First-Line Catheter Ablation of Monomorphic Ventricular Tachycardia in Cardiomyopathy Concurrent With Defibrillator Implantation: The PAUSE-SCD Randomized Trial.

BACKGROUND: Catheter ablation as first-line therapy for ventricular tachycardia (VT) at the time of implantable cardioverter defibrillator (ICD) implantation has not been adopted into clinical guidelines. Also, there is an unmet clinical need to prospectively examine the role of VT ablation in patients with nonischemic cardiomyopathy, an increasingly prevalent population that is referred for advanced therapies globally. METHODS: We conducted an international, multicenter, randomized controlled trial enrolling 180 patients with cardiomyopathy and monomorphic VT with an indication for ICD implantation to assess the role of early, first-line ablation therapy. A total of 121 patients were randomly assigned (1:1) to ablation plus an ICD versus conventional medical therapy plus an ICD. Patients who refused ICD (n=47) were followed in a prospective registry after stand-alone ablation treatment. The primary outcome was a composite end point of VT recurrence, cardiovascular hospitalization, or death. RESULTS: Randomly assigned patients had a mean age of 55 years (interquartile range, 46-64) and left ventricular ejection fraction of 40% (interquartile range, 30%-49%); 81% were male. The underlying heart disease was ischemic cardiomyopathy in 35%, nonischemic cardiomyopathy in 30%, and arrhythmogenic cardiomyopathy in 35%. Ablation was performed a median of 2 days before ICD implantation (interquartile range, 5 days before to 14 days after). At 31 months, the primary outcome occurred in 49.3% of the ablation group and 65.5% in the control group (hazard ratio, 0.58 [95% CI, 0.35-0.96]; P=0.04). The observed difference was driven by a reduction in VT recurrence in the ablation arm (hazard ratio, 0.51 [95%CI, 0.29-0.90]; P=0.02). A statistically significant reduction in both ICD shocks (10.0% versus 24.6%; P=0.03) and antitachycardia pacing (16.2% versus 32.8%; P=0.04) was observed in patients who underwent ablation compared with control. No differences in cardiovascular hospitalization (32.0% versus. 33.7%; hazard ratio, 0.82 [95% CI, 0.43-1.56]; P=0.55) or mortality (8.9% versus 8.8%; hazard ratio, 1.40 [95% CI, 0.38-5.22]; P=0.62]) were observed. Ablation-related complications occurred in 8.3% of patients. CONCLUSIONS: Among patients with cardiomyopathy of varied causes, early catheter ablation performed at the time of ICD implantation significantly reduced the composite primary outcome of VT recurrence, cardiovascular hospitalization, or death. These findings were driven by a reduction in ICD therapies. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02848781.

Selective anatomical catheter ablation of left atrial ganglionated plexus for vasovagal syncope: Left superior and right anterior ganglionated plexus ablation.

BACKGROUND: Vasovagal syncope (VVS) is one of the most common causes of syncope. Traditional treatment has not achieved satisfactory results. The purpose of this study was to assess the feasibility and efficacy of selective anatomical catheter ablation of left atrial ganglionated plexus (GP) as a therapeutic strategy for the patients of symptomatic VVS. METHODS: A total of 70 patients with at least once recurrent syncopal episode of VVS with a positive head-up tilt test were enrolled. They were divided into GP ablation group and control group. Patients in GP ablation group received anatomical catheter ablation of left superior ganglionated plexus (LSGP) and right anterior ganglionated plexus (RAGP). Patients in the control group were guideline-directed conventional therapy. The primary endpoint was VVS recurrences. The secondary endpoint was the recurrence of syncope and prodrome events. RESULTS: There were no statistical differences in clinical characteristics between the ablation group (n = 35) and the control group (n = 35). Over a follow-up of 12 months, the ablation group had significantly lower syncope recurrence compared with the control group (5.7% vs. 25.7%, p = .02), and the ablation group had significantly lower syncope and prodrome recurrence compared with the control group (11.4% vs. 51.4%, p < .001). In GP ablation, 88.6% of the patients showed significant vagal response during LSGP ablation, and 88.6% of the patients showed significantly increased heart rate during RAGP ablation. CONCLUSIONS: For patients with recurrent VVS, selective anatomical catheter ablation of LSGP and RAGP is superior to conventional therapy in reducing syncope recurrence.

Chinese expert consensus on the construction of the fluoroless cardiac electrophysiology laboratory and related techniques.

Transcatheter radiofrequency ablation has been widely introduced for the treatment of tachyarrhythmias. The demand for catheter ablation continues to grow rapidly as the level of recommendation for catheter ablation. Traditional catheter ablation is performed under the guidance of X-rays. X-rays can help display the heart contour and catheter position, but the radiobiological effects caused by ionizing radiation and the occupational injuries worn caused by medical staff wearing heavy protective equipment cannot be ignored. Three-dimensional mapping system and intracardiac echocardiography can provide detailed anatomical and electrical information during cardiac electrophysiological study and ablation procedure, and can also greatly reduce or avoid the use of X-rays. In recent years, fluoroless catheter ablation technique has been well demonstrated for most arrhythmic diseases. Several centers have reported performing procedures in a purposefully designed fluoroless electrophysiology catheterization laboratory (EP Lab) without fixed digital subtraction angiography equipment. In view of the lack of relevant standardized configurations and operating procedures, this expert task force has written this consensus statement in combination with relevant research and experience from China and abroad, with the aim of providing guidance for hospitals (institutions) and physicians intending to build a fluoroless cardiac EP Lab, implement relevant technologies, promote the standardized construction of the fluoroless cardiac EP Lab.

Current understanding of atrial fibrillation recurrence after atrial fibrillation ablation: From pulmonary vein to epicardium.

Recurrence of atrial fibrillation (AF) after catheter ablation is common, with pulmonary vein (PV) reconnection considered the most likely cause. However, technologies such as contact force-sensing, irrigated catheters, and ablation index (AI)-guided ablation strategies have resulted in more durable PV isolation. As a result, it is difficult to predict which patients will develop AF recurrence despite durable PV isolation, with evolving non-PV atrial substrates thought to be a key contributor to late recurrences. Deciphering the complex mechanisms of AF recurrence beyond the cornerstone of PV isolation therefore remains challenging. Recently, there have been several important advances that may lead to better understanding and treatment of this challenging clinical entity: percutaneous epicardial access and mapping, late gadolinium enhancement magnetic resonance imaging (LGE-MRI), improvements in high-resolution electroanatomic mapping, and new ablation energy sources, specifically pulsed-field ablation. This review aims to synthesize the current literature in an effort to better understand arrhythmia mechanisms and treatment targets in patients with AF/Atrial tachycardia (AT) recurrence post-ablation.

Efficacy of ablation index-guided pulmonary vein isolation in patients with paroxysmal atrial fibrillation.

BACKGROUND: Ablation index (AI) is a novel technology of ablation lesion quality to help improve homogeneity of lesion size and continuity. In this study, we aim to evaluate whether AI-guided PVI improves clinical outcomes compared to CF-guided PVI in patients with paroxysmal AF (PAF). METHODS: Patients undergoing first-time radiofrequency ablation for PAF were randomized in a 2:1 ratio to two groups: AI-guided PVI and CF-guided PVI. In the AI group, AI ≥500 was recommended at the anterior/superior/inferior walls, 350-400 at the posterior wall, and inter-lesion distance ≤4 mm. The primary endpoint is the freedom from atrial arrhythmia recurrence during 12 months follow-up, without antiarrhythmic drug therapy (ADT). The key secondary endpoints include intra-procedural efficiency and peri-procedural complications. RESULTS: Two hundred twenty five patients were randomized (AI group [n = 149] and CF group [n = 76]). First-pass isolation rate in AI group was significantly higher than that in CF group (58.3% vs. 43.4%, p = .035). After a median follow-up of 12.2 months, 154/225 (68.4%) of patients were free from atrial arrhythmia recurrence without ADT, which was higher in AI group compared with CF group, but without significant difference (71.1% vs. 63.2%, p = .253). The incidence of peri-procedural complications is low and without difference between two groups. CONCLUSIONS: AI-guided ablation provided higher acute efficacy than CF-guided ablation in PV isolation for patients with paroxysmal AF. The long-term success rate in AI group was higher than CF group, but did not reach statistical significance.

Intraprocedural endpoints to predict durable pulmonary vein isolation: a randomized trial of four post-ablation techniques.

AIMS: The optimal procedural endpoint to achieve permanent pulmonary vein isolation (PVI) during ablation of atrial fibrillation (AF) remains unknown. We aimed to compare the impact of prolonged waiting periods and adenosine triphosphate (ATP) testing after PVI on long-term freedom from AF. METHODS AND RESULTS: In total, 538 patients (median age 61 years, 62% male) undergoing first-time radiofrequency ablation for paroxysmal AF were randomized into four groups: Group 1 [PVI (no testing), n = 121], Group 2 (PVI + 30min waiting phase, n = 151), Group 3 (PVI+ATP, n = 131), and Group 4 (PVI + 30min+ATP, n = 135). The primary endpoint was freedom from AF. Repeat mapping to assess for late pulmonary vein (PV) reconnection was performed in patients who remained AF-free for >3 years (n = 46) and in those who had repeat ablation for AF recurrence (n = 82). During initial procedure, acute PV reconnection was observed in 33%, 26%, and 42% of patients in Groups 2, 3, and 4, respectively. At 36 months, no significant differences in freedom from AF recurrence were observed among all four groups (55%, 61%, 50%, and 62% for Groups 1, 2, 3, and 4, respectively; P = 0.258). Late PV reconnection was commonly observed, with a similar incidence between patients with and without AF recurrence (74% vs. 83%; P = 0.224). CONCLUSION: Although PVI remains the cornerstone for AF ablation, intraprocedural techniques to assess for PV reconnection did not improve long-term success. Patients without AF recurrence after 3 years exhibited similarly high rates of PV reconnection as those that underwent repeat ablation for AF recurrence. The therapeutic mechanisms of AF ablation may not be solely predicated upon durable PVI.

Prevention of left atrium esophagus fistula: Appraisal of existing technologies and strategies.

Catheter ablation has emerged as an effective treatment for atrial fibrillation (AF). Atrial esophageal fistula (AEF) is a rare, but feared complication. With increasing utilization of ablation therapy for AF, the understanding of the relationship between AEF and ablation has been improved in recent years. Efforts to reduce the risk of AEF have focused on decreasing the risk of severe esophageal injury (EI) and the presumed subsequent progression from EI to AEF, including esophageal temperature monitoring, esophageal cooling systems, esophageal deviation devices, and decreasing and/or curtailing ablation energy delivery. Periprocedural assessment may help identify higher risk patients and detect early esophageal lesions. This review systematically summarizes and evaluates the current strategies and techniques utilized to reduce the risk of AEF in the clinical workflow for AF ablation. We expect that this review will help clinicians to better understand the principles, advantages, and disadvantages of these methods, and to find suitable strategies using current available tools.

Impact of Anatomically Guided Ganglionated Plexus Ablation on Electrical Firing from Isolated Pulmonary Veins.

BACKGROUND: The mechanisms underlying atrial fibrillation (AF) initiation and pulmonary vein isolation (PVI) effectiveness remain unclear. Ganglionated plexus (GPs) have been implicated in AF initiation and maintenance. In this study, we evaluated the impact of GP ablation in patients with pulmonary vein (PV) firing after PVI. METHODS: Patients with drug-refractory paroxysmal AF undergoing radiofrequency catheter ablation therapy with PVI were screened. Among 840 cases over a 3.75-year period, 12 cases were identified with persistent PV firing (left = 4 and right = 8) after PVI was achieved and left atrial sinus rhythm restored. Adjacent GP ablation was performed anatomically and followed if necessary by additional PV ablation. RESULTS: In eight patients, PV firing was terminated during GP ablation outside of the circumferential ablation line. In one patient, additional PV ablation resulted in cessation of PV firing and in the remaining three patients, firing could not be terminated by GP ablation or additional PVI. CONCLUSION: GP ablation outside of wide antral circumferential line frequently results in the cessation of rapid firing from electrically isolated PVs. These observations suggest that interactions between left atrium and PV beyond electrical conduction warrant consideration in AF mechanisms.

LINC01559 promotes lung adenocarcinoma metastasis by disrupting the ubiquitination of vimentin.

BACKGROUND: Distant metastasis is the major cause of lung adenocarcinoma (LUAD)-associated mortality. However, molecular mechanisms involved in LUAD metastasis remain to be fully understood. While the role of long non-coding RNAs (lncRNAs) in cancer development, progression, and treatment resistance is being increasingly appreciated, the list of dysregulated lncRNAs that contribute to LUAD pathogenesis is also rapidly expanding. METHODS: Bioinformatics analysis was conducted to interrogate publicly available LUAD datasets. In situ hybridization and qRT-PCR assays were used to test lncRNA expression in human LUAD tissues and cell lines, respectively. Wound healing as well as transwell migration and invasion assays were employed to examine LUAD cell migration and invasion in vitro. LUAD metastasis was examined using mouse models in vivo. RNA pulldown and RNA immunoprecipitation were carried out to test RNA-protein associations. Cycloheximide-chase assays were performed to monitor protein turnover rates and Western blotting was employed to test protein expression. RESULTS: The expression of the lncRNA LINC01559 was commonly upregulated in LUADs, in particular, in those with distant metastasis. High LINC01559 expression was associated with poor outcome of LUAD patients and was potentially an independent prognostic factor. Knockdown of LINC01559 diminished the potential of LUAD cell migration and invasion in vitro and reduced the formation of LUAD metastatic lesions in vivo. Mechanistically, LINC01559 binds to vimentin and prevents its ubiquitination and proteasomal degradation, leading to promotion of LUAD cell migration, invasion, and metastasis. CONCLUSION: LINC01559 plays an important role in LUAD metastasis through stabilizing vimentin. The expression of LINC01559 is potentially an independent prognostic factor of LUAD patients, and LINC01559 targeting may represent a novel avenue for the treatment of late-stage LUAD.

Regional ganglionated plexus ablation eliminated rapid firing in an electrically isolated pulmonary vein.

Atrial fibrillation (AF) was initiated by rapid firing from left superior pulmonary vein (PV) by administration of isoproterenol (ISP) and adenosine triphosphate (ATP) before ablation. After successful isolation of all PVs, ISP and ATP were administered again. PVs were still isolated but an episode of rapid firing was observed inside the left PV isolation line during sinus rhythm. Radiofrequency energy was then delivered to the areas of superior left ganglionated plexus (GP) and inferior left GP. Then, PV firing could no longer be initiated. It suggests additional GP ablation may have additional benefit to circumferential PV isolation, to reduce the incidence of AF recurrence.

Circumferential Pulmonary Vein Isolation Plus Low-Voltage Area Modification in Persistent Atrial Fibrillation: The STABLE-SR-II Trial.

BACKGROUND: Benefits of adjunctive ablation strategies beyond circumferential pulmonary vein isolation (CPVI) are uncertain in patients with persistent atrial fibrillation (PeAF). OBJECTIVES: This study sought to compare clinical outcomes of CPVI plus low-voltage area (LVA) modification during STABLE-SR (SubsTrate ABlation in the LEft Atrium during Sinus Rhythm) vs circumferential pulmonary vein isolation (CPVI) alone in patients with PeAF. METHODS: From March 2018 to August 2019, 300 patients with PeAF who underwent de novo ablation were recruited and prospectively randomized to either STABLE-SR group (n = 150) or CPVI alone (n = 150) group. In the STABLE-SR group, after CPVI, high-density voltage mapping of left atrium (LA) was performed during sinus rhythm, and additive ablation targeted LVA and complex electrograms, if any were present. All the ablations were titrated by ablation index. The primary endpoint was freedom from documented atrial arrhythmias lasting for ≥30 s without the use of antiarrhythmic drugs, after a single ablation procedure and blanking period of 3 months. RESULTS: After 18 months, atrial-arrhythmia-free survival did not differ significantly between STABLE-SR group and CPVI alone group (67.2% vs 67.4%; HR: 0.89; 95% CI: 0.55-1.36; P = 0.52). Only around one-half of the patients (50.2%) had abnormal LA substrate with a medium LVA burden of 4.6% (2.1%-9.5%). However, the success rate differs dramatically between patients with normal vs abnormal LA substrate (84.8% vs 60.9%; P < 0.001). CONCLUSIONS: Additional LVA ablation did not improve successful rates of CPVI in this PeAF cohort, of whom one-half had normal LA substrate. Voltage map could identify patients with PeAF with normal LA substrate who can achieve excellent rhythm control with CPVI alone. (CPVI Alone Versus CPVI Plus Electrophysiological Substrate Ablation in the LA During SR for the Treatment of Non-PAF [STABLE-SR_II]; NCT03448562).

PV isolation guided by esophageal visualization with a tailored ablation strategy for the avoidance of esophageal thermal injury: a randomized trial.

PURPOSE: Radiofrequency ablation along the posterior wall of the left atrium may lead to atrioesophageal fistula due to esophageal thermal injury. The purpose of our study was to prospectively investigate whether ablation guided by soluble contrast esophageal visualization (SCEV) reduces injury during atrial fibrillation (AF) ablation. METHODS: Seventy-eight patients with paroxysmal AF undergoing circumferential pulmonary vein isolation (PVI) were randomized to a SCEV group (n = 39) and control group without visualization (n = 39). Cine imaging of the esophagus was performed during soluble contrast swallowing at the beginning of ablation, after adjacent ipsilateral PVI and at the end of the procedure. The ablation lesion set was modified to avoid radiofrequency delivery within the contrast esophagram boundaries. In the control group, a single final ingestion was performed at the end of the procedure. Esophageal injury was assessed by esophagogastroscopy within 24 h in all patients. RESULTS: In the control group, the ablation lesion crossed over the esophagus in 46.2% of patients, whereas in SCEV group, the ablation line violated the boundaries of the esophagus unavoidably in 15.4% of patients (confidence interval (CI); 1.61-13.98, p = 0.003). The incidence of esophageal injury was significantly lower in patients that underwent ablation with SCEV (5.1% vs. 20.5%, CI; 0.04-1.06, p = 0.042). Regardless of randomization group, patients who received ablation which overlapped the esophagus had a higher incidence of esophageal injury compared with those without overlap (37.5 vs. 1.9%, CI; 3.73-271.37, p = 0.000). CONCLUSIONS: Esophageal contrast visualization helps to reduce the potential for esophageal injury during paroxysmal AF ablation. This simple procedural adjunct has important implications to improve safety of paroxysmal AF ablation procedures globally.