Recurrence Of Syncope Research Articles

Electrophysiological Characteristics and Ablation Outcomes in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia.

Catheter ablation of premature ventricular contractions (PVCs) that trigger polymorphic ventricular tachycardia (PVT) or ventricular fibrillation has been reported as a novel therapy to reduce the syncope events in patients with catecholaminergic PVT, whereas the long-term ablation outcome and its value in improving exercise-induced ventricular arrhythmias remain unclear. Fourteen consecutive selected patients with catecholaminergic PVT (mean±SD age, 16±6 years; 43% male patients) treated with maximum β-blockers with no possibility of adding flecainide were prospectively enrolled for catheter ablation. The primary end point was syncope recurrence, and the secondary end point was the reduction of the ventricular arrhythmia score during exercise testing. Twenty-six PVT/ventricular fibrillation-triggering PVCs were identified for ablation. The trigger beats arose from the left ventricle in 50% of the cases and from both ventricles in 36% of the cases. Purkinje potentials were observed at 27% of the targets. After a mean follow-up of 49 months after ablation, 8 (57%) patients were free from syncope recurrence. Ablation of trigger beat significantly reduced the syncope frequency (mean±SD, 4.3±1.6 to 0.5±0.8 events per year; P<0.001) and improved the ventricular arrhythmia scores at the 3-month (5 [range, 3-6] to 1.5 [range, 0-5]; P=0.002) and 12-month (5 [range, 3-6] to 2 [range, 0-5]; P=0.014) follow-ups. The induction of nontriggering PVCs postablation was closely associated with syncope recurrence (hazard ratio, 6.8 [95% CI, 1.3-35.5]; P=0.026). Catheter ablation of PVT/ventricular fibrillation-triggering PVCs in patients with catecholaminergic PVT who cannot receive flecainide treatment seems to be a safe and feasible adjunctive treatment that may reduce the syncope burden and improve exercise-related ventricular arrhythmias. Induction of nontriggering PVCs after ablation is associated with a higher risk of syncope recurrence.

Cardioneuroablation for reflex asystolic syncope: Mid-term safety, efficacy, and patient’s acceptance

BackgroundCardioneuroablation (CNA) is a promising therapy for reflex asystolic syncope; however, convincing data on the mid-term safety and efficacy of this procedure are lacking. ObjectiveThe purpose of this study was to assess the mid-term safety, efficacy, and patient acceptance of CNA. MethodsThis prospective observational single-center study included 115 consecutive patients (mean age 39 ± 13 years; 58% female) treated between 2016 and 2022 who completed at least 1-year follow-up. ResultsNo significant procedure-related acute complications occurred. During median follow-up of 28 months (range 12–75), 95 (83%) remained free from syncope. Of the 20 patients (17%) with syncope recurrence, syncope burden decreased from a mean 17 (median 6.5) to 3.75 (median 2.5) episodes (P = .015). In 9 of 10 patients, pacing system removal was possible. Repeated CNA was needed in 3 patients (3%), whereas pacemaker implantation was performed in 5 (4%). The most frequent mid-term complication of CNA was sinus rhythm acceleration (from 60 ± 14 bpm to 90 ± 16 bpm; P <.0001), which was symptomatic in 31 patients (27%); 8 patients (7%) required chronic beta-blocker and/or ivabradine. Sinus node modification was necessary in 1 patient. Other complaints included dyspnea, chronic chest pain, and decreased exercise capacity, which were mild and reported by 16 patients (14%). Patient acceptance of CNA was very high: 96% stated that it was worth undergoing the procedure. ConclusionsMid-term efficacy of CNA exceeds 80%, and acute complications are absent. The most frequent mid-term chronic complication is inappropriate sinus tachycardia, which in 7% required chronic treatment. The procedure is well accepted by patients.

Management of Patients With Unexplained Syncope: Derivation and Validation of a Simplified 2-Step Diagnostic Approach.

The aim of this study was to develop a structured 2-step approach, based on noninvasive diagnostic criteria, that led to an electrophysiology study in patients with unexplained syncope. Two independent cohorts were used: the derivation cohort with 665 patients based on electronic health record data to develop our 2-step diagnostic approach, and the validation cohort based on 160 prospectively screened patients, presenting with unexplained syncope episodes. Noninvasive electrocardiographic and imaging markers and an electrophysiology study-based invasive assessment were combined. A positive diagnostic approach according to our study's prespecified criteria resulted in a decision to proceed with a permanent pacemaker/implantable cardioverter-defibrillator. The primary end point was the time until the event of recurrent syncope (syncope-free survival). Number needed to treat was calculated for patients with a positive diagnostic approach. The number of patients with unexplained syncope and borderline sinus bradycardia needed to treat was 5, and the number of patients with unexplained syncope and bundle branch block needed to treat was 3 over a mean follow-up of ≈4 years. After the structured 2-step approach, the primary outcome occurred in 14 of 82 (17.1%) with a pacemaker/implantable cardioverter-defibrillator and 19 of 57 (33%) with a negative approach, with a mean follow-up of ≈2.5 years (29.29±12.58 months, P=0.03). The low number needed to treat in the derivation cohort and the low percentage of syncope recurrence in the validation cohort supports the proposed 2-step electrophysiology-inclusive algorithm as a potentially low-cost, 1-day, structured tool for these patients.

Serotonin reuptake inhibition for the prevention of vasovagal syncope: a systematic review and meta-analysis.

Vasovagal syncope is a common clinical condition that lacks effective medical therapies despite being associated with significant morbidity. Current guidelines suggest that serotonin-specific reuptake inhibitors might suppress vasovagal syncope but supporting studies have been small and heterogenous. The purpose of this study was to evaluate the efficacy of serotonin-specific reuptake inhibitors to prevent syncope in patients with recurrent vasovagal syncope by conducting a systematic review and meta-analysis of published studies. Relevant randomized controlled trials were identified from the MEDLINE and Embase databases without language restriction from inception to August 2022, and ClinicalTrials.gov. All studies were conducted in clinical syncope populations and compared the benefit of serotonin versus placebo. Weighted relative risks were estimated using random effects meta-analysis techniques. Three studies (n = 204) met inclusion criteria. Patients were 42 ± 13years of age and 51% female. Serotonin-specific reuptake inhibitors were found to substantially reduce the likelihood of a patient having at least one recurrence of vasovagal syncope [relative risk (RR) 0.34 (0.20-0.60), p < 0.01] with minimal between-study heterogeneity (I2 = 0%, p = 0.67). Serotonin-specific reuptake inhibitors in two reports provided significant protection against clinical presyncope [RR 0.43 (0.24-0.77), p < 0.01], with minimal between-study heterogeneity (I2 = 0%, p = 0.80). Serotonin-specific reuptake inhibitors may be effective in preventing syncope induced by head-up tilt testing and in syncope in the community in randomized, double-blinded clinical trials.

Head-up tilt test induced asystole and recurrent syncope: a follow-up study

Abstract Introduction Head-up tilt test (HUTT) is a valuable diagnostic tool in unexplained and recurrent syncope, especially when reflex etiology is suspected. If asystole is the dominant feature of reflex syncope, permanent pacemaker therapy may be effective for reducing syncope recurrence. Purpose To investigate syncope recurrence, pacemaker implantation and death of patients with syncope and asystole induced by HUTT and carotid sinus message (CSM). Methods Retrospective analysis of consecutive patients referred for HUTT between January 2017 and December 2021 and selection of those with cardioinhibitory response, defined by syncope or pre-syncope and asystolic pause ≥3 seconds. Patients’ follow-up (FUP) was performed via a phone interview and analysis of clinical records, to assess recurrence of syncope, treatments, and death. Results A total of 44 patients were included: 30 (68,2%) were men, with a median age of 69 years (interquartile range (IQR) of 24). Asystole was experienced after CSMin 41 patients and during tilt test alone in 3 patients. Median FUP was 26 months (IQR 23). There were 19 (44,2%) patients who implanted pacemaker (PM), all with cardioinhibitory carotid sinus syndrome ( I-CSS), 57,9% men, with median age of 74 years (IQR 19) and median duration of asystole during CSMof 6,3 seconds (IQR 3,8). Of these, 5 (26,3%) implanted a unicameral PM and the remaininga bicameral PM, with AAI-DDD mode programming. Two patients had PM-related complications: infection and dislodgment of ventricular lead, both in the first 15 days after implantation. Median atrial and ventricular pacing percentage at last PM consultation was 7% (IQR 28) and 1% (IQR 4), respectively. There was a positive strong correlation between the percentage of atrial pacing at first and at last appointment (p&amp;lt;0,001, r=0,867) and a positive moderated correlation between the percentage of ventricular pacingat first and at last appointment (p=0,022, r=0,586), suggesting a similar degree of pacing along FUP-time. Only three patients (6,8%) had syncope recurrence, all men with CI-CSS, median age of 78; one patient had syncope before implantation PM, other relapsed 2-times with a PMimplanted and the third refused PMimplantation despite 5-time recurrence of symptoms. There was no association between the duration of the asystole during HUTT with implantation of PM nor syncope recurrence (p&amp;gt;0.2). Age at HUTT was significantly associated both with CI-CSS and PM implantation (p=0,001 and p=0,045, respectively). Two patients died, both of oncologic causes. Conclusion In agreement with the literature, our cohort of patients with cardioinhibitory response during HUTT and CSM experienced an overall good prognosis, with no cardiac deaths; there was very low syncope recurrence, not allowing a comparison between the groups with and without pacemaker. Age at HUTT was significantly associated both with CI-CSS and PMimplantation.

Heart rate variability and syncope free survival after endocardial ablation of ganlionated plexi in patiens with recurrent vasovagal syncope and functional sinus node dysfunction and AV block

Abstract Introduction Cardioneuroablation (CNA) or ablation of the ganglionated plexi (GP) is an emergent procedure that has been used in the treatment of vasovagal syncope Conclusions: (VVS), functional sinus node dysfunction (SND) and functional atrioventricular block (AVB), however long term effects of this technique are not well defined. The aim of the present study was to describe our initial experience with this technique and to assess long term hear rate (HR) variability. Methods Prospective, unicentric, observational study of consecutive patients which were referred to our institution for VVS, functional SND or functional AVB. Prior the procedure, all the patients underwent atropine test and 24-hour holter monitoring. Heart rate variability was assessed at 3 and 6 months with repeated 24-hour holter monitoring. Survival from syncope and pacemaker implantation was calculated in the cohort. Results 24 patients (52 ± 10 years, 70.8% males) were included in the study. 83.3% of the cohort had history of syncope (1.3 ± 3.4 episodes/month) and 95.8% of presyncope. Indication for CNA was SND 29.2%, AVB 25% and recurrent VVS in 45.8%. After a median follow up of 9.9 (4.3-20.7) months, 91.7% were free from syncope recurrence and only 29.2% had presyncope (p&amp;lt;0.001) (Figure 1). There was also a significant increase in minimum HR (p=0.01) and medium HR (p=0.02), without any differences in the maximum HR (p=NS). There was also a decrease in all the parameters used to assess HR variability (SDNN24 p=0.02; rMSSD p=0.017; pNN50 p&amp;lt;0.01) that was constant during the 6 months (Figure 2). Conclusions In our cohort, CNA was associated with a syncope free survival of 91.7% and could be a reasonable choice for patients with functional SND or AVB and recurrent VVS. There was an increase in the maximum and medium HR and a decrease in HR variability that remained constant at 6 months.Figure 1Figure 2

Serum uric acid predicts therapeutic response to midodrine hydrochloride in children with vasovagal syncope: a pilot study

Serum uric acid (UA) level has been proven to be related to several cardiovascular and metabolic diseases. In the present study, we examined if baseline serum UA level could predict the therapeutic efficacy of midodrine hydrochloride on vasovagal syncope (VVS) in children. The pediatric VVS patients who received midodrine hydrochloride from November 2008 to October 2022 were enrolled. After a median treatment duration of 3 months, the therapeutic effect was evaluated. According to the patients’ responses to midodrine hydrochloride, which was determined by the recurrence of syncope, they were divided into effective and ineffective groups. The baseline variables were explored using univariable and multivariate logistic analysis. The predictive efficacy was assessed by receiver operating characteristic curve (ROC), precision-recall curve (PR), Hosmer–Lemeshow test, calibration curve, and decision curve analysis (DCA). Totally, 53 participants were included in the study. Among the 51 patients who were successfully followed up, 29 (56.9%) responded to midodrine hydrochloride (effective group), and the other 22 (43.1%) failed to respond to midodrine hydrochloride (ineffective group). The participants in effective group had lower baseline serum UA level than those in ineffective group (276.5 ± 73 μmol/L vs. 332.7 ± 56 μmol/L, p = 0.004). Multivariable logistic analysis showed that serum UA was associated with the therapeutic response (odds ratio (OR): 0.985, 95% confidence interval (CI): 0.974–0.997, p = 0.01). ROC analysis indicated that using baseline serum UA < 299 μmol/L as a threshold value yielded a sensitivity of 77.3% and a specificity of 79.3% in predicting the treatment response to midodrine hydrochloride. The area under the PR curve was 0.833. Hosmer–Lemeshow test yielded a p value of 0.58, and calibration plot indicated that the model was well-fitted. DCA demonstrated that treatment decision depending on the baseline serum UA level resulted in a favorable net benefit. Conclusion: This pilot study suggested that the baseline serum UA level could be taken as a predictor of therapeutic effect of midodrine hydrochloride on VVS in children.What is Known:• Empirical and unselected use of midodrine hydrochloride has an unfavorable therapeutic effect on VVS in children. Serum uric acid (UA) is closely linked to cardiovascular events.What is New:• A low baseline serum UA level successfully predicts the therapeutic effectiveness of midodrine hydrochloride on VVS in children.

Selective anatomical catheter ablation of left atrial ganglionated plexus for vasovagal syncope: Left superior and right anterior ganglionated plexus ablation.

Vasovagal syncope (VVS) is one of the most common causes of syncope. Traditional treatment has not achieved satisfactory results. The purpose of this study was to assess the feasibility and efficacy of selective anatomical catheter ablation of left atrial ganglionated plexus (GP) as a therapeutic strategy for the patients of symptomatic VVS. A total of 70 patients with at least once recurrent syncopal episode of VVS with a positive head-up tilt test were enrolled. They were divided into GP ablation group and control group. Patients in GP ablation group received anatomical catheter ablation of left superior ganglionated plexus (LSGP) and right anterior ganglionated plexus (RAGP). Patients in the control group were guideline-directed conventional therapy. The primary endpoint was VVS recurrences. The secondary endpoint was the recurrence of syncope and prodrome events. There were no statistical differences in clinical characteristics between the ablation group (n=35) and the control group (n=35). Over a follow-up of 12 months, the ablation group had significantly lower syncope recurrence compared with the control group (5.7%vs. 25.7%, p=.02), and the ablation group had significantly lower syncope and prodrome recurrence compared with the control group (11.4%vs. 51.4%, p<.001). In GP ablation, 88.6% of the patients showed significant vagal response during LSGP ablation, and 88.6% of the patients showed significantly increased heart rate during RAGP ablation. For patients with recurrent VVS, selective anatomical catheter ablation of LSGP and RAGP is superior to conventional therapy in reducing syncope recurrence.

Recurrence of syncope after valve replacement in severe aortic stenosis

ObjectiveThe recurrence of syncope after valve intervention in severe aortic stenosis (SAS) and its impact on outcome are unknown. We hypothesised that syncope on exertion will disappear after intervention, whereas...

Syncope and Traffic Crash: A Population-Based Case-Crossover Analysis

BackgroundAmong individuals with recent syncope, recurrence of syncope while driving might incapacitate a driver and cause a motor vehicle crash. Current driving restrictions assume that some forms of syncope transiently increase crash risk. We evaluated whether syncope is associated with a transient increase in crash risk. MethodsWe performed a case-crossover analysis of linked administrative health and driving data from British Columbia, Canada (2010 to 2015). We included licensed drivers who visited an emergency department with "syncope and collapse" and who were involved as a driver in an eligible motor vehicle crash, both within the study interval. Using conditional logistic regression, we compared the rate of emergency visits for syncope in the 28 days before crash (the "pre-crash interval") with the rate of emergency visits for syncope in 3 self-matched 28-day control intervals (ending 6, 12, and 18 months before the crash). ResultsAmong eligible crash-involved drivers, 47 of 3026 pre-crash intervals and 112 of 9078 control intervals had emergency visits for syncope, indicating syncope was not significantly associated with subsequent crash (1.6% vs 1.2%; adjusted odds ratio [OR], 1.27; 95% confidence interval [CI], 0.90-1.79; P = 0.18). There was no significant association between syncope and crash in subgroups at higher risk for adverse outcomes after syncope (eg, age > 65 years, cardiovascular disease, cardiac syncope). ConclusionsIn the context of prevailing modifications of driving behaviour after syncope, an emergency department visit for syncope did not transiently increase the risk of subsequent traffic collision. Overall crash risks after syncope appear to be adequately addressed by current driving restrictions.

Cardioneuroablation for severe neurocardiogenic syncope

Introduction and objectivesCardioneuroablation (CNA), a technique based on radiofrequency ablation of cardiac vagal ganglia, was developed to treat recurrent vasovagal syncope (VVS) with a predominant cardioinhibitory component, as an alternative to pacemaker implantation. The aim of our study was to evaluate the safety and success rate of CNA guided by extracardiac vagal stimulation in patients with highly symptomatic cardioinhibitory VVS. MethodsProspective study of patients who underwent anatomically guided CNA at two cardiology centers. All patients had a history of recurrent syncope with a predominant cardioinhibitory component and refractory to conventional measures. Acute success was determined by the absence or significant reduction of cardiac parasympathetic response to extracardiac vagal stimulation. The primary endpoint was the recurrence of syncope during follow-up. ResultsIn total, 19 patients (13 males; mean age 37.8±12.9 years) were included. Ablation was acutely successful in all patients. One patient had a convulsive episode after the procedure, which was deemed unrelated to the ablation, requiring admission to intensive care but without sequelae. No other complications occurred. At a mean follow-up of 21.0±13.2 months (range 3–42 months), 17 patients remained free of syncope. The remaining two patients had recurrence of syncope and, despite undergoing a new ablation procedure, required pacemaker implantation during follow-up. ConclusionCardioneuroablation, confirmed by extracardiac vagal stimulation, appears to be an effective and safe treatment option for highly symptomatic patients with refractory VVS with a predominant cardioinhibitory component, providing a new potential approach as an alternative to pacemaker implantation.

Syncope with autonomic dysfunction assessed with the Thai-COMPASS 31 questionnaire

IntroductionAlteration of autonomic function is the main pathophysiology of most types of syncope, including syncope due to orthostatic hypotension and neurally mediated syncope or reflex syncope. The aim of this study was to investigate the difference in autonomic dysfunction assessed between each type of syncope and to evaluate the association between the severity of autonomic dysfunction and the recurrence of syncope. MethodologyThree hundred and six participants, including 195 syncope and 109 healthy control participants, were recruited to this retrospective cohort study. Autonomic function was initially assessed by the Thai version of the Composite Autonomic Symptom Score 31 (COMPASS 31), a self-administered questionnaire. ResultAccording to one hundred and ninety-five syncope participants, twenty-three participants had syncope due to orthostatic hypotension, 61 had reflex syncope, 79 had presyncope, and 32 had unclassified syncope. Participants in the syncope due to orthostatic hypotension and reflex syncope groups had significantly higher COMPASS 31 scores than the control and presyncope groups, of which the syncope due to orthostatic hypotension group had the highest score. The cutoff score of 32.9 for COMPASS 31 had a sensitivity of 50.0% and a specificity of 81.9% to predict the recurrence of syncope. ConclusionThe degree of autonomic dysfunction, which was assessed by COMPASS 31, could vary depending on the syncope type. The COMPASS 31, which is an easy-to-use self-administered questionnaire utilized for the assessment of autonomic symptoms and function, was a helpful tool for classifying some types of syncope and predicting the recurrence of syncope, which could lead to appropriate further management.

Therapeutic options for syncope: a meta-analysis of trials with and without placebo control

Abstract Funding Acknowledgements Type of funding sources: None. Background 8% of the population suffer recurrent episodes of syncope which can cause physical injury and psychological morbidity. The extent to which therapeutic options effectively reduce syncope recurrence beyond placebo remain unclear. Methods We performed a meta-analysis of randomised trials including pharmacological, cardiac pacing and physical interventions for syncope. We assessed the effect of these therapeutic interventions on clinical syncope recurrence. We stratified the trials by use of placebo control. Results There were 50 eligible trials: 22 pacing, 19 pharmacological and 9 of physical interventions including 3,975 patients. Trials assessing syncope recurrence with placebo control were neutral for Beta-Blockers (RR 1.11, 95% CI 0.85 to 1.45, p=0.36), Fludrocortisone, (RR 0.83, 95% CI: 0.63 to 1.11 p=0.83) and conventional dual-chamber pacing (RR 0.81, 95% CI 0.61 to 1.09 p=0.287). However, they were favourable for Selective Serotonin Reuptake Inhibitors [SSRIs] (RR 0.40, 95% CI 0.25 to 0.63 p&amp;lt;0.001), Midodrine (RR 0.70, 95% CI 0.53 to 0.94, p=0.016) and Closed-Loop-Stimulation (CLS) pacing (RR 0.21, 95% CI 0.12 to 0.34, p &amp;lt; 0.001). Non-placebo-controlled trials reported significant benefit for every category of therapy including conventional dual-chamber pacing, medicines (Beta-Blockers, Midodrine and Oral rehydration salts) and physical interventions including tilt-training. Three categories of therapy have been trialled with and without placebo control: the non-placebo-controlled studies showed significantly different results from their placebo-controlled counterparts (beta-blockers p=0.024, midodrine p=0.006, dual-chamber pacing p=0.017) (figure 2). Conclusion Under placebo-controlled conditions, CLS pacing reduces risk of syncope recurrence by ~75%, whereas conventional pacing does not. SSRIs and midodrine also show significant efficacy under placebo-controlled conditions. Without placebo control, trials consistently show artefactually larger benefits. Future non-placebo-controlled trials for syncope should not be conducted.

Head up tilt test response patterns in patients undergoing cardioneuroablation

Abstract Funding Acknowledgements Type of funding sources: None. Background Vasovagal syncope (VVS) is the most common cause of transient loss of consciousness. It severely affects quality of life and can often lead to severe trauma and fatal accidents. Effective treatment of some of these patients can be obtained with cardioneuroablation (CNA). Head-up tilt test (HUT) plays a major role during the evaluation of syncope patients and helps to differentiate syncope subtypes. Data on the HUT response patterns and its usefulness for the recommendation of CNA and the evaluation of the results is lacking. Purpose To assess HUT response patterns before and after CNA. Methods We included patients with repetitive episodes or considered clinically relevant episodes of vasovagal syncope in the previous 6 months and symptomatic patients with documentation of functional sinus bradycardia or functional AV node block. Before performing CNA, all patients underwent a comprehensive baseline evaluation to analyze sinus node and AV node function. CNA was considered in those patients in whom intrinsic sinus node or AV node disease has been excluded in the electrophysiological study (response to atropine was also assessed), had a VASIS type 2A, 2B or type 1 (mixed) response to the HUT and provided signed informed consent. CNA was performed under general anesthesia and ablation strategy was based on presumed anatomical localization of GP. Follow-up of these patients was performed in the outpatient clinic with scheduled visits at 1, 6 and 12 months including 24-hour Holter monitoring. A control HUT was performed at 3 months. Results We included 36 patients. 22 males (61.1%), mean age 51 (18-82 years). The average number of syncope events per year per patient prior to the procedure was 5 ±3. The mean HR on Holter Pre CNA was 65 ± 12 and 72 ± 9 post CNA. Of the HUT, 9 (25%) had mixed type response; 9 (25%) cardioinhibitory type 2A and 18 (50%) cardioinhibitory type 2B. The response in type 2B was sinus arrest in 12 (33.3%), AV block in 5 (13.9%) and both in 1 (2.8%) patient. During a mean of 9 ±4 months follow-up, only 3 patients had a syncope recurrence. At the three-month HUT we observed complete elimination of the cardioinhibitory component present prior to CNA in 34 (94.4%) patients. During the HUT, 18 (50%) had no syncope whereas the remaining 17 had HUT-induced syncope. In 16 (44.4%) of them due to vasodepressor mechanism and only 1 due to cardioinhibitory type 2A response (Figure 1). This patient also had a syncopal recurrence in the follow up. We did not perform the control HUT in 1 patient because of an early recurrence and the patient decided to undergo a pacemaker implantation. We had another recurrence at 11 months post CNA in a patient in whom the control tilt test was negative. The syncope-free survival curve can be seen in Figure 2. Conclusions CNA changes the response pattern of the HUT by eliminating the cardioinhibitory component and can be useful in the evaluation of the long-term CNA outcomes.

P453 RECURRENT SYNCOPAL EPISODES IN A YOUNG PATIENT: TO IMPLANT THE PM OR NOT TO IMPLANT THE PM, ALWAYS A DIFFICULT DECISION!

Abstract Introduction Syncope represents one of the main causes of access to the Emergency Department and outpatient visits, accounting for up to 13% of hospital admissions. Although usually benign, syncopal episodes are a source of considerable distress for the patient and family members, particularly when dealing with otherwise healthy young patients. We report the case of a young patient who presented with recurrent syncopal episodes with important psychological and professional implications. Case Report A 33–year–old man comes to our Syncope Unit with a long history of repeated syncopal episodes preceded by fleeting warning signs, sometimes with minor trauma, occurring during daily activities, in conjunction with minor injuries or post–voiding but never during exertion. The patient began to limit his activities for fear of syncope and was inhibited from driving work vehicles and performing tasks at height. The various cardiological examinations performed over the years were normal. The study of syncope evoked a syncope with a 13 sec pause on carotid sinus massage while the Head–up Tilt Test was negative. A Loop Recorder (ILR) was then implanted to correlate the syncopal episodes with any slowing or pathological pauses in the heart rhythm. At remote monitoring of the ILR, an asystole of about 16 seconds symptomatic for syncope was documented. In relation to the recurring syncopal episodes, the important professional limitations imposed on the patient, as well as at the explicit request of the patient himself, despite the lacking scientific evidences availables, we proceeded to implant a dual–chamber pacemaker with a frequency response algorithm. In the 4 years after the implant there were no syncopal recurrences and the patient resumed his normal daily and professional activities with a marked improvement also in his psychological setting. After 2.5 years, however, the ventricular lead broke and required its extraction and reimplantation. Conclusions The decision to implant the device was not easy, precisely in relation to the possible complications over the years, but this allowed the patient to resume a normal private and professional life. However, an accurate risk–benefit assessment is required, sharing the "weight" of the decision with the patient and his family.

PO-05-233 CARDIONEUROABLATION IN PATIENTS WITH A PRIOR PACEMAKER IMPLANT

Cardioneuroablation (CNA) is an alternative therapeutic method for patients with functional bradyarrhythmias who are otherwise candidates for permanent pacing. In a specific clinical scenario, CNA can also be a treatment option for patients with previously implanted pacemakers. We investigated whether CNA could substitute permanent pacing in selected patients with a pacemaker associated with complications, technical failures, or decreased quality of life. Among 198 patients who underwent CNA by radiofrequency energy between 2014 and 2022, there were 13 patients (7%) with a pacemaker in whom CNA was indicated as a "substitute" treatment. The reasons were as follows: lead failure (n = 6), low-grade infection in the device pocket (n = 1), infective endocarditis (n = 1), recurrent syncope even after pacemaker implantation (n = 1), and discomfort associated with the implanted device (n = 4). In 4 patients, the pacemaker was explanted shortly before CNA because of serious complications. Biatrial CNA was guided anatomically using a 3D mapping system and intracardiac echocardiography. Empirical sites of ganglionated plexi were targeted. The procedural endpoint was the unresponsiveness of sinus and AV nodes to extracardiac vagal nerve stimulation. Patients (n = 13, 77% male, age: 41 ± 12 years) had a pacemaker implanted 11 ± 7 years ago. They responded to atropine (2 mg IV) administration by accelerating the sinus rhythm by 55 ± 33%. CNA was technically successful and uncomplicated in all of them. During the follow-up of 40 ± 16 months (range 16 - 66 months), two patients (15%) had a recurrence of syncope. In both, the syncope was reproduced by tilt testing and classified as a pure vasodepressor event. In the remaining patients, the follow-up was uneventful. Elective explantation of the pacing system has so far been performed in 5 of 9 patients and is planned in 4 remaining patients after reaching a sufficient length of post-procedural follow-up. CNA is an effective and safe method, which is not only an alternative to the pacemaker implant but can also be used in patients with functional bradyarrhythmias, and previously implanted pacemakers who experience significant adverse events associated with the pacing system.

PO-03-072 CARDIONEUROABLATION AS AN ALTERNATIVE TREATMENT FOR PATIENTS WITH CAROTID SINUS SYNDROME - A MULTICENTER EXPERIENCE

Carotid sinus syndrome (CSS) is an uncommon condition caused by sudden vagal overactivity resulting in sinus arrest, AV block (AVB) and syncope commonly treated with pacemaker (PM). Cardioneuroablation (CNA) aims vagal denervation removing cardio inhibition by endocardial ablation Study outcomes of CNA controlled by extracardiac vagal stimulation (ECVS) and carotid sinus massage (CSM) in CSS. Prospective, controlled, clinical study including 11 patients with a clinical history of repetitive syncope caused by CSS, in 3 hospital centers in Brazil and 1 in Spain. Presenting positive carotid sinus massage, with pauses > 3 seconds, and positive response to atropine test, ruling out hypotensive component as cause of syncope. Bi-atrial CNA identifying AF-Nests (AFN), ablating the P point and the 4 main areas related to ganglionic plexuses (GP). Vagal denervation control by ECVS was used to define extension of the denervation, and in addition CSM was performed to confirm immediate success at the end of the ablation, defining the higher CNA effect. Primary endpoint: eliminate pauses and AVB caused by ECVS and CSM. Secondary end points: Time to syncope event after CNA, time to diagnose of cardio inhibition induced by CSM after CNA Mean age 55,9(±16,3), mean syncope episodes 7,7 (±6,9). Pre-CNA ECVS and CSM response: sinus pauses (5,7 ±1,4secs), transient AVB 4/11. Post-CNA, ECVS, CSM and Atropine responses were completely abolished in 100%. Obtained HR increase (59.1±11,1/80,3±5,1bpm). Follow-up 25,7(±17,1) months, no syncope recurrence. ECVS was successfully performed in 10/11, in 1 patient it was not possible to advance the catheter through any jugular vein, ECVS was not performed; 1 patient had positive CSM at 6 months FU, had PM implanted, without any spontaneous syncope events. No complications or proarrhythmic effect were registered. Bi atrial CNA AFN/GP based ablation guided by abolishment ECVS and CSM response was effective, feasible, and reproducible for eliminating syncope recurrence in all patients with CSS. Control of vagal denervation using ECVS defined the extent of denervation and confirmed immediate success. CNA may be considered as an option for CSS treatment.

PO-03-073 CARDIONEUROABLATION FOR THE MANAGEMENT OF PATIENTS WITH RECURRENT VASOVAGAL SYNCOPE AND SYMPTOMATIC BRADYARRHYTHMIAS: THE CNA-FWRD CROSS-OVER TRIAL AND PROSPECTIVE REGISTRY

Cardioneuroablation (CNA) has been introduced as a potential alternative treatment strategy in appropriately selected patients for prevention of recurrent cardioinhibitory vasovagal syncope (VVS) and functional atrioventricular block (AVB). The Cardioneuroablation for the Management of Patients with Recurrent Vasovagal Syncope and Symptomatic Bradyarrhythmias (CNA-FWRD) Registry is a multicenter prospective registry and Cross-Over Trial with the objective of examining acute and long-term outcomes of CNA in appropriately selected patients with recurrent VVS and AVB. The main study will be a prospective cross-over design with patients randomized to two groups receiving 6-month treatment interventions in alternate order: Medical therapy followed by CNA (Group 1) or CNA followed by Medical therapy (group 2). Patients declining the cross-over study will be eligible for inclusion in a parallel prospective registry. Details of inclusion and exclusion criteria are provided in Table 1. Functional AVB is defined as sudden change from physiologic atrioventricular conduction to transient second- or third-degree AVB resulting in symptomatic pauses longer than 2 seconds. All fragmented EGMs that demonstrated 3 or more deflectionsin the regions that are known to be consistent with probable localization of ganlionated plexus (GP) will be identified and tagged (Figure 1). In each VVS patient, the GPs will be targeted in the following order: the superior left atrial GP, the Marshall tract GP (MTGP), the inferior left atrial GP, the superior right atrial GP (RSGP), and finally the inferior right atrial GP. Additional right atrial ablation on the superior aspect on the interatrial septum will be performed for RSGP. In patients with AVB, the posteromedial left atrial GP, MTGP and RSGP will be ablated, respectively. The primary outcome is 12-month syncope recurrence post catheter ablation. Secondary outcomes include procedure-related complications, freedom from syncope at 12 months, freedom from AVB at 12 months, need for repeat GP ablation, quality of life at 12 months. Study enrollment began for (8) sites on June 20, 2022. So far, 59 patients have been enrolled into the registry. There remains lack of procedural standardization CNA as a treatment strategy and limited long-term data for key outcomes including recurrence of syncope, durable impact of disruption of the autonomic nervous system and long-term complications. CNA-FWRD has the potential to help fill this information gap.Tabled 1Inclusion and Exclusion Criteria for Study Cohort (PO-03-073)DiagnosisInclusion criteriaExclusion criteriaVVSAt least 3 vasovagal syncope episodes in the preceding 12 monthsPresence of arrhythmic conditions that can cause syncopeAge < 60 yearsPresence of evidence related to structural heart disease> 3s asystole on head-up tilt testingPrevious history of catheter ablation> 3s asystole on ambulatory ECG monitoringPresence of inheritable arrhythmic conditionsPositive response to atropine testOrthostatic hypotension on Head-up tilt table testUnresponsiveness to conventional treatment modalitiesPseudo-syncopePresence of proven indication for Pacemaker implantationAbnormal thyroid function levelsUsage of negative chronotropic drugsChronotropic incompetence at exercise stress testAVBAll AVB casesHistorySymptomatic bradycardiaUse of negative chronotropic or dromotropic drugsLaboratoryassessmentNormal thyroid function testsThyroid function abnormalitySuspicionof obstructive sleep apneaNegative polysomnogramPositive polysomnogramBaselineECGLeft bundle brunch blockExerciseStress TestChronotropic incompetenceOccurrence or worsening of AVB with exerciseEPSSupra-Hisian AVBIntra/infra-Hisian AVBParoxysmal AVBBaselineECGNormal PR interval or first degree AVBSecond or third degree AVBHolter RecordingPR prolongation before second or third degree AVB episodeConstant PR before second or third degree AVB episodeDecrease in sinus rate during or just prior to second or third degree AVB episodeIncrease in sinus rate during second or third degree AVB episodeResolution of AVB with an increase in sinus rateResolution of AVB with a constant sinus rateEPSBaseline H-V interval <55msecBaseline H-V interval ≥55 msecIntra/infra-Hisian AVB by atrial pacing at rates of 150 bpm or lessPersistent AVBBaselineECGSecond or third degree AVBAtropine responseComplete resolution of atrioventricular conduction or conversion to first degree AVB with atropine infusionAVB unresponsive to atropine testExercise stress testComplete resolution of AVB or conversion to first degree AVB with exercise testAVB unresponsive to exercise stress testEPSBaseline H-V interval <55msecBaseline H-V interval ≥55 msecIntra/infra-Hisian AVB by atrial pacing at rates of 150 bpm or less Open table in a new tab

The Seventh Prevention of Syncope Trial (POST VII)—A randomized clinical trial of atomoxetine for the prevention of vasovagal syncope: Rationale and study design

Vasovagal syncope (VVS) is common, recurs, and is associated with markedly reduced quality of life, anxiety, and frequent injuries. The few pharmacological therapies for VVS proven to have a moderate benefit in reducing recurrences are limited to patients without coexisting conditions such as hypertension or heart failure. Although there is some data to suggest Atomoxetine, a norepinephrine reuptake transport inhibitor (NET), may be a promising treatment option, an adequately powered randomized placebo-controlled trial is needed. POST VII is a multicenter, randomized, double-blind, placebo-controlled, crossover study that will randomize 180 patients with VVS and at least 2 syncopal spells in the preceding year to a target daily dose of atomoxetine 80 mg daily or to a matching placebo, with an observation period of 6 months in each phase and with a 1-week washout period between phases. The primary end point will be the proportion of patients with at least one syncope recurrence in each arm analyzed with an intention-to-treat approach. The secondary end points include total syncope burden, quality of life, cost, and cost-effectiveness. Assuming a 33% relative risk reduction in syncope recurrence with atomoxetine, and a dropout rate of 16%, the enrollment of 180 patients will give an 85% power of reaching a positive conclusion about atomoxetine, with P=.05. This will be the first adequately powered trial to determine whether atomoxetine is effective in preventing VVS. If proven effective, atomoxetine might become the first-line pharmacological treatment for recurrent VVS.

Clinical controversy: methodology and indications of cardioneuroablation for reflex syncope.

Observational studies and a recent randomized controlled trial have provided some evidence that cardioneuroablation (CNA) may prevent syncope recurrence in patients affected by cardioinhibitory reflex syncope during the first 2 years following the procedure. Nevertheless, many issues concerning clinical indications, methodology, and long-term results remain unresolved. These issues constitute the background of this manuscript in which pioneers in CNA and experts in syncope debated critical aspects aimed at finding agreement or, if not possible, that highlighting the controversies could be addressed in future studies.