Cardiac autonomic patterns preceding occasional vasovagal reactions in healthy humans

BACKGROUND: The wide range of clinical presentation of orthostatic vasovagal syncope suggests different underlying changes in the cardiac autonomic modulation. METHODS AND RESULTS: To evaluate the beat-by-beat modifications in the neural control of heart period preceding a syncopal event, we studied RR interval variability in 22 healthy subjects who experienced fainting for the first time during a 90 degrees head-up tilt and in 22 control subjects by means of time-variant power spectral analysis. Sympathetic and vagal modulations to the sinoatrial node were assessed by the normalized power of the low-frequency (LF, approximately 0.1-Hz) and high-frequency (HF, approximately 0.25-Hz) oscillatory components of RR variability. When the patients were supine, no differences were observed in the hemodynamic and spectral parameters of the 2 groups. During the tilt procedure, RR, LFNU, and HFNU (NU=normalized units) values were relatively stable in control subjects. During early tilt (T1), subjects with syncope had reduced RR intervals compared with control subjects. In 13 subjects with syncope, RR decreased while LFNU and LF/HF increased in the last minute of tilt before syncope (T2). Conversely, in the remaining 9 fainters, LFNU and LF/HF decreased from T1 to T2 and HFNU increased slightly. CONCLUSIONS: Two different patterns may be recognized in the cardiac autonomic changes preceding an occasional vasovagal event, namely, one characterized by a progressive increase of the marker of cardiac sympathetic modulation up to the onset of syncope, the other by a sympathetic inhibition with an impending vagal predominance. The recognition of different pathophysiological mechanisms in fainters may have important therapeutic implications.     

Power spectral analysis of heart rate variability during graded head-up tilting in patients with vasodepressor syncope

1. Two groups of age- and sex-matched subjects, eight healthy controls and 10 patients, suffering from recurrent vasodepressor syncope, participated in a study to examine autonomic function and sequential changes in power distribution of heart rate (HR) variability during graded head-up tilt. 2. The following autonomic function tests were performed: valsalva ratio, HR responses to deep breathing and posture, BP responses to sustained handgrip and postural change. Each subject was tilted at 15 degrees, 30 degrees, 45 degrees, 60 degrees and 80 degrees head-up, each for 15 min, or until symptoms occurred. The eight control subjects completed the tilt study without any symptoms, while all 10 patients developed presyncope and/or syncope at various tilt angles. 3. Resting blood pressure (BP) was lower in the patient group, while resting HR, autonomic function tests and resting HR variability components were similar in the two groups. 4. The control group showed a progressive increase in low frequency power component (LF) from supine to end tilt (delta LF 20.06 +/- 14.50%) and a progressive fall in high frequency (HF) component (delta HF - 24.62 +/- 10.64%). In contrast, in the patient group, LF fell during tilt in the presyncope period (delta LF - 10.57 +/- 12.93%, P < 0.01 vs control group). HF and HF:LF ratio responses did not differ significantly in the two groups. 5. At end tilt, the increase in plasma noradrenaline was significantly greater in the control group than in the patient group (delta NA 0.83 +/- 0.27 vs 0.28 +/- 0.14 pmol/mL, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

A 30-year-old woman with headache

Recent studies have reported a close association between chronic fatigue syndrome and neurally mediated hypotension. We hypothesized that this association may result from an abnormality in autonomic function among patients with chronic fatigue syndrome, which may be detectable using an analysis of heart rate variability. We prospectively studied 19 patients who fulfilled the Centers for Disease Control criteria for chronic fatigue syndrome and 11 controls. Each subject underwent a two-stage tilt-table test while wearing a Holter monitor. Heart rate variability was assessed in the supine baseline position and during upright tilt using frequency domain parameters. In the baseline supine position, high frequency (HF) power, low frequency (LF) power, and the ratio of low frequency power to high frequency power (LF/HF ratio) were similar. In both patient groups, upright tilt resulted in a similar decrease in HF power, increase in LF power, and increase in the LH/HF ratio. In conclusion, autonomic function, as assessed using an analysis of heart rate variability, does not differ in the baseline supine state, nor in response to upright tilt among patients with chronic fatigue syndrome and healthy controls.     

Effects of head-up tilting on vagal nerve activity in man

OBJECTIVES: To evaluate the contribution of the vagal nerve activity in the cardiovascular postural adaptation, effects of decremental head-up tilting (90 degrees, 64 degrees, 53 degrees, 44 degrees, 37 degrees, 30 degrees, 24 degrees, 17 degrees, 12 degrees, 6 degrees and 0 degree) on time- and frequency-domain heart rate variability variables were analyzed in healthy young female. BACKGROUND: During head-up tilting, a hydrostatic venous pooling in the extremities occurs owing to gravity. To pump up the blood toward the upper body, the sympathetic nerve activity has been shown to play an important role. So, to date, few studies evaluated the effects of vagal nerve activity to stabilize the cerebral blood flow during head-up tilting. METHODS: Eight young female volunteers (age, 23.3 +/- 0.8 years; mean +/- SD) were evaluated. The electrocardiogram (ECG) by bipolar chest leads was recorded continuously during procedures, and the bed was tilted at 0.1 interval of sine function of tilting angle from upright position (90 degrees) to supine position (0 degree). The time domain measurements of cycle length variability (co-efficient of variance in percent for R-R intervals [CVRR], number of differences between adjacent R-R intervals that are > 50ms [RR50]) and the frequency domain measurements of low (0.08 to 0.15Hz, LF), high (0.15 to 0.40Hz, HF) and total (0.08 to 0.40, TF) power were performed to assess the cardiac sympathetic and vagal nerve activity. RESULTS: The CVRR showed no significant change during decremental head-up tilting, whereas the RR50 and the square root of HF power, more specific indices of cardiac parasympathetic tone, showed significant negative linear correlations to the sine of the tilting angle. In markers of cardiac sympathetic tone, there were significant positive correlations between the sine of the tilting angle and the normalized LF power or the LF-to-HF power ratio (LF/HF). CONCLUSION: These findings suggest that, in healthy young female, not only cardiac sympathetic nervous system but also cardiac vagal nervous system respond linearly to the change in body axis component of gravity, and they may contribute reciprocally and coordinately to cardiovascular postural adaptation.     

Solitary plasmacytoma of the lung with light chain extracellular deposits: a case report and review of the literature

We studied a possible correlation between autonomic cardiac activity and the level of the red blood cell acetylcholinesterase (AChE) in patients with probable Alzheimer disease (AD). The influence of cholinesterase inhibitor treatment on this autonomic activity was evaluated. Twelve patients satisfying the NINCDS-ADRDA criteria of probable AD and 10 healthy controls were studied. Autonomic cardiac activity was evaluated by means of power spectral analysis (PSA) of heart rate variability (HRV) using an autoregressive algorithm on 250 consecutive electrocardiographic R-R intervals. All patients received oral eptastigmine, a new cholinesterase inhibitor, for 1 month. Before treatment, a simultaneous recording of the electrocardiographic and respiratory activities was performed at rest and subsequently during head-up tilt test at 700. Recording was repeated on the last day of treatment. The level of AChE activity during each recording was also evaluated. Spectrum power was calculated in three main frequency bands: high frequency (HF), 0.15-0.4 Hz; low frequency (LF), 0.04-0.15 Hz; very low frequency (VLF), <0.04 Hz. In addition, we calculated the total spectrum power (TSP) and the LF/HF ratio. The TSP and the absolute value of each spectral component were significantly lower in AD patients than in controls. In contrast with controls, AD patients did not show any significant change before treatment in either the LF and HF components or in the LF/HF ratio during the tilt test. However, the modification in the LF component, induced by tilting, showed a significant correlation with the level of AChE activity (p < 0.03). During the tilt test, the treatment caused changes in LF and HF components and in the LF/HF ratio similar to those observed in controls. These results suggest that the presence of autonomic cardiac dysfunction in AD patients might be due to a cholinergic deficit in the peripheral autonomic nervous system. Some aspects of this autonomic dysfunction can be normalized by cholinesterase inhibitor treatment.     

Comparison of sensitivity and specificity of tilt protocols with and without isoproterenol in children with unexplained syncope

Head-up tilt testing with or without isoproterenol is extensively used in the evaluation of patients with unexplained syncope. However, sensitivity and specificity of tilt protocols with and without isoproterenol have not been clarified in children, due to lack of age matched control subjects. This study was designed to assess and to compare the sensitivity and specificity of tilting alone and tilting in conjunction with isoproterenol. Thirty children with unexplained syncope (group I) and 15 age-matched control subjects (control group I) underwent successive 60 degrees head-up tilts for 10 minutes during infusions of 0.02, 0.04, and 0.06 microgram/kg/min of isoproterenol, after a baseline tilt to 60 degrees for 25 minutes. Also, 35 children (group II) with unexplained syncope and 15 healthy control subjects (control group II) were evaluated by head-up tilt to 60 degrees for 45 minutes without an infusion of isoproterenol. In response to tilt protocol with graded isoproterenol, 23 (76.6%) of the patients in group I and 2 of the 15 (13.3%) control subjects developed syncope. Accordingly, the sensitivity of tilt testing with isoproterenol was 76.6%, and its specificity was 86.7%. Tilt testing without isoproterenol was positive in 17 (48.5%) of the patients in group II but in only 1 of the 15 (6.6%) control subjects. Thus, sensitivity and specificity of tilt testing without isoproterenol were 48.5% and 93.4%, respectively. The mean heart rate and systolic blood pressure decreased significantly (P < 0.001) in all tilt positive patients during syncope. In conclusion, the head-up tilt test is a valuable diagnostic test in the evaluation of children with unexplained syncope, and isoproterenol is likely to increase the sensitivity of the test without decreasing its specificity.     

Improved orthostatic tolerance in familial amyloidotic polyneuropathy with unnatural noradrenaline precursor L-threo-3,4-dihydroxyphenylserine

Disabling orthostatic hypotension, due to insufficiency of the autonomic nervous system, is a common complication of type I familial amyloidotic polyneuropathy (FAP). We investigated whether oral treatment with L-threo-3,4-dihydroxyphenylserine (L-threo-Dops), a noradrenaline precursor, might be of therapeutical benefit. In twenty untreated FAP patients, aged 33 to 44 years, who, because of severe orthostatic hypotension, were bedridden or constrained to a sitting life, supine and erect blood pressure (BP), plasma noradrenaline and tilting time, defined as the interval (s) between the beginning of a 60 degrees head-up tilt and the occurrence of orthostatic symptoms (dizziness, blurred vision or near syncope) were determined before and at repeated intervals during oral treatment with L-threo-Dops, 100 mg bid, for 6 months. Before treatment supine mean BP was 80 (76-85) mmHg (mean and 95% CI), supine plasma noradrenaline was low, 59 (41-77) pg/ml and tilting time ranged from 38 to 118 s. In response to tilt, mean BP immediately fell by 36 (31-41) mmHg, whereas plasma noradrenaline increased by only 11 (0-21) pg/ml (p = 0.05). After 3 to 5 days of treatment with L-threo-Dops all patients experienced marked improvement of their orthostatic tolerance as reflected by their ability to walk freely around. This effect sustained throughout the six months of treatment. Plasma noradrenaline increased moderately by 37 (11-63) pg/ml (p = 0.02) and supine mean BP increased by 8.6 (5.8-12.4) mmHg (p < 0.001) during chronic treatment. Supine or nocturnal hypertension did not develop, the fall in mean BP in response to tilt diminished by 12.5 (6.5-17.3) mmHg (p < 0.001) and tilting time became longer than 600 s in all patients. Because of its efficacy, its sustained duration of action and the lack of side effects, L-threo-Dops is advocated to improve orthostatic tolerance in patients with autonomic insufficiency due to FAP.     

Role of autonomic reflexes in syncope associated with paroxysmal atrial fibrillation

OBJECTIVES: The purpose of this study was to evaluate the role of autonomic reflexes in the genesis of syncope associated with the onset of paroxysmal atrial fibrillation. BACKGROUND: Syncope associated with paroxysmal atrial fibrillation has been interpreted as an ominous finding predictive of rapid ventricular rates. However, various mechanisms may be involved when heart rate is not particularly high. METHODS: Forty patients (age 60 +/- 14 years, 20 men, 20 women) with syncope and atrial fibrillation were compared with atrial fibrillation without syncope. Carotid sinus massage and head-up tilt testing (at 60 degrees for 60 min at baseline and during isoproterenol infusion) were performed during sinus rhythm. A positive response was defined as the induction of syncope. Atrial fibrillation was also induced on a tilt table at 60 degrees by means of short bursts of atrial pacing. RESULTS: Results of carotid sinus massage were positive in 15 (37%) of 40 patients but in no control subjects (p = 0.002). Head-up tilt test findings were positive in 25 (66%) of 38 patients and in 2 (12%) of 16 control subjects (p = 0.0004). The induction of atrial fibrillation in the upright position elicited syncope in 16 (42%) of 38 patients but in none of 16 control subjects (p = 0.001). At the beginning of atrial fibrillation, systolic blood pressure was lower in patients than in control subjects (88 +/- 32 vs. 127 +/- 32 mm Hg), whereas mean heart rate was similar (142 +/- 35 vs. 134 +/- 25 beats/min). The correlation between heart rate and systolic blood pressure was weak (r = 0.35), and in five patients syncope occurred at a heart rate < or = 130 beats/min. At the time of syncope, heart rate decreased (-12 +/- 21 beats/min) in patients with induced syncope, whereas it remained unchanged in patients without induced syncope (+1 +/- 17 beats/min, p = 0.04) or slightly increased in control subjects (+9 +/- 21 beats/min, p = 0.009). CONCLUSIONS: Patients with syncope associated with paroxysmal atrial fibrillation are predisposed to an abnormal neural response during both sinus rhythm and arrhythmia. In some patients the onset of atrial fibrillation triggers vasovagal syncope.     

Cerebral circulation dysfunction and hemodynamic abnormalities in syncope during upright tilt test

OBJECTIVE: To assess the hemodynamic features, including monitoring of cerebral circulation, blood pressure and heart rate, in syncope patients during upright tilt test. DESIGN: Nonrandomized sequential patients with history of syncope of uncertain etiology compared with healthy subjects. SETTING: Noninvasive hemodynamic laboratory of a tertiary referral centre. PATIENTS: Twenty patients with history of syncope and 10 controls without syncope. PROCEDURES: Transcranial Doppler measurement or middle cerebral artery flow velocity, noninvasive and invasive blood pressure monitoring, electrocardiography and pulse oximetry monitoring during upright tilt testing. Measurements were taken in patients at the height of symptoms in supine and upright posture. MAIN RESULTS: Ten patients, while still normotensive, had a drop of 53 +/- 10% (mean +/- SD) in cerebral bloodflow velocity (P = 0.0001) and an increase in heart rate by 58 +/- 35%. The remaining 10 patients had a 58 +/- 15% reduction in cerebral bloodflow velocity (P = 0.0001), a drop in blood pressure of 33 +/- 8% (P = 0.0001) and no change in heart rate. The controls showed no significant changes in cerebral bloodflow velocity and a 25 +/- 12% increase in heart rate (P = 0.0002). CONCLUSIONS: Transcranial Doppler monitoring of cerebral bloodflow velocity during upright tilt testing may improve insight into the complex physiology of syncope.     

Endometrial connexin expression in the mare and pig: evidence for the suppression of cell-cell communication in uterine luminal epithelium

AIMS: To study the dose-response effects of intravenous terbutaline on the cardiovascular and respiratory autonomic nervous regulation. METHODS: The study followed a randomized, placebo-controlled crossover design in six healthy adult volunteers. The terbutaline dose ranged from 10 to 30 microg min(-1) We continuously measured electrocardiogram, finger systolic arterial pressure (SAP) and flow-volume spirometry in supine and upright positions at baseline and during 3 h drug infusion. The periodic variability components of R-R intervals (time between successive heart beats) and SAP in relation to respiration were assessed using spectral analysis techniques. The regularity of the time series was assessed by approximate entropy (ApEn) and the convolutedness by fractal dimension (FD). RESULTS: Terbutaline dose-dependently decreased total variability of R-R intervals, low frequency (LF) variability of R-R intervals (10 s waves), high frequency (HF) variability of R-R intervals (respiratory variability), total variability of SAP, HF variability of SAP, baroreflex sensitivity, plasma potassium concentration, approximate entropy of R-R interval and of SAP as well as fractal dimension of R-R interval. Terbutaline dose-dependently increased heart rate, LF/HF ratios of R-R intervals and of SAP, LF variability of SAP, minute ventilation and plasma terbutaline concentration. CONCLUSIONS: Terbutaline infusion decreases parasympathetic cardiovascular reactivity, baroreflex sensitivity, dimensionality of heart rate and plasma potassium concentration; it increases sympathetic dominance in cardiovascular autonomic balance, minute ventilation, and the regularity of heart rate and blood pressure time series.     

The role of serotonin re-uptake inhibitors in preventing recurrent unexplained childhood syncope -- a preliminary report

To assess the efficacy of a serotonin re-uptake inhibitor, sertraline hydrochloride, in preventing recurrent neurocardiogenic syncope, we studied 15 patients (10 female; mean age 12.9 +/- 2 years) with positive head-upright tilt test and resistant to standard pharmacotherapy, atenolol or disopyramide. The patients were given 50 mg oral sertraline hydrochloride daily for 6 weeks. Intolerance to the drug was seen in 3 patients and 2 had syncopal episodes during the therapy. A head-upright tilt table test was then repeated in 10 patients. Six were tilt negative and asymptomatic over a mean follow up period of 7 +/- 3 months while four remained tilt positive: two experienced marked hypotension and bradycardia, characterized as mixed type syncope, and two had cardiac asystole, lasting > 10 s, during tilting, thereby exhibiting a cardio-inhibitory response. CONCLUSION: Sertraline hydrochloride may be useful in preventing recurrent neurocardiogenic syncope resistant to standard pharmacotherapy but careful clinical studies are essential before such a treatment strategy can be recommended since serious asystole could develop.     

Effects of clonidine on power spectral analysis of heart rate variability in mild essential hypertension

Patients with essential hypertension often show alterations of the autonomic nervous system. We evaluated the sympathetic and parasympathetic drive to the heart in 12 mildly hypertensive patients and 9 healthy subjects by power spectral analysis of heart rate variability. All subjects underwent measurements of RR interval, low (LF) and high frequency (HF) components of heart rate variability, LF/HF ratio and blood pressure in the resting and sitting positions, both before and after oral clonidine (300 microg), a central sympatholytic agent. In the supine position before clonidine, hypertensive patients had higher blood pressure and lower HF values than healthy subjects. Clonidine induced increases in RR interval and HF in both groups, while LF and LF/HF ratio decreased in healthy subjects, but not in hypertensive patients. On assuming the sitting position, both groups showed reductions in RR and HF and increments in LF and LF/HF. In healthy subjects, the response to the postural challenge was unaffected by clonidine. In contrast, hypertensive patients showed no changes in LF and LF/HF ratio, and a significantly lower decrease in HF. These differences were probably due to the existence of two subsets of patients, one exhibiting similar responses to clonidine as healthy subjects, and the other showing no appreciable response to the drug. These results suggest that hypertensive patients have an altered sympatho-vagal balance to the heart, which can be unmasked by clonidine. This phenomenon should be taken into account to achieve a better control of the overall cardiovascular risk of hypertensive patients.     

Heart and autonomic nervous system in connective tissue disorders

Heart rate variability (HRV) is a suitable diagnostic tool in identifying patients with autonomic nervous system (ANS) disorders even in pre-clinical stage. We have enrolled in this study all patients with large variety of connective tissue disorders, given the possibility of an involvement of ANS in these diseases. The study population consisted in eighty-five patients (68 females and 17 males), 35 of whom affected by systemic lupus erythematosus, 16 by rheumatoid arthritis, 14 by Sj?gren syndrome, 12 by progressive systemic sclerosis, 3 by Beh?et syndrome and 5 by antiphospholipid antibodies syndrome. The mean age ranged between 33.7 of patients with lupus erythematosus and 51.8 of those with Sj?gren syndrome. As control, we enrolled healthy subjects of different age, divided into two groups, to rule out the aging as potential source of considered parameters alteration. The autonomic function has been evaluated by 24 hours ambulatory monitoring, using a Zymed 1210 Scanner with Zymed 3.74-PC 1990 software. We have considered: in the time domain, the standard deviation of the RR intervals average (SDNN) and the percentage of RR adjacent intervals differing each other more than 50 msec (pNN50); in the frequency domain, the low (LF) and high (HF) frequencies, the LF/HF ratio, and the total power (RT). The HRV parameters resulted abnormal in every type of the connective tissue diseases considered: particularly SDNN, pNN50, LF, HF and RT (p < or = 0.01). In conclusion: the results of our study suggest that autonomic neuropathy may be present in any kind of connective tissue disorders even in preclinical stage.     

Mycophenolate mofetil, a new immunosuppressive agent. Is pharmacokinetic monitoring justified?

The aim of this study was to evaluate the usefulness of head up tilt testing in patients with syncope of unknown origin. Between January 1994 and September 1995, 93 patients were referred for tilt table assessment due to recurrent syncope of uncertain etiology. There were 42 men (mean age 59 years). Thirty healthy volunteers served as a control group. The specific protocol used involved an initial period of supine rest for 15'. Baseline blood pressure (BP) and heart rate (HR) were recorded. This was followed by a tilt to 80 degrees for 30', BP and HR were measured every minute during the procedure. The test was considered positive when symptoms appeared associated with one of the following responses: systolic BP decreased more than 30 mmHg (vasodepressor), bradicardia or asystolia for up to 3" (cardioinhibitory) or mixed. RESULTS: The tilt test was positive in 31 of 93 patients (33%). Seventeen patients (55%) had a vasodepressor response, 3 patients (9%) a cardioinhibitory response and 11 patients (36%) mixed responses. The clinical manifestations were 62% near syncope, 19% syncope and the other patients presented dypsnea or dizziness. The symptoms disappeared promptly after adopting the supine position. None of the 30 healthy volunteers developed symptoms. We conclude that head up tilt test is a safe and effective method for identifying a neurocardiogenic origin in a syncope of uncertain etiology.     

Sleep position, autonomic function, and arousal

AIMS: To investigate and compare heart rate variability (HRV) and responses of heart rate and arousal to head-up tilting in infants sleeping prone and supine. METHODS: Thirty seven healthy infants aged 2-4 months were studied. HRV was measured for 500 beats while they were in a horizontal position. Subjects were then tilted 60 degrees head-up, and heart rate recorded over 1 minute and arousal responses observed. Data were collected during both quiet and active sleep for both prone and supine sleep positions. RESULTS: HRV, as assessed by the point dispersion of Poincaré plots, was significantly reduced in the prone position for both sleep states. Sleep position did not influence the changes in heart rate seen during a head-up tilt. Full awakening to the tilt was common in active sleep but significantly less so in the prone position (15% of prone tests vs 54% supine). Full awakening to the tilt rarely occurred during quiet sleep in either sleep position. CONCLUSION: This study provides some evidence that blunted arousal responses and/or altered autonomic function are a feature of the prone sleeping position. Decreased HRV may be a sign of autonomic impairment. It is seen in many disease states and in infants who later die of sudden infant death syndrome (SIDS).     

Isoproterenol infusion provokes vasovagal response without upright tilt in a patient exhibiting syncopal episodes

We report a case of a patient with vasovagal syncope, in whom isoproterenol infusion provoked vasovagal response without upright tilting. We subjected the patient, who had had two previous syncopal and several presyncopal episodes, to upright tilting with isoproterenol infusion. Before a control tilt was performed for 10 min (80 degrees), the patient was placed in the supine position for 5 min. The control tilt did not provoke a vasovagal response. With isoproterenol being infused at a dose of 1 mu g/min, the sequence of positioning in the supine position for 5 min and upright tilting for 10 min was repeated. This dose of isoproterenol infusion did not provoke any vasovagal response in the patient, either in the supine or in the upright position. When the dose of isoproterenol infusion was then increased to 2 mu g/min, the heart rate increased to 121/min, but then suddenly dropped to 74/min; systemic arterial pressure simultaneously fell from 148/80 to 108/80 mmHg. The patient complained of palpitation and anxiety, and showed profound cold sweating. The drop in the heart rate and the fall in blood pressure occurred when the patient was in the supine position, indicating that, unlike upright tilting with isoproterenol infusion, venous return was not decreased at the beginning of vasovagal response in this setting. This observation suggests that isoproterenol infusion, even without upright tilting, may provoke the vasovagal response in some patients.     

A multicentre serosurvey on diphtheria immunity in a French population of 1004 subjects

Syncope is a common medical problem with multiple potential causes and it is very frequent in pediatric population . Neurocardiogenic syncope has been increasingly recognized with the introduction of head-up tilt test (HUTT). The study investigates the clinical utility of HUTT in the evaluation and management of children with recurrent syncope and structurally normal heart. Two-hundred-forty-three consecutive young patients with recurrent unexplained syncope, 100 males and 143 females (mean age 11.4 years, range 5 to 20) underwent HUTT using a 60 degree tilt for 45 min. The test was considered positive when it provoked symptoms of syncope with hypotension and/or bradycardia. Twenty-six patients (10.7%) were positive for neurocardiogenic syncope. Of the 26 patients with the positive tilt, 5 (19.2%) had cardioinhibitory response, 5 (19.2%) mixed response and 16(61.6%) vasodepressive response. Nineteen of 143 females (13.3%) and 7 of 100 males (7%) resulted positive (NS). Among patients < 10 years of age 3/41 (9.8%) were positive and among > 10 years 22/202 patients (10.9%) resulted positive (NS). The cardioinhibitory response is more frequent in males (p = 0.01), and the vasodepressive in females (p = 0.05). In our study, concerning a non selected pediatric population a positive test resulted in a lower percentage than previously reported; moreover, the tilt test has appeared a promising method of identifying patients requiring pharmacotherapy. Additional randomized controlled studies are necessary to better define the prognosis and treatment of neurocardiogenic syncope in children and adolescents with positive tilt test. Finally, an assessment of the outcome of young patients with syncope and a negative tilt test is needed.     

Hemodynamic mechanism of vasovagal syncope

Vasovagal syncope is a common clinical problem, however the hemodynamic mechanism is not clearly understood. The aim of the present study was to investigate the circulatory control mechanism of vasovagal syncope provoked by the head-up tilt test. Thirty two patients with recurrent unexplained syncope were studied using a head-up (60 degrees) tilt test. The electrocardiogram, arterial blood pressure, pulmonary arterial pressure and central venous pressure were monitored continuously, and the cardiac output was measured by the thermodilution method. Twenty patients (62.5%) had positive tilt test responses, of which 12 developed typical vasovagal syncope with marked hypotension and bradycardia; the others developed hypotension without bradycardia. There were five women and seven men with a mean age (+/- SD) of 53.3 +/- 15 years. The effect of head-up tilt resembled that of hypovolemia. The central venous pressure, pulmonary capillary wedge pressure and cardiac output declined with an increase of heart rate and systemic vascular resistance. However the mean blood pressure was maintained. During vasovagal syncope, the heart rate and blood pressure fell precipitously and significantly, the cardiac index was reduced from 2.22 +/- 0.43 to 1.51 +/- 0.32 liters/min/m2 (p value < 0.05) and the systemic vascular resistance index decreased from 3,689 +/- 859 to 1,999 +/- 543.9 dynes s cm5/m2 (p value < 0.05). The results of our study showed that both reduction of cardiac output and withdrawal of sympathetic vasoconstriction tone contribute to the development of hypotension in vasovagal syncope.