Efficacy and safety of pulsed field ablation for accessory pathways: a pilot study.

AIMS: Radiofrequency ablation is used as a first-line therapy for accessory pathways (APs). However, data regarding the effects of pulsed field ablation (PFA) on APs are limited. We sought to evaluate the acute procedural and 6-month success and safety of PFA in a cohort of patients with APs. METHODS AND RESULTS: A focal contact force-sensing PFA catheter was used for patients with APs. Pulsed field ablation generator generated a bipolar and biphasic waveform (±1000 V) with a duration of 100 ms from the tip of the PFA catheter. A 100% acute procedural success was achieved in 10 conscious patients with APs (7 left anterolateral, 2 left inferolateral, and 1 right posteroseptal APs) including 6 (60%) patients after an initial application. The average total ablation time was 6.3 ± 4.9 s for 4.7 ± 1.8 ablation sites (ASs), including 3.1 ± 2.4 s at targets and 3.2 ± 2.9 s at 3.2 ± 2 bolus ASs. The mean skin-to-skin time was 59.3 ± 15.5 min, and PFA catheter dwell time was 29.4 ± 7.8 min. One patient encountered transient sinus arrest during PFA due to parasympathetic overexcitation. Sinus rhythm was restored in all patients without any significant adverse events during the short-term follow-up. CONCLUSION: Pulsed field ablation of APs was feasible, effective, and safe. Its efficiency was remarkable for its ultrarapid termination of AP conduction. Further studies are warranted to prove whether utilization of PFA with current parameters can extend to manifold AP ablation.

Visfatin aggravates transverse aortic constriction-induced cardiac remodelling by enhancing macrophage-mediated oxidative stress in mice.

Previous studies have reported that visfatin can regulate macrophage polarisation, which has been demonstrated to participate in cardiac remodelling. The aims of this study were to investigate whether visfatin participates in transverse aortic constriction (TAC)-induced cardiac remodelling by regulating macrophage polarisation. First, TAC surgery and angiotensin II (Ang II) infusion were used to establish a mouse cardiac remodelling model, visfatin expression was measured, and the results showed that TAC surgery or Ang II infusion increased visfatin expression in the serum and heart in mice, and phenylephrine or hydrogen peroxide promoted the release of visfatin from macrophages in vitro. All these effects were dose-dependently reduced by superoxide dismutase. Second, visfatin was administered to TAC mice to observe the effects of visfatin on cardiac remodelling. We found that visfatin increased the cross-sectional area of cardiomyocytes, aggravated cardiac fibrosis, exacerbated cardiac dysfunction, further regulated macrophage polarisation and aggravated oxidative stress in TAC mice. Finally, macrophages were depleted in TAC mice to investigate whether macrophages mediate the regulatory effect of visfatin on cardiac remodelling, and the results showed that the aggravating effects of visfatin on oxidative stress and cardiac remodelling were abrogated. Our study suggests that visfatin enhances cardiac remodelling by promoting macrophage polarisation and enhancing oxidative stress. Visfatin may be a potential target for the prevention and treatment of clinical cardiac remodelling.

Outcomes of Focal Pulsed Field Ablation for Paroxysmal Supraventricular Tachycardia.

BACKGROUND: Pulsed field ablation (PFA) is primarily used for treatment of atrial fibrillation as it provides better safety and efficacy. However, there are limited data available on the use of PFA for paroxysmal supraventricular tachycardia (PSVT). The study sought to describe the outcomes of PSVT ablation with a novel focal contact force (CF)-sensing PFA. METHODS: In this first-in-human pilot study, a focal CF-sensing PFA catheter was used for mapping and ablation navigated with an electroanatomic mapping system (EAMS). Pulsed field energy was delivered as biphasic/bipolar electrical pulse trains with 2000 V/delivery. CF was controlled from 2 g to 10 g during PFA. RESULTS: Procedural acute success was achieved without general anaesthesia or conscious sedation in all 10 patients, including 7 patients diagnosed with typical atrioventricular nodal re-entrant tachycardias and 3 patients with orthodromic reciprocating tachycardias. Successful target ablation time was 2.0 ± 0.5 seconds per patient, and the acute procedural success at the first single site was achieved in 5 patients. The mean skin-to-skin procedure time was 79.4 ± 15 minutes, PFA catheter dwell time was 50.1 ± 14 minutes, and fluoroscopy time was 6.2 ± 7 minutes. Maintenance of sinus rhythm was observed in all patients within 6-month follow-up. No serious adverse events occurred in any subjects during PFA or during the 6-month follow-up. CONCLUSIONS: A focal CF-sensing PFA catheter could effectively, rapidly, and safely ablate PSVT in conscious patients. CLINICAL TRIAL REGISTRATION: NCT05770921.

Sulfiredoxin 1 ameliorates doxorubicin-induced cardiotoxicity by suppressing oxidative stress and inflammation via the Sirt1/NLRP3 pathway.

BACKGROUND: Doxorubicin (DOX) is limited in clinical use due to its cardiotoxic side effects. Oxidative stress and inflammation are pivotal mechanisms underlying doxorubicin-induced cardiotoxicity (DIC). Sulfiredoxin 1 (Srxn1) plays a central role in antioxidant effects. However, the role of Srxn1 in DIC has not yet been fully elucidated. This study aims to explore the effects and underlying mechanisms of Srxn1 on DIC. METHODS: We overexpressed Srxn1 in the myocardium using an adeno-associated virus 9 (AAV9) system, delivered through tail vein injection. C57BL/6 mice received intraperitoneal injections of DOX (4 mg/kg) weekly for four consecutive weeks to establish a mouse model of DIC. We used echocardiography, histopathological, and molecular techniques to elucidate the effects and mechanisms. RESULTS: Our findings demonstrate that overexpression of Srxn1 significantly enhanced cardiac function and mitigated myocardial injury in mice exposed to DOX. Overexpressing Srxn1 attenuated oxidative stress and inflammation induced by DOX. Furthermore, Srxn1 overexpression led to upregulation of sirtuin 1 (Sirt1) expression and inhibited the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome. Notably, the protective effects of Srxn1 were significantly abrogated by the Sirt1 inhibitor EX527. CONCLUSION: The protective effects of Srxn1 against DOX-induced cardiac oxidative stress and inflammation operate by targeting the Sirt1/NLRP3 signaling pathway to alleviate DIC. Srxn1 could be a potential candidate for the treatment of DOX-induced myocardial injury.

Unexpected transient atrioventricular block and slow junctional rhythm using pulsed field ablation for slow pathway modification: excited or cautious for ablators.

BACKGROUND: Data regarding the effects of pulsed field ablation (PFA) on atrioventricular nodal reentrant tachycardia (AVNRT) are limited. OBJECTIVE: To evaluate the outcomes of PFA for AVNRT, and its impact on dual-pathway electrophysiology. METHODS: A larger cohort of patients with typical AVNRT underwent slow pathway (SP) modification (SPM) using a focal PFA catheter in a biphasic/bipolar manner. The primary endpoints were the efficacy and safety of PFA during the procedure and 6-month follow-up. RESULTS: The acute success of SPM was achieved in all 40 patients. The total ablation time was 7.9±3.8 seconds for 6.4±2.2 ablation sites (ASs). Slow junctional rhythm (SJR) was induced in 32 (80%) patients lasting 28.9±10.3 seconds in 3.0±1.1 ASs per patient. SP was located 11.1±1.2 mm from the largest His activation (LHA). At 9 ASs, SJR could be reinduced after an increase of contact force (CF) from 1.3±0.5g to 6.4±1.3g (P<0.0001). Transient atrioventricular block (AVB) was recorded in 7(17.5%) patients (1 second-degree and 6 third-degree AVB) lasting 435.3±227.4 seconds, with a shorter AS-LHA distance than patients without AVB (7.7±0.6 mm vs. 11.3±1 mm, P<0.0001). PFA-related delayed atrial-His (n=6) and His-atrial (n=1) conduction preceded transient AVB with a constant His-ventricular interval. Normal PR interval was restored within 24 hours. All patients maintained sinus rhythm without any significant adverse events during 6-month follow-up. CONCLUSION: Despite the high efficiency of PFA for SPM, the notable incidence of transient AVB warranted caution when applying it near the His bundle. SJR frequently occurred during SPM and was dependent on moderate CF.