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Background: Pulsed field ablation (PFA) is a novel technology for catheter-based atrial arrhythmia treatment. Evidence of its application for ventricular arrhythmia ablation is still limited. In this study, we describe the feasibility and efficacy of focal PFA for premature ventricular contraction (PVC) ablation., Methods: A prospective cohort of 20 patients referred for PVC ablation at 2 centers was enrolled, regardless of the presence of structural heart disease, PVC morphology, or previous ablation attempts. All procedures were performed using the CENTAURI System in combination with contact force sensing catheters and 3-dimensional electroanatomical mapping systems. Energy output and the number of applications were left to the operator's discretion., Results: Eleven (55%) procedures were conducted under general anesthesia, 6 (30%) under deep sedation, and 3 (15%) under light sedation. Muscular contraction was observed in one case (5%). Median procedural and fluoroscopy times were 95.5 and 6.55 minutes, respectively. The median number of PFA applications was 8 with a median contact force of 10 g . A statistically significant (76%) reduction was observed in mean peak-to-peak bipolar electrogram voltage before and after ablation (0.707 versus 0.098 mV; P =0.008). Ventricular irritative firing was observed in 11 (55%) patients after PFA. The median follow-up was 120 days. Acute procedural success was achieved in 17 of 20 (85% [95% CI, 0.70-1]) patients. Two of the patients with procedural failure had late success with >80% clinical PVC burden suppression during follow-up, and 2 of 17 patients with acute success had late PVC recurrence, which accounts for a total of 17 of 20 (85% [95% CI, 0.70-1]) patients with chronic success. Transient ST-segment depression occurred in 1 patient, and the right bundle branch block was induced in 2 others (permanently only in one case)., Conclusions: PVC ablation using a focal PFA is feasible, effective, and safe, with promising acute and long-term results in several ventricular locations. Irritative firing is frequently observed. Coronary evaluation should be considered when targeting the outflow tract., Competing Interests: Dr La Meir is a consultant for AtriCure. Dr Chierchia received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. Dr Chierchia received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. Dr de Asmundis received research grants on behalf of the center from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus and compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, LivaNova, Boston Scientific, AtriCure, Acutus Medical, and Daiichi Sankyo. Dr Sorgente is a consultant for Biosense Webster and Abbott and received compensation for teaching purposes from Medtronic, Biotronik, and Microport. The other authors report no conflicts.

Background: We tested the hypothesis that ICa,L is important to the development of cardiac memory., Methods and Results: The effects of L-type Ca2+ channel blockade and beta-blockade were tested on acutely anesthetized and on chronically instrumented, conscious dogs. Short-term memory (STM) was induced by 2 hours of ventricular pacing and long-term memory (LTM) by ventricular pacing for 21 days. STM dogs received placebo, nifedipine, or propranolol, and LTM dogs received placebo, atenolol, or amlodipine. AT1 receptor blockade (candesartan) and ACE inhibition (trandolapril) were also tested in LTM. Microelectrodes were used to record transmembrane potentials from isolated epicardial and endocardial slabs using a protocol simulating STM in intact animals. Left ventricular epicardial myocytes from LTM or sham control dogs were dissociated, and ICa,L was recorded (whole-cell patch-clamp technique). Evolution of STM and LTM was attenuated by ICa,L blockers but not beta-blockers. Neither AT1 receptor blockade nor ACE inhibition suppressed LTM. In microelectrode experiments, pacing induced an epicardial-endocardial gradient change mimicking STM that was suppressed by nifedipine. In patch-clamp experiments, peak ICa,L density in LTM and control were equivalent, but activation was more positive and time constants of inactivation longer in LTM (P<0.05)., Conclusions: ICa,L blockade but not beta-adrenergic blockade suppresses cardiac memory. LTM evolution is unaffected by angiotensin II blockade and is associated with altered ICa,L kinetics.

Background: Previous studies have suggested that atrial fibrillation (AF) is associated with the activation of the atrial angiotensin system. However, it is not known whether the expression of angiotensin II receptors changes during AF. The purpose of this study was to determine the atrial expression of angiotensin II type 1 and type 2 receptors (AT(1)-R and AT(2)-R) in patients with AF., Methods and Results: Atrial tissue samples from 30 patients undergoing open heart surgery were examined. Eleven patients had chronic persistent AF (> or =6 months; cAF), 8 patients had paroxysmal AF (pAF), and 11 patients were in sinus rhythm. AT(1)-R and AT(2)-R were localized in the atrial tissue by immunohistochemistry and quantified at the protein and mRNA level by Western blotting and quantitative polymerase chain reaction. Both types of AT-R were predominantly expressed in atrial myocytes in all groups. The amount of AT(1)-R was reduced to 34.9% during cAF (P<0.01) and to 51.7% during pAF (P<0.05) compared with patients in sinus rhythm. In contrast, AT(2)-R was increased during cAF (246%; P=NS) and pAF (505%; P<0.01). AT(1)-R/AT(2)-R mRNA content was similar in all groups., Conclusions: AF is associated with the down-regulation of atrial AT(1)-R and the up-regulation of AT(2)-R proteins. These findings may help define the pathophysiological role of the angiotensin system in the structural remodeling of the fibrillating atria.

Background: "Cardiac memory" refers to persistent T-wave changes on ECG that follow resumption of sinus rhythm after a period of altered activation sequence. Previous studies demonstrated that cardiac memory in intact dogs was abolished by 4-aminopyridine (4-AP), which blocks both the transient outward potassium current, Ito, and IK., Methods and Results: We used standard microelectrode techniques to study the mechanism for cardiac memory in canine ventricular subepicardial and subendocardial slabs measuring 15 x 30 x 1 to 2 mm. Bipolar electrodes were used to stimulate slabs parallel to fiber axis, simulating normal activation, and perpendicular to fiber axis, simulating ventricular pacing. Four 30-minute periods of normal activation at a basic cycle length of 650 milliseconds were interrupted by three 20-minute periods of ventricular pacing at a basic cycle length of 450 milliseconds. We first recorded action potentials differentially from epicardial and endocardial slabs. The stimulation protocol induced changes in the "T" wave of the difference signals that mimicked cardiac memory and that could be explained on the basis of the transmural gradient in repolarization between epicardium and endocardium. This result was not obtainable with slow and rapid pacing from one site only. In subsequent experiments, action potential characteristics of epicardial and endocardial slabs were studied by the same pacing protocol with alternation between simulated normal activation and ventricular pacing. During ventricular pacing, the epicardial phase 1 notch and plateau amplitude decreased compared with normal activation. 4-AP (3 mmol/L) decreased notch size and plateau amplitude during normal activation in epicardium but not endocardium. In contrast, the local anesthetic lidocaine did not change notch size or plateau amplitude in epicardium or endocardium., Conclusions: These results suggest that the contribution to repolarization of specific potassium channels influences the memory phenomenon and that by blocking Ito and reducing the transmural voltage gradient for repolarization, 4-AP abolishes cardiac memory.