Clinician needs and perceptions about cardioneuroablation for recurrent vasovagal syncope: An international clinician survey.

BACKGROUND: Cardioneuroablation (CNA) targets the intrinsic cardiac autonomic nervous system ganglionated plexi located in the peri-atrial epicardial fat. There is increasing interest in CNA as a treatment of vasovagal syncope (VVS), despite no randomized clinical trial (RCT) data. OBJECTIVE: The purpose of this study was to poll the opinion on CNA) for VVS. METHODS: A REDCap (Research Electronic Data Capture) survey was administered to international physicians treating patients with VVS on their opinion about patient selection criteria, ablation approach, RCT design, and most appropriate end points for CNA procedures. RESULTS: The survey was completed by 118 physicians; 86% were cardiac electrophysiologists. The majority of respondents (79%) would consider referring a patient with refractory VVS for CNA, and 27% have performed CNA for VVS themselves. Most felt patient selection should require a head-up tilt test with a cardioinhibitory response (67%) and suggest a minimum age of 18 years with a median of 3 (interquartile range 2-5) episodes in the past year. There were differences in patient selection between physicians who have performed CNA themselves and those who have not. The majority felt that the ablation strategy should include both atria (70%) with an anatomical approach in combination with autonomic stimulation (85%). Performing a sham procedure in the control arm was supported by 56% of respondents, providing equipoise in RCT design. The preferred primary outcome was freedom from syncope within 1 year of follow-up. CONCLUSION: There is widespread support for well-designed RCTs to confirm the hypothesized clinical benefit of CNA, provide data to guide the risk-benefit equations during patient selection, and appropriately estimate the placebo effect.

Repolarization disparity as a predictor of response to Head up Tilt-table Test in pediatric syncope.

BACKGROUND: Head up Tilt-table Test (HUTT) is a practical examination of the most common type of pediatrics syncope. The electrocardiographic (ECG) changes during this test, show the autonomic defects that cause neuraly-mediated syncope in response to tilting process. METHODS: All pediatric syncope patients referred to our center in a 1-year period, were included in the study. HUTT was performed and patients were classified into two groups of Negative and Positive HUTT results, and the latter group was subclassified as three subgroups of "vasodepressor", "cardioinhibitory" and "mixed type" responses to HUTT. QT and corrected QT (QTc) dispersion was measured by the baseline standard 12-lead ECG obtained before HUTT. RESULTS: Eighty-six patients with a mean age of 12.19 ± 5.34 were included. Patients with positive HUTT were significantly younger and male gender was more prevalent in this group. Mean QT dispersion was significantly higher in patients with positive HUTT result and also in patients with mixed response to HUTT compared to isolated vasodepressor response. Duration of QTc interval did not change between different study groups. Reciever-Operating-Characteristic (ROC) analysis showed that QT dispersion higher than 32 ms is a significant predictor of positive HUTT result (with 92% sensitivity and 98% specificity) and values higher than 40 ms can predict the mixed type of response to HUTT (with 84% sensitivity and 63% specificity). CONCLUSIONS: Baseline myocardial repolarization disparity significantly correlates with susceptibility to symptomatic vasovagal syncope. This pathology seems to play its role mainly via excessive vagotonic response to sympathetic activation during HUTT process (known as cardioinhibitory response).

New hemodynamic criteria to separate classical orthostatic hypotension from vasovagal syncope.

OBJECTIVE: To define and evaluate hemodynamic criteria to distinguish between classical orthostatic hypotension (cOH) and vasovagal syncope (VVS) in tilt table testing (TTT). METHODS: Inclusion criteria for VVS were a history of VVS and tilt-induced syncope defined as a blood pressure (BP) decrease and electroencephalographic changes during syncope with complaint recognition. Criteria for cOH were a history of cOH and a BP decrease meeting published criteria. Clinical diagnoses were established prior to TTT. We assessed (1) whether the decrease of systolic BP accelerated, "convex," or decelerated, "concave"; (2) the time from head-up tilt to when BP reached one-half its maximal decrease; (3) the difference between baseline heart rate (HR) and HR at BP nadir. We calculated the diagnostic yield of optimized thresholds of these features and their combinations. RESULTS: We included 82 VVS cases (40% men, median age 44 years) and 65 cOH cases (66% men, median age 70 years). BP decrease was concave in cOH in 79% and convex in VVS in 94% (p < 0.001). The time to reach half the BP decrease was shorter in cOH (median 34 sec, interquartile range (IQR) 19-98 sec) than in VVS (median 1571 sec, IQR 1381-1775 sec, p < 0.001). Mean HR increased by 11 ± 11 bpm in cOH and decreased by 20 ± 19 bpm in VVS (p < 0.001). When all three features pointed to VVS, sensitivity for VVS was 82% and specificity was 100%. When all three pointed to cOH, sensitivity for cOH was 71% and specificity was 100%. INTERPRETATION: These new hemodynamic criteria reliably differentiate cOH from VVS.

Diagnosis and prevention of the vasodepressor type of neurally mediated syncope in Japanese patients.

We investigated circulatory dynamics in patients with vasodepressor type neurally mediated syncope (VT-NMS) by performing high-resolution Holter electrocardiography and a correlation analysis of changes in adenylate cyclase activity, blood pressure, and pulse during the head-up tilt test. Holter electrocardiography was performed for 30 patients. Adenylate cyclase activity was evaluated in lymphocytes from blood samples taken at rest and during the head-up tilt test. There was no change in autonomic nerve fluctuation during electrocardiography in VT-NMS patients, but our results showed a significant difference in blood pressure and adenylate cyclase activity between VT-NMS patients and healthy volunteers; the systolic blood pressure of VT-NMS patients decreased after 5 min, while at 10 min, the adenylate cyclase activity was the highest (0.53%) and the systolic blood pressure was the lowest (111.8 mm Hg). Pulse rates increased after 10 min. VT-NMS patients showed higher blood pressure, pulse rate, and adenylate cyclase activity during the tilt test than did healthy volunteers. In patients with syncope, standing for longer than 10 minutes may increase the risk of VT-NMS. From our results, we consider it likely that high systolic blood pressure and adenylate cyclase activity at rest cause fainting in VT-NMS patients. Our findings may be helpful for identifying individuals with a high risk of developing NMS in the healthy population.

Durable Physiological Changes and Decreased Syncope Burden 12 Months After Unifocal Right-Sided Ablation Under Computed Tomographic Guidance in Patients With Neurally Mediated Syncope or Functional Sinus Node Dysfunction.

[Figure: see text].

Implementation of measures to reduce vasovagal reactions: Donor participation and results.

BACKGROUND: There are several strategies to reduce donor reactions. We report donor participation and reaction rates before and after implementing multiple measures at Canadian Blood Services. STUDY DESIGN AND METHODS: We introduced a structured program of 500 mL of water and a salty snack pre-donation and applied muscle tension (AMT) during donation. Donors were not deferred for out of range blood pressure (BP); however, BP was measured in first time donors. Time on the donation chair post-donation was decreased from 5 to 2 min for repeat donors. We assessed participation rates using our quarterly survey of 10,000 recent donors. We extracted vasovagal reactions with loss of consciousness (LOC) from our operational database and compared pre-implementation (Oct 12,018-March 31,2019) and post-implementation (Oct 12,019-March 31,2020) periods. RESULTS: Survey response rates varied from 11% to 16%. The percentage of donors who drank the water and ate the salty snack increased from 58% to 82% and 44% to 70% over 4 quarters; those performing AMT increased from 24% to 41%. Reactions decreased from 19.07 per 10,000 (744 reactions in 390,123 donations) to 14.04 per 10,000 (537 in 382,382 donations) (p < .0001). No first-time donors with high BP (n = 684) but 5 with low BP (n = 718) had reactions, CI were very large. CONCLUSIONS: Achieving optimal participation was challenging. After implementation of a donor wellness initiative based on best practice, rates of vasovagal reactions with LOC decreased by 25%. A larger dataset is necessary to assess the safety contribution of BP deferrals when other mitigation measures are in place.

Extracardiac Abnormalities of Preload Reserve: Mechanisms Underlying Exercise Limitation in Heart Failure with Preserved Ejection Fraction, Autonomic Dysfunction, and Liver Disease.

While many of the cardiac limitations to exercise performance are now well-characterized, extracardiac limitations to exercise performance have been less well recognized but are nevertheless important. We propose that abnormalities of cardiac preload reserve represents an under-recognized but common cause of exercise limitations. We further propose that mechanistic links exist between conditions as seemingly disparate as heart failure with preserved ejection fraction, nonalcoholic fatty liver disease, and pelvic venous compression/obstruction syndromes (eg, May-Thurner). We conclude that extracardiac abnormalities of preload reserve serve as a major pathophysiologic mechanism underlying these and other disease states.

Are women really more affected by vasovagal syncope than men?

It is commonly reported that vasovagal syncope (VVS) is more frequent in women. Presently, this issue has never been investigated. The purpose of this review was to evaluate, through an extensive review of the literature, whether women are really more affected by VVS than men. The gender distribution was investigated in individuals with classical and nonclassical VVS. The database PubMed was searched using the terms 'syncope', 'vasovagal syncope', 'neurally mediated syncope' and 'tilt testing'. Twelve studies dealing with classical and 75 with nonclassical VVS were eligible. In the individuals with classical (N = 1861) and nonclassical VVS (N = 9696), a trend towards a greater percentage of women emerged (P = 0.14 and 0.07, respectively). In the total population with VVS (N = 11 557), the percentage of women was significantly higher than that of men (58 versus 42%, P = 0.03). Most of the individuals were young or middle-aged. In 84% of the studies, the percentage of women was greater than that of men. A separate analysis was carried out in older VVS patients (≥60 years) and only two studies were eligible to be evaluated. Considering that almost all the studies were carried out in the western nations, where the number of men and women is almost superimposable until the age of 65 years and a bias by gender has never been reported in the management of VVS, these data strongly suggest that young and middle-aged women are more affected by VVS than their male counterparts. At present, data are too scant to draw a definitive conclusion in older VVS patients.

The Diagnostic Value of Cardiac Deceleration Capacity in Vasovagal Syncope.

BACKGROUND: Increased parasympathetic activity is thought to play important roles in syncope events of patients with vasovagal syncope (VVS). However, direct measurements of the vagal control are difficult. The novel deceleration capacity (DC) of heart rate measure has been used to characterize the vagal modulation. This study aimed to assess vagal control in patients with VVS and evaluate the diagnostic value of the DC in VVS. METHODS: Altogether, 161 consecutive patients with VVS (43±15 years; 62 males) were enrolled. Tilt table test was positive in 101 and negative in 60 patients. Sixty-five healthy subjects were enrolled as controls. DC and heart rate variability in 24-hour ECG, echocardiogram, and biochemical examinations were compared between the syncope and control groups. RESULTS: DC was significantly higher in the syncope group than in the control group (9.6±3.3 versus 6.5±2.0 ms, P<0.001). DC was similarly increased in patients with VVS with a positive and negative tilt table test (9.7±3.5 and 9.4±2.9 ms, P=0.614). In multivariable logistic regression analyses, DC was independently associated with syncope (odds ratio=1.518 [95% CI, 1.301-1.770]; P=0.0001). For the prediction of syncope, the area under curve analysis showed similar values when comparing single DC and combined DC with other risk factors (P=0.1147). From the receiver operator characteristic curves for syncope discrimination, the optimal cutoff value for the DC was 7.12 ms. CONCLUSIONS: DC>7.5 ms may serve as a good tool to monitor cardiac vagal activity and discriminate VVS, particularly in those with negative tilt table test.

Long-Term Evaluation of the Vagal Denervation by Cardioneuroablation Using Holter and Heart Rate Variability.

BACKGROUND: Several disorders present reflex or persistent increase in vagal tone that may cause refractory symptoms even in a normal heart patient. Cardioneuroablation, the vagal denervation by radiofrequency ablation of the neuromyocardial interface, was developed to treat these conditions without pacemaker implantation. A theoretical limitation could be the reinnervation, that naturally grows in the first year, that could recover the vagal hyperactivity. This study aims to verify the vagal denervation degree in the chronic phase after cardioneuroablation. Additionally, it intends to investigate the arrhythmias behavior after cardioneuroablation. METHODS: Prospective longitudinal study with intrapatient comparison of 83 very symptomatic cases without significant cardiopathy, submitted to cardioneuroablation, 49 (59%) male, 47.3±17 years old, having vagal paroxysmal atrial fibrillation 58 (70%) or neurocardiogenic syncope 25 (30%), New York Heart Association class0.05) suggesting that the reinnervation has halted. There was also an important reduction in all bradyarrhythmias and tachyarrhythmias pre-cardioneuroablation versus post-cardioneuroablation (P<0.01). CONCLUSIONS: There is an important and significant vagal and sympathetic denervation after 2 years of cardioneuroablation with a significant reduction in bradyarrhythmia and tachyarrhythmia in the whole group. There were no complications.

Isoproterenol Causing Coronary Vasospasm and ST Elevations During Tilt Table Testing.

Syncope is a sudden but reversible brief loss of consciousness secondary to an acute reduction of cerebral perfusion. Reflex syncope denotes neurologically mediated syncope, which includes vasovagal, carotid sinus syndrome, and other situational syncope. The most frequent form of syncope is vasovagal, which is triggered by emotional stress or prolonged standing, and may be diagnosed with the tilt table test. A thorough investigation of syncope is necessary as serious cardiovascular disorders may also be a cause. A tilt table test is a widely used tool utilized by clinicians to diagnose vasovagal syncope and is sometimes augmented with isoproterenol, a ß-sympathomimetic that acts on the heart. This report seeks to explain a case of a 48-year-old previously healthy woman who experienced inferior wall ST elevations during tilt table test supplemented with isoproterenol. There is reason to believe that the results of this patient's tilt table test were due to vasovagal syncope in conjunction with right coronary artery vasospasm.

Clinical values of creatine kinase and its isoenzymes in children and adolescents with vasovagal syncope.

BACKGROUND AND AIM: Vasovagal syncope (VVS) in children and adolescents is a common disorder. There may be an internal relationship between creatine kinase (CK) and its isoenzymes (CKMB) and syncope. The aim of this study was to evaluate the changes of CK and CKMB in children and adolescents with VVS. METHODS AND RESULTS: The VVS group included 218 patients (93 male and 125 female). The control group included 129 healthy children (78 male and 51 female). Serum CK and CKMB levels were estimated. We founded ①Serum CK and CK-MB levels decreased in VVS group than that in control group (P < 0.05). ②The CK levels of female were significantly lower than those of male in VVS group (P < 0.05). ③Serum level of CK-MB were in negative correlation with age, height, weight, BMI whereas in positively correlation with HR. ④CK was effected by CK-MB (ß = 0.147, P = 0.037) while CK-MB was independently influenced by age (ß = -0.203, P = 0.002) and DBP (ß = 0.171, P = 0.011). ⑤Both CK and CK-MB significantly influenced on VVS occurrence after adjusting for the effects of gender, age, height, weight, BMI and HR. CONCLUSION: The serum CK and CKMB levels decrease in children and adolescents with VVS. CK and CK-MB are the independent protective factors with VVS.

Lymphoma with superimposed tuberculosis and fungal infection mimicking parapharyngeal abscess complicated with recurrent neurocardiogenic syncope: a case report.

INTRODUCTION: Lymphoma of parapharyngeal space (PPS) is a rare condition. The clinical presentations may vary and often masquerades as infection or an inflammatory condition. A misdiagnosis will lead to a delay in treatment of the disease. Due to the complex anatomy of PPS, any attributed pressure from masses can lead to a life-threatening event such as cardiac syncope. CASE REPORT: We report a rare case of PPS B-cell non-Hodgkin lymphoma with superimposed Tuberculosis (TB) and fungal infection that presents with several episodes of syncope and hemodynamic depression. DISCUSSION: The clinical entities in PPS lesions syncope and its associated syndromes, pathophysiology, and differential diagnosis together with possible managements are further discussed.

Characterization of an Artificial Liver Support System-Related Vasovagal Reaction.

OBJECTIVE: An artificial liver support system (ALSS) is an effective therapy for patients with severe liver injury. A vasovagal reaction (VVR) is a common complication in various treatment settings but has not been reported previously in ALSS. METHODS: This study retrospectively evaluated patients who suffered an ALSS-related VRR between January 2018 and June 2019. We collected data from VVR episodes including onset time, duration, changes in heart rate (HR) and blood pressure (BP), and drug treatment. RESULTS: Among 637 patients who underwent ALSS treatment, 18 were included in the study. The incidence of VVR was approximately 2.82%. These patients were characterized by a rapid decrease in BP or HR with associated symptoms such as chest distress, nausea, and vomiting. The majority of patients (78%) suffered a VVR during their first ALSS treatment. Sixteen patients (89%) had associated symptoms after treatment began. Sixteen patients (89%) received human albumin or Ringer's solution. Atropine was used in 11 patients (61%). The symptoms were relieved within 20 min in 15 patients and over 20 min in 3 patients. CONCLUSIONS: A VVR is a rare complication in patients with severe liver injury undergoing ALSS treatment. Low BP and HR are the main characteristics of a VVR.

Comparative effects of intensive ganglionated plexus ablation in treating paroxysmal atrial fibrillation and vasovagal syncope.

BACKGROUND: Ganglionated plexus (GP) ablation is used to treat atrial fibrillation (AF) and vasovagal syncope (VVS). However, the comparative effects of GP ablation in treating paroxysmal atrial fibrillation (PAF) and VVS have not been well studied. OBJECTIVE: The purpose of this study was to investigate the effects of intensive GP ablation on PAF and VVS. METHODS: PAF and VVS patients were enrolled in this study. Pulmonary vein isolation (PVI) was performed in the PAF group, and additional ablation was performed at GP sites. Anatomic ablation of left atrial GPs was performed in the VVS group. The primary endpoint was freedom from AF or other sustained atrial tachycardia and syncope recurrence. RESULTS: A total of 195 patients were enrolled: 146 patients with PAF, including eight patients with combined VVS (PAF group), and 49 patients with VVS (VVS group). Vasovagal response (VR) was achieved in 78 (53.4%) patients in the PAF group and 48 patients (98.0%) in the VVS group (P < .05). During the 17.8 ± 10.5 (range, 3-42) month follow-up, 126 (86.3%) patients were free of AF in the PAF group, and 45 (91.8%) patients in the VVS group had no syncope recurrence and significantly improved symptoms. CONCLUSIONS: Anatomically guided intensive GP ablation showed efficient clinical outcomes for both groups of patients. Compared with PAF patients, VVS patients had more VR during ablation in the left atrium. Furthermore, VR during ablation indicated a better prognosis in PAF patients.

Symptom Score: A New Instrument to Assess Orthostatic Intolerance in Children and Adolescents.

OBJECTIVE: To develop an orthostatic intolerance symptom scoring system to assess orthostatic intolerance and then to compare the symptom score among different head-up tilt test responses. METHODS: 272 subjects (5-18 years) presenting with orthostatic intolerance symptoms finished questionnaire and head-up tilt test. According to head-up tilt test hemodynamic responses, the subjects were divided into head-up tilt test negative, vasovagal syncope, and postural tachycardia syndrome groups. RESULTS: We built up a symptom score according to the frequency of dizziness, headache, blurred vision, palpitations, chest discomfort, gastrointestinal symptoms, profuse perspiration, and syncope. The median score in postural tachycardia syndrome subjects was highest. A score of 2.5 for predicting vasovagal syncope yielded a sensitivity of 75.0% and specificity of 50.3%, a score of 5.5 for predicting postural tachycardia syndrome yielded a sensitivity of 69.7% and specificity of 72.0%. Furthermore, the median score in postural tachycardia syndrome subjects was significantly higher than that in head-up tilt test negative subjects with heart rate increment of 30-39 beats/min (P < .01). CONCLUSIONS: This suggests that the symptom score has some predictive value in head-up tilt test results, which can be served as a preliminary assessment instrument.

Todd's paresis following vasovagal syncope provoked by tilt-table testing.

A 38-year-old woman presented with a history of recurrent episodes of transient loss of consciousness (TLOC) with seizure-like activity and post-TLOC left sided paresis. Electroencephalogram and MRI of the brain were normal, and events were not controlled by anti-convulsant therapy. Tilt testing produced reflex mixed pattern vasovagal syncope, with exact symptom reproduction, including bilateral upper and lower limb myoclonic movements and post-TLOC left hemiparesis that persisted for 27 min. A witness for the tilt event confirmed reproduction of patients 'typical' TLOC event. Syncope is the most frequent cause of TLOC. Myoclonic movements during syncope are not uncommon and can be misdiagnosed as epilepsy. It is rare to experience paresis after syncope, which in this case, lead to misdiagnosis and unnecessary anti-convulsant treatment.

An analysis of vascular properties using pulse wave analysis in patients with vasovagal syncope.

BACKGROUND: Vasovagal syncope (VVS) is a common cause of recurrent syncope. Nevertheless, the exact hemodynamic mechanism has not been elucidated. Pulse wave analysis (PWA) is widely used to evaluate vascular properties, as it reflects the condition of the entire arterial system. HYPOTHESIS: Cardiovascular autonomic modulation may influence the hemodynamic mechanism and result in different vascular properties between VVS patients and healthy individuals. METHODS: We enrolled consecutive patients diagnosed with VVS on head-up tilt testing from January 2014 to August 2019. Healthy subjects were enrolled as the control group. We performed PWA on all participants. Using propensity score matching, we assembled a study population with similar baseline characteristics and compared hemodynamic parameters. RESULTS: A total of 111 VVS patients (43 ± 18 years, 72 females) and 475 healthy control subjects (48 ± 13 years, 192 females) were enrolled. Compared to the healthy control subjects, the VVS patients had a higher augmentation index (AIx) adjusted to a heart rate of 75 beats per minute (AIx@HR75, 20.5 ± 13.1% vs 16.7 ± 11.9%, P = .003). After 1:1 matched comparison (111 matched control), VVS patients consistently showed higher AIx@HR75 (20.5 ± 13.1% vs 16.7 ± 12.9%, P = .02) than the matched control group. According to age distribution, VVS patients showed significantly higher AIx@HR75 (10.6 ± 11.7% vs 2.5 ± 11.1%, P = .01) in a young age (15-33 years) group. CONCLUSIONS: VVS patients had greater arterial stiffness than healthy subjects. This is one of the plausible mechanisms of the pathophysiology of VVS.