Long-term outcomes of cardioneuroablation with and without extra-cardiac vagal stimulation confirmation in severe cardioinhibitory neurocardiogenic syncope.

BACKGROUND: Cardioneuroablation (CNA) is a novel therapeutic approach for functional bradyarrhythmias, specifically neurocardiogenic syncope or atrial fibrillation, achieved through endocardial radiofrequency catheter ablation of vagal innervation, obviating the need for pacemaker implantation. Originating in the nineties, the first series of CNA procedures was published in 2005. Extra-cardiac vagal stimulation (ECVS) is employed as a direct method for stepwise denervation control during CNA. OBJECTIVE: This study aimed to compare the long-term follow-up outcomes of patients with severe cardioinhibitory syncope undergoing CNA with and without denervation confirmation via ECVS. METHOD: A cohort of 48 patients, predominantly female (56.3%), suffering from recurrent syncope (5.1 ± 2.5 episodes annually) that remained unresponsive to clinical and pharmacological interventions, underwent CNA, divided into two groups: ECVS and NoECVS, consisting of 34 and 14 cases, respectively. ECVS procedures were conducted with and without atrial pacing. RESULTS: Demographic characteristics, left atrial size, and ejection fraction displayed no statistically significant differences between the groups. Follow-up duration was comparable, with 29.1 ± 15 months for the ECVS group and 31.9 ± 20 months for the NoECVS group (p = .24). Notably, syncope recurrence was significantly lower in the ECVS group (two cases vs. four cases, Log Rank p = .04). Moreover, the Hazard ratio revealed a fivefold higher risk of syncope recurrence in the NoECVS group. CONCLUSION: This study demonstrates that concluding CNA with denervation confirmation via ECVS yields a higher success rate and a substantially reduced risk of syncope recurrence compared to procedures without ECVS confirmation.

Effect of dexmedetomidine added to retrobulbar blockade with lignocaine and bupivacaine in dogs undergoing enucleation surgery.

OBJECTIVE: To investigate the effect of the addition of dexmedetomidine (BLD) to retrobulbar blockade with combined lignocaine and bupivacaine on nociception. ANIMALS: A total of 17 eyes from 15 dogs. METHODS: Prospective, randomized, masked clinical comparison study. Dogs undergoing unilateral enucleation were randomly assigned into two groups; a retrobulbar administration of lignocaine and bupivacaine in a 1:2 volume ratio combined with either BLD or 0.9% saline (BLS). The total volume of the intraconal injection was calculated at 0.1 mL/cm cranial length. Intraoperative parameters were recorded: heart rate (HR), respiratory rate (RR), end-tidal CO2 (EtCO2 ) arterial blood pressure (BP), and inspired isoflurane concentration (ISOinsp). Pain scores, heart rate and RR were recorded postoperatively. RESULTS: Dogs receiving BLD (n = 8) had significantly lower intraoperative RR (p = 0.007), and significantly lower ISOinsp (p = 0.037) than dogs in the BLS group (n = 9). Postoperatively heart rate was significantly lower in the BLD group at 1 min (p = 0.025) and 1 h (p = 0.022). There were no other significant differences in intraoperative or postoperative parameters, or in postoperative pain scores (p = 0.354). Dogs receiving BLD had a higher rate of anesthetic events of bradycardia and hypertension (p = 0.027). Analgesic rescue was not needed in either group. CONCLUSIONS: The addition of BLD to retrobulbar anesthesia did not result in a detectable difference in pain scores relative to blockade with lignocaine and bupivacaine alone. Dogs receiving retrobulbar BLD had a significantly lower intraoperative RR and isoflurane requirement and an increased incidence of intraoperative bradycardia and hypertension.

Clinical impact of aging on outcomes of cardioneuroablation for reflex syncope or functional bradycardia: Results from the cardionEuroabLation: patiEnt selection, imaGe integrAtioN and outComEs-The ELEGANCE multicenter study.

BACKGROUND: Cardioneuroablation (CNA) is a novel treatment for reflex syncope. The effect of aging on CNA efficacy is not fully understood. OBJECTIVE: The purpose of this study was to assess the impact of aging on candidacy and efficacy of CNA for treating vasovagal syncope (VVS), carotid sinus syndrome (CSS), and functional bradyarrhythmia. METHODS: The ELEGANCE (cardionEuroabLation: patiEnt selection, imaGe integrAtioN and outComEs) multicenter study assessed CNA in patients with reflex syncope or severe functional bradyarrhythmia. Patients underwent pre-CNA Holter electrocardiography (ECG), head-up tilt testing (HUT), and electrophysiological study. CNA candidacy and efficacy was assessed in 14 young (18-40 years), 26 middle-aged (41-60 years), and 20 older (>60 years) patients. RESULTS: Sixty patients (37 men; mean age 51 ± 16 years) underwent CNA. The majority (80%) had VVS, 8% had CSS, and 12% had functional bradycardia/atrioventricular block. Pre-CNA Holter ECG, HUT, and electrophysiological findings did not differ across age groups. Acute CNA success was 93%, without differences between age groups (P = .42). Post-CNA HUT response was negative in 53%, vasodepressor in 38%, cardioinhibitory in 7%, and mixed in 2%, without differences across age groups (P = .59). At follow-up (8 months, interquartile range 4-15), 53 patients (88%) were free of symptoms. Kaplan-Meier curves did not show differences in event-free survival between age groups (P = .29). The negative predictive value of a negative HUT was 91.7%. CONCLUSION: CNA is a viable treatment for reflex syncope and functional bradyarrhythmia in all ages, and is highly effective in mixed VVS. HUT is a key step in postablation clinical assessment.

The future of cardioneuroablation in cardiovascular medicine.

INTRODUCTION: Cardioneuroablation is increasingly being utilized to improve outcomes in patients with vagally mediated bradyarrhythmias. However, there are still controversial issues in the field including patient selection, safety and efficacy, and procedural end-points. AREAS COVERED: In this review, the current role of cardioneuroablation is summarized, and controversial issues related to the modality are discussed. EXPERT OPINION: According to small open-label cohort studies, overall freedom from syncope recurrence was higher than 90% after cardioneuroablation in patients with vasovagal syncope (VVS). Use of the electrogram-based strategy or high-frequency stimulation demonstrate similar success rate except in procedures limited to the right atrium. Based on a recently published randomized controlled trial and metanalysis, it may be possible now to make a strong recommendation for cardioneuroablation in patients <40 years of age, and those with the cardioinhibitory or mixed type of VVS who continue to experience frequent and/or burdensome syncope recurrences. Considering patients with VVS are prone to significant placebo/expectation effect, sham-controlled trials may help to quantify the placebo effect. In well-selected patients with functional atrioventricular block and sinus bradycardia, may result in encouraging medium-term outcomes. However, functional bradycardia is identified in a minority of patients presenting with high-grade atrioventricular block or sinus node dysfunction.

The Importance of Selecting Permanent Pacemaker, Evaluating the Heart and Assessing Quality of Life in Cardiac Patient.

The use of pacemakers is necessary for patients with symptomatic bradycardia. Pacemaker implantation also acts as a life-saving procedure. However, there are several reports that patients with a pacemaker (the most widely used pacemaker is on the right ventricle, known as single chamber pacemaker) had disturbances in left ventricle contraction lead to left ventricular systolic dysfunction. Global Longitudinal Strain (GLS) Echocardiography can confirm these left ventricular disturbances. Echocardiography examination is best carried out before and after single-chamber PPM implantation. This study compares PPM placement in apical Right Ventricle (RV) and Right Ventricular Outflow Tract (RVOT) and compares paced QRS duration 150 ms and > 150 ms. Pacing burden >40% causes subclinical left ventricular systolic dysfunction after a month of PPM implantation with decreased GLS in apical RV pacing.This study gives additional information that PPM placement is preferably in RVOT with some specific settings. However, there are many ways to reduce the effects of impaired left ventricular function due to lead installation on the PPM single-chamber device. By using the PPM device which has a dual chamber, the leads will be placed in RVOT and also in the right atrium with atrial-ventricle synchronization. The aim is to avoid impaired left ventricular pump function as supported by a systematic review which states the superiority of dual-chamber PPM over single-chamber PPM in reducing atrial fibrillation and pacemaker syndrome. In the importance of quality of life related to heart disease, the Indonesian version of the MacNew questionnaire can be used. This questionnaire seeks the quality of life of patients with coronary heart disease after revascularization surgery and has undergone rehabilitation. Another important thing is the suitability of the adaptation to the original English version.

Medium-term results of cardioneuroablation for clinical bradyarrhythmias and vasovagal syncope: effects on QT interval and heart rate.

PURPOSE: Although parasympathetic effects of cardioneuroablation (CNA) in vagally mediated bradyarrhythmias (VMB) were studied, sympathetic effects have not been elucidated, yet. We aimed to investigate the acute and medium-term outcomes of CNA as well as the impact of CNA on ventricular repolarization by using corrected QT interval (QTc) measurements. METHODS: Sixty-five patients (58.5% men; age 39.4 ± 14 years) undergoing CNA were included in the study. Patients who underwent CNA due to VMB were divided into two groups: (1) bi-atrial CNA and (2) right-sided CNA. QTc was calculated at 3 time points: before the procedure (time point 1); 24 h post-ablation (time point 2); and at the last follow-up visit (time point 3). RESULTS: The mean follow-up time was 20.0 ± 20 months. Acute success was achieved in 64 (98.4%) of cases. In the whole cohort, from time point 1 to 2, a significant shortening in QTcFredericia, QTcFramingham, and QTcHodges was observed which remained lower than baseline in time point 3. Although the difference between measurements in time point 1 and 2 was not statistically significant for QTcBazett, a significant shortening was detected between time point 1 and 3. There was significant difference between groups for shortening in QTcFredericia and QTcFramingham (p = 0.01). Event-free survival was detected in 90.7% (59/65) of cases. CONCLUSIONS: Our results demonstrate a significant shortening of QTc in addition to high acute and medium-term success rates after CNA. The most likely mechanism is the effect of CNA on the sympathetic system as well as on the parasympathetic system. Bi-atrial ablation was found related to higher QTc shortening effect.

Right anterior ganglionated plexus: The primary target of cardioneuroablation?

BACKGROUND: Catheter ablation of ganglionated plexus (GP) as cardioneuroablation in the left atrium (LA) has been used to treat vasovagal syncope (VVS). OBJECTIVE: The purpose of this study was to assess the effects of ablation of GPs on heart rate and to observe the acute, short-term, and long-term effects after cardioneuroablation. METHODS: A total of 115 consecutive patients with VVS who underwent cardioneuroablation were enrolled. GPs of the LA were identified by high-frequency stimulation and/or anatomic landmarks being targeted by radiofrequency catheter ablation. RESULTS: During ablation of right anterior ganglionated plexus (RAGP), heart rate increased from 61.3 ± 12.2 bpm to 82.4 ± 14.7 bpm (P <.001), whereas during ablation of other GPs only vagal responses were observed. During follow-up of 21.4 ± 13.1 months (median 18 months), 106 participants (92.2%) had no recurrence of syncope or presyncope. Holter data showed that minimal heart rate significantly increased at all follow-up time points (all P<.05), and mean heart rate remained higher than baseline 12 months after ablation (P = .001). CONCLUSION: Cardioneuroablation via GP ablation in the LA effectively inhibited the recurrence of VVS. Ablation of RAGP could increase heart rate immediately and for the long term. This unique phenomenon may provide a new potential approach for treatment of neural reflex syncope or bradyarrhythmias.

Catheter Ablation of Bradyarrhythmia: From the Beginning to the Future.

Enhanced parasympathetic tone may cause sinus bradycardia or pauses, transient or permanent atrioventricular block, with resultant vasovagal syncope. A substantial portion of these patients may be highly symptomatic and refractory to the conventional therapies and may require cardiac pacemaker implantation. Cardioneuroablation is a little known technique for management of patients with excessive vagal activation based on radiofrequency catheter ablation of main parasympathetic autonomic ganglia around the heart. Due to complicated inclusion criteria, ganglia detection methods, and ablation endpoints, routine usage of the procedure cannot be recommended at this time. In this comprehensive review, we aimed to discuss all aspects of cardioneuroablation procedure in bradyarrhythmias.

Targets and End Points in Cardiac Autonomic Denervation Procedures.

BACKGROUND: Autonomic denervation is an alternative approach for patients with symptomatic bradycardia. No consensus exists on the critical targets and end points of the procedure. The aim of this study was to identify immediate end points and critical atrial regions responsible for vagal denervation. METHODS AND RESULTS: We enrolled 14 patients (50% men; age: 34.0±13.8 years) with cardioinhibitory syncope, advanced atrioventricular block or sinus arrest, and no structural heart disease. Anatomic mapping of ganglionated plexuses was performed, followed by radiofrequency ablation. Heart rate, sinus node recovery time, Wenckebach cycle length, and atrial-His (AH) interval were measured before and after every radiofrequency pulse. Wilcoxon signed-rank test was used for comparison. Significant shortening of the R-R interval (P=0.0009), Wenckebach cycle length (P=0.0009), and AH intervals (P=0.0014) was observed after ablation. The heart rate elevation was 23.8±12.5%, and the Wenckebach cycle length and AH interval shortening was 18.1±11% and 24.6±19%, respectively. Atropine bolus injection (0.04 mg/kg) did not increase heart rate further. Targeting a single spot of the left side (64% of the patients) or right side (36%) of the interatrial septum was observed to be responsible for ≥80% of the final R-R and AH interval shortening during ablation. CONCLUSIONS: Targeting specific sites of the interatrial septum is followed by an increase in heart rate and atrioventricular nodal conduction properties and might be critical for vagal attenuation. The R-R interval, Wenckebach cycle length, and AH interval shortening, associated with a negative response to atropine, could be considered immediate end points of the procedure.

Catheter ablation of atrial fibrillation in patients with concomitant sinus bradycardia-Insights from the German Ablation Registry.

AIMS: This investigation addresses procedural characteristics of catheter ablation in patients with atrial fibrillation (AF) and sinus bradycardia. METHODS: From the prospective, multi-center German Ablation Registry 1073 patients with sinus rhythm at the time of AF ablation were divided into two groups according to heart rate at start of procedure (A, <60 beats per minute (bpm), n=197; B, 60-99bpm, n=876). RESULTS: Acute procedural success was high (≥98%) and similar between groups. Procedure duration and energy application time were increased in group A (180min vs. 155min and 2561s vs. 1879s, respectively). Major complications were more frequent in group A (2.2% vs. 0.5%), and a greater proportion of these patients was discharged under antiarrhythmic medication (64% vs. 52%). CONCLUSION: Catheter ablation of AF with concomitant sinus bradycardia is associated with high procedural efficacy, longer procedure- and energy application durations, and a slightly elevated complication rate.

A practical approach to perioperative management of cardiac implantable electronic devices.

With the increased use of cardiac implantable electronic devices (CIEDs), it is increasingly important to recognise the unique challenges involved in the management of patients with CIEDs who are undergoing surgery. Practice advisories and consensus statements have been issued by the American Society of Anesthesiologists and the Heart Rhythm Society, advocating a multidisciplinary approach. This review discusses and presents a practical approach to perioperative CIED management in the Singapore context.

Permanent pacemaker implanted into patient's left ventricle via subclavian artery by mistake: a case report.

BACKGROUND: Although various iatrogenic complications could be observed in the process of permanent pacemaker implantation, pacemaker electrode mistakenly implanted into left ventricle via subclavian artery and aortic valve has not been reported. CASE PRESENTATION: Herein, we reported a 71-year-old woman with permanent pacemaker mistakenly implanted into the left ventricle. During the operation of permanent pacemaker implantation, puncture was performed on her subclavian artery by mistake, and then the pacemaker electrode was put into the cardiac apex of left ventricle via ascending aorta reversely. CONCLUSION: The further operation could be conducted.

The integration and functional evaluation of rabbit pacing cells transplanted into the left ventricular free wall.

To evaluate the feasibility of cell transplantation to treat bradyarrhythmia, we analyzed the in vivo integration and pacing function after transplantation of mHCN4-modified rabbit bone marrow mesenchymal stem cells (MSCs) into the rabbit left ventricle free wall epicardium. In our investigation, we injected MSCs transduced with or without mHCN4 into the rabbit left ventricle free wall epicardium. Chemical ablation of the sinoatrial node was performed and bilateral vagus nerves were sequentially stimulated to observe premature left ventricular contraction or left ventricular rhythm. We found that the mHCN4-transduced MSC group had a significantly higher ventricular rate and a shorter QRS duration than that of the control and EGFP group. Furthermore, the mHCN4-transduced MSCs, but not the control cells, gradually adapted long-spindle morphology and became indistinguishable from adjacent ventricle myocytes. The modified MSCs showed pacing function approximately 1 week after transplantation and persisted at least 4 weeks after transplantation. In conclusion, a bradyarrhythmia model can be successfully established by chemical ablation of the sinoatrial node and sequential bilateral vagus nerve stimulation. The mHCN4-modified rabbit MSCs displayed evident dynamic morphology changes after being transplanted into rabbit left ventricle free wall epicardium. Our studies may provide a promising strategy of using modified stem cell transplantation to treat bradyarrhythmia.