Distinct Substrates of Idiopathic Ventricular Fibrillation Revealed by Arrhythmia Characteristics on Implantable Cardioverter-Defibrillator.

BACKGROUND: Idiopathic ventricular fibrillation (IVF) can be associated with undetected distinct conditions such as microstructural cardiomyopathic alterations (MiCM) or Purkinje (Purk) activities with structurally normal hearts. OBJECTIVE: This study sought to evaluate the characteristics of recurrent VF recorded on implantable defibrillator electrograms, associated with these substrates. METHODS: This was a multicenter collaboration study. At 32 centers, we selected patients with an initial diagnosis of IVF and recurrent arrhythmia at follow-up without antiarrhythmic drugs, in whom mapping demonstrated Purk or MiCM substrate. We analyzed variables related to previous ectopy, sinus rate preceding VF, trigger, and initial VF cycle lengths. Logistic regression with cross validation was used to evaluate the performance of criteria to discriminate Purk or MiCM substrates. RESULTS: Among 95 patients (35 women, age 35 ± 11 years) meeting the inclusion criteria, IVF was associated with MiCM in 41 and Purk in 54 patients. A total of 117 arrhythmia recurrences including 91% VF were recorded on defibrillator. Three variables were mostly discriminant. Sinus tachycardia (≤570 ms) was more frequent in MiCM (35.9% vs 13.4%, P = 0.014) whereas short-coupled (<350 ms) triggers were most frequent in Purk-related VF (95.5% vs 23.1%, P = 0.001), which also had shorter VFCLs (182 ± 15 ms vs 215 ± 24 ms, P < 0.001).The multivariable combination provided the highest prediction (accuracy = 0.93 ± 0.05, range 0.833-1.000), discriminating 81% of IVF substrates with a high probability (>80%). Ectopy were inconsistently present before VF. CONCLUSIONS: Characteristics of arrhythmia recurrences on implantable cardioverter- defibrillator provide phenotypic markers of the distinct and hidden substrates underlying IVF. These findings have significant clinical and genetic implications.

Rescue retrograde coronary venous ethanol ablation of ventricular tachycardia storm in a patient with Lamin A/C cardiomyopathy: a case report.

Background: Left ventricular (LV) summit arrhythmias account for up to 14% of LV arrhythmias. The ablation of LV summit arrhythmias is challenging, as testified by the fact that radiofrequency (RF) catheter ablation failure is frequent. Retrograde coronary venous ethanol infusion has been proposed as an alternative approach for the ablation of LV summit arrhythmias. Case summary: A 47-year-old man with Lamin A/C cardiomyopathy was referred for the ablation of a pleiomorphic ventricular tachycardia (VT) storm, with dominant morphology compatible with LV summit origin. He first received a combined endo- and epicardial RF ablation with the elimination of three clinically relevant VTs. However, the dominant VT could not be ablated due to the proximity of the coronary vasculature and phrenic nerve and remained inducible. Accordingly, an urgent rescue redo procedure consisting of retrograde coronary venous ethanol ablation was performed. Based on the best pace-match and precocity, the first septal, retro-pulmonary branch and the first diagonal branch were infused with ethanol with immediate cessation of the tachycardia and non-inducibility. Anti-arrhythmic drugs were withdrawn, while guideline-directed medical therapy for heart failure was continued. No complications occurred. After 3 months, the patient remained free from any arrythmias. Discussion: Ablation of LV summit arrythmias is challenging, especially in the context of an electrical storm or in patients with structural heart disease. In such a situation, rescue ablation with retrograde coronary venous ethanol infusion represents an attractive alternative ablation modality.

Risk assessment of esophageal ulceration following left atrial radiofrequency linear ablation.

INTRODUCTION: Esophageal safety following radiofrequency (RF) left atrial (LA) linear ablation has not been established. To determine the esophageal safety profile of LA linear RF lesions, we performed systematic esophagogastroduodenoscopy in all patients with intraesophageal temperature rise (ITR) ≥ 38.5°C. METHODS AND RESULTS: Between December 2021 and July 2023, a total of 200 consecutive patients with atrial tachyarrhythmia (ATA) underwent linear ablation with posterior dome (roof or floor) or posterior mitral isthmus line transection. Patients with ITR ≥ 38.5°C were scheduled for esophageal endoscopy ~3 weeks after ablation. Patient and ATA characteristics, procedural parameters, endoscopy findings and ablation lesion data were collected and analyzed. One hundred thirty-three out of 200 (67%) patients showed ITR ≥ 38.5°C during LA linear ablation. ITR (with maximal temperature of 45.7°C) was more frequently observed during floor line ablation (82% of cases). ITR was less observed during roof line ablation (34%) and posterior mitral isthmus ablation (4%). Endoscopy, performed in 115 patients after 24 ± 10 days, showed esophageal ulceration in four patients (two patients Kansas City classification [KCC] 2a and two patients KCC 2b). No patient showed esophageal perforation or fistula. CONCLUSION: Temperature rise during LA linear ablation is frequent and ulceration risk exists, particularly when floor line is performed. Safety measures are needed to avoid potential severe complications like esophageal perforation and fistula.

Vein of Marshall Ethanol Infusion for AF Ablation; A Review.

The outcomes of persistent atrial fibrillation (AF) ablation are modest with various adjunctive strategies beyond pulmonary vein isolation (PVI) yielding largely disappointing results in randomised controlled trials. Linear ablation is a commonly employed adjunct strategy but is limited by difficulty in achieving durable bidirectional block, particularly at the mitral isthmus. Epicardial connections play a role in AF initiation and perpetuation. The ligament of Marshall has been implicated as a source of AF triggers and is known to harbour sympathetic and parasympathetic nerve fibres that contribute to AF perpetuation. Ethanol infusion into the Vein of Marshall, a remnant of the superior vena cava and key component of the ligament of Marshall, may eliminate these AF triggers and can facilitate the ease of obtaining durable mitral isthmus block. While early trials have demonstrated the potential of Vein of Marshall 'ethanolisation' to reduce arrhythmia recurrence after persistent AF ablation, further randomised trials are needed to fully determine the potential long-term outcome benefits afforded by this technique.

Comparing pulsed field electroporation and radiofrequency ablation for the treatment of paroxysmal atrial fibrillation: design and rationale of the BEAT PAROX-AF randomized clinical trial.

AIMS: Using thermal-based energy sources [radiofrequency (RF) energy/cryo energy] for catheter ablation is considered effective and safe when performing pulmonary vein isolation (PVI) in patients with paroxysmal atrial fibrillation (AF). However, treatment success remains limited and complications can occur due to the propagation of thermal energy into non-target tissues. We aim to compare pulsed field ablation (PFA) with RF ablation in terms of efficacy and safety for patients with drug-resistant paroxysmal AF. METHODS AND RESULTS: The BEAT PAROX-AF trial is a European multicentre, superiority, open-label randomized clinical trial in two parallel groups. A total of 292 participants were recruited in 9 high-volume European clinical centres in 5 countries. Patients with paroxysmal AF were randomized to PFA (FARAPULSE Endocardial Ablation System©, Boston Scientific) or RF using the CLOSE protocol with contact force sensing catheter (SmartTouch© catheter and CARTO© Biosense Webster). The primary endpoint will be the 1-year recurrence of atrial arrhythmia, and the major secondary safety endpoint will be the occurrence of acute (<7 days) procedure-related serious adverse events, or pulmonary vein stenosis, or atrio-oesophageal fistula up to 12 months. Additionally, five sub-studies investigate the effect of PFA on oesophageal safety, cerebral lesions, cardiac autonomic nervous system, durability of PVI as assessed during redo ablation procedures, and atrial and ventricular function. The study began on 27 December 2021 and concluded recruitment on 17 January 2024. Results will be available in mid-2025. CONCLUSION: The BEAT PAROX-AF trial aims to provide critical insights into the optimal treatment approach for patients with paroxysmal AF.

Validation of a machine learning algorithm to identify pulmonary vein isolation during ablation procedures for the treatment of atrial fibrillation: results of the PVISION study.

AIMS: Pulmonary vein isolation (PVI) is the cornerstone of ablation for atrial fibrillation. Confirmation of PVI can be challenging due to the presence of far-field electrograms (EGMs) and sometimes requires additional pacing manoeuvres or mapping. This prospective multicentre study assessed the agreement between a previously trained automated algorithm designed to determine vein isolation status with expert opinion in a real-world clinical setting. METHODS AND RESULTS: Consecutive patients scheduled for PVI were recruited at four centres. The ECGenius electrophysiology (EP) recording system (CathVision ApS, Copenhagen, Denmark) was connected in parallel with the existing system in the laboratory. Electrograms from a circular mapping catheter were annotated during sinus rhythm at baseline pre-ablation, time of isolation, and post-ablation. The ground truth for isolation status was based on operator opinion. The algorithm was applied to the collected PV signals off-line and compared with expert opinion. The primary endpoint was a sensitivity and specificity exceeding 80%. Overall, 498 EGMs (248 at baseline and 250 at PVI) with 5473 individual PV beats from 89 patients (32 females, 62 ± 12 years) were analysed. The algorithm performance reached an area under the curve (AUC) of 92% and met the primary study endpoint with a sensitivity and specificity of 86 and 87%, respectively (P = 0.005; P = 0.004). The algorithm had an accuracy rate of 87% in classifying the time of isolation. CONCLUSION: This study validated an automated algorithm using machine learning to assess the isolation status of pulmonary veins in patients undergoing PVI with different ablation modalities. The algorithm reached an AUC of 92%, with both sensitivity and specificity exceeding the primary study endpoints.

Procedural performance and outcome after pulsed field ablation for pulmonary vein isolation: comparison with a reference radiofrequency database.

Aims: Pulsed field ablation (PFA) is a promising ablation technique for pulmonary vein isolation (PVI) with appealing advantages over radiofrequency (RF) including speed, tissue selectivity, and the promise of enhanced durability. In this study, we determine the procedural performance, efficacy, safety, and durability of PFA and compare its performance with a dataset of optimized RF ablation. Methods and results: After propensity score matching, we compared 161 patients who received optimized RF-guided PVI in the PowerPlus study (CLOSE protocol) with 161 patients undergoing PFA-guided PVI for paroxysmal or persistent atrial fibrillation (AF; pentaspline basket catheter). The median age was 65 years with 78% paroxysmal AF in the PFA group (comparable characteristics in the RF group). Pulsed field ablation-guided PVI was obtained in all patients with a procedure time of 47 min (vs. 71 min in RF, P < 0.0001) and a fluoroscopy time of 15 min (vs. 11 min in RF, P < 0.0001). One serious adverse event [transient ischaemic attack] occurred in a patient with thrombocytosis (0.6 vs. 0% in RF). During the 6-month follow-up, 24 and 27 patients experienced a recurrence with 20 and 11 repeat procedures in the PFA and the RF groups, respectively (P = 0.6 and 0.09). High-density mapping revealed a status of 4 isolated veins in 7/20 patients in the PFA group and in 2/11 patients in the RF group (35 vs. 18%, P = 0.3). Conclusion: Pulsed field ablation fulfils the promise of offering a short and safe PVI procedure, even when compared with optimized RF in experienced hands. Pulmonary vein reconnection is the dominant cause of recurrence and tempers the expectation of a high durability rate with PFA.

Early atrial fibrillation recurrence post catheter ablation: Analysis from insertable cardiac monitor in the era of optimized radiofrequency ablation.

BACKGROUND: Early recurrence of atrial tachyarrhythmia (ERAT) is associated with ablation-induced proarrhythmogenic inflammation; however, existing studies used intermittent monitoring or nonoptimized radiofrequency (RF) applications (noncontiguous or without ablation index target value). OBJECTIVE: The purpose of this study was to investigate the relationship between ERAT and late recurrence based on insertable cardiac monitor (ICM) data. METHODS: We compiled data from Close-To-Cure and Close Maze studies, which enrolled patients who underwent RF ablation for paroxysmal or persistent atrial fibrillation (AF). All patients were implanted with an ICM 2-3 months before ablation. RESULTS: We studied 165 patients (104 with paroxysmal AF, 61 with persistent AF). Over the 1-year follow-up period, 41 of the patients experienced late recurrence. The risk of late recurrence was higher in patients experiencing ERAT (hazard ratio [HR] 6.2; 95% confidence interval [CI] 3.0-13.0), with negative and positive predictive values of 90.5% and 45.7%, respectively. Median burden of AF during the blanking period was significantly higher in patients with late recurrence (7.9% [0.0%-99.6%]) compared to those without recurrence (0.0% [0.0%-6.0]; P <.001). For each 1% increase in AF burden during the blanking period, late recurrence increased by 4.6% (HR 1.046; 95% CI 1.035-1.059). The best tradeoff for predicting AF from ERAT occurrence was AF burden of 0.6% and last ERAT at 64 days. CONCLUSION: In patients ablated for paroxysmal and persistent AF with a durable RF lesion set and implanted with a continuous monitoring device, postablation early AF recurrence and burden significantly predict late recurrence. The post-AF ablation blanking period should be reduced to 2 months.

No Effect of Continued Antiarrhythmic Drug Treatment on Top of Optimized Pulmonary Vein Isolation in Patients With Persistent Atrial Fibrillation: Results From the POWDER-AF2 Trial.

BACKGROUND: In patients with persistent atrial fibrillation (PersAF), catheter ablation aiming for pulmonary vein isolation (PVI) is associated with moderate clinical effectiveness. We investigated the benefit of continuing previously ineffective class 1C or 3 antiarrhythmic drug therapy (ADT) in the setting of a standardized PVI-only ablation strategy. METHODS: In this multicenter, randomized controlled study, patients with PersAF (≥7 days and <12 months) despite ADT were prospectively randomized 1:1 to PVI with ADT continued versus discontinued beyond the blanking period (ADT ON versus ADT OFF). Standardized catheter ablation was performed aiming for durable isolation with stable, contiguous, and optimized radio frequency applications encircling the pulmonary veins (CLOSE protocol). Clinical visits and 1-to-7-day Holter were performed at 3, 6, and 12 months. The primary end point was any documented atrial tachyarrhythmia lasting >30 seconds beyond 3 months. Prospectively defined secondary end points included repeat ablations, unscheduled arrhythmia-related visits, and quality of life among groups. RESULTS: Of 200 PersAF patients, 98 were assigned to ADT OFF and 102 to ADT ON. The longest atrial fibrillation episode qualifying for PersAF was 28 (10-90) versus 30 (11-90) days. Clinical characteristics and procedural characteristics were similar. Recurrence of atrial tachyarrhythmia was comparable in both groups (20% OFF versus 21.2% ON). No differences were observed in repeat ablations and unscheduled arrhythmia-related visits. Marked improvement in quality of life was observed in both groups. CONCLUSIONS: In patients with PersAF, there is no benefit in continuing previously ineffective ADT beyond the blanking period after catheter ablation. The high success rate of PVI-only might be explained by the high rate of durable isolation after optimized PVI and the early stage of PersAF (POWDER-AF2). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03437356.

Impact of Catheter Ablation on Arrhythmia Burden in Patients With Shock-Resistant Persistent Atrial Fibrillation.

BACKGROUND: Persistent shock-resistant atrial fibrillation (AF) is a challenging entity, with modest results from catheter ablation according to conventional survival analysis. OBJECTIVES: The aim of this study was to determine the effect of catheter ablation on atrial tachyarrhythmia (ATA) burden in persistent AF patients undergoing first-time ablation with the use of an implantable cardiac monitor (ICM). METHODS: Patients with drug-resistant ongoing persistent AF and at least 1 previous failed cardioversion were implanted with an ICM 2 months before the procedure. All patients underwent pulmonary vein isolation with or without additional substrate ablation depending on the presence of self-terminating AF on ICM and left atrium size. Median AF burden before and after ablation, off antiarrhythmic medication, was determined from ICM recordings after review by 2 independent investigators. RESULTS: Sixty patients were recruited (mean age 66 ± 9 years, 70% male). Mean left atrial diameter was 48 ± 6 mm and median CHA2DS2VASc score was 2. Ten patients (17%) unexpectedly demonstrated self-terminating AF before ablation. The median burden of ATA before ablation was 100% (95% CI: 19.6%-100%), decreasing to 0% (95% CI: 0%-95.8%) after ablation during the post-blanking follow-up period (median reduction 100%; 95% CI: 4%-100%; P < 0.001). Twenty-seven patients (45%) experienced recurrent ATA during 12-month follow-up. In these patients, median burden before ablation was 100% (95% CI: 26.9%-100%), decreasing to 11.4% (95% CI: 0.35%-99.7%) after ablation (P < 0.001). Quality of life improved significantly from baseline, driven by lack of recurrence. CONCLUSIONS: Patient-tailored catheter ablation results in a significant reduction in ATA burden (off antiarrhythmic medication) in shock-resistant persistent AF patients using ICMs implanted 2-months pre-procedure. These data suggest that conventional arrhythmia-free survival analysis does not capture the true impact of catheter ablation in this challenging cohort.

Very High-Power Ablation for Contiguous Pulmonary Vein Isolation: Results From the Randomized POWER PLUS Trial.

BACKGROUND: Very high-power, short-duration (90-W/4-second) ablation for pulmonary vein isolation (PVI) may reduce procedural times. However, shorter applications with higher power may impact lesion quality. OBJECTIVES: In this multicenter, randomized controlled trial, the authors compared procedural efficiency, efficacy, and safety of PVI using 90-W/4-second ablation to 35/50-W ablation. METHODS: Patients with paroxysmal or persistent atrial fibrillation undergoing first-time PVI were randomized to pulmonary vein encirclement with contiguous applications using very high-power, short-duration applications (90 W over 4 seconds) or 35/50-W applications (titrated up to ablation index >550 anteriorly and >400 posteriorly). Prospective endpoints were procedural efficiency (procedure time and first-pass isolation), safety (including esophageal endoscopic evaluation), and 6-month effectiveness using repetitive Holter monitoring. RESULTS: A total of 180 patients were randomized, 90 to the 90-W group (mean age: 64.2 ± 8.9 years) and 90 to the 35/50-W group (mean age: 62.3 ± 10.8 years). Procedural time was shorter in the 90-W group vs the 35/50-W group (70 [IQR: 60-80] minutes vs 75 [IQR: 65-88.3] minutes; P = 0.009). A nonsignificant trend towards lower rates of first-pass isolation was seen in the 90-W group (83.9% vs 90%; P = 0.0852). No major complications were observed in both groups with esophageal injury occurring in 1 patient per group. At 6 months, 17% of patients in the 90-W group vs 15% in the 35/50-W group experienced recurrent arrhythmia (P = 0.681). CONCLUSIONS: Contiguous ablation using very high-power, short-duration applications results in a significant but modest reduction in procedure time with similar safety and 6-month efficacy vs a conventional approach. A hybrid approach combining both ablation modalities might be the most optimal strategy. (POWER PLUS [Very High Power Ablation in Patients With Atrial Fibrillation Schedule for a First Pulmonary Vein Isolation]; NCT04784013).

Evaluation of a standardized approach using optimized and contiguous RF applications for electrical isolation of the superior vena cava.

The superior vena cava (SVC) is well described as one of the most common non-pulmonary vein (PV)-triggers for atrial tachyarrhythmias (ATA). In our study we evaluated a standardized approach for electrical isolation of the SVC from the right atrium using a horseshoe-shaped lesion set with optimized and contiguous ostial RF lesions. The results are promising, demonstrating a very high rate of acute SVC isolation in a safe and time efficient manner (mostly less than 10 min).

Atrial tachycardia occurring after a prior atrial fibrillation ablation procedure: Does non-inducibility matter?

Recurrent atrial tachycardia (AT) is a common phenomenon after catheter ablation for AF, particularly in the setting of additional substrate ablation, with many studies demonstrating gap-related macro re-entrant AT (predominantly mitral and roof dependent) to be the dominant mechanism. Although multiple inducible ATs after ablation of the clinical AT are commonly described at repeat procedures, the optimal ablation strategy, and procedural endpoints are unclear in this setting. A recent randomized study addressing the question of non-inducibility as a procedural endpoint demonstrated no additional benefits to the ablation of all induced, non-clinical ATs, but it was limited by small numbers and high rates of non-inducibility. Nevertheless, once ablation of the clinical AT has been successfully performed, ensuring durable linear block and PV isolation may be sufficient for the prevention of further AT. Durable linear block, particularly at the mitral isthmus, is difficult to achieve but may be facilitated by the real-time evaluation of lesion quality and contiguity and the novel technique of vein of Marshall ethanol infusion. Large-scale, randomized trials are needed, nonetheless, to fully assess the optimal ablation strategy in the setting of recurrent AT post-AF ablation.

DG-Mapping: a novel software package for the analysis of any type of reentry and focal activation of simulated, experimental or clinical data of cardiac arrhythmia.

In this work, we present the release of a novel easy to use software package called DGM or Directed-Graph-Mapping. DGM can automatically analyze any type of arrhythmia to find reentry or focal sources if the measurements are synchronized in time. Currently, DGM requires the local activation times (LAT) and the spatial coordinates of the measured electrodes. However, there is no requirement for any spatial organization of the electrodes, allowing to analyze clinical, experimental or computational data. DGM creates directed networks of the activation, which are analyzed with fast algorithms to search for reentry (cycles in the network) and focal sources (nodes with outgoing arrows). DGM has been mainly optimized to analyze atrial tachycardia, but we also discuss other applications of DGM demonstrating its wide applicability. The goal is to release a free software package which can allow researchers to save time in the analysis of cardiac data. An academic license is attached to the software, allowing only non-commercial use of the software. All updates of the software, user and installation guide will be published on a dedicated website www.dgmapping.com . Graphical Abstract Direct-Graph-Mapping is a method to automatically analyze a given arrhythmia by converting measured data of the electrodes in a directed network. DGM requires the local activation times (LAT) and the spatial coordinates of the measured electrodes. There is no requirement for any spatial organization of the electrodes, allowing to analyze clinical, experimental or computational data (see left). An example could be the LATs and coordinates from a CARTO file. DGM creates a directed network of the activation by (1) determining the neighbors of each node, 2 (2) allowing a directed arrow between two neighbors if propagation of the electrical wave is possible, (3) repeating this process for all nodes, (4) if necessary, redistributing the nodes more uniformly and repeating step (1)-(3). Two possible steps are (5) to visualize the wavefront by creating an average graph or (6) find the cycles in the network which represent the reentry loops. Focal sources are nodes with only outgoing arrows.