© 2005 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.
SYNCOPE
Distribution of syncopal episodes in children and adolescents with neurally mediated cardiac syncope through the day
lu
l
Gazi University, Medical Faculty, Gazi Hospital, Paediatric Cardiology Department 06500 Be
evler, Ankara, Turkey
Manuscript submitted 20 April 2004. Accepted after revision 19 June 2005.
*Corresponding author. Tel.: +90 312 2025626; fax: +90 312 2025636. E-mail address: kula{at}gazi.edu.tr
Abstract
AIMS: To assess the relation between the timing of syncopal attacks and tilt test positivity.
METHOD AND RESULTS: Prospective comparisons of distribution of syncopal attacks in 49 consecutive neurally mediated cardiac syncope (NMCS) patients (19 boys, 30 girls, mean age 13.7 ± 0.68) were evaluated. Head-up tilt test (HUT) was positive in 28 patients and negative in 21. A questionnaire was given to every patient about the time and number of the syncopal attacks, presyncopal symptoms or signs before HUT. Although syncopal attacks were found to be concentrated in the morning especially between 10 AM and 12 noon in HUT positive patients (P < 0.001), there was a concentration in the late afternoon and evening period of the day especially between 2 PM and 6 PM in HUT negative patients (P < 0.001).
CONCLUSION: It was assumed that diurnal variation in autonomic function may be the factor in the timing of syncopal events during morning hours in the HUT positive NMCS children and adolescents.
Key Words: syncope, tilt test, children, diurnal variation in autonomic nervous system
Introduction
Syncope is defined as a sudden temporary loss of consciousness associated with a loss of postural tone and with spontaneous recovery. Several authors have reported that in the pre-fainting period of neurally mediated syncope (NMS) the functional pattern of the autonomic nervous system modulation of heart and peripheral vessels determines the reflex response leading to hypotension and bradycardia[1,
2].
Since 1986, the tilt-table test (HUT) has become an important tool in the diagnosis of NMS[3]. The tilt-table test yields a range of positive results from 60% to 70%, with a specificity greater than 85%[4].
It has been suggested that sympathetic innervation is more dominant in patients with positive HUT NMS than in HUT negative patients[5]. Also, these HUT positive patients had different circadian rhythms of autonomic nervous function from those with HUT negative patients[6]. So it seemed interesting to investigate the correlation between the time of syncope and tilt test results.
Patients and methods
This study was carried out on 49 consecutive patients with NMS who were referred to our institute for evaluation. All patients underwent HUT. Twenty-eight of the 49 patients were positive (19 female, 9 male). The remaining 11 females and 10 males were negative.
All patients had two or more episodes of transient loss of consciousness (range 2–12) with the median number of 4.98 ± 2.32. The diagnosis of NMS was made from the clinical history, and on the exclusion of cardiac, neurological and psychiatric diseases. Physical examination, electrocardiography and echocardiography were included in the diagnostic work-up of these patients; 24 h Holter, electroencephalography and blood chemistry were also included when necessary[7]. Head-up tilt test protocol was as follows.
The tilt-table test was performed at 10.00 AM for each patient to avoid the effect of diurnal rhythm in the fasting state. A 20–21 gauge intravenous line was placed in the left hand or forearm for medication. Patients were connected to a standard electrocardiographic monitor for continuous evaluation of heart rate and rhythm. A standard sphygmomanometer was used for blood pressure measurement at 3 min intervals. After a 30-min rest period baseline measurements of blood pressure and heart rate were recorded; each patient was positioned at an angle of 60° from horizontal position for up to 45 min on a standard electrically driven tilt table with footboard. An experienced medical person was in attendance throughout the procedure. If syncope or presyncope developed, the table was rapidly lowered to the supine position and the test was stopped; if no syncope occurred the test lasted for 45 min. Patients who had syncope or presyncope were classified as tilt positive, and those who had no response as tilt negative. Response patterns to tilting were classified as follows:
Tilt negative response: no syncope or presyncope symptoms occurred.
Tilt positive response:
- Vasodepressor type syncope: 60% fall in systolic blood pressure (hypotension)
- Cardioinhibitory type syncope: heart rate below 60 bpm (bradycardia)
- Mixed type syncope: hypotension + bradycardia
- Presyncope: symptoms such as dizziness, nausea, fatigue without fainting and minimum 40 mmHg fall in systolic blood pressure
Although according to the updated guidelines on management (diagnosis and treatment) of syncope, presyncope is not accepted as an accurate surrogate for syncope diagnosis[7], we potentially accepted it as a HUT positive result. During HUT testing there was no patient with presyncopal symptoms in our study.
Repeat tilt testing with isoprenaline infusion was not performed.
A questionnaire was given to every patient about the time and number of syncope attacks and presyncopal symptoms. Later, this questionnaire was assessed by a physician who was blinded to the tilt test results.
Statistical analysis
Results were presented as mean values ± SD. Intra- and inter group variables were compared with the paired and unpaired Student's t-test (SPSS for Windows 7.0). P values of <0.05 were considered to be statistically significant.
Results
The mean age of the study group, 19 males and 30 females, was 13.7 ± 0.68 (8–18) years. The age of the patients ranged from 10 to 18 years (mean ± SD, 14 ± 0.72 years) in the HUT positive group, and 8–17 years (mean ± SD, 13.5 ± 0.81 years) in the HUT negative group (Table 1). There was no significant difference regarding age and gender between the groups.
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The blood pressure measurements were not different between groups at baseline (Table 1).
Positive head-up tilt test results were cardioinhibitory in type in 18 patients and vasodepressor in 10 patients. There were no mixed responses and no presyncopal symptoms.
The answers to the questionnaire showed that the number of syncopal episodes were 7.0 ± 1.54 times for HUT positive patients and 2.26 ± 0.83 times in the HUT negative patients. The difference between these groups was significant (P < 0.001) (Table 1).
Time to syncope was 20.46 ± 1.47 (6–36) min during HUT.
Syncopal episodes were found to be concentrated in the morning especially between 10 AM and 12 noon in HUT positive patients (P < 0.001). However, there was a concentration in late afternoon and evening, especially between 2 PM and 6 PM, in patients with a HUT negative response (P < 0.001) (Table 2 and Fig. 1).
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There was no statistical difference between the groups regarding the frequency of syncopal episodes during the remainder of the day.
Discussion
Neurally mediated syncope is the most common cause of syncope in children. Transient insufficiency of autonomic cardiovascular control mechanisms is responsible for this clinical event[8]. As was shown in a previous study, HUT positive patients have greater capacity for noradrenaline storage in cardiac adrenergic neuronal tissue and this led to sympathetic nervous dysfunction in these patients which triggered the Bezold-Jarish reflex[5].
It is known that almost all functions of the cardiovascular system display circadian variations. Also, there are many studies which show circadian rhythm in heart rate and blood pressure in both healthy subjects and cardiac patients[9].
There are some studies which show anginal attacks, myocardial infarcts and sudden death have a peak incidence in the morning hours[10,11]. Also, syncopal attacks in our patients with HUT positive response tended to occur in the morning. As in a previous study, it was shown that there was a significant difference in circadian rhythm of the autonomic nervous system between HUT positive and HUT negative patients assessed by QTc dispersion[6]. It is well known that sympathetic nervous system is very important in the regulation of cardiovascular function. Plasma noradrenaline level is the main mediator of sympathetic activity which also shows circadian rhythm (it is higher in the day and lower at night)[9].
According to these results, it can be assumed that patients with positive HUT test may have important sympathetic nervous activity especially in the morning.
Diurnal variations in autonomic function may, therefore, be a factor in the concentration of syncopal events during the morning hours in HUT positive NMS patients. This finding also corroborates reports of an increase in myocardial infarction and sudden death incidence in the morning hours because of increased sympathetic nervous activity. This point should be considered in the management of patients with NMS.
Study limitations
Head-up tilt test has become an accepted diagnostic tool in the study of neurocardiogenic syncope. But false positive and false negative responses may have influenced the results of this test[12].
References
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[10] Beamar A.D., Lee T.A., Cook E.F., Brand D.A., Rouan G.W., Weisberg M.C., et al. Diagnostic implications for myocardial ischemia of the circadian variation in the onset of chest pain. Am J Cardiol 1987; 60: 998–1002.[CrossRef][Medline]
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