Aims: Clinical studies with protocol-mandated workflow and monitoring have analysed performance of pulsed field ablation (PFA) for treating atrial fibrillation (AF). The FARADISE registry captures global use of the pentaspline PFA catheter in real-world clinical practice with a follow-up of 3 years. Methods and results: FARADISE is a prospective, non-randomized, multi-national registry (NCT05501873) that enrolled subjects clinically indicated for ablation using the pentaspline PFA catheter per medical judgement and hospital standard-of-care. Procedural characteristics, safety, and clinical effectiveness up to 12-months were collected. In total, 1158 AF patients received PFA across 48 centres in 21 countries (64 ± 11 years, 33% female, 90% de novo, 65% paroxysmal AF). Pulmonary vein isolation (PVI)-only procedures were performed in 80.8% of paroxysmal vs. 57.5% for non-paroxysmal patients (P < 0.01). Median procedure, left atrial dwell, and fluoroscopy times were 51[40–70], 31[24–41], and 12[8–17] min, respectively. The rate of early onset serious adverse events was 1.5% and did not differ by ablation strategy or AF indication. At 1-year, clinical effectiveness was 80.8% for paroxysmal AF and 67.7% for non-paroxysmal AF, with no difference within indication by lesion set (paroxysmal: 81.2% PVI-only vs. 79.0% PVI+, P = 0.65; non-paroxysmal: 67.5% PVI-only vs. 67.7% PVI+, P = 0.79). Acute results reinforce a short procedural learning curve with no difference in 1-year effectiveness by operator experience. Conclusion: The FARADISE registry provides a snapshot of real-world clinical use of the pentaspline PFA catheter. Acute results demonstrate favourable procedural and safety outcomes regardless of AF indication. One-year outcomes are encouraging, with no differences seen within indication based on ablation strategy.

Ventricular arrhythmias contribute significantly to morbidity and mortality in patients with heart failure (HF). Pathomechanisms underlying arrhythmogenicity in patients with structural heart disease and impaired cardiac function include myocardial fibrosis and the remodeling of ion channels, affecting electrophysiologic properties of ventricular cardiomyocytes. The dysregulation of ion channel expression has been associated with cardiomyopathy and with the development of arrhythmias. However, the underlying molecular signaling pathways are increasingly recognized. This review summarizes clinical and cellular electrophysiologic characteristics observed in dilated cardiomyopathy (DCM) with ionic and structural alterations at the ventricular level. Furthermore, potential translational strategies and therapeutic options are highlighted.

Promising as a treatment option for life-threatening ventricular arrhythmias, cardiac stereotactic body radiotherapy (cSBRT) has demonstrated early antiarrhythmic effects within days of treatment. The mechanisms underlying the immediate and short-term antiarrhythmic effects are poorly understood. We hypothesize that cSBRT has a direct antiarrhythmic effect on cellular electrophysiology through reprogramming of ion channel and gap junction protein expression. Following exposure to 20Gy of X-rays in a single fraction, neonatal rat ventricular cardiomyocytes (NRVCs) were analyzed 24 and 96h post-radiation to determine changes in conduction velocity, beating frequency, calcium transients, and action potential duration (APD) in both monolayers and single cells. Additionally, the expression of gap junction proteins, ion channels, and calcium handling proteins was evaluated at protein and mRNA levels. Following irradiation with 20Gy, NRVCs exhibited increased beat rate and conduction velocities 24 and 96h after treatment. mRNA and protein levels of ion channels were altered, with the most significant changes observed at the 96h-mark. Upregulation of Cacna1c (Ca_v1.2), Kcnd3 (K_v4.3), Kcnh2 (K_v11.1), Kcnq1 (K_v7.1), Kcnk2 (K_2P2.1), Kcnj2 (K_ir2.1), and Gja1 (Cx43) was noted, along with improved gap junctional coupling. Calcium handling was affected, with increased Ryr2 (RYR2) and Slc8a1 (NCX) expression and altered properties 96h post-treatment. Fibroblast and myofibroblast levels remained unchanged. CSBRT modulates expression of various ion channels, calcium handling proteins, and gap-junction proteins. The described alterations in cellular electrophysiology may be the underlying cause of the immediate antiarrhythmic effects observed following cSBRT.

Background: Catheter ablation is the primary treatment option for idiopathic ventricular tachycardia (VT). It plays a key role in acute therapy of electrical storm, treatment of VTs in patients with structural heart disease (SHD), and can reduce VT burden. Here we report on 10‐year clinical outcomes following VT ablation from patients enrolled in the prospective German Ablation Registry. Methods and Results: Long‐term follow‐up was conducted on 334 patients undergoing VT ablation (118/334, 35%) with structurally normal hearts and 216 out of 334 (65%) with SHD, including 161 out of 216 (75%) with ischemic heart disease at 38 centers. Follow‐up was completed in 94.8% of patients. Median observation time was 10.8 (4.3–12.3) years, with a 10‐year all‐cause mortality rate of 39.4%. VT ablation in patients with SHD was associated with worse outcome when compared with patients with structurally normal hearts (estimated 10‐year mortality for SHD 54.8% versus structurally normal hearts 12.1%). Estimated 10‐year mortality following VT ablation was highest in patients with ischemic heart disease (62.4%). Significant predictors of mortality following VT ablation included age (hazard ratio [HR], 2.35 [1.90–2.92] per decade), left ventricular ejection fraction ≤30% (HR, 2.11 [1.44–3.10]), diabetes (HR, 1.73 [1.14–2.61]), incessant VT (HR, 2.96 [1.74–5.03]), linear lesion (HR, 1.46 [0.99–2.16]), and acute procedural failure (HR, 2.57 [1.39–4.77]). Procedural failure was the only statistically significant predictor for VT recurrence during follow‐up (HR, 3.76 [1.59–8.91]). Conclusions: Within an all‐comer patient cohort, estimated 10‐year all‐cause mortality following VT ablation is 39.4%. Mortality after VT ablation is worse in patients with SHD and highest for patients with ischemic heart disease. Acute procedural success plays a major role in predicting VT recurrence and long‐term mortality.

The sodium-glucose co-transporter-2 (SGLT2) inhibitor dapagliflozin is increasingly used in the treatment of diabetes and heart failure. Dapagliflozin has been associated with reduced incidence of atrial fibrillation (AF) in clinical trials. We hypothesized that the favorable antiarrhythmic outcome of dapagliflozin use may be caused in part by previously unrecognized effects on atrial repolarizing potassium (K⁺) channels. This study was designed to assess direct pharmacological effects of dapagliflozin on cloned ion channels K_v11.1, K_v1.5, K_v4.3, K_ir2.1, K_2P2.1, K_2P3.1, and K_2P17.1, contributing to I_Kur, I_to, I_Kr, I_K1, and I_K2P K⁺ currents. Human channels coded by KCNH2, KCNA5, KCND3, KCNJ2, KCNK2, KCNK3, and KCNK17 were heterologously expressed in Xenopus laevis oocytes, and currents were recorded using the voltage clamp technique. Dapagliflozin (100 µM) reduced K_v11.1 and K_v1.5 currents, whereas K_ir2.1, K_2P2.1, and K_2P17.1 currents were enhanced. The drug did not significantly affect peak current amplitudes of K_v4.3 or K_2P3.1 K⁺ channels. Biophysical characterization did not reveal significant effects of dapagliflozin on current–voltage relationships of study channels. In conclusion, dapagliflozin exhibits direct functional interactions with human atrial K⁺ channels underlying I_Kur, I_Kr, I_K1, and I_K2P currents. Substantial activation of K_2P2.1 and K_2P17.1 currents could contribute to the beneficial antiarrhythmic outcome associated with the drug. Indirect or chronic effects remain to be investigated in vivo.