Stroke Prevention in Atrial Fibrillation: Atrial Appendage Closure

The left atrial appendage (LAA) is the primary nonvalvular cause of cardioembolic stroke in patients with atrial fibrillation (AF). Warfarin and direct thrombin inhibitors such as dabigatran are presumed to prevent formation of LAA thrombus, and are first-line treatments to prevent ischemic stroke in AF. However, these medications carry many contraindications such as hemorrhage, and can interact with many drugs and supplements. Epicardial and endovascular techniques for occlusion of LAA are being explored, whether to mitigate the need for anticoagulation in patients at risk of bleeding or as a first-line therapy to reduce the risk of thromboembolic stroke. The purposes of this article are to 1) review the LAA structure and its potential contribution to ischemic stroke; 2) discuss the results of surgical and endovascular trials of LAA occlusion on risk of stroke and adverse events in AF patients; and 3) present early data on devices in development.     

左心耳封堵策略选择

心房颤动是临床上最常见的心律失常之一,血栓栓塞并发症是其致残、致死的主要原因。经食管超声检查发现,非瓣膜性房颤患者心房内血栓90%位于左心耳。因此,预防左心耳血栓形成可能会减少血栓栓塞事件的发生。口服抗凝药是预防房颤血栓栓塞并发症的有效方法,但是很多患者不能耐受口服抗凝药药物治疗。随着心血管介入治疗和器械研发的进展,经皮左心耳封堵预防卒中越来越受到关注,已经成为一种替代华法林预防房颤并发卒中的有效方法。     

Incomplete Closure of the Left Atrial Appendage: Implication and Management

Incomplete left atrial appendage closure (LAAC) occurs in ～30–40 % of cases following both surgical and percutaneous closure methods. Incomplete surgical LAAC may further be classified as incompletely surgically ligated LAA (ISLL) or LAA stump. ISLL is associated with a significantly increased risk of thrombus formation/thromboembolism. Moreover, this risk is highest in the absence of oral anticoagulation (OAC) and inversely correlates with the size of the ISLL neck. Not only routine screening for ISLL seems critical, but also long-term OAC should strongly be considered in this high-risk cohort. Alternatively, complete endocardial occlusion using a surrogate method may represent a reasonable option, particularly in those intolerant to long-term OAC therapy. Although thrombus formation/thromboembolic events have also been described in patients with incomplete LAAC following percutaneous occlusion, an association between the two remains less clear. However, given the rise and growing interest in percutaneous LAAC methods, additional research in this area is clearly warranted.     

Percutaneous Left Atrial Appendage Closure in a Patient with Diffuse Alveolar Hemorrhaging Associated with Anticoagulant Therapy and Atrial Fibrillation

Diffuse alveolar hemorrhaging (DAH) due to oral anticoagulation (OAC) is a life-threatening condition that leads to severe respiratory failure. There is a clinical dilemma in that OAC-induced DAH often forces the discontinuation of OAC therapy and the administration of high-dose corticosteroids, which increases the risk of stroke and cardiovascular events. We herein report the first case of OAC-induced DAH and atrial fibrillation (AF) in a patient who completely discontinued OAC therapy and high-dose corticosteroids after experiencing percutaneous left atrial appendage (LAA) occlusion. This case suggests that percutaneous LAA closure may aid in the management of OAC-induced DAH and AF.     

Perkutaner Vorhofohrverschluss

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia affecting up to 10–15?% of the population aged over 80 years. Oral anticoagulation (OAC) is necessary in the majority of AF patients for prevention of left atrial thrombus formation and thromboembolism of cardiac origin which are responsible for approximately 20–30?% of strokes. Thus, a considerable risk reduction can be achieved; however, OAC is associated with an increased bleeding risk. Many AF patients are not treated by OAC due to a history of bleeding complications or an increased bleeding risk. As over 90?% of thrombi in non-valvular AF develop in the left atrial appendage (LAA) percutaneous occlusion of the LAA is an alternative concept for the prevention of cardiovascular thromboembolism in AF patients. Currently, the most widely used occlusion devices are the WATCHMAN device and the Amplatzer Cardiac Plug. Available data records indicate that closure of the LAA is as equally effective as OAC. Moreover, with increasing experience percutaneous occlusion of the LAA can be performed with low complication rates. Therefore, according to the current guidelines of the European Society of Cardiology (ESC) this intervention is recommended as an alternative therapy, especially in patients with a high stroke risk and contraindications for OAC.     

Left Atrial Appendage Occlusion Study (LAAOS): a randomized clinical trial of left atrial appendage occlusion during routine coronary artery bypass graft surgery for long-term stroke prevention

Background Many patients undergoing coronary artery bypass graft (CABG) surgery have risk factors for both atrial fibrillation (AF) and stroke. The left atrial appendage (LAA) is a main source of thrombus coming from the left atrium. LAA occlusion should be tested as a means to reduce future cerebral ischemic events in these patients.Methods The Left Atrial Appendage Occlusion Study (LAAOS) is a randomized clinical trial designed to evaluate the feasibility, safety, and efficacy of LAA occlusion for prevention of ischemic stroke in patients undergoing CABG. The target population consists of patients at risk of AF and stroke who are having routine CABG surgery. The main study will be a prospective, controlled, unblinded trial. Patients at risk of future development of AF, or having AF, will be randomly assigned to undergo or not undergo LAA occlusion. A total of 2500 patients will be randomly assigned and followed for 5 years for the primary outcome of stroke. This study of 2500 patients will have 90% power to detect a relative reduction of 20% in stroke, from a 5-year incidence of 20% in the control group to 16% in the intervention group. Currently, a pilot trial is underway that will enroll 100 patients to assess feasibility, safety, and rates of successful LAA occlusion as assessed by postoperative transesophageal echocardiography. The most suitable surgical technique will also be assessed during the pilot trial. In the pilot study, the main outcomes are safety and rate of successful obliteration of the LAA after surgical occlusion.Conclusions The clinical trial designed to evaluate LAA occlusion at the time of routine CABG surgery is currently in the pilot phase. (Am Heart J 2003;145:174-8.)     

Left Atrial Appendage Exclusion for Prevention of Stroke in Atrial Fibrillation: Review of Minimally Invasive Approaches

Stroke prevention is of vital importance in the management of atrial fibrillation (AF), though the proven strategy of systemic anticoagulation for thromboembolic prophylaxis is underutilized for a variety of reasons. The left atrial appendage (LAA) has long been suspected as the principal source of arterial emboli, particularly in nonvalvular AF, and a variety of techniques for its exclusion from the circulation have been developed. This review highlights the history of the LAA as a target of intervention, and the parallel advances in three minimally invasive strategies for its exclusion: percutaneous occlusion of the LAA orifice from within the left atrium, closed-chest ligation via a percutaneous pericardial approach, and minimally invasive thoracoscopic surgery. While further study is necessary, available evidence suggests that effective LAA exclusion is becoming a viable alternative to anticoagulation for stroke prevention in nonvalvular AF.     

Interventioneller Vorhofohrverschluss zur Schlaganfallprophylaxe bei Vorhofflimmern

Ischemic stroke is a major risk factor for morbidity and mortality in western societies. Besides oral anticoagulation (OAC), interventional left atrial appendage (LAA) occlusion has been recently introduced for stroke prophylaxis in patients with atrial fibrillation. This procedure has proven its non-inferiority to OAC in terms of safety and efficacy in randomized trials. So far mainly patients with contraindications to OAC or with an elevated risk for both embolic and bleeding events have been treated with LAA occlusion devices. Various devices are currently in use in the clinical routine, mainly using a transseptal access to the LAA. It has been shown that in experienced centers the procedure can be performed with a minimum risk for serious complications. After successful LAA occlusion dual anti-platelet therapy or OAC is necessary until the device is fully endothelialized after approximately 3 months. In the clinical practice a dual platelet inhibition is often used; however, data from large registries imply that OAC can most likely be safely discontinued directly after implantation. Interventional LAA occlusion is therefore a viable option for stroke prevention in atrial fibrillation.     

Patientenauswahl für die Implantation eines Vorhofohr-Okkluders in der Primär- und Sekundärprävention des kardioembolischen Schlaganfalls bei Vorhofflimmern

The implantation of a left atrial appendage (LAA) occluder has evolved into an established non-pharmacological alternative to oral anticoagulation (OAC) in the prevention of cardioembolic stroke in patients with atrial fibrillation. While 2 randomized trials investigated the LAA occluder as an alternative treatment in patients who can also undergo OAC, current guidelines recommend the LAA occluder rather as a second line therapy if permanent OAC is not possible due to contraindications. This is in line with current practice where an LAA occluder is usually only implanted if OAC is contraindicated or stopped due to bleeding. The LAA occluder seems most promising for patients with a high risk for both, stroke without OAC and severe bleeding with OAC. After patient informed consent, the LAA occluder may also represent an option for patients who are unwilling to undergo OAC. Since a large proportion of patients do not receive OAC despite an indication (because of contraindications or mere fear of bleeding) and since the majority of patients have to stop OAC during the course of 2 years, mostly due to bleeding, the LAA occluder may play an important role in the long-term prophylaxis of cardioembolic stroke due to atrial fibrillation.     

Initial worldwide experience with the WATCHMAN left atrial appendage system for stroke prevention in atrial fibrillation.

OBJECTIVES: This study assessed the feasibility of implanting a device in the left atrial appendage (LAA) in patients with atrial fibrillation (AF) to prevent thromboembolic stroke. BACKGROUND: Meta-analyses confirmed that in cases of left atrial thrombus in nonrheumatic AF patients approximately 90% of them are in the LAA. METHODS: The WATCHMAN Left Atrial Appendage System (Atritech Inc., Plymouth, Minnesota) is a nitinol device implanted percutaneously to seal the LAA. Patients were followed by clinical and transesophageal echocardiography at 45 days and 6 months with annual clinical follow-up thereafter. RESULTS: Sixty-six patients underwent device implantation. Mean follow-up was 740 +/- 341 days. At 45 days, 93% (54 of 58) devices showed successful sealing of LAA according to protocol. Two patients experienced device embolization, both successfully retrieved percutaneously. No embolizations occurred in 53 patients enrolled after modification of fixation barbs. There were 2 cardiac tamponades, 1 air embolism, and 1 delivery wire fracture (first generation) with surgical explantation but no long-term sequelae for the patient. Four patients developed a flat thrombus layer on the device at 6 months that resolved with additional anticoagulation. Two patients experienced transient ischemic attack, 1 without visible thrombus. There were 2 deaths, neither device related. Autopsy documented a stable, fully endothelialized device 9 months after implantation. No strokes occurred during follow-up despite >90% of patients with discontinuation of anticoagulation. CONCLUSIONS: Preliminary data suggest LAA occlusion with the WATCHMAN System to be safe and feasible. A randomized study is ongoing comparing oral anticoagulation with percutaneous closure.     

Percutaneous transcatheter left atrial appendage exclusion in atrial fibrillation

Stroke is one of the leading causes of mortality, morbidity and serious disability in the developed world. Atrial fibrillation (AF), one of the most common cardiac arrhythmias, is a well-known predisposing factor for stroke, raising the risk significantly. Oral anticoagulation with warfarin is currently the most effective therapy for stroke risk reduction; however, this therapy increases the risk of bleeding and is often underutilized, contraindicated, or when administered, often subtherapeutic. It has been documented that the left atrial appendage (LAA) is the main source of left atrial thrombus, especially in non-rheumatic AF. Therefore, LAA exclusion may reduce the risk of stroke in AF, and retrospective surgical data have demonstrated a reduced risk of embolic events if surgical LAA exclusion was also performed during mitral valve replacement. Recently, several less invasive percutaneous transcatheter techniques of LAA exclusion - the PLAATO device, the Watchman device, and the Amplatzer Septal Occluder - have been employed with initially encouraging results. There is currently an ongoing randomized trial comparing percutaneous LAA exclusion to long-term oral anticoagulation therapy. Until such data are available, however, oral anticoagulation should remain the standard of care for stroke prevention in patients with AF.     

An overview of current and emerging devices for percutaneous left atrial appendage closure

Atrial fibrillation (AF) is common and is a prominent risk factor for ischemic stroke. Oral anticoagulant (OAC) therapy has been the main strategy for stroke prevention in AF patients; however, OAC therapy carries a bleeding risk and is not tolerated by all patients. Left atrial appendage (LAA) closure offers a non-pharmacological alternative for stroke prevention in patients with non-valvular AF. In this update, an overview of current and emerging LAA occluders is given – with special attention to the key design features of every single device and, if available, preclinical or clinical data.     

Alternatives to chronic warfarin therapy for the prevention of stroke in patients with atrial fibrillation

Atrial fibrillation (AF) is associated with a fivefold increased risk for stroke due to thromboembolic events. Warfarin remains the standard medical therapy for decades in these patients but is difficult to use safely and conveniently. Chronic warfarin therapy is contraindicated in 14% to 44% of patients with AF who are at risk for stroke. In clinical practice, warfarin is prescribed to only 15% to 60% of patients with AF who are at high risk for thromboembolic events and have no clear contraindication to their use. Alternatives to warfarin include (i) antiplatelet therapy; (ii) new oral anticoagulants; and (iii) exclusion of the left atrial appendage (LAA) as a major embolic source. Dual antiplatelet therapy with aspirin and clopidogrel was superior to aspirin alone in reducing the risk of stroke in patients unsuitable to warfarin. Furthermore, a number of newer oral anticoagulants are currently under investigation for stroke prevention in AF. Oral direct thrombin or factor Xa inhibitors are in the most advanced stages of development. Given that about 90% of the source of thromboembolism occurs in the LAA in patients with non-valvular AF, occlusion of flow into the LAA may prevent thrombus formation in the appendage and hence reduction of stroke. Recently, several devices have been employed percutaneously with encouraging results in selected patients. Current review summarizes the latest clinical trial data pertinent to dual-antiplatelet therapy, several newer antithrombotic agents and LAA occlusion.     

Left atrial appendage closure for stroke prevention in atrial fibrillation: state of the art and current challenges

Atrial fibrillation (AF) is a major risk factor for disabling ischemic strokes. Anticoagulation is highly effective for stroke prevention in patients with AF, but a substantial number of patients are unable to sustain chronic therapy with warfarin. Most strokes in patients with AF are thought to arise from thrombus formation in the left atrial appendage (LAA); therefore, occlusion of the orifice of the LAA provides a theoretically appealing option for stroke prevention. Surgical exclusion of the LAA is increasingly performed in patients undergoing open-heart surgery, and thoracoscopic epicardial occlusion of the LAA has yielded promising early results. Percutaneous LAA occlusion devices have shown some success initial trials, but additional safety and efficacy data are required before this approach can be routinely considered. Here we discuss the LAA in relation to AF-related embolic stroke, and how LAA occlusion devices could be used in stroke prevention in patients who cannot tolerate chronic anticoagulant therapy.     

Left atrial appendage closure with amplatzer cardiac plug in atrial fibrillation: Initial european experience

Background: In most patients with atrial fibrillation (AF) and stroke, there is thrombotic embolization from the left atrial appendage (LAA). Percutaneous closure of the LAA is a novel alternative for the treatment of patients with AF at a high risk of stroke, in whom long‐term anticoagulation therapy is not possible or not desired. This study details the initial experience with the Amplatzer Cardiac Plug (ACP) in humans. Methods: Investigator‐initiated retrospective preregistry data collection to evaluate procedural feasibility and safety up to 24 hr after implantation of the ACP, a nitinol device designed for percutaneous trans‐septal implantation in LAA of patients with paroxysmal, permanent, or persistent AF. Results: In 137 of 143 patients, LAA occlusion was attempted, and successfully performed in 132 (96%). There were serious complications in 10 (7.0%) patients (three patients with ischemic stroke; two patients experienced device embolization, both percutaneously recaptured; and five patients with clinically significant pericardial effusions). Minor complications were insignificant pericardial effusions in four, transient myocardial ischemia in two, and loss of the implant in the venous system in one patient. Conclusion: The implantation of the ACP device is a feasible method for percutaneous occlusion of the LAA. © 2011 Wiley‐Liss, Inc.     

Left Atrial Appendage Devices for Stroke Prevention in Atrial Fibrillation

Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia, and stroke prevention remains an integral part of management of AF. Long-term therapy with oral anticoagulants, though effective, has many limitations, and these limitations have encouraged the search for device-based alternatives. In patients with non-valvular AF, approximately 90 % of thrombi are thought to arise from the left atrial appendage (LAA). The LAA can be obliterated surgically or percutaneously, and this should reduce the incidence of systemic thromboembolic events in AF, ideally without the need for further anticoagulation. We explore the currently available LAA occlusion devices and the evidence behind these devices. Although additional evidence from randomized trials is required to fully characterize the safety and efficacy of all of these devices, LAA occlusion has the potential to offer an attractive alternative for those at high stroke risk but are under-protected because of contraindications to anticoagulant therapy.     

Role for the left atrial appendage occlusion device in managing thromboembolic risk in atrial fibrillation

Only 50% of patients who would benefit from warfarin therapy for atrial fibrillation (AF) receive treatment because of clinical concerns regarding chronic anti-coagulation. Percutaneous strategies to treat AF, including pulmonary vein isolation with a curative intent or atrioventricular nodal ablation and implantation of a permanent pacemaker for palliative rate control, have not eliminated the need to manage thromboembolic risk. With the development of a percutaneous left atrial appendage (LAA) occlusion device (the WATCHMAN percutaneous left atrial appendage occluder - Atritech Inc., Plymouth, MN, USA) for thromboembolic protection in non-valvular AF a significant therapeutic option for select patients may be available. We present the first case performed in Australia (24 November 2009) and explore this new methodology.     

经皮左心耳封堵术在非瓣膜性心房颤动患者卒中预防中的应用

心房颤动(atrial fibrillation,AF)导致的卒中很常见,而且常常是灾难性的.尽管口服抗凝药是预防栓塞性卒中的基石,但它们也存在许多局限性,而且并非所有患者均能长期耐受.左心耳已被认定为非瓣膜性AF患者血栓形成的来源.目前已研发出多种左心耳封堵装置,并成功用于非瓣膜性AF患者的卒中预防,且围手术期并发症较少.文章对经皮左心耳封堵术在非瓣膜性AF患者卒中预防方面的应用进行了综述.     

Oral anticoagulation during atrial fibrillation ablation: Facts and controversies

On the background of population ageing atrial fibrillation (AF) has reached epidemic dimensions in developed countries. This condition is associated with major cardiovascular morbidity and mortality mainly due to its thrombo-embolic and heart failure related complications. Left atrial (LA) catheter ablation has emerged as a suitable alternative to antiarrhythmic drugs for sinus rhythm maintenance at least for paroxysmal atrial fibrillation in the settings of no/mild LA dilatation. Chronic oral anticoagulation (OAC) is helpful to prevent AF thromboembolic complications in high-risk patients. OAC is also protective around ablation procedures in patients with or without an indication for long-term OAC therapy, emphasizing a slight increase in periprocedural risk of stroke. Due to the potential catastrophic hemorrhagic complications during trans-septal LA instrumentation, traditional approach on LA ablations involved warfarin discontinuation with periprocedural heparin bridging. Recent observational data suggests that radiofrequency (RF) catheter ablation of AF under therapeutic OAC (mainly vitamin K antagonists [VKA]) may reduce the periprocedural risk of complications, mainly thromboembolic events (possibly including silent strokes). Uninterrupted OAC has been acknowledged as an alternative to heparin bridging by the recently published consensus and guidelines update on AF ablation. Currently the recommended therapeutic level of OAC during ablation is low (such as an INR of 2–2.5). In the general AF settings new OAC (NOAC) have shown non-inferiority compared to VKA for stroke prevention, with better safety. Rapidly acting NOAC seems a tempting alternative to VKA at least for the patients taken off OAC before the ablation, possibly avoiding any post-procedural heparin bridging. However, limited experience with periprocedural use of NOAC (mainly dabigatran) suggests an increased risk of bleeding or thromboembolic complications compared with VKA.     

Usefulness of intensity variation in the left atrial appendage with contrast echocardiography to predict ischemic stroke recurrence in patients with atrial fibrillation

The left atrial appendage (LAA) is 1 of the common thromboembolic sources in patients with atrial fibrillation (AF) with stroke. The aim of this study was to examine the usefulness of LAA opacification seen on contrast echocardiography for predicting stroke recurrence in patients with AF. In 192 patients with stroke with AF who underwent transesophageal echocardiography within 7 days after the onset, intracardiac intensity variation at the orifice of the LAA just after intravenous infusion of Levovist (1,500 mg) was measured. During a mean follow-up of 450 days, the association between LAA intensity variation and recurrence of cerebrovascular events was assessed. LAA intensity variation was markedly lower in 19 patients with stroke recurrence than 173 patients without stroke recurrence (8.1 +/- 4.7 vs 12.1 +/- 5.1 dB; p <0.001). LAA thrombus-negative patients with low LAA intensity variation (< or =9.2 dB; n = 45) had higher cerebrovascular recurrent event rates than those with high LAA intensity variation (>9.2 dB; n = 109; 20.0% vs 3.7%; p <0.001) and thrombus-positive patients (15.8%). Cox multivariate hazard analysis showed that of routine echocardiographic parameters, decreased LAA intensity variation was the only independent predictor of stroke recurrence (hazard ratio 5.244, p <0.01). In conclusion, LAA intensity variation on contrast transesophageal echocardiography is a new sensitive index for LAA flow stagnation and recurrent cerebrovascular events in patients with AF with stroke.