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Title: Usefulness of tilt test and heart rate variability in diagnosis of syncope in children


The term „syncope” denotes sudden, transient loss of consciousness resulting from temporarily decreased cerebral blood flow accompanied by loss of muscle tone. Consciousness is regained promptly and spontaneously. Syncope episodes pose a common (they occur in 15-50% of children) and serious clinical problem, since they may lead to dangerous injuries or else be a sign of a serious underlying disease. Since syncope is associated with an increased risk of sudden death, it is a source of anxiety for the patients and their families. The following causes of syncope are described: neurogenic (neurocardiogenic), orthostatic, cardiological (resulting from serious cardiac anomalies and diseases or arrhythmias and/or conduction disturbances) and cerebrovascular. Neurocardiogenic syncope (NS) is a sudden loss of consciousness resulting from abnormal autonomous reflex reactions, which affect heart rate variability and peripheral vascular resistance. An inexpensive, simple and effective test in diagnostic management of NS is the tilt test (TT) employed in accordance with the Westminster protocol (the target tilt angle: 60o, duration: 45-60 min., non-invasive blood pressure assessment). There are three general types of reactions to TT, where the basis of diagnosis is determination of the dominant sign: - hypotension (the vasodepressive reaction – VD), - depressed heart rhythm (the cardioinh ; ibitory reaction - CI), - depressed heart rhythm and hypotension (the mixed reaction - MX). Valuable indirect indices of the autonomous system activity, the dysfunction of which leads to neurocardiogenic syncope, include heart rate variability (HRV) detected in 24-hour EKG Holter monitoring. As it follows from the observations of numerous investigators, in individuals with NS, tilting reveals disturbances in sympathetic-parasympathetic balance, manifested by HRV changes, in particular in the value of specific parameters of temporal and frequential HRV analysis. Such balance disturbances are also observed in some patients with mitral valve prolapse (MVP). Assuming that the background of NS and disturbances observed in MVP lies in dysfunction and dyscoordination of the vegetative system components, the analysis of heart rate variability may be of assistance in determination of the incidence of NS and selection of appropriate therapeutic management. The objective of the investigation was: 1. to select from children and adolescents seen due to syncope episodes a group of patients with NS (along with assessment of their age and gender) and to determine the prevalence of NS among other causes of follow-up examinations in patients of Cardiology Outpatient Department, 2. to establish the type of cardiovascular reaction and the time of its occurrence in reaction to TT in childre ; n with NS, 3. to analyze the type of changes in selected temporal and frequential HRV parameters in EKG Holter monitoring as compared to the type of reaction observed during TT in children with NS, 4. to evaluate the type of reaction to TT and HRV result during 24-hour EKG monitoring in children with MVP, 5. to determine whether children with NS without any other cardiac abnormalities and children with MVP and a history of NS, demonstrate disturbances in basic sympathetic-parasympathetic balance, detectable by means of HRV analysis, 6. to develop an examination protocol aiming at optimizing diagnostic management in children and adolescents with syncope of unclear etiology. The clinical material consisted of the total of 185 (103 F and 82 M) children aged between 7.4 and 18.5 years diagnosed at Cardiology Outpatient Department, University Children’s Hospital of Cracow, in the years 2005-2008. The children were divided into three groups: Group 1 - children with NS, Group 2 – patients with MVP, Group 3 – the controls, consisting of normal children. Group 1 included 71 children (41 F and 30 M) aged between 8.75 and 17.8 years (x=13.8 ± 2.21), Group 2 - 62 subjects (35 F and 27 M) aged 7.42-18.5 years (x=14.2± 2.39), and the controls - 52 children (27 F and 25 M) aged 7.75-17.6 years (x=13.2± 2.93). The diagnostic management included subjective and objective clinical a ; ssessment, EKG and chest X-ray, transthoracic echocardiography, tilt test and 24-hour EKG Holter monitoring. In the tilt test, the type of vasovagal reaction and the time of its occurrence were assessed. EKG Holter monitoring allowed for analyzing the following parameters of temporal and frequential HRV analysis: 1. temporal domain: standard deviation of normal RR intervals (SDNN), mean of the standard deviations of RR intervals for all 5-minute segments of the entire recording (SDNNI), standard deviation of all 5-minute mean normal RR intervals (SDANN), root mean square difference among successive RR normal intervals (RMSSD) and percentage of successive RR interval differences > 50 ms (pNN50), 2. frequential domain: low frequency (LF), high frequency (HF) and LF/HF ratio. The results of TT and the values of HRV parameters were compared between Groups 1, 2 and 3. Groups 1 and 2 were additionally subdivided into subgroups with a positive and negative result of the tilt test [TT(+) and TT(-)]. In the thus formed subgroups, correlations were also performed between the reaction to TT and the investigated HRV parameters. p < 0.05 was accepted as denoting statistical significance. Results. Tilt test: In Group 1 (children with NS), TT was positive in 41 (58%) and negative in 30 (42%) subjects. Vasovagal reaction of the MX type was the most commonly observed (24 children), while ; the VD reaction was less frequent (15 children) and the CI reaction was the least common (2 patients). In Group 2 (children with MVP), TT was positive in 18 (28%) and negative in 44 (71%) patients. Also in this group the MX type reaction was the most frequent (12 children), with VD being less common (5 patients), and CI showing the least prevalence (1 child). In Group 3 (the controls), TT was positive only in 2 children (4%), with one patient showing the MX type reaction and the other - VD. The time till the onset of symptoms in TT-positive children ranged from 7 to 57 min. (x = 26.9 ±9.3 min.), amounting, respectively, to 7-54 min., (x = 23 ±10.1 min. - Group 1), 7-57 min, (x = 26.5 ±14.1 min. - Group 2) and 28-34 min., (x = 31 ± 4.2 min. - Group 3). To assess sensitivity and specificity of the tilt test, the author compared TT results in children from Group 1 and 3, arriving at the following results: sensitivity 58%, specificity 96%, positive predictive value 95%, and negative predictive value 63%. The TT results were also analyzed with respect to their dependence on age (in three age groups: <12 years, 12-15 years and >15 years) and gender. In children aged <12 years, the mixed type of reaction (MX) was noted in 4/16 (25%) of Group 1 patients and in 2/9 (22%) of Group 2 children, while the VD type was observed in 5/16 (31%) of Group 1 patients and only in 1 children f ; rom the control group. In children in the 12-15 year age group, MX was seen in 16/33 (48%) of Group 1 patients and only in 6/26 (23%) of Group 2 patients. The VD type was noted in 3/33 (9.1%) of Group 1 patients and in 2/26 (7.7%) of Group 2 patients. Among the oldest children (>15 years), the MX type reaction was found in 4/22 (18.2%) of Group 1 patients and in 4/27 (14.8%) of Group 2 subjects, while the VD type was observed in 7/22 (32%) of Group 1 patients and 3/27 (11.1%) of Group 2 children. In the controls, the MX type was demonstrated in one case only (5.9%). NS was noted to occur non-significantly more often in boys [28/82 (34%)] as compared to girls [33/103 (32%)]. Positive TT results were noted in 19/30 (63%) of Group 1 and 9/27 (33%) of Group 2 boys. Correspondingly, in girls, TT (+) was seen in 22/41 (54%) of Group 1 and 9/35 (26%) of Group 2 subjects. In the controls, TT (+) was seen only in 2 girls. However, in the age group of 12-15 years when Group 1 and 2 were combined, TT was more often positive in girls as compared to boys [Group 1: 11/17(65%) F vs. 9/16 (56%) M, Group 2: 7/15 (47%) F vs. 2/11 (13%) M]. HRV analysis: While comparing the mean values of HRV analysis parameters in children from Groups 1, 2 and 3, no significant differences were noted between the values of SDNN, SDNNI, SDANN and RMSSD in normal children and the two patient groups. On the ; other hand, Group 1 and 2 demonstrated a significant decrease of pNN50 as compared to healthy subjects of Group 3 (Group 1 - 22.7 vs. 24.5 %, p<0.003and Group 2 - 22.1 vs. 24.5 %, p<0.002 ), depressed HF values (Group 1 - 3040.8 vs. 3373.1 ms2, p<0.003 and Group 2 - 2764.5 vs. 3373.1 ms2, p<0.002) and an increased LF/HF ratio (Group 1 - 1.7 vs. 1.3 and Group 2 - 2.1 vs. 1.3). The author also compared the mean values of HRV parameters in children with NS and TT(+), with NS and TT(-) and in Group 3 children. The values of pNN50 showed no significant differences in children with NS and TT(-) as compared to normal children (23.0 vs. 24.5%, p=0.13), but they were significantly different in children with NS and TT(+) and in healthy children (22.5 vs. 24.5%, p<0.003). Although regardless of the TT result, the value of HF in children with NS was lower than the corresponding value in normal children, yet it did not reach the level of statistical significance. The LF/HF ratio in children with NS was statistically higher in children with NS as compared to normal Group 3 children [TT(-) 1.47 vs.1.3, p<0.003 and TT(+) 1.39 vs.1.3, p<0.05]. A similar comparison was carried out between HRV parameters in Group 2 children taking into consideration their TT results and the corresponding values in Group 3 subjects. With the exception of pNN50, also RMSSD was significantly lower in children with ; MVP irrespectively of their TT results when compared to the healthy subjects [RMSSD: TT(-) - 59.8 vs. 67.0 ms, p<0.002 and TT(+) - 54.6 vs. 67.0 ms, p<0.001; pNN50: TT(-) - 23.3 vs. 24.5%, p<0.003 and 19.3 vs. 24.5%, p<0.002 ). The HF power was significantly lower in children with MVP, irrespectively of their TT results, as compared to normal children [TT(-) - 2872.7 vs. 3373.1 ms2, p<0.003 and TT(+) - 2500.0 vs. 3373.1 ms2, p<0.001]. The LF/HF ratio was significantly higher in children with MVP, regardless of their TT results, as compared to healthy children [TT(-) - 2.0 vs. 1.3, p<0.004 and TT(+) - 1.62 vs.1.3, p<0.002 ]. The complex origin of LF may cause the parameter to behave differently in children with NS (showing a decrease: 4329.6 vs. 4367.3 ms2) as compared to children with MVP (demonstrating an increase: 4512.9 vs. 4367.3 ms2). However, in view of the pronounced drop in the HF value in the two compared groups, the LF/HF ratio increased. Changes observed in the 24-hour analysis of HRV, i.e. an increase in the LF/HF ratio and a decrease in the pNN50 and HF values in children with NS and with MVP as compared to the controls support the thesis on disturbed sympathetic-parasympathetic balance in Group 1 and 2 children, with predominance of the sympathetic system. Under favorable conditions, the excessive adrenergic predominance may trigger the Bezold-Jarisch reflex and c ; ause syncope. The above results allowed for formulating the following conclusions: 1. Among children referred to diagnostic management of syncope, patients with NS constitute a significant percentage (approximately 60%). 2. Positive TT results are the most commonly seen in children with NS, showing a preponderance of female gender in the 12-15 years age group, what supports their value in diagnostic management of this type of syncope. 3. In children with MVP without prior history of syncope, TT demonstrates dysfunction of the autonomous system, what under certain conditions may lead to development of NS and also explain other unclear vegetative disturbances that are periodically observed in these patients. 4. The most common vasovagal reaction to TT, irrespectively of the age and gender of patients, is the mixed type (MX), and the least frequent - the cardioinhibitory type (CI), what may indirectly indicate the type of the therapy employed. 5. The time to reaction onset is the shortest in patients with NS, what also indirectly points to a dysfunction of the autonomous system. 6. Some HRV parameters (pNN50, HF, LF/HF) confirm disturbances of the sympathetic-parasympathetic balance in the vegetative nervous system in patients prone to NS; the most important of these parameters is the LF/HF ratio, although no differences have been demonstrated in the results of HRV a ; nalysis depending on the reaction type according to VASIS.

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Level of degree:

2 - studia doktoranckie

Degree discipline:

choroby układu krążenia ; pediatria

Degree grantor:

Wydział Lekarski


Rudziński, Andrzej

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Jul 21, 2022

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ZB-110208 Jul 21, 2022


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