Predictors of the need for atrioventricular nodal ablation following redo ablation for atrial fibrillation.

Background: Patients who have recurrent atrial fibrillation (AF) following redo catheter ablation may eventually be managed with a pace-and-ablate approach, involving pacemaker implant followed by atrioventricular nodal ablation (AVNA). We sought to determine which factors would predict subsequent AVNA in patients undergoing redo AF ablation. Methods: We analyzed patients undergoing redo AF ablations between 2013 and 2019 at our institution. Follow-up was censored on December 31, 2021. Patients with no available follow-up data were excluded. Time-to-event analysis with Cox proportional hazard regression was used to compare those who underwent AVNA to those who did not. Results: A total of 467 patients were included, of whom 39 (8.4%) underwent AVNA. After multivariable adjustment, female sex (aHR 4.68 [95% CI 2.30-9.50]; p < 0.001), ischemic heart disease (aHR 2.99 [95% CI 1.25-7.16]; p = 0.014), presence of a preexisting pacemaker (aHR 3.25 [95% CI 1.10-9.60]; p = 0.033), and persistent AF (aHR 2.22 [95% CI 1.07-4.59]; p = 0.032) were associated with increased risk of subsequent AVNA requirement. Conclusion: Female sex, ischemic heart disease, and persistent AF may be useful clinical predictors of the requirement for subsequent AVNA and may be considered as part of shared clinical decision making.

Delineating postinfarct ventricular tachycardia substrate with dynamic voltage mapping in areas of omnipolar vector disarray.

Background: Defining postinfarct ventricular arrhythmic substrate is challenging with voltage mapping alone, though it may be improved in combination with an activation map. Omnipolar technology on the EnSite X system displays activation as vectors that can be superimposed onto a voltage map. Objective: The study sought to optimize voltage map settings during ventricular tachycardia (VT) ablation, adjusting them dynamically using omnipolar vectors. Methods: Consecutive patients undergoing substrate mapping were retrospectively studied. We categorized omnipolar vectors as uniform when pointing in one direction, or in disarray when pointing in multiple directions. We superimposed vectors onto voltage maps colored purple in tissue >1.5 mV, and the voltage settings were adjusted so that uniform vectors appeared within purple voltages, a process termed dynamic voltage mapping (DVM). Vectors in disarray appeared within red-blue lower voltages. Results: A total of 17 substrate maps were studied in 14 patients (mean age 63 ± 13 years; mean left ventricular ejection fraction 35 ± 6%, median 4 [interquartile range 2-8.5] recent VT episodes). The DVM mean voltage threshold that differentiated tissue supporting uniform vectors from disarray was 0.27 mV, ranging between patients from 0.18 to 0.50 mV, with good interobserver agreement (median difference: 0.00 mV). We found that VT isthmus components, as well as sites of latest activation, isochronal crowding, and excellent pace maps colocated with tissue along the DVM border zone surrounding areas of disarray. Conclusion: DVM, guided by areas of omnipolar vector disarray, allows for individualized postinfarct ventricular substrate characterization. Tissue bordering areas of disarray may harbor greater arrhythmogenic potential.

Cost, efficiency, and outcomes of pulsed field ablation vs thermal ablation for atrial fibrillation: A real-world study.

BACKGROUND: With the exponential growth of catheter ablation for atrial fibrillation (AF), there is increasing interest in associated health care costs. Pulsed field ablation (PFA) using a single-shot pentaspline multielectrode catheter has been shown to be safe and effective for AF ablation, but its cost efficiency compared to conventional thermal ablation modalities (cryoballoon [CB] or radiofrequency [RF]) has not been evaluated. OBJECTIVE: The purpose of this study was to compare cost, efficiency, effectiveness, and safety between PFA, CB, and RF for AF ablation. METHODS: We studied 707 consecutive patients (PFA: 208 [46.0%]; CB: 325 [29.4%]; RF: 174 [24.6%]) undergoing first-time AF ablation. Individual procedural costs were calculated, including equipment, laboratory use, and hospital stay, and compared between ablation modalities, as were effectiveness and safety. RESULTS: Skin-to-skin times and catheter laboratory times were significantly shorter with PFA (68 and 102 minutes, respectively) than with CB (91 and 122 minutes) and RF (89 and 123 minutes) (P < .001). General anesthesia use differed across modalities (PFA 100%; CB 10.2%; RF 61.5%) (P < .001). Major complications occurred in 1% of cases, with no significant differences between modalities. Shorter procedural times resulted in lower staffing and laboratory costs with PFA, but these savings were offset by substantially higher equipment costs, resulting in higher overall median costs with PFA (£10,010) than with CB (£8106) and RF (£8949) (P < .001). CONCLUSION: In this contemporary real-world study of the 3 major AF ablation modalities used concurrently, PFA had shorter skin-to-skin and catheter laboratory times than did CB and RF, with similarly low rates of complications. However, PFA procedures were considerably more expensive, largely because of higher equipment cost.

Durability of thermal pulmonary vein isolation in persistent atrial fibrillation assessed by mandated repeat invasive study.

BACKGROUND: No study has assessed the durability of pulmonary vein isolation (PVI) with radiofrequency (RF) and cryoballoon (CB) in patients with persistent atrial fibrillation. These data are especially lacking for those with significantly diseased left atria (LA). OBJECTIVES: The goals of this study were to assess PVI durability in patients with significant LA disease and to compare reconnection rates between RF and CB. METHODS: Forty-four patients (mean age 63 years; 34 (77%) male; median time since atrial fibrillation diagnosis 22.5 months; median indexed LA volume 36 mL/m2) were randomized 1:1 to RF or CB PVI. A redo procedure using ultra-high-density electroanatomic mapping was mandated at 2 months, where PV reconnections were identified and reisolated. RESULTS: Thirty-eight patients underwent both procedures (CB n = 17; RF n = 21). Index RF procedures were longer (median 158 minutes vs 97 minutes; P < .001) but required less fluoroscopy (9.5 minutes vs 23 minutes; P < .001). At the index RF procedure, a median of 47% of LA myocardium had voltage < 0.5 mV, suggesting that half of the mapped LA comprised scar. PV reconnection was observed in 73 of 152 PVs (48.0%) and was more frequent with CB (58.8%) than with RF (39.3%) (P = .022). Reconnection of at least 1 PV was detected in >75% of patients. Significantly more ablation was required during the redo procedure to reisolate PVs in the CB arm (median 10.8 minutes vs 1.2 minutes; P < .001). CONCLUSION: PVI durability may be poor in those with significant LA scarring and dilatation, even with modern thermal ablation technologies. RF resulted in significantly better PVI durability than did CB in this complex population. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT04111731.

UltraSOUND-based characterization of ventricular tachycardia SCAR and arrhythmogenic substrate: The SOUNDSCAR study.

BACKGROUND: Intracardiac echocardiography (ICE) represents a valuable image integration technique, with the unique advantage of dynamic real-time scar characterization. OBJECTIVES: The goals of this study were to assess the correlation between ICE-defined and electroanatomic mapping (EAM)-defined scar in patients with ischemic cardiomyopathy and to define the outcomes of ICE-guided ventricular tachycardia (VT) ablation. METHODS: Thirty-eight patients with ischemic cardiomyopathy (SOUNDSCAR cohort) underwent full left ventricular (LV) ICE imaging and EAM. ICE-defined scar parameters (end-diastolic and end-systolic wall diameter [EDWD and ESWD], end-systolic wall thickening [percentage difference between EDWD and ESWD with respect to EDWD], slope [end-diastole to end-systole wall thickening], and American Heart Association wall motion scoring) were correlated with EAM-defined scar (voltage <1.5 mV). In a separate cohort (n = 21), outcomes of an ICE-guided VT ablation approach (EAM focused to ICE-defined scar regions) were compared with those of conventional ablation (full left ventricular mapping with EAM only; n = 21). RESULTS: In the 38 SOUNDSCAR patients (mean age 67 ± 11 years; 35 male [92%]; left ventricular ejection fraction 31% ± 10%; 2474 ICE segments; 524 ICE sectors), all ICE-defined parameters strongly predicted EAM-defined scar (area under the curve: American Heart Association score 0.873; ESWD 0.880; EDWD 0.827; slope 0.855; percentage difference between EDWD and ESWD with respect to EDWD, 0.851). All ICE-defined parameters had large effect sizes for predicting EAM-defined scar (logistic regression, P < .001). A detailed topographical comparison of ICE-defined (slope) and EAM-defined scar was possible in 25 patients and demonstrated 88% ± 10% overlap. Compared with conventional VT ablation, ICE-guided ablation was associated with shorter procedure times and comparable VT-free survival (ICE-guided vs conventional: procedure time 240 ± 20 minutes vs 298 ± 39 minutes; P < .001; VT recurrence 3 [14%] vs 7 [31%]; P = .19). CONCLUSION: ICE-defined scar demonstrates a strong correlation with EAM-defined scar. ICE-guided VT ablation is associated with enhanced procedural efficiency.

Silent pulmonary veins at redo ablation for atrial fibrillation: Implications and approaches.

BACKGROUND: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation. Despite promising success rates, redo ablation is sometimes required. At redo, PVs may be found to be isolated (silent) or reconnected. We studied patients with silent vs reconnected PVs at redo and analysed associations with adverse outcomes. METHODS: Patients undergoing redo AF ablations between 2013 and 2019 at our institution were included and stratified into silent PVs or reconnected PVs. The primary outcome was a composite of further redo ablation, non-AF ablation, atrioventricular nodal ablation, and death. Secondary outcomes included arrhythmia recurrence. RESULTS: A total of 467 patients were included with mean 4.6 ± 1.7 years follow-up, of whom 48 (10.3%) had silent PVs. The silent PV group had had more often undergone >1 prior ablation (45.8% vs 9.8%; p<0.001), had more persistent AF (62.5% vs 41.1%; p=0.005) and had more non-PV ablation performed both at prior ablation procedures and at the analysed redo ablation. The primary outcome occurred more frequently in those with silent PVs (25% vs 13.8%; p=0.053). Arrhythmia recurrence was also more common in the silent PV group (66.7% vs 50.6%; p=0.047). After multivariable adjustment, female sex (aHR 2.35 [95% CI 2.35-3.96]; p=0.001) and ischaemic heart disease (aHR 3.21 [95% CI 1.56-6.62]; p=0.002) were independently associated with the primary outcome, and left atrial enlargement (aHR 1.58 [95% CI 1.20-2.08]; p=0.001) and >1 prior ablation (aHR 1.88 [95% CI 1.30-2.72]; p<0.001) were independently associated with arrhythmia recurrence. Whilst a finding of silent PVs was not itself significant after multivariable adjustment, this provides an easily assessable parameter at clinically indicated redo ablation which informs the clinician of the likelihood of a worse future prognosis. CONCLUSIONS: Patients with silent PVs at redo AF ablation have worse clinical outcomes.

An approach to help differentiate postinfarct scar from borderzone tissue using Ripple Mapping during ventricular tachycardia ablation.

BACKGROUND: Ventricular scar is traditionally highlighted on a bipolar voltage (BiVolt) map in areas of myocardium <0.50 mV. We describe an alternative approach using Ripple Mapping (RM) superimposed onto a BiVolt map to differentiate postinfarct scar from conducting borderzone (BZ) during ventricular tachycardia (VT) ablation. METHODS: Fifteen consecutive patients (left ventricular ejection fraction 30 ± 7%) underwent endocardial left ventricle pentaray mapping (median 5148 points) and ablation targeting areas of late Ripple activation. BiVolt maps were studied offline at initial voltage of 0.50-0.50 mV to binarize the color display (red and purple). RMs were superimposed, and the BiVolt limits were sequentially reduced until only areas devoid of Ripple bars appeared red, defined as RM-scar. The surrounding area supporting conducting Ripple wavefronts in tissue <0.50 mV defined the RM-BZ. RESULTS: RM-scar was significantly smaller than the traditional 0.50 mV cutoff (median 4% vs. 12% shell area, p < .001). 65 ± 16% of tissue <0.50 mV supported Ripple activation within the RM-BZ. The mean BiVolt threshold that differentiated RM-scar from BZ tissue was 0.22 ± 0.07 mV, though this ranged widely (from 0.12 to 0.35 mV). In this study, septal infarcts (7/15) were associated with more rapid VTs (282 vs. 347 ms, p = .001), and had a greater proportion of RM-BZ to RM-scar (median ratio 3.2 vs. 1.2, p = .013) with faster RM-BZ conduction speed (0.72 vs. 0.34 m/s, p = .001). Conversely, scars that supported hemodynamically stable sustained VT (6/15) were slower (367 ± 38 ms), had a smaller proportion of RM-BZ to RM-scar (median ratio 1.2 vs. 3.2, p = .059), and slower RM-BZ conduction speed (0.36 vs. 0.63 m/s, p = .036). RM guided ablation collocated within 66 ± 20% of RM-BZ, most concentrated around the RM-scar perimeter, with significant VT reduction (median 4.0 episodes preablation vs. 0 post, p < .001) at 11 ± 6 months follow-up. CONCLUSION: Postinfarct scars appear significantly smaller than traditional 0.50 mV cut-offs suggest, with voltage thresholds unique to each patient.

Incidence of vascular complications for electrophysiology procedures in the ultrasound era: a single-centre experience over 10,000 procedures in the long term.

BACKGROUND: Ultrasound (US) is being increasingly used to guide vascular access for electrophysiology (EP) procedures in many centres. Nonetheless, the incidence and predictors of vascular complications in the US era are limited. In this study, we describe our experience of vascular access-related complications associated with EP procedures which were performed with the routine use of US-guided vascular access. METHODS: A total of 10,158 consecutive EP procedures in 8361 patients performed from April 2014 (when our centre moved to a policy of routine US-guided vascular access for EP procedures) to March 2022 were included. The outcome of interest was any vascular access-related complication that occurred within 7 days of the procedure; these were classified as severe if surgical intervention and/or blood transfusion was required, major if non-surgical intervention or delayed hospital discharge was required, or minor if it did not fulfil the criteria for severe or major. RESULTS: During the study period, 2 (0.02%) severe vascular complications occurred, including 1 pseudo-aneurysm requiring surgery and 1 retroperitoneal haemorrhage requiring blood transfusion. Nine (0.09%) major complications occurred, including 6 hematomas managed by compression devices, 1 type B aortic dissection, 1 AV fistula managed conservatively and 1 haematoma managed conservatively but delayed hospital discharge. Eighteen (0.18%) minor haematomas were seen that did not require any intervention or delayed hospital discharge. On multivariable analysis, female sex [OR (95% CI): 2.5 (1.2, 5.4)] and use of an arterial access [OR (95% CI): 19.3 (7.1, 52.3)] were seen to be independent predictors of the 29 vascular complications. CONCLUSION: With the use of US-guided vascular access in EP procedures, major vascular complications are exceedingly rare, particularly those needing surgical intervention. Our results provide additional evidence for scientific guidelines to support US use.

Impact of COVID-19 on patients awaiting ablation for atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) ablation services were significantly affected by the COVID-19 pandemic. We aimed to evaluate a symptom-based clinician prioritisation scheme for waiting list management compared with patient-completed quality of life (QoL) scores. We also sought to understand factors influencing QoL, particularly the impact of COVID-19, on patients awaiting AF ablation, via a bespoke questionnaire. METHODS: Patients awaiting AF ablation were sent two QoL questionnaires (Atrial Fibrillation Effect on QualiTy of Life (AFEQT) and EuroQol 5D (EQ5D-5L)) and the bespoke questionnaire. At a separate time point, patients were categorised as C1-urgent, C2-priority or C3-routine by their cardiologist based on review of clinic letters. RESULTS: There were 118 patients included with priority categorisation available for 86 patients. Median AFEQT scores were lower in C2 (30.4; 17.2-51.9) vs C3 patients (56.5; 32.1-74.1; p<0.01). Unplanned admission occurred in 3 patients in C3 with AFEQT scores of <40. Although 65 patients had AF symptoms during the pandemic, 43.1% did not seek help where they ordinarily would have. An exercise frequency of ≥3-4 times a week was associated with higher AFEQT (56.5; 41.2-74.1; p<0.001) and EQ5D (0.84; 0.74-0.88; p<0.0001) scores. CONCLUSION: The QoL of patients awaiting AF ablation is impaired and AFEQT helps to identify patients at risk of admission, over and above physician assessment. COVID-19 influenced patients seeking medical attention with symptomatic AF when they normally would. Regular exercise is associated with better QoL in patients awaiting AF ablation.

Complication rates following ventricular tachycardia ablation in ischaemic and non-ischaemic cardiomyopathies: a systematic review.

BACKGROUND: Catheter ablation of ventricular tachycardia (VT) is associated with potential major complications, including mortality. The risk of acute complications in patients with ischaemic cardiomyopathy (ICM) and non-ischaemic cardiomyopathy (NICM) has not been systematically evaluated. METHODS: PubMed was searched for studies of catheter ablation of VT published between September 2009 and September 2019. Pre-specified primary outcomes were (1) rate of major acute complications, including death, and (2) mortality rate. RESULTS: A total of 7395 references were evaluated for relevance. From this, 50 studies with a total of 3833 patients undergoing 4319 VT ablation procedures fulfilled the inclusion criteria (mean age 59 years; male 82%; 2363 [62%] ICM; 1470 [38%] NICM). The overall major complication rate in ICM cohorts was 9.4% (95% CI, 8.1-10.7) and NICM cohorts was 7.1% (95% CI, 6.0-8.3). Reported complication rates were highly variable between studies (ICM I2 = 90%; NICM I2 = 89%). Vascular complications (ICM 2.5% [95% CI, 1.9-3.1]; NICM 1.2% [95% CI, 0.7-1.7]) and cerebrovascular events (ICM 0.5% [95% CI, 0.2-0.7]; NICM, 0.1% [95% CI, 0-0.2]) were significantly higher in ICM cohorts. Acute mortality rates in the ICM and NICM cohorts were low (ICM 0.9% [95% CI, 0.5-1.3]; NICM 0.6% [95% CI, 0.3-1.0]) with the majority of overall deaths (ICM 75%; NICM 80%) due to either recurrent VT or cardiogenic shock. CONCLUSION: Overall acute complication rates of VT ablation are comparable between ICM and NICM patients. However, the pattern and predictors of complications vary depending on the underlying cardiomyopathy.

Relationship between sodium channel function and clinical phenotype in SCN5A variants associated with Brugada syndrome.

The identification of a pathogenic SCN5A variant confers an increased risk of conduction defects and ventricular arrhythmias (VA) in Brugada syndrome (BrS). However, specific aspects of sodium channel function that influence clinical phenotype have not been defined. A systematic literature search identified SCN5A variants associated with BrS. Sodium current (INa ) functional parameters (peak current, decay, steady-state activation and inactivation, and recovery from inactivation) and clinical features (conduction abnormalities [CA], spontaneous VA or family history of sudden cardiac death [SCD], and spontaneous BrS electrocardiogram [ECG]) were extracted. A total of 561 SCN5A variants associated with BrS were identified, for which data on channel function and clinical phenotype were available in 142. In the primary analysis, no relationship was found between any aspect of channel function and CA, VA/SCD, or spontaneous BrS ECG pattern. Sensitivity analyses including only variants graded pathogenic or likely pathogenic suggested that reduction in peak current and positive shift in steady-state activation were weakly associated with CA and VA/SCD, although sensitivity and specificity remained low. The relationship between in vitro assessment of channel function and BrS clinical phenotype is weak. The assessment of channel function does not enhance risk stratification. Caution is needed when extrapolating functional testing to the likelihood of variant pathogenicity.

The feasibility and effectiveness of a streamlined single-catheter approach for radiofrequency atrial fibrillation ablation.

BACKGROUND: Catheter ablation for atrial fibrillation (AF) traditionally requires the use of circular mapping catheter (CMC) for pulmonary vein isolation (PVI). This study aimed to assess the feasibility and effectiveness of a CMC-free approach for AF ablation performed by a contiguous optimized (CLOSE) ablation protocol. METHODS: A CLOSE-guided and CMC-free PVI protocol with a single transseptal puncture was attempted in 67 patients with AF. Left atrial (LA) CARTO voltage mapping was performed with the ablation catheter pre- and postablation to demonstrate entry block into the pulmonary veins, and pacing maneuvers were used to confirm exit block. RESULTS: The CMC-free approach was successful in achieving PVI in 66 (98.5%) cases, with procedure time of 148 ± 32 minutes, ablation time of 27.5 ± 5.7 minutes, and fluoroscopy time of 7.8 ± 1.0 minutes. First-pass PVI was seen in 58(86.5%) patients, and pacing maneuvers successfully identified the residual gap in eight of the other nine cases. No complication was observed. At 12 months follow-up, 60 (89.6%) patients remained free from AF. The CMC-free approach resulted in a cost saving of £47,190. CONCLUSION: A CMC-free CLOSE-guided PVI approach is feasible, safe, and cost-saving, and is associated with excellent clinical outcomes at 1 year.

Same-day discharge in selected patients undergoing atrial fibrillation ablation.

BACKGROUND: Atrial fibrillation (AF) ablation is a complex procedure, generally requiring at least one overnight hospital stay. We investigated the safety and feasibility of early mobilization and same-day discharge following streamlined peri-ablation management for AF. METHODS: From 2014, we offered same-day discharge to selected patients who underwent uncomplicated AF ablation on the morning lists, with ultrasound-guided femoral access, uninterrupted warfarin or minimal interruption in novel oral anticoagulants, and reversal of intraprocedural heparin with protamine. Patients were discharged 6-8 h postprocedure and offered access to a dedicated nurse helpline. RESULTS: Of 1599 AF ablation cases performed from April 2014 to March 2017, 811 (50.7%) were performed on the morning lists and 169/811 (20.8%) were discharged on the same day. Excluding 26 research cases, 1/143 (0.7%) had transient right phrenic nerve palsy and five (3.5%) cases experienced minor problems that did not preclude same-day discharge; three (2.1%) needed rehospitalization postdischarge: one for pericarditic chest pain and two for nausea/vomiting. Compared to 642 overnight cases, day-case procedures were shorter, more likely to be redos, to be performed under sedation rather than general anesthesia, and less likely to involve linear lesions and electrical cardioversion. There were no significant differences in patient age, gender, body mass index, CHA2 DS2 -VASc, in preprocedural anticoagulation regimen (warfarin vs novel anticoagulants vs no anticoagulation) and in choice of ablation method (cryoballoon vs radiofrequency). CONCLUSIONS: Selective same-day discharge after AF ablation is safe and feasible using a streamlined peri-procedural care protocol. Wider adoption can potentially reduce health-care costs while improving patient experience.

Early experience of thoracoscopic vs. catheter ablation for atrial fibrillation.

AIMS: Video-assisted thoracoscopic surgery (VATS) ablation has been advocated as a treatment option for non-paroxysmal atrial fibrillation (AF) in recent guidelines. Real-life data on its safety and efficacy during a centre's early experience are sparse. METHODS AND RESULTS: Thirty patients (28 persistent/longstanding persistent AF) underwent standalone VATS ablation for AF by an experienced thoracoscopic surgeon, with the first 20 cases proctored by external surgeons. Procedural and follow-up outcomes were collected prospectively, and compared with 90 propensity-matched patients undergoing contemporaneous catheter ablation (CA). Six (20.0%) patients undergoing VATS ablation experienced ≥1 major complication (death n = 1, stroke n = 2, conversion to sternotomy n = 3, and phrenic nerve injury n = 2). This was significantly higher than the 1.1% major complication rate (tamponade requiring drainage n = 1) seen with CA (P < 0.001). Twelve-month single procedure arrhythmia-free survival rates without antiarrhythmic drugs were 56% in the VATS and 57% in the CA cohorts (P = 0.22), and 78% and 80%, respectively given an additional CA and antiarrhythmic drugs (P = 0.32). CONCLUSION: During a centre's early experience, VATS ablation may have similar success rates to those from an established CA service, but carry a greater risk of major complications. Those embarking on a programme of VATS AF ablation should be aware that complication and success rates may differ from those reported by selected high-volume centres.

Systematic re-evaluation of SCN5A variants associated with Brugada syndrome.

BACKGROUND: A large number of SCN5A variants have been reported to underlie Brugada syndrome (BrS). However, the evidence supporting individual variants is highly heterogeneous. OBJECTIVE: We systematically re-evaluated all SCN5A variants reported in BrS using the 2015 American college of medical genetics and genomics and the association for molecular pathology (ACMG-AMP) guidelines. METHODS: A PubMed/Embase search was performed to identify all reported SCN5A variants in BrS. Standardized bioinformatic re-analysis (SIFT, PolyPhen, Mutation Taster, Mutation assessor, FATHMM, GERP, PhyloP, and SiPhy) and re-evaluation of frequency in the gnomAD database were performed. Fourteen ACMG-AMP rules were deemed applicable for SCN5A variant analysis. RESULTS: Four hundred and eighty unique SCN5A variants were identified, the majority of which 425 (88%) were coding variants. One hundred and fifty-six of 425 (37%) variants were classified as pathogenic/likely pathogenic. Two hundred and fifty-eight (60%) were classified as variants of uncertain significance, while a further 11 (3%) were classified as benign/likely benign. When considering the subset of variants that were considered "null" variants separately, 95% fulfilled criteria for pathogenicity/likely pathogenicity. In contrast, only 17% of missense variants fulfilled criteria for pathogenicity/likely pathogenicity. Importantly, however, only 25% of missense variants had available functional data, which was a major score driver for pathogenic classification. CONCLUSION: Based on contemporary ACMG-AMP guidelines, only a minority of SCN5A variants implicated in BrS fulfill the criteria for pathogenicity or likely pathogenicity.

Use of Ablation Index-Guided Ablation Results in High Rates of Durable Pulmonary Vein Isolation and Freedom From Arrhythmia in Persistent Atrial Fibrillation Patients: The PRAISE Study Results.

Background Catheter ablation for persistent atrial fibrillation (AF) is associated with less favorable outcomes than for paroxysmal AF. Substrate modification is often added to pulmonary vein isolation (PVI) to try to improve success rates. Recent studies have shown improved clinical outcomes with use of regional ablation index (AI) targets for PVI. We hypothesized that prospective use of AI-guided PVI in persistent AF patients would result in a low rate of PV reconnection at repeat electrophysiology study and that a high success rate can be achieved with durable PVI alone. Methods Forty consecutive patients with persistent AF underwent AI-guided PVI with target values of 550 for anterior and 400 for posterior left atrial regions, followed by a protocol-mandated repeat procedure after 2 months. Patients were monitored for atrial tachyarrhythmia recurrence via daily plus symptom-initiated ECG recordings for 12 months. Recurrence was defined as ≥30 seconds of any atrial tachyarrhythmia after a 3-month blanking period. Results PV reconnection was seen at repeat electrophysiology study in 22% of patients, affecting 7% of PVs. Ablation on the intervenous carina was required in 44% patients to achieve durable PVI. Atrial tachyarrhythmia recurrence was documented in 8 (20%) patients, only one of whom had PV reconnection at repeat study. At 12 months, 38/40 (95%) patients were in sinus rhythm, with 4 (10%) patients having started antiarrhythmic drugs. Higher body mass index and excess alcohol consumption were the only significant factors associated with atrial tachyarrhythmia recurrence. Conclusions Use of AI targets results in a high level of durable PVI. A good clinical outcome can be achieved in the great majority of persistent AF patients with AI-guided PVI alone. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02628730.

Demonstration of pulmonary vein exit block following pulmonary vein isolation: A novel use for adenosine.

INTRODUCTION: Demonstration of exit block after pulmonary vein isolation (PVI) is the cornerstone of ablation for atrial fibrillation (AF). It requires the demonstration of local pulmonary vein (PV) capture and absence of conduction to the atrium but is often challenging due to the inability to see local paced PV-evoked potentials. We retrospectively examined the ability of adenosine to augment this technique during CARTO-based radiofrequency ablation procedures. METHODS: Retrospective analysis of evoked PV potentials during adenosine administration while testing for PV exit block at a single UK center. RESULTS: One hundred and twenty-nine PVs in 33 patients were isolated using radiofrequency energy to demonstrate entry block. Of those, the pacing of 24 veins under baseline conditions did not clearly demonstrate local PV-evoked potentials sufficient to be sure that the local vein was truly captured and dissociated from the atrium. Adenosine was administered in 19 of these, with 10 of 19 (52.6%) veins then demonstrating clear local PV-evoked potentials transiently during adenosine administration, sufficient to allow assessment of definite exit block. CONCLUSION: Adenosine administered during PV pacing allows transient visualization of local PV-evoked potentials after PVI facilitating the clearer demonstration of PV exit block in over 50% veins.