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.     

Response to head-up tilt testing in patients with situational syncope

The results of head-up tilt testing were compared between 24 patients with situational syncope and 44 age-matched patients with typical vasovagal syncope. Patients with situational syncope showed poor positive responses, especially in the passive tilt results (8.3% vs. 39%, p = 0.0078).     

Adhesion of leukocytes to growing arterial thrombi

BACKGROUND: The purpose of this study was to study the effect of enalapril on neurally mediated syncope (NMS). Several agents (except for angiotensin-converting enzyme [ACE] inhibitors) have been used to treat patients with NMS. It is unknown whether ACE inhibitors have beneficial effects on NMS. METHODS AND RESULTS: Thirty subjects who had reproducible NMS induced with head-up tilt table test (HUT) were randomly assigned and divided in double-blind fashion into placebo and enalapril (an ACE inhibitor) groups. Hemodynamics and plasma catecholamine concentrations were studied. Before administration of enalapril, syncope induced by HUT was associated with vigorous hypotension and bradycardia. Plasma catecholamine concentrations were significantly elevated during NMS compared with the supine position before tilt. Oral enalapril rather than placebo produced a marked reduction in diastolic blood pressure during supine positioning before tilt. Administration of enalapril prevented HUT-induced NMS and increase of plasma catecholamine concentrations in all patients examined. Conversely, placebo had no effect in the majority of patients with NMS (12 of 15 subjects). Follow-up data showed that NMS disappeared in 14 (93%) of 15 patients treated with enalapril. CONCLUSIONS: This study demonstrates that ACE inhibitors may efficiently prevent NMS, presumably through inhibition of sympathetic system activation and peripheral hypotensive effect.     

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.     

Time and frequency domain analyses of heart rate variability during orthostatic stress in patients with neurally mediated syncope

The role of autonomic balance during upright tilt in patients with neurally mediated syncope is unclear. To assess the characteristics of autonomic tone during orthostatic stress, 15 patients (mean age 32 years) with recurrent episodes of syncope (> or = 2) and a positive response to a 30-minute 60 degrees upright tilt were compared with the following control groups: (1) 15 patients (mean age 33.5 years) with > or = 2 episodes of recurrent syncope and a negative tilt response, and (2) 15 age- and sex-matched healthy volunteers (mean age 34 years) with no previous history of presyncope or syncope. Time domain measurements assessed were mean RR interval, standard deviation of normal RR intervals, and percentage of normal consecutive RR intervals differing by > 50 ms. Frequency domain measurements of the low-frequency (LF) and high-frequency (HF) bands were obtained, and the LF/HF ratio was also calculated. All variables were calculated in the supine position and during the first 5 minutes of upright tilt. No significant difference was observed in the time and frequency domain variables in the supine position between control groups with a negative head-up tilt response and the group with a positive response. The percentage of normal consecutive RR intervals differing by > 50 ms during the first 5 minutes of head-up tilt was significantly higher in the group with positive tilt tests than in the controls (25 +/- 12% vs 7 +/- 4%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Autonomic nervous function of the patients with neurally mediated syncope

Although diagnosis of neurally mediated syncope (NMS) using head-up tilt (HUT) test has been established, the exact mechanism of NMS has not yet been elucidated. We evaluated beta and alpha-adrenergic function in NMS patients by pharmacological autonomic function test. The alpha-adrenergic sensitivity of NMS patients was significantly lower than that of control subjects. The patients who need low dose isoproterenol for provocation of syncope showed higher beta-adrenergic sensitivity than patients who developed syncope without isoproterenol. Thus, pharmacological autonomic function test was useful for evaluation of NMS patients.     

Observations on midodrine in a case of vasodepressor neurogenic syncope

A 43-year-old man presented with recurrent syncope and dizziness after he had a dual chamber pacemaker fitted for presumed sino-atrial disease. Head-up tilt produced vasodepressor neurocardiogenic syncope, despite appropriate heart rate support during pacing, and reproduced symptoms. Symptoms were not improved by disopyramide. A double-blind cross-over trial of midodrine, an alpha-receptor agonist, was effective in reducing symptoms: it abolished syncope and reduced frequency and severity of dizziness, coupled with improved haemodynamic responses to head-up tilt.     

Long-term effects of pharmacological therapy for vasovagal syncope on the basis of reproducibility during head-up tilt testing

The purpose of this study was to determine the efficacy of long-term pharmacological therapy selected on the basis of a head-up tilt test (HUT) in patients in whom reproducibility of the HUT response was demonstrable in the initial study. The HUT (80 degrees upright) was performed for 15 min with or without an infusion of isoproterenol (0.01-0.03 microgram/kg per min) in 54 patients with recurrent unexplained syncope. When vasovagal syncope was induced (positive response), the HUT was repeated to examine the test reproducibility. Vasovagal syncope was induced in 24 patients during HUT alone, and in 30 patients during the HUT with isoproterenol. Acute reproducibility was observed in 49/54 (91%) patients. In the tilt-positive patients, HUT was repeated after an intravenous administration of propranolol (0.1 mg/kg) or disopyramide (1 mg/kg) (acute test). Propranolol proved effective in 21 (80%) of 26 patients, and disopyramide in 13 (56%) of 23 patients. Thereafter, evaluation was done on the long-term clinical follow-up of the pharmacological intervention selected on the basis of the acute test in the 34 patients in whom the HUT could not induce vasovagal syncope after the oral administration of the pharmacological agent (propranolol 60 mg/day, disopyramide 300 mg/day). Thirty-two of 34 patients (94%) did not develop syncopal attacks during a 44 +/- 12-month period. Thus, in patients with unexplained syncope, HUT appears to have a high degree of acute reproducibility, and the acute drug response guided by HUT may be used to develop an effective long-term pharmacological therapy.     

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.     

Evaluation of the effects of diverse therapeutic treatments versus no treatment of patients with neurocardiogenic syncope

Head-up tilt test was introduced in clinical practice to assess vasovagal syncope and its use has further been extended to evaluate the efficacy of drug administration in these patients. Nevertheless, the effects of tilt test on vasovagal syncope have never been compared with those obtained by ethylephrine or propranolol administration. One hundred and sixty-nine consecutive patients with vasovagal syncope and positive baseline or nitrate-potentiated tilt test (60 degrees upright position for 45 min, or until syncope occurred; 5 mg sublingual isosorbide dinitrate administration if no symptoms occurred) were randomly distributed among three groups: Group A (57 control patients discharged without medical therapy); Group B (56 patients discharged with 75 mg/die ethylephrine); Group C (56 patients discharged with 80 mg/die propranolol). Tilt test was repeated after 1 month, while clinical outcome was evaluated monthly for a mean follow-up of 37.1 +/- 15.6 months. No significant differences in acute tilt-induced syncope recurrence rates were obtained among groups at test repetition since 70.2% of Group A, 69.6% of Group B and 62.5% of Group C experienced syncope. At 3-year follow-up 82.4% of Group A, 83.9% of Group B and 87.5% of Group C (NS among groups) remained symptom free, the most important clinical result being obtained in untreated patients. These data suggest that tilt test execution may prevent syncope recurrence as ethylephrine or propranolol administration. Irrespective of the therapeutical choice, the "controlled reproduction" of symptoms and some psychophysical training of patients to avoid precipitating circumstances, to recognize early symptoms promptly to be reverted by Trendelemburg position, may produce the same clinical improvement as (empiric) ethylephrine or propranolol therapy.     

Urodynamic and cardiovascular measurements in patients with micturition syncope

We describe the findings of urodynamic studies, together with blood pressure and heart rate monitoring, in five patients with micturition syncope. All patients had almost normal storage and evacuation function and no evidence of prostate hypertrophy. Conventional head-up tilt testing with an empty urinary bladder caused no change in arterial blood pressure, but a moderate increase in heart rate. Urinary bladder filling caused minimal increases of the arterial pressure and heart rate. The sitting posture with a distended bladder caused mild orthostatic hypotension. Urinary bladder evacuation caused a fall in arterial pressure with a decrease in heart rate. These responses were similar to those described in vasovagal syncope. The central mechanism for the initiation of urinary evacuation, or sensory input from the lower urinary tract, may trigger micturition syncope.     

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INTRODUCTION: Syncope occasionally may occur in the supine patient due to severe brady- or tachyarrhythmia. However, recurrent syncope upon assumption of the supine position as a result of a neurally mediated reflex mechanism has not been reported previously. METHODS AND RESULTS: Two young patients, both of whom had significant systemic illnesses, experienced recurrent episodes of presyncope and/or syncope shortly after assuming the supine position. During ambulatory ECG monitoring, symptoms were provoked only by lying down and were associated with transient bradycardia. Head-up tilt table testing was undertaken as part of the syncope evaluation and was nondiagnostic in both cases. However, both patients exhibited a transient cardioinhibitory response with reproduction of typical symptoms upon return of the table to the supine position ("reverse tilt"). During follow-up (8 and 14 months), both patients improved with pharmacologic treatment (disopyramide in one case and midodrine in the other). CONCLUSION: Presyncope or syncope upon lying down can be an unusual manifestation of the neurally mediated faint.     

Recurrent unexplained syncope: the role of head-upright tilt table testing

Recurrent episodes of sudden unexplained syncope are a common complaint of patients referred to health care professionals for evaluation. Traditional evaluations are both time consuming and expensive and leave many patients without a diagnosis. Although vasovagally mediated episodes of hypotension and bradycardia have been thought to be a common cause of unexplained syncope, this was traditionally a diagnosis of exclusion. Head-upright tilt table testing has recently emerged as a valuable method for confirming the diagnosis of vasovagal syncope and has allowed a better understanding of this phenomena. This article reviews the pathophysiology of vasovagal syncope, the use of head-upright tilt table testing in its diagnosis, and potential therapies used to prevent recurrences.     

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)     

Prenatal diagnosis by FISH of a 22q11 deletion in two families

OBJECTIVE: To investigate the predictive value of an intravenous fluid bolus during tilt table testing on clinical outcome and to evaluate of oral therapy is an effective treatment for patients with vasodepressor syncope. DESIGN: Retrospective cohort. SETTING: Regional pediatric cardiology outpatient clinic. PATIENTS: Patients (N = 58) with a positive baseline tilt table testing result who were treated with oral fluid therapy between February 1991 and March 1996. INTERVENTIONS AND MAIN OUTCOME MEASURES: Patients with a positive tilt table test result were given an intravenous bolus of isotonic saline solution. Responders were identified as having a negative tilt table test result after the bolus. Patients were prescribed a protocol of oral fluid therapy. Data were obtained from the medical record and a mailed survey. RESULTS: Of the 58 subjects, 90% had no recurrent syncope while receiving oral fluid therapy. During tilt table testing, the mean decrease in mean arterial pressure seen with symptomatic events was lower after the intravenous fluid. The heart rate, which dropped during the initial test, increased during the rests after the intravenous bolus. In the nonresponders, symptomatic episodes occurred significantly later in the tilt table test when given fluids. The response to intravenous fluid bolus had positive predictive value of 92% and negative predictive value of 11% of clinical outcome. CONCLUSIONS: Our data suggest that oral fluid therapy is an effective treatment for vasodepressor syncope in our population. Fluid bolus response during tilt table testing has a high positive but a low negative predictive value of response to oral fluid therapy. We now recommend oral fluid therapy as a primary intervention and reserve tilt table testing for oral fluid therapy failures.     

Tilt table testing of young adult patients: improved speed and sensitivity using an isoproterenol bolus and a continuous 60 degrees tilt

The tilt table is a diagnostic device used to induce vagal syncope and determine etiology. Sensitivity enhancing techniques, such as the administration of isoproterenol, can be applied to children and young adults to compensate for the otherwise low sensitivity (20%-30%) observed in that population. This study describes an improved test that offers a simplified approach while decreasing the amount of time involved by up to 50%, without compromising sensitivity. This 45-minute procedure relies on sensitization with isoproterenol administered as a 2- to 80 micrograms bolus instead of a continuous infusion. The isoproterenol is injected at the 30th minute of a 45-minute 60 degrees tilt test without returning the patient to the supine position. In this study, the isoproterenol bolus tilt test was found to be "positive" in 24 of 30 patients reporting unexplained syncope: 10 cases before the 30th minute (11.2 +/- 8.4 min) and 14 cases after administration of 5.1 +/- 1.9 micrograms of isoproterenol.     

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OBJECTIVE: To determine electroencephalographic (EEG) changes occurring during syncope induced by headup tilt table testing. DESIGN: Prospective observational study. SETTING: Calgary General Hospital Syncope Clinic, Calgary, Alberta. PATIENTS: Eighteen patients with a history of recurrent syncope who developed syncope while undergoing diagnostic isoproterenol tilt table testing. INTERVENTIONS: Continuous EEGs were recorded in 18 sequentially consenting patients while they underwent diagnostic headup tilt table testing. MAIN RESULTS: Patients developed presyncope after 2.6 +/- 2.4 mins and syncope after 3.7 +/- 2.5 minutes. Systolic blood pressure dropped from 117 +/- 17 mmHg to 65 +/- 9 mmHg, and heart rate dropped from 124 +/- 26 beats/min to 65 +/- 27 beats/min. Fourteen patients developed presyncope, while five developed syncope without appreciable presyncope. Abnormal EEGs were recorded in 13 of 14 patients during presyncope and in 18 of 18 patients during syncope. No patients developed EEG abnormalities before the onset of presyncope, and the proportion of patients with EEG abnormalities gradually increased throughout presyncope. During presyncope, theta and delta wave slowing, and background suppression were noted in eight of 14, nine of 14 and one of 14 patients, respectively. During syncope, theta and delta wave slowing, and background suppression were noted in nine of 18, 11 of 18 and six of 18 patients, respectively (not significant versus presyncope). There were strikingly abrupt changes in the EEG rhythm within 15 s of the transition to syncope in 14 of 18 patients. Six patients developed new theta wave slowing, 11 developed new delta wave slowing, and seven developed background suppression. No epileptiform activity was recorded. CONCLUSIONS: Both presyncope and syncope induced by tilt testing are associated with EEG abnormalities, and no single EEG pattern is pathognomonic of either. The transition from presyncope to syncope is marked by abrupt EEG changes.     

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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.