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BACKGROUND: The clinical outcome of pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF) is suboptimal. Mapping studies have demonstrated atrial sites outside of the pulmonary veins displaying focal activation patterns during AF. We sought to determine whether adding catheter ablation of focal activation sites to PVI improves clinical outcomes of catheter ablation for persistent AF. METHODS: In this multicenter, randomized, single-blinded trial, we assigned patients with persistent AF to either PVI alone or to mapping-guided ablation of focal activation sites in addition to PVI in a 1:1 ratio. In the mapping-guided group, both atria were mapped after PVI using a Pentaray catheter (Biosense-Webster) and focal activation sites identified by CARTOFINDER (Biosense-Webster) were ablated. The primary end point was freedom from AF or atrial tachycardia without antiarrhythmic drugs beyond a 90-day blanking period. RESULTS: A total of 98 patients were assigned to the mapping-guided group and 102 to the PVI alone group. In the mapping-guided group, focal activation sites were identified at 2.6±0.3 and 2.5±0.2 sites per patient in the left and right atrium, respectively. Patients were followed up for 768.5 (interquartile range, 723.75-915.75) and 755.5 days (interquartile range, 728.5-913.75) in the mapping-guided ablation and the PVI alone groups, respectively. Freedom from AF/atrial tachycardia without antiarrhythmic drugs at 2-year follow-up was 66.8% and 75.2% in the mapping-guided ablation and the PVI alone groups, respectively (hazard ratio, 1.26 [95% CI, 0.76-2.10]; P=0.37). Adverse events occurred in 3 patients (3.0%) and none (0%) in the mapping-guided ablation and the PVI alone groups, respectively (P=0.12). CONCLUSIONS: In patients with persistent AF, the addition of mapping-guided ablation of focal activation sites to PVI did not improve clinical outcomes compared with PVI alone. REGISTRATION: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/index.cgi?function=02; Unique identifier: UMIN000037569.

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Understanding the initiating role of pulmonary veins in atrial fibrillation (AF) has led to the development of pulmonary vein isolation (PVI). The efficacy of PVI is high for paroxysmal AF, whereas it is limited for non-paroxysmal AF. This fact highlights the necessity of understanding the mechanism through which AF is maintained, to develop ablation strategies that would be required in addition to the PVI. Mapping AF in animal models and humans has led to the identification of focal or rotational drivers. New technologies have been developed to identify those AF drivers and are used as a guide for catheter ablation. This review article aims to provide a comprehensive overview of the current state of knowledge regarding AF drivers and the various mapping approaches used to identify them.

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BACKGROUND: The FlexAbility™ SE catheter has a laser-cut 8Fr 4-mm flexible tip irrigated through laser-cut kerfs with a thermocouple 0.3 mm from the distal end. The TactiCath™ SE catheter has an 8Fr 3.5-mm tip and 6-irrigation port with a thermocouple 2.67 mm proximal to the tip. We investigated the impact of these differences on the efficacy and safety of radiofrequency (RF) applications. METHODS: RF applications at a range of powers (20 W, 30 W, and 40 W), contact forces (5 g, 15 g, and 25 g), and durations (10-60 s) using perpendicular/parallel catheter orientation were performed in excised porcine hearts. Lesion characteristics and incidence of steam pops were compared. RESULTS: A total of 540 lesions were examined. The FlexAbility™ SE catheter produced smaller lesion depths (4.0 mm vs. 4.4 mm, p = 0.014 at 20 W; 4.6 mm vs. 5.6 mm, p = 0.015 at 30 W), surface areas (22.7mm2 vs. 29.2mm2 at 20 W, p = 0.005; 23.2mm2 vs. 28.7mm2, p = 0.009 at 30 W), and volumes (126.1mm3 vs. 175.1mm3, p = 0.018 at 20 W; 183.2mm3 vs. 304.3mm3, p = 0.002 at 30 W) with perpendicular catheter placement. However, no differences were observed with parallel catheter placement. Steam-pops were significantly less frequently observed with the FlexAbility™ SE catheter (4% vs. 22%, p < 0.001) irrespective of catheter direction to the tissue. Multivariate analysis showed that use of the TactiCath™ SE catheter, power ≥ 40 W, contact force ≥ 25 g, RF duration > 30 s, parallel angle, and impedance drop ≥ 20Ω were significantly associated with occurrence of steam-pops. CONCLUSIONS: The FlexAbility™ SE catheter reduced the risk of steam-pops but produced smaller lesions with perpendicular catheter placement compared to the TactiCath™ SE catheter.

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Background: Contrast-enhanced computed tomography (CT) is commonly used to diagnose pulmonary embolism (PE). However, a history of iodine contrast allergy presents a dilemma in the management of patients with PE. As an alternative approach, X-ray fluoroscopic video analysis has been recently reported to be useful in diagnosing PE. Case summary: A 78-year-old man with dyspnoea of 1-month duration visited our hospital. His oxygen saturation was 89%, and echocardiography demonstrated right heart strain. We could not perform contrast-enhanced CT because the patient had a history of contrast allergy and refused to undergo premedicated contrast CT with anti-histamine and/or corticosteroid. Therefore, a video analysis of pulmonary circulation using dynamic chest X-ray (DCR) was performed. The reconstructed pseudo-colour video showed defects of pulmonary circulation in both lung areas. We diagnosed PE and started anticoagulant therapy. Multiple segmental defects were also observed in pulmonary perfusion scintigraphy on Day 3, which confirmed the diagnosis of PE. He was discharged on Day 9, and an improvement of the pulmonary circulation as assessed with DCR was observed. He had no symptoms at the last follow-up visit at 1 year after discharge. Discussion: We describe the successful visualization of PE using DCR in a patient with iodine contrast allergy.

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BACKGROUND: Recent studies have found that atrial fibrillation (AF) is a risk factor for cognitive impairment. Brain hypoperfusion is hypothesized as an underlying mechanism of cognitive decline in AF patients. OBJECTIVES: This study sought to assess changes in cerebral blood flow (CBF) and brain volume after catheter ablation of AF. METHODS: Patients undergoing catheter ablation of AF were enrolled in this prospective study. AF patients being treated with pharmaceuticals alone served as a control group. Brain magnetic resonance imaging was performed before and 6 months after catheter ablation. CBF was assessed by 2-dimensional phase-contrast magnetic resonance angiography. Brain volume and bilateral hippocampal volume were measured using FreeSurfer software. RESULTS: Of the 57 study patients (age 64 ± 11 years; 45 men; paroxysmal AF: n = 22; nonparoxysmal AF: n = 35), 48 patients were freed from tachyarrhythmia recurrence beyond a 3-month blanking period. Changes in CBF and brain perfusion over 6 months were significantly greater in the study patients than control (CBF: 39.26 vs -34.86 mL; P = 0.01, ANCOVA; brain perfusion: 3.78 vs -3.02 mL/100 mL/min; P = 0.009, ANCOVA), while changes in total brain volume and bilateral hippocampal volume were similar between 2 groups (total brain volume: 2.57 vs -2.15 mL; P = 0.32, ANCOVA; bilateral hippocampal volume: 0.03 vs 0.04 mL; P = 0.8, ANCOVA). Nonparoxysmal AF at baseline was an independent predictor of an increase in CBF of >32.6 mL/min. CONCLUSIONS: Catheter ablation of AF has favorable effects on CBF, particularly in nonparoxysmal AF. Our results may partially explain the association between cognitive decline and AF.

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BACKGROUND: Although differential pacing conventionally has been used to confirm the achievement of block across linear lesion sets, high-resolution mapping demonstrates that pseudo-block is observed in 20%-30% of cases. OBJECTIVES: The purpose of this study was to examine the reliability and versatility of a method using "activation vectors" based on omnipolar technology to confirm the block line. METHODS: Linear ablation was performed during pacing, with the HD Grid catheter (Abbott) placed beside the linear lesion opposite the pacing site. The endpoint of complete linear lesion was complete inversion of the activation vectors to the opposite direction. When inversion of the activation vectors was not observed after 10 minutes of radiofrequency (RF) application, high-resolution mapping was performed to assess whether complete block was achieved. RESULTS: In 33 patients, 24 cavotricuspid isthmus lines, 11 mitral isthmus (MI) lines, 16 posterior lines, and 2 intercaval lines were performed using this method. Of the total of 53 lines, 10 (18.9%) required intermediate evaluation of the block line with high-resolution mapping because of the absence of inversion of activation vectors despite 10 minutes of RF application, resulting in incomplete block with endocardial gaps or epicardial conductions. Additional RF applications finally achieved inversion in direction of activation vectors in the 10 lines. In total, the present method can diagnose achievement of complete block line with 100% accuracy, whereas conventional differential pacing misdiagnosed incomplete block with epicardial conduction in posterior lines in 3 cases and in MI lines in 2 cases. CONCLUSION: Confirmation of complete linear lesions using "activation vectors" based on omnipolar technology is a reliable and versatile method.

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PURPOSE: Local impedance (LI) measurement from an ablation catheter is useful in predicting lesion size and acute success of pulmonary vein isolation (PVI). The LI variation can be described by absolute LI drop (ΔLID) or ΔLID/initial LI (%LID). We evaluated the utility of these parameters in predicting acute lesion durability during PVI using a novel catheter capable of measuring both LI and contact force (CF). METHODS: PVI with a targeted CF, power, and duration was performed in 23 consecutive patients with paroxysmal atrial fibrillation. LI was blinded to operators during ablation. Parameters for each RF application were collected and compared for acute successful lesions and gaps. RESULTS: A total of 1633 RF applications including 97 (5.9%) gap lesions were analyzed. Successful lesions were more frequently observed at non-carinal sites and those with higher contact force, FTI, initial LI, and larger variation of LI and generator impedance (GI). Multivariate analysis demonstrated that absolute GI drop (ΔGID) [OR 1.09 (1.04-1.15), p < 0.001], ΔLID [1.12 (1.09-1.16), p < 0.001], ΔGID/initial GI (%GID) [OR 1.04 (1.01-1.07), p = 0.01], and %LID [OR 1.15 (1.12-1.28), p < 0.001] were significantly associated with successful lesions, and carinal site [OR 0.15(0.09-0.24), p < 0.001] was significantly related to gaps. Both ΔLID and %LID equally predicted the acute durability of lesions during PVI. ΔLID ≥ 24Ω and %LID ≥ 15% at the carina, and ΔLID ≥ 21Ω and %LID ≥ 14% at non-carinal sites significantly predicted acute successful lesions with negative predictive values of 93-99%. CONCLUSIONS: Both ΔLID and %LID were equally useful in predicting acute successful lesions during PVI. Larger cut-off values should be applied to carinal sites.

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AIMS: The efficacy of left atrial posterior wall isolation (PWI) is controversial. Lesion durability may be a major cause of arrhythmia recurrence. The use of the lesion size prediction module improves lesion durability. This study aimed to compare the clinical outcomes of pulmonary vein isolation (PVI) alone and PWI in addition to PVI (PVI + PWI) in patients with non-paroxysmal atrial fibrillation (AF) using a lesion size prediction module. METHODS AND RESULTS: This study is a sub-analysis of the recently published prospective multicentre observational study called ALCOHOL-AF (association of alcohol consumption with outcome of catheter ablation of AF). In this sub-analysis, patients with non-paroxysmal AF in whom PVI alone or PVI + PWI was performed using the lesion size prediction module were included. Freedom from atrial tachyarrhythmia was compared between PVI alone and PVI + PWI groups using propensity score analyses. Of the 3474 patients registered in the ALCOHOL-AF study, 572 patients (age 65.6 ± 10.1 years, male 77.4%, longstanding persistent AF 25.5%) were included in this sub-analysis. We selected 212 patients treated with PVI alone and 212 treated with PVI + PWI using one-to-one propensity score matching. During the follow-up period, atrial tachyarrhythmia recurrence was documented in 92 (43.4%) and 50 (23.6%) patients in the PVI alone and PVI + PWI groups, respectively. Freedom from atrial tachyarrhythmia recurrence without anti-arrhythmic drugs after a single procedure was significantly higher in PVI + PWI than in PVI alone groups (hazard ratio: 0.452, 95% confidence interval: 0.308-0.664, P < 0.001). CONCLUSION: In this hypothesis-generating study, lesion size prediction module-guided PVI + PWI was associated with better clinical outcomes than PVI alone in patients with persistent or longstanding persistent AF.

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PURPOSE: Atrial fibrillation (AF) mainly originates from the pulmonary vein (PV). However, some AF triggers originate from other sites, namely non-PV foci, which are related to recurrence after AF ablation. This study aimed to evaluate the effects of isolation feasibility (isolability) of non-PV foci on the efficacy of AF ablation. METHODS: Overall, 1855 patients with AF (age, 64.6 ± 10.9 years; 82% paroxysmal) underwent PV isolation, followed by induction and ablation of non-PV foci. Among them, 545 (29%) patients had non-PV foci; these patients were categorized into those with isolable non-PV foci (n = 196, 36%) and those with non-isolable non-PV foci (n = 349, 64%). RESULTS: During a mean follow-up of 31.2 ± 15.6 months, recurrence was higher in the non-isolable group than in the isolable group (34% vs. 19%, P < 0.01). Kaplan-Meier analyses revealed a significantly better 1-year clinical outcome in the isolable group than in the non-isolable group (88.0% vs. 78.4%, P < 0.001; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.39-0.81). This outcome was not inferior to that of patients without non-PV foci (88.3% vs. 90.8%, P = 0.81). The non-isolable group showed poorer clinical outcomes than patients without non-PV foci (78.4% vs. 90.8%, P < 0.001; HR, 1.37; 95% CI, 1.22-1.53). Cox regression analysis revealed that isolability (HR, 0.56; 95% CI, 0.36-0.89) and unmappability (HR, 2.89; 95% CI, 1.55-5.37) of non-PV foci were significant predictors of arrhythmia recurrence. CONCLUSION: The isolability of non-PV foci was a significant factor affecting the achievement of better clinical outcomes following AF ablation in patients with non-PV foci.

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BACKGROUND: Atrial anti-tachycardia pacing (A-ATP) of the right atrium (RA) has been shown to decrease the burden of atrial fibrillation (AF) in patients with dual-chamber pacemakers. The aim of this study is to identify the novel predictors of effective A-ATP for terminating AF in patients with AF undergoing catheter ablation. METHODS: This study included 41 consecutive patients undergoing a first ablation procedure for paroxysmal (PAF: n = 21) or persistent (PEF: n = 20) AF. We prospectively evaluated predictors of AF termination after A-ATP. The coefficient of variation (CoV = SD/mean × 100) of the dominant frequencies (DFs) was calculated to evaluate the variability in atrial activation. RESULTS: AF was terminated by A-ATP in 29% of PAF and 5% of PEF patients. In these patients, simultaneous high-rate pacing from the RA and the coronary sinus (CS) terminated AF in 71% of patients, in whom the mean AF cycle length (CL) before A-ATP was longer (214 ± 23 vs. 177 ± 35 ms, p = 0.02) and became slower after A-ATP (234 ± 37 vs. 176 ± 32 ms, p < 0.01), compared to unsuccessful patients. The CoV of the DFs before A-ATP were lower in both RA (6.2 ± 2.0 vs. 15.3 ± 7.9, p = 0.02) and CS (11.0 ± 7.9 vs. 24.3 ± 9.3, p < 0.01) in successful patients. CONCLUSIONS: Simultaneous biatrial A-ATP from the RA and CS could terminate AF in patients with PAF. The predictors for successful termination include longer AF CL and higher AF stability.

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Abstract We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (I) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (I) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e. g. catheter­electrode combinations) for signal processing (e. g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future.

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BACKGROUND: Although ablation energy (AE) and force-time integral (FTI) are well-known active predictors of lesion characteristics, these parameters do not reflect passive tissue reactions during ablation, which may instead be represented by drops in local impedance (LI). This study aimed to investigate if additional LI data improves predicting lesion characteristics and steam pops. METHODS: RF applications at a range of powers (30 W, 40 W, and 50 W), contact forces (8 g, 15 g, 25 g, and 35 g), and durations (10-180 s) using perpendicular/parallel catheter orientations were performed in excised porcine hearts (N = 30). The correlation between AE, FTI, and lesion characteristics was examined, and the impact of LI (%LI drop (%LID) defined by the ΔLI divided by the initial LI) was additionally assessed. RESULTS: Three hundred seventy-five lesions without steam pops were examined. Ablation energy (W × s) and FTI (g × s) showed a positive correlation with lesion depth (ρ = 0.824:P < 0.0001 and ρ = 0.708:P < 0.0001), surface area (ρ = 0.507:P < 0.0001 and ρ = 0.562:P < 0.0001), and volume (ρ = 0.807:P < 0.0001 and ρ = 0.685:P < 0.0001). %LID also showed a positive correlation individually with lesion depth (ρ = 0.643:P < 0.0001), surface area (ρ = 0.547:P < 0.0001), and volume (ρ = 0.733:P < 0.0001). However, the combined indices of AE × %LID (AE multiplied by %LID) and FTI × %LID (FTI multiplied by %LID) provided significantly stronger correlation with lesion depth (ρ = 0.834:P < 0.0001 and ρ = 0.809:P < 0.0001), surface area (ρ = 0.529:P < 0.0001 and ρ = 0.656:P < 0.0001), and volume (ρ = 0.864:P < 0.0001 and ρ = 0.838:P < 0.0001). This tendency was observed regardless of the catheter placement (parallel/perpendicular). AE (P = 0.02) and %LID (P = 0.002) independently remained as significant predictors to predict steam pops (N = 27). However, the AE × %LID did not increase the predictive power of steam pops compared to the AE alone. CONCLUSION: LI, when combined with conventional parameters (AE and FTI), may provide stronger correlation with lesion characteristics.

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PURPOSE: Clinical implication of local impedance (LI) for radiofrequency (RF) ablation has not been fully established. This study aimed to investigate this point using IntellaNav MiFi OITM catheter. METHODS: LI and generator impedance drops (ΔLI and ΔGI) were evaluated in excised porcine hearts (N = 16) during RF applications at a range of powers (30 and 50 W), contact forces (5-40 g), and durations (10-180 s) using perpendicular or parallel catheter orientation. Additionally, temporal LI changes were assessed. RESULTS: Of the 240 lesions without steam pops (92.3%), ΔLI showed better correlations with lesion surface area (ρ = 0.55 vs 0.36, P = 0.004), maximum depth (ρ = 0.53 vs 0.14, P < 0.001), and lesion volume (ρ = 0.64 vs 0.23, P < 0.001) than ΔGI. Furthermore, %LI-drop (ΔLI/initial LI) demonstrated stronger correlations with lesion surface area (ρ = 0.60 vs 0.55, P < 0.001), maximum depth (ρ = 0.57 vs 0.53, P < 0.001), and volume (ρ = 0.69 vs 0.64, P < 0.001) than ΔLI. Parallel catheter orientation improved correlation of ΔLI with lesion surface area (ρ = 0.63 vs 0.40, P = 0.015) and depth (ρ = 0.68 vs 0.45, P = 0.008) and created a larger surface lesion (36.3[29.2-42.7] mm2 vs 28.8[21.6-34.2] mm2, P < 0.001) than the perpendicular. LI of the lesions significantly differed between baseline, immediately after RF, and 5 min after (P < 0.01). LI reaching plateau, larger initial LI, ΔLI, and %LI-drop, and larger RF power and longer duration were observed in pop lesions (P < 0.05). CONCLUSIONS: %LI-drop demonstrated a better correlation with lesion size than ΔLI. LI may be used as an additional parameter to predict lesion size and steam pops. Temporal variation and catheter orientation should be considered to interpret LI.

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We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (i) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (i) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e.g. catheter-electrode combinations) for signal processing (e.g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future.

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The consensus of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation (AF) has been published in 2017 which provided useful clinical guidance for cardiologists, neurologists, geriatricians, and general practitioners in the Asia-Pacific region. In these years, many important new data regarding stroke prevention in AF were reported. The practice guidelines subcommittee members comprehensively reviewed updated information on stroke prevention in AF, and summarized them in this 2021 focused update of the 2017 consensus guidelines of the APHRS on stroke prevention in AF. We highlighted and focused on several issues, including the importance of the AF Better Care pathway, the advantages of non-vitamin K antagonist oral anticoagulants (NOACs) for Asians, the considerations of use of NOACs for Asian AF patients with single one stroke risk factor beyond gender, the role of lifestyle factors on stroke risk, the use of oral anticoagulants during the "coronavirus disease 2019" pandemic, etc. We fully realize that there are gaps, unaddressed questions, and many areas of uncertainty and debate in the current knowledge of AF, and the physician's decision remains the most important factor in the management of AF.

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The consensus of the Asia Pacific Heart Rhythm Society (APHRS) on stroke prevention in atrial fibrillation (AF) has been published in 2017 which provided useful clinical guidance for cardiologists, neurologists, geriatricians, and general practitioners in Asia-Pacific region. In these years, many important new data regarding stroke prevention in AF were reported. The Practice Guidelines subcommittee members comprehensively reviewed updated information on stroke prevention in AF, and summarized them in this 2021 focused update of the 2017 consensus guidelines of the APHRS on stroke prevention in AF. We highlighted and focused on several issues, including the importance of AF Better Care (ABC) pathway, the advantages of non-vitamin K antagonist oral anticoagulants (NOACs) for Asians, the considerations of use of NOACs for Asian patients with AF with single 1 stroke risk factor beyond gender, the role of lifestyle factors on stroke risk, the use of oral anticoagulants during the "coronavirus disease 2019" (COVID-19) pandemic, etc. We fully realize that there are gaps, unaddressed questions, and many areas of uncertainty and debate in the current knowledge of AF, and the physician's decision remains the most important factor in the management of AF.

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A 58-year-old woman with nonischemic cardiomyopathy underwent an ablation for refractory ventricular fibrillation (VF). In addition to elimination of the premature ventricular contraction triggering VF, substrate ablation entailed elimination of dormant Purkinje potentials, which were unmasked in regions where local pacing revealed a narrow QRS with stimulus QRS latency. VF trigger and abnormal Purkinje ablation completely eliminated the refractory VF. (Level of Difficulty: Intermediate.).

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BACKGROUND: Brugada syndrome (BrS) is associated with mutations in the cardiac sodium channel gene, SCN5A. However, genetic studies of patients with BrS with arrhythmic events have been limited. We sought to compare various clinical, ECG, and electrophysiological parameters according to SCN5A genotype in a large cohort of BrS probands with first arrhythmic event. METHODS: Survey on Arrhythmic Events in Brugada Syndrome is a survey of 10 Western and 4 Asian countries, gathering 678 patients with BrS with first arrhythmic event. Only probands were included, and SCN5A genotype adjudicated. Patients without appropriate genetic data were excluded. Associations of genotype with clinical features were analyzed. RESULTS: The study group comprised 392 probands: 92 (23.5%) SCN5A+(44 pathogenic/likely pathogenic [P/LP] and 48 variants of unknown significance) and 300 (76.5%) SCN5A-.SCN5A missense variants and the patients hosting them were similar regardless of adjudication. A higher proportion of patients with P/LP were pediatric (<16 years) compared with SCN5A- (11.4% versus 3%, P=0.023). The proportion of females was higher among patients with P/LP compared with SCN5A- (18.2% versus 6.3%, P=0.013). P/LP probands were more likely to have a family history of sudden cardiac death compared with SCN5A- (41.9% versus 16.8%, P<0.001). A higher proportion of patients with P/LP were White compared with SCN5A- (87.5% versus 47%, P<0.001). Ethnicity (odds ratio, 5.41 [2.8-11.19], P<0.001) and family history of sudden cardiac death (odds ratio, 2.73 [1.28-5.82], P=0.009) were independent variables associated with P/LP genotype following logistic regression. CONCLUSIONS: The genetic basis of BrS has a complex relationship with gender, ethnicity, and age. Probands hosting a P/LP variant tended to experience their first arrhythmic event at a younger age and to have events triggered by fever compared with patients with SCN5A-. In addition, they were more likely to be White and to have family history of sudden cardiac death. Among females, a P/LP variant suggests an increased risk of being symptomatic. This association should be further studied on an ethnically specific basis in large prospectively collected international cohorts.

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[Figure: see text].

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