, determines LAA as the most likely location of LA thrombosis. Di Biase et al.[5] investigated the LAA by CT and MRI to categorize different LAA morphologies in 932 patients with drug-refractory AF who were planning to undergo catheter ablation. In their study, LAAs were categorized into four different morphologies by CT scan and MRI (based on length, angle and leaf number structure characteristics and so on): Cactus, chicken wing, windsock, and cauliflower. Chicken wing was the most prevalent LAA morphology (48%) and 18% in cactus, windsock, and cauliflower, respectively. Among patients with a CHASD2 score 0–1, chicken Wing LAA had the lowest risk of previous stroke/transient ischemic attack (TIA). Stroke was significantly more prevalent in nonchicken wing morphology compared with the chicken wing category (4.6% vs. 0.7%). After controlling for CHASD2 score, gender, AF types, and so on in a multivariable logistic model, chicken wing morphology was found to be 79% less likely to have a stroke/TIA history. Kimura et al.[6] conducted a study to clarify the anatomical characteristics of the LAA morphology as a new risk stratification of strokes in patients with nonvalvular AF who had low CHASD2 score. The authors found that LA size, LAA flow velocity, left ventricular function, and serum brain natriuretic peptide (BNP) level were unable to predict strokes. However, a “cauliflower” LAA was an independent predictor of a stroke. Thus, the morphology of LAA is closely related to the occurrence of thromboembolic events.
LAA has systolic and diastolic function, systolic function is involved in left ventricular filling, and diastolic function is related to LA capacity-pressure adjustment. In sinus rhythm, LAA rarely form thrombus due to normal contractility. Special blood flow spectrum in LAA is identified by transesophageal echocardiography (TEE): The upper evacuation wave is caused by LAA active contraction and the subsequent filling wave is caused by LAA elastic recoil or pulmonary veins filling LA and LAA when atrioventricular pressure disappears.[3] Under the pathological condition, to ensure adequate filling of left ventricular, LA and LAA have to increase inner diameter and enhance contraction force to relieve LA pressure when the pressure of LA increases. With the increase of LAA, the orifice of LA is significantly broadened and turns into spherical or hemispherical, which finally causes gradually decreasing in the filling and emptying rate of LAA. In AF rhythm, introvert motion of atrial appendage is hard to empty LAA, leading to pooling in LAA, and forming the pathological basis of thrombus. A low-velocity and saw-tooth-shaped outflow signals can be found by TEE.[6],[7] Studies have showed that the formation of thrombosis in LAA depends on the LAA contractility in patients with AF. LAA thrombus is more common in patients with reduced LAA contractile function.[8],[9]
Left atrial appendage and atrial fibrillation thrombosis
LAA is the main site forming thrombosis in patients with AF. Studies show that 57% of atrial thrombi in patients with valvular AF and 90% of atrial thrombi in patients with nonvalvular AF are from LAA.[10] LAA structure remodeling, damage of vascular endothelial structure and function, activation of coagulation, and some other factors may compose the critical mechanisms in LAA thrombus in AF patients.[2],[11]
Left atrial appendage function and atrial fibrillation thrombus
In sinus rhythm, LAA has normal contractile function and it is not easy to form thrombus. While in AF rhythm, the blood flow velocity in LAA significantly decreases, which causes an increase of LA pressure. Thus, LA and LAA have to increase inner diameter and enhance contraction force to relieve LA pressure and ensure adequate blood filling in left ventricular. With the increase of size of LAA, the filling and voiding rate of LA will further decreases. Besides, the broadened ostium of LA, the spherical or hemispherical changes of LA, the introvert motion of atrial appendage and the bumpy of trabecular make it easy to form vortex and pooling in LAA and thus more likely to form thrombosis.[2] Zateyshchikov et al.[12] found that LAA filling and emptying velocity <20 cm/s is an independent risk factor of developing thrombus in LAA for patients with sustained AF.
Iatrogenic LAA functional damage can easily lead to thrombosis in LA. LA contractile function is mainly completed by atrial appendage. When LAA is isolated, the contractile function of LA is severely impaired, which may lead to the formation of thrombosis more easily even in sinus rhythm.
Clinical risk factors for thrombosis in left atrial appendage
Scherr et al.[13] found that CHADS2 score ≥2 and large LA diameter are increased risk factors of LA thrombus in patients with AF, while the type of AF and the rhythm at the time of check are not related to risk of LA thrombus. A subsequent study also confirmed that CHADS2 score is closely associated with LA thrombus. Other predictors of LA thrombus include heart dysfunction, history of stroke/TIA, and diabetes. The duration of sustained AF and spontaneous echocardiographic contrast is also a high risk factor for LAA thrombus.[14] Zateyshchikov et al. [12] found that age >75 years is also a risk factor for LA thrombosis in patients with sustained AF. LAA thrombus in elderly AF patients may be an important cause of stroke.[15]
Recently, Boyd et al.[16] found that left ventricular mass was the strongest predictor of LAA thrombus in patients with AF. Increase of left ventricular mass can lead to decreased left ventricular diastolic function, followed by LA enlargement and hemodynamic changes, which makes it easy to form LAA thrombus. Tang et al.[17] studied 433 consecutive patients with nonvalvular AF who underwent catheter ablation, and found 6% patients with LA thrombus after TEE screening. Moreover, the body mass index ≥27.0 kg/m 2 is an independent risk factor of thrombosis. The LA thrombosis in obese patients may be related to the level of some hormones and level changes of cytokines, growth factors secreted by fat cells.
Left atrial appendage structure and atrial fibrillation thrombus
In addition to the clinical factors, the morphologic structure of LAA may be related to local thrombosis. Beinart et al.[18] identified the relationship between LAA features (volume, depth, number of lobulation, short and long axis of the LAA neck) with a higher stroke/TIA risk in patients with AF using MRI. They found that besides age and aspirin use, the only statistically significant multivariable predictor of events was the LAA dimension (short axis × long axis). Di Biase et al.[5] analyzed 932 (14% had CHADS2 ≥2) patients with drug-refractory AF who were planning to undergo catheter ablation. In their study, all patients underwent cardiac CT or MRI of the LAA. The distribution of different LAA morphologies was cactus (30%), chicken wing (48%), windsock (19%), and cauliflower (3%). Of all patients, 8% patients had a history of ischemic stroke or TIA. After controlling for CHADS2 score, gender, and AF types in a multivariable logistic model, chicken wing morphology was found to be the least likely type to have a stroke/TIA history. Compared with chicken wing, cactus was 4.08 times (P = 0.046), windsock was 4.5 times (P = 0.038), and cauliflower was 8.0 times (P = 0.056) more likely to have a stroke/TIA. Kimura et al.[6] selected 80 patients who underwent catheter ablation of AF with contrast-enhanced computed tomography, the LAA characteristics were compared between 30 patients with histories of strokes and 50 age-matched controls. The CHA2 DS2-VASC score-adjusted logistic regression analysis revealed the cauliflower LAA as an independent predictor of a stroke (odds ratio: 3.355; 95% confidence interval: 1.243–9.055; P = 0.017). However, the exact mechanism of different LAA types resulting in difference in the risk of stroke is not clear.
In conclusion, LAA systolic dysfunction combined with many clinical factors and the special morphological structure of LAA, facilitates the formation of LA thrombus.
| Indications and Contraindications of Left Atrial Appendage Intervention | | |
Surgical left atrial appendage intervention
Surgical LAA intervention to prevent AF thrombus mainly includes excision or exclusion by sutures or stapling. Kanderian et al.[19] enrolled 137 patients with AF who underwent surgical LAA closure. Of the 137 patients, 52 (38%) underwent excision and 85 (62%) underwent exclusion. All patients had a TEE after surgery to evaluate LAA blood flow and thrombus. Patent LAA, remnant LAA (residual stump >1 cm), or excluded LAA with persistent flow into the LAA were identified as unsuccessful closure. The study showed 82 (60%) patients who underwent LAA closure were unsuccessful. Successful LAA closure occurred more often with excision (73%) than suture exclusion (23%) and stapler exclusion (0). Adams et al.[20] enrolled 12 patients with permanent AF and an indication for elective cardiac surgery. During the cardiac procedure, circular ligation of the appendage was performed. At 3-month follow-up, cardiac-gated CT demonstrated that 75% (9/12) of the patients had communication of contrast dye from the LAA to the body of left atrium, which was suggestive of incomplete long-term exclusion. Bartus et al.[21] reported 11 patients underwent ligation of the LAA by pericardium. Only one of the 11 procedures was terminated owing to the lack of echocardiography guidance of the snare over the marker balloon. One patient with pectus excavatum did have ligation of his LAA; however, a thorascopic procedure was required to remove the snare from the LAA owing to compression of the LARIAT by the concave sternum. Six patients were followed up for 2 months, in which two patients were found incomplete exclusion. All of the previous studies indicate that after surgical LAA intervention, the follow-up should focus on whether there is LAA incomplete exclusion, because it is easy to develop later thrombus. The surgical LAA ligation is easy to develop incomplete exclusion, and the success rate of suture for LAA exclusion is higher than ligation, in which the success rate of linear suture after string suture has the highest success rate. Ailawadi et al.[22] performed an open cardiac surgery at seven USA centers to assess the safety and efficacy of a novel LAA exclusion clip-atriclip. The LAA in one patient was too small to meet eligibility criteria. Intraprocedural successful LAA exclusion was confirmed in 67 patients (95.7%). At 3-month follow-up, 60 of 61 patients available for the assessment (98.4%) had successful LAA exclusion by CT or TEE. However, how to locate the exclusion ostium of LAA and how to occlude LAA needs more clinical evidence.
Indications for surgical left atrial appendage intervention
For AF patients undergoing selective thoracotomy, surgical LAA intervention and prevention of thrombosis are recommended during the operation at the same time. Surgical LAA interventions include surgical suture, ligation, and excision. Surgical suture or ligation of LAA may develop incomplete LAA occlusion and there is still thromboembolism risk, thus excision of LAA is served as the first choice for surgical LAA intervention.
The specific recommendations are as follows: (1) for AF patients who underwent mitral valve surgery and AF ablation, it is recommended to perform LAA excision at the same time; (2) for persistent AF patients who underwent aortic valve surgery and AF ablation, without increasing the risk of surgery (extend operation time may increase the risk of bleeding), it is recommended to perform LAA excision at the same time; (3) for persistent AF patients who underwent coronary artery bypass grafting and AF ablation, without increasing the risk of surgery (extend operation time may increase the risk of bleeding), it is recommended to perform LAA excision at the same time; (4) for persistent AF patients who underwent cardiac surgery treatment toward critical congenital heart disease and AF ablation without increasing the risk of surgery (extend operation time may increase the risk of bleeding), it is recommended to perform LAA excision at the same time; (5) for young AF patients without cardiopulmonary disease who underwent minimally invasive ablation, it is recommended to perform LAA treatment at the same time.
Contraindication of surgical left atrial appendage intervention
LAA local tissue is friable and easily bleeding or patients whose life expectancy is <1 year.
Percutaneous left atrial appendage occlusion
Surgical excision or suturing LAA is still traumatic. Percutaneous LAA closure developed in recent years can effectively prevent thromboembolic events from occurring. Till date, there are three devices on the market for percutaneous LAA occlusion: PLAATO, WATCHMAN, AMPLATZER Cardiac Plug (ACP). The basic structure of PLAATO and WATCHMAN are similar, which is a self-expanding nitinol cage covered with an occlusive expanded polytetrafluoroethylene (ePTFE) membrane, and there is an anchor (such as barbs on fishhook) on the rod of nickel titanium alloy stent, which can assist device to fix in atrial appendage to avoid shedding. The purpose of the membrane is both to occlude the ostium of the LAA and to allow tissue incorporation into the device.
The ACP is a dedicated device for LAA occlusion; its structure is similar to AMPLATZER interatrial septum occlusion device. It consists of a lobe and disc, connected by an extensible and flexible waist. The device is filled with polyester to enhance endothelialization and prevent blood flow into the LAA. After implantation, LA endothelial cells will creep growth on the surface of in polyester membranes, and develop new endothelium after a period of time. The device is released via a specially designed interatrial punctures septum and releases catheter. Percutaneous LAA occlusion developed in recent years is a kind of treatment with fewer complications, easy-to-handle and lower time-consumption. Studies that apply this technology to prevent AF thromboembolic events have also confirmed its effectiveness that is not inferior to warfarin therapy.
Indications for percutaneous left atrial appendage closure
AF patients with CHA2 DS2-VASC score ≥2 combined with one of the following conditions: (1) Ineligible for long-term oral anticoagulation (OAC); (2) patients taking warfarin with International Normalized Ratio (INR) between 2 and 3, but still develop stroke or thromboembolic events; (3) HAS-BLED score ≥3. Before operation, related imaging examination should be performed to identify structure of atrial appendage, and the patients whose structure is not suitable for the implantation of occluder should be excluded. Taking into account of the learning curve and risk at the primary stage of LAA occluder implantation, it is recommended that this technology should be carried out in hospitals with advanced heart surgery facility.
Contraindications for percutaneous left atrial appendage closure
(1) LA diameter >65 mm, intracardiac thrombus/dense spontaneous contrast by TEE, significant mitral stenosis, or an existing pericardial effusion >3 mm; (2) life expectancy <1 year; low risk for stroke (CHA (2) DS2-[VASC] = 0 or 1) or low risk for bleeding (HAS-BLED score <3; (3) Patients with warfarin for other diseases; (4) A patent foraman ovale with atrial septal aneurysm and right to left shunt; complex atheroma which has the characteristic of “movable,” “ruptured,” or “thickness 4 mm” in the ascending aorta/aortic arch;[23],[24],[25] (5) LARIAT is not recommended in patients with pleural adhesions (including patients who undergo heart operation, pericarditis and chest radiotherapy); (6) patients undergo elective cardiac surgery; (7) although there is no direct evidence confirming that cardiac dysfunction is a negative factor of percutaneous LAA occlusion, patients with left ventricular ejection fraction <0.35 or untreated New York Heart Function Class IV are not recommended.
| Methods for Left Atrial Appendage Occlusion | | |
Percutaneous left atrial appendage occlusion
Percutaneous LAA occlusion was first applied to clinical in August 2001.[26] PLAATO system was used in AF patients with high risk for stroke who have contraindications for Warfarin in European and American Centers. Since then, WATCHMEN, ACP, LARIAT were also utilized in clinical. After up to 5 years follow-up, the PLAATO study [24] showed that the annualized stroke/TIA rate was 3.8% which was lower than the anticipated stroke/TIA rate with the CHADS2 scoring method (6.6%/year). Thus, PLAATO was evaluated as a treatment strategy for non-warfarin candidate AF patients at high risk for stroke. Another study PROTECT AF was conducted to determine whether percutaneous LAA closure with a filter device (WATCHMAN) was noninferior to warfarin for stroke prevention in AF. After 2.3 years of follow-up, the “local” strategy of LAA closure is confirmed noninferior to “systemic” anticoagulation with warfarin. In addition, preliminary results showed that the implantation of the ACP and LARIAT device is feasible and effective with acceptably low access complications.[28],[29] Although the concept of LAA closure seems reasonable for prevention of stroke caused by AF, adequately powered, randomized studies in patients with high stroke risk and long-term follow-up, comparing interventional/percutaneous/surgical LAA closure with OAC therapy including novel oral anticoagulants (NOAC) drugs, are needed for adequate assessment of such techniques. Guidelines of AF in European Society for Cardiology in 2012[30] point out that interventional, percutaneous LAA closure may be considered in patients with a high stroke risk and contraindications for long-term OAC.
LAA device implantation should be performed under general anesthesia though it can also be carried out under local anesthesia, if the patient cannot tolerate the general anesthesia. A 5-F sheath is advanced into the LAA by left femoral artery puncture, and then the tip of pigtail catheter is placed to the ascending aorta for pressure measurement. Right femoral venous access is preferred, and then enters LA by trans-septal punctures. The operation and interatrial septum puncture should be guided by TEE whenever necessary. Intravenous heparin is administered before or immediately following trans-septal puncture to maintain an activated clotting time (ACT) >250 s. Following trans-septal puncture, using hard wire go through interatrial septum puncture sheath, and implant the capitular head in LAA, then withdraw interatrial septum puncture sheath, delivery special delivery sheath for LAA occlusion into the LA via steel wire, with capitular head in LAA. Usually, a right anterior oblique 20° and cranial view (CRA) +20° are optimal in visualizing the maximum diameter of LAA ostium. According to the results of angiography and TEE, the diameter of LAA is evaluated. If necessary, other positions can be added to evaluate the anatomy of LAA including the shape of atrial appendage neck, the length of atrial appendage, the existence of sublobe, the positional between LAA and pulmonary vein. Appropriate size of occlude is selected according to the measurement diameter of LAA ostium and structure characteristics. Usually, the diameter of the occluder is 20–40% greater than the maximum diameter of LAA ostium to ensure that there is enough supporting force to fix after releasing the occluder. The occluder is sent to LAA ostium via delivery sheath and released after confirming that the occluder is in the optimal place by LAA angiography and TEE. In order to identify the effectiveness of occlusion and exclude that the occluder is at the ostium of left upper pulmonary vein openings, redetection should be made to confirm whether there is blood flow into LAA by TEE and angiography. Under the fluoroscopy guidance, the device stability is then tested by retracting and pulling the device. If the effectiveness is satisfactory, release the device and withdraw the sheath. Otherwise, retreat the occluder and then replace the device or exchange with a new one of different diameter until achieving the optimal effectiveness.
Surgical left atrial appendage intervention
Madden performed the first LAA exclusion in 1949,[31] but the incidence of complications is high at the early stage, thus that LAA exclusion had not been carried out widely.[32] Subsequently, Cox III technique was confirmed by clinical trials and became an effective treatment method of permanent AF. The Cox III technique usually includes LAA exclusion or occlusion. Therefore, LAA exclusion made headlines again. A number of surgical centers conventionally perform exclusion or ligation of LAA during the operation to reduce the risk of stroke.[33],[34],[35] In 2006, the Guideline of American College of Cardiology [36] recommended that LAA should be cut during mitral valve replacement surgery. Update Abstract for AF Guideline, European Society of Cardiology 2012[37] indicates that LAA occlusion (including surgical LAA resection) can be served as a treatment for AF patients who cannot take any type of oral anticoagulant drug for long-term and have a high risk of stroke (IIb, c). 2014 AHA/ACC/HRS Guidelines [37] recommend: AF patients undergoing cardiac surgery may be considered for LAA resection (IIb, IIc).
The surgical technique in LAA intervention has experienced three generation. The first generation is LAA resection, i.e., suture after resection of atrial appendage or anastomat resection. The second generation is LAA ligation or inward suture,[38] it may be the method for silk ligature or device occlusion. The third generation is the currently application of new LAA occlusion device.[39],[40]
Methods for direct operation
(1) LAA resection: Cutting the majority of LAA, continuously suture incision; (2) LAA suture and ligation: Directly making suture and ligation LAA, the defect is that LAA suture and ligations are often incompletely closed, leading to residual blood flow with the thrombosis risk;[41],[42] (3) purse suture:[43] Suturing a cycle long LAA base, a continuous suture is then added; (4) LAA segment ligation:[44] Ligating at LAA bottom with two waved line from outside of the heart, or ligating LAA every 5 mm in turn.
Methods for special instruments
Atricure Occlusion Device (West Chester Ohio, USA) has been approved by Food and Drug Administration, USA. The studies [22],[45] shows that this device is safe and effective in permanently blocking the blood flow from LAA to LA and reducing the risk of stroke. An animal experiment [46] in 7 baboons used this clip to occlude LAA, after 180 days performed MRI examination, the study suggested that LAA was completely occluded. In another animal experiment,[35] using Atrial Exclusion Device (AtriCure, Inc., Cincinnati, Ohio, USA) to occlude LAA, the exclusion device included two stainless steel pieces, one was flexible, the other was not easy to be bent, covered with polyester fiber fabric outside. After 7, 30, 90 days, the effectiveness of occlusion was evaluated by echocardiography, LA angiography, and pathology of gross specimen, LAAs were completely occluded. A multicenter clinical study in the USA [22] selected 71 patients with CHADS2 score >2, used this device to evaluate the safety and effectiveness of LAA occlusion, one case was exclude because the atrial appendage was too small to fit the device, 67 cases in the remaining 70 cases (95.7%) were occluded successfully, and there was no device-related complications, no perioperative death. During the follow-up, one patient died and in 61 patients receiving CT confirmation, LAA in 60 patients (98.4%) was completely occluded. Another clinical study [46] enrolled 10 patients with coronary heart disease and paroxysmal AF, during coronary artery bypass grafting, this device was used to perform LAA occlusion, the mean time of occlusion procedure was (4 ± 1) min, the LAA occlusion could completely isolate LAA.
Endo GIA II Anastomat (United States Surgical Corporation, Norwalk, Conn., USA): Cleveland Heart Center in 2005 reported [47] that 222 cases of LAA resection were performed with this device. Before the operation, TEE was used to examine whether there was LAA thrombus, if thrombus presented, standard resection was performed. Otherwise this device was implanted. There was no staple line bleeding; however, 10% of patients required additional sutures beneath the staple line to repair tears. There were five perioperative strokes (2%). One patient was suffered from laminar LA thrombus adjacent to a mitral bioprosthesis. Reoperation was required in seven cases (3%) which was due to bleeding, while no bleeding case derived from the LAA.
Tiger Paw Device System (Livermore, CA, USA): A multicenter prospective study [48] used Tiger Paw device to perform LAA occlusion in 60 patients. The average operation time was 27 s, 54 cases were followed-up for 90 days, no residual was showed by TEE.
Perform left atrial appendage intervention via thoracoscopes
LAA occlusion via thoracoscopes to prevent AF embolization has been used in clinic,[49],[50] but the reliability and superiority of this technique remains to be studied.[51],[52]
Issues in surgical left atrial appendage intervention
LAA with more fragile texture is prone to have perioperative bleeding after LAA excision. The rate of successful LAA closure relies on the cardiovascular surgeons' experience and skills. Successful closure is defined as the absence of blood flow into the distal part of the appendage, with the residual LAA tissue <1 cm. One study showed that among patients who had stapler exclusion of the LAA, 60% had a remnant LAA and 27% with residual stump >1 cm, which posing a risk for harboring thrombus.[19]
| Percutaneous Left Atrial Appendage Occlusion Devices | | |
In the past 10 years, with the development of percutaneous LAA occlusion technology, the development of LAA occlusion device is rapidly progressed, and till date, there are four devices in the market for percutaneous LAA occlusion.
The PLAATO left atrial appendage occlusion system
The PLAATO LAA Occlusion System (Ev3, Inc., Plymouth, MN, USA) was the first approved percutaneous device for LAA occlusion, and was first applied in clinic in 2001.[26] The PLAATO Occlusion System consists of an implantable device and a controllable catheter. The device consists of a self-expanding nitinol cage (range of diameter 15–32 mm), covered with ePTFE. Three rows of anchors along the struts help stabilize the occluder in the appendage [Figure 1]. The implantable device is fixed at the orifice of LAA via a trans-septal approach. Contrast agent can be injected into LAA through the controllable catheter. Once the optimal position is identified, the device is deployed, and then sheath and catheter are withdrawn [Figure 2]. | Figure 1: (a) The implant is constructed of a nitinol frame and an implant occlusion membrane consisting of a laminated expanded polytetrafluoroethylene. Small anchors along the frame and passing through the occlusive membrane assist with device anchoring. (b) Implant attached to a controllable catheter.[26] ePTFE: Expanded polytetrafluoroethylene.
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 | Figure 2: Left atrial angiography. (a) After trans-septal puncture and left atrial appendage cannulation, contrast injection outlines left atrial appendage from which an ostial diameter can be measured; (b) contrast injection via a lumen through the implant reveals hang up of dye behind the sealing surface, indicating proper position and occlusion; (c) after device release, contrast injection in the left atrial establishes complete seal.[26]
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Several studies have indicated that PLAATO system is effective for stroke prevention. In a multi-center study, percutaneous LAA occlusion was successful in 108 of 111 patients with nonrheumatic AF of at least 3 months, who were at high risk for ischemic stroke and not candidate for long-term anticoagulation with warfarin (97.3%). Of the 111 enrolled patients, one patient needed for emergent cardiovascular surgery, and neurological death in-hospital, three patients experienced cardiac temponade. After 9.8-month follow-up, in the remaining 108 patients with LAA occlusion, two patients experienced a stroke. In another prospective multi-center study, after up to 5 years of follow-up, the annualized stroke/TIA rate was 3.8%, while the anticipated annualized stroke/TIA rate (with the CHADS2 scoring method) was 6.6%. Although clinical studies showed that PLAATO system was safe and effective, the device had withdrawn from the market in 2006 under the consequence of more complications such as cardiac tamponade, device dislocation, as well as vascular complications.
The WATCHMAN left atrial appendage occlusion system
The WATCHMAN Device (Atritech, Inc., Plymouth, MN, USA) is the second percutaneous LAA occlusion device, which was first applied to clinic in Europe in 2002.[54] The system consists of three parts: An implantable nitinol device, a delivery catheter, a 12-F trans-septal access sheath. The WATCHMAN implant (range of diameter 21–33 mm) compromises a self-expandable nitinol frame structure with fixation barbs and a permeable polyester fabric [Figure 3]. The PROTECT AF study, which was conducted to determine whether percutaneous LAA closure with a filter device was noninferior to warfarin for stroke prevention in nonvalvular AF (with a CHADS2 risk score of 1 or more), is a multicenter, randomized controlled trial.[55],[56] Patients (n = 707) with nonvalvular AF, who need continued warfarin treatment, were randomized to either the WATCHMAN device or continued warfarin in a 2:1 ratio. The device was successfully implanted in 91% of patients in whom implantation was attempted. During follow-up, 86.8% of the patients stopped taking warfarin after evaluation at 45 days, and clopidogrel plus aspirin was substituted until 6 months after device implantation, after which clopidogrel was stopped and aspirin alone was continued. After 18 months follow-up, the composite primary efficacy end point (including stroke, systemic embolism, and cardiovascular death) rates were 3.0% and 4.9% in the WATCHMAN and warfarin groups respectively. | Figure 3: WATCHMAN left atrial appendage occlusion implant. WATCHMAN device, nitinol cage with a polytetrafluoroethylene membrane on the surface, and fixation barbs around the perimeter.[54]
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Hemorrhagic strokes, cardiovascular death, and all-cause mortality were less frequent in the WATCHMAN group than those in the control group (0.1% vs. 1.6%, 0.7 vs. 2.7%, 3% vs. 4.8%). However, the rate of ischemic stroke was higher in the WATCHMAN group than in the control group (2.2% vs. 1.6%). In addition, five patients had peri-procedural events, mainly air embolism. Compared with the control group, the primary safety end points in the WATCHMAN group were not satisfying: Peri-procedural complications occurred in 10.6% of the patients, serious pericardial effusion occurred in 4.8% of the patients, device embolization occurred in three patients; two patients underwent surgery to remove the device. The rate of device-related severe adverse events was 2.2% in WATCHMAN group, for which surgery was needed. However, there was no device-related death.
The AMPLATZER cardiac plug system
The ACP Device (AGA, Inc., Minneapolis, MN, USA) is the third one applied in clinic for LAA occlusion. The ACP is a three-part system consisting of a self-expandable device, a delivery catheter and a trans-septal access sheath [Figure 4].[57] It was developed on the basis of the AMPLATZER double-disk septal occluders. It is constructed from a nitinol mesh and consists of a lobe and a disk connected by a short central waist. Stabilizing wires on the lobe can assure retention. The disc seals the outer shape of the LAA orifice. | Figure 4: AMPLATZER cardiac plug device. White arrow indicates distal lobe; long black arrow indicates the proximal disk; short black arrows indicate the stabilizing wires.[57]
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The device is available in 8 diameter sizes referring to the lobe, i.e., 16–30 mm. The appropriate size is chosen to be 10–20% larger than narrowest diameter of the LAA body 1–2 cm distal to the orifice in order to have sufficient compression of the lobe in the surrounding LAA myocardium for stable positioning of the device. The device has threaded screw attachments at each end for connection to the position and delivery cable, which can support retrieval or reposition of the device. In 2011, Park et al.[28] first reported the results of clinical application of ACP. In 10 European centers, successful implantation of the ACP device was achieved in 132 of the enrolled 143 patients with AF (96%). There were serious adverse events in 10 (7%) patients, three of them experienced an ischemic stroke. Device embolization occurred in two patients (both devices were successfully recaptured). Clinical significant pericardial effusion was documented in five patients. Minor adverse events were insignificant pericardial effusions in four and TIA in two patients. In one patient, the implantable device was lost in the venous system. All patients were received aspirin and clopidogrel for 1–3 months after the procedure, and aspirin only for 5 months thereafter.
The LARIAT system
The LARIAT [21] system (Sentre HEART, Redwood City, California, USA) consists of three parts, including a compliant balloon catheter (EndoCATH), 0.025-inch and 0.035-inch magnet-tipped guidewires (findr WIRZ, two guide wires have the opposite poles, which can be mutually attracted and can achieve end-to-end union), and a 12 F suture delivery device (LARIAT). The LARIAT procedure includes four basic steps: (1) Pericardial puncture, introduction of the 0.035 inch epicardial wire into the pericardial space; (2) trans-septal puncture, placement of the endocardial magnet-tipped guidewire in the apex of the LAA with balloon identification of the LAA (confirmed by TEE); (3) connection of the epicardial and endocardial magnet-tipped guidewires, developing a “slide;” (4) snare capture of the LAA with closure confirmation and release of the pre-tied suture for LAA ligation [Figure 5]. | Figure 5: Fluoroscopic guidance to assist in the closure of the left atrial appendage (LAA) (all images are in the right anterior oblique projection). Left atrial (LA) angiography identifies the ostium and body of LAA (a). Attachment of the magnet-tipped endocardial and epicardial guidewires (b) allows for the LARIAT suture delivery device to be guided over the LAA by the magnet-tipped epicardial guidewire using an over-the-wire approach (c). After verification of the correct position of the snare with the balloon catheter (d), an LA angiogram is performed prior to the release of the pre-tied suture to exclude the existence of a remnant trabeculated LAA lobe (e). A final LA angiogram is performed to verify LAA exclusion (f) angiography confirms the LAA was ligated completely. [Bartus K. J Am Coll Cardiol, 2013, 62(2):108-118.].
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One study published in 2012 showed complete LAA closure was achieved in 96% (85 of 89 AF patients) of successful LAA ligation, in which 81 cases were fully sutured, and three cases with residual channel. Three patients experienced pericardial effusions. The diagnosis of pericarditis was made in two patients. Sudden unexpected death occurred in two cases, two patients suffered from nonembolic stroke, no complications directly related to LARIAT device. At the 1-year clinical follow-up, 98% patients achieved complete LAA suture ligation.[29]
| Perioperative Management of Left Atrial Appendage Intervention | | |
Perioperative management for percutaneous left atrial appendage occlusion
Preoperative preparation
After the informed consent is signed, patients should have detailed clinical examination, including clinical symptoms evaluation of AF and assessment of other cardiovascular diseases and heart function (NYHA classification), stroke and bleeding risk stratification as well as LAA anatomical assessment. Related laboratory examinations should be developed, including serum creatinine, blood routine test, myocardial bio-markers, coagulation function, and INR monitoring. For patients with a history of stroke, cranial CT or MRI examination should be performed before the procedure. All patients should take trans-thoracic echocardiography (TTE) examination before the procedure in order to exclude LA and LA thrombus and have a deeper insight into the LAA anatomy. Before operation, LAA anatomic structure should be fully evaluated by TEE, especially the shape, length, size of orifice, neck shape, area of “landing zone” (landing zone, a place where the device was implanted) of the LAA, and the number, shape, and location of the lobes. In addition, the position between LAA and pulmonary vein should be assessed; if the anatomical structure of the LAA is complex, a CT or MRI examination is needed to identify specific anatomical structure.
For patients with long-term oral warfarin, the dosage of warfarin should be adjusted to make INR <2.0 before operation. All patients take aspirin 300 mg twice a day and clopidogrel 75 mg twice a day 48 h before operation. Prophylactic antibiotics should be used 1 h before operation.[53]
Device implantation
The procedure of implanting a LAA occlusion device [53],[55],[59] is performed under general or local anesthesia with the guidance of fluoroscopy, multiple projection angiogram, rotational X-ray angiography, and TEE, if necessary.
All procedures should follow the standard cardiac catheterization routines, including measures to avoid air embolism and thrombosis. After venous and trans-septal puncture, the device was delivered under TEE or intracardiac echocardiology (ICE) guidance through a specially designed 12–14-F trans-septal sheath [Figure 6] into the LAA.[54] Intravenous heparin (immediately after trans-septal puncture) is administered in order to keep the activated clotting time (ACT) above 250 s.[53] | Figure 6: Trans-septal access system. 14 F device introduction sheath is available with single and double curve.
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The sheath is advanced up to the LAA orifice and atriography is performed in multiple projections. Under fluoroscopic [Figure 7]a TEE guidance, diameter of LAA ostium is measured.[26] Appropriate LAA occlusion device is chosen according to the LAA anatomies and measurements. Generally, the PLAATO LAA Occlusion System [53] is chosen to be 20–50% larger than diameter of the LAA orifice, the WATCHMAN [55] device to be 10–20% larger than diameter of the LAA, in order to have sufficient compression for stable positioning of the device. The LAmbre™ device [Figure 8] and the second generation ACP device [Figure 9][60] are now still at the stage of clinical test. Besides TEE, ICE is able to provide imaging support for device implantation as well, including LAA ostial size. The device is advanced into the LAA orifice and then deployed. During the procedure, LAA angiography performed by delivery sheath [Figure 7]b or the TEE image can be used to ascertain the optimal deploying position. The AMPLATZER device is implanted in a relatively proximal position in the LAA, a relatively shallow position in the LAA, thus only seals the ostium of the LAA; while the WATCHMAN device is implanted more distally into the LAA, therefore it can achieve more distal occlusion within the LAA, such as a complex anatomy of the distal LAA or a proximal LAA lobe.[61] | Figure 7: Angiography display left atrial appendage condition during the device implantation. (a) After trans-septal puncture, left atrial appendage angiography can be used for left atrial appendage measurement. (b) Injection of contrast agent through occluder atrium may determine the location and occlusion conditions by dyeing contrast agent behind occlusion side; (c) after releasing device left atrial angiography may display occluder complete occlude left atrial appendage.
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 | Figure 9: Comparison of first generation (left) with second generation (right) AMPLATZER Cardiac Plug device. Caudal lobe (a and b) and lumbar of second generation AMPLATZER Cardiac Plug occlude caudal lobe (a and b) and lumbar (b) has a larger diameter, stable wire (a) and plate screw (c) have more number of turn.
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After deployment, blood flow around the device is observed to make sure whether the device is complete sealed or not. The degree of sealing after device deployment is assessed by proximal dye flow according to LAA angiography and subdivided into four categories: Grade 1, “severe leak,” well-defined flow of dye completely filling the appendage; Grade 2, “moderate leak,” filling two-third; Grade 3, “mild leak,” filling one-third; and Grade 4, “trace leak or absent leak,” barely detectable or no detectable blush of dye flowing into the appendage. In addition, the degree of sealing can also be assessed by transesophageal Doppler color flow and graded on a five-point scale:[62] Grade 1, “severe leak,” multiple jets of free flow; Grade 2, “moderate leak,” >3 mm diameter jet; Grade 3, “mild leak,” 1–3 mm diameter jet; Grade 4, “trace leak,” <1; mm diameter jet; Grade 5, “absent leak,” no jet. Successful LAA occlusion is defined as no forward or reverse flow filling the appendage and residual forward or reverse flow jet around the device <3 mm in width [a grade of 3 or higher, [Figure 10], with the guidance of TEE or fluoroscopy. If an inadequate seal or sub-optimal position of the device is identified, the device is collapsed, re-positioned and re-expanded, or exchanged for a device of different size while trans-septal access is maintained. Then, the plane of the maximum diameter of the device is measured to ensure its dilation pressure. The device should be 80–90% of the original size. Device stability is tested by gently pulling with the fluoroscopic and TEE guidance. Until the final release, the delivery system is withdrawn. Once the device has been completely released, a final angiography is performed to confirm the closure of LAA [Figure 7]c. | Figure 10: Comparison of first generation (left) with second generation (right) AMPLATZER Cardiac Plug device.
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Operators should have to anticipate immediate resolution of cardiac perforation or device embolization.[58] Potential causes for cardiac perforation may include the use of stiff guidewires to guide catheters, repeated device repositioning and deep device implantation into the LAA. If a cardiac perforation occurs, immediate percutaneous drainage and transfusion should be performed. Thus, red blood cells and surgical back-up should be available. Additionally, retrieval tools (such as snares, forceps, etc.) should be prepared in case of device embolization.
Postprocedural follow-up
After the procedure, patients are monitored for at least 24 h. A chest X-ray should be taken after 24 h to identify the device position,[53],[55] and a control TTE is obtained in all patients to evaluate for procedural complications such as pericardial effusion and cardiac tamponade. If no complications occur, patients can be discharged one day after the procedure.[59] Implantation success is defined as successful delivery and deployment of the LAA occlusion device implant into the LAA and the absence of major adverse events. Success performance of the device can be defined as successful delivery and deployment of the device implant into the LAA and LAA occlusion, as visualized by the investigator with TEE, before discharge or after 7 days.
After the implantation procedure, low molecular weight heparin (LMWH) is used until an INR of 2 is achieved with warfarin. Currently, there are no formal guidelines for antithrombotic therapy after the device implantation. The only antithrombotic protocol that was consistently applied in a clinical study after implantation derives from the PROTECT AF study, including the use of warfarin for at least 45 days.[56] During this period, coagulation function should be examined once a week to keep the INR between 2 and 3. At 45 days, for patients with a history of stroke, NIH Stroke Scale (NIHSS), Barthel index (BI), modified Rankin scale (MRS) as well as SF12v2 health survey are used to assess the severity of the stroke and long-term function change after stroke.[55]
If a TEE shows successful LAA closure (a residual flow jet around the device <3 mm in width) at 45 days, warfarin is discontinued and replaced by a dual antiplatelet therapy (DPI or a combination of aspirin and clopidogrel). At 6 months, clopidogrel is discontinued and aspirin is continued indefinitely.[56] If the TEE shows incomplete LAA closure at 45 days, the consideration should be given to keep the patient on warfarin. TEE should be performed after procedure, at 3, 6, and 12 months to exclude device embolization and detect residual leaks. CT scan and cardiac MRI are alternatives to detect thrombus and/or residual leaks after LAA occlusion. Currently, it is considered to be safe for an MRI examination under the following conditions: static magnetic field ≤3 T; magnetic field gradient space ≤720 G/cm; scanning for 15 min under 3 W/KG of maximal general mean specific absorption rate The above MRI safety conditions are nonclinical test results and just for reference. In addition, the image quality of MRI may be affected.
In the PROTECT AF study,[55] patients after the WATCHMAN device implantation were discharged from hospital with aspirin 81–100 mg daily and warfarin for at least 45 days. The dosage of warfarin was adjusted to keep the INR between 2 and 3. If complete LAA closure was confirmed by TEE at 45 days, warfarin therapy was discontinued, a clopidogrel on 75 mg/day therapy was given for at least 6 months, and aspirin on 325 mg/day therapy was continued. About 4.2% of the patients had thrombus on the device and 13% did not discontinue warfarin during follow-up. The need for OAC in response to the presence of residual flow around the device during follow-up is still controversial. In the PROTECT AF trial, TEE at 12 months postprocedure revealed that 32% of the implanted patients had at least some degree of peri-device flow. Nevertheless, these do not imply a relationship with an increased risk of thromboembolism.[63] In ASAP Registry,[25] warfarin-ineligible patients who implanted with WATCHMAN device received 6 months of treatment with clopidogrel and lifelong aspirin; 77% fewer ischemic stroke events were observed; the annual hemorrhagic stroke rate was 0.6%; device-associated thrombus was observed in 4.2%.
However, there are no large scale randomized controlled studies with respect to postprocedural antithrombotic therapy for ACP device implantation. Chun et al.[64] found that, compared with WATCHMAN device, in patients receiving dual antiplatelet therapy for 6 weeks after ACP device implantation, device-related thrombosis rate could be reduced to 1.7%, while ischemic stroke rate was more than 4.2%, which is higher than expected. Larger population clinical studies are needed to confirm the findings.
Furthermore, given the fact that the majority of patients who implanted LAA occlusion device have an OAC-associated bleeding risk, careful consideration is needed with respect to antithrombotic therapy after device implantation. So far, the consensus seems to be reached for the application of a dual antiplatelet therapy during the first 3–6 months after device implantation, and then switching to lifelong aspirin alone. This approach has been proved in recent registry studies with satisfactory results.[61]
After the procedure, patients with stroke history should visit the neurology clinic at 6, 12 months and every year thereafter. During the follow-up, NIHSS, BI, and MRS can be reassessed. If any neurological symptoms or signs occur, or NIHSS scores increase ≥2, or BI scores decrease ≥15, or MRS scores increase ≥1, especially when these changes are not associated with neurological diseases, patients should consult neurologists. All patients should take SF12v2 health survey forms at 12 months after the procedure.
Perioperative management of surgical left atrial appendage intervention
Preoperative management
All patients prepared for surgical LAA intervention should be evaluated before operation in order to make a personalized operation plan for each patient according to their general conditions, which can ensure a safe and efficient operation.
Cardiac vascular ultrasound and/or CTA scan provide better understandings of the anatomies of pulmonary veins, LAA and LA, LA and LAA thrombosis, conditions of cardiac valves, cardiac size, and function. Cardiac vascular ultrasound and/or CTA scan also provide evidence for operation plan making and surgical risk evaluation.
Coronary artery examination
For patients suspected with coronary lesions, if necessary, coronary angiography is needed to exclude coronary artery diseases. If a coronary artery disease is combined, corresponding operation plan should be considered.
For patients with suspected LAA thrombosis, warfarin anticoagulant therapy (INR 2.0–3.0) should be performed for 3 months before the operation. A TEE is performed to detect the LAA thrombus at 3 months. If there remains a LAA thrombus, an open surgical approach is recommended, which can make it possible to remove the LAA thrombus while have an AF ablation, as well as perform a LAA occlusion. When a patient, who has diseases such as mitral stenosis requiring surgical operation, is found to have suspected LAA thrombosis, a surgery is needed as soon as possible.
Heart and pulmonary function examination
Status of cardiopulmonary function of the patient should be evaluated, to assess whether or not he/she can tolerate the surgery as well as general anesthesia.
Laboratory examination
Liver and kidney function, blood glucose level, blood electrolytes, thyroid function, Atrial natriuretic peptide, BNP, cTn, INR, etc., should be examined before operation. Patients with hyperthyroidism/hypothyroidism should not have an operation until the lab indicators such as thyroid-stimulating hormone, T3, and T4 return to normal levels after appropriate treatment.
Except for emergency surgery, patients receiving aspirin or warfarin therapy are recommended to discontinue antithrombotic therapy for 72 h before operation. And LMWH is used instead.
Operation management
All patients undergo general anesthesia, tracheal intubation, deep venous puncture catheter placement radial artery catheter placement, continuous real-time monitoring of the vital signs such as heart rates, blood pressure, respiration, SaO2, central venous pressure, temperature, and timely examination of arterial blood gas, electrolytes, ACT, and so on. Emergency medications and equipment, operating instruments as well as defibrillators should be prepared for emergency cases.
Postoperative management
After operation, all patients are sent to intensive care unit for monitoring. Vital signs, arterial blood gas, blood electrolytes, and so on should be monitored timely. Continuously intravenous amiodarone (50 mg/h) can be administered after operation, if heart rate can tolerate (≥65 times/min); thereafter, oral amiodarone (200 mg/day) can be considered. For patients with amiodarone contraindication, metoprolol is recommended.
For patient who has recurrent AF with hemodynamic instability, synchronized cardioversion is recommended. If antiarrhythmic drug therapy does not work for patients with recurrent AF 3–6 months after operation, synchronized cardioversion is also recommended.
For patient with normal amount of pleural fluid exudation, LMWH is recommended 24 h after operation; Patients should receive warfarin therapy for 1–3 months after operation.
Holter, echocardiography, chest X-ray, and other examinations should be performed before discharge to evaluate heart rhythm, heart rate, pulmonary veins, and LAA conditions.
| Treatment of Complications of Left Atrial Appendage Interventions | | |
Complications and treatment for percutaneous left atrial appendage occlusion
For AF patients contraindicated to OAC, percutaneous occlusion of the LAA would be an effective way to prevent most cardioemboli. And its complication incidence is lower (6–7%),[28],[56] and gradually decreased as the operator's experience accumulated.[1] Main periprocedural complications include the following: Pericardial effusion/cardiac tamponade, procedure-related stroke (gas embolism, cerebral hemorrhage), device embolization, device-associated thrombus, residual leakage, bleeding, blood vessel puncture complications. The proportion of complications that need emergent cardiovascular surgery is 1.1% (0.2–6.3%),[1],[23
,[24],[53],[65],[66] which is mainly caused by pericardial effusion and tamponade, followed by device embolization. The mortality rate of LAA occlusion is relatively low. Studies have showed that the average periprocedural mortality rate is 1.1% (0–1.6%).[23],[24],[53],[66],[67],[68] Causes of death include the following: Anesthetic induced congestive heart failure,[53] device removal-caused iliac artery rupture leading hemorrhaging shock,[53] device dislodgement causing left ventricular outflow occlusion.[66] The main periprocedural complications and treatment are as follows.
Pericardial effusions/cardiac tamponade
The most common complications related to the procedure are pericardial effusions and cardiac tamponade with a total incidence at 4.1% (0–6.7%).[1],[23],[24],[26],[28],[53],[54],[56],[59],[66],[67] The serious effusion cases with hemodynamic significance were discovered within 24 h of the procedure. But there were very few patients presenting with delayed cardiac tamponade, even 2 weeks to 1 month after the procedure. Common causes of pericardial effusion/cardiac tamponade are improperly operation of guide wires/catheters, repeated device repositioning, deep device implantation into the LAA and inappropriate trans-septal puncture, and so on. Emergent treatment for myocardial perforation includes immediate percutaneous pericardiocentesis, transfusion, and cardiac surgery, in which the most important resolution is immediate pericardiocentesis drainage under fluoroscopic and angiographic guidance. Data from the PROTECT AF trial and the CAP registry study [1] suggest that by these approaches the vast majority of patients with cardiac tamponade (76.5%) can avoid cardiac surgeries; even if a cardiac surgery is inevitable, these approaches can save time for surgery. Thus, units of red blood cells and surgical back-up are still crucial for emergent treatment of the pericardial effusion/cardiac tamponade. Recently, a case reported that an atrial septal defect closure device was used to seal the larger bore perforation of the LAA.[69] In this case, it suggested that when free-wall perforation occurred, it was important to leave the catheter or sheath plugging the perforation. An atrial septal defect closure device was selected to accomplish perforation sealing, and then a LAA occlusion device was used for LAA occlusion. In addition, a preevaluation TEE, CT or MRI examination should be performed to fully explore the anatomy of the LAA. The appropriate device should be selected. Multiple angiographic views or rotational angiography should be used for performing trans-septal puncture. TEE or ICE should be used to monitor the implantation process throughout the procedure. By using a pigtail catheter, the risk for perforation of the LAA by the tip of the sheath can be strongly reduced; when checking for device stability, contrast should be injected into the LAA to visualize the LAA chamber. Multiple inappropriate device repositioning should be avoided. The operator should be experienced and perform precisely. All these above methods can effectively prevent pericardial effusions and cardiac tamponade. Overall, after catheter or surgical drainage of the pericardial effusion, all patients functionally recover well; and there is no long-term disability or death related to these effusions. However, the mean duration of hospitalization should be extended by an average of 6 days for patients requiring either percutaneous pericardiocentesis or surgical intervention.[1]
Procedure-related stroke
Stroke is a severe complication of percutaneous LAA occlusion, and the total incidence of occlusion related cerebral embolism and cerebral hemorrhage is 0.6% (0–2.2%).[1],[28],[56],[66] The stroke getting most attention in the literature reports is cerebral embolism. The cause of cerebral embolism may be gas embolism or thrombotic embolism. PROTECT AF study [1] reported five patients with stroke (0.9%) in total, and three of them are gas embolism, which was confirmed by X-ray and ultrasound during operation that gas entered into left circulatory system. Although the remaining two cases could not be fully explained, it was very likely that they were also caused by gas embolism. Gas embolism is an acute complication that mostly occurs in the same day or within 48 h after surgery. Because of using 12 F trans-septal sheath with relatively large diameter, it is very important to continuously flush sheath to prevent air. In addition, preoperative fasting can cause dehydration and further lead to LA pressure reduction, which can easily induce gas embolism. Therefore, before unfolding the occluder, normal saline should be routinely used to increase LA pressure to about 10 mmHg.[70]
Occluder embolization
The incidence of perioperative occluder embolization is 0.7% (0–6.3%).[1],[23],[26],[28],[54],[56],[65],[66],[67] The PROTECTAF study reported three cases (0.6%) of occluder embolization, in which one case was found during operation, and the other two cases were found by TEE during follow-up at 45 days. For the patient found during operation, the occluder was dislodged to left ventricular outflow tract, thus surgical operation was performed. For the other two cases, the dislocated occluders were located in the aorta (one located in thoracic aorta, the other in the bifurcation of abdominal aorta iliac artery). The ASAP study [25] reported two cases (1.3%) of occluder dislodgement occurring in the operation. The occluders were both embolized in the descending aorta and successfully captured through percutaneous hitching device, in which one patient required a larger size occluder for successful occlusion. Therefore, retrieval tools (hitching device, foreign body clamping) should be routinely prepared to prevent the occurrence of occluder embolization.
Occluder thrombosis
The incidence of occluder related thrombosis is 4% (2.4–6.8%).[1],[25],[54],[71],[72] The results of the PROTECT AF study [1] showed that 20 out of 478 patients had occluder-related thrombosis in postoperative follow-up. Three of them had TIA, and other patients had no symptoms and achieved completely endothelialization after taking anticoagulant drugs. Occluder thrombus was mobile in four patients and nonmobile in ten cases, the rest of thrombotic state was unknown. Among those patients with TIA, the thromus in one patient was clearly mobile and had a pedicle. The ASAP study [25] reported six cases of occluder related thrombosis, only one presented cerebral infarction at the 341st day after operation. In the other five asymptomatic patients, four underwent 4–8 weeks of LMWH therapy, and the other one patient did not undergo treatment. An earlier study [54] reported four cases of patients with occluder thrombosis at 45 days during follow-up. TIA occurred in one case, the author [54] thought that endothelialization was incomplete at 45 days thus aspirin combined with clopidogrel should be used for 6 months after discontinuation of warfarin. In addition, a case report showed that in patients without LAA thrombus by preoperative TEE, at 6 months of routine follow-up, some mobile masses were found on the surface of occluder surface which were highly suggestive of thrombosis. It presented a challenge for the effectiveness of percutaneous LAA occlusion and postoperative anticoagulation strategy. Since many patients who underwent percutaneous LAA occlusion with oral anticoagulant had bleeding risk, the postoperative anti thrombotic treatment strategy must be taken with great caution. Currently, it is more preferable to give combined antithrombotic treatments, which uses the combination of aspirin and clopidogrel at 3–6 months after operation followed by aspirin monotherapy.[25],[72],[73] But by the adjustment of other factors, the main determinant for postoperative antithrombotic treatment strategies is the ratio of occluder-related thrombosis and residual leakage. Therefore, more individualized antithrombotic strategy should be developed according to occluder-related thrombosis formation and residual leakage evaluation by postoperative TEE. Although the impact of residual leakage on prognosis is still under debate, once occluder thrombosis is found after operation, anticoagulation must be performed. Possible treatment can be aspirin alone or the combination of aspirin and clopidogrel. Further study is needed to determine which antithrombotic strategy is more reasonable.
Residual leakage
The definition of residual leakage is not uniform across studies. The PROTECT AF study [27] defined it to be blood flow width around occlude ≥5 mm measured by TEE, while the PLAATO research [24],[53] defined residual leakage as blood flow width >3 mm. However, a true successful occlusion should have no residual blood flow. The results of latest study [57] showed that the incidence of residual leakage for ACP occluder was 16.2% after follow-up for 6 months. Moderate residual leakage were found in five patients who had no residual leakage until the 6th month of follow-up, whose lower left ventricular ejection fraction may be related to newly emerging residual leakage. The PROTECT AF subgroup analysis [65] evaluated various degree of residual blood flow around WATCHMAM occluder, in which the results showed that the incidence of residual leakage decreased with the extension of time, from 40.9% at 45 d after operation to 33.8% at 6 months after operation, and reached 32.1% at the 12th month after operation. Of all patients who were recorded to have residual blood flow, mild (<1 mm) accounted for only 7.7%, while moderate (1–3 mm) and severe (>3 mm) were more common, accounting for 59.9% and 32.4%, respectively. The results revealed that the severity of residual blood flow around LAA occluder was not related to the application of warfarin and clinical prognosis (including thromboembolic events). The ratio of adverse events did not increase in patients with residual blood flow around occluder, and extended duration of warfarin anticoagulation did not significantly reduce the incidence of adverse events either. Although the study suggested that at 45 days after operation warfarin could be discontinued, this conclusion remained to be discussed since some patients in the study with residual blood flow continued to take warfarin which might affect the accuracy of the results of the study. Moreover, other studies [25],[27] reported that after LAA occlusion only aspirin and clopidogrel should be prescribed instead of anticoagulants. The degree of residual leakage should not be the basis for application of anticoagulant drugs after operation.[74] Thus, how the residual leakage around occluder affect patients' clinical prognosis and postoperative antithrombotic strategy choice remains controversial.
Other complications
Other perioperative or occluder related complications include bleeding events, (0.7%)[1],[54],[55],[56],[67] puncture site hematoma (0.4%), arteriovenous fistula (0.2%), arrhythmia (0.2%), and pseudoaneurysm (0.2%). Other complications are esophageal tear caused by TEE probe, the first generation of occluder conveying guide wire fracture,[54] airway injury, postoperative respiratory failure).[1]
Complications and treatment for surgical left atrial appendage intervention
LAA surgical intervention is an operation performed within pectoral cavity and pericardial cavity thoracoscopically and in a minimally-invasive manner. Therefore, general anesthesia and vital signs monitoring were required. Emergent management must be available when complications occur.
Anesthesia accidents include ventricular fibrillation or cardiac arrest, and drug allergies.
Lung injury
Lung injuries may occur, with elevated operational difficulties, when there is adhesion in the thoracic cavity during a thoracoscopic operation, especially for the lack of evaluation of the adhesion severity. If the adhesions are found, the operator should carefully separate adhesions from several directions, try not to damage the lung tissue, and perform repairment for damage if necessary.
Phrenic nerve injury
When dissecting pericardium to reveal LA, LAA, pulmonary vein, and inferior vena venous, the operator tries to distinguish the position of left and right phrenic nerve to avoid injury to phrenic nerve. Phrenic nerve injury may lead to ipsilateral diaphragmatic elevation and lower lobe compression, which affects pulmonary function. Sometimes, phrenic nerve injury may cause the occurrence of atelectasis and pneumonia. Therefore, the physician should encourage patients with phrenic nerve injury to perform respiratory exercise to improve lung function. If pneumonia occurs, the appropriate anti-infection treatment should be given.
Left atrial appendage bleeding
Bleeding is the most common and serious complication in surgical LAA intervention. Once LAA bleeding occurs, the location and size of the lesion should be check out quickly, and then design operative approach. The operators should stop the bleeding by compression and prepare for transfusion, extend the incision to ensure thorough exposure for the operator if the lesion is large. The operator performs the repairment with extracorporeal circulation in severe conditions. Note that the base of LAA is adjacent to left coronary artery circumflex branch, when performing LAA intervention or bleeding repair, do not accidentally damage left circumflex branch. Endo-GIA stapler is recommended over ligation or suture, for the latter options may cause re-bleeding under off-pump operation. If bleeding occurs during ligation and suture, first compress with gauze, then give abovementioned treatment according to bleeding condition.
Major bleeding at other locations: Surgical operation may injure pulmonary artery, pulmonary vein, and arteries and veins of LA or heart surface around LAA. Once injury occurs, firstly suspend operation, locate bleeding site, and then take effective measures. Major vessels bleeding are generally more serious. On the one hand, prepare for blood, surgical instruments, necessaries, extracorporeal circulation; on the other hand extend operation incision and reveal bleeding site.
Residual communication after left atrial appendage intervention
After surgical LAA intervention, the opportunity for thrombosis within LAA is greatly reduced if occlusion of the LAA is complete. However, when LAA occlusion is not complete (especially in the case of ligation or suture), blood flow remains in atrial appendage, which is easy to form thrombus. Therefore, during operation, TEE to monitor exact LAA closure is recommended. Once residual communication is found, perform additional suture or ligation, or use an Endo-GIA stapler to eliminate the residual transfer, occlude LAA completely.
Operation incision converted to sternum median incision. Because minimally invasive surgical LAA intervention mostly use intercostal incision, bleeding is not easy to deal with when bleeding of atrial appendage or other locations happens. At that time, use sternum median incision for bleeding treatment.
Infection and pneumonia
Infections affect the outcomes of operation. Therefore, operational sterility, postoperative respiratory exercise, and appropriate anti-infection treatment are required.
Pleural and pericardial effusion
Chest tubes may be removed postoperatively when pericardial secretion and effusion mostly decrease in 2–3 days after operation. For a few patients with more pericardial and pleural effusion, take a small dose of steroids to decrease exudation after operation. Pericardial puncture may be performed when it's necessary.
Dysfunction of brain and kidney
Brain or renal function damage is rare. Brain damage may be associated with micro-embolus resulting from vascular intima damage during intraoperative ablation, which forms with blood flowing into the brain. Renal damage may be related to changes of anesthesia or hemodynamics, which was rarely reported by literatures, the real reason is still to be further studied.
| Follow-Up for Left Atrial Appendage Intervention | | |
Left atrial appendage occlusion postoperative anti thrombus therapy
Several large scale clinical studies have currently demonstrated the effectiveness of LAA occlusion intervention for preventing stroke in patients with AF. With the improvement of instruments and accumulation of clinical experience, the operation can be conducted with less perioperative complications and improved safety. However, embolization associated with device implantation is still one of the major concerns that affect the safety of patients' perioperative period. Therefore, great attention should be drawn to the antithrombotic therapy after LAA occlusion. Studies have demonstrated that thrombosis of device implantation and LAA remnant blood flow found via TEE examination may be associated with embolization events after LAA occlusion, but there is no sufficient clinical data to verify the intension of its influence. In the PROTECT AF study, 20 of 478 patients (4.2%) were found to have thrombosis on LAA implanted devices, among which ischemic stroke occurred in three cases, and 32% of 12 month-postoperative patients were found to have residual blood flow present around implanted device.[1],[56] In another study, 32% of 197 late postoperative (>7 days) via TEE patients were found to have a thrombus on implanted device.[72]
So far, there is no further recognition and experience for the anti-thrombus therapy after LAA occlusion. In several clinical studies, such as the PROTECT AF study, patients continued to take anticoagulant drugs (warfarin) after operation for 45 days, and discontinued warfarin and changed to dual antiplatelet therapy (aspirin and clopidogrel) if TEE confirmed that LAA occlusion was completed or width of residual blood flow around device <5; mm. After 6 months, stop clopidogrel while continue aspirin indefinitely.[56] However, there is no further clinical results on postoperative anti thrombus therapy for patients with high risk of bleeding.
As for residual blood flow around device found via TEE in postoperative follow-up, whether OAC clinically is necessary or not is still controversial. In several recently published registration studies, patients without taking oral anticoagulant (warfarin) after LAA occlusion but using aspirin combined with clopidogrel antiplatelet therapy (3–6 months), and later continuing with long term aspirin [61],[63] show satisfactory treatment results.
Combining the foreign clinical study [58] with domestic preliminary clinical experience, it is recommended to have dual antiplatelet therapy as basic program of antithrombotic therapy after LAA occlusion, which uses aspirin and clopidogrel for 3–6 months after operation and then take only aspirin for long-term. In addition, antithrombotic therapy should take individual condition of patients into consideration. If implanted device related thrombus or remnant blood flow around device is found in postoperative follow-up by TEE, combined with risk assessment of postoperative thromboembolism events in patients, oral anticoagulant (warfarin) could be considered as appropriate treatment with close attention to anticoagulant related bleeding risks, including regular monitoring of INR. Due to a lack of targeted clinical research support, NOAC are currently not recommended as antithrombotic therapy drugs after LAA occlusion.
Whether antithrombotic therapy is necessary after surgical LAA intervention still requires further recognition. And there is no suggestion for the use or disable so far as for postoperative antithrombotic therapy. The major problems in surgical LAA intervention are postoperative leakage and residual stump (>1 cm). In LAAOS trials, patients were randomly divided into LAA intervention group (tunica intima suture, atrial appendage cutting suture), or drug control group. Before discharge, TEE confirmed that the success rate of tunica intima suture group was 45%, whereas 72% in atrial appendage cutting suture group are successful.[75] Forty present patients were found with LAA thrombus among those who have unsuccessful LAA intervention. Evidence of stroke/TIA (P > 0.05) was found in the 6 months follow-up, which has six cases of successful atrial appendage occlusion (11%) and 12 cases of unsuccessful occlusion (15%).[19] For the antithrombotic therapy after the surgical LAA intervention, as well as whether having antithrombotic therapy for patients who were found with postoperative leakage or stump via TEE examination in postoperative follow up, more supporting clinical research is needed.
Left atrial appendage occlusion postoperative efficacy judgment and follow-up
Purpose, frequency and content of follow-up
The patients should be followed regularly after LAA occlusion. This can not only evaluate the effect of LAA occlusion, but also discover and deal with related complications in time. The recommended time for follow-up are prior to discharge, 1 week, 30–45 days, 6 months and 1 year after operation, and once every 2 years thereafter.[1],[27],[57] The contents of follow-up include the following: Assessing the patient's general status and improvement for quality of life; existence of stroke/peripheral arterial embolism or bleeding events; use of antithrombotic drugs; effectiveness of LAA occlusion; existence of delayed cardiac tamponade and other related complications, also the electrocardiogram (ECG) and routine laboratory tests (such as cardiac markers), and so on. If stroke (including ischemic and hemorrhagic stroke), severe cardiovascular events and peripheral arterial embolism occur in follow-up interval, the patient should seek the treatment in time. Regardless of existence of stroke, neurological assessment should be performed at one or two years after operation.
Evaluation of percutaneous left atrial appendage occlusion performance
In each node of follow-up after LAA occlusion, TEE should be used to assess the effectiveness evaluation. The related indicators include the following: The position of occluder within LAA; existence of residual leakage around implanted device and thrombosis on surface of device etc., According to the study of the PROTECE AF,[63] the residual leakage between LAA and atrium after LAA occlusion can be divided into three levels: Mild, moderate and severe. Mild is when the diameter of residual leakage is smaller than1mm, moderate is when the diameter of residual leakage is between 1 and 3 mm, severe is when diameter of residual leakage is >3 mm. Residual leakage <3 mm generally needs no special treatment. However, for the residual leakage, diameter >3 mm or even >5 mm, whether the condition is related to stroke events is still need for further study, and close follow-up or appropriate treatment is required.
Recommendations for antithrombotic drug application
Two options are available for the antithrombotic program after percutaneous LAA occlusion. One is to take Warfarin for at least 45 days and maintain INR between 2.0 and 3.0, followed by aspirin 81–325 mg/day and clopidogrel 75 mg/day until 6 months after operation, and then take aspirin 81–325 mg/day for long-term.[1],[27] The other one is to take dual antiplatelet drugs (aspirin 81–325 mg/day plus clopidogrel 75 mg/day) for 1–6 months, and then take single antiplatelet drugs for long-term (aspirin is recommended).[25],[27]
According to the results of previous studies, after percutaneous LAA occlusion, it is not suggested to stop OAC therapy if the following conditions occur: Residual leakage around device that is larger than 3 mm; thromboembolism events; and thrombosis on surface of implanted device after operation.
Follow-up of surgical left atrial appendage intervention
Methods testing follow-up indicators include mortality, stroke or peripheral arterial embolism rate, cardiac function, laboratory examination, ECG, and chest X-ray; evaluating the completeness of LAA resection are TEE,[22],[48] CT,[22],[48] and MRI.[40],[76]
Left atrial appendage resection related follow-up report
One study reported that 136 patients performed LAA resection at the same period of mitral valve surgery;[77] during a mean follow-up of 3.6 years, 14 cases (10%) had embolization events. In these 14 cases, 10 cases were mitral valvuloplasty (71%), three cases were mitral valve biological valve replacement (21%), and one case was mitral valve mechanical valve replacement (7%). Thus, it is considered that LAA resection has no obvious effect on preventing embolism.
Reports on the left atrial appendage ligation
Kim et al.[78] reported that 1405 patients received LAA ligation at the same period of cardiac surgery, and were followed for 1 month. In this study, the probability of AF occurrence in patients without LAA ligation is 1.36 times greater than that with LAA ligation (95% confidence interval [CI]: 1.03–1.80). And patients who underwent LAA ligation had no cerebrovascular complications, whereas seven cases of cerebrovascular complications occurred in those who did not receive LAA ligation.
Left atrial appendage closure related follow-up report
Salzberg et al.[45] applied LAA closure to 34 patients between September 2007 and October 2008. The results showed that there is no device-related complication or device related morality. Moreover, all patients were confirmed to have the effective occlusion via TEE during operation. The persistent effectiveness of occlusion was also verified via CT at 3 months after operation. However, due to the lack of control group, the effectiveness of prevention from embolization had not been proved.
The performance of suture and ligation or occlusion (Ethicon TX30/TX60) is studied in a work by Healey et al.[75] TEE was used in operation to evaluate the completeness of ligation. Nine cases with atrial appendage tear were successfully repaired. Forty-five percent patients used suture method for LAA complete occlusion and 72% used closure for complete occlusion (P = 0.14), with 13 ± 7 months follow-up and the effectiveness evaluation of postoperative LAA occlusion via the TEE at 8 weeks postoperation, the satisfactory rate was 66%, and 2.6% patients have thromboembolism.
Thoracoscopes application related follow-up report
Blackshear et al.[52] performed LAA occlusion via thoracoscopy in 15 patients, in which one case underwent median incision operation due to bleeding and remaining 14 cases were successful. Follow-up for 8–60 months, stroke occurred in two cases at 55 months after operation; two death, one of them was the patient who underwent coronary bypass surgery and the other died of hepatic failure. Among patients with high risk, the annual stroke incidence (5.2%) was lower than that of patients treated with aspirin alone (13%). Therefore, it is considered that thoracoscopic technology for LAA intervention is safe without risk for early neurological complications and death. In high-risk patients with AF, occurrence of thromboembolism events showed a downward trend, but had no statistical significance.
Wolf et al.[76] performed 27 cases of bilateral atrial pulmonary vein isolation and LAA resection (using EZ45 stapler [Ethicon EndoSurgery]) under non extracorporeal circulation via thoracoscopy (18 cases of paroxysmal AF, 4 cases of persistent AF, 5 patients with permanent AF), and followed 23 cases for 6 months, 21 cases (91.3%) showed no AF recurrence.
Domestically, Li et al.[79] reported that from December 2006 to September 2007, 56 patients with AF underwent cardiac and bilateral pulmonary vein isolation with assistance of thoracoscopy. The main methods were bilateral pulmonary vein isolation and radiofrequency ablation between pulmonary vein and LAA and LAA resection. The WOLF separator and Atricure bipolar radiofrequency ablation clips, EZ45G soft tissue cutting suture were used in the operations. The results showed that pulmonary vein was confirmed to be completely isolated by inspection after ablation, without any case of LAA severe bleeding. Except for 14 cases with postoperative electrical conversion, all other cases maintained sinus rhythm. The procedure time was 150 ± 23 min and no death occurred. There were only two patients appeared serious complications after operation, assistance of intra-aortic balloon pump due to acute left cardiac insufficiency, and re-cannulation due to postoperative hypoxemia. The average hospitalization time was (7.5 ± 2.3) days after operation. After a follow-up period of 6 months, no death and stroke occurred.
Postoperative follow-up for surgical left atrial appendage intervention
The time generally includes 3, 6, and 12 months after operation, and once every 12 months thereafter. The contents of follow-up includes: Dosage of anticoagulant, embolism, and thromboembolism events, ECG or Holter, cardiac ultrasound, the presence of LAA residual leakage, and other adverse events.
Present of the Expert Committee
Congxin Huang (President of Chinese Society of Pacing and Electrophysiology)
Yong Huo (President of Chinese Society of Cardiology)
Shu Zhang (President of Chinese Society of Arrhythmias)
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]
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