Wenckebach Point Research Articles

The impact of spinal cord stimulation on a chronic model of atrial fibrillation in a mini-pig experiment

Introduction: Despite the advancement interventional methods for treating atrial fibrillation, the effectiveness of catheter ablation remains poor, especially in patients with persistent and long-persistent atrial fibrillation. Thus, experts continue to explore new treatments for this arrhythmia. The issue of experimental studies investigating the association between spinal cord stimulation and atrial fibrillation is mainly attributed to the lack of optimal algorithms for spinal cord stimulation in animal experiments. Therefore, it is important to develop adequate algorithms for spinal cord stimulation in the chronic model of atrial fibrillation.Objective: To evaluate the impact of spinal cord stimulation on the model of atrial fibrillation in mini-pigs.Methods: In a series of experiments, 6 (100%) successful implantations of electrodes and pacemakers, and spinal cord stimulation electrodes were performed. The electrodes were used to stimulate the atria, creating a model of atrial fibrillation, while the spinal cord stimulation was carried out using an electrode implanted into the spinal canal. During the experiment, an electrophysiological study was performed using an implanted pacemaker. The inducibility of atrial fibrillation was assessed before and after the experiment using various spinal cord stimulation algorithms.Results: There were no complications associated with surgery or stimulation of the atria and spinal cord. Spinal stimulation had a modeling effect on the autonomic nervous system, significantly changing the average heart rate, Wenckebach point, and effective refractory period. When comparing spinal stimulation algorithms, algorithm 1 was found to significantly reduce the atrial fibrillation inducibility.Conclusion: Spinal cord stimulation had a modeling effect on the autonomic nervous system, significantly changing the average heart rate, Wenckebach point, and effective refractory period. Inducibility of atrial fibrillation decreases with changes in the spinal pacing algorithm. Received 15 September 2023. Revised 30 October 2023. Accepted 31 October 2023. Funding: The study was supported by Russian Science Foundation (project No. 22-25-00672). Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: A.G. Filippenko, V.V. Shabanov, V.I. MurtazinData collection and analysis: A.G. Filippenko, T.U. Khalkhoghaev, V.V. BeloborodovStatistical analysis: A.G. Filippenko, V.V. ShabanovDrafting the article: A.G. Filippenko, V.V. BeloborodovCritical revision of the article: V.V. ShabanovFinal approval of the version to be published: V.V. Shabanov, A.G. Filippenko, V.V. Beloborodov, T.U. Khalkhoghaev, V.I. Murtazin

Cardioneuroablation for symptomatic bradyarrhythmia: for whom it fails?

Abstract Background Cardioneuroablation (CNA) has been proposed as a new therapeutic approach in selected patients with symptomatic functional bradyarrhythmia including recurrent neurally-mediated syncope. Purpose In patients after CNA, we investigated the potential predictors of the recurrence of clinically significant bradyarrhythmia. Methods A retrospective study included 187 consecutive patients (age: 40±12 years; 57 % of males; predominant AV nodal phenotype of the disorder in 37 % of patients; post-atropine sinus rate acceleration by 72±31 %) who underwent their first CNA at our centre from 2014 to 2022 and were followed for the minimum of 3 months. Biatrial radiofrequency ablation was performed under general anaesthesia by irrigated-tip catheter at empirical sites of ganglionated plexi (GP) with the navigation by 3D electroanatomic mapping system and intracardiac echocardiography. Anterior right GP and posteromedial left GP were always targeted to modulate the innervation of both sinoatrial and atrioventricular nodes, irrespective of the clinical manifestation of the disease. The loss of responsiveness of both nodes to extracardiac vagus nerve stimulation (frequently bilateral) was the procedural endpoint. The association of baseline, procedural, and early follow-up characteristics with the recurrence of clinically significant bradyarrhythmia was analyzed. Results CNA with the procedural duration of 154±32 min and radiofrequency time of 14±7 min resulted acutely in sinus rate acceleration by 27±13 bpm, shortening of AH interval by 16±28 ms, an increase of Wenckebach point by 26±28 bpm, shortening of AV node effective refractory period by 114±128 ms, and sinus node recovery time by 462±867 ms. At the 3-month visit, the sinus rate was still significantly higher (83±14 bpm) than at baseline (61±13 bpm); with acceleration by 23±14 bpm. During a median follow up of 33 months (IQR: 18-48 months), recurrence of clinically significant bradyarrhythmia was documented in 18 (10 %) patients. Re-CNA was performed in 11 patients and was scheduled in 3 patients. In 6 (3 %) patients, a pacemaker was finally implanted. Compared to the rest of the population, patients with bradyarrhythmia recurrence were non-significantly younger (36±12 vs. 40±12 years, P=0.16) and had non-significantly less acceleration of sinus rate at the 3-month post-CNA visit (by 18±11 vs. 23±13 bpm, P=0.10) suggesting a trend to more pronounced reinnervation of the sinus node. Conclusion Long-term clinical efficacy of CNA is reasonably high. We did not identify practically useful predictors of CNA failure. This investigation was significantly limited by the low rate of clinical events.

Overlapping and Distinct Features of Cardiac Pathology in Inherited Human and Murine Ether Lipid Deficiency.

Inherited deficiency in ether lipids, a subgroup of glycerophospholipids with unique biochemical and biophysical properties, evokes severe symptoms in humans resulting in a multi-organ syndrome. Mouse models with defects in ether lipid biosynthesis have widely been used to understand the pathophysiology of human disease and to study the roles of ether lipids in various cell types and tissues. However, little is known about the function of these lipids in cardiac tissue. Previous studies included case reports of cardiac defects in ether-lipid-deficient patients, but a systematic analysis of the impact of ether lipid deficiency on the mammalian heart is still missing. Here, we utilize a mouse model of complete ether lipid deficiency (Gnpat KO) to accomplish this task. Similar to a subgroup of human patients with rhizomelic chondrodysplasia punctata (RCDP), a fraction of Gnpat KO fetuses present with defects in ventricular septation, presumably evoked by a developmental delay. We did not detect any signs of cardiomyopathy but identified increased left ventricular end-systolic and end-diastolic pressure in middle-aged ether-lipid-deficient mice. By comprehensive electrocardiographic characterization, we consistently found reduced ventricular conduction velocity, as indicated by a prolonged QRS complex, as well as increased QRS and QT dispersion in the Gnpat KO group. Furthermore, a shift of the Wenckebach point to longer cycle lengths indicated depressed atrioventricular nodal function. To complement our findings in mice, we analyzed medical records and performed electrocardiography in ether-lipid-deficient human patients, which, in contrast to the murine phenotype, indicated a trend towards shortened QT intervals. Taken together, our findings demonstrate that the cardiac phenotype upon ether lipid deficiency is highly heterogeneous, and although the manifestations in the mouse model only partially match the abnormalities in human patients, the results add to our understanding of the physiological role of ether lipids and emphasize their importance for proper cardiac development and function.

Study of Electrophysiological Properties of Atrioventricular Node in Permanent Cardiac Pacing under Influence of Trimetazidine Dihydrochloride

INTRODUCTION: Dual-chamber cardiac pacing permits to maintain permanent atrial-ventricular synchronization. Physiological sequence of propagation of the impulse from atria to ventricles is provided with an artificial delay analogous to delay of propagation of excitation through the atrioventricular (AV) node of a heathy individual. The delay interval is formed so that to minimize stimulation of the right ventricle. This preserves the left ventricular ejection fraction, reduces the risk of development of the chronic heart failure (CHF) and of atrial fibrillation, and increases functional abilities of the patient. On the other hand, critical increase in the atrioventricular delay leads to pacemaker syndrome: impairment of circulation function, shortness of breath, reduced tolerance to exercise, dizziness, syncopal state. The question of the influence of the permanent electrical pacing on the AV node conduction remains unsolved.
 AIM: To study the effect of trimetazidine dihydrochloride on the AV node conduction in conditions of permanent cardiac pacing, to determine the effect of cardiac pacing on the AV node in the studied time period.
 MATERIALS AND METHODS: The study involved 86 patients. The AV node activity was assessed by antegrade intraoperative determination of Wenckebach point on the basis of electrocardiography data in 2448 hours after pacemaker implantation, in 68 hours, 7, 14, 9 and 180 days after intake of trimetazidine dihydrochloride and in 7, 14, 21 and 30 days after its cancellation. To compare the extent of influence of the studied drug on the AV node activity, the patients were divided to three groups depending on the basic pathology: group 1 ― patients with the sick sinus node syndrome (n = 38, 44.2%); group 2 ― patients with II degree AV block (n = 25, 29.1%); group 3 ― patients with III degree AV block (n = 23, 26.7%).
 RESULTS: Trimetazidine dihydrochloride improved the electrophysiological properties of the AV node in the first and second groups: increase in the mean value of Wenckebach point antegrade in the first group was in total 3.26% (р = 0.022), in the second group 4.68% (р = 0.001). In the third group of patients no improvement was noted, but it should be said that under the action of this drug, in 4 of 23 patients with III degree AV block, antegrade AV conduction appeared (р = 0.236).
 CONCLUSION: Trimetazidine dihydrochloride has a positive effect on the AV node activity as early as in 68 hours of intake, which reaches maximum in 3 weeks. Cardiac pacing had no effect on AV node within the follow-up period (6 months).

Atrioventricular conduction in PM recipients after transcatheter aortic valve implantation: Implications using Wenckebach point measurement.

BackgroundAtrioventricular (AV) conduction disturbances requiring permanent pacemaker implantation (PPI) are a common complication after transcatheter aortic valve implantation (TAVI). However, a significant proportion of patients might recover AV conduction at follow-up.ObjectivesThe aim of our study was to evaluate the recovery of AV conduction by determination through Wenckebach point in patients with PPI and therefore identify patients who could benefit from device reprogramming to avoid unnecessary RV pacing.MethodsWe enrolled 43 patients that underwent PM implantation after TAVI at our Department from January 2018 to January 2021. PM interrogation was performed at follow-up and patients with native spontaneous rhythm were further assessed for AV conduction through WP determination.ResultsA total of 43 patients requiring a PM represented the final study population, divided in patients with severely impaired AV conduction (no spontaneous valid rhythm or WP < 100; 26) and patients with valid AV conduction (WP ≥ 100; 17). In the first group patients had a significantly higher number of intraprocedural atrioventricular block (AVB) (20 vs. 1, p < 0.005), showed a significant higher implantation depth in LVOT (7.7 ± 2.2 vs. 4.4 ± 1.1, p < 0.05) and lower ΔMSID (−0.28 ± 3 vs. −3.94 ± 2, p < 0.05).ConclusionAV conduction may recover in a significant proportion of patients. In our study, valve implantation depth in the LVOT and intraprocedural AV block are associated with severely impaired AV conduction. Regular PM interrogation and reprogramming are required to avoid unnecessary permanent right ventricular stimulation in patients with AV conduction recovery.

New onset of AV-nodal reentrant tachycardia (AVNRT) in the elderly- an uncommon diagnosis?

Abstract Funding Acknowledgements Type of funding sources: None. Background Arrhythmias in elderly patients (pat) are common. In this subset of pat, atrial fibrillation is by far the most frequent sustained arrhythmia but not the only one. Clinical, ECG and electrophysiological (EP) features of AV-nodal reentrant tachycardia (AVNRT) have rarely been described in the elderly, and this represents the aim of the current study. Methods At 2 EP-centres in Germany, data from all pat undergoing an EP-study (EPS) and diagnosed with AVNRT between January 2018 and May 2021 were collected and analysed. Pat &amp;gt; 65 years constituted the study population. Results During the study period AVNRT was diagnosed in a total of 329 pat. 93 pat (28%) were &amp;gt; 65 years and represent the study population [median age 74 (65-89) years, 48% female]. In the majority (85%), the duration of symptoms was short (&amp;lt; 1 year), 14 pat had symptoms of paroxysmal tachycardia for longer than 10 years. Most of the pat (n=88, 94%) had at least one ECG-documentation. In SR, the PR interval was relatively long [median 180 (120-380) ms)]. In 84% of pat, sustained AVNRT [median cycle length (CL) 400 (270-800) ms] was induced during EPS. In the remaining pat, at least 2 typical AV-nodal-echo beats were induced. Slow pathway (SP) ablation/modification was performed in all but one patient presenting with a very long baseline PR-interval, low antegrade Wenckebach-point (WP) and very slow AVNRT. In this case, the pat was treated with ß-blocker after pacemaker (PM) implantation. In 3 additional pat, PM implantation was necessary after ablation due to intermittent high-degree AV-block. In comparison to the rest of the study population, these four pat had a longer baseline PQ interval [median 275 (IQR 248- 303) ms vs. 180 (IQR 160- 192) ms], a longer baseline AH interval [median 207ms (IQR 185- 234) ms vs. 95 (IQR 80- 107) ms], a lower baseline antegrade WP CL [median 510 (IQR 435- 645) vs. 390ms (IQR 355- 470) ms], and a longer tachycardia CL [TCL 557 (IQR 454- 661) ms vs. 400 (IQR 364- 443) ms; p value &amp;lt;0,01 for all comparisons]. The overall complication rate (other than AV block) was low (2 pat with AV fistula treated conservatively) and comparable to the one described in younger pat. Discussion Elderly pat also have AVNRT, there are a slight differences in physiology (i.e. relatively long baseline PR-interval and TCL, likely due to changes of the conduction system with aging), and as in young pat, ablation is curative treatment with similar (low) complication rate. A subset of pat, characterized by longer PR- and AH-intervals, lower WP and longer TCL may be at higher risk for AV-block after SP modification. Whether this is due to pre-existing damage or to posterior location of the FP remains unknown. SP ablation is safe and effective even in elderly pat. In pat presenting with EP characteristics presumptive of a baseline impairment of the conduction properties of the FP, ablation of the FP could be attempted to avoid postprocedural high degree AV block.

Anatomically-guided cardioneuroablation for recurrent neurally mediated syncope

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardioneuroablation (CNA) has been proposed as a new therapeutic approach in selected patients with recurrent neurally mediated syncope and documented cardioinhibitory component. Purpose We report on procedural data and clinical outcomes of consecutive patients who underwent anatomically-guided CNA at our center in the period of 2014 - 2021. Methods A study investigated 145 otherwise healthy patients (age: 40 ± 14 years, 56% males) with recurrent reflex syncope and the physiological result of the atropine test. Biatrial radiofrequency (RF) ablation was performed under general anesthesia by irrigated-tip catheter at empirical sites of ganglionated plexi (GP) with the navigation by CARTO-3 system and intracardiac echocardiography. Anterior right GP and posteromedial left GP were always targeted to modulate the innervation of both sinoatrial (SAN) and atrioventricular (AVN) nodes, irrespective of clinical manifestation of the disease. The loss of responsiveness of both nodes to extracardiac vagus nerve stimulation was the procedural endpoint. Right vagus or bilateral vagus nerve stimulation was used in 86% and 54% of procedures, respectively. Results Enrolled patients had documented cardioinhibitory disorder of SAN (59%), AVN (30%), or both nodes (11%). CNA (duration: 157 ± 31 min; RF time: 15 ± 6 min; radiation dose: 84 ± 135 µGy.m²) resulted in sinus rate acceleration by 28 ± 12 bpm, shortening of AH interval by 15 ± 31 ms, an increase of Wenckebach point by 28 ± 33 bpm, shortening of AVN effective refractory period by 110 ± 115 ms, and sinus node recovery time by 508 ± 666 ms. During a median follow up of 26 (IQR: 12-39) months, CNA was repeated in 9 patients and is scheduled in 3 other (total 8%). Pacemaker was implanted only in 4 (3%) patients after single (n = 2) or repeated CNA (n = 2). Corresponding Kaplan-Meier curves are provided in the Figure. Any-syncope-free survival is comparable to that reported in active arms of historical and recent pacemaker studies. Conclusions CNA is a reasonably effective treatment option for patients with functional cardioinhibitory syncope. CNA can be performed by anatomically-guided ablation at empirical GP sites. Our study corroborates the clinical utility of CNA as a viable alternative to pacemaker implant in selected patients.

High-rate atrial pacing to reduce left-sided filling pressures: a combined computational and clinical pilot study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by the Netherlands Organisation for Scientific Research (NWO- ZonMw, VIDI grant 016.176.340 to J.L.) and the Dutch Heart Foundation (ERA-CVD JTC2018 grant 2018T094; Dr. Dekker Program grant 2015T082 to J.L.) Background In heart failure patients, interventions to reduce elevated left ventricular (LV) filling pressure improve symptoms and reduce the risk of hospitalization. In this combined computational-clinical study, we explore high-rate atrial pacing as an alternative intervention to reduce LV filling pressure. Methods First, the theoretical basis was explored in a computational model of reduced LV compliance and various fixed atrioventricular delays. Second, an explorative clinical study was conducted in 19 paroxysmal atrial fibrillation (AF) patients undergoing pulmonary vein isolation (PVI) with sinus rhythm at the beginning of the procedure. Prior to the PVI, atrial pacing rate was gradually increased from resting heart rate to Wenckebach point with 10bpm increments. LA pressure was continuously monitored with a fluid-filled transseptal catheter. Results Computational modelling demonstrated a parabolic relationship between atrial pacing rate and LA pressure depending on atrioventricular delay (Figure A). In patients (Figure B), intermediately increased rates (60bpm[60-70], median[IQR], to 90bpm[73-100], respectively) reduced LA pressure from 16.0mmHg[14.0-20.5] to 14.0mmHg[10.8-16.8]. Highly increased rates (130bpm[120-140]) significantly increased LA pressure to 26.0mmHg[21.5-27.8]. Conclusions Both the model simulations and the subsequent clinical pilot study support the hypothesis that high-rate atrial pacing can reduce left-sided filling pressure. However, inter-patient variability of response to high-rate pacing was observed, to which simulations identified atrioventricular conduction to be a potential source.

P376 INTRACAVITARY ABLATION OF PARASYMPATHETIC ATRIAL GANGLIONATED PLEXUS, A NEW APPROACH FOR SINUS BRADYCARDIA IN YOUNG PATIENTS

Abstract Sinus bradycardia might be a severe clinical problem, if symptomatic pacemaker implantation is needed. In younger patients this will lead to several battery changes, higher infectious risk and psychological issues. When sinus bradycardia seems related to vagal hypertone, intracavitary ablation of atrial ganglionated plexus has recently been proposed as an alternative to pacemaker implantation in symptomatic younger patients. A 44–year–old patient was admitted to the emergency department for lipothymia and fatigue. The ECG showed marked sinus bradycardia with a heart rate of 35 bpm and continuous ECG monitoring revealed episodes of Mobitz I second degree AV block and 2:1 AV block. The transthoracic echocardiography was normal. In order to reduce the effect of vagal hypertone on the heart, catheter ablation of parasympathetic atrial ganglionated plexus was performed. In the right atrium the electrophysiological study showed fragmented potentials near caval vein openings and coronary sinus osthium, while in the left atrium these were found in the posterior wall close to the pulmonary veins and near the left part of coronary sinus. Catheter stimulation of these zones determined asystolic pauses and induction of atrial fibrillation with spontaneous resolution. Catheter radio–frequency ablation was performed, at the end of the procedure increase of heart rate at 70 bpm was observed and atrial fibrillation was no more inducible during pacing. Atrioventricular Wenckebach point recorded before the procedure was 730 ms and it passed to 430 ms. At continuous ECG monitoring the heart rate remained higher than 65 bpm all over the hospitalization, without any other meaningful arrhythmias. Ablation of parasympathetic atrial ganglionated plexus is still an experimental technique but it is proving to be very interesting and promising. In the case we described the patient took a real advantage from the procedure that was measurable both with the improve of heart rate and reduction of Wenckebach point. During the procedure we associated the site of fragmented potentials with the position of each plexus; stimulation of these sites evocated a strong vagal response, confirming that fragmented potentials can be used to localize the plexus. Some authors affirmed that ablation only on right atrium might be sufficient; however, we preferred to ablate in both atria in order to make the procedure more effective. More studies are needed to identify the correct site.

PO-630-08 INFLUENCE OF TWO NARCOSIS REGIMENS ON CARDIAC ELECTROPHYSIOLOGY IN MICE

Mouse models are commonly used to study arrhythmia mechanisms in vivo. Different narcosis regimens have proven feasibility in rodents with medetomidine (0.5 mg/kg), midazolam (5 mg/kg) and fentanyl (0.005 mg/kg) (MMF) and isoflurane (1-3 %)/fentanyl (0.05 mg/kg) (IF) among the most commonly used regimens, but little data is available regarding their effects on cardiac electrophysiology. To investigate the effects of MMF and IF narcosis in C57BL/6 wildtype mice on cardiac electrophysiology in vivo. Telemetry transmitters were implanted in 4 C57/BL6 mice which served as controls for ECG analysis without narcosis. In 22 mice ECG and invasive electrophysiology studies were performed under narcosis (n=10 MMF, n=12 IF). We assessed ECG, heart rate variability (HRV), sinus node recovery time (SNRT), atrial, atrioventricular and ventricular refractory periods (AERP, AVERP and VERP), Wenckebach point, VA conduction and arrhythmia inducibility by burst stimulation. MMF causes significant bradycardia (452 bpm baseline vs. 271 bpm MMF, ****p < 0.0001), affects HRV indicated by increased pRR50 (1.6 % baseline vs. 67.4 % MMF, ****p < 0.0001), reduced LF/HF ratio (0.62 baseline vs. 0.16 MMF, *p = 0.019) and both increased SD1 (15 ms baseline vs. 94 ms MMF, ****p < 0.0001) and SD2 (19.6 ms baseline vs. 48.5 ms MMF *p =0.017), and prolongs QRS duration (8.1 ms baseline vs. 11.6 ms MMF, *p = 0.015) and QT interval (50 ms baseline vs. 68 ms MMF, ****p < 0.0001). MMF prolongs SNRT (at 120 ms basic cycle length 234 ms MMF vs. 145 ms IF, ***p < 0.001), antegrade (69 ms MMF vs. 56 ms IF, ****p < 0.0001), and retrograde conduction in the AV node (118 ms MMF vs. 89 ms IF, ***p < 0.001), AVERP (67 ms MMF vs. 50 ms IF, **p < 0.01) and ultimately leads to increased susceptibility for ventricular arrhythmias (1.3 % MMF vs. 0 % IF, **p < 0.01) compared to IF. Our results highlight a significant impact of MMF narcosis on cardiac electrophysiology in mice. While IF only moderately reduces heart rate, MMF leads to significant bradycardia, QRS/QT prolongation and HRV alterations as well as impaired sinus node and AV node function, ultimately resulting in an increased inducibility of ventricular arrhythmias. Based on these effects we suggest using IF narcosis to study cardiac electrophysiology in mice.

Electrophysiological and therapeutic effects of amiodarone in patients with preexcited atrial fibrillation.

Atrial fibrillation (AF) with fast ventricular response over an overt accessory pathway (AP) (preexcited AF) with a short anterograde refractory period is a potentially malignant arrhythmia. This study aimed to evaluate the safety and efficacy of amiodarone for preexcited AF management. This study enrolled 103 patients with evidence of AP in electrocardiography. Patients with preexcited AF were included in the study. Intravenous amiodarone (300 mg) was infused for 30 min for all patients in the AF rhythm. Electrophysiological parameters were evaluated before amiodarone injection and 2 h after pharmacological or electrical cardioversion. Antegrade and retrograde refractory periods of the atrioventricular node (AVN) and AP, as well as antegrade and retrograde Wenckebach points of AVN, were increased significantly after amiodarone infusion. Furthermore, the mean of the shortest preexcited RR interval was increased during the monitoring period. Comparing the preexcited index at the beginning of the study and before cardioversion (2 h later) revealed that the QRS complexes changed to a wider pattern as the preexcitation index changed from 80.61 to 92.26 (P < 0.001). Nineteen (18.4%) patients converted to the sinus rhythm with amiodarone infusion. No ventricular arrhythmia was detected during monitoring. Amiodarone could be considered a safe drug in patients with preexcited AF for rate control despite its relatively low efficacy in conversion to the sinus rhythm.

Avoidance of Vagal Response During Circumferential Pulmonary Vein Isolation: Effect of Initiating Isolation From Right Anterior Ganglionated Plexi.

Circumferential pulmonary vein isolation (CPVI) often cause unavoidable vagal reflexes during procedure due to the coincidental modification of ganglionated plexus which are located on pulmonary vein (PV) antrum. The right anterior ganglionated plexi (RAGP) which located at superoanterior area of right superior PV antrum is an essential station to regulate the cardiac autonomic nerve activities and is easily coincidentally ablated during CPVI. The aim of this study is to assess the effect of RAGP ablation on vagal response (VR) during CPVI. A total of 80 patients with paroxysmal atrial fibrillation who underwent the first time CPVI were prospectively enrolled and randomly assigned to 2 groups: group A (n=40), CPVI started with right PVs at RAGP site; group B (n=40): CPVI started with left PVs first, and the last ablation site is RAGP. Electrophysiological parameters include basal cycle length, A-H interval, H-V interval, sinus node recovery time, and atrioventricular node Wenckebach point were recorded before and after CPVI procedure. During CPVI, the positive VR were only observed on 1 patient in group A and 25 patients in group B (P<0.001). A total of 21 patients with positive VR in group B needed for temporary ventricular pacing during procedure, while the only patient with positive VR in group A did not need for temporary ventricular pacing (P<0.001). Compared with baseline, basal cycle length, sinus node recovery time, and atrioventricular node Wenckebach point were decreased significantly after CPVI procedure in both groups (all P<0.05) and without differences between 2 groups. Circumferential PV isolation initiated from RAGP could effectively inhibit VR occurrence and significantly increase heart rate during procedure.

Expression of Lmna-R225X nonsense mutation results in dilated cardiomyopathy and conduction disorders (DCM-CD) in mice: Impact of exercise training

AimsTo recapitulate progressive human dilated cardiomyopathy (DCM) and heart block in the Lmna R225X mutant mice model and investigate the molecular basis of LMNA mutation induced cardiac conduction disorders (CD); To investigate the potential interventional impact of exercise endurance. Methods and resultsA Lmna R225X knock-in mice model in either heterozygous or homozygous genotype was generated. Electrical remodeling was observed with higher occurrence of AV block from neonatal and aged mutant mice as measured by surface electrocardiogram and atrio-ventricular Wenckebach point detection. Histological and molecular profiles revealed an increase in apoptotic cells and activation of caspase-3 activities in heart tissue. Upon aging, extracellular cellular matrix (ECM) remodeling appeared with accumulation of collagen in Lmna R225X mutant hearts as visualized by Masson’s trichrome stain. This could be explained by the upregulated ECM gene expression, such as Fibronectin: Fn1, collagen: Col12a1, intergrin: Itgb2 and 3, as detected by microarray gene chip. Also, endurance exercise for 3 month improved the ventricular ejection fraction, attenuated fibrosis and cardiomyocytes apoptosis in the aged mutant mice. ConclusionsThe mechanism of LMNA nonsense mutation induced cardiac conduction defects through AV node fibrosis is due to upregulated ECM gene expression upon activation of cardiac apoptosis. Lmna R225X mutant mice hold the potential for serving as in vivo models to explore the mechanism and therapeutic methods for AV block or myopathy associated with the aging process.

P1011Electrophysiological trends in Wolff-Parkinson-White patients: a 33 years follow-up study

Abstract Background The Wolff-Parkinson-White (WPW) syndrome can be associated with sudden cardiac death, therefore risk assessment (RA) with electrophysiological (EP) testing (EPT) is mandatory to identify patients (pts) requiring catheter ablation (CAb). Our retrospective cohort study aimed to evaluate the variability of EP parameters during follow-up of WPW pts and the reliability of trans-esophageal EPT (TEEPT) for RA, evaluation of treatment efficacy, and EP follow-up of untreated athletes/pts. Method Data of 335 WPW pts, studied with TEEPT between 1985 and 2018, were retrospectively analyzed. Anterograde effective refractory period (ERP) of accessory pathways (AP) and of the atrioventricular node, Wenckebach point, shortest preexcited RR intervals (SPERRI) during atrial fibrillation (AF) and/or atrial pacing (At-P) and inducibility of supraventricular arrhythmias were assessed, at rest (supine and standing) and during effort. An AP was defined at high arrhythmogenic risk (HAR) if the anterograde AP-ERP and/or SPERRI (in AF or At-P) were ≤240 ms at rest or ≤200 ms during effort test. All patients were followed-up as outpatients or telephonically, as clinically required. 195 pts (17% female) were included, having exhaustive clinical information, two or more TEEPT and exhaustive clinical follow-up until late 2018. Time-evolution of EP parameters was evaluated, using parametric and non-parametric tests, as appropriate. Results and discussion Median age at first TEEPT was 20 years (IQR 16–29 years). Median follow- up was 44.3 months (IQR 16.4–122.9 months). Two pts (both identified at HAR and scheduled for surgery when ablation was unavailable) died suddenly, at rest. No other serious arrhythmic complication occurred, during the FU. Out of 19 pts (9.7% - Group A) showing enhanced AP conductivity at follow-up (mean ERP/SPERRI shortening: 30.8 ms, range 10–80 ms), 4 pts were found at HAR and underwent CAb. 176 pts (90.3% – Group B) showed a stable or impaired (25% under pharmacological treatment) AP conductivity during the follow-up. Their mean ERP/SPERRI increase was 39.7 ms (range 0–130 ms). Group A pts were significantly younger (20 vs 28 years old; 88% of Group A pts were &lt;30 years old) and more frequently male (94.1% vs 80.6%). A non-significant trend toward Group A was found for antero-septal APs (35% Group A vs 15.4% Group B). Conclusions TEEPT is a safe, non-invasive tool to stratify arrhythmogenic risk of WPW pts. Our data suggest that a watchful waiting is safe for low to moderate risk pts. Younger males with an antero-septal Kent bundle may deserve a more intensive EP follow-up. Aggressive therapy should be considered as mandatory only for symptomatic HAR pts, taking into account complications, risk/benefit ratio and pts' preferences. In other cases, medical therapy and watchful observation could be applied safely under periodical TEEPT, as appropriate.

P3752Ablation of the superior left ganglionic plexus is not necessary for effective denervation of the sinoatrial and atrioventricular nodes

Abstract Background Cardioneuroablation by targeting of atrial ganglionic plexi (GP) has been proposed as a new therapeutic option in selected patients with reflex syncope. Contribution of individual GPs to cardiac autonomic regulations is not fully established. Purpose Because consistent vagal responses have been observed during left superior pulmonary vein isolation in patients undergoing ablation for atrial fibrillation, we investigated whether standalone ablation of the superior left GP modifies the vagal input into the sinoatrial (SAN) and atrioventricular node (AVN). Methods Study hypothesis was investigated in otherwise healthy patients undergoing cardioneuroablation for symptomatic bradyarrhythmias. All had preprocedural atropine test suggesting functional disorder. Anatomically-navigated (CARTO-3) radiofrequency (RF) ablation (25–30 W/30 s/20 ml/min) at empirical GP sites was performed in general anaesthesia. Extracardiac high-frequency vagal nerve stimulation (25–60 V/30–50 Hz/0.05–0.1 ms) via right jugular vein was performed at baseline, after initial superior left GP ablation, and after the ablation of remaining septal and inferior GPs. High-frequency vagal nerve stimulation was always done in both sinus rhythm and atrial pacing. The elimination of all stimulation-induced vagal responses was the endpoint of the procedure. Results A study included 8 patients (34±8 years; 5 males). Six of them had recurrent syncope with cardioinhibitory response at the SAN (n=4), AVN (n=1) or both nodes (n=1); and 2 patients had symptomatic sinus bradycardia. At baseline, high-frequency vagal nerve stimulation induced long episodes of sinus arrest and advanced AV block in all patients. Cluster ablation at the superior left GP (RF time: 192±28 s) did not change the sinus rate (59±14 vs 60±15, NS), PQ interval (174±37 vs 173±37, NS), and did not induce any tangible change in SAN/AVN response to high-frequency vagal nerve stimulation. Subsequently, anterior right GP was targeted from the aspect of right atrium (n=7), from the anterior antrum of right pulmonary veins (n=6), and inferior GPs were targeted from the aspect of left atrium (n=7). This lesion set finally resulted in complete non-responsiveness of SAN and AVN to high-frequency vagal nerve stimulation in all patients. Ablation procedure overall (duration: 172±15 min; RF time: 988±306 s; radiation dose: 70±34 μGy·m2) led to sinus rate acceleration by a median of 29 (IQR: 18–38) bpm, increase of Wenckebach point by 21 (IQR: 9–28) bpm, and shortening of AVN effective refractory period by 40 (IQR: 15–73) ms. Conclusions Cardioneuroablation guided by extracardiac high-frequency vagal nerve stimulation can achieve complete denervation of SAN and AVN by ablation of postero(para)septal and inferior GPs only. Ablation of the superior left GP appears unnecessary and can be eliminated from the lesion set design.

Intravenous antazoline, a first-generation antihistaminic drug with antiarrhythmic properties, is a suitable agent for pharmacological cardioversion of atrial fibrillation induced during pulmonary vein isolation due to the lack of influence on atrio-venous conduction and high clinical effectiveness (AntaEP Study).

Antazoline is a first-generation antihistaminic drug used primarily in eye drop formulations. When administered intravenously, antazoline displays antiarrhythmic properties resulting in a rapid conversion of recent-onset atrial fibrillation (AF) to sinus rhythm (SR). The aim of the study was to assess the influence of antazoline on atrio-venous conduction and other electrophysiological parameters in patients undergoing AF ablation. An experimental prospective study. Patients scheduled for the first-time AF ablation, in SR and not on amiodarone were enrolled. Atrio-venous conduction assessment and invasive electrophysiological study (EPS) were performed before and after intravenous administration of 250mg of antazoline. In case of AF induction during EPS, antazoline was administered until conversion to SR or a cumulative dose of 300mg. We enrolled 14 patients: 13 (93%) men, mean age 63.4 (59.9-66.8) years, mean CHA2 DS2 -VASc score 1.6 (1.0-2.2). Antazoline was administered in a mean dose 257.1 (246.7-267.6) mg. Pulmonary vein potentials and atrial capture during pulmonary vein stimulation were present before and after the administration of antazoline. Wenckebach point and atrial conduction times did not change significantly, but atrio-ventricular node effective refractory period improved-324.7 (275.9-373.5) ms vs 284.3 (256.2-312.4) ms, P=0.02. Antazoline was effective in all 5 (100%) cases of AF induction during EPS. There were no serious adverse events. Due to the lack of influence on atrio-venous conduction and high clinical effectiveness, antazoline may be suitable for pharmacological cardioversion of AF occurring during AF ablation.

Characteristics of dynamic electrocardiogram, heart rate variability, and electrophysiological study in a Chinese population with vasovagal syncope

Background: Little is known about characteristics of dynamic electrocardiogram (DCG), heart rate (HR) variability (HRV), and invasive electrophysiological study (EPS) in the presence, pattern, and stage of vasovagal syncope (VVS) during head-up tilt test (HUTT). The present study aims to explore predictive value of these tests for HUTT outcomes with underlying mechanisms. Subjects and Methods: This retrospective study consecutively enrolled 519 patients with VVS from January 2007 to December 2017. Parameters of DCG, HRV, and EPS were evaluated according to the presence, pattern, and stage of syncope during HUTT. Results: Mixed pattern was the predominant subtype of VVS, and vasodepressor patients had a positive response earlier than in cardioinhibitory patients. Compared with negative group, positive group with mixed and cardioinhibitory patterns had significantly slower maximal HR and mean HR all day, at daytime, nighttime, and each hour point. No significance was observed in parameters of HRV between negative and positive groups. There was no significant difference in HR, spectral power components, and time-domain variables among syncopal patterns and syncopal stages. Positive group had longer durations of A-H interval, sinus node recovery time, Wenckebach point, and Wenckebach 2:1 point than negative group. There was a significant difference only in sinus node recovery time among syncopal patterns as well as A-H interval among syncopal stages. Conclusion: DCG-derived HR and EPS properties rather than 24-h HRV may be used to predict positive responses, but they could not predict syncopal patterns and syncopal stages.

Effect of Antazoline on Electrophysiological Properties of Atrial Muscle and Conduction System of the Heart

PurposeAntazoline is a first-generation antihistaminic agent with additional anticholinergic properties and antiarrhythmic potential. Recent data shows its high effectiveness in sinus rhythm restoration among patients with paroxysmal atrial fibrillation. The effect of antazoline on electrophysiological parameters of the heart in vivo has not yet been examined. The aim of this study was to evaluate changes in electrophysiological parameters of the heart muscle and conduction system as a response to increasing doses of antazoline.MethodsAfter successful ablation of supraventricular arrhythmias, the electrophysiological parameters: sinus rhythm cycle length (SRCL), AH, HV, QRS, QT, QTc intervals, Wenckebach point (WP), sinus node recovery period (SNRT), intra- (hRA-CSos) and interatrial conduction time (hRA-CSd), right and left atrium refractory period (RA-; LA-ERP), and atrioventricular node refractory period (AVN-ERP) were assessed initially and after 100, 200, and 300 mg of antazoline given intravenously.ResultsFifteen patients (8 males, 19–72 years old) undergoing EPS and RF ablation were enrolled. After 100 mg bolus, a significant reduction in SRCL was noticed. After antazoline administration, significant prolongation of HV, QRS, QTc, hRA-CSos, hRA-CSd intervals, RA– and LA-ERP and reduction of SRCL were observed. After a total dose of 300 mg, QT interval prolonged significantly. Increasing the dose of antazoline had no impact on AH, Wenckebach point, AVN-ERP, and SNRT.ConclusionAntazoline has an effect on electrophysiological parameters of the atrial muscle and has rapid onset of action. No negative effect on sinus node function and atrioventricular conduction in a unique property among antiarrhythmic drugs.

Effect of 5-fluorouracil on sinoatrial node and conduction system of heart

Background: 5-FU a cytostatic agent is used to treat various malignancies. Cardiotoxicity is infrequent complication of 5-FU. Previously we had observed ECG changes in our patients on 5-FU viz sinus bradycardia, atrial fibrillation. We also found that 5-FU bradycardia might be a hypervagotonia as vagolytics abolished it. This study was undertaken to assess the impact of this commonly used chemotherapeutic agent on basic physiologic parameters of impulse initiation and conduction in human heart. The aim was to study effect of 5-FU on electrophysiological properties of SA node and conduction system of heart.Methods: Pre -5 FU state patients were subjected to electrophysiological study and following parameters were checked viz heart rate, CSNRT. SACT, AH and HV intervals and wenckebach point. Post 5- FU state these parameters were again checked. Response to Atropine was seen in patients who developed sinus bradycardia.Results: Sinus bradycardia was seen in 8% (n=2) of patients in post 5FUstate Their electrophysiological parameters SNRT, CSNRT, SACT, AH were mildly prolonged (above the normal) in post 5FU state. Post atropine there was increase in heart rate and the deranged electrophysiological parameters came back to normal. Atrial fibrillation was seen in two patients while performing sinus nodal functions in post 5FU state.Conclusions: Sinus bradycardia is a rare cardiotoxic side effect of 5FU, is a result of an autonomic imbalance viz hypervagotonia which is abolished by atropine and more common in infusuion form than bolus. Infra-his conduction is not altererd and threshold for inducing atrial arrhythmias is decreased in post 5-FU state.

Intracardiac electrophysiological conduction parameters in adult dogs

ABSTRACTBackground: Invasive electrophysiology study (EPS) is one of the most important adjunct tests for the evaluation of arrhythmias in human medicine. However, EPS is neither well known nor widely used in veterinary medicine.Objective: To define the values for intracardiac conduction parameters determined during invasive EPS in dogs.Animals and methods: The study included 16 admitted dogs of various breeds, sex and ages and 6 control Beagles. In the Beagles, EPS was performed twice at 6-month intervals in order to verify the reproducibility of the results. Results: No significant differences were found between the results of the baseline and repeated EPS performed in the Beagles. We found retrograde conduction in 13 (59%) out of 22 dogs and including 4 (31%) animals with concomitant ‘jumps’ in the atrioventricular node conduction curve, pointing to the presence of dual conduction in this node. The mean values of the AV and retrograde VA Wenckebach points equaled to 220 and 360 ms, respectively, suggesting that the capability of the descending route is higher than that of the ascending route.Conclusion: The values determined in this study may be helpful in early detection of abnormalities in the electrical conduction system of the heart.