Cardioneuroablation for the treatment of reflex syncope and functional bradyarrhythmias. A Scientific Statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS) and the Latin American Heart Rhythm Society (LAHRS).

Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy. This document aims to review and interpret available scientific evidence and provide a summary position on the topic.

Procedural and Intermediate-term Results of the Electroanatomical-guided Cardioneuroablation for the Treatment of Supra-Hisian Second- or Advanced-degree Atrioventricular Block: the PIRECNA multicentre registry.

AIMS: Prior case series showed promising results for cardioneuroablation in patients with vagally induced atrioventricular blocks (VAVBs). We aimed to examine the acute procedural characteristics and intermediate-term outcomes of electroanatomical-guided cardioneuroablation (EACNA) in patients with VAVB. METHODS AND RESULTS: This international multicentre retrospective registry included data collected from 20 centres. Patients presenting with symptomatic paroxysmal or persistent VAVB were included in the study. All patients underwent EACNA. Procedural success was defined by the acute reversal of atrioventricular blocks (AVBs) and complete abolition of atropine response. The primary outcome was occurrence of syncope and daytime second- or advanced-degree AVB on serial prolonged electrocardiogram monitoring during follow-up. A total of 130 patients underwent EACNA. Acute procedural success was achieved in 96.2% of the cases. During a median follow-up of 300 days (150, 496), the primary outcome occurred in 17/125 (14%) cases with acute procedural success (recurrence of AVB in 9 and new syncope in 8 cases). Operator experience and use of extracardiac vagal stimulation were similar for patients with and without primary outcomes. A history of atrial fibrillation, hypertension, and coronary artery disease was associated with a higher primary outcome occurrence. Only four patients with primary outcome required pacemaker placement during follow-up. CONCLUSION: This is the largest multicentre study demonstrating the feasibility of EACNA with encouraging intermediate-term outcomes in selected patients with VAVB. Studies investigating the effect on burden of daytime symptoms caused by the AVB are required to confirm these findings.

Cardioneuroablation for treatment of carotid sinus syndrome secondary to oropharyngeal squamous cell cancer.

Head and neck tumors can rarely cause carotid sinus syndrome and this often resolves by surgical intervention or palliative chemoradiotherapy. If these modalities are not an option or are ineffective, the most preferred treatment is permanent pacemaker therapy. Here, we present the first case of cardioneuroablation treatment performed in patient with oropharyngeal squamous cell cancer who developed recurrent asystole and syncope attacks due to compression of the carotid sinus on neck movement.

Impact of cryoballoon application abortion due to phrenic nerve injury on reconnection rates: a YETI subgroup analysis.

AIMS: Cryoballoon (CB)-based pulmonary vein isolation (PVI) is an effective treatment for atrial fibrillation (AF). The most frequent complication during CB-based PVI is right-sided phrenic nerve injury (PNI) which is leading to premature abortion of the freeze cycle. Here, we analysed reconnection rates after CB-based PVI and PNI in a large-scale population during repeat procedures. METHODS AND RESULTS: In the YETI registry, a total of 17 356 patients underwent CB-based PVI in 33 centres, and 731 (4.2%) patients experienced PNI. A total of 111/731 (15.2%) patients received a repeat procedure for treatment of recurrent AF. In 94/111 (84.7%) patients data on repeat procedures were available. A total of 89/94 (94.7%) index pulmonary veins (PVs) have been isolated during the initial PVI. During repeat procedures, 22 (24.7%) of initially isolated index PVs showed reconnection. The use of a double stop technique did non influence the PV reconnection rate (P = 0.464). The time to PNI was 140.5 ± 45.1 s in patients with persistent PVI and 133.5 ± 53.8 s in patients with reconnection (P = 0.559). No differences were noted between the two populations in terms of CB temperature at the time of PNI (P = 0.362). The only parameter associated with isolation durability was CB temperature after 30 s of freezing. The PV reconnection did not influence the time to AF recurrence. CONCLUSION: In patients with cryoballon application abortion due to PNI, a high rate of persistent PVI rate was found at repeat procedures. Our data may help to identify the optimal dosing protocol in CB-based PVI procedures. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03645577?term=YETI&cntry=DE&draw=2&rank=1 ClinicalTrials.gov Identifier: NCT03645577.

Pericarditis following left atrial ablation.

INTRODUCTION: We aimed to evaluate the incidence of acute pericarditis following cardioneuroablation (CNA) and to compare this with patients undergoing left atrial (LA) radiofrequency ablation for atrial fibrillation (AF). METHODS AND RESULTS: This is a single-center prospective study. During the study period, CNA for vasovagal syncope was performed in 42 patients, pulmonary vein isolation (PVI) for paroxysmal AF in 46 patients, and posterior wall isolation (PWI) in addition to PVI for persistent AF in 22 patients. Pericarditis was reported by 18 (16.4%) patients overall: 1 (2.4%) patient in CNA group, 8 (17.4%) patients in PVI group, and 9 (40.9%) patients in PWI (p < .001). On univariable logistic regression analysis, CNA was associated with a lower risk of pericarditis (odds ratio 0.11, 95% confidence interval [CI] 0.01-0.97), while ablation of PWI plus PVI was associated with a higher risk of pericarditis compared with PVI (odds ratio 3.29, 95% CI 1.05-10.3). CONCLUSION: This study shows that pericarditis is extremely uncommon following CNA and is significantly less frequent than following AF ablation. This difference is likely related to the much lower amount of LA ablation necessary in this group.

Cardioneuroablation for vasovagal syncope and atrioventricular block: A step-by-step guide.

Catheter-based cardioneuroablation is increasingly being utilized to improve outcomes in patients with vasovagal syncope and atrioventricular block due to vagal hyperactivity. There is now increasing convergence among enthusiasts on its various aspects, including patient selection, technical steps, and procedural end-points. This pragmatic review aims to take the reader through a step-by-step approach to cardioneuroablation: we begin with a brief overview of the anatomy of intrinsic cardiac autonomic nervous system, before focusing on the indications, preprocedure and postprocedure management, necessary equipment, and its potential limitations.

Procedural and short-term results of electroanatomic-mapping-guided ganglionated plexus ablation by first-time operators: A multicenter study.

INTRODUCTION: Single-center observational studies have shown promising results with fragmented electrogram (FE)-guided ganglionated plexus (GP) ablation in patients with vagally mediated bradyarrhythmia (VMB). We aimed to compare the acute procedural characteristics during FE-guided GP ablation in patients with VMB performed by first-time operators and those of a single high-volume operator. METHODS AND RESULTS: This international multicenter cohort study included data collected over 2 years from 16 cardiac hospitals. The primary operators were classified according to their prior GP ablation experience: a single high-volume operator who had performed > 50 GP ablation procedures (Group 1), and operators performing their first GP ablation cases (Group 2). Acute procedural characteristics and syncope recurrence were compared between groups. Forty-seven consecutive patients with VMB who underwent FE-guided GP ablation were enrolled, n = 31 in Group 1 and n = 16 in Group 2. The mean number of ablation points in each GP was comparable between groups. The ratio of positive vagal response during ablation on the left superior GP was higher in Group 1 (90.3% vs. 62.5%, p = .022). Ablation of the right superior GP increased heart rate acutely without any vagal response in 45 (95.7%) cases. The procedure time was longer in group 2 (83.4 ± 21 vs. 118.0 ± 21 min, respectively, p < .001). Over a mean follow-up duration of 8.0 ± 3 months (range 2-24 months), none of the patients suffered from syncope. CONCLUSION: This multi-center pilot study shows for the first time the feasibility of FE-guided GP ablation across a large group of procedure-naïve operators.

Intrinsic cardiac autonomic nervous system: What do clinical electrophysiologists need to know about the "heart brain"?

It is increasingly recognized that the autonomic nervous system (ANS) is a major contributor in many cardiac arrhythmias. Cardiac ANS can be divided into extrinsic and intrinsic parts according to the course of nerve fibers and localization of ganglia and neuron bodies. Although the role of the extrinsic part has historically gained more attention, the intrinsic cardiac ANS may affect cardiac function independently as well as influence the effects of the extrinsic nerves. Catheter-based modulation of the intrinsic cardiac ANS is emerging as a novel therapy for the management of patients with brady and tachyarrhythmias resulting from hyperactive vagal activation. However, the distribution of intrinsic cardiac nerve plexus in the human heart and the functional properties of intrinsic cardiac neural elements remain insufficiently understood. The present review aims to bring the clinical and anatomical elements of the immune effector cell-associated neurotoxicity together, by reviewing neuroanatomical terminologies and physiological functions, to guide the clinical electrophysiologist in the catheter lab and to serve as a reference for further research.

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.

QTc shortening effect of ganglionated plexi ablation.

BACKGROUND: In previous studies, patients undergoing ablation of ganglionated plexi (GPA) for vagally mediated bradyarrhythmias were noted to have shortening of their corrected QT interval (QTc). AIMS: To compare the effects of GPA (group 1) to pulmonary vein isolation + GPA (group 2) on QTc. MATERIAL AND METHODS: We enrolled 39 patients, n = 25 in group 1 and n = 14 in group 2. QTc was calculated at baseline, at 24 h after ablation, and at 9-12 months in the follow-up. Recurrent syncope, asystole >2 s, and/or second- or third-degree AVB episodes were carefully documented as the primary outcome in group 1. Any atrial arrhythmia ≥30 seconds documented on 24-h Holter monitoring was defined as the primary outcome in group 2. RESULTS: The mean follow-up time was 14.9 ± 4 months. Acute success was achieved in all cases. In whole cohort, a significant shortening on QTcBazett, QTcFramingham, QTcFredericia, and QTcHodges was observed [416 vs 398ms (p = .002), 411vs 378 ms (p < .001), 412 vs 379ms (p < .001), and 420 vs 383ms (p < .001), respectively]. In the linear mixed model analysis, the longitudinal reduction tendency in the QTc level was more pronounced in group 1. Event-free survival was detected in 90.7% (59/65) of cases. DISCUSSION: Our results demonstrate a significant shortening of QTc in addition to high medium-term success rates after GPA. Pulmonary vein isolation + GPA was associated with lower QTc shortening effect which implies structural disease may change electrophysiological response to ablation. The most likely mechanism is the effect of GPA on the sympathetic system.

Cardioneuroablation for cardioinhibitory vasovagal syncope.

BACKGROUND: Cardioneuroablation (CNA) is an emerging technique being used to treat patients with cardioinhibitory vasovagal syncope (VVS). We describe a case of CNA in targeting atrial ganglionated plexi (GP) based upon anatomical landmarks and fractionated electrogram (EGM) localization in a patient with cardioinhibitory syncope. CASE PRESENTATION: A 20-year-old healthy female presented with malignant VVS and symptomatic sinus pauses, with the longest detected at 10 s. She underwent acutely successful CNA with demonstration of vagal response (VR) noted after ablation of left sided GP, and tachycardia noted with right sided GP ablation. All GP sites were defined by anatomical landmarks and EGM analysis. By using the fractionation mapping software of Ensite Precision mapping system with high density mapping, fragmented EGMs were successfully detected in each GP site. One month after vagal denervation, there were no recurrent syncopal episodes or sinus pauses. Longer term follow-up with implantable loop recorder is planned. CONCLUSION: We performed CNA in a patient with VVS by utilizing a novel approach of combined use of high density mapping and fractionation mapping software. With this approach, we were able to detect fractionation in all GP sites and demonstrate acute VR. This workflow may allow for a new, standardized technique suitable for widespread use.

Effect of conscious sedation and deep sedation on the vagal response characteristics during ganglionated plexus ablation.

INTRODUCTION: We aimed to determine the effects of conscious and deep sedation on vagal response (VR) characteristics during ganglionated plexus (GP) ablation. METHODS: Forty consecutive patients undergoing GP ablation for vasovagal syncope were divided to receive conscious sedation with midazolam (Group 1, n = 29) or deep sedation with the midazolam-propofol combination (Group 2, n = 11). VR was defined on three levels. R-R interval increase of >50% (Level 1); R-R interval increase of 20%-50% (Level 2); and R-R interval increase of <20% (Level 3). RESULTS: The ratio of Level 1 VR during ablation on left superior and inferior GPs was significantly lower in Group 2 (p < .0001 and p = .034, respectively). Once the cut-off for VR was decreased to Level 2, the ratio of (+) VR was similar between groups during ablation of left-sided GPs. Positive VR in any level was lower than 20% during ablation of right-sided GPs. CONCLUSIONS: The autonomic tone might be affected in different ways by the level or type of intravenous sedation. Awareness of anesthesia-related differences may be important if GP ablation will be performed by using VR characteristics during ablation.

Permanent pacing for recurrent vasovagal syncope: New answers or just more questions?

Vasovagal syncope (VVS) is a clinical condition related to bradycardia (cardioinhibitory response) and/or hypotension (vasodepressor response), likely mediated by parasympathetic overactivity and sympathetic withdrawal. Although clinical presentation is usually related to a self-limited event, frequent episodes or events without prodrome might be debilitating. There are limited medical therapies proven effective in randomized clinical trials. In patients not responsive to standard therapy, permanent pacemaker therapy may be suggested. However, the role of cardiac pacing for the prevention of syncope recurrences remains controversial due to difficulties to exclude potential role of the vasodepressor component during the episode.

Effects of permanent cardiac pacing on ventricular repolarization when compared to cardioneuroablation.

INTRODUCTION: The impact of cardioneuroablation (CNA) on ventricular repolarization by using corrected QT interval (QTc) measurements has been recently demonstrated. The effects of cardiac pacing (CP) on ventricular repolarization have not been studied in patients with vasovagal syncope (VVS). We sought to compare ventricular repolarization effects of CNA (group 1) with CP (group 2) in patients with VVS. METHODS: We enrolled 69 patients with age 38 ± 13 years (53.6% male), n = 47 in group 1 and n = 22 in group 2. Clinical diagnosis of cardioinhibitory type was supported by cardiac monitoring or tilt testing. QTc was calculated at baseline (time-1), at 24 h after ablation (time-2), and at 9-12 months (time-3) in the follow-up. RESULTS: In the group 1, from time-1 to time-2, a significant shortening in QTcFredericia (from 403 ± 27 to 382 ± 27 ms, p < 0.0001), QTcFramingham (from 402 ± 27 to 384 ± 27 ms, p < 0.0001), and QTcHodges (from 405 ± 26 to 388 ± 24 ms, p < 0.0001) was observed which remained lower than baseline in time-3 (373 ± 29, 376 ± 27, and 378 ± 27 ms, respectively). Although the difference between measurements in time-1 and time-2 was not statistically significant for QTcBazett, a significant shortening was detected between time-1 and time-3 (from 408 ± 30 to 394 ± 33, p = 0.005). In the group 2, there was no time-based changes on QTc measurements. In the linear mixed model analysis, the longitudinal reduction tendency in the QTcFredericia and QTcFramingham was more pronounced in group 1. CONCLUSIONS: Our results demonstrate that CNA reduces QTc levels through neuromodulation effect whereas CP has no effect on ventricular repolarization in patients with VVS.

Fractionation mapping software to map ganglionated plexus sites during sinus rhythm.

Ablation of ganglionated plexuses (GPs) is a relatively new technique in patients with vasovagal syncope. Due to individual variation of GP settlement, reproducible GP detection methods are needed to during electrophysiologic study. In the present case, fractionation mapping software of Ensite system was tested to detect localization of GPs and first compared with previously validated fractionated electrograms based strategy.

Usefulness of post-procedural heart rate response to predict syncope recurrence or positive head up tilt table testing after cardioneuroablation.

AIMS: Previous reports have suggested that cardioneuroablation (CNA) can be effective in reducing syncopal recurrences in patients with vasovagal syncope (VVS). This study assessed the efficacy of CNA in preventing a positive response to head-up tilt testing (HUT). METHODS AND RESULTS: This is a single-centre retrospective study reviewing prospectively collected data. Fifty-one consecutive patients with VVS were included in the study. After confirmation of >3 s asystole on HUT, all patients underwent CNA. Head-up tilt testing was repeated 1 month after CNA. The main outcome measures were recurrence of syncope episode and positive response on HUT. During a median follow-up period of 11 months (interquartile range 3-27 months), all but 3 (5.8%) of 51 patients were free of syncope. Repeated HUTs were negative in 44 (86.2%) patients. When patients with recurrent syncope were excluded, vasodepressor response was seen in three cases and cardioinhibitory response in one case, respectively. Cardioneuroablation caused significant and durable shortening of RR interval in all cases. This effect was significantly higher in patients without positive HUT responses. CONCLUSION: This pilot study shows that CNA can effectively prevent recurrent syncopal episodes in patients with refractory VVS. Head-up tilt testing seems as a valuable diagnostic tool not only to select suitable candidates and but also to evaluate success of CNA.

Why is pulmonary vein isolation not enough for vagal denervation in all cases?

Pulmonary vein isolation (PVI) may cause vagal response during radiofrequency application or increase on heart rate after ablation. All those responses are related to inadvertent ablation effect on ganglionated plexi. In the present case, we aimed to explain why vagal response effects of PVI are not same in all cases.

Ultrasound-guided combined pectoral nerve block and axillary venipuncture for the implantation of cardiac implantable electronic devices.

BACKGROUND: Combined ultrasound (US)-guided pectoral nerves (PECS) block and axillary vein (AV) puncture for cardiac implantable electronic devices can be effective to achieve optimal perioperative pain management and prevent access-related complications. METHODS: A total of 36 patients who underwent combined US-guided PECS block and AV puncture were included. All routinely recorded parameters, including clinical and demographic characteristics, periprocedural medical administrations, the time taken for both PECS block and AV puncture, procedure time, postprocedural pain score, and procedure-related complications, were collected and analyzed. RESULTS: In total, 54 leads were placed in 36 patients. The combined US-guided PECS block and AV puncture was performed successfully in 35 (97.2%) patients without the need for fluoroscopy or venography. AV access for each lead was achieved in a single attempt in 80.6% of cases. The time for both PECS block and AV puncture was 223.6 ± 52.1 s, including the time to apply incision site anesthesia. Additional sedatives and/or local anesthetics were required in two patients during procedure. Visual analog scale average of the patients in the 1st, 6th, and 24th h was 3.7 ± 1.14. 1.61 ± 1.29, and 0.08 ± 0.28, respectively. After the procedure, four patients (three of them woman) needed analgesics. There were no venous access-related complications. CONCLUSIONS: This new combined technique maintains both surgical and postoperative analgesia and prevents vascular access-related complications without significant increase on procedure time.