Left Atrial Ganglionated Plexi Research Articles

Pacing or ablation for vasovagal syncope: one size does not fit all.

Practical decision pathway for the management of vasovagal syncope. Please see text for details. White circles demonstrate sites of grouping of autonomic ganglia defined as ganglionated plexi (GP). The superior right atrial GP (RSGP) located on the posterosuperior surface of the right atrium adjacent to the junction of the superior vena cava and the right atrium; the superior left atrial GP (LSGP) is on the posterosuperior surface of the left atrium between the pulmonary veins; the inferior (posterior) right atrial GP (RIGP) located adjacent to the interatrial groove; the inferior left atrial GP (LIGP) is identified on the posterolateral surface of the left atrium; and the Marshall tract GP (MTGP) located adjacent the vein of Marshall. *Response to atropine which accelerates sinus node automaticity and increases the speed of atrioventricular conduction should be evaluated in all cases prior recommending CNA to confirm adequate procedural response. A sinus rate increase of ≥25% or a sinus rate ≥90 bpm in the first 15 min after infusion should be considered as a positive response.7,13 CLS, closed loop stimulation; CNA, cardioneuroablation; HUT, head-up tilt table test; and ILR, implantable loop recorder.

The impact of the clinical diagnosis on the vagal response and heart rate after ganglionated plexus ablation.

Ganglionated plexi (GP) ablation may be associated with improved syncope or arrhythmia-free survival arrhythmia patients with vasovagal syncope (VVS) and atrial fibrillation (AF), respectively. We aimed to compare the characteristics of vagal response (VR) and clarify the effect on heart rate after GP ablation based on clinical diagnosis. A total of 83 consecutive patients undergoing GP ablation were divided following two groups: (1) GP ablation for VVS (VVS group, n = 43) and (2) GP ablation in addition to pulmonary vein isolation (AF group, n = 40). We examined VR characteristics during RF ablation and high frequency stimulation, respectively, in the VVS and AF groups. To evaluate immediate and long-term heart rate response, a standard 12-lead ECG was obtained at baseline at 24h after ablation and at the last follow-up visit. In the VVS group, the superior and inferior left atrial GPs were the most common GP sites at which a VR was observed. No VR was seen during radiofrequency application in the superior and inferior right atrial GPs in the VVS group. On the contrary, VR was more prevalent in the right-sided GPs during high-frequency stimulation in the AF group. VR was observed during ablation in only one patient with AF. Although the heart rate increased significantly after ablation in both groups, the effect was more prominent and durable in the VVS group. The autonomic response during GP ablation is different in VVS compared to AF, suggesting that VVS and AF may represent distinct forms of autonomic hyperactivity.

The relationship between global cardiac and regional left atrial sympathetic innervation and epicardial fat in patients with atrial fibrillation.

To investigate the relationship between epicardial adipose tissue (EAT) volume and distribution and the parameters of global cardiac and regional left atrial (LA) sympathetic activity in patients with atrial fibrillation (AF). The data of the 45 consecutive patients scheduled for an index catheter ablation (CA) for AF were analyzed. Total and peri-atrial EAT volumes were measured by cardiac CT. Parameters of global cardiac sympathetic activity and discrete sympathetic regions around LA were assessed by 123I-mIBG SPECT/CT. The patients were followed up for AF recurrences assessment during 12months after CA. A total of 133 (mean per patient 2.96 ± 1.07) discrete 123I-mIBG uptake areas (DUAs), corresponding to typical anatomical locations of LA ganglionated plexi (GP), were identified. Peri-atrial EAT volume was associated with the number of DUAs (regression estimate, 5.1 [95% CI, 0.3-9.9], p = 0.03). There was no statistically significant association between either total or peri-atrial EAT volumes and risks of AF recurrence. The washout rate (WR) was associated with reduced risk of AF recurrence (HR = 0.95; 95% CI 0.92-0.99; p = 0.01), while left ventricular (LV) myocardium 123I-mIBG summed defect score (SDS) was linked to increased hazards of AF recurrence (HR = 1.04; 95% CI 1.01-1.08; p = 0.03). Peri-atrial EAT volume is associated with regions of sympathetic activity corresponding to typical anatomical locations of LA GP. The WR was associated with reduced risk of AF recurrence while LV myocardial SDS was linked to increased hazards of AF recurrence.

The anatomical basis behind the neuromodulation effects associated with pulmonary vein isolation.

The anatomical basis underlying the neuromodulation effects seen with pulmonary vein (PV) isolation (PVI) is not fully understood. Left atrial (LA) electro-anatomical maps of 38 patients who underwent catheter cardioneuroablation for vagally mediated bradycarrhythmias were studied. During the procedure, LA ganglionic plexi (GPs) were systematically identified and ablated. Design PVI lines were created on these maps by a blinded observer, and the degree of overlap between four GPs and individual PVs was assessed. Here, 1.7 ± 7 (35.5 ± 17.0%) of the total 31.6 ± 10 GP ablation sites per patient were found to overlap with the design PVI lines. The overlap was higher for the right-sided GPs, p < .001. The degree of GP-PV overlap varied: 1 PV in 5 (13.2%) patients, 2 PVs in 15 (39.2%), 3 PVs in 16 (42.1%), and all 4 PVs in 2 (5.3%). No patient had zero GP-PV overlap. A vagal response was most commonly observed during ablation at the left superior GP (89.5%), while a sympathetic response was observed most often during the right superior GP ablation (97.4%). Some degree of GP-PV antral overlap is the norm, and this is more pronounced for the right-sided PVs. There is significant individual variability in the degree of overlap which may explain why neuromodulation effects are not seen universally following PVI.

Epicardial injection of nanoformulated calcium into cardiac ganglionic plexi suppresses autonomic nerve activity and postoperative atrial fibrillation

Imbalanced activation of the cardiac autonomic nervous system triggers postoperative atrial fibrillation (POAF). Neuronal calcium overload induces apoptosis. We hypothesize that epicardial injection of timed-release nanoformulated CaCl2 (nCaCl2) into left atrial ganglionic plexi (GP) modulates autonomic function and suppresses POAF. The purpose of this study was to determine whether nCaCl2 GP therapy suppresses POAF. We used a novel canine model of POAF with implanted radiotelemetry to record nerve activity (NA) from the left stellate ganglion (SNA), left cardiac vagus nerve, and GP. At week 3, nCaCl2 (n = 7) or vehicle control (sham; n = 3) was injected into left pulmonary vein GP (LGP), followed by right pulmonary vein GP at week 4. Atrial effective refractory period (AERP) and atrial fibrillation vulnerability (AFV) were assessed invivo. Resting and exercise NA and heart rate (HR) were assessed before and after LGP treatment. AERP decreased (P < .0001) and AFV increased (P=.008) at week 3 vs baseline. However, nCaCl2-LGP treatment reversed these changes and restored them to baseline after 1week (P = .04). Subsequent nCaCl2-right pulmonary vein GP treatment further reduced AFV (P = .03). In contrast, AFV increased (P=.001) and AERP remained decreased (P = .01) 1 week after sham-LGP treatment vs baseline. nCaCl2-LGP treatment reduced NA from GP (P < .02) and NA from the left cardiac vagus nerve (P<.05) and increased SNA (P < .02). Despite increased SNA, HR was decreased (P < .01) with loss of HR-SNA correlation (R=0.62). After sham-LGP treatment, NA was unchanged and HR-SNA remained correlated (R = 0.95). Histology confirmed nCaCl2-GP colocalization, apoptosis, and loss of immunoreactivity in nCaCl2-treated somas. Epicardial injection of nCaCl2 into left atrial GP induced neuroapoptosis and modulated autonomic function. This reversed a postoperative reduction in AERP and suppressed POAF.

19Neuro-specific stimulation of the left atrial ganglionated-plexi sites reveals triggered atrial activity

19Neuro-specific stimulation of the left atrial ganglionated-plexi sites reveals triggered atrial activity

Long-term outcomes of minimally invasive surgical ablation for atrial fibrillation: A single-center experience

Minimally invasive surgical atrial fibrillation (AF) ablation (MISAA) delivers radiofrequency energy via a thoracoscopic approach to perform pulmonary vein isolation and left atrial ganglionic plexi ablation. Data on long-term outcomes of MISAA are lacking. We report 5-year follow-up data from a prospective cohort of patients who underwent MISAA at a single center. One hundred nine consecutive patients (60 paroxysmal, 49 persistent; mean age 62.7 ± 9.3 years) underwent MISAA with left atrial appendage exclusion by a single surgeon between 2006 and 2012. Patients were followed with transtelephonic monitoring at 1, 6, and 12 months and annually thereafter for up to 5 years. Recurrence was defined as any atrial tachyarrhythmia lasting ≥30 seconds from 90 days after surgery onward. Mean follow-up duration was 1738.5 ± 661.5 days. Single-procedure success rate was 38% (37 of 98 patients). Atrial arrhythmias occurred in 22%, 42%, 55%, 59%, and 62% of patients by 1, 2, 3, 4, and 5 years. Seventy-eight (79.6%) patients remained AF free with or without additional interventions including catheter ablation, antiarrhythmic drugs, or cardioversion. There was no significant difference in AF-free survival between paroxysmal and persistent AF groups (P = .725). Multivariate analyses showed hypertension to be a significant predictor of AF recurrence (odds ratio 6.6, confidence interval 1.41-30.80; P= .016). Five (5.1%) patients had a stroke or transient ischemic attack during follow-up. AF-free survival was 38% at 5 years after MISAA. A total of 79.6% of patients remained AF free with or without additional intervention. Patients may have an ongoing risk of stroke even in the absence of AF recurrences.

Interconnections between Left Atrial Ganglionic Plexi: Insights from Minimally Invasive Maze Procedures and Their Outcomes.

Ganglionic plexi (GPs) have been implicated as triggers of atrial fibrillation (AF) and are known to have functional interconnections. Understanding these connections could result in a more effective ablation. The objective of this study is to assess relationships between right- and left-sided GPs in patients undergoing mini-maze (MM) surgery. We also analyzed the impact of these findings on AF recurrence. The GPs were accessed thoracoscopically right side first (group 1) or left side first (group 2). GPs were identified by high-frequency stimulation at 20 predetermined sites and ablation of GPs was performed using a selective or an empiric anatomic approach. Ganglionic plexus (GP) activity was then assessed on the contralateral side and ablated. Sixty-seven patients underwent MM (45 patients in group 1 and 22 in group 2). Fewer patients with active left GPs (LGP) were noted in group 1 (13, 29%) as compared to group 2 (18, 82%). The number of active LGP was also lower (0.6 ± 1.2) in group 1 compared to group 2 (4.7 ± 2.7); P < 0.0001. No significant differences were noted in the frequency of identifiable right GPs (RGP) between groups 1 and 2 (P > 0.05). There were no differences in atrial tachyarrhythmia (AT)/AF recurrence rates between groups 1 and 2 (P = 0.21). However, group 1 patients who underwent selective GP ablation alone had higher recurrence rates (P = 0.016). Mapping and ablation of RGPs first decreased identifiable LGP activity. With selective GP ablation, patients who underwent RGP ablation first had higher AT/AF recurrence.

Оценка качества жизни у пациентов с ишемической болезнью сердца в сочетании c фибрилляцией предсердий после радиочастотной аблации анатомичесих зон ганглионарных сплетений левого предсердия

Оценка качества жизни у пациентов с ишемической болезнью сердца в сочетании c фибрилляцией предсердий после радиочастотной аблации анатомичесих зон ганглионарных сплетений левого предсердия

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

The aim of this study was to investigate whether the combination of conventional pulmonary vein isolation (PVI) by circumferential antral ablation with ganglionated plexi (GP) modification in a single ablation procedure, yields higher success rates than PVI or GP ablation alone, in patients with paroxysmal atrial fibrillation (PAF). Conventional PVI transects the major left atrial GP, and it is possible that autonomic denervation by inadvertent GP ablation plays a central role in the efficacy of PVI. A total of 242 patients with symptomatic PAF were recruited and randomized as follows: 1) circumferential PVI (n = 78); 2) anatomic ablation of the main left atrial GP (n = 82); or 3) circumferential PVI followed by anatomic ablation of the main left atrial GP (n = 82). The primary endpoint was freedom from atrial fibrillation (AF) or other sustained atrial tachycardia (AT), verified by monthly visits, ambulatory electrocardiographic monitoring, and implantable loop recorders, during a 2-year follow-up period. Freedom from AF or AT was achieved in 44 (56%), 39 (48%), and 61 (74%) patients in the PVI, GP, and PVI+GP groups, respectively (p = 0.004 by log-rank test). PVI+GP ablation strategy compared with PVI alone yielded a hazard ratio of 0.53 (95% confidence interval: 0.31 to 0.91; p = 0.022) for recurrence of AF or AT. Fluoroscopy duration was 16 ± 3 min, 20 ± 5 min, and 23 ± 5 min for PVI, GP, and PVI+GP groups, respectively (p < 0.001). Post-ablation atrial flutter did not differ between groups: 5.1% in PVI, 4.9% in GP, and 6.1% in PVI+GP. No serious adverse procedure-related events were encountered. Addition of GP ablation to PVI confers a significantly higher success rate compared with either PVI or GP alone in patients with PAF.

Identification of left atrium ganglionated plexi by dense epicardial mapping as ablation targets for the treatment of concomitant atrial fibrillation

Purpose: Autonomic ganglionated plexi (GP) have great plasticity in the initiation and maintenance of atrial fibrillation. GP ablation may be an important component for a maze procedure. The purpose of this study was to identify the localization of left atrial GP based on dense epicardial mapping during a maze IV procedure with concomitant AF patients. Methods: Sixteen patients (age, 68±10 years; 11 males, 69%; left atrial diameter, 53±8 mm; and left ventricular ejection fraction, 57±12%) with heart failure and concomitant atrial fibrillation underwent intraoperative epicardial electrophysiological mapping and GP ablation using the maze procedure at our institution. The mean duration of atrial fibrillation was 55±86 months; atrial fibrillation was paroxysmal in 4 patients (25%). Twenty-four site, high-frequency stimulation (1000/min; output, 18 V; pulse width, 0.75 ms) was performed by placing tweezers directly onto the potential GP sites on the left atrial epicardium. Diagram of epicardial mapping locations is shown in the figure. Results: Active GP were found in 13 (81%) of the 16 patients, and all of those patients had active GP between the right pulmonary veins and the interatrial groove. (R6, R10, R12) A 7-day event-loop recording demonstrated that 13 (81%) of the 16 patients were maintained in sinus rhythm 3 months after the operation. For those patients with active GP locations, 12 (92%) out of 13 patients were maintained in sinus rhythm (92%). ![Figure][1] Conclusions: Dense epicardial mapping in the potential GP areas identified active GP locations in a high percentage of patients. GP between the pulmonary veins and the interatrial groove have high potential as ablation targets for treatment of atrial fibrillation. [1]: pending:yes

Identification of Left Atrial Ganglionated Plexi by Dense Epicardial Mapping as Ablation Targets for the Treatment of Concomitant Atrial Fibrillation

BackgroundAutonomic ganglionated plexi (GPs) play a significant role in the initiation and maintenance of atrial fibrillation (AF). GPs are key targets for a maze procedure. The purpose of this study was to identify the location of the left atrial GPs based on dense epicardial mapping during a maze procedure in patients with concomitant AF.MethodsSixteen patients (age, 68 ± 10 years; 11 males, 69%) with heart failure and concomitant AF (duration 55 ± 86 months) underwent intraoperative epicardial electrophysiological mapping and a GP ablation using the maze procedure at our institution. Twenty-four-site, high-frequency stimulation (1,000/min; output, 18 V; pulse width, 0.75 ms) was performed by placing tweezers directly onto the potential GP sites on the left atrial epicardium.ResultsActive GPs were found in 13 (81%) of the 16 patients, and 12 (92%) of 13 patients had active GPs between the right pulmonary veins (PVs) and the interatrial groove. For those patients with active locations, a 7-day event-loop recording demonstrated that 12 (92%) of 13 patients were maintained in sinus rhythm 3 months after the operation.ConclusionDense epicardial mapping in the potential GP areas identified active GP locations in a high percentage of patients. GPs between the PVs and interatrial groove have a high potential as ablation targets for treatment of concomitant AF.

Characterization of the Left Atrial Neural Network and its Impact on Autonomic Modification Procedures

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.

049 The role of the neural networks in identification and ablation of pulmonary vein ectopic triggers

IntroductionThe cardiac neural network comprises ganglionated plexi (GP) adjacent to each pulmonary vein (PV) which can trigger AV block and PV ectopy. We hypothesised that AV block in response to...

The Relationship between Acute Termination by Ganglionated Plexi Ablation and Cycle Length of Atrial Fibrillation

The antifibrillatory effect of ganglionated plexi (GP) ablation is not well established. The aim of this study was to evaluate the factors associated with termination during GP ablation in patient with paroxysmal AF. Methods: Thirty-two consecutive paroxysmal AF patients (age 61±10 years, 25 male) who underwent the selective GP ablation guided by high frequency stimulation (HFS) were enrolled in this study. The five major left atrial GP were localized by delivering HFS (20 Hz, 20 V, 10 ms pulse width). Radiofrequency current is then applied to that site to eliminate the parasympathetic response. We ablated GP first, and antrum PV electrical isolation (APVI) adjunctively. We measured cycle length (CL) in each PV, left atrial appendage (LAA), coronary sinus (CS), RA, during AF before any ablation. We investigated the termination of AF in relation with GP ablation. Results: AF was induced and sustained in 29 patients. AF terminated during GP ablation in 14 patients (48%), during APVI in 6 patients (21%). Two of 3 patients without sustained AF had SVC foci. The LAA and CS AFCL (142±22 ms, 138±19 ms) in 9 patients without termination were shorter than that in 20 patients with termination (170±33 ms, 171±27 ms, p<0.05). Conclusions: Selective GP ablation alone showed antifibrillatory effects particularly in patients with the low degree atrium remodeling. Adjunctive APVI strengthened these effects.

Left Atrial Ablation at the Anatomic Areas of Ganglionated Plexi for Paroxysmal Atrial Fibrillation

Modification of left atrial ganglionated plexi (GP) is a promising technique for the treatment of paroxysmal atrial fibrillation (AF) but its therapeutic efficacy is not established. This study aimed at evaluating the effectiveness of anatomic GP modification by means of an implantable arrhythmia monitoring device. In 56 patients with paroxysmal AF, radiofrequency ablation at anatomic sites, where the main clusters of GP have been identified in the left atrium, was performed. In all patients, an electrocardiogram monitor (Reveal XT, Medtronic Inc., Minneapolis, MN, USA) was implanted before (n = 7) or immediately after (n = 49) AF ablation. Average duration of the procedure was 142 ± 18 min and average fluoroscopy time 20 ± 7 min. In total, 53-81 applications of RF energy were delivered (mean of 18.2 ± 3.8 at each of the four areas of GP ablation). Heart rate variability was assessed in 31 patients. Standard deviation of RR intervals over the entire analyzed period, the root mean square of differences between successive RR intervals, and high frequencies decreased, while HRmin, HRmean, and LF to HF ratio increased immediately postablation; these values returned to baseline 6 months after the procedure. At end of 12-month follow-up, 40 (71%) patients were free of arrhythmia recurrence. Ten patients had AF recurrence, two patients had left atrial flutter, and four patients had episodes of flutter as well as AF recurrence. Duration of episodes of AF after ablation gradually decreased over the follow-up period. Regional ablation at the anatomic sites of the left atrial GP can be safely performed and enables maintenance of sinus rhythm in 71% of patients with paroxysmal AF for a 12-month period.

Results of a Minimally Invasive Surgical Pulmonary Vein Isolation and Ganglionic Plexi Ablation for Atrial Fibrillation

Background— The Cox Maze procedure for treatment of medically refractory atrial fibrillation (AF) is limited by its complexity and requirement for cardiopulmonary bypass. Long-term follow-up and success using criteria established by the Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society consensus statement have not been reported for surgical AF ablation. We describe the results of using a thorascopic approach and radiofrequency energy to perform bilateral pulmonary vein isolation and left atrial ganglionic plexi ablation for treatment of AF. Methods and Results— Forty-five (33 paroxysmal; 12 persistent) consecutive patients underwent thorascopic bilateral radiofrequency pulmonary vein isolation, ganglionic plexi ablation, ligament of Marshall ablation, and left atrial appendage exclusion by a single surgeon. Forty-three patients were prospectively followed without antiarrhythmic drugs for a minimum of 1 year with a 30-day continuous event monitor or pacemaker interrogation at 6 and 12 months. Failure was defined as any atrial tachyarrhythmia of &gt;30 seconds’ duration occurring &gt;90 days after surgery. Mean follow-up was 516�181 days (202 to 858 days). Twenty-eight (65%) patients had no atrial tachyarrhythmia &gt;30 seconds by 1 year, and 15 (35%) patients had atrial tachyarrhythmia recurrences by 1 year. Eight of 15 patients with recurrent AF had catheter ablation resulting in elimination and/or reduction of AF episodes in 7 of 8 patients. Four of 15 patients had AF elimination or reduction with antiarrhythmic drugs alone. Three patients did not benefit from surgery and received rate control only. There were no deaths; 1 phrenic nerve injury and 2 pleural effusions were the only major complications. Conclusions— The single procedure success at 1-year follow-up for surgical pulmonary vein isolation and ganglionic plexi ablation is 65%. Atrial tachyarrhythmia recurrences after surgery are usually responsive to catheter ablation and/or antiarrhythmic drugs.

Anatomic Approach for Ganglionic Plexi Ablation in Patients With Paroxysmal Atrial Fibrillation

There is evidence that parasympathetic denervation may prevent atrial fibrillation (AF) recurrences. This study aimed at applying an anatomic approach for ablation of atrial ganglionic plexi (GPs) in patients with paroxysmal AF. Nineteen patients with symptomatic, paroxysmal AF underwent anatomically guided radiofrequency ablation at the location of the 4 main left atrial GPs and were prospectively assessed for recurrence of AF or other atrial arrhythmia. This group was compared with 19 age- and gender-matched patients who previously underwent conventional circumferential pulmonary vein ablation. All ablation procedures were uneventful. Circumferential and GP ablations were accomplished with a radiofrequency delivery time of 28 +/- 5 versus 18 +/- 3 min (p <0.001) and a fluoroscopy time of 31 +/- 5 versus 18 +/- 5 min (p <0.001), respectively. Parasympathetic reflexes during radiofrequency ablation were elicited in 4 patients (21%). Arrhythmia recurred in 7 patients (37%) with circumferential ablation and 14 patients (74%) with GP ablation, during 1-year follow-up (p for log-rank test = 0.017). In 2 patients with GP ablation, left atrial flutters were documented in addition to AF during follow-up. Patients who underwent GP ablation had an almost 2.5 times higher risk of AF recurrence compared with those who underwent circumferential ablation (hazard ratio 2.6, 95% confidence interval 1.0 to 6.6, p = 0.038). In conclusion, anatomically guided GP ablation is feasible and safe in the electrophysiology laboratory, but this approach yields inferior clinical results compared with circumferential ablation.

Electrical Stimulation to Identify Neural Elements on the Heart: Their Role in Atrial Fibrillation

Anesthetized dogs were subjected to a right then left thoracotomy. Two modes of electrical stimulation were used to activate ganglionated plexi (GP) on the epicardium of the atria: (1) Near the base of each pulmonary vein (PV), trains of high frequency stimuli (HFS) were coupled to each atrial paced beat so as to fall within the refractory period to achieve nerve stimulation without atrial excitation; and (2) Continuous HFS was applied via plaque electrodes sutured to epicardial fat pads (containing a GP) near the right superior (RS) and left superior (LS) PVs. The chest was then closed. An ablation catheter, inserted percutaneously, was positioned fluoroscopically in the right atrium across from the epicardial plaque electrode near the RSPV. Transeptal puncture was used to place an ablation catheter at the LSPV-left atrial junction. HFS applied to each of the epicardial fat pads induced atrial fibrillation (AF) and also caused high grade AV block due to a strong parasympathetic effect on the AV node. Radiofrequency ablation from the right and left atrial endocardium abolished the vagal response to HFS delivered to the plaque electrodes on the fat pads close to the RSPV and LSPV, respectively. Sixty (60) patients with paroxysmal or persistent AF underwent PV antrum isolation (27 patients) or PV antrum isolation plus left atrial GP ablation (33 patients). Endocardial HFS at the border of the PV antra near the 4 GPs produced AF and high grade AV block (vagal response) during AF. RFA at these sites abolished the vagal response. Testing in a small number of patients with very short follow-up suggests that adding GP ablation to PV antrum isolation may increase ablation success (absence of AF recurrence) from 70% to 91%. These basic and clinical studies suggest that localized cardiac autonomic ganglia (GPs) may play a critical role in the initiation and maintenance of AF.