Cardioinhibitory Vasovagal Syncope Research Articles

Cardioneuroablation guided by extracardiac vagal stimulation for cardioinhibitory vasovagal syncope

Abstract Introduction Vasovagal Syncope (VVS) is often linked to abnormal autonomic reflexes, with hypervagotonia identified as a key mechanism, especially in cases with pronounced cardioinhibition. Cardioneuroablation (CNA), which involves radiofrequency ablation of cardiac vagal ganglia, targets parasympathetic hyperactivity, offering a promising treatment for recurrent VVS. This study evaluates the effectiveness and safety of anatomically guided CNA, which may provide an alternative treatment option to pacemaker implantation for younger patients with severe cardioinhibitory VVS. Methods Consecutive patients between January 2019 and October 2023 who underwent CNA at two cardiology centers were enrolled. All patients had a history of recurrent syncope, predominantly cardioinhibitory and unresponsive to conventional treatments. Patients showed no signs of conduction system disease, evidenced by normal rate responses in treadmill stress tests and 24-hour Holter monitoring. Electroanatomic mapping of the left atrium and pulmonary veins was performed. Extracardiac vagal stimulation (ECVS) through the right internal jugular vein, with or without atrial pacing, was utilized to assess baseline responses of the sinus and atrioventricular (AV) nodes. The ablation strategy was tailored based on rhythm disturbances triggered by ECVS, using sequential and anatomically guided ablation of ganglionated parasympathetic plexuses. Radiofrequency ablation, conducted with an irrigated catheter, was guided by the ablation index. Acute success was defined as the absence or significant reduction of cardiac parasympathetic response to ECVS, indicated by the elimination of asystole, severe bradycardia, or AV block. The primary endpoint was syncope recurrence during follow-up. Results The study included 25 patients (16 males; mean age 36 ± 12 years). All had documented cardioinhibition, identified through ECG monitoring (N=12), implantable loop recorders (N=5), or head-up tilt tests (N=8). The average number of syncopal episodes per patient in the year preceding ablation was 2.7, ranging from 1 to 10. Ablation was acutely successful in all cases. Post-ablation, there were no immediate complications related to the procedure, except for one convulsion deemed unrelated. Over a mean follow-up of 17 ± 14 months, 23 patients remained syncope-free. Two patients experienced syncope recurrence; despite undergoing a repeat ablation, they eventually required pacemaker implantation. Conclusion The results of this study suggest that CNA guided by ECVS, may offer a promising treatment for patients with refractory cardioinhibitory VVS. While the procedure showed a high rate of acute success and a notable reduction in syncope recurrence, further research is warranted to fully establish its role as an alternative to pacemaker implantation.

Cardioneuroablation for vasovagal syncope. Results from an EHRA Survey

Abstract Background Cardioneuroablation (CNA) is a recently introduced catheter-based therapy for vasovagal syncope (VVS), involving the modulation of the cardiac autonomic nervous system. Over the past decade, the body of evidence supporting CNA has consistently grown, sparking increased interest, and leading to broader adoption of this novel therapy for VVS treatment. However, several knowledge gaps persist, particularly concerning clinical indications, methodology, and long-term outcomes. Purpose The aim of this survey is to provide a comprehensive overview of the daily utilization of CNA in Europe. Methods and Results Among 204 participants, half reported that they are already performing CNA in their centres. The survey indicated CNA as an emerging therapy, with most centres initiating this treatment within the last two years. A significant majority of those who responded (71%) adopted a systematic approach by targeting ganglionated plexuses (GPs) in both the right atrium (RA) and left atrium (LA) as their first-line approach. The second most common approach (16%) involved performing ablation LA GPs only in the cases where there is no response following RA ablation. Figure 1 shows the GPs usually targeted for ablation. The most frequent procedural endpoint was the increase in the heart rate. Ninety percent of respondents relied on an anatomical approach for GP localization, while 59% also guided the procedure using electrogram analysis. Less frequently used approaches included pre-procedural imaging (20%), high-frequency stimulation (17%), and spectral analysis (10%). Only 11% of physicians discharged patients who underwent CNA without anticoagulation or antiplatelet therapy. In most cases (58%), respondents discharged their patients with anticoagulation, while 28% on single antiplatelet therapy. Overall, CNA is considered an effective procedure (80% of responders rating its effectiveness at or above 70%) and a safe procedure (with an estimated 1% rate of procedure-related complications, with symptomatic sinus tachycardia being the most frequently reported). Conclusions This survey confirmed high expectations for the future of this therapy, as most responders anticipate that CNA will be indicated as a first-line therapy for patients with recurrent cardioinhibitory VVS. Future efforts are necessary to standardize the procedural flow and peri-procedural patient management.

Cardioneuroablation for Cardioinhibitory Vasovagal Syncope: Rationale, Approaches, and Its Role in Long-Term Management.

Cardioneuroablation (CNA) has emerged as a potential alternative to pacemaker therapy in well-selected cases with vasovagal syncope (VVS). In recent years, the number of CNA procedures performed by electrophysiologists has considerably risen. However, some important questions, including proper patient selection and long-term results, remain unanswered. The present article aims to critically review and interpret latest scientific evidence for clinical indications and how to approach long-term management. CNA is a new approach that has been supported mainly by retrospective or observational data for its use in syncope. Overall, in mixed population studies treated with CNA, 83.3 to 100% have been reported to be free of syncope over follow-up periods of 6 to 52.1 months. For studies including patients who underwent CNA with pure VVS, 73.2 to 100% have been reported to be syncope-free over follow-up periods of 4 to 45.1 months. One large meta-analysis showed 91.9% freedom from syncope after CAN. To date, only one randomized controlled trial with small case number has been performed of CNA compared to non-pharmacological treatment in VVS. In this study of 48 patients with an average of 10 ± 9 spontaneous syncopal episodes prior to study enrollment and 3 ± 2 episodes in the year prior to CNA. After CNA, 92% were free of syncope compared with 46% treated with optimal non-pharmacological treatment to prevent new syncope episodes (P = 0.0004). To date, most studies have included younger patients (< 60 years of age). There are only limited data in patients older than 60, and some studies suggest less of an effect in relatively older patients. Cardioneuroablation can be performed to decrease syncope recurrence in adult patients aged < 60 years, with severe or recurrent cardioinhibitory syncope without prodromal symptoms, after proven failure of conventional therapies. Due to a paucity of data supporting efficacy in older individuals or for vasodepressor components, CNA in adult patients aged > 60 years or in the presence of a dominant vasodepressor should be considered investigational in severely symptomatic patients after proven failure of pharmacological and non-pharmacological therapies.

Cardioneuroablation for the management of patients with recurrent vasovagal syncope and symptomatic bradyarrhythmias: the CNA-FWRD Registry.

Cardioneuroablation has been emerging as a potential treatment alternative in appropriately selected patients with cardioinhibitory vasovagal syncope (VVS) and functional AV block (AVB). However the majority of available evidence has been derived from retrospective cohort studies performed by experienced operators. The Cardioneuroablation for the Management of Patients with Recurrent Vasovagal Syncope and Symptomatic Bradyarrhythmias (CNA-FWRD) Registry is a multicenter prospective registry with cross-over design evaluating acute and long-term outcomes of VVS and AVB patients treated by conservative therapy and CNA. The study is a prospective observational registry with cross-over design for analysis of outcomes between a control group (i.e., behavioral and medical therapy only) and intervention group (Cardioneuroablation). Primary and secondary outcomes will only be assessed after enrollment in the registry. The follow-up period will be 3years after enrollment. There remains a lack of prospective multicentered data for long-term outcomes comparing conservative therapy to radiofrequency CNA procedures particularly for key outcomes including recurrence of syncope, AV block, durable impact of disruption of the autonomic nervous system, and long-term complications after CNA. The CNA-FWRD registry has the potential to help fill this information gap.

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.

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

PO-04-138 FINDING THE SIGNAL TO BURN: OPTIMIZED FRACTIONATION MAPPING FOR IDENTIFYING GANGLION PLEXUSES DURING CARDIONEURAL ABLATION

Cardioneural ablation (CNA) is a novel catheter-based technique to treat patients with clinically significant bradyarrhythmia due to cardioinhibitory response in vasovagal syncope (VVS). Three common techniques used to locate areas of ganglion plexuses (GPs) prior to CNA include high frequency stimulation, fractionation mapping (FM), and empiric ablation based on presumed anatomical location of GPs. Optimal intra-procedural diagnostic parameters of fractionation mapping which predict GP location remain ill-defined. To determine the parameters of FM which most precisely locate successful GP ablation sites. Consecutive patients with cardioinhibitory VVS underwent CNA at a single center between March and April 2021. GP sites were targeted with radiofrequency (RF) ablation based on areas demonstrating fractionation, response to high-frequency stimulation, and overall anatomic location. GP sites exhibiting abrupt sinus rate increases with RF delivery were tagged as successful. Following the case, multiple FMs were retrospectively analyzed at 5 sensitivities (range 0.01-0.10 mV), each utilizing 4 combinations of EGMs with width (range 5-10 ms) and refractory interval (range 6-25 ms). Each FM was reviewed and deemed predictive if it identified all successful RF sites without incorrectly annotating sites lacking an RF response. We identified 40 unique FMs for analysis. Setting EGM width to 5 ms and refractory interval to 6 ms predicted all successful ablation sites (positive predictive value [PPV] 100%, p < 0.01). Broadening annotation parameters diminished predictability in a stepwise fashion (5 ms/15 ms, 10 ms/15 ms, 10 ms/25 ms yielded PPV 90%, 70%, 40%, respectively, p < 0.01). Sensitivity settings did not correlate with map utility (PPV 75%, p = 0.98). The optimal fractionation parameters which identified successful ablation sites were those with the narrowest electrogram width and shortest refractory interval. Analysis in a larger cohort is needed to confirm these findings.

Cardioneuroablation for Reflex Syncope: Efficacy and Effects on Autonomic Cardiac Regulation-AProspective Randomized Trial.

Treatment of cardioinhibitory vasovagal syncope (VVS) is difficult. Recently, cardioneuroablation (CNA) has emerged as a new therapeutic option. This study sought to assess the effects of CNA on syncope recurrences in patients with VVS. This study was a prospective, open, randomized, controlled, investigator-initiated trial comparing CNA versus optimal nonpharmacologic therapy in patients with cardioinhibitory VVS. Patients were included if they had documented symptomatic cardioinhibitory or mixed VVS and positive atropine test. CNA was performed using radiofrequency ablation of the ganglionated plexi from the left and right atria. Follow-up lasted 2 years. Primary endpoint was time to first syncope recurrence. Secondary endpoints included changes in sinus rhythm and heart ratevariability measured in Holter electrocardiography at baseline and 3, 12, and 24months after CNA, as well as changesin quality of life at baseline and after completion of follow-up. A total of 48 patients (17 male, mean age 38 ± 10 years, 24 in CNA group, 24 in control group) entered thestudy. The primary endpoint occurred in 2 patients (8%) from the CNA group versus 13 control patients (54%) (P=0.0004). After CNA the mean sinus rhythm at 24-hour Holter electrocardiography was significantly faster and heart rate variability parameters significantly changed toward parasympathetic withdrawal compared with baseline values. Quality of life significantly improved in the CNA group (30 ± 10 points vs 10 ± 7 points; P = 0.0001), whereas it remained stable in control patients (31 ± 10 points vs 30 ± 10 points; P = 0.5501). This is the first randomized study documenting efficacy of CNA in patients with cardioinhibitory VVS. Larger studies are needed to confirm these findings. (Cardioneuroablation for Reflex Syncope [ROMAN]; NCT03903744).

Permanent pacing versus cardioneuroablation for cardioinhibitory vasovagal syncope.

We compared the efficacy and safety of cardioneuroablation (CNA) vs. permanent pacing (PM) for recurrent cardioinhibitory vasovagal syncope (CI-VVS). One hundred sixty-two patients (CNA = 61, PM = 101), age 36 + 11years) with syncope frequency of 6.7 ± 3.9/year were included in this multicenter study. All patients with CNA were provided by a single center, while patients with PM were provided by 4 other centers. In the CNA arm, an electroanatomic mapping guided approach was used to detect and ablate ganglionated plexus sites. Dual chamber rate drop response (RDR) or close loop stimulation (CLS) transvenous and leadless pacemakers were implanted using standard technique. The primary endpoint was freedom from syncope. Of 101 patients in the PM group, 39 received dual-chamber pacemaker implants with the CLS algorithm, 38 received dual-chamber pacemakers with the RDR algorithm, and 24 received a leadless pacemaker. At 1-year follow-up, 97% and 89% in the CNA and PM group met the primary endpoint (adjusted HR = 0.27, 95% CI 0.06-1.24, p = 0.09). No significant differences in adverse events were noted between groups. There was no significant association between age (HR:1.01, 95% CI 0.96-1.06, p = 0.655), sex (HR:1.15, 95% CI 0.38-3.51, p = 0.809), and syncope frequency in the past year (HR:1.10, 95% CI 0.97-1.25, p = 0.122) and the primary outcome in univariable analyses. After adjustment for patient characteristics, the medium-term syncope recurrence risk of CI-VVS patients who underwent CNA was similar to that of a population of patients undergoing pacemaker implantation with a similar safety profile.

SGLT2-inhibitors reduce the cardiac autonomic neuropathy dysfunction and vaso-vagal syncope recurrence in patients with type 2 diabetes mellitus: the SCAN study

BackgroundIn patients with type 2 diabetes mellitus (T2DM) the vaso-vagal syncope (VVS) recurrence could be due to the alteration of autonomic system function, evaluated by heart rate variability (HRV), and by 123I-metaiodobenzylguanidine (123I-mIBG) myocardial scintigraphy indexes: Heart to Mediastinum ratio (H/Mlate), and Washout rate (WR). The SGLT2-I could modulate/reduce autonomic dysfunction in T2DM patients with VVS. This effect could reduce the VVS recurrence in T2DM patients. MethodsIn a prospective multicenter study, after propensity score matching, we studied a population of 324 T2DM patients with VVS, divided into 161 SGLT2-I-users vs. 163 Non-SGLT2-I users. In these patients as SGLT2-I-users vs. Non-SGLT2-I users, we investigated the HRV and 123I-MIBG modifications and VVS recurrence at 12 months of follow-up. ResultsAt follow-up end, the SGLT2-I-users vs. Non-SGLT2-I users had best glucose homeostasis and lower values of inflammatory markers, and resting heart rate (p < 0.05). The SGLT2-I-users vs. Non-SGLT2-I users evidenced the lowest low frequency/high frequency ratio (LF/HFr), a significant difference for all the indexes of autonomic dysfunction via ECG Holter analysis, and higher values of H/Mlate (p < 0.05). Finally, comparing SGLT2-I-users vs. Non-SGLT2-I users, we found a higher rate of VVS recurrence events, specifically of the vasodepressor VVS recurrence at 1-year follow-up (p < 0.05). We did not find a significant difference of mixed and cardio-inhibitory VVS recurrence events at 1 year of follow-up in the study cohorts (p > 0.05). At the Cox regression analysis H/Mlate (0.710, [0.481–0.985]), and SGLT2-I therapy (0.550, [0.324–0.934]) predicted all causes of syncope recurrence at 1 year of follow-up. ConclusionsNon-SGLT2-I users vs. SGLT2-I-users had alterations of the autonomic nervous system, with a higher rate of VVS recurrence at 1 year of follow-up. The indexes of cardiac denervation predicted the VVS recurrence, while the SGLT2-I reduced the risk of VVS recurrence.Clinical trial registration number: NCT03717207.

Cardiac deceleration capacity as an indicator for cardioneuroablation in patients with refractory vasovagal syncope.

Cardioneuroablation is an emerging therapy for refractory vasovagal syncope (VVS), but the standard enrollment criterion is undetermined. Mainstream studies empirically enroll patients with cardioinhibitory and mixed types of VVS on the basis of the head-up tilt (HUT). However, a variety of studies have shown that the results of HUT exhibit unpleasant reproducibility. We aimed to investigate the prognostic value of baseline deceleration capacity in patients with refractory VVS after cardioneuroablation. This study enrolled 123 patients (mean age 42.2±17.7 years; 54 males [43.9%]) with the diagnosis of VVS, of whom 16 patients had a negative result of HUT (13.0%), 8 (6.5%) had vasodepressive VVS, 32 (26.0%) cardioinhibitory VVS, and 67 (54.5%) mixed VVS. All patients underwent cardioneuroablation that was performed in the left atrium. After a mean follow-up of 4.0±1.1 years, 33 patients experienced syncope/presyncope events (26.8%). Patients with recurrent syncope/presyncope have a lower baseline deceleration capacity level than do those without (8.9±3.2 ms vs 11.3±3.7 ms; P < .001). Each 1-ms increase in deceleration capacity had a 34% (95% confidence interval [CI] 12%-50%) reduced risk of syncope/presyncope recurrence after cardioneuroablation. Nighttime deceleration capacity had the highest discrimination value (area under the curve 0.757; 95% confidence interval 0.657-0.858). At a high-risk threshold of 51% (nighttime deceleration capacity at a cutoff of 9.9 ms), the nighttime deceleration capacity enrollment strategy additionally benefited 18 per 100 patients after cardioneuroablation without syncope/presyncope recurrence as compared with the HUT strategy in decision curve analyses. Baseline nighttime deceleration capacity ≥ 10 ms may act as an indication for cardioneuroablation in patients with refractory VVS.

Cardioneuroablation for Treatment of Atrioventricular Block.

[Figure: see text].

B-PO01-027 PERMANENT PACING VERSUS CARDIONEUROABLATION FOR CARDIOINHIBITORY VASOVAGAL SYNCOPE

Permanent cardiac pacing (PM) can reduce syncopal events in patients with refractory cardioinhibitory (CI) vasovagal syncope (VVS). Cardioneuroablation (CNA) has been shown to be effective in reducing syncopal recurrences in patients with CI-VVS. To compare the safety and efficacy of CNA with PM in patients with recurrent CI-VVS. We conducted a 5-center, retrospective study of all patients who underwent CNA or received PM for recurrent, severe, CI-VVS. Clinical diagnosis of CI-VVS was supported by cardiac monitoring or positive cardioinhibitory response to head-up tilt testing. All patients had disabling symptoms with traumatic syncope despite conservative therapies. The primary efficacy endpoint was freedom from syncope during follow up. Any procedure-related adverse events (AE) were also assessed. 162 patients (CNA [n=61], PM [n=101]) with age 36+11 years (64 % female) and syncope frequency of 6.7±3.9/year were included. In patients undergoing CNA, age (35 + 12 vs 36 + 11, p =0.581) and pre-procedure syncope frequency [median 5 (IQR 4-8) vs median 6 (IQR (4-10), p = 0.52) were similar, and proportion of women lesser compared to the PM group (40.9% vs 77.2%, p <0.001). At 1-year, 96.7% (59/61) and 89.1% (90/101) met primary efficacy endpoint in the CNA and PM groups (unadjusted HR=0.30, 95% CI 0.07 - 1.34, p=0.119, p=NS, adjusted HR=0.27, 95% CI 0.06 - 1.24, p=0.09) (Figure 1). Major and minor AE occurred in 5/61 in the CNA and 11/101 in the cardiac pacing groups (p=0.79). In patients with CI-VVS, CNA demonstrated equivalent efficacy in reducing syncopal events when compared to cardiac pacing, with a similar safety profile.

Effectiveness of Closed Loop Stimulation pacing in patients with cardio-inhibitory vasovagal reflex syncope is questionable.

Effectiveness of Closed Loop Stimulation pacing in patients with cardio-inhibitory vasovagal reflex syncope is questionable.

Causes of syncopal recurrences in patients treated with permanent pacing for bradyarrhythmic syncope: Findings from the SYNCOPACED registry

Few studies have examined the causes of syncope/collapse recurrences in patients with a previously implanted pacemaker for bradyarrhythmic syncope. The purpose of this study was to assess the causes of syncope/collapse recurrences after pacemaker implantation for bradyarrhythmic syncope in a large patient population. The SYNCOpal recurrences in patients treated with permanent PACing for bradyarrhythmic syncope (SYNCOPACED) registry was a prospective multicenter observational registry enrolling 1364 consecutive patients undergoing pacemaker implantation for bradyarrhythmic syncope. During follow-up, the time to the first syncope/collapse recurrence was recorded. Patients with syncope/collapse recurrences underwent a predefined diagnostic workup aimed at establishing the mechanism of syncope/collapse. During a median follow-up of 50 months, 213 patients (15.6%) reported at least 1 syncope/collapse recurrence. The risk of syncope/collapse recurrence was highest in patients who underwent implantation for cardioinhibitory vasovagal syncope (26.4%), followed by unexplained syncope and chronic bifascicular block (21.5%), cardioinhibitory carotid sinus syndrome (17.2%), atrial fibrillation needing pacing (15.5%), atrioventricular block (13.6%), and sinus node disease (12.5%) (P = .017). The most frequent cause of syncope/collapse recurrence was reflex syncope (27.7%), followed by orthostatic hypotension (26.3%), pacemaker or lead malfunction (5.6%), structural cardiac disease (5.2%), and atrial and ventricular tachyarrhythmias (4.7% and 3.8%, respectively). In 26.8% of cases, the mechanism of syncope/collapse remained unexplained. In patients receiving a pacemaker for bradyarrhythmic syncope, reflex syncope and orthostatic hypotension are the most frequent mechanisms of syncope/collapse recurrence after implantation. Pacing system malfunction, structural cardiac diseases, and tachyarrhythmias are rare mechanisms. The mechanism remains unexplained in >25% of patients.

Pacing Therapies for Vasovagal Syncope.

Vasovagal Syncope (VVS) is mediated by a cardiac autonomic reflex with resultant bradycardia and hypotension, precipitating syncope. While benign and mostly well controlled, recurrent VVS can be debilitating and warrants intervention. Non-pharmacological management of VVS have had variable success. In patients with recurrent cardioinhibitory VVS, permanent pacing can be effective. The utility of pacing to preempt the syncopal depends on the prominent temporal role of bradycardia during the vasovagal reflex. Current guidelines recommend pacing as a therapy to consider in older patients with recurrent VVS. Although younger patients can benefit, one should be cautious given the long-term risk of complications. Available data appears to favor a dual chamber pacemaker with closed loop stimulation algorithm to prevent recurrent cardioinhibitory VVS. Several aspects, including mechanistic understanding of VVS and appropriate patient selection, remain unclear, and require further study.

Safety and efficacy of leadless pacemaker for cardioinhibitory vasovagal syncope

Single-chamber leadless pacemakers (LPs) have been shown to be an effective alternative to conventional transvenous pacemakers (CTPs), but their benefit in the context of cardioinhibitory vasovagal syncope (CI-VVS) is unknown. The purpose of this study was to evaluate the safety and efficacy of LP compared with dual-chamber CTP for CI-VVS. We conducted a multicenter, retrospective study comparing patients who received LP or dual-chamber CTP for drug-refractory CI-VVS. CI-VVS was diagnosed clinically and supported by cardiac monitoring and head-up tilt table testing. The primary efficacy endpoint was freedom from syncope during follow-up. Secondary endpoints included device efficacy and safety estimated by device-related major and minor adverse events (AEs). Seventy-two patients (24 LP, 48 CTP; age 32 ± 5.5 years; 90% female; syncope frequency 7.6 ± 3.4 per year) were included. At 1 year, 91% of patients (22/24) in the LP group and 94% of patients (43/48) in the CTP group met the primary efficacy endpoint (P = .7). Device efficacy endpoint was met in 92% of the LP group and 98% of the CTP group (P = .2). Early major AEs occurred in 2 of 24 in the LP group and 3 of 48 in the CTP group (P = .4). Late major AEs occurred in 0 of 24 in the LP group and 2 of 48 in the CTP group (P = 1). In patients with CI-VVS, single-chamber LP demonstrated equivalent efficacy in reducing syncopal events compared to dual-chamber CTP, with a similar safety profile.

Pacing for Patients Suffering From Cardioinhibitory Vasovagal Syncope Using the Closed-Loop System.

One in three vasovagal syncope (VVS) patients has syncopal recurrence after diagnosis, despite the standard recommendations for the avoidance of a recurrence, and one in five patients has more than one syncopal recurrence in the medium term. Given the high prevalence of VVS, there is a large population that continues to need effective treatment. There are numerous studies that use the implantable loop recorder (ILR) to document a cardioinhibitory response during VVS, with one study, ISSUE-3, demonstrating the efficacy of pacing using the rate-drop-response algorithm to trigger pacing and prevent syncopal recurrence in this population. There are more uncertainties in the studies that have used head-up tilt test (HUT) to select the population for pacing. We have recently performed the SPAIN randomized, controlled clinical trial using HUT to select the patients for pacing. The conclusion of the study was that, with the closed-loop system to introduce pacing, there was a significant reduction in the burden of syncope and a seven-fold increase in the time to first recurrence of syncope, which was greater than in the ISSUE-3 study. Since the completion of the SPAIN trial and its inclusion in the European guidelines, in our daily clinical practice, the use of this therapy is still recommended with caution in the context of the available literature, but it has increased our confidence in so doing. One in five patients with VVS needs treatment because of a high syncopal load. If an ILR is used to select the patients for pacing, the rate-drop-response algorithm can be recommended. In patients who have asystole on HUT, pacing with the closed-loop system has higher success and must now be considered as a tenable option for VVS patients.

Myoclonus and Recurrent Cardioinhibitory Vasovagal Syncope after Abdominal Surgery in a Critical Care Setting

Myoclonus and Recurrent Cardioinhibitory Vasovagal Syncope after Abdominal Surgery in a Critical Care Setting

A systematic review on recurrent cardioinhibitory vasovagal syncope: Does pacing therapy break the fall?

Vasovagal reflex is the most common cause of syncope. Pacemaker with rate drop response (RDR) or closed-loop stimulation (CLS) anti-syncope algorithms have been studied in recurrent vasovagal syncope (VVS), with conflicting results. We aim to investigate the role of pacemaker therapy and anti-syncope pacing mode in cardioinhibitory recurrent VVS. MEDLINE, Cochrane Library and registered clinical trials were searched for single or double-blind randomized controlled trials on pacing as a treatment for recurrent VVS. Five studies were eligible, overall enrolling 228 patients. After pooling data from all trials, pacemaker therapy showed a 63% reduction in syncope recurrence compared to control [Risk Ratio (RR): 0.37; 95% CI: 0.14-0.98; I2 =67%)]. Subgroup analyses suggested that the effect was greater in single-blind studies (RR: 0.07; 95% CI: 0.01-0.52, I2 =0%). When comparing pacing algorithms, the results from RDR versus no pacing trials (n=2) did not show a significant reduction in syncope recurrence (RR: 0.73; 95% CI: 0.25-2.16, I2 60=75%). In contrast, the data from the CLS versus standard pacing trials (n=3) evidenced a statistically meaningful reduction in syncopal burden (RR: 0.18; 95% CI: 0.07-0.47, I2 =0%). It is unclear whether pacemaker therapy reduces syncopal burden in cardioinhibitory recurrent VVS. However, our results suggest effectiveness of CLS pacing mode.