Effect of ganglionated plexi ablation by high-density mapping on long-term suppression of paroxysmal atrial fibrillation – The first clinical survey on ablation of the dorsal right plexusus

Left atrial (LA) ganglionated plexi (GP) are part of the intrinsic cardiac autonomic nervous system and implicated in the pathogenesis of atrial fibrillation. High frequency stimulation is used to identify GP sites in humans. The effect of ablation on neural pathways connecting GPs in humans is unknown. Thirty patients undergoing LA ablation with autonomic modification were recruited. In patients with persistent atrial fibrillation, endocardial continuous high frequency stimulation identified GP sites producing AV block. After right lower GP ablation (N=5), 2 of 15 sites remained positive, whereas after ablation of other GPs (N=5), leaving right lower GP intact, all 19 sites remained positive (right lower GP versus other GP, P<0.005), indicating that neural pathways between LAGPs and the AV node are via the right lower GP. In 20 patients with paroxysmal atrial fibrillation, synchronized high frequency stimulation identified sites initiating pulmonary vein (PV) ectopy. After PV isolation (N=8), no sites remained positive. After local GP ablation (N=9), 3 of 14 sites remained positive, suggesting neural connections to the PV were disrupted by both PV isolation and GP ablation. Heart rate variability indices reduced significantly after right upper GP ablation alone, suggesting that neural pathways from the LA to the SA node travel via the right upper GP. We have demonstrated neural pathways connecting LA GPs with the PVs, AV node, and SA node. The effects of high frequency stimulation at GP sites can be prevented by ablating the GP site or the neural pathway. This further delineates the mechanism via which PV isolation prevents atrial fibrillation and highlights important caveats for autonomic modification end points.

Adjunctive ganglionic plexus (GP) ablation may increase the efficacy of pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF). Prior meta-analyses examining PVI with adjunctive GP ablation have included non-randomized trials and have included trials evaluating thorascopic epicardial ablation. The objective of this study is to perform a meta-analysis of randomized controlled trials (RCTs) comparing endocardial catheter-based PVI to PVI with adjunctive GP ablation. Summary odds ratio (OR) and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed with I2 values. Sub-group analysis was performed comparing arrhythmia recurrence between patients with paroxysmal versus persistent AF at trial baseline. Meta-regressions were performed with mean left atrial diameter and left ventricular ejection fraction at trial baseline as the moderator variables. Five RCTs were identified including 814 patients: 406 PVI + GP ablation and 408 PVI alone. The mean age of participants was 56.5years and 74.7% were male. Four of these trials evaluated catheter-based endocardial ablation for a total of 574 patients: 289 PVI + GP ablation and 285 PVI alone. The odds of arrhythmia recurrence in patients undergoing adjunctive GP ablation with PVI compared with PVI alone were a reduced: odds ratio (OR) 0.58, 95% confidence interval (CI) 0.41-0.82, I2 = 40.2%. In the subgroup analysis, the odds of arrhythmia recurrence with adjunctive GP ablation were reduced in those with paroxysmal AF (OR 0.396, 95% CI 0.23-0.69, I2 = 0%). A non-significant trend to reduced arrhythmia recurrence was also observed in those with persistent AF (OR 0.726, 95% CI 0.475-1.112, I2 = 0%). When performing the meta-regression, increased left atrial diameter was associated with decreased treatment effect of adjunctive GP ablation (R2 index = 1.0, I2 = 0%). The addition of GP ablation to PVI was associated with reduced arrhythmia recurrence. Adjunctive GP ablation was more effective in paroxysmal AF and in patients with smaller atria. Larger RCTs are needed to confirm the efficacy of GP + PVI ablation.

A novel ablation strategy for refractory atrial fibrillation based on the fractionated signal area in the atrial muscle

Background. Catheter pulmonary vein isolation (PVI) is the main interventional procedure for treatment of atrial fibrillation (AF). Recurrences of arrhythmia paroxysms in the postoperative period are mainly determined by reconnection of conduction from the pulmonary veins. However, non-pulmonary vein triggers and a positive vagal response of ganglionated plexi (GP) to high frequency stimulation after PVI confirmed by drug testing may affect the long-term efficacy of catheter AF ablation.Aim. To evaluate the efficacy of PVI isolation after drug testing and a negative response to high-frequency stimulation and a positive response to high-frequency stimulation but without subsequent ablation in patients with paroxysmal AF, as well as the efficacy of PVI confirmed by drug testing in patients having nonpulmonary vein triggers.Methods. The present analysis is a part of the randomized study on the comparison of PVI confirmed by drug testing with the absence of non-pulmonary vein triggers and a positive response of GP to high-frequency stimulation with and without GP ablation. PVI was performed in 311 patients. Ninety-six patients were excluded because they required additional GP ablation. Two hundred and fourteen patients were divided into three groups: PVI with a positive GP response (posGP) to high-frequency stimulation without GP ablation (group I, n = 97), PVI with a negative GP response (negGP) to high-frequency stimulation (group II, n = 79) and PVI with non-pulmonary vein triggers (group III, n = 38). The primary endpoint of the study was the freedom from any atrial tachyarrhythmias after 12 months of follow-up confirmed by 24-hour Holter monitoring. The secondary endpoints included the frequency of detecting dormant pulmonary vein conduction, non-pulmonary vein triggers, negative GP response to high-frequency stimulation after catheter PVI. The patients were followed 3, 6, 9, 12 months after the ablation procedure.Results. At the end of the follow-up 57 (72.2%) patients in the PVI + negGP group (group II), 58 (59.8%) patients in the PVI + posGP group (group I) and 20 (52.6%) patients in the PVI + NPT (group III) were free from any atrial tachyarrhythmia (р=0.07; log-rank test). A statistical significance in the efficacy was observed when group II was compared with group III (72.2% and 52.6%, р = 0.028, log-rank test). In the course of primary ablation following PVI, when performing drug testing, dormant atriovenous conduction sites were observed in 105 (33.8%) patients, while non-pulmonary vein triggers (n = 79) were recorded in 38 (12.2%) patients. The frequency of negative GP responses to high-frequency stimulation after PVI accounted for 28.3%.Conclusion. Pulmonary vein isolation confirmed by drug testing, without a response of GP to high-frequency stimulation tends to provide higher efficacy in maintaining the sinus rhythm as compared with PVI and a positive GP response to high-frequency stimulation, but without a statistical significance, whereas nonpulmonary vein triggers after PVI are associated with lower efficacy in the long-term follow-up. Received 31 July 2018. Revised 8 August 2018. Accepted 14 August 2018. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest. Author contributionsConception and study design: Yu.S. Krivosheev, D.I. Bashta, V.N. KolesnikovData collection and analysis: Yu.S. Krivosheev, D.I. Bashta, N.A. TihonovaDrafting the article: Yu.S. Krivosheev, A.A. SimonyanCritical revision of the article: V.N. Kolesnikov, K.V. Modnikov, T.A. MyznikovaFinal approval of the version to be published: Yu.S. Krivosheev, D.I. Bashta, A.A. Simonyan, N.A. Tihonova, K.V. Modnikov, T.A. Myznikova, Z.A. Mishodzheva,V.N. Kolesnikov

AB-453070-1 NOVEL INSIGHTS OF GANGLIONATED PLEXI ABLATION FOR ATRIAL FIBRILLATION: FINDINGS FROM RECURRENCE CASES

Adjunctive ganglionated plexi (GP) ablation may improve success rates for treatment of atrial fibrillation (AF) when combined with pulmonary vein (PV) isolation. Existing meta-analyses on GP ablation have included observational studies and have not incorporated more recent randomized clinical trial data. Moreover, the impact of AF subtype (paroxysmal vs. persistent) on outcomes of GP ablation has not been well established. We performed a meta-analysis of randomized controlled trials (RCTs) comparing GP ablation + pulmonary vein (PV) isolation versus PV isolation alone according to the subtype of AF. The primary endpoint was freedom from sustained AF or atrial tachyarrhythmia (AT) after a single procedure. Across four RCTs, 718 patients (358 and 360 that underwent GP ablation + PV isolation [intervention] vs. PV isolation alone [control], respectively) were included in the study. Mean left atrial size and left ventricular ejection fraction were 45.7mm and 54.8%, respectively. Among paroxysmal AF patients, GP ablation was linked to significantly higher freedom from AT/AF (75.8 vs. 60.0% for the intervention vs. control arms respectively; OR [95% CI]: 2.22 [1.36-3.61], P=0.001). Among persistent AF patients, GP ablation was associated with a non-significant trend towards higher rates of freedom from AT/AF (54.7 vs. 43.3% for the intervention vs. control arms respectively; OR [95% CI]: 1.55 [0.96-2.52], P=0.08). In all cases, heterogeneity was found to be low (I 2 of 32% or lower). Compared to PV isolation alone, GP ablation + PV isolation is associated with better outcomes in patients with paroxysmal AF and without significant structural heart disease.

POSTER PRESENTATIONS

Background. Pulmonary vein isolation (PVI) is the gold standard of interventional atrial fibrillation (AF) treatment, however, it doesn't provide a stable clinical effect and durable PVI in the long-term follow-up due to reconnections within the ablation line. To increase the efficacy of surgery, modulation of the autonomic nervous system can be combined with pulmonary vein isolation.Aim. The study was focused on the evaluation of efficacy of ganglionated plexi (GP) ablation combined with PVI, and intraoperative drug testing of dormant pulmonary vein conduction and exclusion of non-pulmonary vein triggers in patients with paroxysmal atrial fibrillation.Methods. There hundred sixty-seven patients with paroxysmal AF scheduled for catheter ablation were initially screened. PVI was performed in all patients. After testing with adenosine triphosphate and isoprenaline for dormant conduction following PVI and exclusion of non-pulmonary vein triggers, 194 patients with a positive response to high-frequency stimulation in the main GP sites of the left atrium were randomized in two groups: PVI (group I, n = 97), PVI with anatomical GP ablation (group II, n = 97). To perform continuous ECG monitoring, 53 patients received implantable cardiac monitors. The primary endpoint of the study was the freedom from any atrial tachyarrhythmias after 12 months of follow- up as recorded by 24-hour Holter monitoring. The secondary endpoints included AF burden based on implantable cardiac monitors data and predictors of AF recurrences. The patients were followed 3, 6, 9, 12 months after the ablation procedure.Results. The mean follow-up was 12.5±2.2 months. By the end of the follow-up, 79 (81.4%) patients in the PVI with GP ablation group and 58 (59.8%) patients in the PVI only group were free from any atrial tachyarrhythmia (р=0.0012; log-rank test, HR 0.41, 95% CI [0.23–0.72], р=0.002; Cox regression). Implantable cardiac monitors data revealed that AF burden was significantly lower in the PVI with GP group as compared with the PVI only group (14.8±1.7% and 5.4±0.7%, р&lt;0.001). According to the multivariable regression analysis, the independent predictors of AF recurrences were AF duration and presence of diabetes mellitus, while GP ablation reduced the risk of AF recurrence by 61%.Conclusion. Ganglionated plexi ablation combined with pulmonary vein isolation confirmed by testing dormant conduction and excluding non-pulmonary triggers provides higher efficacy in maintaining the sinus rhythm as compared with PVI only in patients with paroxysmal atrial fibrillation. Received 17 July 2018. Revised 7 August 2018. Accepted 10 August 2018. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest. Author contributionsConception and study design: Yu.S. Krivosheev, L.I. Vilenskiy, V.N. KolesnikovData collection and analysis: Yu.S Krivosheev, D.I. Bashta, A.A. SimonyanDrafting the article: Yu.S. Krivosheev, A.A. Simonyan, D.I. Bashta, S.Yu. KrasilnikovaCritical revision of the article: V.N. KolesnikovFinal approval of the version to be published: Yu.S. Krivosheev, D.I. Bashta, A.A. Simonyan, S.Yu. Krasilnikova, L.I. Vilenskiy, T.A. Myznikova, Z.A. Mishodzheva, V.N. Kolesnikov

ORAL PRESENTATION

Ablation of Ganglionic Plexi During Combined Surgery for Atrial Fibrillation

Left Atrial Ganglion Ablation as an Adjunct to Atrial Fibrillation Surgery in Valvular Heart Disease

Autonomic Denervation Added to Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation: A Randomized Clinical Trial

Wide-area antral pulmonary vein and posterior wall isolation by way of segmental nonocclusive applications using a novel radiofrequency ablation balloon

Ganglionated plexi (GP) is claimed to be potentially responsible for atrial fibrillation (AF). The efficacy and safety of GP ablation remains controversial. This meta-analysis aimed to assess the efficacy of procedure with or without ablation of GP. We included controlled clinical trials or randomized controlled trials comparing procedures of GP ablation plus pulmonary vein isolation (PVI), GP ablation plus Maze, or GP ablation alone (experimental arm), with PVI or Maze without GP ablation (control arm). The early episodes of atrial arrhythmia recurrence (early recurrence) and freedom from AF (primary efficacy endpoint) were estimated. Six trials with a total of 342 patients (172 per experimental arm, 170 per control arm) were included in the meta-analysis. Subgroup analysis demonstrated that there was no significant difference in early recurrence between additional GP ablation to PVI or Maze, and PVI or Maze without ablation of GP (P = 0.06). However, early recurrence was significantly higher after GP ablation alone, compared with PVI alone (P = 0.02). Freedom from AF recurrence was significantly improved by additional GP ablation to PVI and Maze, compared with PVI and Maze without ablation of GP (P < 0.01). However, it was significantly aggravated by GP ablation alone, compared with PVI alone (P = 0.006). The short and relatively long-term success rate of additional GP ablation to PVI or Maze is superior to PVI or Maze without ablation of GP. GP ablation alone is less effective than PVI alone for the treatment of AF. Future studies are necessary to establish and standardize the targeting sites, endpoints, and methods of GP ablation.

Ganglion Plexus Ablation in Advanced Atrial Fibrillation: The AFACT Study