Abstract
Background: Atrial fibrillation is a major stroke risk, with >90% of thrombi originating from the left atrial appendage (LAA). Oral anticoagulation is effective, but many patients cannot use it long term. Current percutaneous LAA occlusion devices reduce stroke risk but are limited by device-related thrombus (DRT) and peridevice leak.
Objectives: The aim of this study was to assess the safety and performance of the novel Zenith LAA occlusion system in both preclinical canine models and a prospective first-in-human (FIH) clinical study.
Methods: A multistage evaluation included 3 preclinical trials in 17 canines (≤90-day follow-up) and a single-arm, prospective FIH study in 10 nonvalvular atrial fibrillation patients. This novel LAA device consists of a conformable Nitinol scaffold covered with a polyethylene terephthalate membrane, a self-closing central conduit to minimize exposed metal, and an independently deployed dynamic anchoring system. Primary imaging follow-up was 45-day transesophageal echocardiography.
Results: In a preclinical canine model (n = 17), explant analysis at 45 days demonstrated complete endothelialization with no evidence of DRT or significant inflammation. In the FIH study, 9 of 10 patients (90%) underwent successful implantation. The a priori primary safety endpoint of acute procedural success was achieved in 9 of 9 patients (100%), and the a priori primary performance endpoint of mechanical device closure at 45 days was also achieved in 9 of 9 patients (100%). At 45-day transesophageal echocardiography, all implants were stable, with complete protocol-defined LAA closure and no DRT. No device- or procedure-related serious adverse events occurred.
Conclusions: This novel LAA occlusion system demonstrated favorable early safety and performance in both preclinical and FIH evaluation. The novel design features enabled effective LAA sealing and absence of DRT, supporting further investigation in larger trials.