The Role of α7nAChR-Mediated Cholinergic Anti-Inflammatory Pathway in Vagal Nerve Regulated Atrial Fibrillation.

The aim was to investigate the role of the α7nAChR-mediated cholinergic anti-inflammatory pathway in vagal nerve regulated atrial fibrillation (AF).18 beagles (standard dogs for testing) were used in this study, and the effective refractory period (ERP) of atrium and pulmonary veins and AF inducibility were measured hourly during rapid atrial pacing at 800 beats/minute for 6 hours in all beagles. After cessation of 3 hours of RAP, the low-level vagal nerve stimulation (LL-VNS) group (n = 6) was given LL-VNS and injection of salinne (0.5 mL/GP) into four GPs, the methyllycaconitine (MLA, the antagonist of α7nAChR) group (n = 6) was given LL-VNS and injection of MLA into four GPs, and the Control group (n = 6) was given saline into four GPs and the right cervical vagal nerve was exposed without stimulation. Then, the levels of the tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), acetylcholine (ACh), STAT3, and NF-κB proteins were measured. During the first 3 hours of RAP, the ERPs gradually decreased while the dispersion of ERPs (dERPs) and AF inducibility gradually increased in all three groups. During the last 3 hours of 6 hours' RAP in this study, the ERPs in the LL-VNS group were higher, while the dERPs and AF inducibility were significantly lower when compared with the Control and MLA groups at the same time points. The levels of ACh in the serum and atrium in the LL-VNS and MLA groups were higher than in the Control group, and the levels of TNF-α and IL-6 were higher in the Control and MLA groups than in the LL-VNS group. The concentrations of STAT3 in RA and LA tissues were higher in the LL-VNS group while those of NF-κB were lower.In conclusion, the cholinergic anti-inflammatory pathway mediated by α7nACh plays an important role in low-level vagal nerve-regulated AF.

Heart rate increase after pulmonary vein isolation predicts freedom from atrial fibrillation at 1 year.

INTRODUCTION: Ablation of atrial vagal ganglia has been associated with improved pulmonary vein isolation (PVI) outcomes. Disruption of vagal reflexes results in heart rate (HR) increase. We investigated the association between HR change after PVI and freedom from atrial fibrillation (AF) at 1 year. METHODS AND RESULTS: Patients who underwent PVI for paroxysmal AF were identified from the Johns Hopkins Hospital AF registry. Electrocardiograms taken pre-PVI and post-PVI were used to determine the change in HR. Patients followed-up at 3, 6, and 12 months. Of 257 patients (66% male, age 59+/-11 years), 134 (52%) remained free from AF at 1 year. The average HR increased from 60.6 ± 11.3 beats per minute (bpm) pre-PVI to 70.7 ± 12.0 bpm post-PVI. Patients with recurrence of AF had lower post-PVI HR than those who remained free from AF (67.8 ± 0.2 vs 73.3 ± 13.0 bpm; P <.001). The probability of AF recurrence at 1-year decreased as the change in HR increased (estimated odds ratio [OR], 0.83; 95% confidence interval [CI, 0.74-0.93]; P = .002). HR increase more than 15 bpm was associated with the lowest odds of AF recurrence (estimated OR, 0.39; 95% [0.17-0.85]; P = .018) compared to HR decrease. CONCLUSIONS: Resting HR was found to increase after PVI. Increase in HR more than 15 bpm has a positive association with remaining free from atrial fibrillation at 1 year.

Different effects of additional ganglion plexus ablation on catheter and surgical ablation for atrial fibrillation: a systemic review and meta-analysis.

The effect of ganglion plexus (GP) ablation in addition to pulmonary veins isolation (PVI) for atrial fibrillation (AF) remained controversial between the catheter and surgical-based studies. Eleven studies (five randomized controlled trials and six nonrandomized studies) of 1750 patients were included in a meta-analysis to elucidate the incremental benefit of additional GP ablation in patients undergoing catheter or surgical ablation. Risk ratios were calculated for freedom from AF or AT recurrence after a single procedure. Additional GP ablation was associated with a better rhythm outcome for patients undergone catheter ablation but did not seem to increase freedom from AF/AT for surgical patients. Both paroxysmal and non-paroxysmal AF showed a positive outcome comparing additional GP ablation with PVI alone.

Coincidental ganglionated plexus modification during radiofrequency pulmonary vein isolation and post-ablation arrhythmia recurrence.

AIMS: Vagal responses (VR) during left atrial ablation for atrial fibrillation (AF) treatment have been reported to be associated with less recurrences, presumably because they are a sign of ganglionated plexi modification. Our objective was to evaluate whether coincidentally elicited VR during left atrial ablation are associated with lower AF recurrence rates. METHODS AND RESULTS: This is a post hoc analysis of a prospective study of 291 patients with paroxysmal AF undergoing radiofrequency pulmonary vein isolation (PVI). Vagal responses were defined as episodes of heart rate <40 bpm or asystole lasting >5 s elicited during energy application. Sixty-eight patients (23.4%) had a VR during ablation. In Kaplan-Meier analysis, mean recurrence-free survival was 449 days (95% confidence interval 411-488) in patients with VR when compared with 435 days (95% confidence interval 415-455) in those without (P = 0.310). The 12-month recurrence rate estimates were 25 and 27%, respectively. In an unadjusted Cox model, VR was associated with an odds ratio for recurrence of 0.77 (95% confidence interval 0.46-1.28). CONCLUSION: Coincidentally elicited VR during radiofrequency PVI in patients with paroxysmal AF do not appear to be related to lower risk of arrhythmia recurrence. This may mean that, even if a VR is truly a sign of coincidental ablation of a ganglionated plexus, this does not necessarily mean that a therapeutic modification has been effected, at least to a degree associated with clinical benefit.

The Hot and the Cold: Radiofrequency Versus Cryoballoon Ablation for Atrial Fibrillation.

Catheter ablation is superior to antiarrhythmic drugs in maintaining sinus rhythm for patients with atrial fibrillation (AF). Pulmonary vein (PV) isolation is the cornerstone of any AF ablation procedure. Conventionally, this is achieved by performing point by point lesions using radiofrequency (RF) energy. However, this is technically challenging, time consuming and is associated with a number of complications. Long-term durability of PV isolation is also a concern. To address these issues, 'one-shot' energy delivery systems and alternative energy sources have been developed. The cryoballoon system has emerged as the most commonly used alternative to point by point RF technology. In this paper, we compare the technology, biophysics and clinical data of cryoballoon to conventional RF ablation for AF. The safety and efficacy of cryoballoon compared to RF ablation is critically reviewed. We conclude by looking at future applications of this technology.

[Catheter Isolation of Pulmonary Veins in a Patient With Paroxysmal Atrial Fibrillation After Repair of Interventricular Septum With a Xeno-Pericardial Patch].

Catheter radiofrequency ablation of focal atrial fibrillation was successfully performed in a patient after closure of interventricular septal defect with a xeno-pericardial patch and plastic of tricuspid valve. The case demonstrates feasibility of carrying out such interventions under intracardiac echocardiographic guidance in patients with disturbed anatomy and complicated access to the left atrium.

[Predictors of Efficacy of Radiofrequency Ablation of Pulmonary Veins Performed During Coronary Bypass Surgery in Patients With Ischemic Heart Disease and Paroxysmal Atrial Fibrillation].

We performed simultaneous coronary artery bypass grafting (CABG) and radiofrequency ablation (RFA) ostia of pulmonary veins in 254 patients (147 men and 107 women) with ischemic heart disease and paroxysmal atrial fibrillation (AF). In-hospital mortality in patients with early recurrence of AF was 8.4%, in patients without recurrence of AF 1.9% (χ2 = 4.65; p = 0.03). The patients were followed-up during 12 months after operation. During follow-up 166 patients (69.5%) had no recurrence of AF without receiving antiarrhythmic drugs (AAP), 33 patients (13.8%) had recurrences of AF, and 40 patients (16.7%) receiving AAD had repeated rare paroxysms of AF. Main predictors of late AF recurrence were age > 65 years, AF duration > 5 years, preoperative atrial effective refractory period < 240 ms, frequency threshold of AF induction < 400 counts/min, anteroposterior left atrial size > 50 mm, glomerular filtration rate < 60 ml/min/1.73 m2. Reverse dynamics of structural, functional and electrophysiological parameters of the heart due to CABG and RFA, use of ß-blockers, angiotensin converting enzyme inhibitors and aldosterone antagonists were associated with the preservation of a stable sinus rhythm. The cardiovascular mortality during 12 months follow-up accounted for 2.1% and 1.2% in groups of patients with and without late recurrences of AF respectively (p > 0.05) to coronary artery bypass grafting surgery and RFA, taking drugs--ß-blockers, angiotensin converting enzyme inhibitors and aldosterone antagonists--were associated with the preservation of a stable sinus rhythm.

Additional benefit of cryoballoon-based atrial fibrillation ablation beyond pulmonary vein isolation: modification of ganglionated plexi.

AIMS: It has been known that cryoballoon-based pulmonary vein isolation (PVI) is an efficacious and a safe therapeutic option to eliminate triggers of atrial fibrillation (AF). However, the effect of cryoablation on external modifiers of AF-like ganglionated plexi (GP) has never been investigated. In this study, we aimed to investigate whether vagal reactions probably due to GP modification during cryoablation, are associated with success rates during follow-up. METHODS AND RESULTS: A total of 145 patients (age: 54.5 ± 10.1, 52.4% males and 80.7% paroxysmal AF) who were symptomatic despite treatment with ≥ 1 antiarrhythmic drug underwent PVI with cryoballoon. Occurrences of intraprocedural vagal reactions were recorded in all patients. Intraprocedural vagal reaction was observed in 59 patients (40.7%). Vagal reaction characterized by bradycardia and hypotension was more common in patients free of AF recurrence as was the requirement of atropine administration or temporary pacing (46.2 vs. 15.4%, P = 0.004 and 38.7 vs. 7.7%, P = 0.002, respectively). At a median 17 (4-27) months follow-up, AF recurrence was observed in 26 (17.9%) patients. Multivariate Cox regression analysis showed that non-paroxysmal AF, left atrial diameter, and early recurrence significantly increased AF recurrence; however, requirement of atropine administration or temporary pacing (hazard ratio: 0.064; 95% confidence interval: 0.008-0.48, P = 0.008) decreased AF recurrence. CONCLUSION: Our findings indicate that vagal reactions during cryoablation, as a surrogate marker of cardiac ANS modification, decrease AF recurrence in a subgroup of patients with paroxysmal and persistent AF. This finding may be attributed to the concomitant ablation of GP during antral PVI.

Stand alone surgical ablation for atrial fibrillation.

BACKGROUND: Trials to maintain sinus rhythm in patients with atrial fibrillation (AF) and refractory symptoms have been complicated by lack of success or intolerance of medications. Experience with minimally invasive AF surgery is relatively new, and early results have been promising. However, the study populations and techniques were heterogeneous, and the follow-up periods were short in many series. METHODS: We present a single center experience through a retrospective review of medical records of patients who had minimally invasive AF surgery. RESULTS: The surgical techniques addressed several possible mechanisms of AF and causes of recurrence, including pulmonary vein isolation, underlying substrates modification, ligament of Marshall interruption, ganglion plexus ablation, and left atrial appendage exclusion. Thirty-three cases were identified. The mean duration of follow-up was 23.2 months, and 58.6% were maintained in a sinus rhythm and were off antiarrhythmic drugs at the end of the follow-up period. Cases with persistent AF had a lower success rate. CONCLUSION: Results with minimally invasive surgery are suboptimal at two years of follow-up, particularly for patients with persistent AF.

Epicardial confirmation of conduction block during thoracoscopic surgery for atrial fibrillation--a hybrid surgical-electrophysiological approach.

BACKGROUND: Totally thoracoscopic epicardial pulmonary vein ablation is an emerging treatment of atrial fibrillation (AF). A hybrid surgical-electrophysiological procedure with periprocedural confirmation of conduction block might reduce recurrences of AF or atrial tachycardia and improve surgical success. METHODS AND RESULTS: We report our joint surgical-electrophysiological approach for confirmation of conduction block across pulmonary vein ablation lines and those compartmentalizing the left atrium during totally thoracoscopic surgery. A diagnostic electrophysiology (EP) catheter positioned under the left atrium is used as reference and a custom-made multi-electrode for recording. Determination of conduction block across the pulmonary vein (PV) ablation lines requires measurement of activation time differences of milliseconds. Second, a stable reference electrogram to which to relate local activation time is required. Third, the recording electrode terminals and the inter-electrode distance should be small to prevent recording of far field activity and to allow recording of very small electrograms. We confirm entry and exit block and determine conduction block across linear ablation lines with differential pacing. CONCLUSION: A joint surgical-electrophysiological protocol for confirmation of conduction block across PV isolation lines and left atrial ablation lines is feasible and might prevent recurrences and further improve the success of minimally invasive surgery for AF.

[Efferent innervation of pulmonary blood vessels and bronchi in rat (an immunohistochemical study)].

In this investigation the peculiarities of innervation of bronchi and blood vessels of the lung were studied in 20 rats using immunohistochemical demonstration of synaptophysin and alpha-actin. The results obtained have showen that the densest innervation is typical for bronchial walls, particularly, for the muscular lamina. Synaptophysin-immunoreactive terminals (SFIT) were detected in the bronchi in close association with both circular bundles of smooth muscle cells and microganglia. Dense network of SFIT was found in the pulmonary vein--in its middle tunic formed by cardiomyocytes. In contrast to the bronchi and pulmonary vein, large branches of the pulmonary artery contained no SFIT. We briefly discuss the problem of the origin of the nerve fibers described and their functions and suggest that SFIT are formed by efferent fibers (axons) of neurons arising from either the intrapulmonary parasympathetic ganglia.

Human Pulmonary Vein Myocardial Sleeve Autonomic Neural Density and Cardiovascular Mortality.

Myocardial sleeves around pulmonary veins (PVs) are highly innervated structures with heterogeneous morphological and electrophysiological characteristics. Autonomic nerve dysfunction in the myocardium may be associated with an increased risk of cardiovascular morbidity and mortality. This article studied autonomic neural remodeling in myocardial sleeves around PVs and atrial-PV ostia with immunohistochemical and morphometric methods with clinicopathological correlations. PVs were collected from 37 and atrial-PV ostia from 17 human autopsy hearts. Immunohistochemical analysis was performed using antibodies against tyrosine hydroxylase (TH), choline acetyltransferase (CHAT), and growth-associated protein 43 (GAP43). In the PV cohort, subjects with immediate cardiovascular cause of death had significantly decreased sympathetic nerve density in fibro-fatty tissue vs those with non-cardiovascular cause of death (1624.53 vs 2522.05 µm2/mm2, p=0.038). In the atrial-PV ostia cohort, parasympathetic nerve density in myocardial sleeves was significantly increased in subjects with underlying cardiovascular cause of death (19.48 µm2/mm2) than subjects with underlying non-cardiovascular cause of death with no parasympathetic nerves detected (p=0.034). Neural growth regionally varied in sympathetic nerves and was present in most of the parasympathetic nerves. Heterogeneous autonomic nerve distribution and growth around PVs and atrial-PV ostia might play a role in cardiovascular morbidity and mortality. No association in nerve density was found with atrial fibrillation.

Dormant pulmonary vein conduction induced by adenosine in patients with atrial fibrillation who underwent catheter ablation.

BACKGROUND: intravenous administration of adenosine triphosphate (ATP) is used to induce transient pulmonary vein (PV) reconduction (dormant PV conduction) following PV isolation. This study investigated the detailed characteristics of dormant PV conduction in patients with atrial fibrillation (AF) who underwent catheter ablation. METHODS: two hundred sixty consecutive patients (235 men; mean age, 54 ± 10 years) who underwent catheter ablation of their AF were included in this study. ATP was injected following PV isolation to induce dormant PV conduction, which was then eliminated by radiofrequency application. RESULTS: dormant PV conduction was induced by ATP in 60.4% (157/260) of the patients and in 25.3% (258/1,021) of the isolated PVs. This transient PV reconduction was more frequently observed in the left superior PV in comparison with other PVs (P < .0001). There was no significant difference in the prevalence of the dormant PV conduction among patients with paroxysmal AF, persistent AF, and long-lasting AF (62%, 66%, and 48%, respectively; P = .13). During the follow-up period, repeat AF ablation was performed in 70 patients with recurrent AF. The dormant PV conduction was less frequently induced in the repeat procedure than in the initial procedure (60.4% vs 31.4%, P < .0001). CONCLUSIONS: dormant PV conduction was evenly induced among AF types. The repeat PV isolation led to the decrease in incidence of the ATP-induced acute transient pharmacological PV reconduction.

Low-level right vagal stimulation: anticholinergic and antiadrenergic effects.

INTRODUCTION: We sought to extend the use of low-level vagal stimulation by applying it only to the right vagus nerve (LL-RVS) to suppress atrial fibrillation (AF). METHODS: In 10 pentobarbital anesthetized dogs, LL-RVS (20 Hz, 0.1 ms pulse width) was delivered to the right vagal trunk via wire electrodes at voltages 50% below that which slowed the sinus rate (SR) or atrio-ventricular conduction. Electrode catheters were sutured at multiple atrial and pulmonary vein (PV) sites to record electrograms. LL-RVS continued for 3 hours. At the end of each hour, 40 ms of high-frequency stimulation (HFS; 100 Hz, 0.01 ms pulse width) was delivered 2 ms after atrial pacing (during the refractory period) to determine the AF threshold (AF-TH) at each site. Other electrodes were attached to the superior left ganglionated plexi (SLGP) and right stellate ganglion (RSG) so that HFS (20 Hz, 0.1 ms pulse width) to these sites induced SR slowing and acceleration, respectively. Microelectrodes inserted into the anterior right ganglionated plexi (ARGP) recorded neural activity. RESULTS: (1) Three hours of LL-RVS induced a progressive increase in AF-TH at all sites (all P < 0.05). (2) The SR slowing and acceleration response induced by SLGP and RSG stimulation, respectively, was blunted by LL-RVS. (3) The frequency and amplitude of the neural activity recorded from the ARGP were markedly inhibited by LL-RVS. CONCLUSIONS: LL-RVS suppressed AF inducibility and the chronotropic responses to parasympathetic and sympathetic stimulation. Inhibition of neural activity in the GP may be a mechanism underlying these results.

Stimulation of the intrinsic cardiac autonomic nervous system results in a gradient of fibrillatory cycle length shortening across the atria during atrial fibrillation in humans.

INTRODUCTION: The intrinsic cardiac autonomic nervous system (ANS) is implicated in atrial fibrillation (AF) but little is known about its role in maintenance of the electrophysiological substrate during AF in humans. We hypothesized that ANS activation by high-frequency stimulation (HFS) of ganglionated plexi (GP) increases dispersion of atrial AF cycle lengths (AFCLs) via a parasympathetic effect. METHODS AND RESULTS: During AF in 25 patients, HFS was delivered to presumed GP sites to provoke a bradycardic vagal response and AFCL was continuously monitored from catheters placed in the pulmonary vein (PV), coronary sinus (CS), and high right atrium (HRA). A total of 163 vagal responses were identified from 271 HFS episodes. With a vagal response, the greatest reduction in AFCL was seen in the PV adjacent to the site of HFS (16% reduction, 166 ± 28 to 139 ± 26 ms, P < 0.0001) followed by the PV-atrial junction (9% reduction, 173 ± 21 to 158 ± 20 ms, P < 0.0001), followed by the rest of the atrium (3-7% reduction recorded in HRA and CS). Without a vagal response, AFCL changes were not observed. In 10 patients, atropine was administered in between HFS episodes. Before atropine administration, HFS led to a vagal response and a reduction in PV AFCL (164 ± 28 to 147 ± 26 ms, P < 0.0001). Following atropine, HFS at the same GP sites no longer provoked a vagal response, and the PV AFCL remained unchanged (164 ± 30 to 166 ± 33 ms, P = 0.34). CONCLUSIONS: Activation of the parasympathetic component of the cardiac ANS may cause heterogenous changes in atrial AFCL that might promote PV drivers.

[Innervation of cardiac muscle tissue in rat pulmonary veins].

The pulmonary vein (PV) of 16 adult male Wistar rat was studied using synaptophysin immunohistochemistry and staining with toluidine blue and hematoxylin. Its intrapulmonary trunk wall was found to have a unique structure. The middle tunic contained cross-striated muscle tissue that was identical to the cardiac muscle tissue in posterior wall of the myocardial atrium. The thickness of the muscular tunic increased with the increase of vein diameter. The thickest layer of cardiac muscle fibers was located in the orifice of the main trunk, and the thinnest - in the lateral veins (50-100 microm in diameter), carrying the arterial blood from the respiratory portion of pulmonary lobe. Along their whole length, cardiac muscle fibers are densely innervated. Efferent synaptophysin-positive endings of the terminal plexus were found to be tightly associated with cardiac muscle fibers, capillaries of the media in the area of PV orifice and vasa vasorum of the adventitia.

Baroreflex Sensitivity in Patients With Atrial Fibrillation.

Background It has been reported that atrial fibrillation (AF) may contribute to impairment of baroreflex sensitivity (BRS). However, the difference of BRS between patients with persistent AF (PeAF) and those with paroxysmal AF (PAF) is unknown. We tested the hypothesis that patients with PeAF have a more impaired BRS compared with those with PAF. Methods and Results From October 2015 onwards, a total of 67 patients (14 women [20.9%]; mean age 65.2±10.1 years) with PAF (n=46, 68.7%) and PeAF (n=21, 31.3%), who underwent catheter ablation, were prospectively enrolled. The baseline BRS was evaluated during sinus rhythm. The baseline BRS in patients with PeAF was significantly lower than those with PAF (2.97 [0.52-6.62] ms/mm Hg versus 4.70 [2.36-8.37] ms/mm Hg, P=0.047). The BRS was significantly depressed after catheter ablation in all the patients (4.66 [1.80-7.37] ms/mm Hg versus 0.55 [-0.15 to 1.22] ms/mm Hg, P<0.001). However, the depression of BRS because of catheter ablation appeared attenuated in patients with PeAF when compared with those with PAF. The number of patients who did not show depression of BRS was significantly greater, that is, patients with PeAF (3/12, 25%) than those with PAF (0/46, 0%, P<0.01). Conclusions Our findings demonstrated that the baseline BRS was more depressed in patients with PeAF compared with PAF. Catheter ablation depressed BRS irrespective of the type of AF, with a greater effect in patients with PAF than PeAF.

Early recovery of pulmonary vein conduction after cryoballoon ablation for paroxysmal atrial fibrillation: a prospective study.

AIMS: To assess the incidence of early pulmonary vein (PV) reconnection, characterize the anatomic features of the reconducting veins, and analyse the time course of their recovery in a series of consecutive patients with paroxysmal atrial fibrillation (AF) undergoing ablation with the Arctic Front Cryoballoon. METHODS AND RESULTS: We prospectively enrolled 26 patients (20 males; age 55.4 +/- 4.1) for circumferential PV cryoballoon isolation for highly symptomatic paroxysmal AF. Following isolation of all veins, we analysed PV potentials in each vein after 30 and 60 min with a circular mapping catheter. After successful electrical isolation of all 104 PV's, recurrence was observed only in three veins (2.8%) after 30 min. Two further cryoballoon applications in each of these veins lead to their isolation. These veins were still electrically disconnected at 60 min. No PV reconnection was observed in any of the other 101 veins (97.1%) at 30 and 60 min. CONCLUSION: Cryoballoon ablation of the PV's ostia is a very effective technique to achieve electrical isolation, with a very low rate of early reconnection.

The local repolarization heterogeneity in the murine pulmonary veins myocardium contributes to the spatial distribution of the adrenergically induced ectopic foci.

An atrial tachyarrhythmias is predominantly triggered by a proarrhythmic activity originate from the pulmonary veins (PV) myocardial sleeves; sympathetic or adrenergic stimulation facilitates PV proarrhythmia. In the present study the electrophysiological inhomogeneity, spatiotemporal characteristics of the adrenergically induced ectopic firing and sympathetic nerves distribution have been investigated in a murine PV myocardium to clarify mechanisms of adrenergic PV ectopy. Electrically paced murine PV demonstrate atrial-like pattern of conduction and atrial-like action potentials (AP) with longest duration in the mouth of PV. The application of norepinephrine (NE), agonists of α- and ß-adrenergic receptors (ARs) or intracardiac nerves stimulation induced spontaneous AP in a form of periodical bursts or continuous firing. NE- or ARs agonists-induced SAP originated from unifocal ectopic foci with predominant localization in the region surrounding PV mouth, but not in the distal portions of a murine PV myocardium. A higher level of catecholamine content and catecholamine fiber network density was revealed in the PV myocardial sleeves relative to LA appendage. However, no significant local variation of catecholamine content and fiber density was observed in the murine PV. In conclusion, PV mouth region appear to be a most susceptible to adrenergic proarrhythmia in mice. Intrinsic spatial heterogeneity of AP duration can be considered as a factor influencing localization of the ectopic foci in PV.

Quantification of acute parasympathetic denervation during cryoballoon ablation by using extracardiac vagal stimulation.

AIMS: The purpose of this study was to systematically quantify the level of acute parasympathetic denervation in a stepwise fashion by means of extracardiac vagal stimulation (ECVS) by positioning a quadripolar catheter in the internal jugular vein, in a cohort of patients undergoing second-generation cryoballoon ablation for paroxysmal atrial fibrillation. METHODS: Fifty patients with symptomatic paroxysmal atrial fibrillation, having undergone extracardiac vagal stimulation before and after ablation by means of second-generation cryoballoon second-generation cryoballoon ablation, were included. RESULTS: The extracardiac vagal stimulation performed preablation provoked cardioinhibitory responses in all patients with mean pause duration of 10130.6 ± 3280.0 ms. At the end of the procedure, the VRs were significantly diminished with mean pause of 1687.5 ms ± 2183.7 ms (P = 0.00 compared with the pause before the procedure). CONCLUSION: The ECVS proved to be a reproducible, feasible and reliable method to quantify the degree of parasympathetic denervation during CB-A. In all patients, significant cardiac parasympathetic denervation could be observed at the end of the procedure. Responses to ECVS were more specific to quantify the vagal denervation than the increase in the heart rate. However larger studies are needed to confirm this observation.