Left atrial appendage closure for stroke prevention in atrial fibrillation: current status and perspectives

Abstract

Atrial fibrillation (AF) is associated with an increased risk of stroke and systemic embolism, and the left atrial appendage (LAA) has been identified as a principal source of thromboembolism in these patients. While oral anticoagulation is the current standard of care, LAA closure (LAAC) emerges as an alternative or complementary treatment approach to reduce the risk of stroke or systemic embolism in patients with AF. Moderate-sized randomized clinical studies have provided data for the efficacy and safety of catheter-based LAAC, largely compared with vitamin K antagonists. LAA device iterations, advances in pre- and peri-procedural imaging, and implantation techniques continue to increase the efficacy and safety of LAAC. More data about efficacy and safety of LAAC have been collected, and several randomized clinical trials are currently underway to compare LAAC with best medical care (including non-vitamin K antagonist oral anticoagulants) in different clinical settings. Surgical LAAC in patients with AF undergoing cardiac surgery reduced the risk of stroke on background of anticoagulation therapy in the LAAOS III study. In this review, we describe the rapidly evolving field of LAAC and discuss recent clinical data, ongoing studies, open questions, and current limitations of LAAC.

Keywords: Atrial fibrillation; Left atrial appendage closure; Oral anticoagulation; Stroke prevention.

Graphical Abstract

Rationale for left atrial appendage closure. Because of changing demographics, the number of atrial fibrillation patients is expected to double in industrialized countries within the next two decades. Patients with high risk for stroke have an indication for stroke preventive therapies consisting of either oral anticoagulation, percutaneous left atrial appendage closure in case of high bleeding risk, or surgical left atrial appendage closure in patients undergoing cardiac surgery. Several ongoing studies will more precisely define the optimal therapeutic approach for the individual patient. AF, atrial fibrillation, CABG, coronary artery bypass grafting; OAC, oral anticoagulation; LAAC, left atrial appendage closure.

Figure 1

Present recommendations for left atrial appendage closure. Current guideline recommendations for left atrial appendage closure (ESC 2020, published before LAAOS III, and ACC/AHA/ACCP/HRS 2023). AF, atrial fibrillation; LAA, left atrial appendage; LAAC, LAA closure; OAC, oral anticoagulation; pLAAO, percutaneous left atrial appendage occlusion

Figure 2

Proposed pathophysiology of left atrial appendage thrombus formation. Several anatomical, cellular, and physiological features contribute to thrombus formation within the left atrial appendage. Of note, different thromboembolic risk might be attributed to anatomic configurations of the left atrial appendage as well as flow and fluid dynamics.^, LAA, left atrial appendage; EC, endothelial cell; eNOS, endothelial nitric oxide synthase; NO, nitric oxide; NOS, nitric oxide synthase; PGI₂, prostaglandin I2; ROS, reactive oxygen species; TXA₂, thromboxane A2; vWF, von Willebrandt factor; arrows indicate increase or decrease.

Figure 3

Implant success and peri-procedural safety of left atrial appendage closure. Over the last decade, implantation success and peri-procedural safety have improved due to developments in implantation technique, accumulating operator experience, and device development. (A) Implantation success is illustrated for multicentre registries and randomized trials over time. (B) Severe adverse events within 7 days post-implantation are shown consisting of vascular complications/bleeding, pericardial effusion/tamponade, stroke, and device embolization

Figure 4

Present and potential future indications for left atrial appendage closure. Current guidelines recommend percutaneous left atrial appendage closure for atrial fibrillation patients with high risk of stroke not eligible for long-term oral anticoagulation. Because of an improved safety profile of left atrial appendage closure and encouraging data from prospective registries and randomized trials, current and additional indications for left atrial appendage closure are being extensively studied in randomized controlled trials. GFR, glomerular filtration rate.

Figure 5

Percutaneous left atrial appendage closure devices and methods for surgical left atrial appendage closure. (A) Ball-type device (plug): endovascular delivery of a lobe or umbrella and closure by obstructing the neck of the left atrial appendage (Watchman, WAveCrest). (B) Disc-type device (pacifier): endovascular device of a lobe or umbrella (anchoring/obstructing the neck of the left atrial appendage) with an additional disc attached (sealing of the left atrial appendage ostium; Amplatzer Amulet, LAmbre). Left atrial appendage closure is dependent on sealing and endothelialization of the corpus/umbrella and/or disc (pacifier principle). (C) Ligation: endocardial and epicardial snaring and percutaneous suture ligation of the left atrial appendage (Lariat). (D) Surgical left atrial appendage closure: amputation by suture or Atriclip are depicted. Future devices: aims of future developments are better conformability (foam-based devices such as CLAAS), reducing the footprint of foreign material (left atrial appendage obliteration, i.e. Laminar device), and less thrombogenicity by anti-thrombotic covering. IVC, inferior vena cava; LIPV, left inferior pulmonary vein; LSPV, left superior pulmonary vein; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein; S-LAAC, surgical left atrial appendage closure; SVC, superior vena cava.

Figure 6

Post-implant anti-thrombotic therapy and rates of device-related thrombus. (A) Post-implant anti-thrombotic regimens used in multicentre clinical registries and device-related thrombus rates dependent on patient risk and physicians’ preference. (B) Different schemes of post-implant anti-thrombotic therapy according to patients’ risk profile. DAPT, dual antiplatelet therapy; DOAC, direct oral anticoagulants; DVT, device-related thrombus; SPT, single antiplatelet therapy.

Figure 7

Factors for leak generation following percutaneous left atrial appendage closure. Patient factors such as length of atrial fibrillation or ostial anatomy, device characteristics such as deformability, and implantation technique (coaxial device implantation, oversizing) play an important role in leak generation. Special care for device selection should be taken in complex anatomies, i.e. disc-type device for oval ostium in stiff left atrial appendage (red circle) or ball-type device for irregular ostial plane (red line).

Figure 8

Clinical evidence for left atrial appendage closure. Published and ongoing randomized studies in percutaneous and surgical left atrial appendage closure are depicted. BMC, best medical care; LAAC, left atrial appendage closure.