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.

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.

Cardiac resynchronization therapy using conduction system pacing after double-switch surgery for congenitally corrected transposition of the great arteries: a case report.

Background: Patients with congenitally corrected transposition of the great arteries (ccTGA) are at risk of developing conduction disease and complete atrio-ventricular block and this risk increases after corrective cardiac surgery. However, the optimum pacing modality remains controversial. Case summary: Twelve years after a double-switch surgery with ventricular septal defect correction, a 16-year-old ccTGA female was referred with an indication for cardiac resynchronization therapy. In the absence of coronary sinus (CS) or direct access to the conduction system, several therapeutic options were considered. Finally, using a three-dimensional navigation system and customized sheaths, a left bundle branch area pacing (LBBAP) lead was successfully implanted. The implantation resulted in stable pacing parameters and positive haemodynamic changes. At 9-month follow-up, pacing parameters were stable and the patient reported a significant improvement in quality of life. Discussion: Cardiac resynchronization therapy in adults with repaired congenital heart disease remains challenging, especially in the absence of CS or direct access to the conduction system. In such a situation, LBBAP appears as an attractive alternative pacing modality. However, pre-operative management is critical to the success of the implantation.

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.

Provocation and localization of atrial ectopy in patients with atrial septal defects.

BACKGROUND: Atrial fibrillation (AF) is associated with atrial septal defects (ASDs), but the mechanism of arrhythmia in these patients is poorly understood. We hypothesised that right-sided atrial ectopy may predominate in this cohort. Here, we aimed to localise the origin of spontaneous and provoked atrial ectopy in ASD patients. METHODS: Following invasive calibration of P-wave axes, 24-h Holter monitoring was used to determine the chamber of origin of spontaneous atrial ectopy. Simultaneous electrogram recording from multiple intra-cardiac catheters was used to determine the chamber of origin of isoprenaline-provoked ectopy. Comparison was made to a group of non-congenital heart disease AF patients. RESULTS: Amongst ASD patients, a right-sided origin for spontaneous atrial ectopy was significantly more prevalent than a left-sided origin (24/30 patients with right-sided ectopy vs. 14/30 with left-sided ectopy, P = 0.015). Amongst AF patients, there was no difference in the prevalence of spontaneous right vs. left-sided ectopy. For isoprenaline-provoked ectopy, there was no significant difference in the proportions of patients with right-sided or left-sided ectopy in either group. CONCLUSIONS: When spontaneous atrial ectopy occurs in ASD patients, it is significantly more prevalent from a right-sided than left-sided origin. Isoprenaline infusion did not reveal the predilection for right-sided ectopy during electrophysiology study.

Vein of Marshall Ethanol Infusion as First Step for Mitral Isthmus Linear Ablation.

OBJECTIVES: In this study, the authors sought to investigate the added value of vein of Marshall ethanol infusion (VOMEt) as first step in facilitating radiofrequency (RF)-guided mitral isthmus (MI) block. BACKGROUND: Achieving MI block with the use of RF ablation is challenging. METHODS: Seventy patients planned for MI ablation were randomized 1:1 to VOMEt as a first step preceding RF (endocardial and epicardial, VOMFIRST group) vs RF ablation as a first step preceding VOMEt (RFFIRST group). The study end point was incidence of MI block after RF ablation and after the 2 steps. RESULTS: In VOMFIRST, VOMEt was successful in 30/35 patients (86%) resulting in a low-voltage area of 12 ± 7.4 cm2 and MI block in 2/35 patients (6%). VOMFIRST, compared with RFFIRST, was associated with higher incidence of MI block after endocardial (46% vs 11%; P < 0.001) and epicardial ablation (94% vs 43%; P < 0.001), with fewer endocardial applications (4 vs 11 vs 4; P < 0.001) and similar epicardial applications (7 vs 8; P = 0.68). Incidence of MI block after the 2 steps was 94% vs 63% (P = 0.001) in VOMFIRST vs RFFIRST, respectively. Additional touch-up RF ablation in both groups resulted in final MI block in all but 1 patient (99%). CONCLUSIONS: VOMEt as a first step in RF-guided MI line ablation significantly reduced the number of RF applications needed to achieve MI block, even if the sequence of the ablation steps did not affect the final incidence of block. (Evaluation of Vein of Marshall Ethanol Infusion During Left Atrial Linear Ablation in Patients With Persistent Atrial Fibrillation [MARSHALINE]; NCT04124328).

Left bundle branch area pacing guided by continuous uninterrupted monitoring of unipolar pacing characteristics.

INTRODUCTION: During left bundle branch area pacing (LBBAP) lead implantation, intermittent monitoring of unipolar pacing characteristics confirms LBB capture and can detect septal perforation. We aimed to demonstrate that continuous uninterrupted unipolar pacing from an inserted lead stylet (LS) is feasible and facilitates LBBAP implantation. METHODS: Thirty patients (mean age 76 ± 14 years) were implanted with a stylet-driven pacing lead (Biotronik Solia S60). In 10 patients (comparison-group) conventional implantation with interrupted unipolar pacing was performed, with comparison of unipolar pacing characteristics between LS and connector-pin (CP)-pacing after each rotation step. In 20 patients (uninterrupted-group) performance and safety of uninterrupted implantation during continuous pacing from the LS were evaluated. RESULTS: In the comparison group, LS and CP-pacing impedances were highly correlated (R2 = 0.95, p < .0001, bias 12 ± 37 Ω) with comparable sensed electrograms and paced QRS morphologies. In the uninterrupted group, continuous LS-pacing allowed beat-to-beat monitoring of impedance and QRS morphology to guide implantation. This resulted in successful LBBAP in all patients, after a mean of 1 ± 0 attempts, with mean threshold 0.81 ± 0.4 V, median sensing 6.5 mV [IQR 4.4-9.5], and mean impedance 624 ± 101 Ω. Positive LBBAP-criteria were seen in all patients with median paced QRS duration of 120 ms [IQR 112-152 ms] and median pLVAT 73 ms [IQR 68-80.5 ms]. No septal perforation occurred. CONCLUSION: Unipolar pacing from the LS allows accurate determination of pacing impedance and generates similar paced QRS morphologies and sensed electrograms to CP pacing. Continuous LS pacing allows real-time monitoring of impedance and paced QRS morphology, which facilitates safe and successful LBBAP lead implantation.

CArdiac MagnEtic resonance assessment of bi-Atrial fibrosis in secundum atrial septal defects patients: CAMERA-ASD study.

AIMS: Atrial septal defects (ASD) are associated with atrial arrhythmias, but the arrhythmia substrate in these patients is poorly defined. We hypothesized that bi-atrial fibrosis is present and that right atrial fibrosis is associated with atrial arrhythmias in ASD patients. We aimed to evaluate the extent of bi-atrial fibrosis in ASD patients and to investigate the relationships between bi-atrial fibrosis, atrial arrhythmias, shunt fraction, and age. METHODS AND RESULTS: Patients with uncorrected secundum ASDs (n = 36; 50.4 ± 13.6 years) underwent cardiac magnetic resonance imaging with atrial late gadolinium enhancement. Comparison was made to non-congenital heart disease patients (n = 36; 60.3 ± 10.5 years) with paroxysmal atrial fibrillation (AF). Cardiac magnetic resonance parameters associated with atrial arrhythmias were identified and the relationship between bi-atrial structure, age, and shunt fraction studied. Bi-atrial fibrosis burden was greater in ASD patients than paroxysmal AF patients (20.7 ± 14% vs. 10.1 ± 8.6% and 14.8 ± 8.5% vs. 8.6 ± 6.1% for right and left atria respectively, P = 0.001 for both). In ASD patients, right atrial fibrosis burden was greater in those with than without atrial arrhythmias (33.4 ± 18.7% vs. 16.8 ± 10.3%, P = 0.034). On receiver operating characteristic analysis, a right atrial fibrosis burden of 32% had a 92% specificity and 71% sensitivity for predicting the presence of atrial arrhythmias. Neither age nor shunt fraction was associated with bi-atrial fibrosis burden. CONCLUSION: Bi-atrial fibrosis burden is greater in ASD patients than non-congenital heart disease patients with paroxysmal AF. Right atrial fibrosis is associated with the presence of atrial arrhythmias in ASD patients. These findings highlight the importance of right atrial fibrosis to atrial arrhythmogenesis in ASD patients.

Long-term clinical outcome of atrial fibrillation ablation in patients with history of mitral valve surgery.

Aims: Atrial fibrillation (AF) occurs frequently after mitral valve (MV) surgery. This study aims to evaluate the efficacy and long-term clinical outcomes after the first AF ablation in patients with prior MV surgery. Methods: Sixty consecutive patients with a history of MV surgery without MAZE referred to three European centers for a first AF ablation between 2007 and 2017 (group 1) were retrospectively enrolled. They were matched (propensity score match) with 60 patients referred for AF ablation without prior MV surgery (group 2). Results: After the index ablation, 19 patients (31.7%) from group 1 and 24 (40%) from group 2 had no recurrence of atrial arrhythmias (ATa) (p = 0.3). After 62 (48-84) months of follow-up and 2 (2-2) procedures, 90.0% of group 1 and 95.0% of group 2 patients were in sinus rhythm (p = 0.49). In group 1, 19 (31.7%) patients had mitral stenosis, and 41 (68.3%) had mitral regurgitation. Twenty-seven (45.0%) patients underwent mechanical valve replacement and 33 (55.0%) MV annuloplasty. At the final follow-up, 28 (46.7%) and 33 (55.0%) patients were off antiarrhythmic drugs (p = 0.46). ATa recurrence was seen more commonly in patients with prior MV surgery (54 vs. 22%, respectively, p < 0.05). No major complication occurred. Conclusion: Long-term freedom of atrial arrhythmias after atrial fibrillation catheter ablation is achievable and safe in patients with a history of mitral valve surgery. In AF patients without a history of mitral valve surgery, repeated procedures are needed to maintain sinus rhythm.

Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Assessment of Substrate for Ventricular Tachycardia With Hemodynamic Compromise.

Background: The majority of data regarding tissue substrate for post myocardial infarction (MI) VT has been collected during hemodynamically tolerated VT, which may be distinct from the substrate responsible for VT with hemodynamic compromise (VT-HC). This study aimed to characterize tissue at diastolic locations of VT-HC in a porcine model. Methods: Late Gadolinium Enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging was performed in eight pigs with healed antero-septal infarcts. Seven pigs underwent electrophysiology study with venous arterial-extra corporeal membrane oxygenation (VA-ECMO) support. Tissue thickness, scar and heterogeneous tissue (HT) transmurality were calculated at the location of the diastolic electrograms of mapped VT-HC. Results: Diastolic locations had median scar transmurality of 33.1% and a median HT transmurality 7.6%. Diastolic activation was found within areas of non-transmural scar in 80.1% of cases. Tissue activated during the diastolic component of VT circuits was thinner than healthy tissue (median thickness: 5.5 mm vs. 8.2 mm healthy tissue, p < 0.0001) and closer to HT (median distance diastolic tissue: 2.8 mm vs. 11.4 mm healthy tissue, p < 0.0001). Non-scarred regions with diastolic activation were closer to steep gradients in thickness than non-scarred locations with normal EGMs (diastolic locations distance = 1.19 mm vs. 9.67 mm for non-diastolic locations, p < 0.0001). Sites activated late in diastole were closest to steep gradients in tissue thickness. Conclusions: Non-transmural scar, mildly decreased tissue thickness, and steep gradients in tissue thickness represent the structural characteristics of the diastolic component of reentrant circuits in VT-HC in this porcine model and could form the basis for imaging criteria to define ablation targets in future trials.

Catheter Ablation in Persistent AF, the Evolution towards a More Pragmatic Strategy.

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and represents a heterogeneous disorder with a complex pathological basis. While significant technological advances have taken place over the last decade in the field of catheter ablation of AF, response to ablation varies and long-term success rates in those with persistent AF remain modest. Mechanistic studies have highlighted potentially different sustaining factors for AF in the persistent AF population with substrate-driven focal and re-entrant sources in the body of the atria identified on invasive and non-invasive mapping studies. Translation to clinical practice, however, remains challenging and the application of such mapping techniques to clinical ablation has yet to demonstrate a significant benefit beyond pulmonary vein isolation (PVI) alone in the persistent AF cohort. Recent advances in catheter and ablation technology have centered on improving the durability of ablation lesions at index procedure and although encouraging results have been demonstrated with early studies, large-scale trials are awaited. Further meaningful improvement in clinical outcomes in the persistent AF population requires ongoing advancement in the understanding of AF mechanisms, coupled with continuing progress in catheter technology capable of delivering durable transmural lesions.

How Close Are We toward an Optimal Balance in Safety and Efficacy in Catheter Ablation of Atrial Fibrillation? Lessons from the CLOSE Protocol.

Catheter ablation for atrial fibrillation (AF) is a common treatment strategy in patients with drug-resistant, symptomatic AF. In patients with paroxysmal and short-standing persistent AF, pulmonary vein isolation (PVI) is often enough to prevent recurrence of atrial tachyarrhythmia (ATA). Point-by-point encircling of the PVs with radiofrequency (RF) applications, together with cryoballoon ablation, have been the mainstay strategies for the last 10 to 20 years. Each of these strategies, however, suffers from the delicate balance between preventing PV reconnection, on the one hand (toward more energy), and preventing (mainly esophageal) complications (toward less energy), on the other. The CLOSE protocol was developed as an RF ablation strategy that would result in the safe creation of durable isolation leading to improved outcomes. Basically, the aim of the protocol is to enclose the pulmonary veins with stable, contiguous (intertag distance, ITD ≤ 6 mm) and optimized lesions (35 Watts, W, RF applications up to ablation index targets of ≥400 and ≥550 at the posterior and anterior wall). In this review, we describe the background of the CLOSE protocol and the studies from the St Jan Bruges research group on procedural performance, efficacy, and safety of the CLOSE protocol in (a) single-center prospective PILOT study (CLOSE-PILOT), (b) a single-center prospective study with continuous rhythm monitoring (CLOSE to CURE), (c) a database of systematic esophageal endoscopic studies, (d) a multicenter prospective study (VISTAX), and (e) the CLOSE database (comprising > 400 patients). We also discuss the results of the randomized POWER-AF study comparing conventional CLOSE to high power CLOSE (up to 50 W). Finally, we discuss the performance, safety, and efficacy of the CLOSE protocol in light of the emerging changes in the field of catheter ablation being ultra-short high-power ablation and electroporation.