Rapid changes in cerebrovascular compliance during vasovagal syncope.

PURPOSE: The compensatory mechanisms supporting cerebral perfusion throughout head-up tilt (HUT) in patients with vasovagal syncope (VVS) remain unclear. We tested the hypothesis that increased cerebrovascular compliance (Ci) and decreased cerebrovascular resistance (CVR) support cerebral blood velocity (CBV) during pre-syncope in VVS. METHODS: Finger arterial blood pressure (ABP) and right middle cerebral artery blood velocity (CBV) were recorded in 15 individuals diagnosed with VVS (n = 11 female, mean age: 40 ± 16 years, mean body mass index: 24.9 ± 4.0 kg/m2) at supine rest and during HUT (80 degree angle). Individual ABP and CBV waveforms during VVS were input into a modified Windkessel model to calculate Ci and ohmic CVR. Gosling's pulsatility index (Pi; pulse amplitude/mean CBV) was calculated. RESULTS: Diastolic ABP, systolic ABP, mean ABP (72 ± 11 to 51 ± 12 mmHg), and CVR decreased progressively during presyncope (all P ≤ 0.04). As expected, systolic CBV was sustained (all P ≥ 0.29) while diastolic and mean CBV (51 ± 13 to 38 ± 13 mmHg) fell during presyncope (all P ≤ 0.04). Both Ci and Pi increased during presyncope (128 ± 97 and 60 ± 41%, respectively; all P ≤ 0.049) and were positively correlated (R2 = 0.79, P < 0.01). Increased Ci contributed to changes in mean CBV (P < 0.01) but decreased CVR did not (P = 0.28). CONCLUSIONS: These data provide evidence that Ci increases during presyncope in patients with VVS and is likely involved in the maintenance of systolic CBV during a fall in diastolic CBV. However, this regulation is not sufficient to preserve CBV in the presence of such extreme and progressive reductions in ABP.

Differences in Heart Rate Variability in the Frequency Domain between Different Groups of Patients.

Background and Objectives: Heart rate variability (HRV) is defined as a physiological variation in duration between sinus beats. The aim of this study was to research and analyze the HRV between various groups of patients. Materials and Methods: A retrospective study was conducted in an outpatient setting. Patients who had undergone a tilt-table test were selected for this study and were divided into three groups based on their self-reported health anamnesis: group 1 (n = 84, mean age 45.8 ± 17.8) consisted of patients with no known orthostatic intolerance or neurodegenerative disease, group 2 consisted of patients with a known or suspected orthostatic intolerance (n = 50, mean age 46.5 ± 18.6), and group 3 consisted of patients with a known or suspected neurodegenerative disorder (n = 29, mean age 55.6 ± 20.4). During the tilt-table test, HRV frequency-domain parameters-normalized low frequency (LFnu) and high frequency (HFnu), absolute powers-absolute low frequency (LF-RRI), absolute high frequency (HF-RRI), and LF/HF ratio-were recorded during 5 min rest in the supine position. Results: Group 1 had a reduced LFnu at 52.93% (SD: 18.00) compared to group 2 at 58.57% (18.06) and group 3 at 61.80% (SD: 17.74), and group 1 had increased HFnu: group 1-47.08% (SD: 17.97), group 2-41.41% (SD: 18.03), and group 3-38.16% (SD: 14.7). LFnu and HFnu differences were statistically significant (p < 0.05). LF-RRI was reported as follows: group 1-531.32 ms2 (SD: 578.57), group 2-346.2 ms2 (SD: 447.96), and group 3-143.21 ms2 (SD: 166.96). HF-RRI was reported as follows: group 1-835.87 ms2 (SD: 1625.42), group 2-297.46 ms2 (SD: 507.15), and group 3-70.83 ms2 (SD: 75.67). LF-RRI and HF-RRI comparisons between groups were statistically significant (p < 0.001). LF/HF ratios were reported as follows: group 1-1.91 (SD: 2.29), group 2-2.43 (SD: 2.33), and group 3-2.54 (SD: 2.17). LF/HF ratio comparisons between groups were statistically significant at p < 0.05. Conclusions: This study shows that patients with known or suspected orthostatic intolerance and neurodegenerative disorders have reduced HRV, possibly caused by reduced parasympathetic modulation. HRV in patients with known or suspected neurodegenerative disorders is reduced more severely than in patients with orthostatic disorders. Other studies in HRV have indicated a possible increase of risk in cardiovascular disorders in patients with reduced HRV, and therefore, HRV analysis could be a potential clinical diagnostic tool. However, the lack of universally agreed upon methodology, reference values, and possible external and internal factor influence hinders the introduction of HRV examinations into wider clinical practice.

Differential hemodynamic adaptations to tilt test in patients with idiopathic atrial fibrillation.

The hemodynamic response during the transition from the supine to standing position in idiopathic atrial fibrillation (AF) patients is not completely understood. This study aimed to analyze the hemodynamic changes that occur during the head-up tilt test in idiopathic AF patients. We investigated the hemodynamic changes during the head-up tilt test with impedance cardiography in 40 AF patients (12 with AF rhythm-AFr and 28 with sinus rhythm-AFsr) and 38 non-AF controls. Patients with AFr had attenuated SVI decrease after standing when compared to AFsr and non-AF [ΔSVI in mL/m2: -1.3 (-3.4 to 1.7) vs. -6.4 (-17.3 to -0.1) vs. -11.8 (-18.7 to -8.0), respectively; p < 0.001]. PVRI decreased in AFr but increased in AFsr and non-AF [ΔPVRI in dyne.seg.m2/cm5: -477 (-1148 to 82.5) vs. 131 (-525 to 887) vs. 357 (-29 to 681), respectively; p < 0.01]. Similarly, compared with non-AF patients, AFr patients also had a greater HR and greater CI increase after standing. The haemodynamic response to orthostatic challenge suggests differential adaptations between patients with AF rhythm and those reverted to sinus rhythm or healthy controls. Characterizing the hemodynamic phenotype may be relevant for the individualized treatment of AF patients.

Adult vasovagal syncope with abdominal pain diagnosed by head-up tilt combined with transcranial doppler: a preliminary study.

BACKGROUND: Syncope is a common condition that increases the risk of injury and reduces the quality of life. Abdominal pain as a precursor to vasovagal syncope (VVS) in adults is rarely reported and is often misdiagnosed.​. METHODS: We present three adult patients with VVS and presyncopal abdominal pain diagnosed by synchronous multimodal detection (transcranial Doppler [TCD] with head-up tilt [HUT]) and discuss the relevant literature. RESULTS: Case 1: A 52-year-old man presented with recurrent decreased consciousness preceded by six months of abdominal pain. Physical examinations were unremarkable. Dynamic electrocardiography, echocardiography, head and neck computed tomography angiography, magnetic resonance imaging (MRI), and video electroencephalogram showed no abnormalities. Case 2: A 57-year-old woman presented with recurrent syncope for 30 + years, accompanied by abdominal pain. Physical examination, electroencephalography, and MRI showed no abnormalities. Echocardiography showed large right-to-left shunts. Case 3: A 30-year-old woman presented with recurrent syncope for 10 + years, with abdominal pain as a precursor. Physical examination, laboratory analysis, head computed tomography, electrocardiography, and echocardiography showed no abnormalities. Syncope secondary to abdominal pain was reproduced during HUT. Further, HUT revealed vasovagal syncope, and synchronous TCD showed decreased cerebral blood flow; the final diagnosis was VVS in all cases. CONCLUSIONS: Abdominal pain may be a precursor of VVS in adults, and our findings enrich the clinical phenotypic spectrum of VVS. Prompt recognition of syncopal precursors is important to prevent incidents and assist in treatment decision-making. Abdominal pain in VVS may be a sign of sympathetic overdrive. Synchronous multimodal detection can help in diagnosing VVS and understanding hemodynamic mechanisms.

Classification of vasovagal syncope from physiological signals on tilt table testing.

BACKGROUND: The diagnostic test for vasovagal syncope (VVS), the most common cause of syncope is head-up tilt test (HUTT) assessment. During the test, subjects experienced clinical symptoms such as nausea, sweating, pallor, the feeling of palpitations, being on the verge of passing out, and fainting. The study's goal is to develop an algorithm to classify VVS patients based on physiological signals blood pressure (BP) and electrocardiography (ECG) obtained from the HUTT. METHODS: After 10 min of supine rest, the subject was tilted at a 70-degree angle on a tilt table for approximately a total of 35 min. 400 µg of glyceryl trinitrate (GTN) was administered sublingually after the first 20 min and monitoring continued for another 15 min. Mean imputation and K-nearest neighbors (KNN) imputation approaches to handle missing values. Next, feature selection techniques were implemented, including genetic algorithm, recursive feature elimination, and feature importance, to determine the crucial features. The Mann-Whitney U test was then performed to determine the statistical difference between two groups. Patients with VVS are categorized via machine learning models including Support Vector Machine (SVM), Gaussian Naïve Bayes (GNB), Multinomial Naïve Bayes (MNB), KNN, Logistic Regression (LR), and Random Forest (RF). The developed model is interpreted using an explainable artificial intelligence (XAI) model known as partial dependence plot. RESULTS: A total of 137 subjects aged between 9 and 93 years were recruited for this study, 54 experienced clinical symptoms were considered positive tests, while the remaining 83 tested negative. Optimal results were obtained by combining the KNN imputation technique and three tilting features with SVM with 90.5% accuracy, 87.0% sensitivity, 92.7% specificity, 88.6% precision, 87.8% F1 score, and 95.4% ROC (receiver operating characteristics) AUC (area under curve). CONCLUSIONS: The proposed algorithm effectively classifies VVS patients with over 90% accuracy. However, the study was confined to a small sample size. More clinical datasets are required to ensure that our approach is generalizable.

Temporal relationship between haemodynamic changes and activation of closed-loop stimulation during a tilt-induced vasovagal syncope.

AIMS: A dual-chamber pacemaker with closed-loop stimulation (CLS) mode is effective in reducing syncopal recurrences in patients with asystolic vasovagal syncope (VVS). In this study, we explored the haemodynamic and temporal relationship of CLS during a tilt-induced vasovagal reflex. METHODS AND RESULTS: Twenty patients underwent a tilt test under video recording 3.9 years after CLS pacemaker implantation. Three patients were excluded from the analysis because of no VVS induced by the tilt test (n = 1) and protocol violation (n = 2). In 14 of the remaining 17 patients, CLS pacing emerged during the pre-syncopal phase of circulatory instability when the mean intrinsic heart rate (HR) was 88 ± 12 b.p.m. and systolic blood pressure (SBP) was 108 ± 19 mmHg. The CLS pacing rate thereafter rapidly increased to 105 ± 14 b.p.m. within a median of 0.1 min [inter-quartile range (IQR), 0.1-0.7 min] when the SBP was 99 ± 21 mmHg. At the time of maximum vasovagal effect (syncope or pre-syncope), SBP was 63 ± 17 mmHg and the CLS rate was 95 ± 13 b.p.m. The onset of CLS pacing was 1.7 min (IQR, 1.5-3.4) before syncope or lowest SBP. The total duration of CLS pacing was 5.0 min (IQR, 3.3-8.3). Closed-loop stimulation pacing was not observed in three patients who had a similar SBP decrease from 142 ± 22 mmHg at baseline to 69 ± 4 mmHg at the time of maximum vasovagal effect, but there was no significant increase in HR (59 ± 1 b.p.m.). CONCLUSION: The reproducibility of a vasovagal reflex was high. High-rate CLS pacing was observed early during the pre-syncopal phase in most patients and persisted, although attenuated, at the time of maximum vasovagal effect. REGISTRATION: ClinicalTrials.gov identifier: NCT06038708.

Tilt table testing, methodology and practical insights for the clinic.

Tilt table testing (TTT) has been used for decades to study short-term blood pressure (BP) and heart rate regulation during orthostatic challenges. TTT provokes vasovagal reflex in many syncope patients as a background of widespread use. Despite the availability of evidence-based practice syncope guidelines, proper application and interpretation of TTT in the day-to-day care of syncope patients remain challenging. In this review, we offer practical information on what is needed to perform TTT, how results should be interpreted including the Vasovagal Syncope International Study classification, why syncope induction on TTT is necessary in patients with unexplained syncope and on indications for TTT in syncope patient care. The minimum requirements to perform TTT are a tilt table with an appropriate tilt-down time, a continuous beat-to-beat BP monitor with at least three electrocardiogram leads and trained staff. We emphasize that TTT remains a valuable asset that adds to history building but cannot replace it, and highlight the importance of recognition when TTT is abnormal even without syncope. Acknowledgement by the patient/eyewitness of the reproducibility of the induced attack is mandatory in concluding a diagnosis. TTT may be indicated when the initial syncope evaluation does not yield a certain, highly likely, or possible diagnosis, but raises clinical suspicion of (1) reflex syncope, (2) orthostatic hypotension (OH), (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT in the patient with a certain, highly likely or possible diagnosis of reflex syncope, may be to educate patients on prodromes. In patients with reflex syncope with OH TTT can be therapeutic to recognize hypotensive symptoms causing near-syncope to perform physical countermanoeuvres for syncope prevention (biofeedback). Detection of hypotensive susceptibility requiring therapy is of special value.

Brain MRI and EEG overemployment in patients with vasovagal syncope: results from a tertiary syncope unit.

BACKGROUND: The diagnosis of vasovagal syncope (VVS) is mainly based on history-taking and physical examination. However, brain Magnetic Resonance Imaging (MRI) and Electroencephalogram (EEG) are commonly used in the diagnostic course of VVS, despite not being indicated in the guidelines. This study aims to find the possible associated factors with the administration of brain MRI and EEG in patients with VVS. METHODS: Patients with a diagnosis of VVS from 2017 to 2022 were included. Several demographic and syncope features were recorded. The association of these was assessed with undergoing MRI, EEG, and either MRI or EEG. Univariate and multivariable logistic regression models were also used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: A total of 1882 patients with VVS were analyzed, among which 810 underwent MRI (43.04%), 985 underwent EEG (52.34%), and 1166 underwent MRI or EEG (61.96%). Head trauma (OR 1.38, 95% CI 1.06 to 1.80), previous neurologist visit (OR 6.28, 95% CI 4.24 to 9.64), and gaze disturbance during syncope (OR 1.75, 95% CI 1.13 to 2.78) were all positively associated to the performance of brain MRI/EEG. Similar results were found for urinary incontinence (OR 2.415, 95% CI 1.494 to 4.055), amnesia (OR 1.421, 95% CI 1.053 to 1.930), headache after syncope (OR 1.321, 95% CI 1.046 to 1.672), and tonic-clonic movements in head-up tilt table test (OR 1.501, 95% CI 1.087 to 2.093). However, male sex (OR 0.655, 95% CI 0.535 to 0.800) and chest pain before syncope (OR 0.628, 95% CI 0.459 to 0.860) had significant negative associations with performing brain MRI/EEG. CONCLUSION: Based on our findings, performing MRI or EEG was common among VVS patients while it is not indicated in the majority of cases. This should be taken into consideration to prevent inappropriate MRI/EEG when there is a typical history compatible with VVS.

Tilt testing.

Tilt testing can help to diagnose unexplained syncope, by precipitating an episode during cardiac monitoring. The Italian protocol, now most widely used, involves giving sublingual nitroglycerine after 15 min, while monitoring beat-to-beat blood pressure (BP) and recording on video. Tilt testing is time-consuming but it is clinically useful and can guide therapy. Complications are rare. Syncope types include vasovagal syncope where BP falls after >3 min of tilt-up and later the heart rate falls; classic orthostatic hypotension where there is an immediate, progressive BP fall with minimal heart rate change; delayed orthostatic hypotension with a late BP fall after a stable phase but little or no heart rate rise; psychogenic pseudosyncope with apparent loss of consciousness, but no BP fall and a moderate heart rate rise; and postural orthostatic tachycardia syndrome where there is a significant heart rate rise but no BP fall.

Clinical and Autonomic Profile, and Modified Calgary Score for Children and Adolescents with Presumed Vasovagal Syncope Submitted to the Tilt Test. / Perfil Clínico, Autonômico e Escore de Calgary Modificado de Crianças e Adolescentes com Presumida Síncope Vasovagal Submetidos ao Teste de Inclinação.

BACKGROUND: In the pediatric population, syncope is mainly from vasovagal (VVS) origin. Its evaluation must be done by clinical methods, and the tilt test (TT) can contribute to the diagnosis. OBJECTIVES: To analyze the clinical profile, Calgary and modified Calgary scores, response to TT and heart rate variability (HRV) of patients aged ≤ 18 years with presumed VVS. To compare the variables between patients with positive and negative responses to TT. METHOD: Observational and prospective study, with 73 patients aged between 6 and 18 years, submitted to clinical evaluation and calculation of scores without previous knowledge of the TT. It was done at 70º under monitoring for HRV analysis. P-value < 0.05 was the statistical significance criterion. RESULTS: Median age was 14.0 years; 52% of participants were female, 72 had Calgary ≥ -2 (mean 1.80), and 69 had modified Calgary ≥ -3 (mean 1.38). Prodromes were observed in 59 patients, recurrence in 50 and trauma in 19. The response to TT was positive in 54 participants (49 vasovagal, with 39 vasodepressor responses), with an increase in the low frequency (LF) component and a decrease in the high frequency (HF) component (p < 0,0001). In the supine position, LF was 33.6 in females and 47.4 in normalized units for males (p = 0.02). When applying the operating characteristic curve for positive TT, there was no statistical significance for HRV and scores. CONCLUSION: Most children and adolescents with a presumed diagnosis of VVS presented a typical clinical scenario, with a Calgary score ≥ -2, and a predominant vasodepressor response to TT. Greater sympathetic activation was observed in the supine position in males. Calgary scores and sympathetic activation did not predict the response to TT.

FUNDAMENTO: A síncope, na população pediátrica, tem como sua principal causa, a vasovagal (SVV). Sua avaliação deve ser feita por métodos clínicos e o teste de inclinação (TI) pode contribuir para seu diagnóstico. OBJETIVOS: Analisar o perfil clínico, os escores de Calgary e de Calgary modificado, a resposta ao TI e a variabilidade da frequência cardíaca (VFC) de pacientes ≤ 18 anos de idade, com presumida SVV. Comparar as variáveis entre pacientes com resposta positiva e negativa ao TI. MÉTODO: Estudo observacional e prospectivo, com 73 pacientes com idades entre 6 e 18 anos, submetidos à avaliação clínica e ao cálculo dos escores, sem o conhecimento do TI. Este foi feito a 70º sob monitoramento para análise da VFC. Valor-p < 0,05 foi considerado como o critério de significância estatística. RESULTADOS: A mediana de idade foi de 14,0 anos, sendo que 52% eram no sexo feminino, 72 apresentaram Calgary ≥ -2 (média 1,80) e 69 com Calgary modificado ≥ -3 (média 1,38). Ocorreram pródromos em 59 pacientes, recorrência em 50 e trauma em 19. A resposta ao TI foi positiva em 54 (49 vasovagal, com 39 vasodepressora), com aumento do componente de baixa frequência (BF) e diminuição da alta frequência (AF) (p < 0,0001). Na posição supina, o BF foi de 33,6 no sexo feminino e 47,4 em unidades normalizadas no sexo masculino (p = 0,02). Aplicando-se a curva de operação característica para TI positivo, não houve significância estatística para VFC e os escores. CONCLUSÕES: A maioria das crianças e adolescentes com diagnóstico presumido de SVV apresentaram um cenário clínico típico, com escore de Calgary ≥ -2, e resposta vasodepressora predominante ao TI. Verificou-se uma maior ativação simpática na posição supina no sexo masculino. Os escores de Calgary e a ativação simpática não permitiram predizer a resposta ao TI.

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

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

Short-duration head-up tilt test potentiated with sublingual nitroglycerin in suspected vasovagal syncope: the fast Italian protocol.

BACKGROUND: The traditional nitroglycerin (NTG) head-up tilt test (HUTT) is time-consuming and the test duration is a barrier to widespread utilization in clinical practice. It was hypothesized that a short-duration protocol is not inferior to the traditional protocol regarding the positivity rate and has a similar distribution of hemodynamic response. METHODS AND RESULTS: Patients undergoing HUTT were randomized 1:1 to a 10 min passive phase plus a 10 min 0.3 mg NTG if the passive phase was negative (Fast) or to a 20 min passive phase plus a 15 min 0.3 mg NTG if the passive phase was negative (Traditional). A sample size of 277 patients for each group achieved 80% power to detect an expected difference of 0% with a non-inferiority margin of -10% using a one-sided t-test and assuming a significant level alpha of 0.025. A total of 554 consecutive patients (mean age 46.6 ± 19.3 years, 47.6% males) undergoing HUTT for suspected vasovagal syncope were randomly assigned to the Fast (n = 277) or Traditional (n = 277) protocol. A positive response was defined as the induction of syncope in presence of hypotension/bradycardia, and was observed in 167 (60.3%) patients with Fast and in 162 (58.5%) patients with the Traditional protocol. There was a trend of lesser vasodepressor response (14.8% Fast vs. 20.6% Traditional) which was significant during the passive phase (P = 0.01). CONCLUSION: The diagnostic value of the Fast HUTT protocol is similar to that of the Traditional protocol and therefore the Fast protocol can be used instead of the Traditional protocol.

Prevalence of asystole during tilt test-induced vasovagal syncope may depend on test methodology.

This review addresses tilt-testing methodology by searching the literature which reports timing of asystole and loss of consciousness (LOC). Despite the Italian protocol being the most widely adopted, its stipulations are not always followed to the letter of the European Society of Cardiology guidelines. The discrepancies permit reassessment of the incidence of asystole when tilt-down is early, impending syncope, compared with late, established LOC. Asystole is uncommon with early tilt down and diminishes with increasing age. However, if LOC is established as test-end, asystole is more common, and it is age-independent. Thus, the implications are that asystole is commonly under-diagnosed by early tilt-down. The prevalence of asystolic responses observed using the Italian protocol with a rigorous tilt down time is numerically close to that observed during spontaneous attacks by electrocardiogram loop recorder. Recently, tilt-testing has been questioned as to its validity but, in selection of pacemaker therapy in older highly symptomatic vasovagal syncope patients, the occurrence of asystole has been shown to be an effective guide for treatment. The use of head-up tilt test as an indication for cardiac pacing therapy requires pursuing the test until complete LOC. This review offers explanations for the findings and their applicability to practice. A novel interpretation is offered to explain why pacing induced earlier may combat vasodepression by raising the heart rate when sufficient blood remains in the heart.

Clinical Associations of Injuries Caused by Vasovagal Syncope: A Cohort Study From a Tertiary Syncope Unit.

Background Recent research has revealed that vasovagal syncope (VVS) leads to a high incidence of injuries; however, clinical associations of injury are not well-established. We present data from an ongoing VVS cohort and aimed to determine characteristics associated with VVS-related injury. Methods and Results Between 2017 and 2020, consecutive patients ≥18 years of age presenting to a tertiary syncope unit and diagnosed with VVS were included. Clinical characteristics relevant to syncope were obtained for the index episode. The outcome was incidence of injury during VVS, documented by clinical evaluation at the syncope clinic. Among 1115 patients (mean age, 45.9 years; 48% women), 260 injuries (23%) occurred. History of VVS-related injuries (adjusted relative risk [aRR], 1.80 [95% CI, 1.42-2.29]), standing position (aRR, 1.34 [95% CI, 1.06-1.68]), and female sex (aRR, 1.30 [95% CI, 1.06-1.60]) were associated with injury, whereas recurrent VVS (aRR, 0.63 [95% CI, 0.49-0.81]) and syncope in the noon/afternoon (aRR, 0.70 [95% CI, 0.56-0.87]) and evening/night (aRR, 0.43 [95% CI, 0.33-0.57]) compared with morning hours were associated with lower risk. There was a trend for higher rates of injury with overweight/obesity (aRR, 1.23 [95% CI, 0.99-1.54]) and syncope occurring at home (aRR, 1.22 [95% CI, 0.98-1.51]). In a per-syncope analysis considering up to 3 previous episodes (n=2518, 36% traumatic), syncope at home (aRR, 1.33 [95% CI, 1.17-1.51]) and absence of prodromes (aRR, 1.34 [95% CI, 1.09-1.61]) were associated with injury. Conclusions Patient characteristics, VVS presentations, the circumstances, and surroundings can determine the risk of injury. These associations of VVS-related injury identify at-risk individuals and high-risk situations. Future prospective studies are needed to investigate potential strategies for prevention of post-VVS injury in recurrent cases.

Atomoxetine for suppression of vasovagal syncope.

OBJECTIVE: Vasovagal syncope (VVS) is a common clinical condition with few effective medical therapies. The study aimed to evaluate the effectiveness of atomoxetine in suppressing syncope in patients with recurrent VVS. METHODS: This was a retrospective, open-label, observational case series of 12 patients taking atomoxetine for suppression of recurrent vasovagal syncope. We compared syncope frequency in the 1 year before atomoxetine and while subjects were taking atomoxetine. We used novel applications of the Poisson distribution to describe the results as a collection of n = 1 studies. RESULTS: There were 12 subjects, eight female, with a mean age 47 ± 22 years and a mean Calgary Syncope Symptom Score of 2 (diagnostic of vasovagal syncope). The patients received a mean dose of atomoxetine of 66 ± 16 mg (1.06 ± 0.21 mg/kg). The mean follow-up period was 1.21 ± 1.01 years. While taking atomoxetine, 11/12 patients appeared to improve and 7/12 had no syncope in follow-up (p = 0.0046). The annualized syncope frequency decreased from a median 5.5 (IQR 4, 6.75) syncope per year to 0 (IQR 0, 0.88) syncope per year (p = 0.002, Wilcoxon rank-sum test). According to the Poisson distribution, 7/12 subjects significantly improved with p values of < 0.0001 to 0.0235, 3/12 did not faint but had too brief follow-up times to detect significance, and 2/12 did not improve significantly. CONCLUSIONS: In this case series, atomoxetine was a promising oral agent for the prevention of vasovagal syncope. The Poisson distribution permits individual patient-level assessment of improvement and detects insufficient follow-up despite apparent improvement.

The Role of Adenosine and Its Degradation Enzymes - Adenosinedeaminase and Adenosinekinase in Pathogenesis of Vasovagal Syncope.

INTRODUCTION: Adenosine is mediator regulating physiological and pathological processes in organism. It probably plays a role in pathogenesis of vasovagal syncopes (VVS), too. Adenosine, its receptors and degradation enzymes- adenosinedeaminase (ADA) and adenosinekinase (ADK), are called the adenosinergic system. AIM: We aimed to evaluate serum levels of adenosine, ADA and ADK in patients with tilt-induced VVS and compare them to tlit-negative controls. Secondary aim was to compare the levels between the types of VVS and correlate them with hemodynamic parameters. SUBJECTS AND METHODS: Altogether 132 individuals were involved in this study (age 39,88±15,64 years, 51 males). All patients underwent head up tilt test (HUTT) in differential diagnosis of syncope. Blood sampling was performed before and after HUTT. Baseline and stimulated serum levels of adenosine, ADA and ADK were evaluated by ELISA method. RESULTS: HUTT was positive in 91 patients (HUTT+), 41 individuals were negative (HUTT-). HUTT+ patients had higher baseline and stimulated adenosine levels, when compared to HUTT- population. The rise in adenosine was higher in HUTT+ group. On the other hand, the increase of ADA was significantly higher in HUTT- subjects. Among HUTT+ group, the highest adenosine was found during vasodepressoric VVS. CONCLUSION: Adenosinergic system may play role in pathogenesis of VVS. Patients with VVS have higher adenosine levels, that may be caused by attenuated degradation. Adenosine seems to be involved predominantly in vasodepressoric type of VVS. Further research evaluating complex function of adenosinergic system in these patients is needed.

Influence of Age on Magnitude and Timing of Vasodepression and Cardioinhibition in Tilt-Induced Vasovagal Syncope.

BACKGROUND: Cardioinhibition may diminish with age, but the changing balance of cardioinhibition and vasodepression with age has not been quantified, leaving the mechanism of vasovagal syncope (VVS) in old age unclear. OBJECTIVES: This study sought to quantify age-related changes of vasodepression and cardioinhibition in tilt-induced VVS. METHODS: We studied 163 cases of tilt-induced VVS, evoked using the Italian protocol with blood pressure, heart rate, and video-electroencephalographic monitoring. Presyncope was excluded. Cardioinhibition was defined as the heart rate decrease before syncope; asystolic pauses (≥3 seconds) were divided into early and late asystole, ie, beginning early enough to or too late to be the major cause of loss of consciousness. The log-ratio method was used to quantify contributions of cardioinhibition and vasodepression, assessed in 2 10-second periods before the onset of cardioinhibition and before syncope. RESULTS: With increasing age, cardioinhibition decreased, ie, heart rate decreased less and more slowly near syncope (P < 0.0001), while vasodepression increased. Asystolic pauses were less frequent in the older one-half of the group than the younger one-half (26% vs 57%; P < 0.00001), but when it did, late asystole occurred more often (58% vs 15%; P < 0.001). CONCLUSIONS: The shift toward less cardioinhibition and more vasodepression with increased age probably reflects a physiological shift in circulatory control. The weakening of cardioinhibition with age may detract from the efficacy of pacing in older patients with VVS. Cardioinhibition-vasodepression balance should be considered in pacing decisions in older subjects with VVS.

Vasovagal syncope triggered by recent moderate weight loss?

AIM: In adults, the onset of vasovagal syncope is often unexplained. We wished to explore if moderate weight loss triggers the onset of vasovagal syncope (VVS). METHODS: A retrospective case-control study comparing demographic characteristic, syncope symptoms, and tilt-table results of patients who had recently lost weight (n=57), with randomly selected weight-stable patients (n=73), and controls, patients without syncope (n=24). RESULTS: VVS was diagnosed in 480 out of 1,209 clinic patients of whom 57 (11.9%) reported moderate weight loss. The mean (SD) reported weight loss was 11.5 (7) kg over 18.7 (13) months. Age and gender did not differ between groups: in the weight loss, weight stable, and control groups the mean age was 44.8, 45.2, and 44 years respectively; and proportion female 60%, 64%, and 54%. Body weight, mass index and calculated blood volume at presentation were also similar in the different groups. Weight loss preceded or coincided the onset of syncope in 80% of patients; the length of time over which weight loss occurred was associated with the length of time of syncope symptoms, product moment correlation coefficient 0.45, p=0.001. Syncope in childhood and teenage years was less frequent in the weight loss group compared to the weight stable group: 37% vs 53%. After 10 minutes of head-up tilt, stroke volume was preserved in both syncope groups compared to controls; percentage of baseline mean (SD) in the weight loss, weight stable, and control groups: 71(18), 69(10), and 61 (11) respectively; despite lower blood pressure in the weight loss groups with mean (SD) 90 (14) mmHg, 93 (13) and 103 (14) respectively. CONCLUSIONS: Some patients have onset of VVS within a few months of weight loss resulting in earlier presentation to clinic. The physiological mechanism for this is uncertain.