Background: Pulmonary vein isolation (PVI) constitutes the established strategy for atrial fibrillation (AF) ablation. With the advent of PV stenosis risk-free pulsed field ablation (PFA), we explored the feasibility and safety of additional ablation within PV sleeves (PVA). Moreover, we assessed the durability of PVI through PFA in a deep sedation setting, comparing a 3D Electroanatomical Mapping (3D-EAM)-based navigation approach with the standard fluoroscopy-based one. Methods: In this single-center, first-in-human study ([NCT07035288][1]), 40 AF patients underwent first time PFA-based PVI+PVA (4 additional applications inside the PVs) between November 2024 and April 2025 using a circular array PFA catheter (PulseSelect, Medtronic, Minneapolis, MN), randomized to either 3D-EAM-based (Carto3 prime, J&J, Irvine, CA) or fluoroscopy-based navigation, in a propofol-based deep sedation setting. Rate of conversion from 3D-EAM to fluoroscopy-based navigation was recorded. First-pass isolation was assessed immediately post-ablation. Venography and 3D-EAM were performed at remapping at 2 to 3 months after the index procedure. Results: No major procedure-related adverse events were noted, as well as no acute kidney injury, significant hemolysis or phrenic nerve palsy. First-pass isolation was successfully achieved in 95% of patients (3D-EAM: 95%, fluoroscopy: 95%, p=NS) and in 98.7% of PVs. Venography performed at remapping revealed no PV stenosis. PVI durability per patient was 92.5% (3D-EAM: 90%, fluoroscopy: 95%, p=NS) and per vein was 97.5% (3D-EAM: 97.5%, fluoroscopy: 97.5%, p=NS between navigation methods). Half of 3D-EAM cases were converted to fluoroscopy due to map shift. Conclusions: PFA-based PVA is safe. Catheter performance, as depicted by 97.5% durable PVI, was such that adding a 3D-EAM system was not associated with improved efficacy and exhibited high conversion rate to fluoroscopy-based navigation in a deep sedation setting. ### Competing Interest Statement Dimitris Tsiachris has been a member of advisory board for PulseSelect Catheter, received honoraria for lectures and presentations on PulseSelect Catheter and support for attending meetings Athanasios Kordalis and Konstantinos Tsioufis received honoraria for lectures and presentations on PulseSelect Catheter and support for attending meetings ### Clinical Trial NCT07035288 ### Funding Statement The present study was funded by Medtronic through the ERP-2024-13979 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Ethics Committee of General Hospital of Athens, Hippokratio I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are available when required [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT07035288&atom=%2Fmedrxiv%2Fearly%2F2025%2F10%2F30%2F2025.10.22.25338592.atom

ABSTRACT Background Cryoablation is an established treatment for atrial fibrillation (AF), offering effective rhythm control and symptomatic improvement. However, short‐term trajectories of quality‐of‐life (QoL) recovery—particularly regarding age‐ and sex‐related differences—remain insufficiently characterized. This study evaluated patterns of functional and emotional improvement within 3 and 6 months after cryoablation. Methods A prospective observational cohort of 150 patients undergoing cryoablation for AF was analyzed. QoL was assessed using the 36‐item short form (SF) (Physical and Mental Component Scores PCS and MCS) survey at baseline, 3 months, and 6 months. Results Significant improvements were observed across all SF‐36 (57.5 at baseline to 77.1 at 3‐months and 80.1 at 6‐months, p < 0.001), PCS and MCS between baseline and follow‐up (main effect of time p < 0.001). An age × time interaction showed that younger patients (≤ 65 years) demonstrated greater functional gains both in 3 and 6 months compared to older adults ( p < 0.001 for all). A sex × time interaction was also noted for SF‐36 ( p = 0.046) and PCS ( p = 0.038), reflecting a trend for a more rapid improvement in men versus women. These sex differences were non‐significant after Bonferroni adjustment. Multivariable regression confirmed younger age as the strongest independent predictor of improvement (β = 18.2, p < 0.001), followed by paroxysmal AF type and baseline ejection fraction. Conclusions Cryoablation leads to substantial QoL improvements. While age is a robust independent predictor of recovery, sex‐specific differences in physical and emotional trajectories appear as notable trends requiring further investigation. These findings emphasize the need for individualized post‐procedural counseling and follow‐up tailored to demographic recovery profiles.

BACKGROUND Pulmonary vein (PV) isolation is the mainstay in atrial fibrillation (AF) ablation. However, additional arrhythmogenic foci seem to contribute to AF initiation and maintenance. A great proportion of those non-PV foci have been reported to be located in the superior vena cava (SVC). AIM To investigate the effectiveness of SVC as an adjunctive therapy to PV isolation. METHODS We performed a meta-analysis of MEDLINE and CENTRAL. Inclusion criteria were cohort studies with a control group or randomized clinical trials, comparing patients undergoing AF ablation without additional SVC isolation to those receiving ablation with concurrent SVC isolation, in effects of freedom from atrial tachycardia. RESULTS A total of 10 studies, incorporating 2176 patients, were included. The majority of the patients (91.5%) expressed paroxysmal AF. The additional SVC isolation strategy in patients undergoing AF ablation was more effective than the non-SVC isolation strategy [odds ratio (OR) = 0.71; 95% confidence interval (CI): 0.55-0.92]. In a subgroup analysis, radiofrequency ablation demonstrated effectiveness (OR = 0.69; 95%CI: 0.53-0.92). Conversely, the use of cryoablation did not alter clinical outcomes (OR = 0.69; 95%CI: 0.13-3.61). In a distinct subgroup analysis, SVC isolation guided by induction of SVC-originating AF triggers - vs no isolation when no AF-inducing triggers were observed - yielded no superiority (OR = 0.73; 95%CI: 0.46-1.16). CONCLUSION The outcomes of AF ablation are favorable when additional SVC isolation is conducted. In a tailored care approach, radiofrequency energy should be preferred. Periprocedural induction of SVC-originating AF triggers, either by isoproterenol infusion or burst atrial pacing, should not be used as a criterion for performing SVC isolation. These findings support integrating SVC isolation into individualized ablation strategies to optimize patient outcomes.

Introduction:The PRESERVE EF study proposed a two-step algorithm for risk stratification in post-myocardial infarction (MI) patients with mid-range and preserved left ventricular ejection fraction (LVEF). This method assessed the performance of a two-step, programmed ventricular stimulation (PVS)-inclusive approach in identifying high-risk post-MI patients with LVEF ≥40%. This report presents findings from the 8-year follow-up. Methods:The primary endpoint was the occurrence of a major arrhythmic event, defined as sustained ventricular tachycardia/fibrillation, appropriate implantable cardioverter-defibrillator (ICD) activation, or sudden cardiac death (SCD). We included a total of 575 consecutive patients (mean age 57 years, LVEF 50.8%). Of them, 204 (35.5%) had at least one positive non-invasive risk factor. Forty-one of 152 patients undergoing PVS were inducible; 37 (90.2%) of them received an ICD. Results:During a mean follow-up of 106 ± 14.5 months, no SCDs were observed, while 12 ICDs (the major arrhythmic event prevalence in patients with ICD implantation reaching 29.3%) were appropriately activated. The updated performance metrics of the proposed approach were as follows: sensitivity 100% (95% CI: 73.5%-100%), specificity 94.8% (95% CI: 92.5-96.5%), positive predictive value 29.3% (95% CI: 17.2-45.0%), and negative predictive value 100% (95% CI: 99.3%-100%). Notably, events occurred only in patients with an LVEF 40%-50% and a history of ST-Elevation Myocardial Infarction. Conclusion:The PRESERVE EF study demonstrates that a simple, two-step, non-invasive risk factor-guided approach, followed by programmed ventricular stimulation, can effectively identify a subgroup of post-MI patients with preserved or mid-range LVEF ≥40 who are at high risk for major arrhythmic events. Clinical Trial Registration:Clinicaltrials.gov, identifier NCT02124018.

Idiopathic premature ventricular complexes (PVCs) commonly originate from the right and left ventricular outflow tracts (RVOT and LVOT, respectively). The surface 12-lead ECG is commonly used to differentiate the anatomic site of origin, prior to catheter ablation. Multiple ECG algorithms have been published to assist preprocedural localization. We sought to evaluate the diagnostic performance of three commonly implemented algorithms. This study included 18 patients (47.4% women, mean age 52 ± 22.9 years), who underwent successful catheter ablation of outflow tract- originating idiopathic PVCs. The diagnostic algorithms evaluated were the V2S/V3R index, the transition zone index and the lead I R wave amplitude (an R wave amplitude ≥ 0.1 mV in lead I predicts LVOT origin). The diagnostic accuracy of the algorithms was assessed by the area under the receiver- operating characteristics curve (AUC). Specificity and sensitivity of each algorithm were measured. Electroanatomic 3D mapping depicted as site of origin the RVOT in 7 patients (42.9% women, mean age 33.9 ± 21.4 years) and the LVOT in 11 patients (54.5% women, mean age 64.1 ±14.7 years). The V2S/V3R index yielded a sensitivity of 0.86 and a specificity of 0.73. The AUC was 0.94 (Figure 1). As for the transition score index, sensitivity and specificity were 0.83 and 0.63, respectively, with an AUC 0.86. Lead I R wave amplitude demonstarted a sensitivity of 0.57 and a specificity of 0.9, respectively. The AUC was 0.7. Published diagnostic algorithms can reliably differentiate right ventricular from left ventricular originating outflow tract arrhythmias.ROC Curve of each algorithm

Atrial fibrillation (AF) is a supraventricular arrhythmia and the most common heart rhythm disorder in the adult population worldwide with an estimated prevalence of 2% to 4% of the population. Cases of AF have shown an increasing trend in recent decades, while its frequency is expected to rise even more. Given the significant impact on patients’ quality of life, as well as its major complications, including thromboembolic events, effective rhythm control strategies other than antiarrhythmic medication have emerged, with catheter ablation (CA) being the cornerstone of these. In recent years, CA has been upgraded to a first-line treatment for selected patients. However, complications do exist and arrhythmia-free survival is not always guaranteed. The need to better identify patients more suitable for this specific therapeutic measure is crucial in improving outcomes and preventing arrhythmia recurrences. This review aims to present currently identified predictors of AF recurrence after catheter ablation based on clinical characteristics and electrocardiographic and echocardiographic parameters, in an era of increasing interventional rhythm control approaches for the management of atrial fibrillation.

Background:Brugada syndrome (BrS) is associated with an increased risk of major arrhythmic events (MAEs), particularly in patients with a spontaneous type 1 electrocardiographic (ECG) pattern. Objective:Because previous meta-analyses used mainly crude or unadjusted data from observational studies, we conducted an updated meta-analysis on the prognostic role of spontaneous type 1 ECG in BrS patients combining adjusted and unadjusted data separately. Methods:We conducted a systematic search of PubMed and Cochrane Central Register of Controlled Trials from inception to May 2024. Studies providing hazard ratios for MAEs associated with spontaneous type 1 ECG in BrS patients were included. Results:Eighteen studies comprising 7238 patients were included, with 10 providing adjusted and 17 providing unadjusted data. Separate pooled analyses using a random-effects model demonstrated a significantly increased risk of MAEs in BrS patients with spontaneous type 1 ECG compared with those without, with a pooled adjusted hazard ratio (aHR) of 2.05 (95% CI 1.38-3.03) and an unadjusted hazard ratio of 2.97 (95% CI 2.04-4.34). Subgroup analysis revealed higher risks in studies with non-Asian populations and those including patients with no history of aborted cardiac arrest (aHR 2.36, 95% CI 1.35-4.11; and aHR 3.56, 95% CI 2.35-5.41, respectively) and a persistent significant risk in studies accounting for syncope as a covariate (aHR 2.01, 95% CI 1.24-3.27). Conclusion:Our analysis indicates that patients with BrS and spontaneous type 1 ECG are at higher risk of MAEs. This is consistent across various subgroups, including asymptomatic individuals.

Persistent high Premature Ventricular Contraction (PVC) burden (>10%) may result in PVC-induced cardiomyopathy. Current guidelines, supported by limited evidence, recommend treatment with flecainide for PVCs originating in the ventricular outflow tract (Class IIa). UNIFLECA is a prospective cohort study aimed to assess the efficacy and safety of flecainide in PVC burden reduction in adults (irrespective of PVC origin), focusing secondarily on symptom relief and improvement in left ventricular ejection fraction (LVEF) in patients with PVC-induced cardiomyopathy. Participants were adults with a PVC burden >5%, confirmed by two 24-hour Holter recordings taken at least one month apart, who denied catheter ablation treatment. Flecainide treatment was initiated with dosage adjustments based on follow-up Holter results and QRS increases. Changes in PVC burden, LVEF, symptoms, and treatment adherence were evaluated. As of September 2024, a cohort of 50 patients was screened. Persistent high PVC burden and eligibility criteria were met in 35 patients who initiated flecainide slow release treatment (Median time between Holter recordings: 162 days and 5 had previously undergone PVC ablation procedures). A daily dose of 100 mg slow-release flecainide was administered in 63.2% of patients, while the remaining patients were on a 200 mg daily regimen. Among them 19 were monitored over a one-month period following treatment initiation. A significant reduction was present in the mean PVC burden (mean decrease: 76.2% in the first month), with 63.1% of patients achieving a PVC reduction greater than 80%. Symptomatic improvement was observed in 74% of patients, with 25.8% reporting complete resolution of symptoms. Among those with baseline left ventricular ejection fraction (LVEF) impairment, functional improvement was noted, and 68% required dose adjustments to achieve optimal efficacy. No patients presented with QRS increase of >25% and no major adverse effects were observed. Flecainide effectively reduces PVC burden and enhances symptomatic and functional outcomes in adults with persistent high PVC burden, irrespective of PVC origin, presenting a valuable alternative for patients ineligible or denying catheter ablation therapy.

Idiopathic premature ventricular contractions (PVCs) is a frequently encountered clinical arrhythmia. Current guidelines define idiopathic PVCs as those occurring in the absence of structural heart disease. Among the most frequent sites of PVCs origin are the right ventricular outflow tract (RVOT) and the left ventricular outflow tract (LVOT). The study aimed to assess whether increasing age is associated with an RVOT or LVOT origin of PVCs. We included 79 patients (29 women, men age 55.7 ± 16.2), who underwent successful idiopathic PVC ablation, originating from either RVOT or LVOT, as determined by 3-D electroanatomical mapping, from 2015 to 2024. Univariate logistic regression was applied, to correlate the patients age with the site of the arrhythmia origin. The site of origin was identified as the RVOT in 37 patients and the LVOT in 42 patients. Advancing age was positively associated with an arrhythmia origin from the LVOT, rather the RVOT (Odds Ratio: 1.06, 95% C.I. 1.03- 1.11, p < 0.001, per year increase). The area under the curve was calculated to be 0.76 (Image 1). The age difference among the two sites of origin is also illustrated in Image 2. No differences were noted in the 24-hour burden among RVOT and LVOT originating arrhytmias (20.2% vs 19.0%, p = 0.9). Patients with RVOT-originating arrhythmia were more likely to be symptomatic on initial presentation (45.9% vs 20.0 %, p < 0.01). Procedural duration was similar (131.6 vs 127.8 min, p = 0.8) for RVOT and LVOT, respectively. Activation mapping depicted similar prematurity, irrespectively of RVOT or LVOT origin (30 vs 26 msec, p = 0.2). Increasing age is positively correlated with LVOT- originating PVCs, compared with RVOT-originating aortic cusps. The finding is possibly attributed to increased calcium deposition within the aortic cusps and the aortic annulus with increasing age, which leads to micro- reentry circuits and arrhythmogenesis.Area under the curve Age by outflow tract origin

The increasing rates of AF-related ED visits and admissions underscore the need for efficient strategies to safely restore sinus rhythm [1,2]. Amiodarone remains the preferred choice for patients with coronary artery disease (CAD) due to its established safety profile. However, flecainide’s efficacy and safety in CAD patients is an area warranting further exploration, as recent analyses seem to suggest [3,4]. The primary objectives are to prove the superiority of flecainide over amiodarone in the successful cardioversion of PAF within 6 hours and to demonstrate that the safety of flecainide is non-inferior to amiodarone in patients with CAD without residual ischemia and an EF > 35%. The secondary goals of the study are to prove the superiority of flecainide over amiodarone in the reduction in hospitalizations from the ED, in the time taken to achieve cardioversion, and in the reduction in electrical cardioversion incidence. The FLECA-ED trial (NCT05549752) is a randomized, controlled, multi-center study, enrolling patients with paroxysmal AF, CAD without residual ischemia and EF >35% based on with recent PCI/CABG and/or negative cardiac stress imaging. Continuous ECG monitoring is employed directly before randomization to IV flecainide or amiodarone for 24 hours post-administration, with 30-day follow-up. Study endpoints include SR restoration within 6 hours, time to cardioversion, and incidence of adverse events. To date, a total of 25 patients have been enrolled; 10 in the flecainide group and 15 in the amiodarone group. Initial analysis indicates that median time to cardioversion was 35 minutes (IQR 30.8) in the flecainide group and 679 minutes (IQR 1000) in the amiodarone group, p < 0.001. Ten out of 10 patients (100%) receiving flecainide were discharged safely from the ED in SR within 6 hours. 11 out of 15 (73%) patients who received amiodarone required hospitalization. One significant adverse event was reported in the amiodarone group which required hospitalization prolongation with the patient making full recovery. Preliminary data from the FLECA-ED study suggest that flecainide may provide a faster and effective alternative to amiodarone for pharmacologic cardioversion in CAD patients with preserved EF. If these trends are confirmed, flecainide could represent a valuable option for enhancing ED efficiency and potentially reducing hospitalization rates.

Premature ventricular complexes (PVCs) constitute a commonly encountered arrhythmia. Catheter ablation has emerged as a safe and effective therapeutic modality. However, long term follow-up data are still lacking. We conducted long term follow-up of patients who underwent catheter ablation for frequent PVCs, defined as more than 10.000, during at least two 24- hour ambulatory ECG- monitoring. This retrospective cohort study included 152 patients (34.2% female; median age 58.4, IQR 24.1 years) who underwent catheter ablation at a single center from 2015 to 2022. PVC burden ranged from 10 to 30% in 113 patients (74.34%) and over 30% in 39 patients (25.6%). We sought to evaluate the following factors: Patient demographics, procedural characteristics and outcomes, complication rates and long-term clinical outcomes. There were 37 (24.3%) patients with already diagnosed structural heart disease (27 with ischemic heart disease, 7 with dilated cardiomyopathy, 1 with valvular heart failure, 1 with hypertensive heart failure and 1 with non- dilated left ventricular cardiomyopathy). A diagnosis of PVC induced cardiomyopathy, prior to ablation, was established in 21 (13.8) % of cases. Prior to catheter ablation, 142 patients had received beta-blockers and 22 had received class IC or III antiarrhythmics, without PVCs suppression. Acute procedural success was achieved in 139 (91.4 %) of patients. In the long term follow up of the successful cases (mean follow up 3.6 ± 2.3 years), 6 recurrences were observed (among them, a new origin of PVCs was noted in one patient, 4 years after the index procedure). Patients with PVCs originating from sites other than the outflow tracts were more likely to experience arrhythmia recurrence (log- rank test, p = 0.029). PVC induced cardiomyopathy resolved in 18 out of 21 patients, post catheter ablation. Among the failed cases, one procedure was discontinued due to intraprocedural tamponade. The rest of the failed cases were attributed to inaccessible site of origin, mainly left ventricular summit (n= 4) and papillary muscle (n = 5). No procedure-related mortality was recorded. Cardiac tamponade occurred interprocedurally in two patients (1.32%) and was successfully treated with pericardiocentesis. Both were attributed to the use of non- contact force technology. Temporal conduction system disturbances (less than 24 hours duration) were noted in 6 patients (3.9%). One patient suffered intraprocedural ischemic stroke, which was successfully treated with thrombectomy. One patient suffered vascular access-related complication, namely femoral hematoma, which required vascular surgery. Mean procedural duration was 134.7 ± 48 minutes. In the long term follow up, catheter ablation of frequent PVCs demonstrates safety and effectiveness, and requires multidisciplinary approach of complications management.Long Term follow-up