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Ablation of atrial fibrillation (AF) with high-power-short-duration (HPSD) radiofrequency (RF) technology is emerging as a new standard of care in many electrophysiology laboratories. While procedural short-term efficacy and efficiency is very promising, little is known about mid- to long-term effects of HPSD ablation for pulmonary vein isolation (PVI) and left atrial substrate modification.In a single-center registry, 412 AF procedures were performed in 400 individual patients using a standardized CLOSE protocol-guided fixed 50 W HPSD ablation, aiming for an ablation index (AI) of 400 on the posterior and 550 on the anterior wall. Additional substrate-tailored lines were performed when required.After a mean clinical follow-up of 337 ± 134 days, 15 patients suffered from AF recurrence beyond the blinding period. Twelve gave consent to the indicated reablation. Here, 11 of 12 patients had chronic isolation of all four pulmonary veins (PV). In three of six patients, a reconnection of additional left atrial ablation lines was revealed. Ten out of 12 patients showed progressive fibrous atrial cardiomyopathy and required additional left atrial substrate modification or reisolation of left-atrial lines. During the follow-up no clinical case of atrioesophageal fistula was registered. No PV stenosis after initial HPSD PVI was documented.Patients requiring reablation of AF or other atrial tachycardia after a fixed 50 W HPSD circumferential PVI and substrate modification predominantly suffer from progressive fibrous atrial cardiomyopathy, while PV reconnection appears to be a rare cause of AF recurrence.

INTRODUCTION Ablation index (AI)-guided ablation according to the CLOSE protocol is very effective in terms of chronic pulmonary vein isolation (PVI). However, the optimal radiofrequency (RF) power remains controversial. Here, we thought to investigate the efficiency and safety of an AI-guided fixed circumferential 50 W high-power short-duration (HPSD) PVI using the CLOSE protocol. METHODS AND RESULTS In a single-center trial, 40 patients underwent randomized PVI using AI-guided ablation without esophageal temperature monitoring. In 20 patients a CLOSE protocol guided fixed 50 W HPSD was followed irrespective of the anatomical localization. Twenty subjects were treated according to the CLOSE protocol with standard power settings (20 W posterior and 40 W roof and anterior wall). In addition, 80 consecutive patients were treated according to the HPSD protocol to gather additional safety data. All patients underwent postprocedural esophagogastroduodenoscopy to reveal esophageal lesions (EDELs). The mean total procedural time was 80.3 ± 22.5 in HPSD compared to control 109.1 ± 27.4 min (p

In this study, we describe the synthesis and biological evaluation of a set of bis‐3‐chloropiperidines (B−CePs) containing rigid aromatic linker structures. A modification of the synthetic strategy also enabled the synthesis of a pilot tris‐3‐chloropiperidine (Tri‐CeP) bearing three reactive meta‐chloropiperidine moieties on the aromatic scaffold. A structure–reactivity relationship analysis of B−CePs suggests that the arrangement of the reactive units affects the DNA alkylating activity, while also revealing correlations between the electron density of the aromatic system and the reactivity with biologically relevant nucleophiles, both on isolated DNA and in cancer cells. Interestingly, all aromatic 3‐chloropiperidines exhibited a marked cytotoxicity and tropism for 2D and 3D cultures of pancreatic cancer cells. Therefore, the new aromatic 3‐chloropiperidines appear to be promising contenders for further development of mustard‐based anticancer agents aimed at pancreatic cancers., As keen as mustard: Aromatic 3‐chloropiperidines designed to improve the therapeutic potential of mustard‐based DNA alkylating agents have been synthesized and evaluated. These small molecules exhibited a marked anti‐proliferative effect preferentially against BxPC‐3 pancreatic adenocarcinoma cells in 2D and 3D cultures, thus demonstrating themselves to be promising candidates for the further development of sustainable chemotherapeutics active against pancreatic tumors.