Preclinical evaluation of safety and efficacy of the Coherent Sine-Burst Electroporation (CSE) ablation system in a chronic porcine beating heart model

Abstract Background First-generation Pulsed Field Ablation (PFA) technologies implement square waveforms delivered via focal, multi-spline, or basket catheter designs. Coherent Sine-Burst Electroporation (CSE) is a novel PFA platform that uses coherent sine waveforms to deliver bipolar, unipolar, and phased PFA energy. This new platform features a multi-configurable catheter to produce linear, circular, or focal lesions with no catheter exchange required. Purpose This study aims to evaluate the safety and efficacy of the CSE Ablation System when ablating at both nominal dose and high dose (twice the nominal dose) at clinically relevant anatomical locations. Methods Fourteen female porcine (85-95 kg) underwent a procedure for ablation in the left and right atrium (LA, RA) with a 28 ± 2 day survival. The animals were divided into two treatment groups. In Group 1, seven specimens received the nominal dose to evaluate efficacy. To demonstrate safety, Group 2 was comprised of seven specimens that received twice the nominal dose. Pulmonary Vein Isolation (PVI) in the right superior pulmonary vein (RSPV) and the inferior pulmonary vein (IPV) was performed by ablating all eight electrodes using the circular catheter configuration (Figure 1). The catheter was reconfigured using the linear stylet to perform linear lesions in both the RA and LA (Figure 2). PVI was confirmed using entrance and exit block pacing as well as high-resolution activation mapping (HRM) during CS pacing. Linear lesions were assessed for block conduction and residual conduction using HRM. Coronary angiography, phrenic nerve function, PV ostial diameter and assays for hemolysis were performed. Results 28 of 28 (100%) pulmonary veins were electrically disconnected from the LA at 20 min post-ablation in the index procedure. 14 of 14 (100%) linear lesions demonstrated conduction block using HRM at 20 min post-ablation in the index procedure. Voltage and activation high-density mapping 28 days post-index procedure resulted in 27 of 28 (96.4%) pulmonary veins electrically disconnected from the LA. One vein (RSPV) was reconnected in the mapping procedures at 28 days post index procedure. 13 of 14 linear lesions (93%) showed conduction block and demonstrated transmurality in gross pathological evaluation. No clinically significant PV stenosis was documented between the index and termination procedures. No incidence of microbubbles, electrical arcing, thrombus formation, charring, perforation, or pericardial effusion were experienced. Conclusion(s) The CSE Ablation System can deliver safe and efficacious cardiac ablation lesions in the pulmonary veins and RA/LA anatomical targets. Based on acute and chronic evaluation, all predefined study endpoints were achieved. This study resulted in a 96% PVI and 93% linear block effectiveness. CSE ablation did not result in injury to the phrenic nerve, coronary arteries, or the esophagus.Voltage Map and Gross Tissue Inspection Multi-configurable CSE Ablation Catheter