背景:与主要针对细胞膜的“常规”微秒脉冲电场不同,纳秒脉冲被认为主要是电穿孔细胞内的细胞器。我们对猪的基于导管的心内膜纳秒脉冲场消融(nsPFA)进行了全面的临床前评估。方法:在总共25头猪中评估了一种新型的心内膜nsPFA系统。使用低剂量(5秒持续时间)或高剂量(15秒持续时间)策略,胸静脉和离散的心房和心室部位被消融。猪存活<1(n=1),~2(n=7),~7(n=6),14(n=2),或〜28(n=9)天,并在处死前评估静脉隔离。安全性评估包括评估食道效果,膈神经功能,以及静脉口径的变化.对所有组织进行仔细的大体病理学和组织病理学检查。结果:所有(100%)静脉(13个低剂量,34高剂量)被急性分离,和所有重新评估的静脉(6次低剂量,15个高剂量)被持久分离。所有检查的静脉病变(10个低剂量,22个高剂量)是透壁的。静脉直径(n=15)没有显著改变。在评估膈麻痹的动物中(n=9),3(33%)仅表现为短暂性麻痹。给药策略之间没有差异。分析了13个二尖瓣峡部病变,所有13个(100%)均为透壁(深度6.4±0.4mm)。心室病变宽14.7±4.5mm,深7.1±1.3mm,高剂量病变比低剂量病变更深(7.9±1.2mmvs6.2±0.8mm,p=0.007)。在消融后早期(2天)处死的5只动物中,有5只(100%)的食道显示出非透壁外膜表面病变。在后来(14-28天)处死的10只动物中,所有动物都表现出明显的食道愈合-8具有完全的分辨率,只有微量纤维化。结论:一部小说,心内膜纳秒PFA系统提供急性和持久的静脉隔离和线性病变。短暂性膈损伤和非透壁性食管损伤可能发生,最坏的情况评估表明PFA组织选择性受到限制,并且需要在临床研究期间进行专门评估。
UNASSIGNED: Unlike conventional microsecond pulsed electrical fields that primarily target the cell membranes, nanosecond pulses are thought to primarily electroporate intracellular organelles. We conducted a comprehensive preclinical assessment of catheter-based endocardial nanosecond pulsed field ablation in swine.
UNASSIGNED: A novel endocardial nanosecond pulsed field ablation system was evaluated in a total of 25 swine. Using either a low-dose (5-second duration) or high-dose (15-second duration) strategy, thoracic veins and discrete atrial and ventricular sites were ablated. Predetermined survival periods were <1 (n=1), ≈2 (n=7), ≈7 (n=6), 14 (n=2), or ≈28 (n=9) days, and venous isolation was assessed before euthanasia. Safety assessments included evaluation of esophageal effects, phrenic nerve function, and changes in venous caliber. All tissues were subject to careful gross pathological and histopathologic examination.
UNASSIGNED: All (100%) veins (13 low-dose, 34 high-dose) were acutely isolated, and all reassessed veins (6 low-dose, 15 high-dose) were durably isolated. All examined vein lesions (10 low-dose, 22 high-dose) were transmural. Vein diameters (n=15) were not significantly changed. Of the animals assessed for phrenic palsy (n=9), 3 (33%) demonstrated only transient palsy. There were no differences between dosing strategies. Thirteen mitral isthmus lesions were analyzed, and all 13 (100%) were transmural (depth, 6.4±0.4 mm). Ventricular lesions were 14.7±4.5 mm wide and 7.1±1.3 mm deep, with high-dose lesions deeper than low-dose (7.9±1.2 versus 6.2±0.8 mm; P=0.007). The esophagus revealed nontransmural adventitial surface lesions in 5 of 5 (100%) animals euthanized early (2 days) post-ablation. In the 10 animals euthanized later (14-28 days), all animals demonstrated significant esophageal healing-8 with complete resolution, and 2 with only trace fibrosis.
UNASSIGNED: A novel, endocardial nanosecond pulsed field ablation system provides acute and durable venous isolation and linear lesions. Transient phrenic injury and nontransmural esophageal lesions can occur with worst-case assessments suggesting limits to pulsed field ablation tissue selectivity and the need for dedicated assessments during clinical studies.