Distance-dependent neuromodulation effect during thermal ablation for atrial fibrillation.

INTRODUCTION: Thermal atrial fibrillation (AF) ablation exerts an additive treatment effect on the cardiac autonomic nervous system (CANS). This effect is mainly reported during ablation of the right superior pulmonary vein (RSPV), modulating the right anterior ganglionated plexus (RAGP), which contains parasympathetic innervation to the sinoatrial node in the epicardial fat pad between RSPV and superior vena cava (SVC). However, a variable response to neuromodulation after ablation is observed, with little to no effect in some patients. Our objective was to assess clinical and anatomic predictors of thermal ablation-induced CANS changes, as assessed via variations in heart rate (HR) postablation. METHODS: Consecutive paroxysmal AF patients undergoing first-time PV isolation by the cryoballoon (CB) or radiofrequency balloon (RFB) within a 12-month time frame and with preprocedural cardiac computed tomography (CT), were evaluated. Preablation and 24-h postablation electrocardiograms in sinus rhythm were collected and analyzed to assess HR. Anatomic evaluation by CT included the measurement of the shortest distance between the SVC and RSPV ostium (RSPV-SVC distance). RESULTS: A total of 97 patients (CB, n = 50 vs. RFB, n = 47) were included, with similar baseline characteristics between both groups. A significant HR increase postablation (ΔHR ≥ 15 bpm) occurred in a total of 37 patients (38.1%), without difference in number of patients between both thermal ablation technologies (CB, 19 [51%]), RFB, 18 [49%]). Independent predictors for increased HR were RSPV-SVC distance (odds ratio [OR]: 0.49, CI: 0.34-0.71, p value < .001), and age (OR: 0.94, CI: 0.89-0.98, p value = .003). CONCLUSIONS: Thermal balloon-based PV isolation influences the CANS through its effect on the RAGP, especially in younger patients and patients with shorter RSPV-SVC distance.

Shortened radiofrequency delivery time to optimize efficiency and safety of pulmonary vein isolation with the radiofrequency balloon: insights from the COLLABORATE registry.

AIMS: Previous clinical studies on pulmonary vein isolation (PVI) with a radiofrequency balloon (RFB) reported safe and effective procedures using conventional ablation settings with 20/60 s RF delivery via posterior/anterior (PST/ANT) electrodes. The latest evidence suggests that reducing the application time to 15 s (s) on the posterior wall when facing the oesophageal region is as effective as applying 20 s. To prospectively assess whether reducing RF time on PST/ANT segments to 15/45 s can ensure sufficient quality of lesion metrics and compare the new shortened ablation settings with the conventional one in terms of safety, and effectiveness at 1-year. METHODS AND RESULTS: A total of 641 patients from seven European centres were enrolled in a collaborative registry, with 374 in the conventional RF delivery group and 267 in the shortened RF delivery group. Procedural outcomes, lesion metrics, and safety profiles were assessed and compared between the groups. Freedom of any atrial tachycarrythmias at one year was 85.4% and 88.2% in the SHRT and CONV groups, respectively. The shortened RF delivery strategy was associated with significantly shorter procedure times (median 63.5 vs. 96.5 min, P < 0.001) and shortened fluoroscopy exposure (median 10.0 vs. 14.0 min, P < 0.001) compared to conventional delivery. Efficacy metrics, including first-pass isolation rates and time to isolation, were comparable between groups. Shortened RF delivery was associated with a lower incidence of procedural complications (1.4% vs. 5.3%, P = 0.04) and optimized thermal characteristics. CONCLUSION: Analyses from the COLLABORATE registry demonstrate that shortening RF energy delivery times to 15/45 s (PST/ANT) during PVI with the RFB resulted in comparable freedom from recurrent atrial tachyarrhythmia compared to conventional delivery times with comparable efficiency and safety.

Multielectrode catheter-based pulsed field ablation of persistent and long-standing persistent atrial fibrillation.

AIMS: Rhythm control of non-paroxysmal atrial fibrillation (AF) is significantly more challenging, as a result of arrhythmia perpetuation promoting atrial substrate changes and AF maintenance. We describe a tailored ablation strategy targeting multiple left atrial (LA) sites via a pentaspline pulsed field ablation (PFA) catheter in persistent AF sustained beyond 6 months (PerAF > 6 m) and long-standing persistent AF (LSPAF). METHODS AND RESULTS: The ablation protocol included the following stages: pulmonary vein antral and posterior wall isolation plus anterior roof line ablation (Stage 1); electrogram-guided substrate ablation (Stage 2); atrial tachyarrhythmia regionalization and ablation (Stage 3). Seventy-two [age:68 ± 10years, 61.1%males; AF history: 25 (18-45) months] patients with PerAF > 6 m (52.8%) and LSPAF (47.2%) underwent their first PFA via the FarapulseTM system. LA substrate ablation (Stage 1 and 2) led to AF termination in 95.8% of patients. AF organized into a left-sided atrial flutter (AFlu) in 46 (74.2%) patients. The PFA catheter was used to identify LA sites showing diastolic, low-voltage electrograms and entrainment from its splines was performed to confirm the pacing site was inside the AFlu circuit. Left AFlu termination was achieved in all cases via PFA delivery. Total procedural and LA dwell times were 112 ± 25 min and 59 ± 22 min, respectively. Major complications occurred in 2 (2.8%) patients. Single-procedure success rate was 74.6% after 14.9 ± 2.7 months of follow-up; AF-free survival was 89.2%. CONCLUSION: In our cohort, PFA-based AF substrate ablation led to AF termination in 95.8% of cases. Very favourable clinical outcomes were observed during >1 year of follow-up.

Quantitative assessment of transient autonomic modulation after single-shot pulmonary vein isolation with pulsed-field ablation.

INTRODUCTION: Pulmonary vein isolation (PVI) with thermal energy is characterized by concomitant ablation of the surrounding ganglionated plexi (GP). Pulsed-field ablation (PFA) selectively targets the myocardium and seems associated with only negligible effects on the autonomic nervous system (ANS). However, little is known about the dynamic effects of PFA on the GP immediately after PVI. This study sought to investigate the degree and acute vagal modulation induced by the FarapulseTM PFA system during PVI compared with single-shot thermal ablation. METHODS: A total of 76 patients underwent first-time PVI with either FarapulseTM PFA (PFA group, n = 40) or cryoballoon ablation (thermal ablation group, n = 36) for paroxysmal atrial fibrillation (AF). The effect on the ANS in the two groups was assessed before and after PVI with extracardiac vagal stimulation (ECVS). To capture any transient effects of PFA on the ANS, in a subgroup of PFA patients ECVS was repeated at three predefined timepoints: (1) before PVI (T0); (2) immediately after PVI (T1); and (3) 10 min after the last energy application (T2). RESULTS: Despite similar baseline values, the vagal response induced by ECVS after PVI almost disappeared in the thermal ablation group but persisted in the PFA group (thermal group: 840 [706-1090] ms, p < .001 compared to baseline; PFA group: 11 466 [8720-12 293] ms, p = .70 compared to baseline). Intraprocedural vagal reactions (defined as RR increase >50%, transitory asystole, or atrioventricular block) occurred more frequently with PFA than thermal ablation (70% vs. 28%, p = .001). Moreover, heart rate 24 h post-PVI increased more with thermal ablation than with PFA (16.5 ± 9.0 vs. 2.6 ± 6.1 beats/min, p < .001). In the subgroup of PFA patients undergoing repeated ANS modulation assessment (n = 11), ECVS demonstrated that PFA determined a significant acute suppression of the vagal response immediately after PVI (p < .001 compared to baseline), which recovered almost completely within 10 min. CONCLUSION: PVI with the FarapulseTM PFA system is associated with only transitory and short-lasting vagal effects on the ANS which recover almost completely within a few minutes after ablation. The impact of this phenomenon on AF outcome needs to be further investigated.

Outcomes of pulmonary vein isolation with radiofrequency balloon vs. cryoballoon ablation: a multi-centric study.

AIMS: Cryoballoon (CB) ablation is the mainstay of single-shot pulmonary vein isolation (PVI). A radiofrequency balloon (RFB) catheter has recently emerged as an alternative. However, these two technologies have not been compared. This study aims to evaluate the freedom from atrial tachyarrhythmias (ATas) at 1 year: procedural characteristics, efficacy, and safety of the novel RFB compared with CB for PVI in patients with paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: This prospective multi-centre study included consecutive patients with symptomatic drug-resistant paroxysmal AF who underwent PVI with RFB or CB between July 2021 and January 2022 from three European centres. A total of 375 consecutive patients were included, 125 in the RFB group and 250 in the CB. Both groups had comparable clinical characteristics. At 12.33 ± 4.91 months, ATas-free rates were 83.20% and 82.00% in the RFB and CB groups, respectively (P > 0.05). Compared with the CB group, the RFB group showed a shorter procedure time [59.91 (45.80-77.12) vs. 77.0 (35.13-122.71) min (P < 0.001)], dwell time [19.59 (14.41-30.24) vs. 27.03 (17.11-57.21) min (P = 0.04)], time to isolation, and thermal energy delivery in all pulmonary veins (P < 0.001). First-pass isolation was comparable. No major complications occurred in either group, with no stroke, atrio-oesophageal fistula, or permanent phrenic nerve injury. Transient phrenic nerve palsy occurred more frequently with CB than RFB (7.20% vs. 3.20%; P = 0.02). Oesophageal temperature rise occurred in 21 (16.8%) patients in the RFB group, and gastroscopy showed erythema in two of them with complete recovery after 30 days. CONCLUSIONS: The RFB appears to have a safety and efficacy profile similar to that of the CB for PVI. Shorter procedural times appear to be driven by shorter left atrial dwell and thermal delivery times.

Pulmonary vein isolation with the radiofrequency balloon catheter: a single centre prospective study.

AIMS: The multielectrode radiofrequency balloon catheter (RFB) has been developed to achieve safe and effective pulmonary vein isolation (PVI) for atrial fibrillation (AF) ablation. This single-centre study aimed to evaluate the midterm clinical outcome and predictors of single-shot PVI with the novel RFB. METHODS AND RESULTS: All consecutive patients with symptomatic paroxysmal or persistent AF undergoing first-time PVI with the RFB were prospectively included. Clinical and procedural parameters were systematically collected. The primary safety endpoint was defined as any major periprocedural complications. The primary efficacy endpoint consisted of freedom from any atrial tachyarrhythmias (ATas) lasting >30 s during the follow-up after a 3-month blanking period. Persistent single-shot PVI was defined as PVI achieved with a single RFB application without acute reconnection. A total of 104 consecutive patients (mean age 64.3 ± 11.4 years, 56.7% males) were included. 15 patients (14.4%) presented with persistent AF. The procedure time was 59.0 min with a dwell time of 20.0 min. One major complication occurred in one patient. At a mean follow-up of 10.1 ± 5.3 months, freedom from ATas was 82.9%. ATas occurred in 14 patients, 11/69 patients (15.9%) with paroxysmal AF and 3/13 (23.1%) with persistent AF. The best cut-offs to predict persistent single-shot PVI were impedance drop >19.2 Ω [area under the receiver operator characteristic curve (AUC) 0.74] and temperature rise >11.1° C (AUC 0.77). CONCLUSION: In a large cohort of patients undergoing PVI with the RFB, the complication rate was 1%. At a mid-term follow-up of 10.1 ± 5.3 months, freedom from ATas was 82.9%. Specific cut-offs of impedance drop and temperature rise may be useful to predict persistent single-shot isolation.

Coronary artery disease in atrial fibrillation ablation: impact on arrhythmic outcomes.

AIMS: Catheter ablation (CA) is an established treatment for atrial fibrillation (AF). A computed tomography (CT) may be performed before ablation to evaluate the anatomy of pulmonary veins. The aim of this study is to investigate the prevalence of patients with coronary artery disease (CAD) detected by cardiac CT scan pre-ablation and to evaluate the impact of CAD and revascularization on outcomes after AF ablation. METHODS AND RESULTS: All consecutive patients with AF diagnosis, hospitalized at Universitair Ziekenhuis Brussel, Belgium, between 2015 and 2019, were prospectively screened for enrolment in the study. Inclusion criteria were (i) AF diagnosis, (ii) first procedure of AF ablation with cryoballoon CA, and (iii) contrast CT scan performed pre-ablation. A total of 576 consecutive patients were prospectively included and analysed in this study. At CT scan, 122 patients (21.2%) were diagnosed with CAD, of whom 41 patients (7.1%) with critical CAD. At survival analysis, critical CAD at CT scan was a predictor of atrial tachyarrhythmia (AT) recurrence during the follow-up, only in Cox univariate analysis [hazard ratio (HR) = 1.79] but was not an independent predictor in Cox multivariate analysis. At Cox multivariate analysis, independent predictors of AT recurrence were as follows: persistent AF (HR = 2.93) and left atrium volume index (HR = 1.04). CONCLUSION: In patients undergoing CT scan before AF ablation, critical CAD was diagnosed in 7.1% of patients. Coronary artery disease and revascularization were not independent predictors of recurrence; thus, in this patient population, AF ablation should not be denied and can be performed together with CAD treatment.

Hybrid atrial fibrillation ablation: long-term outcomes from a single-centre 10-year experience.

AIMS: Hybrid atrial fibrillation (AF) ablation is a promising approach in non-paroxysmal AF. The aim of this study is to assess the long-term outcomes of hybrid ablation in a large cohort of patients after both an initial and as a redo procedure. METHODS AND RESULTS: All consecutive patients undergoing hybrid AF ablation at UZ Brussel from 2010 to 2020 were retrospectively evaluated. Hybrid AF ablation was performed in a one-step procedure: (i) thoracoscopic ablation followed by (ii) endocardial mapping and eventual ablation. All patients received PVI and posterior wall isolation. Additional lesions were performed based on clinical indication and physician judgement. Primary endpoint was freedom from atrial tachyarrhythmias (ATas). A total of 120 consecutive patients were included, 85 patients (70.8%) underwent hybrid AF ablation as first procedure (non-paroxysmal AF 100%), 20 patients (16.7%) as second procedure (non-paroxysmal AF 30%), and 15 patients (12.5%) as third procedure (non-paroxysmal AF 33.3%). After a mean follow-up of 62.3 months ± 20.3, a total of 63 patients (52.5%) experienced ATas recurrence. Complications occurred in 12.5% of patients. There was no difference in ATas between patients undergoing hybrid as first vs. redo procedure (P = 0.53). Left atrial volume index and recurrence during blanking period were independent predictors of ATas recurrence. CONCLUSION: In a large cohort of patients undergoing hybrid AF ablation, the survival from ATas recurrence was 47.5% at ≈5 years follow-up. There was no difference in clinical outcomes between patients undergoing hybrid AF ablation as first procedure or as a redo.

Genetic testing in children with Brugada syndrome: results from a large prospective registry.

AIMS: A pathogenic/likely pathogenic (P/LP) variant in SCN5A is found in 20-25% of patients with Brugada syndrome (BrS). However, the diagnostic yield and prognosis of gene panel testing in paediatric BrS is unclear. The aim of this study is to define the diagnostic yield and outcomes of SCN5A gene testing with ACMG variant classification in paediatric BrS patients compared with adults. METHODS AND RESULTS: All consecutive patients diagnosed with BrS, between 1992 and 2022, were prospectively enrolled in the UZ Brussel BrS registry. Inclusion criteria were: (i) BrS diagnosis; (ii) genetic analysis performed with a large gene panel; and (iii) classification of gene variants following ACMG guidelines. Paediatric patients were defined as ≤16 years of age. The primary endpoint was ventricular arrhythmias (VAs). A total of 500 BrS patients were included, with 63 paediatric patients and 437 adult patients. Among children with BrS, 29 patients (46%) had a P/LP variant (P+) in SCN5A and no variants were found in 34 (54%) patients (P-). After a mean follow-up of 125.9 months, 8 children (12.7%) experienced a VA, treated with implanted cardioverter defibrillator shock. At survival analysis, P- paediatric patients had higher VA-free survival during the follow-up, compared with P+ paediatric patients. P+ status was an independent predictor of VA. There was no difference in VA-free survival between paediatric and adult BrS patients for both P- and P+. CONCLUSION: In a large BrS cohort, the diagnostic yield for P/LP variants in the paediatric population is 46%. P+ children with BrS have a worse arrhythmic prognosis.

Pulsed electric field, cryoballoon, and radiofrequency for paroxysmal atrial fibrillation ablation: a propensity score-matched comparison.

AIMS: Pulsed field ablation (PFA) has emerged as a novel, non-thermal energy source to selectively ablate cardiac tissue. We describe a multicentre experience on pulmonary vein isolation (PVI) via the pentaspline Farapulse™ PFA system vs. thermal-based technologies in a propensity score-matched population of paroxysmal atrial fibrillation (PAF) patients. METHODS AND RESULTS: Propensity score matching was adopted to compare PVI-only ablation outcomes via the Farawave™ system (Group PFA), cryoballoon (Group CRYO), or focal radiofrequency (Group RF) (PFA:CRYO:RF ratio = 1:2:2). Among 1572 (mean age: 62.4 ± 11.3 years; 42.5% females) PAF patients undergoing first time PVI with either PFA (n = 174), CRYO (n = 655), or RF (n = 743), propensity score matching yielded 174 PFA, 348 CRYO, and 348 RF patients. First-pass isolation was achieved in 98.8% of pulmonary veins (PVs) with PFA, 81.5% with CRYO, and 73.1% with RF (P < 0.001). Procedural and dwell times were significantly shorter with PFA, whereas the availability of a 3D mapping system led to a significant reduction in X-ray exposure with RF. Overall complication rates were 3.4% (n = 6) with PFA, 8.6% (n = 30) with CRYO, and 5.5% (n = 19) with RF (P = 0.052). The 1-year Kaplan-Meier estimated freedom from any atrial tachyarrhythmia was 79.3% with PFA, 74.7% with CRYO, and 72.4% with RF (log-rank P-value: 0.24). Among 145 repeat ablation procedures, PV reconnection rate was 19.1% after PFA, 27.5% after CRYO, and 34.8% after RF (P = 0.01). CONCLUSION: Pulsed field ablation contributed to significantly shorter procedural times. Follow-up data showed a similar arrhythmia freedom, although a higher rate of PV reconnection was documented in post-CRYO and post-RF redo procedures.

Multiparametric identification of subclinical atrial fibrillation after an embolic stroke of undetermined source.

BACKGROUND: Subclinical atrial fibrillation (SCAF) may represent a cause of embolic stroke of undetermined source (ESUS) and its detection has important implications for secondary prevention with anticoagulation. Indications to implantable cardiac monitors (ICM) include SCAF detection. The aims of this study were to (1) evaluate the frequency of ICM-detected SCAF; (2) determine predictors of SCAF; and (3) identify patients who would benefit most from ICM implantation. METHODS: Between February 2017 and November 2020, all consecutive patients referred for ICM implantation after a diagnosis of ESUS and without previous history of atrial fibrillation or atrial flutter were included in this study. SCAF was diagnosed if the ICM electrogram demonstrated an episode of irregularly irregular rhythm without distinct P waves lasting > 2 min. RESULTS: We enrolled 109 patients (age 66, SD = 13 years; 36% females). During a median follow-up of 19.2 (IQR 11.0-27.5) months, SCAF episodes were detected in 36 (33%) patients. Only abnormal P wave terminal force in lead V1, left atrial end-systolic indexed volume > 34 ml/m2, and BMI > 25 kg/m2 were independently associated with an increased risk of SCAF (HR 2.44, 95% CI 1.14-5.21, p = 0.021; HR 2.39, 95% CI 1.11-5.13, p = 0.026; and HR 2.64, 95% CI 1.06-6.49, p = 0.036 respectively). The ROC curve showed that the presence of all three parameters had the best accuracy (74%) to predict SCAF detection (sensitivity 39%, specificity 91%). CONCLUSION: A multiparametric evaluation has the best accuracy to predict SCAF in ESUS patients and may help identifying those who would benefit most from ICM.

Prevalence and clinical significance of isolated low QRS voltages in young athletes.

AIMS: Low QRS voltages (peak to peak <0.5 mV) in limb leads (LQRSV) on the athlete's electrocardiogram (ECG) may reflect an underlying cardiomyopathy, mostly arrhythmogenic cardiomyopathy (ACM) or non-ischaemic left ventricular scar (NILVS). We studied the prevalence and clinical meaning of isolated LQRSV in a large cohort of competitive athletes. METHODS AND RESULTS: The index group included 2229 Italian competitive athletes [median age 18 years (16-25), 67% males, 97% Caucasian] without major ECG abnormalities at pre-participation screening. Three control groups included Black athletes (N = 1115), general population (N = 1115), and patients with ACM or NILVS (N = 58). Echocardiogram was performed in all athletes with isolated LQRSV and cardiac magnetic resonance (CMR) in those with ventricular arrhythmias or echocardiographic abnormalities. The isolated LQRSV pattern was found in 1.1% index athletes and was associated with increasing age (median age 28 vs. 18 years; P < 0.001), elite status (71% vs. 34%; P < 0.001), body surface area, and body mass index but not with sex, type of sport, and echocardiographic left ventricular mass. The prevalence of isolated LQRSV was 0.2% in Black athletes and 0.3% in young individuals from the general population. Cardiomyopathy patients had a significantly greater prevalence of isolated LQRSV (12%) than index athletes, Black athletes, and general population. Five index athletes with isolated LQSRV and exercise-induced ventricular arrhythmias underwent CMR showing biventricular ACM in 1 and idiopathic NILVS in 1. CONCLUSIONS: Unlike cardiomyopathy patients, the ECG pattern of isolated LQRSV was rarely observed in athletes. This ECG sign should prompt clinical work-up for exclusion of an underlying cardiomyopathy.

Fulminant myocarditis parvovirus B19 related in a young woman.

We present the case of a 18-year-old female with fulminant lymphocytic myocarditis caused by Parvovirus B19 (PVB19), successfully treated using temporary LVAD. In the literature there is no consensus on the surgical strategy. While some surgeons prefer to use a single device supporting only the LV, others prefer to start immediately with a biventricular supporting. At pre-procedural ultrasound evaluation, her anatomical features were not suitable for a percutaneous device such as the Impella. Thus, a temporary paracorporeal continuous flow LVAD was inserted. The heart recovery allowed LVAD removal 9 days after the implant.

Posterior wall isolation via a multi-electrode radiofrequency balloon catheter: feasibility, technical considerations, endoscopic findings and comparison with cryoballoon technologies.

BACKGROUND: Posterior wall (PW) isolation is an important adjunctive ablation target in patients with non-paroxysmal atrial fibrillation (AF). Traditionally performed with point-by-point radiofrequency (RF) ablation, PW isolation has also been performed with different cryoballoon technologies. We aimed at assessing the feasibility of PW isolation with the novel RF balloon catheter Heliostar™ (Biosense Webster, CA, USA). METHODS: We prospectively enrolled 32 consecutive patients with persistent AF scheduled for first-time ablation with the Heliostar™ device. Procedural data were compared with those from 96 consecutive persistent AF patients undergoing pulmonary vein (PV) plus PW isolation with a cryoballoon device. The ratio RF balloon/cryoballoon was 1:3 for each operator involved in the study, aiming at avoiding any imbalance related to different experience. RESULTS: Single-shot PV isolation was documented in a significantly higher number of cases with the RF balloon technology compared to cryoballoon ablation (89.8% vs. 81.0%; p = 0.02, respectively). PW isolation was achieved with a similar number of balloon applications between the two groups (11 ± 4 with the RF balloon versus 11 ± 2 with the cryoballoon; p = 0.16), but in a significantly shorter time among RF balloon patients (228 ± 72 s versus 1274 ± 277 s with cryoballoon; p < 0.001). Primary safety endpoint occurred in none of the RF balloon patients versus 5 (5.2%) patients in the cryoballoon group (p = 0.33). Primary efficacy endpoint was achieved in all (100%) RF balloon patients versus 93 (96.9%) cryoballoon ones (p = 0.57). Oesophageal endoscopy did not show any signs of thermal lesions in RF balloon patients with luminal temperature rise. CONCLUSIONS: RF balloon-based PW isolation was safe and promoted shorter procedure times compared to similar cryoballoon-based ablation procedures.

SCN5A gene variants and arrhythmic risk in Brugada syndrome: An updated systematic review and meta-analysis.

BACKGROUND: A rare gene variant in SCN5A can be found in approximately 20%-25% of patients with Brugada syndrome (BrS). OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the differences in clinical characteristics of BrS patients with and without SCN5A rare variants and the prognostic role of SCN5A for ventricular arrhythmias in BrS. METHODS: PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched from inception to January 2024 to identify all relevant studies. Studies were analyzed if they included patients diagnosed with BrS in whom genetic testing for SCN5A variants was performed and arrhythmic outcomes were reported. RESULTS: A total of 17 studies with 3568 BrS patients, of whom 3030 underwent genetic testing for SCN5A variants, fulfilled the eligibility criteria and were included. Compared with SCN5A- patients, SCN5A+ BrS patients more frequently had spontaneous type 1 electrocardiogram, history of syncope, and documented arrhythmias. Furthermore, higher PQ and QRS intervals in SCN5A+ BrS patients compared with SCN5A- have been found. The pooled analysis demonstrated a significant association between the presence of SCN5A rare variants in BrS patients and the risk of major arrhythmic events, with a pooled odds ratio of 2.14 (95% confidence interval, 1.53-2.99; I2 = 29%). CONCLUSION: SCN5A+ BrS patients showed a worse clinical phenotype compared with SCN5A-. The pooled analysis demonstrated a significant association between SCN5A+ mutation status and the risk of major arrhythmic events in BrS patients.

Genetic Testing in Brugada Syndrome: A 30-Year Experience.

BACKGROUND: A pathogenic/likely pathogenic variant can be found in 20% to 25% of patients with Brugada syndrome (BrS) and a pathogenic/likely pathogenic variant in SCN5A is associated with a worse prognosis. The aim of this study is to define the diagnostic yield of a large gene panel with American College of Medical Genetics and Genomics variant classification and to assess prognosis of SCN5A and non-SCN5A variants. METHODS: All patients with BrS, were prospectively enrolled in the Universitair Ziekenhuis Brussel registry between 1992 and 2022. Inclusion criteria for the study were (1) BrS diagnosis; (2) genetic analysis performed with a large gene panel; (3) classification of variants following American College of Medical Genetics and Genomics guidelines. Patients with a pathogenic/likely pathogenic variant in SCN5A were defined as SCN5A+. Patients with a reported variant in a non-SCN5A gene or with no reported variants were defined as patients with SCN5A-. All variants were classified as missense or predicted loss of function. RESULTS: A total of 500 BrS patients were analyzed. A total of 104 patients (20.8%) were SCN5A+ and 396 patients (79.2%) were SCN5A-. A non-SCN5A gene variant was found in 75 patients (15.0%), of whom, 58 patients (77.3%) had a missense variant and 17 patients (22.7%) had a predicted loss of function variant. At a follow-up of 84.0 months, 48 patients (9.6%) experienced a ventricular arrhythmia (VA). Patients without any variant had higher VA-free survival, compared with carriers of a predicted loss of function variant in SCN5A+ or non-SCN5A genes. There was no difference in VA-free survival between patients without any variant and missense variant carriers in SCN5A+ or non-SCN5A genes. At Cox analysis, SCN5A+ or non-SCN5A predicted loss of function variant was an independent predictor of VA. CONCLUSIONS: In a large BrS cohort, the yield for SCN5A+ is 20.8%. A predicted loss of function variant carrier is an independent predictor of VA.

Focal Pulsed Field Ablation for Premature Ventricular Contractions: A Multicenter Experience.

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 10g. 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.

Leadless pacemakers in patients with different stages of chronic kidney disease: Real-world data from the updated i-LEAPER registry.

BACKGROUND: Limited data are available on leadless pacemaker (LPM) outcomes according to different stages of chronic kidney disease (CKD). OBJECTIVE: The purpose of this study was to investigate differences in the safety and efficacy of LPMs among patients stratified per different stages of renal function. METHODS: Consecutive patients enrolled in the multicenter international i-LEAPER registry (International LEAdless PacemakEr Registry) were analyzed. Patients were divided into 3 groups according to CKD stage. The primary end point was the comparison of LPM-related major complication rate at implantation and during follow-up. Differences in electrical performance were deemed secondary outcomes. RESULTS: Of the 1748 patients enrolled, 33% were in CKD stage G3a/G3b and 9.4% were in CKD stage G4/G5. Patients with CKD presented cardiovascular comorbidities more frequently. During a median follow-up of 39 months (interquartile range [IQR] 18-59 months), major complication rate did not differ between groups (normal kidney function [NKF] group 1.8% vs CKD stage G3a/G3b group 2.9% vs CKD stage G4/G5 group 2.4%; P = .418). All-cause mortality resulted higher in the CKD stage G4/G5 group than in the NKF group (19.5% vs 9.8%; adjusted hazard ratio 1.9; 95% confidence interval 1.25-2.89; P = .003). LPM electrical performance was comparable between groups, except for patients with CKD who showed a slightly higher pacing threshold during 1-month follow-up (NKF group 0.50 V [IQR 0.35-0.70 V] vs G3a/G3b group 0.56 V [IQR 0.38-0.81 V] vs G4/G5 group 0.51 V [0.38-0.84 V] @ 0.24 ms; P < .001). CONCLUSION: In a real-world setting, patients with advanced CKD who underwent LPM implantation were underrepresented. Although all-cause mortality was higher in end-stage CKD, periprocedural complications and LPM performance were overall comparable between NKF and different stages of CKD, except for higher values of pacing threshold in patients with CKD up to first-month follow-up.

Pulsed field ablation of the right superior pulmonary vein prevents vagal responses via anterior right ganglionated plexus modulation.

BACKGROUND: Pulsed field ablation (PFA) is selective for the myocardium. However, vagal responses and reversible effects on ganglionated plexi (GP) are observed during pulmonary vein isolation (PVI). Anterior-right GP ablation has been proven to effectively prevent vagal responses during radiofrequency-based PVI. OBJECTIVE: The purpose of this study was to test the hypothesis that PFA-induced transient anterior-right GP modulation when targeting the right superior pulmonary vein (RSPV) before any other pulmonary veins (PVs) may effectively prevent intraprocedural vagal responses. METHODS: Eighty consecutive paroxysmal atrial fibrillation patients undergoing PVI with PFA were prospectively included. In the first 40 patients, PVI was performed first targeting the left superior pulmonary vein (LSPV-first group). In the last 40 patients, RSPV was targeted first, followed by left PVs and right inferior PV (RSPV-first group). Heart rate (HR) and extracardiac vagal stimulation (ECVS) were evaluated at baseline, during PVI, and postablation to assess GP modulation. RESULTS: Vagal responses occurred in 31 patients (78%) in the LSPV-first group and 5 (13%) in the RSPV-first group (P <.001). Temporary pacing was needed in 14 patients (35%) in the LSPV-first group and 3 (8%) in the RSPV-first group (P = .003). RSPV isolation was associated with similar acute HR increase in the 2 groups (13 ± 11 bpm vs 15 ± 12 bpm; P = .3). No significant residual changes in HR or ECVS response were documented in both groups at the end of the procedure compared to baseline (all P >.05). CONCLUSION: PVI with PFA frequently induced vagal responses when initiated from the LSPV. Nevertheless, an RSPV-first approach promoted transient HR increase and reduced vagal response occurrence.