Pathogenesis Of Vasovagal Syncope Research Articles

Abstract 14612: The Relationship Between Left Ventricular Geometry and Respiratory Sinus Arrhythmia in Patients With Vasovagal Syncope

Introduction: The study was prompted by our observation that a significant number of patients with vasovagal syncope (VVS) have marked respiratory sinus arrhythmia as well as thin left ventricular (LV) walls. We hypothesized that the geometry of the LV walls may play a role in the pathogenesis of VVS. Hypothesis: The aim of this study was to assess LV geometry in relationship to respiratory sinus arrhythmia in patients with VVS M ethods: We included 191 patients (age 52±20 years, 101 women) with VVS who had either a positive or negative response to tilt table testing TTT (n=64 TTT+, and n=127 TTT-). The VVS group was compared to a group of 75 patients with no syncope (NL) and similar age, sex and BMI distributions. Standard 12-lead electrocardiograms (ECG), vectorcardiograms, and transthoracic echocardiograms were performed to assess electrical activation as well as ventricular geometry and function. The magnitude of respiratory sinus rhythm arrhythmia was measured as the maximum percent change in RR interval on a 10 second 12-lead ECG (dRR) performed before the TTT. Results: When compared to NL group patients with VVS had significantly higher dRR and LV end diastolic diameter (12 ±8% vs 10±8%, p=0.047 and 44±5 vs 46±6mm p=0.006 respectively) The end-diastolic thickness of the interventricular septum (IVS) and that of the LV posterior wall (PWT) in the VVS group were significantly smaller than in the NL group (8.9±1.7mm vs 9.6±1.8mm p value=0.003 and 8.4±1.5mm vs 9.2±1.6mm p value=0.0002). The magnitude of respiratory sinus arrhythmia expressed as dRR correlated inversely and significantly with IVS (r=-0.32; p value=0.042). The was however no significant correlation between dRR and PWT. These results suggest that a more pronounced respiratory sinus arrhythmia could be related to more ample variations in right and left ventricular filling due to increased ventricular interdependence via a thinner and more compliant ventricular septum. Conclusions: The geometry of the LV as well as the cardiovascular impact of respiratory movements may play a role in the pathogenesis of VVS.

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

IntroductionAdenosine 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. AimWe 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 methodsAltogether 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. ResultsHUTT 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. ConclusionAdenosinergic 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.

The role of neuropeptide Y in the pathogenesis of vasovagal syncope

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Association of Polymorphisms in Endothelin-1 and Endothelin Receptor A Genes With Vasovagal Syncope

The endothelin system may play a role in the pathogenesis of vasovagal syncope (VVS) because it is implicated in blood pressure regulation. We hypothesized that endothelin-related genetic polymorphisms might modulate susceptibility to VVS. This study aimed to evaluate the possible influence of endothelin-1 (EDN1) and endothelin receptor A (EDNRA) gene variants on the occurrence of tilt-induced VVS and autonomic nervous system activity during the head-up tilt test (HUT). Results were expressed as mean +/- SEM. In 254 patients with recurrent syncope (age 45.33+/-1.22 years, 94 males, 160 females), heart rate variability (HRV) was measured during HUT. EDN1 rs5370 G>T and EDNRA rs5333 T>C gene polymorphisms were assessed using high-resolution melting analysis. There was no statistically significant association between polymorphisms EDN1 rs5370 and EDNRA rs5333 and positivity of HUT or hemodynamic types of VVS. Patients with GT or TT genotypes at the rs5370 locus of the EDN1 had significantly higher values of high-frequency (HF) and the standard deviation of the average NN intervals at the time of the syncope, and they tended to have lower low-frequency (LF) and LF/HF ratio when compared to homozygotes (GG). No statistically significant differences were found in HRV parameters concerning the EDNRA rs5333 genotypes. Our findings suggest the potential role of EDN1 rs5370 variants in regulating autonomic nervous activity and pathogenesis of VVS.

Тернопольский национальный медицинский университет имени И.Я. Горбачевского Министерства здравоохранения Украины, г. Тернополь, Украина

Актуальность. Результаты последних научных исследований позволяют предположить, что витамин D может оказывать косвенное, а в некоторых случаях и прямое действие в патогенезе вазовагальных синкопе у детей. Цель исследования: изучить уровни витамина D в сыворотке крови детей с вазовагальными синкопе. Материалы и методы. Основную группу составили 30 детей в возрасте 8–17 лет с как минимум одним эпизодом вазовагального синкопе в течение последнего месяца. В контрольную группу вошли 24 практически здоровых ребенка. 25(ОН)D в сыворотке крови определяли методом иммуноферментного анализа с использованием тест-системы Monobind (США). Оценку витамин-D-статуса осуществляли в соответствии с практическими рекомендациями по добавкам витамина D и лечению дефицита в Центральной Европе: дефицит — < 20 нг/мл; субоптимальный уровень (недостаточность) — 20–30 нг/мл; оптимальный уровень — 30–50 нг/мл; высокое содержание — 50–100 нг/мл; опасный уровень — > 100 нг/мл. Результаты. Дети обеих групп были сопоставимы по результатам демографических и клинических показателей, что позволило нивелировать влияние пола, возраста, дефицита и избыточной массы тела, ожирения или артериальной гипертензии на уровень 25(ОН)D. Показатель 25(ОН)D в группе вазовагальных синкопе составил 19,17 ± 1,33 нг/мл и был достоверно ниже по сравнению со здоровыми детьми — 30,91 ± 1,20 нг/мл (р = 0,000001). Оптимальный уровень витамина D регистрировали только у 6,7 % больных с вазовагальными синкопе, тогда как дефицит и недостаточность витамина D — у 33,3 и 60,0 %. Показатели кальция, фосфора и щелочной фосфатазы в сыворотке крови обследованных обеих групп не отличались (p > 0,05). Выводы. У 93,3 % детей с вазовагальными синкопе наблюдается достоверное снижение уровня 25(OH)D в сыворотке крови. Распространенность дефицита витамина D составляет 60,0 %, субоптимального уровня 25(ОН)D — 33,3 %. Дефицит и недостаточность витамина D ассоциируются с сохранением традиционных показателей кальций-фосфорного гомеостаза в пределах референтных значений.

Heart rate variability and heart rate turbulence in patients with vasovagal syncope.

Aim The autonomic nervous system plays an important role in the pathogenesis of vasovagal syncope, but studies on the effect of basal autonomic tone have found confusing results. The aim of this study was to investigate the effect of basal autonomic functions, as assessed by heart rate variability (HRV) and heart rate turbulence (HRT), in patients with vasovagal syncope.Material and methods Patients who underwent head-up tilt test (HUTT) due to unexplained syncope and who had a 24 hr Holter ECG recording in the same period were retrospectively analyzed. Patients with diabetes, a history of myocardial infarction, heart failure, orthostatic hypotension, atrial fibrillation, or use of vasoactive drugs, such as beta blockers, were excluded from the study. 161 patients who met these criteria were included in the study. Time domain HRV parameters from Holter ECG recordings and HRT parameters from patients with sufficient number of ventricular premature contractions were measured.Results The age of the patients varied from 16 to 75 yrs (mean: 44.8±18.5 yrs). HUTT results of 60 (37.2 %) patients were evaluated as positive. There were no significant differences in the basal demographic, clinical, or laboratory findings of the tilt-positive and tilt-negative patient groups. Likewise, there were no significant differences between the time domain HRV parameters and HRT parameters of both groups.Conclusion HRV and HRT parameters reflecting basal autonomic function were not different between HUTT positive and HUTT negative patient groups. These findings suggest that basal autonomic functions have no effect on vasovagal syncope pathogenesis.

Serum pyridoxine, folate, cobalamin, and homocysteine levels in children presenting with vasovagal syncope.

Recent studies confirm the role of B vitamins deficiency and hyperhomocysteinaemia in the development of dysautonomia that has been considered to be the main factor in vasovagal syncope development. The aim of the study was to investigate serum pyridoxine, folate, cobalamin, and homocysteine levels in children presenting with vasovagal syncope and to analyse the correlation between them and main clinical parameters of syncope. We studied 40 children, ages 8-17 years with a history of vasovagal syncope and 24 healthy volunteers. The serum pyridoxine, folate, cobalamin, and homocysteine levels were measured by a quantitative sandwich enzyme immunoassay technique using a commercial kit (Monobind, USA). Twenty-four-hour Holter monitoring and 24-hour ambulatory blood pressure monitoring were conducted for all participated patients. Serum pyridoxine (9.42±4.87, 16.11±5.53µg/L) and cobalamin (307.48±95.50, 447.28±108.85ng/L) levels were reasonably low (p < 0.05) in patients with vasovagal syncope. Although there was no significant change in folate levels between syncope and healthy children (4.00±1.34, 4.71±1.73µg/L; p = 0.20), we detected low folate-level association with longer duration of syncope (r=-0.42) and post syncope (r=-0.43) symptoms (p < 0.05). Finally, there was increased serum homocysteine level (13.55±5.03, 7.81±1.71µmol/L; p < 0.05) in patients with vasovagal syncope. It was positively correlated with the average PQ interval (r = 0.35, p < 0.05) and average QTc interval (r = 0.49, p < 0.05). The results suggested that pyridoxine, folate, cobalamin, and homocysteine may be involved in the pathogenesis of vasovagal syncope. This might provide a new approach for effective treatment of paediatric vasovagal syncope, requiring further study.

Reduced 24-h Sodium Excretion Is Associated With a Disturbed Plasma Acylcarnitine Profile in Vasovagal Syncope Children: A Pilot Study.

Objective: To investigate if the low sodium intake is associated with the plasma carnitine and acylcarnitine profile in children with vasovagal syncope (VVS).Materials and Methods: Twenty-six children suffering from VVS were recruited in the present study and divided into a group of low urinary sodium excretion or a group of normal urinary sodium excretion according to the excretion of 24-h urinary sodium <3 or 3–6 g, respectively. The excretion of 24-h urinary sodium was detected with ion-selective electrode approach. Plasma carnitine and acylcarnitine concentrations were measured with tandem mass spectrometry. Each participant completed the head-up tilt test. The demographics, clinical characteristics, hemodynamic parameters and plasma carnitine and acylcarnitine concentrations were compared between the two groups. A bivariate correlation between plasma acylcarnitine profiles and the excretion of 24-h urinary sodium was conducted with Spearman's correlation coefficients.Results: Of the enrolled VVS patients, 14 patients were assigned to the group of low urinary sodium excretion and the remaining 12 patients were assigned to the group of normal urinary sodium excretion. Symptoms of fatigue were more prevalent in the group of low urinary sodium excretion than in the group of normal urinary sodium excretion (p = 0.009). Aside from fatigue, no other differences in the demographics, clinical characteristics or hemodynamic parameters during the head-up tilt test were found between the two groups (p > 0.05). Concentrations of plasma tiglylcarnitine (C5:1), hydroxyhexadecanoylcarnitine (C16OH), hydroxyoctadecanoylcarnitine (C18OH), and carnitine C22 were significantly higher in the group of low urinary sodium excretion than in the group of normal urinary sodium excretion (all p-values = 0.048); moreover, they were all negatively correlated with 24-h urinary sodium levels (all p-values = 0.016). There were no differences between the two groups in other acylcarnitines or free carnitine.Conclusions: Reduced excretion of 24-h urinary sodium is associated with a disturbed plasma acylcarnitine profile in children with VVS. The findings suggest that restricted sodium intake-induced disturbance of plasma acylcarnitines and related cellular energy metabolism might be involved in the pathogenesis of VVS in children.

Cardiovascular biomarkers and echocardiographic findings at rest and during graded hypovolemic stress in women with recurrent vasovagal syncope.

Vasovagal reflex is the most common type of syncope but its etiology is not fully elucidated. Venous return and cardiac output are key in hemodynamic control. The aim of the study was to assess cardiovascular biomarkers and echocardiographic measures at rest and during hypovolemia in women with and without a history of vasovagal syncope. Fourteen women (aged 18-30) suffering from recurrent vasovagal syncope and 15 age-matched healthy women were included. Graded lower body negative pressure (LBNP) was used to create central hypovolemic stress until signs of presyncope occurred. Echocardiography was applied at rest and throughout LBNP. Cardiovascular biomarkers: copeptin, mid-regional proadrenomedullin, mid-regional pro-ANP, C-terminal proendothelin-1, and plasma norepinephrine were measured both at rest and throughout graded hypovolemia to presyncope. Women prone to vasovagal syncope presented with a narrower right ventricle (RV) (29 ± 1 vs 32 ± 1 mm, P < .05), smaller left atrium (36 ± 2 vs 47 ± 3 cm3 , P < .01) and lower cardiac output at rest (3.1 ± 0.2 vs 3.7 ± 0.2 L/min, P < .05) and during graded hypovolemia (P < .05). Copeptin was elevated at rest (4.3 ± 0.8 vs 2.5 ± 0.2 pmol/L, P < .05) and increased more in women with vasovagal syncope during progression of LBNP (P < .01). At rest, lower C-terminal proendothelin-1 (35 ± 5 vs 46 ± 2 pmol/L, P < .05) and higher norepinephrine levels (1.1 ± 0.1 vs 0.8 ± 0.1 nmol/L, P < .01) were seen in women with vasovagal syncope. Women prone to vasovagal syncope demonstrate reduced cardiac preload, lower cardiac output, as well as increased release of vasopressin in rest and during hypovolemic challenge. The results emphasize the importance of venous return and cardiac output in the pathogenesis of vasovagal syncope.

Changes in creatine kinase and its isoenzymes in children and adolescents with vasovagal syncope

Objective To investigate the changes in creatine kinase (CK) and its isoenzymes (CK-MB) in children and adolescents with vasovagal syncope(VVS). Methods The VVS group included 150 patients with unexplained syncope or prodromata[69 males and 81 females, aged from 4 to 17 years old, with the average age (11.21±2.40) years old], who had been diagnosed as VVS by using head-up tilt table test(HUTT)in the Second Xiangya Hospital, Central South University from October 2015 to August 2017.The healthy control group included 99 healthy children[58 males and 41 females, aged from 4 to 17 years old, with the average age (10.78±2.26)years old]with gender and age-matched.The differences in serum CK and CK-MB levels between 2 groups were compared, and receiver operating characteristic (ROC) curve was used to explore the predictive value of CK and CK-MB for diagnosing VVS. Results (1)Compared with the healthy control group, both CK[(93.77±33.01)U/L vs.(125.02±58.06) U/L] and CK-MB[(21.31±6.99) U/L vs.(26.93±8.78) U/L] levels decreased in the VVS group, and there were statistically significant differences(all P 0.05). Compared with the healthy control group, CK decreased in all the 3 types of VVS (all P<0.05), while CK-MB decreased only in the vasodepressor type and mixed type (all P<0.05). Conclusions Compared with the healthy children and adolescents, the serum CK and CK-MB levels will decrease in children with VVS, which indicates that CK and CK-MB may be involved in the pathogenesis of VVS. Key words: Vasovagal syncope; Creatine kinase; Creatine kinase isoenzyme; Child; Adolescent

Head-up tilt test provokes dynamic alterations in total peripheral resistance and cardiac output in children with vasovagal syncope.

This study examined the total peripheral vascular resistance (TPVR) and cardiac output changes due to the head-up tilt test (HUTT) in children with vasovagal syncope (VVS). From December 2013 to January 2016, we recruited 77 children diagnosed with VVS group at Peking University First Hospital, China, and 28 children without VVS provided the control group. Heart rate, blood pressure, TPVR, cardiac output and baroreflex sensitivity were monitored during the HUTT. In the supine position, TPVR and baroreflex sensitivity were higher in the patients with VVS than the controls, but cardiac output did not differ between the two groups. There were obvious increases in the VVS patients from TPVR in the supine position to the prepositive response period (p<0.05), then the positive response period (p<0.01). However, we noted the opposite trend in cardiac output, from the supine position to the prepositive response period (p<0.01) then the positive response period (p<0.01). During HUTT, children with VVS demonstrated increases in TPVR but decreases in cardiac output, during the transition from the supine position to the positive response. This response might be involved in the pathogenesis of VVS.

Serum vitamin B-12 in children presenting with vasovagal syncope.

The present study aims to determine the serum vitamin B-12 in children presenting with vasovagal syncope. This is a prospective review of 160 children presenting with vasovagal syncope. Subgroup analysis was done based on the results of head up tilt test. Head up tilt test gave positive results in 80 children and yielded negative results in the remaining 80 children. The tilt test positive children had significantly lower thyroid stimulating hormone concentrations (p=0.06), total iron binding capacity (p=0.04) and serum vitamin B-12 (p=0.01). The prevalence of vitamin B-12 deficiency was significantly higher in the tilt positive group (80% vs 52.5%, p=0.001). Out of 80 children with positive tilt test, 8 children (10%) showed cardioinhibitory response, 22 children (27.5%) demonstrated a vasodepressor response, 24 children (30%) displayed mixed response and 26 children (32.5%) had the postural orthostatic tachycardia syndrome. Erythrocyte sedimentation rate was significantly lower in the mixed response group than in the vasodepressor group (6.2±0.8 mm/h vs 14.3±2.5 mm/h, p=0.001). Serum vitamin B-12 was significantly lower in the postural orthostatic tachycardia syndrome (POTS) group than in the vasodepressor group (240.8±38.2 pg/mL vs 392.7±27.1 pg/mL, p=0.001). The prevalence of vitamin B-12 deficiency was significantly higher in the POTS group than in the vasodepressor group (92.3% vs 45.5%, p=0.001). Vitamin B-12 deficiency causes reduction in myelinization, deceleration in nerve conduction and elevation in serum concentrations of noradrenaline. These factors may contribute to the impairment of autonomic functions which are involved in the pathogenesis of vasovagal syncope.

Self-Organization of Blood Pressure Regulation: Clinical Evidence.

The pathogenesis of vasovagal syncope has remained elusive despite many efforts to identify an underlying dysfunction. Catastrophe theory explains the spontaneous occurrence of sudden events in some mathematically complex systems known as self-organized systems poised at criticality. These systems universally exhibit a power law initially described in earthquake occurrence: the Gutenberg Richter law. The magnitude plotted against the total number of earthquakes of at least this magnitude draw a straight line on log-log graph. We hypothesized that vasovagal syncope is a catastrophe occurring spontaneously in the cardiovascular system. We counted the number and magnitude (number of beats) of vasovagal reactions (simultaneous decreases in both blood pressure and heart rate on consecutive beats) in 24 patients with vasovagal symptoms during a head-up tilt test and 24 paired patients with no symptoms during the test. For each patient, we checked whether vasovagal reaction occurrence followed the Gutenberg Richter law. The occurrence followed the Gutenberg Richter law in 43 patients (correlation coefficient |r| = 0.986 ± 0.001, mean ± SEM) out of 48, with no difference between patients with and without symptoms. We demonstrated that vasovagal syncope matches a catastrophe model occurring in a self-organized cardiovascular complex system poised at criticality. This is a new vision of cardiovascular regulation and its related disorders.

Gene Polymorphism of the Adenosine A2a Receptor in Patients with Vasovagal Syncope.

Adenosine may play a role in the pathogenesis of vasovagal syncope (VVS). The aim of the study was to evaluate the adenosine A(2A) receptor gene 1083 T > C polymorphism in patients with syncope and its possible association with results of head-up tilt test (HUT). Three hundred and forty-seven consecutive patients (mean age 47.3 ± 18.5 years, 132 men, 215 women) with one or more syncopal episodes underwent HUT as part of standardized diagnostic evaluation. HUT was positive in 207 patients (75 males, mean age 44.7 ± 18.6 years) and negative in 140 patients (58 males, mean age 48.17 ± 18.8 years). One thousand and eighty-three T > C single nucleotide polymorphism in the adenosine A(2A) receptor gene (rs5751876) was evaluated in 347 patients with syncope and in 85 subjects without history of syncope (54 men, mean age 41.7 ± 16.3). Adenosine A(2A) receptor 1083 T > C polymorphism was not associated with the positivity of HUT. Blood pressure and heart rate response to tilting was similar in all genotypes. Low frequency (LF) power was significantly lower in CC genotype compared to CT genotype in early phase of tilt (log LF 2.69 ± 0.61 vs 3.20 ± 0.60; P = 0.01) and at the time of syncope (log LF 2.60 ± 0.63 vs 2.77 ± 0.48; P = 0.04). Adenosine A(2A) receptor 1083 T > C polymorphism is not associated with the positivity of HUT and its proposed role in predisposition to VVS was not confirmed. CC genotype may be associated with lower sympathetic activity during HUT.

Erythrocytic Hydrogen Sulfide Production Is Increased in Children with Vasovagal Syncope

To explore the differences in erythrocyte hydrogen sulfide (H2S) production in children with vasovagal syncope (VVS). A total of 54 children including 27 with VVS, aged 6-16 years (mean age 11.3 ± 3.3 years), and 27 healthy children, aged 3-17 years (mean age 10.4 ± 1.8 years) were included in the study. Children with VVS had symptoms of dizziness, pallor, blurred vision, nausea, and some had syncope. Erythrocyte H2S production was measured by a sulphur-sensitive electrode. Flow-mediated dilation (FMD) of brachial artery was measured for each patient by vascular ultrasound. H2S production from erythrocytes was significantly increased in the children with VVS compared with controls (P < .01). The erythrocytic H2S production in the VVS-vasoinhibitory subgroup was obviously higher than that in VVS-cardioinhibitory (P < .05) and VVS-mixed inhibitory subgroups (P < .05). FMD in the VVS-vasoinhibitory subgroup was greater than that in the VVS-cardioinhibitory (P < .05) and the VVS-mixed subgroups (P < .05). The erythrocytic H2S production had a positive linear correlation with FMD in children with VVS (P < .05). Increased erythrocyte H2S production may be involved in the pathogenesis of VVS in children.

The relationship between serum iron deficiency and the pathogenesis of vasovagal syncope

Vasovagal syncope is the most common cause of syncope in children. Its pathogenesis is related to hemodynamics, vasodilation, cerebral blood flow abnormalities, nerve and changes in humoral factors. Body iron deficiency also cause these changes. This paper summarizes the intrinsic link between serum iron deficiency and these changes. Key words: Serum iron; Vasovagal syncope

Autonomic modulation and cardiac contractility in vasovagal syncope

BackgroundPrevious studies proposed as one of the main mechanisms involved in neurally mediated syncope, the stimulation of ventricular mechanoreceptors as the final trigger for vagal discharge. ObjectivesThis study aimed to verify the presence of a sympathetic driven increase of cardiac contractility before vasovagal syncope. MethodsWe studied 23 patients with recurrent syncope. All underwent a 60° tilt with pharmacologic challenge (sublingual spray nitrate). Two conditions were used to assess autonomic activity by heart rate variability analysis: in a supine position after 5 min of rest and after 15 min of tilt. Simultaneously, cardiac contractility was quantified by tissue-Doppler echocardiography at the base of the free walls of left ventricle. The peak myocardial velocities during systole (Sw) and late diastole (Aw) were considered. ResultsPassive tilt induced a significant increase of the low frequency component (LF) as well as a decrease of the high frequency component (HF) in positive patients (LF: from 49±18 to 65±18 nu, p<0.05; HF: from 41±21 to 26±16 nu, p<0.05). Tissue-Doppler showed a similar increase in Sw in both positive and negative patients but showed a significant decrease of Aw in syncopal subjects (p<0.005). ConclusionsOur results do not show an increase in ventricular contractility before tilt-induced syncope, or in presence of a valuable increase of sympathetic activity. Instead, we observe a reduction of atrial contractility, which may be a contributory component in the pathogenesis of vasovagal syncope.

Circadian and Infradian Rhythms of Vasovagal Syncope in Young and Middle‐Aged Subjects

The most cardiovascular physiological and pathophysiological events show a circadian rhythm. It is thought that the autonomic nervous system and biologic factors play a key role in the pathogenesis of vasovagal syncope (VVS). In this study, we investigated the circadian and infradian variation of VVS. A prospective consecutive series of 246 patients (142 women; mean age 36+/-7 years) with recurrent syncope and with a positive head-up tilt testing (HUT) were included in this study. The daily and weekly distributions of the syncopal episodes were investigated. The assessments of episodes were done according to the days of the week and three time periods of the day (6 a.m.-12 noon, 12 noon-6 p.m., 6 pm-12 midnight). According to the results of HUT, 76 patients (31%) had cardioinhibitory, 62 patients (25%) had vasodepressor, and 108 patients (44%) had mixed type of VVS. During the initial passive phase, 40% of patients (99/246) showed positive response. Time to syncope was 20+/-2 minutes during HUT. The mean number of syncopal episodes was 4+/-2/years. In all, 1,070 episodes were evaluated. The distribution of the episodes in 6-hour intervals was significantly different from uniform occurrence (38%, 33%, and 29%, respectively) (P=0.02). The frequency of episodes was higher in the morning (P=0.045) and in the middle of the week (P=0.046). A significant difference was found between week and weekend days in terms of the frequency of episodes (75.5% vs 24.5%, P=0.01). VVS may show a circadian and infradian rhythm.

Minor Psychiatric Disorders and Syncope: The Role of Psychopathology in the Expression of Vasovagal Reflex

Background: A high prevalence of minor psychiatric disorders (MPDs) has been reported in patients with vasovagal syncope (VVS). However, the relationship between the psychiatric substrate and syncope remains unclear. Methods: In order to test the hypothesis that MPDs may predispose to VVS, we assessed the prevalence of syncope, the response to head-up tilt test (HUTT) and the efficacy of psychiatric drug treatment in reducing syncopal episodes, in patients with recently diagnosed MPDs. The response to HUTT was compared with that in an equal number of matched (a) patients with VVS and (b) healthy controls. Results: A high rate of patients with MPDs (58%) had a positive HUTT. Additionally, 45% had a history of syncope; among them, the rate of positive HUTT was identical to that in the VVS group (83%). Following psychiatric drug treatment, the number of patients with syncope decreased in the MPD group (6/67 from 30/67, p < 0.01). Psychiatric symptoms and quality of life were also improved. The number of syncopal spells decreased equally in the MPD and VVS groups (0.6 ± 0.5 from 2.5 ± 1.4, p < 0.01, and 0.7 ± 0.5 from 2.7 ± 1.3, p < 0.01, respectively). Conclusion: A high proportion of patients with MPDs experience syncope, associated with a high rate of positive HUTT, comparable to that observed in VVS. Psychiatric treatment results in the improvement of syncopal and psychiatric symptoms. These findings suggest involvement of co-occurring MPDs in the pathogenesis of VVS. Therefore, the diagnosis and treatment of MPDs, when present, may be crucial for the effective therapy of vasovagal syndrome.

Dynamic Changes of P‐Wave Duration and P‐Wave Axis During Head‐Up Tilt Test in Patients with Vasovagal Syncope

The exact role of venous pooling in the pathogenesis of vasovagal syncope (VVS) is not fully elucidated. P-wave duration on an electrocardiogram can serve as a measure of atrial volume. Sixty-six patients (15 men, 51 women, mean age 32 years) with unexplained syncope were enrolled in the study.P-wave duration and the P-wave axis (PWA) were measured during passive head-up tilt test (HUT) in order to evaluate dynamic changes of atrial filling in patients with VVS. HUT was positive in 40 patients (6 men, 34 women, mean age 32 +/- 9 years) and negative in 26 patients (9 men, 17 women, mean age 33 +/- 8 years). The P-wave duration was significantly reduced in HUT-positive patients at the onset of symptoms as compared to 5 minutes (88.8 +/- 11.9 vs 96.2 +/- 12.0 ms, P = 0.008), and baseline (88.8 +/- 11.9 vs 96.8 +/- 13.8 ms, P = 0.005). The P-wave duration was significantly shorter at the onset of presyncope in HUT-positive patients as compared to HUT-negative patients (88.8 +/- 11.9 vs 100.3 +/- 11.2 ms, P = 0.0002). In HUT-positive patients, a significant increase in PWA was found at the onset of symptoms when compared to baseline (67.7 +/- 22.1 degrees vs 47.9 +/- 14.9 degrees, P < 0.0001) and 5 minutes of HUT (67.7 +/- 22.1 degrees vs 54.4 +/- 14.9 degrees, P = 0.005). At the time of syncope, PWA was more inferior in HUT-positive patients than in HUT-negative patients (67.7 +/- 22.1 degrees vs 51.8 +/- 13.8 degrees, P = 0.015). VVS is associated with the reduction in P-wave duration and the increase in PWA, which can be a result of exaggerated venous pooling and reduction in atrial volume.