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BACKGROUND: Recurrence during the 3-month blanking period following radiofrequency ablation of atrial fibrillation (AF) is typically not considered as a predictor for late recurrence. OBJECTIVE: We investigated the significance of early recurrence as a risk factor for late recurrence in AF patients receiving pulsed-field ablation (PFA). METHODS: Consecutive patients undergoing PFA were prospectively followed-up for 1 year. All patients received isolation of pulmonary veins. Additional ablations were performed per operator's discretion. Following the procedure all remained on their previously ineffective antiarrhythmic drugs (AAD) during the 2-month blanking period after which the AADs were discontinued. Early recurrence was defined as atrial arrhythmia of > 30 second duration during the 3-mo blanking period and any recurrence beyond 3-mo was considered as late recurrence. RESULTS: A total of 337 patients undergoing PFA for AF were included. Early recurrence was recorded in 53 (15.7%) patients; 10 in the 1st month, 12 in the 2nd month and 31 in the 3rd month. Of the 10 patients having recurrence during the 1st month, 7 (70%) remained in sinus rhythm after cardioversion whereas 3 (30%) underwent redo because of late-recurrence. At 1 year, all patients with recurrence during the 2nd and 3rd month, experienced late-recurrence of which 10/12 and 27/31 underwent redo and the remaining 6 patients were in sinus on-AAD. CONCLUSION: In this consecutive series of AF patients, early-recurrence in the 2nd or 3rd month following the PFA procedure was associated with high risk of late-recurrence. Thus, blanking period could be redefined as 1-month following PFA.
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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.
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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.
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Background: This study was conducted to evaluate compliance with guideline-directed optimal medical therapy (OMT) and its association with early implantable cardioverter-defibrillator (ICD) activation in patients with heart failure and reduced ejection fraction (HFrEF). Methods: Retrospective data from 307 patients who underwent ICD implantation for primary prevention from 2011 to 2017 were collected and analyzed. Results: Among the study participants, only 23.8% received the maximum tolerated dose of OMT prior to ICD implantation, with 59.0% receiving all three OMT medication groups. No significant difference in OMT compliance was found between patients with ischemic cardiomyopathy (ICM) and those with non-ischemic dilated cardiomyopathy (DCM). However, DCM patients received ICDs more frequently at the time of diagnosis than ICM patients (13.8% vs. 0.7%). Early ICD activation (within 3 months) occurred in only one patient who had not received appropriate OMT, representing 0.7% of all ICM patients. Furthermore, early activation was also infrequent in patients who received OMT (2.9% of ICM patients and 2.6% of DCM patients). Echocardiography follow-up data revealed that 20.4% of ICM patients and 29.8% of DCM patients who did not receive OMT before ICD implantation showed improvement in the left ventricular ejection fraction (EF) to 35% or more. Conclusions: This study found suboptimal compliance with OMT prior to ICD implantation in HFrEF patients. The results showed that early ICD activation was rare in all patient groups, especially those who did not receive the prescribed 3 months of OMT. More research is needed to investigate longer waiting periods for the evaluation of potential EF improvement, and to better evaluate the eligibility of HFrEF patients for ICD. The current findings have potential implications for clinical practice and patient outcomes.
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Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for ~1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Humans , Atrial Fibrillation/surgery , Atrial Fibrillation/therapy , Female , Male , Middle Aged , Catheter Ablation/adverse effects , Catheter Ablation/methods , Aged , Treatment Outcome , Postoperative Complications/epidemiology , Postoperative Complications/etiologyABSTRACT
INTRODUCTION: Three randomised controlled trials (RCTs) have demonstrated that first-line cryoballoon pulmonary vein isolation decreases atrial tachycardia in patients with symptomatic paroxysmal atrial fibrillation (PAF) compared with antiarrhythmic drugs (AADs). The aim of this study was to develop a cost-effectiveness model (CEM) for first-line cryoablation compared with first-line AADs for the treatment of PAF. The model used a Danish healthcare perspective. METHODS: Individual patient-level data from the Cryo-FIRST, STOP AF and EARLY-AF RCTs were used to parameterise the CEM. The model structure consisted of a hybrid decision tree (one-year time horizon) and a Markov model (40-year time horizon, with a three-month cycle length). Health-related quality of life was expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3% per year. Model outcomes were produced using probabilistic sensitivity analysis. RESULTS: First-line cryoablation is dominant, meaning it results in lower costs (-2,663) and more QALYs (0.18) when compared to first-line AADs. First-line cryoablation also has a 99.96% probability of being cost-effective, at a cost-effectiveness threshold of 23,200 per QALY gained. Regardless of initial treatment, patients were expected to receive â¼ 1.2 ablation procedures over a lifetime horizon. CONCLUSION: First-line cryoablation is both more effective and less costly (i.e. dominant), when compared with AADs for patients with symptomatic PAF in a Danish healthcare system.
Subject(s)
Anti-Arrhythmia Agents , Atrial Fibrillation , Cost-Benefit Analysis , Cryosurgery , Drug Costs , Markov Chains , Models, Economic , Quality of Life , Quality-Adjusted Life Years , Randomized Controlled Trials as Topic , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Atrial Fibrillation/economics , Atrial Fibrillation/therapy , Atrial Fibrillation/drug therapy , Atrial Fibrillation/physiopathology , Humans , Cryosurgery/economics , Cryosurgery/adverse effects , Denmark , Anti-Arrhythmia Agents/therapeutic use , Anti-Arrhythmia Agents/economics , Treatment Outcome , Time Factors , Male , Female , Middle Aged , Decision Support Techniques , Aged , Pulmonary Veins/surgery , Pulmonary Veins/physiopathology , Cost Savings , Decision TreesABSTRACT
BACKGROUND AND AIMS: Cardiac ablation is a well-established method for treating atrial fibrillation (AF). Pulsed field ablation (PFA) is a non-thermal therapeutic alternative to radiofrequency ablation (RFA) and cryoballoon ablation (CRYO). PFA uses high-voltage electric pulses to target cells. The present analysis aims to quantify the costs, outcomes, and resources associated with these three ablation strategies for paroxysmal AF. METHODS: Real-world clinical data were prospectively collected during index hospitalization by three European medical centers (Belgium, Germany, the Netherlands) specialized in cardiac ablation. These data included procedure times (pre-procedural, skin-to-skin and post-procedural), resource use, and staff burden. Data regarding complications associated with each of the three treatment options and redo procedures were extracted from the literature. Costs were collected from hospital economic formularies and published cost databases. A cost-consequence model from the hospital perspective was built to estimate the impact of the three treatment options in terms of effectiveness and costs. RESULTS: Across the three centers, N = 91 patients were included over a period of 12 months. A significant difference was seen in pre-procedural time (mean ± SD, PFA: 13.6 ± 3.7 min, CRYO: 18.8 ± 6.6 min, RFA: 20.4 ± 6.4 min; p < .001). Procedural time (skin-to-skin) was also different across alternatives (PFA: 50.9 ± 22.4 min, CRYO: 74.5 ± 24.5 min, RFA: 140.2 ± 82.4 min; p < .0001). The model reported an overall cost of 216,535 per 100 patients treated with PFA, 301,510 per 100 patients treated with CRYO and 346,594 per 100 patients treated with RFA. Overall, the cumulative savings associated with PFA (excluding kit costs) were 850 and 1,301 per patient compared to CRYO and RFA, respectively. CONCLUSION: PFA demonstrated shorter procedure time compared to CRYO and RFA. Model estimates indicate that these time savings result in cost savings for hospitals and reduce outlay on redo procedures. Clinical practice in individual hospitals varies and may impact the ability to transfer the results of this analysis to other settings.
Subject(s)
Atrial Fibrillation , Catheter Ablation , Cost-Benefit Analysis , Humans , Atrial Fibrillation/surgery , Atrial Fibrillation/economics , Male , Female , Middle Aged , Catheter Ablation/economics , Catheter Ablation/methods , Aged , Operative Time , Prospective Studies , Europe , Cryosurgery/economics , Cryosurgery/methods , Postoperative Complications/economics , Health Resources/statistics & numerical data , Health Resources/economicsABSTRACT
Catheter ablation of septal ventricular tachycardia (VT) is challenging. Pulsed field ablation is a promising technology, potentially reaching deep substrates. We report the first sequential unipolar biventricular pulsed field ablation targeting refractory septal VT. Besides, we illustrate the importance of searching underlying cardiomyopathy in patients with recurrent multiple morphology VTs and normal magnetic resonance imaging.
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BACKGROUND: Brugada Syndrome (BrS) is a life-threatening cardiac arrhythmia disorder associated with an increased risk ventricular arrhythmias (VAs) and sudden cardiac death (SCD). Current management primarily relies on implantable cardioverter-defibrillators (ICDs), but patients may experience ICD shocks. Catheter ablation (CA) has emerged as a potential intervention to target the arrhythmogenic substrate. This systematic review aims to evaluate the safety and efficacy of catheter ablation in BrS patients. METHODS AND RESULTS: Studies with BrS patients undergoing catheter ablation for VAs were included. 14 studies that involved a total population of 709 BrS patients, with catheter ablation performed in 528 of them, were included. Catheter ablation resulted in non-inducibility of VAs in 91% (95% CI: 83-99, I2 = 76%) and resolution of Type 1 ECG Brugada pattern in 88% (95% CI: 81-96.2, I2 = 91%) of the patients. After a mean follow-up of 30.7 months, 87% (95% CI: 80-94, I2 = 82%) of patients remained free from VAs. The incidence of VAs during follow-up was significantly lower in the ablation cohort in comparison to the group receiving only ICD therapy (OR = 0.03, 95% CI: 0.01-0.12, I2 = 0%). CONCLUSION: Catheter ablation shows potential as a therapeutic approach to reduce VAs and improve outcomes in BrS patients. While further research with long follow-up period is required to confirm these findings, it represents a valuable tool as an add-on intervention to ICD implantation in BrS patients with high burden of VAs.Protocol registration: CRD42024506439.
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BACKGROUND: Brugada syndrome (BrS) has been associated with sudden cardiac death in otherwise healthy subjects, and drug-induced BrS accounts for 55% to 70% of all patients with BrS. This study aims to develop a deep convolutional neural network and evaluate its performance in recognizing and predicting BrS diagnosis. METHODS AND RESULTS: Consecutive patients who underwent ajmaline testing for BrS following a standardized protocol were included. ECG tracings from baseline and during ajmaline were transformed using wavelet analysis and a deep convolutional neural network was separately trained to (1) recognize and (2) predict BrS type I pattern. The resultant networks are referred to as BrS-Net. A total of 1188 patients were included, of which 361 (30.3%) patients developed BrS type I pattern during ajmaline infusion. When trained and evaluated on ECG tracings during ajmaline, BrS-Net recognized a BrS type I pattern with an AUC-ROC of 0.945 (0.921-0.969) and an AUC-PR of 0.892 (0.815-0.939). When trained and evaluated on ECG tracings at baseline, BrS-Net predicted a BrS type I pattern during ajmaline with an AUC-ROC of 0.805 (0.845-0.736) and an AUC-PR of 0.605 (0.460-0.664). CONCLUSIONS: BrS-Net, a deep convolutional neural network, can identify BrS type I pattern with high performance. BrS-Net can predict from baseline ECG the development of a BrS type I pattern after ajmaline with good performance in an unselected population.
Subject(s)
Ajmaline , Brugada Syndrome , Deep Learning , Electrocardiography , Humans , Brugada Syndrome/diagnosis , Brugada Syndrome/physiopathology , Brugada Syndrome/chemically induced , Electrocardiography/drug effects , Male , Female , Ajmaline/adverse effects , Middle Aged , Adult , Predictive Value of Tests , Retrospective StudiesABSTRACT
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.
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To date, studies assessing the safety profile of 3D printing materials for application in cardiac ablation are sparse. Our aim is to evaluate the safety and feasibility of two biocompatible 3D printing materials, investigating their potential use for intra-procedural guides to navigate surgical cardiac arrhythmia ablation. Herein, we 3D printed various prototypes in varying thicknesses (0.8 mm-3 mm) using a resin (MED625FLX) and a thermoplastic polyurethane elastomer (TPU95A). Geometrical testing was performed to assess the material properties pre- and post-sterilization. Furthermore, we investigated the thermal propagation behavior beneath the 3D printing materials during cryo-energy and radiofrequency ablation using an in vitro wet-lab setup. Moreover, electron microscopy and Raman spectroscopy were performed on biological tissue that had been exposed to the 3D printing materials to assess microparticle release. Post-sterilization assessments revealed that MED625FLX at thicknesses of 1 mm, 2.5 mm, and 3 mm, along with TPU95A at 1 mm and 2.5 mm, maintained geometrical integrity. Thermal analysis revealed that material type, energy source, and their factorial combination with distance from the energy source significantly influenced the temperatures beneath the 3D-printed material. Electron microscopy revealed traces of nitrogen and sulfur underneath the MED625FLX prints (1 mm, 2.5 mm) after cryo-ablation exposure. The other samples were uncontaminated. While Raman spectroscopy did not detect material release, further research is warranted to better understand these findings for application in clinical settings.
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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.
Subject(s)
Atrial Appendage , Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Septal Occluder Device , Humans , Atrial Appendage/surgery , Atrial Appendage/diagnostic imaging , Pulmonary Veins/surgery , Catheter Ablation/methods , Atrial Fibrillation/surgery , Atrial Fibrillation/physiopathology , Atrial Fibrillation/therapy , Male , FemaleABSTRACT
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.
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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.