Introduction
Syncope is the transient loss of consciousness because of cerebral hypoperfusion. However, 15% of the children displayed at least one syncope incident by the age of 18 years. Reference Driscoll, Jacobsen, Porter and Wollan1 The prevalence of syncope in Changsha, China, is 17.37% among children and adolescents aged 2–18 years and occupies 1–2% of paediatric emergencies. Reference Hu, Liu, Chen and Wang2 Vasovagal syncope shows the greatest prevalence among various syncope subtypes, accounting for 74.1% of syncope cases in children and adolescents. Cardiac reasons contribute to approximately 2% of syncopal children; however, such cases display higher mortality rates from sudden cardiac deaths. Hence, determining the aetiology of syncope can be costly and time-consuming because of these reasons. Reference Zhang, Du, Wang, Du, Wang and Tang3 Another study highlighted the importance of history taking and 12-lead standard body surface electrocardiogram in evaluating children with syncope. Reference Zhang, Zhu and Wang4 Furthermore, electrocardiograms have been commonly used to detect structural heart diseases and arrhythmias. Currently, the presence of characteristic manifestations on electrocardiograms of paediatric patients with vasovagal syncope is questionable. Isolated very low QRS voltage of ≤ 0.3 mV in frontal leads can induce positive responses in head-up tilt tests among suspected adult patients with vasovagal syncope. Reference Blendea, McPherson, Pop, Anton, Crisan and Ruskin5 However, whether such electrocardiogram features also exist in paediatric syncope patients remains ambiguous. Hence, this study aimed to evaluate isolated very low QRS voltage in the frontal leads and assess whether isolated very low QRS voltage could be utilised to diagnose vasovagal syncope and predict its recurrence risk.
Materials and methods
We included 118 patients with vasovagal syncope, comprising 70 males and 48 females, with a mean age of 11.4 ± 2.8 years. The study was conducted at the Pediatric Cardiology Department of Peking University First Hospital from January 2020 to January 2021. All patients underwent a head-up tilt test as one of the diagnostic evaluations. According to the Heart Rhythm Society and European Society of Cardiology guidelines, Reference Sheldon, Grubb and Olshansky6,Reference Brignole, Moya and de Lange7 vasovagal syncope can be diagnosed using several clinical characteristics like prodromal symptoms, predisposing situations, postdrome phase, and physical signs denoting reflex mechanism, after excluding competitive diagnoses. Syncope was induced in all patients through long periods of standing in a stuffy and hot environment. The prodromal symptoms included light-headedness, pallor, diaphoresis, nausea, abdominal discomfort, frank vision loss, and a sense of warmth. After fainting, unconsciousness lasted for < 30 s, with no convulsions or urinary incontinence in the supine position. Moreover, the majority of patients reported post-syncopal fatigue. The exclusion criteria were those with left ventricular ejection fraction <40% and patients with overt heart failure, pulmonary hypertension, hypertrophic cardiomyopathy, valvular heart disease, dilated cardiomyopathy, sinus node dysfunction symptoms, supraventricular or ventricular tachycardia, second- or third-degree atrioventricular block, extended QT interval, ventricular preexcitation, arrhythmogenic right ventricular cardiomyopathy, Brugada syndrome, carotid sinus hypersensitivity, symptomatic orthostatic hypotension, subclavian steal syndrome, and nonsyncopal loss of consciousness.
We got approval from the Peking University First Hospital Ethics Committee (2022 [496]). Patients and their parents provided informed consent.
Head-up tilt tests
The positive results of the head-up tilt test were consistent with the previous study’s findings. Reference Qingyou, Junbao and Chaoshu8 The tests were conducted in warm and quiet rooms with subtle lighting in the morning. After fasting for at least 8 hours, all patients discontinued the medications that affected autonomic nerve function for >5 half-lives before testing. Children stayed for 10 min in a supine position to measure heart rate and basal blood pressure. The tilt bed was set at 60° for 45 min or until a positive test occurred. A positive response was defined as obtained in our previous study. All patients’ parents provided complete informed head-up tilt test consent documents.
Twelve-lead electrocardiograms
All children with syncope underwent 12-lead basal electrocardiograms during rest in a supine position with a speed of 25 mm/s speed and 10 mm/mV amplitude. After calibrating for a 25 mm/s paper speed, the QRS voltage measurements were expressed as mm (1 mm = 0.1 mV) in all 12 leads on basal electrocardiogram using the digital callipers under 200% magnification. Moreover, investigators reviewing the electrocardiograms were blinded to head-up tilt test results. Thus, we determined the lowest QRS voltage in precordial and frontal leads, respectively. Isolated very low QRS voltage was defined as the lowest QRS voltage in precordial and frontal leads ≤ 0.3 mV. Reference Blendea, McPherson, Pop, Anton, Crisan and Ruskin5
Follow-up
Our patients were regularly followed up at 4–6-month intervals in the Syncope Clinic Unit for 6–24 months (median, 16 months).
Statistical analysis
SPSS 18.0 version (SPSS Inc., Chicago, IL, USA) was employed for data analysis. The normally distributed continuous and abnormally distributed data were indicated by mean ± standard deviation and median (minimum-maximum) values, respectively. Continuous data were analysed using either the Wilcoxon rank-sum test or the unpaired Student’s t-test. The Shapiro–Wilk test was used to assess the normality of the data distribution. Moreover, categorical data were analysed by Fisher’s exact or Pearson’s X 2 tests for expected frequency <5, respectively. The Kaplan–Meier approach was utilised to depict plot survival, while the log-rank test was used for comparison. A two-tailed p < 0.05 denoted statistical significance.
Results
The study groups’ primary features are presented in Table 1. Based on electrocardiogram parameters, 86 (73%) children displayed isolated very low QRS voltage in frontal leads (Figure 1). However, lead aVL was the lead for displaying isolated very low QRS voltage in 55% of the children, followed by lead I (21%), lead aVF (12%), lead III (11%), and lead aVR (1%), respectively.
Figure 1. A 12-lead electrocardiogram of a paediatric patient with vasovagal syncope and positive tilt-table test. Isolated very low QRS voltage is seen in lead aVL.
Table 1. Clinical characteristics in children with vasovagal syncope with and without isolated very low QRS voltage
VLQV = very low QRS voltage; BMI = body mass index; ORS = oral rehydration solution; HUTT = head-up tilt test.
No significant differences were observed in terms of age, female/male ratio, course of disease, and therapeutic methods in patients with and without isolated very low QRS voltage. When compared to the cases without isolated very low QRS voltage in frontal leads, syncopic spells in the previous 6 months occurred at an enhanced frequency among isolated very low QRS voltage patients (14.5 vs. 6.3, p < 0.05). Children with isolated very low QRS voltage reported a significantly higher frequency of positive head-up tilt test responses than those without isolated very low QRS voltage in the frontal leads (74.4% vs. 53.1%, p < 0.05). During the follow-up period, the syncope recurrence rates for children with and without isolated very low QRS voltage in frontal leads were 64.0% and 28.1%, respectively. Additionally, children with isolated very low QRS voltage in frontal leads displayed an enhanced recurrence rate than those without isolated very low QRS voltage (p < 0.01). Kaplan–Meier curves helped to conduct a time-to-event analysis. The log-rank test suggested a significantly increased syncope recurrence rate in children with isolated very low QRS voltage in frontal leads than those with no isolated very low QRS voltage (p < 0.01, Figure 2).
Discussion
Our results suggested that isolated very low QRS voltage in at least one frontal lead was very frequently seen in children with vasovagal syncope. Isolated very low QRS voltage in frontal leads displayed a higher positive rate of head-up tilt test among the children with vasovagal syncope and induced frequent syncopic spells and their reoccurrence. Thus, these results indicated that isolated very low QRS voltage in at least one frontal lead could be an important electrocardiogram indicator denoting paediatric vasovagal syncope. However, vasovagal syncope in children with isolated very low QRS voltage might have worsened symptoms, frequent syncope episodes, poor treatment response, and enhanced recurrence rates of syncope.
Vasovagal syncope is the most common cause of paediatric syncope. Reference Wang, Li and Liao9 Since syncope is a paroxysmal disorder, paediatricians find diagnosing and treating it challenging. Although precise medical history is the core for diagnosing vasovagal syncope, a few auxiliary tests can be helpful in some conditions. For example, the head-up tilt test can be utilised to identify a few patients without any manifestation of vasovagal syncope. Electrocardiogram is an important part of syncope evaluation. However, electrocardiogram has been mostly used to detect signs of cardiac syncope. Abnormal electrocardiogram values can predict structural cardiac abnormalities (e.g. pulmonary hypertension, hypertrophic cardiomyopathy), conduction system diseases, and signs of inherited arrhythmia syndromes in children experiencing syncope with unknown aetiology. Reference Zhang, J.B., Qin, Chen, Li and Bao10 Moreover, electrocardiograms of patients with vasovagal syncope display a few noticeable characteristics that are closely related to diagnosing and predicting prognosis in such patients. Reference Tentea, Eötvös and Lazar11 For example, the QTd (difference between maximum and minimum QT interval [QTmax and QTmin] on electrocardiogram) rose significantly in the positive head-up tilt test group compared to the negative head-up tilt test group. Furthermore, QTd > 32 ms can be used as a marker of positive head-up tilt test response, according to the study by Khalilian. Reference Bilici, Fidancı-Dedeoğlu and Demir12 Blendea et al. also found that isolated very low QRS voltage in frontal leads could predict positive head-up tilt test results in suspected adult patients with vasovagal syncope Reference Blendea, McPherson, Pop, Anton, Crisan and Ruskin5 ; however, isolated very low QRS voltage in frontal leads also predicted the recurrence of vasovagal syncope, which remained unaffected by other clinical variables. Reference Blendea, McPherson, Pop and Ruskin13 Furthermore, none of the studies have investigated whether isolated very low QRS voltage could also be observed in paediatric patients with vasovagal syncope and if such paediatric vasovagal syncope patients are more prone to recurrence. Thus, we found that isolated very low QRS voltage in at least one frontal lead was a crucial electrocardiogram indicator in paediatric patients with vasovagal syncope.
Nonetheless, the mechanism of isolated very low QRS voltage in frontal leads in paediatric patients with vasovagal syncope is unclear. The lead with the lowest voltage in each patient was almost perpendicular to the QRS axis. However, this finding was different from the specific voltage requirements due to their absence within any frontal lead. Reference Madias14 Blendea et al. suggested that ventricular shape, particularly in vasovagal syncope patients, might be related to elevated cancellation and the resultant decreased lead voltage vertical to the ventricle’s long axis. Reference Blendea, McPherson, Pop and Ruskin13 Additionally, Shalev et al. reported a significant reduction in left ventricular end-systolic dimensions in patients with vasovagal syncope. Reference Shalev, Gal and Tchou15 Moreover, ventricular underfilling and decreased ventricular dimensions in vasovagal syncope might enhance force cancellation along the vertical axis to the ventricle’s long axis. Reference Blendea, McPherson, Pop and Ruskin13 Since electrocardiogram recorded on the body’s surface represents the net non-cancelled potential difference between electrode pairs, this might lead to isolated very low QRS voltage in frontal leads in children with vasovagal syncope.
Our study had certain limitations. First, because of our retrospective design, selection bias might be inevitable. Second, we had a small sample size. Third, as this was a single-centre study, additional research is warranted to evaluate our result’s generalisability. Another limitation is the absence of a healthy control group.
In conclusion, isolated very low QRS voltage in at least one frontal lead predicted positive head-up tilt test results and recurrence risk of syncope in paediatric patients with vasovagal syncope, regardless of their treatment. Thus, our findings might help generate a novel diagnostic indicator and risk factor that determines the recurrence of syncope in children with vasovagal syncope.
Figure 2. Kaplan–Meier survival curves of cumulative syncope-free survival according to the presence of very low QRS voltage (VLQV) in frontal plane leads.
Acknowledgements
None.
Financial support
This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
Competing interests
None.
Ethical standard
All procedures contributing to this work were in accordance with the ethical standards of the institutional and national research committee and with the 1975 Helsinki Declaration and its later amendments or comparable ethical standards and have been approved by the Peking University First Hospital Ethics Committee (2022 [496]). Patients and their parents provided informed consent.
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