Ectopy-triggering ganglionated plexuses ablation to prevent atrial fibrillation: GANGLIA-AF study

Min-Young Kim, Clare Coyle, David R Tomlinson, Markus B Sikkel, Afzal Sohaib, Vishal Luther, Kevin M Leong, Louisa Malcolme-Lawes, Benjamin Low, Belinda Sandler, Elaine Lim, Michelle Todd, Michael Fudge, Ian J Wright, Michael Koa-Wing, Fu Siong Ng, Norman A Qureshi, Zachary I Whinnett, Nicholas S Peters, Daniel Newcomb, Cherith Wood, Gurpreet Dhillon, Ross J Hunter, Phang Boon Lim, Nicholas W F Linton, Prapa Kanagaratnam, Min-Young Kim, Clare Coyle, David R Tomlinson, Markus B Sikkel, Afzal Sohaib, Vishal Luther, Kevin M Leong, Louisa Malcolme-Lawes, Benjamin Low, Belinda Sandler, Elaine Lim, Michelle Todd, Michael Fudge, Ian J Wright, Michael Koa-Wing, Fu Siong Ng, Norman A Qureshi, Zachary I Whinnett, Nicholas S Peters, Daniel Newcomb, Cherith Wood, Gurpreet Dhillon, Ross J Hunter, Phang Boon Lim, Nicholas W F Linton, Prapa Kanagaratnam

Abstract

Background: The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system may play a role in atrial fibrillation (AF).

Objective: We hypothesized that ablating the ectopy-triggering GPs (ET-GPs) prevents AF.

Methods: GANGLIA-AF (ClinicalTrials.gov identifier NCT02487654) was a prospective, randomized, controlled, 3-center trial. ET-GPs were mapped using high frequency stimulation, delivered within the atrial refractory period and ablated until nonfunctional. If triggered AF became incessant, atrioventricular dissociating GPs were ablated. We compared GP ablation (GPA) without pulmonary vein isolation (PVI) against PVI in patients with paroxysmal AF. Follow-up was for 12 months including 3-monthly 48-hour Holter monitors. The primary end point was documented ≥30 seconds of atrial arrhythmia after a 3-month blanking period.

Results: A total of 102 randomized patients were analyzed on a per-protocol basis after GPA (n = 52; 51%) or PVI (n = 50; 49%). Patients who underwent GPA had 89 ± 26 high frequency stimulation sites tested, identifying a median of 18.5% (interquartile range 16%-21%) of GPs. The radiofrequency ablation time was 22.9 ± 9.8 minutes in GPA and 38 ± 14.4 minutes in PVI (P < .0001). The freedom from ≥30 seconds of atrial arrhythmia at 12-month follow-up was 50% (26 of 52) with GPA vs 64% (32 of 50) with PVI (log-rank, P = .09). ET-GPA without atrioventricular dissociating GPA achieved 58% (22 of 38) freedom from the primary end point. There was a significantly higher reduction in antiarrhythmic drug usage postablation after GPA than after PVI (55.5% vs 36%; P = .05). Patients were referred for redo ablation procedures in 31% (16 of 52) after GPA and 24% (12 of 50) after PVI (P = .53).

Conclusion: GPA did not prevent atrial arrhythmias more than PVI. However, less radiofrequency ablation was delivered to achieve a higher reduction in antiarrhythmic drug usage with GPA than with PVI.

Keywords: Autonomic nervous system; Ganglionated plexi; Ganglionated plexuses; Neuromodulation; Paroxysmal atrial fibrillation.

Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Study flowchart. GPA = ganglionated plexuses ablation; PVI = pulmonary vein isolation.
Figure 2
Figure 2
Example of HFS at a GP site. After the second HFS, PV ectopy is triggered (arrow) with the earliest signal in PV 3-4. This is repeated with further trains of synchronized HFS. Simultaneously, there is a progressive R-R prolongation until 2.8 seconds of AV block, followed by AF. This GP site demonstrates colocation of ectopy-triggering GP and AV dissociating GP. AF = atrial fibrillation; AV = atrioventricular; BP = blood pressure; CS = coronary sinus; GP = ganglionated plexuses; HFS = high frequency stimulation; Mapd = mapping catheter distal; Mapp = mapping catheter proximal; PV = pulmonary vein.
Figure 3
Figure 3
Primary end point. A: The primary end points at 12 months of follow-up in the PVI and the overall GPA group were not significantly different from each other. B: The GPA subgroup that had undergone ET-GP ablation only without incessant AF during GP mapping had greater freedom from >30 seconds of AF/AT than did the overall GPA group in panel A. AF = atrial fibrillation; AT = atrial tachycardia; ET-GP = ectopy-triggering ganglionated plexuses; GPA = ganglionated plexuses ablation; PVI = pulmonary vein isolation.
Figure 4
Figure 4
Example of successful ET-GP ablation without PVI. One hundred thirty-five sites were tested with synchronized HFS; 16.5 minutes of RF ablation was performed on 13 ET-GPs. PVs remained electrically connected. Pacemaker interrogation after 12 months showed no evidence of atrial arrhythmia since ET-GP ablation. The patient has remained symptom free and off all antiarrhythmic drugs. AP = anterior posterior; AF = atrial fibrillation; AT = atrial tachycardia; ET-GP = ectopy-triggering ganglionated plexuses; GP = ganglionated plexuses; HFS = high frequency stimulation; LAA = left atrial appendage; LIPV = left inferior pulmonary vein; LSPV = left superior pulmonary vein; PA = posterior anterior; PV = pulmonary vein; RAO = right anterior oblique; RF = radiofrequency; RIPV = right inferior pulmonary vein; RSPV = right superior pulmonary vein.
Figure 5
Figure 5
Acute AF modification with GPA and long-term outcomes. If >2 minutes of sustained AF was triggered during HFS mapping, GPA was attempted to try and restore SR. Acute AF modification included AF termination to SR, organization to AT, or prolongation of AF cycle length by ≥30 ms. There was a range of success in acute AF modification between patients, which was divided into 100% success in acute AF modification and

Figure 6

Univariate and multivariate analyses in…

Figure 6

Univariate and multivariate analyses in GPA and PVI groups. All variables with P…

Figure 6
Univariate and multivariate analyses in GPA and PVI groups. All variables with P values ≤0.05 from the univariate analysis and well-established risk factors for AF recurrence, such as age and hypertension, were entered into the multivariate regression analysis. AF = atrial fibrillation; AT = atrial tachycardia; AVD-GP = atrioventricular dissociating ganglionated plexuses; BMI = body mass index; CHA2DS2-VASc = congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, previous stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65–74 years, sex category (female); CI = confidence interval; ET-GP = ectopy-triggering ganglionated plexuses; GP = ganglionated plexuses; GPA = ganglionated plexuses ablation; HFS = high frequency stimulation; HR = hazard ratio; HTN = hypertension; LA = left atrial; PVI = pulmonary vein isolation; SR = sinus rhythm; RF = radiofrequency.
Figure 6
Figure 6
Univariate and multivariate analyses in GPA and PVI groups. All variables with P values ≤0.05 from the univariate analysis and well-established risk factors for AF recurrence, such as age and hypertension, were entered into the multivariate regression analysis. AF = atrial fibrillation; AT = atrial tachycardia; AVD-GP = atrioventricular dissociating ganglionated plexuses; BMI = body mass index; CHA2DS2-VASc = congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, previous stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65–74 years, sex category (female); CI = confidence interval; ET-GP = ectopy-triggering ganglionated plexuses; GP = ganglionated plexuses; GPA = ganglionated plexuses ablation; HFS = high frequency stimulation; HR = hazard ratio; HTN = hypertension; LA = left atrial; PVI = pulmonary vein isolation; SR = sinus rhythm; RF = radiofrequency.

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Source: PubMed

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