Anti-Arrhythmic Effects of Heart Failure Guideline-Directed Medical Therapy and Their Role in the Prevention of Sudden Cardiac Death: From Beta-Blockers to Sodium-Glucose Cotransporter 2 Inhibitors and Beyond.

Sudden cardiac death (SCD) accounts for a substantial proportion of mortality in heart failure with reduced ejection fraction (HFrEF), frequently triggered by ventricular arrhythmias (VA). This review aims to analyze the pathophysiological mechanisms underlying VA and SCD in HFrEF and evaluate the effectiveness of guideline-directed medical therapy (GDMT) in reducing SCD. Beta-blockers, angiotensin receptor-neprilysin inhibitors, and mineralocorticoid receptor antagonists have shown significant efficacy in reducing SCD risk. While angiotensin-converting enzyme inhibitors and angiotensin receptor blockers exert beneficial impacts on the renin-angiotensin-aldosterone system, their direct role in SCD prevention remains less clear. Emerging treatments like sodium-glucose cotransporter 2 inhibitors show promise but necessitate further research for conclusive evidence. The favorable outcomes of those molecules on VA are notably attributable to sympathetic nervous system modulation, structural remodeling attenuation, and ion channel stabilization. A multidimensional pharmacological approach targeting those pathophysiological mechanisms offers a complete and synergy approach to reducing SCD risk, thereby highlighting the importance of optimizing GDMT for HFrEF. The current landscape of HFrEF pharmacotherapy is evolving, with ongoing research needed to clarify the full extent of the anti-arrhythmic benefits offered by both existing and new treatments.

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 is to evaluate: (1) differences in clinical characteristics of BrS patients with and without SCN5A rare variants and (2) 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 including 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 patients undergone to genetic testing for SCN5A variants, fulfilled the eligibility criteria and were included. Compared with SCN5A- patients, SCN5A+ BrS patients had more frequently spontaneous type I ECG, 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 MAEs, with a pooled OR of 2.14 (95% CI: 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 MAEs 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.

Pericarditis prophylactic therapy after sinus node-sparing hybrid ablation for inappropriate sinus tachycardia/postural orthostatic sinus tachycardia.

Background: Pericarditis is the most common complication following hybrid sinus node-sparing ablation for inappropriate sinus tachycardia (IST)/postural orthostatic tachycardia syndrome (POTS). Objective: The study sought to evaluate the association of prophylaxis therapy on the risk of symptomatic pericarditis following hybrid IST/POTS ablation. Methods: All consecutive patients undergoing to hybrid ablation of symptomatic IST/POTS refractory or intolerant to drugs were retrospectively analyzed. Pharmacological prophylaxis therapy was based on acetylsalicylic acid and colchicine started on the day of the ablation and continued for at least 3 months. The primary endpoint was occurrence of symptomatic pericarditis. The secondary endpoint was occurrence of pericarditis-related complications, including the following: duration of pericarditis >3 months, hospitalization for pericarditis, postpericardiectomy pleuro-pericarditis, and pericardiectomy. Results: A total of 220 patients undergone to hybrid IST/POTS ablation were included and 44 (20%) underwent prophylaxis therapy. Pericarditis occurred in 101 (45.9%) patients, with 97 (96%) in the first 5 days. At survival analysis, prophylaxis was associated with higher rate of freedom from pericarditis (81.9% vs 47.2%, log-rank P < .001). Pericarditis-related complications were low, occurring in 7 (3.2%) patients. There was no difference in pericarditis-related complications between the patients who underwent prophylaxis therapy and patients who did not. At Cox multivariate analysis, predictors of pericarditis were IST (vs POTS) (hazard ratio 0.61, 95% confidence interval0.39-0.99, P = .04) and prophylaxis therapy (hazard ratio 0.27, 95% confidence interval 0.13-0.55, P < .001). Conclusion: In a large cohort of patients undergoing hybrid ablation for IST/POTS, a prophylaxis therapy with acetylsalicylic acid and colchicine was associated with a lower rate of symptomatic pericarditis.

Acute Kidney Injury Resulting From Hemoglobinuria After Pulsed-Field Ablation in Atrial Fibrillation: Is it Preventable?

BACKGROUND: High-voltage pulses can cause hemolysis. OBJECTIVES: The authors evaluated the occurrence of hemoglobinuria after pulsed-field ablation (PFA) and its impact on renal function in patients with atrial fibrillation (AF). METHODS: A consecutive series of patients with AF undergoing PFA were included in this analysis. The initial patients who did not receive postablation hydration immediately after the procedure were classified as group 1 (n = 28), and the rest of the study patients who received planned fluid infusion (0.9% sodium chloride ≥2 L) after the procedure were categorized as group 2 (n = 75). RESULTS: Of the 28 patients in group 1, 21 (75%) experienced hemoglobinuria during the 24 hours after catheter ablation. The mean postablation serum creatinine (S-Cr) was significantly higher than the baseline value in those 21 patients (1.46 ± 0.28 mg/dL vs 0.86 ± 0.24 mg/dL, P < 0.001). Of those 21 patients, 4 (19%) had S-Cr. >2.5 mg/dL (mean: 2.95 ± 0.21 mg/dL). The mean number of PF applications was significantly higher in those 4 patients than in the other 17 patients experiencing hemoglobinuria (94.63 ± 3.20 vs 46.75 ± 9.10, P < 0.001). In group 2 patients, no significant changes in S-Cr were noted. The group 2 patients received significantly higher amounts of fluid infusion after catheter ablation than did those in group 1 (2,082.50 ± 258.08 mL vs 494.01 ± 71.65 mL, P < 0.001). In multivariable analysis, both hydration (R2 = 0.63, P < 0.01) and number of PFA applications (R2 = 0.33, P < 0.01) were independent predictors of postprocedure acute kidney injury. CONCLUSIONS: On the basis of our findings, both the number of PFA applications and postablation hydration were independent predictors of renal insult that could be prevented using planned fluid infusion immediately after the procedure.

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.

Lower rate of major bleeding in very high risk patients undergoing left atrial appendage occlusion: A propensity score-matched comparison with direct oral anticoagulation.

BACKGROUND: Long-term oral anticoagulation is the mainstay therapy for thromboembolic (TE) prevention in patients with atrial fibrillation. However, left atrial appendage occlusion (LAAO) could be a safe alternative to direct oral anticoagulants (DOACs) in patients with a very high TE risk profile. OBJECTIVE: The purpose of this study was to compare the safety and efficacy of LAAO vs DOACs in patients with atrial fibrillation at very high stroke risk (CHA2DS2-VASc [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category] score ≥ 5). METHODS: Data from patients with CHA2DS2-VASc score ≥ 5 were extracted from a prospective multicenter database. To attenuate the imbalance in covariates between groups, propensity score matching was used (covariates: CHA2DS2-VASc and HAS-BLED [hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol] scores), which resulted in a matched population of 277 patients per group. The primary end point was a composite of cardiovascular death, TE events, and clinically relevant bleeding during follow-up. RESULTS: Of 2381 patients, 554 very high risk patients were included in the study (mean age 79 ± 7 years; CHA2DS2-VASc score 5.8 ± 0.9; HAS-BLED score 3.0 ± 0.9). The mean follow-up duration was 25 ± 11 months. A higher incidence of the composite end point was documented with DOACs compared with LAAO (14.9 events per 100 patient-years in the DOAC group vs 9.4 events per 100 patient-years in the LAAO group; P = .03). The annualized clinically relevant bleeding risk was higher with DOACs (6.3% vs 3.2%; P = .04), while the risk of TE events was not different between groups (4.1% vs 3.2%; P = .63). CONCLUSION: In high-risk patients, LAAO had a similar stroke prevention efficacy but a significantly lower risk of clinically relevant bleeding when compared with DOACs. The clinical benefit of LAAO became significant after 18 months of follow-up.

Economic evaluation of first-line cryoballoon ablation versus antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation from an English National Health Service perspective.

INTRODUCTION: Three recent randomised controlled trials have demonstrated that pulmonary vein isolation as an initial rhythm control strategy with cryoablation reduces atrial arrhythmia recurrence in patients with symptomatic paroxysmal atrial fibrillation (PAF) compared with antiarrhythmic drug (AAD) therapy. The aim of this study was to evaluate the cost-effectiveness of first-line cryoablation compared with first-line AADs for treating symptomatic PAF in an English National Health Service (NHS) setting. METHODS: Individual patient-level data from 703 participants with PAF enrolled into Cryo-FIRST (Catheter Cryoablation Versus Antiarrhythmic Drug as First-Line Therapy of Paroxysmal Atrial Fibrillation), STOP AF First (Cryoballoon Catheter Ablation in an Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation) and EARLY-AF (Early Aggressive Invasive Intervention for Atrial Fibrillation) were used to derive the parameters applied in the cost-effectiveness model (CEM). The CEM comprised a hybrid decision tree and Markov structure. The decision tree had a 1-year time horizon and was used to inform the initial health state allocation in the first cycle of the Markov model (40-year time horizon; 3-month cycle length). Health benefits were expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3.5% per year. Model outcomes were generated using probabilistic sensitivity analysis. RESULTS: The results estimated that cryoablation would yield more QALYs (+0.17) and higher costs (+£641) per patient over a lifetime than AADs. This produced an incremental cost-effectiveness ratio of £3783 per QALY gained. Independent of initial treatment, individuals were expected to receive ~1.2 ablations over a lifetime. There was a 45% relative reduction in time spent in AF health states for those initially treated with cryoablation. DISCUSSION: AF rhythm control with first-line cryoablation is cost effective compared with first-line AADs in an English NHS setting.

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.

Pulsed-Field Ablation Does Not Worsen Baseline Pulmonary Hypertension Following Prior Radiofrequency Ablations.

BACKGROUND: Studies have reported development of pulmonary hypertension (PH) secondary to reduced LA compliance following AF ablation. OBJECTIVES: We aimed to compare the risk of worsening of baseline PH between non-paroxysmal AF patients undergoing pulsed-field ablation (PFA) and standard radiofrequency ablation (RFA). METHODS: This multicenter study included 28 nonparoxysmal AF patients with PH undergoing a PFA-based ablation procedure after >1 failed RFA. A cohort of 28 AF patients with PH, scheduled for repeat RFA, 1:1 propensity-score matched using a multivariable logistic model, were used as the comparator group. Right heart catheterization and echocardiography were performed before and after the procedure to assess the pulmonary artery pressure (PAP). PH was defined as resting mean PAP of >20 mm Hg. RESULTS: The baseline characteristics of the PFA and propensity-matched RFA groups were comparable. The mean PAP assessments at baseline, follow-up, and change from baseline were analyzed. The groups had comparable baseline mean pulmonary artery pressures (mPAP) (P = 0.177). After adjustment for baseline mPAP in an analysis of covariance model, the least-squares means change at 3 months after ablation was -1.71 ± 1.03 mm Hg and 19.67 ± 1.03 mm Hg in PFA and RFA, respectively (P <0.001). CONCLUSIONS: In this propensity-matched population, no worsening of mPAP was detected following pulsed-field ablation in patients with pre-existing PH undergoing a repeat procedure for recurrence.

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.

Redo procedures after sinus node sparing hybrid ablation for inappropriate sinus tachycardia/postural orthostatic sinus tachycardia.

AIMS: A novel sinus node (SN) sparing hybrid ablation for inappropriate sinus node tachycardia (IST)/postural orthostatic tachycardia syndrome (POTS) has been demonstrated to be an effective and safe therapeutic option in patients with symptomatic drug-resistant IST/POTS. The aim of this study was to evaluate the long-term rate of redo procedures after hybrid IST ablation and procedural strategy, outcomes and safety of redo procedures. METHODS AND RESULTS: All consecutive patients from 2015 to 2023 were prospectively enrolled in the UZ Brussel monocentric IST/POTS registry. They were analysed if the following inclusion criteria were fulfilled: 1) diagnosis of IST or POTS, 2) symptomatic IST/POTS refractory or intolerant to drugs, and 3) hybrid SN sparing ablation performed. The primary endpoint was redo procedure. The primary safety endpoint was pacemaker (PM) implantation. A total of 220 patients undergone to hybrid IST ablation were included, 185 patients (84.1%) were treated for IST and 61 patients (27.7%) for POTS.After a follow-up of 73.3 ± 16.2 months, 34 patients (15.4%) underwent a redo. A total of 23 patients (67.6%) had a redo for IST recurrence and 11 patients (32.4%) for other arrhythmias. Pacemaker implantation was performed in 21 patients (9.5%). Nine patients (4.1%) had no redo procedure and experienced sick sinus syndrome requiring a PM. Twelve patients (5.4%) received a PM as a shared therapeutic choice combined with SN ablation procedure. CONCLUSION: In a large cohort of patients the long-term free survival from redo procedure after hybrid IST ablation was 84.6% with a low PM implantation rate.

Zero fluoroscopy catheter ablation of premature ventricular contractions: a multicenter experience.

BACKGROUND: Catheter ablation has become an established treatment option for premature ventricular complexes (PVCs). The use of fluoroscopy exposes patients and medical staff to potentially harmful stochastic and deterministic effects of ionizing radiations. We sought to analyze procedural outcomes in terms of safety and efficacy using a "zero fluoroscopy" approach for catheter ablation of PVCs. METHODS: The present retrospective, multicenter, observational study included 131 patients having undergone catheter ablation of PVCs using "zero fluoroscopy" between 2019 and 2020 in four centers compared with another group who underwent the procedure with fluoroscopy. RESULTS: Median age was 51.0 ± 15.9 years old; males were 77 (58.8%). Among the study population, 26 (19.8%) had a cardiomyopathy. The most frequent PVC origin was right ventricular outflow tract (55%) followed by the left ventricle (16%), LVOT and cusps (13.7%), and aortomitral continuity (5.3%). Acute suppression of PVC was achieved in 127 patients (96.9%). At 12 months, a complete success was documented in 109 patients (83.2%), a reduction in PVC burden in 18 patients (13.7%), and a failure was recorded in four patients (3.1%). Only two minor complications occurred (femoral hematoma and arteriovenous fistula conservatively treated). CONCLUSIONS: The PVC ablation with a "zero" fluoroscopy approach appears to be a safe procedure with no major complications and good rates of success and recurrence in our multicenter experience.

The Cost-Effectiveness of First-Line Cryoablation versus First-Line Antiarrhythmic Drugs in Canadian Patients with Paroxysmal Atrial Fibrillation.

BACKGROUND: The EARLY-AF (NCT02825979), STOP AF First (NCT03118518), and Cryo-FIRST (NCT01803438), randomized controlled trials (RCTs) demonstrated that cryoballoon pulmonary vein isolation reduces atrial fibrillation (AF) recurrence compared with antiarrhythmic drugs (AADs) in patients with symptomatic paroxysmal AF (PAF). This study developed a cost-effectiveness model (CEM) of first-line cryoablation compared with first-line AADs for PAF, from a Canadian healthcare payer's perspective. METHODS: Data from the three RCTs were analysed to estimate key CEM parameters. The model structure used a decision tree for the first 12 months and a Markov model, with a three-month cycle length, for the remaining lifetime time horizon. Costs were set at 2023 Canadian dollars, health benefits were expressed as quality-adjusted life years (QALYs), and both were discounted 3% annually. Probabilistic sensitivity analysis (PSA) considered parameter uncertainty. RESULTS: The statistical analysis estimated that first-line cryoablation generates a 47% reduction (p<0.001) in the rate of AF recurrence, a 73% reduction in the rate of subsequent ablation (p<0.001), and a 4.3% (p=0.025) increase in health-related quality of life (HRQoL), compared with first-line AADs. The PSA indicates that an individual treated with first-line cryoablation accrues less costs (-$3,862) and more QALYs (0.19) compared with first-line AADs. Cryoablation is cost saving in 98.4% of PSA iterations and has a 99.9% probability of being cost-effective at a cost-effectiveness threshold of $50,000 per QALY gained. Cost-effectiveness results were robust to changes in key model parameters. CONCLUSION: First-line cryoballoon ablation is cost-effective when compared with AADs for patients with symptomatic PAF.

Catheter ablation in patients with paroxysmal atrial fibrillation and absence of structural heart disease: A meta-analysis of randomized trials.

Introduction: Rhythm control strategy in paroxysmal atrial fibrillation (AF) can be performed with antiarrhythmic drugs (AAD) or catheter ablation (CA). Nevertheless, a clear overview of the percentage of freedom from AF over time and complications is lacking. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) comparing CA versus AAD. Methods: We searched databases up to 5 May 2023 for RCTs focusing on CA versus AAD. The study endpoints were atrial tachyarrhythmia (AT) recurrence, progression to persistent AF, overall complications, stroke/TIA, bleedings, heart failure (HF) hospitalization and all-cause mortality. Results: Twelve RCTs enrolling 2393 patients were included. CA showed a significantly lower AT recurrence rate at one year [27.4 % vs 56.3 %; RR: 0.45; p < 0.00001], at two years [39.9 % vs 62.7 %; RR: 0.56; p = 0.0004] and at three years [45.7 % vs 80.9 %; RR: 0.54; p < 0.0001] compared to AAD. Furthermore, CA significantly reduced the progression to persistent AF [1.6 % vs 12.9 %; RR: 0.14; p < 0.00001] with no differences in overall complications [5.9 % vs 4.5 %; RR: 1.27; p = 0.22], stroke/TIA [0.6 % vs 0.6 %; RR: 1.10; p = 0.86], bleedings [0.4 % vs 0.6 %; RR: 0.90; p = 0.84], HF hospitalization [0,3% vs 0,7%; RR: 0.56; p = 0.37] and all-cause mortality [0,4% vs 0.5 %; RR: 0.78; p = 0.67]. Subgroup analysis between radiofrequency and cryo-ablation or considering RCTs with CA as first-line treatment showed no significant differences. Conclusion: CA demonstrated lower rates of AT recurrence over the time, as well as a significant reduction in the progression from paroxysmal to persistent AF, with no difference in terms of energy source, complications, and clinical outcomes.