A First-in-Man (FIM) Study of the LAmbre™ II Left Atrial Appendage Occluder and Occluder Delivery System for Patients With Non-Valvular Atrial Fibrillation

Worldwide, atrial fibrillation (AF) is the most common cardiac arrhythmia in adults. The prevalence of AF gradually increases with age; its prevalence is 0.5% ~ 0.8% among 45 ~ 59 year-olds, 1.8% ~ 5.9% among 60 ~ 69 year-olds, and 6.7% ~ 17.9% among > 79 year-olds. Thromboembolic complications are the leading cause of death and disability in patients with AF, with ischemic stroke being the most common complication. AF significantly increases the risk of stroke by 3- to 5-fold due to thrombosis caused by abnormal atrial beat. The overall risk of ischemic stroke in patients with AF is 20% ~ 30%, and strokes due to atrial fibrillation account for 20% of all strokes.

Oral anticoagulation (OAC) is the standard of care in the management of non-valvular atrial fibrillation for stroke prevention and is recommended in the USA and European guidelines. However, the use of warfarin, a traditional oral anticoagulant, requires frequent and careful monitoring to ensure adequate anticoagulation as well as to prevent over-anticoagulation. This necessitates frequent laboratory blood tests to maintain the International Normalization Ratio (INR), a measure of the efficacy of the warfarin regimen, which can lead to patient non-adherence. Sub-therapeutic INR does not prevent systemic embolization, and supratherapeutic INR is a risk for haemorrhage. Moreover, the impact of interactions with other drugs, diet, narrow therapeutic window, and other reasons limit the use of warfarin. Several studies have shown that in clinical practice anticoagulation is given to less than 50% ~ 60% of patients with indications and discontinuation rates of warfarin approach 33% per year. Non-vitamin K antagonist oral anticoagulants (NOAC) have been shown to have a non-inferiority or superior effect in stroke reduction compared to warfarin without the need for routine laboratory monitoring. However, due to the high cost of NOACs and the lack of stable and effective antagonists, treatment discontinuation rates of up to 20% have been reported, and there is still an absolute risk of bleeding of 2% to 3% per year. A safe and effective alternative to anticoagulation for the stroke prevention in AF is needed, as the bleeding risk of anticoagulation and the presence of patient refusal/non-adherence/intolerance to long-term anticoagulation.

For a majority of patients with atrial fibrillation, it appears that thrombus formation would be located in the Left atrial appendage (LAA). Previous studies have suggested that more than 90% of thrombi in patients with non-valvular atrial fibrillation (NVAF) are located in the LAA. Therefore, surgical and percutaneous techniques to occlude the LAA could be a solution to reduce the risk of ischemic stroke for patients with AF. Surgical ligation of the LAA during the mitral valve surgery can reduce the risk of stroke, however, it is difficult to completely close the LAA by surgical ligation. Studies evaluating the incidence of incomplete ligation of the LAA during mitral valve surgery have shown that TEE-detected incidence of incomplete LAA ligation is about 36%. The WATCHMAN device (Boston Scientific, Natick, Massachusetts) is the most studied percutaneous left atrial appendage closure (LAAC) device and has shown that safety and efficacy are non-inferior to warfarin. In the current 2023 ACC/AHA/ACCP/HRS Guideline, percutaneous LAAC has been classified as a Class 2a indication for stroke prevention in patients with AF, a moderate to high risk of stroke, and a contraindication to long-term oral anticoagulation due to a non-reversible cause. However, the implantation procedure does have adverse effects which include serious pericardial effusion, procedure-related ischemic stroke, and device embolization. Due to the anatomical diversity of the LAA, certain patients are not candidates for this device.

The LAmbre™ Left Atrial Appendage Closure System, manufactured by Lifetech Scientific (Shenzhen) Co. Ltd., is the first generation of LAmbre LAAO device which is CE-marked and is current approved in Hong Kong Hospital Authority for regular clinical use. It consists of a LAA Occluder and a Delivery System and is a percutaneous transcatheter device intended to prevent thrombus embolization from the left atrial appendage in patients who have nonvalvular atrial fibrillation. This self-expanding LAA Occluder consists of an umbrella and a cover connected by a central waist. Although the first generation of LAmbre LAAO device is associated with high implantation success rate of 99.7% and a relatively low major procedure-related complication rate of 2.9%, to better match the challenging anatomy of the LAA and to further improve procedural safety, the first generation of LAmbre LAA O device has been upgraded.

The LAmbre™ II Left Atrial Appendage Occluder is the second generation of LAmbre LAAO device which is used with the Occluder Delivery System to seal off the left atrial appendage to prevent thrombus embolization from the left atrial appendage (LAA) in patients who have non-valvular atrial fibrillation. As an upgraded version of the LAmbre™ Left Atrial Appendage Occluder, the LAmbre™ II Left Atrial Appendage Occluder has a number of modifications including: the connection of Umbrella and Cover has been changed from the welded connection to the snap connection, which allows the Umbrella and Cover to be freely combined; the PET Membrane of the Cover has been added with a PC coating; the shape of the Cover has been changed from conical shape to disc shape; the structure of the end of U-shaped hook has been changed from a single beam structure to a diamond shape structure; the material of the Cover changed from 72 NiTi wires to 144 NiTi wires This study is a first-in-man study aimed at preliminary assessing the safety and feasibility of the LAmbre™ II Left Atrial Appendage Occluder and Occluder Delivery System. The results of this study will be the basis for the design of subsequent confirmatory studies.