Syncope Burden Research Articles

Procedural heart rate variability and its effect on short-term symptoms after cardioneuromodulation procedure

Abstract Background Syncope is a miscellaneous clinical condition that affects a large portion of the population every year all over the world and responsible for a considerable amount of hospital and particularly emergency department admissions (1) The use of a right-sided approach in catheter ablation of ganglion plexi (GP) has been applied to reduce syncope episodes caused by vasovagal syncope (VVS) and decrease the overall burden of syncope (2). Purpose Our aim is to show that right-sided GP ablation which is known as cardioneuromodulation (CNM) is a new and promising way to cease recurrent syncope episodes and assess its effects on heart rate (HR), P-P intervals, ventricular depolarisation/repolarization parameters (QRS,QTc,Tpe durations, QTc/Tpe ratio), recurrence of syncope episodes, and patients symptoms such as fatigue, dizziness, etc. We also aimed to identify changes between pre and post procedural heart rates and its effects on short-term symptoms during follow-up. Methods A group of 55 patients with positive tilt table response or recurrent vasovagal syncope with pauses >2 sec in holter monitoring was enrolled this study. During the EP study, GPs determined both anatomically and by EP stimulation then autonomic denervation was performed focused by radiofrequency ablation. All patients followed-up for 12 months. Results Right-sided ablation was performed during the procedure and HR increased significantly in all patients after the procedure compared to before. Syncope episodes of the patients decreased significantly after the procedure. The patients who did not complain of syncope at the first, second and third appointment, respectively, 76.4% (n:42), 90.9% (n:50) and 92.7% (n:51). Patients had complaints at most within the first 4 months after the procedure (Table-1). At the first appointment, 4 (7.3%) patients had syncope and 9 (16,4%) patients had sinus tachycardia. Patient group with heart rate variability varying more or less than 20% during the procedure were examined, 81% of those with HR variability <20% did not have any symptoms, while 64.7% of the group with HR variability above 20% did not have any symptoms at first appointment (p:0,461) (Table.2). Tachycardia was seen in 23.5% of those with HR variability >20%, while it was determined as 9.5% in those with a HR variability <20 % Although these comparisons do not show a statistically significant difference due to the number of few patients, it is clinically significant. The same relationship was not observed between HR variability and symptoms in the second and third appointments. Conclusion Cardioneuromodulation is a remarkable treatment modality and it should be taken into consideration that more symptoms may develop in the early post-procedural period in the group who has post-procedure heart rate variability over 20%, and a cut-off should be determined for the target heart rate during the procedure.Table-1Table-2

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.

Trends and Immediate Outcomes of Syncope During Pregnancy: A Narrative Review.

Pregnancy-related syncope presents special difficulties due to the rapid physiological changes that occur throughout gestation. This narrative review provides a thorough summary of the patterns and pregnancy outcomes secondary to syncope during pregnancy. There is an increase in syncope burden during pregnancy, and hence it is critical that medical professionals understand the significance of syncope during pregnancy. Syncope can have a negative impact on the health of the mother as well as the fetus. Therefore, this review summarizes data from studies on syncope in pregnancy. It includes observational studies, case reports, and review articles. Early detection and proper management are very important because pregnant women who experience cardiac syncope are at risk of unfavorable neonatal and maternal outcomes. The review reveals diverse trends in syncope incidence during pregnancy, emphasizing the need for a nuanced understanding of temporal variations. Risks of injury, uteroplacental insufficiency, psychological effects, interruptions in prenatal treatment, possible aggravation of pre-existing diseases, and lifestyle changes are examples of immediate maternal repercussions. Pregnancy-related syncope is a complex condition that affects the health of the mother and the fetus. The study stresses the need for careful clinical treatment due to the rapid results and the diversity in incidence patterns. The unique component of a possible relationship to the brain health of offspring justifies further investigation in this area.

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.

PO-03-036 CARDIONEUROABLATION FOR VAGALLY-MEDIATED BRADYARRHYTHMIA: A SINGLE-CENTER EXPERIENCE

Cardioneuroablation (CNA) is a novel catheter-ablation technique for the treatment of vagally-mediated bradyarrhythmia, which aims to blunt the cardioinhibitory reflex by targeting parasympathetic ganglionated plexi (GPs). Early-phase studies have shown promising results, but clinical evidence remains limited. The aim of our study was to investigate the clinical impact of CNA on our cohort of patients with vaso-vagal syncope (VVS), symptomatic functional atrioventricular block (AVB), and sinus node dysfunction (SND). Baseline and procedural characteristics, procedure-related complications, and clinical outcomes were collected in patients who underwent CNA from December 2018 to October 2022. For GPs localization, our procedural workflow combined 3D-anatomical mapping of both atria with high-amplitude fractionated bipolar electrograms (figure). Statistical analysis was performed using Wilcoxon's -test. A total of 16 patients were included. Patients were young (42±16 years) and without structural heart disease (LVEF 58±4 ml). Ablation indication was mainly VVS (56%), followed by AVB (25%) and SND (19%). Syncope was the most common symptom, with a burden of 10 per person lifetime. Mean procedure time was 94±44 min, with minimal fluoroscopy dose (2.7±1.7 Gy/cm2). RR interval acutely decreased after ablation (1046±290ms vs. 747±133ms, p<0.0001). No major complications occurred, we observed one post-ablation pericarditis and two sinus tachycardia which required medical treatment. At a median follow-up of 523 days (IQR: 1021-228) two patients had recurrences, both cases were syncopal events without documentation at loop-recorder of sinus bradycardia or atrial bradyarrhythmia. Heart rate at last recorded ECG (331 days, IQR: 570-97) was still significantly higher than baseline (60±13 bpm vs. 81±9 bpm, p=0.0001). Patients’ physical health significantly improved after ablation (WHOQOL-BREF score 61.1% vs 75.3%, p=0.03), no significant changes were observed in the other QoL domains (psychological, social relationships, environmental health). CNA reduced the syncope burden and improved the QoL of patients with vagally-mediated bradyarrhythmia. Ablation is reasonably safe in experts’ hands, especially if compared with the long-life risk of device-related complications. Further large-scale randomized studies are needed to support these findings and validate appropriate patient selection criteria.

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.

A randomized study of yoga therapy for the prevention of recurrent reflex vasovagal syncope.

Vasovagal syncope (VVS) is a common cardiovascular dysautonomic disorder that significantly impacts health and quality of life (QoL). Yoga has been shown to have a positive influence on cardiovascular autonomics. This study assessed the effectiveness of yoga therapy on the recurrence of VVS and QoL. We randomized subjects with recurrent reflex VVS (>3 episodes in the past 1 year) and positive head-up tilt test to guideline-directed therapy (Group 1) or yoga therapy (Group 2). Patients in Group 1 were advised guideline-directed treatment and Group 2 was taught yoga by a certified instructor. The primary endpoint was VVS recurrences and QoL. Between June 2015 and February 2017, 97 highly symptomatic VVS patients were randomized (Group 1: 47 and Group 2: 50). The mean age was 33.1 ± 16.6 years, male:female of 40:57, symptom duration of 17.1 ± 20.7 months, with a mean of 6.4 ± 6.1 syncope episodes. Over a follow-up of 14.3 ± 2.1 months Group 2 had significantly lower syncope burden compared with Group 1 at 3 (0.8 ± 0.9 vs. 1.8 ± 1.4, P < 0.001), 6 (1.0 ± 1.2 vs. 3.4 ± 3.0, P < 0.001), and at 12 months (1.1 ± 0.8 vs. 3.8 ± 3.2, P < 0.001). The Syncope functional score questionnaire was significantly lower in Group 2 compared with Group 1 at 3 (31.4 ± 7.2 vs. 64.1 ± 11.5, P < 0.001), 6 (26.4 ± 6.3 vs. 61.4 ± 10.7, P < 0.001), and 12 months (22.2 ± 4.7 vs. 68.3 ± 11.4, P < 0.001). For patients with recurrent VVS, guided yoga therapy is superior to conventional therapy in reducing symptom burden and improving QoL.

Patients with recurrent syncope and implantable loop recorder exhibit better survival than the control group without implantable loop recorder

Abstract Introduction In 30% of patients with syncope, the underlying cause remains unexplained after clinical investigations. Unexplained syncope tends to recur, significantly impacting patients' quality of life of patients and mortality. Thus, there is a need for timely and more accurate diagnosis to initiate treatment. Dedicated care pathways are recommended by ESC guidelines. Purpose Patients with recurrent syncope were followed over time and patient outcomes with ILR were compared to patients with the same syncope burden, age, gender and mortality risk score who did not receive an ILR. Method A representative database of 4.9 million patients insured by German company statuary health insurances (BKK) was analysed over a time period of 10 years, 2007–17. Patients with recurrent syncope (two times ICD-10 GM diagnosis codes R55), age between 45–84 and no diagnosis code for the syncope were included in the analysis and followed for at least 2 years. Patients with ILR were matched to patients without ILR based on age, gender and Charlson Comorbidity index (CCI) using mahalanobis distances. The index event was the device implant in the ILR group and the second syncope event in the control group. Life expectancy, syncope hospitalisations, fall related injuries, health care costs, diagnoses and treatment rates were compared between the groups. Results A total of 412 patients with ILR for recurrent unexplained syncope were matched to the control group. Overall mean age was 68, mean was CCI 2.7, 42% were females. The risk of death was 2.35 times higher in the control group during follow up as shown in Figure 1 (p-value logrank test &amp;lt;0.0001). Cardiovascular related diagnosis and treatment rates were higher in the ILR group with 69% of patients having a cardiology diagnosis compared to 41% in the control group. Over a quarter (27%) of ILR patients received an implantable cardiac device compared to 5% in the control group. Ablation rates were 7% in the ILR group compared to 0% in the control group. Median health care costs were € 3,847 higher in the ILR group including the costs of the ILR implant, follow up and higher rates of cardiac treatments. These extra costs appear moderate given the substantially higher mortality risk in the control group. Conclusion This study of patients with recurrent unexplained syncope shows a remarkable difference in life expectancy in patients with ILR compared to a matched control group. Two large claim data analysis have recently shown higher rates of cardiovascular death as well as all-cause mortality in patients with unexplained syncope. A more vigilant cardiac workup might be needed to identify a possible underlying cardiac condition. Higher rates of cardiac device therapy in the ILR group were likely to play an important role for their better life expectancy. Cardiac therapies such as pacemakers, defibrillators and ablation have also been shown to significantly improve patients' quality of life. Life Expectancy Comparison Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The data analysis was funded by Medtronic

EASILY MEASURED MARKERS OF SYNCOPE SEVERITY PREDICT VASOVAGAL SYNCOPE RECURRENCE DESPITE CLOSED-LOOP STIMULATION

Although Closed Loop Stimulation (CLS) pacemakers (PM) significantly decrease syncope burden in patients with asystolic vasovagal syncope (VVS), occasional recurrence of syncope has been observed in those with a positive head-up tilt (HUT). Since the reason for this discrepancy is still unclear, we searched for other predictors of syncope recurrence that may be confounding factors.

Burden of recurrent syncope and injuries and the usefulness of implantable cardiac monitors: insights from a nationwide longitudinal cohort analysis.

Aim: The study assesses the burden and costs of recurring unexplained syncope and injuries and the effectiveness of implantable loop recorders. Methods: The English national hospital database (Hospital Episode Statistics) was retrospectively analyzed. Results: 12,002 patients were identified with repeated syncope hospitalizations. 25% of patients were hospitalized at least once again for syncope, 9% of the patients were hospitalized at least once for an injury, causing substantial costs. In the second analysis: 10,902 patients implanted with animplantable cardiac monitor were tracked. By year 3, hospitalizations due to syncope had dropped by 60% versus pre-implantable cardiac monitor (ICM) levels. Conclusion: This study shows a high rate of recurrent syncope admissions and a parallel burden of hospitalizations for injuries. Use of an ICM appears to reduce syncope hospitalizations.

The Current and Future Hospitalization Cost Burden of Syncope in Canada

BackgroundSingle-center studies have shown the high costs associated with the hospital evaluation of syncope. National cost estimates for syncope-related hospitalizations are sparse, and none exist in Canada. MethodsThe Canadian Institute for Health Information Discharge Abstract Database was used to identify acute care hospitalizations with a primary diagnosis of syncope between fiscal years (FY) 2004 and 2015 in all provinces and territories (except Quebec). We used multiple linear regression to calculate the trends in prevalence of hospital admissions and generalized linear regression to estimate the costs of a hospitalization. The syncope hospitalization rate and the cost per hospitalization in Quebec were assumed to be the average of the rest of the country. The future hospitalization cost burden of syncope was projected to 2030. ResultsThere were 128,263 hospitalizations for a primary diagnosis of syncope over the 10-year study period, resulting in a total cost of $619.9 million (Canadian). An estimate of 41,044 syncope hospitalizations occurred in Quebec, costing $198.7 million. The total hospitalization cost of syncope in Canada was estimated at $818.5 million. The annual costs of syncope hospitalizations increased from $66.6 to $68.5 million between FY2004 and FY2015, respectively, and are projected to increase to $87.1 million in 2030. ConclusionHospitalization costs for syncope in Canada are high and rising. Research is needed to identify opportunities to deliver more efficient and cost-effective care.

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.

Syncope, Fear of Falling and Quality of Life Among Older Adults: Findings From the Irish Longitudinal Study on Aging (TILDA).

Objective: Syncope is a prevalent condition that has a marked impact on quality of life. We examined the association between syncope and quality of life (QoL) and whether this association was explained by fear of falling (FoF).Methods: We examined data from Wave 3 of The Irish Longitudinal Study on Aging (TILDA), of adults aged ≥50 years (n = 4,946) who were asked to report syncope and who completed the CASP-12 QoL instrument. Analyses were stratified by age and gender.Results: Over 20% of participants reported having a previous syncopal episode, while 8% reported a faint, blackout or unexplained fall in the last year. QoL scores decreased as the burden of syncope increased: linear regression models adjusted for covariates showed that those having had two or more syncopal episodes in the last year reported a significantly lower CASP-12 score compared to those with none (p = 0.011). FoF partially mediated the association between syncope and QoL, particularly among younger participants.Conclusions: Syncope is a common condition among older adults that has a deleterious effect on QoL, with ≥2 recent syncopal episodes having a particularly adverse impact on QoL. FoF is a potential pathway which may both explain this association and allow therapeutic interventions by health practitioners.

Impact of dual-chamber pacing with closed loop stimulation on quality of life in patients with recurrent reflex vasovagal syncope: results of the SPAIN study.

Reflex vasovagal syncope (VVS) is the most common cause of syncope and patients with recurrent episodes may severely impair quality of life (QoL). This pre-specified analysis evaluated whether the clinically significant reduction in syncope burden demonstrated by dual-chamber pacing with closed loop stimulation (DDD-CLS) reported in the SPAIN trial translates into improved QoL. Patients aged ≥40 years with ≥5 VVS episodes and cardioinhibitory response induced by head-up tilt testing were included. Patients were randomized 1:1 to active DDD-CLS pacing algorithm for 12 months followed by sham DDI mode for the remaining 12 months (Group A) or vice versa (Group B). QoL was assessed using the Short Form-36 (SF-36) health survey, Physical Component Score (PCS), and Mental Component Score (MCS) before randomization (baseline) and at 12- and 24-month follow-up. Fifty-four patients were enrolled from 11 participating centres. No significant carryover effect was detected for any variable, and the only period effect was observed in the vitality subdomain (P = 0.033). Mean SF-36 scores were higher in the DDD-CLS group vs. the DDI group for the eight subdomains and significantly different in physical role, bodily pain, and vitality (P < 0.05). The analysis of component summary scores indicated that DDD-CLS benefited both mental and physical components with significant differences in PCS when compared with the DDI group. Dual-chamber pacing with closed loop stimulation determined a significant and clinically relevant improvement in QoL across both mental and physical components in patients with recurrent VVS. Closed Loop Stimulation for Neuromediated Syncope (SPAIN Study); NCT01621464.

Sex Differences in Vasovagal Syncope: A Post Hoc Analysis of the Prevention of Syncope Trials (POST) I and II

BackgroundVasovagal syncope (VVS) occurs in > 40% of individuals at least once in their lifetime. Sex-dependent differences in presentation and outcomes are not understood. We sought to determine differences in clinical presentation, treatment modalities, and outcomes of VVS between men and women. MethodsData were collected as part of the Prevention of Syncope Trials (POST) I and II, 2 multicenter, placebo-controlled, randomized trials testing the effectiveness of metoprolol and fludrocortisone, respectively. Data regarding clinical presentation, outcomes, and time to first syncope event after randomization were compared. ResultsOf the 418 patients (280 women and 138 men), women were younger at the time of first syncope event (21 vs 26 years P = 0.002) and had a lower baseline systolic blood pressure (117 vs 124 mm Hg, P < 0.001). Response to heat as a trigger for syncope was more common in women (68% vs 48%, P = 0.011). Clinical presentation in women consisted more commonly of feeling warm, having seizures, and experiencing more postsyncope fatigue (68% vs 54%, P = 0.048; 10% vs 2.7%, P = 0.045; 75% vs 59%, P = 0.017, respectively). Women were more likely to experience recurrent syncope after adjustment for prerandomization syncope burden and randomization assignment (hazard ratio, 1.56; 95% confidence interval, 1.10-2.22; P = 0.012). ConclusionClinical presentation and provocative factors of VVS differ between men and women, as do recurrent events. Recognition of these differences may help target therapy specifically in men and women.

2167Impact of dual-chamber pacing with closed loop stimulation on quality of life in patients with recurrent reflex vasovagal syncope: results from the SPAIN study

Abstract Background Reflex vasovagal syncope (VVS) is one of the most common causes of syncope and, when recurrent, can have devastating consequences on the quality of life of patients despite pharmacological interventions. The closed loop stimulation (CLS) pacing algorithm converts, during an incipient VVS, variations in right intracardiac impedance into heart rate adaptation. The study SPAIN was the first randomized, double-blind trial robustly showing a strong reduction in syncopal recurrence in patients paced with dual-chamber (DDD)-CLS. (NCT01621464). Purpose To evaluate whether the differences observed in the SPAIN study regarding syncope burden and time to recurrence translate into improvements on quality of life. Methods This study analysed quality of life data from the SPAIN study: a randomized, prospective, double-blind, multicenter trial conducted in 10 Spanish and 1 Canadian centers. Ethics Committee approval was obtained at each participating center. Patients aged ≥40 years, with ≥5 VVS episodes and cardioinhibitory response to head-up tilt testing were included. After implant, patients were randomized 1:1 to active DDD-CLS mode for 12 months followed by sham DDI mode for the remaining 12 months or vice-versa. Quality of life was assessed via the Short Form-36 (SF-36) health survey before randomization (baseline), and at 12- and 24-month follow-up. The change in quality of life during the entire follow-up relative to baseline was compared between each pacing mode (DDD-CLS vs. DDI). Results Fifty-four patients were enrolled with a mean age of 56.3±10.6 years and a median of 12 syncopal episodes before randomization. Median SF-36 scores greatly increased from baseline in the DDD-CLS group across the 8 domains, whereas the response was variable in the DDI group. Comparing both pacing algorithms, median SF-36 scores were higher in the DDD-CLS group, with differences reaching statistical significance for “physical role” and “vitality” domains (p-value =0.006 and 0.014, respectively). Pacing sequence or treatment period did not significantly influence the response (p-value &gt;0.05 for all the domains). Conclusions We demonstrated the beneficial effect of this physiological pacing algorithm on the quality of life of patients, as evidenced by the improvement in all the domains of the SF-36 when stimulated in DDD-CLS as compared to the sham DDI mode.

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.

Risk factors and psychological impact of syncope in migraine patients.

Migraine is associated with syncope. We investigated risk factors for syncope and burden of syncope in migraine patients. Participants were recruited from a headache clinic. All participants provided information on lifestyle, co-morbidity, syncope, headache and suicide, and completed the MIDAS and HADS questionnaires. Genetic data were available for a subset of participants. Risk of syncope in relation to participant's characteristics and migraine susceptibility loci, and risks of psychological disorders associated with syncope, were calculated using logistic regression. Underweight, regular tea intake, diabetes mellitus, and migraine with aura were associated with increased syncope risks, with adjusted ORs of 1.76 (95% CI 1.03-3.03), 1.84 (95% CI 1.22-2.79), 4.70 (95% CI 1.58-13.95), and 1.78 (95% CI 1.03-3.10), respectively. Preliminary results showed that rs11172113 in LRP1 was associated with syncope risks. Comorbid syncope in migraine patients was associated with increased risks of depression (OR 1.95, 95% CI 1.18-3.22) and suicide attempt (OR 2.85, 95% CI 1.48-5.48). Our study showed the potential roles of vascular risk factors in the association between migraine and syncope. Modifiable risk factors for syncope in patients with migraine include body mass index and tea intake. The debilitating psychological impact of co-morbid syncope in migraine patients warrants clinical attention of treating physicians.

Quality of life improves in vasovagal syncope patients after clinical trial enrollment regardless of fainting in follow-up.

Frequent syncope is linked to poorer health-related quality of life (HRQoL). Recurrent syncope has been observed to reduce in all groups after seeing a syncope expert and enrolling in a clinical trial. It is unknown if HRQoL improves with this reduction in syncope recurrence. We examined the change in HRQoL over time in vasovagal syncope (VVS) patients seen by a syncope expert and enrolled in a trial. We also explored whether change differed with treatment or the frequency of fainting during follow up. The Short Form Health Survey (SF36) was completed at baseline (BL), 6 m, and 12 m post-enrollment by VVS patients in the 1st and 2nd Prevention of Syncope Trials, which were multi-centered, randomized, placebo-controlled trials of metoprolol (POST) and fludrocortisone (POST2). Differences in HRQoL at BL, 6 m, and 12 m were analyzed and compared by faints in follow-up and randomization group. Complete study data were available for 143 VVS patients (40 ± 17 years, 62% F). Over 12 months, patients reported improvement in all SF36 dimensions except for bodily pain. Post hoc analyses indicated that differences first occurred between BL and 6 m for all but general health. Fainting in follow-up or drug randomization group did not diminish the improvements. The baseline syncope burden was not different whether patients' HRQoL improved or not. HRQoL of VVS patients improves over time after enrolling in a clinical trial, even with recurrent faints or randomization to placebo. Improvements may result from alternative factors, such as interaction with experts or patient adjustment.

Efficacy of theophylline in patients with syncope without prodromes with normal heart and normal ECG

BackgroundPatients affected by syncope without or with very short (≤5 s) prodrome with normal heart and normal ECG have been seen to present low plasma adenosine levels. We investigated whether chronic treatment of these patients with theophylline, a non-selective adenosine receptor antagonist, results in clinical benefit. MethodsIn a consecutive case-series of 16 patients (mean age 47 ± 25 years, 9 females) who had ECG documentation of asystolic syncope, we compared the incidence of syncopal recurrence during a period without and a period with tailored theophylline therapy. ResultsDuring a median of 60 months before ECG documentation of the index episode, the patients had a median of 2 syncopes per year. During the 6 months of the study phase without therapy, the patients had a median of 2.6 syncopes per year, p = 0.63. During the 23 months of the study phase with theophylline, the patients had a median of 0.4 syncopes per year, p = 0.005 vs history and p = 0.005 vs no therapy. In the 13 patients who had an implantable loop recorder during both study phases, the incidence of asystolic episodes > 3 s decreased from 9.6 per year to 1.1 per year, p = 0.0007. During theophylline treatment, syncope recurred in 1/5 (20%) patients who had an idiopathic atrioventricular block as the index event versus 9/11 (81%) patients who had a sinus arrest, p = 0.005. ConclusionTheophylline is effective in reducing syncopal burden in patients with syncope without prodromes with normal heart and normal ECG. Its efficacy is greater in those with idiopathic atrioventricular block.