Advance in the understanding of vasovagal syncope in children and adolescents



Vasovagal syncope (VVS) accounts for 60–80% of cases of neurally mediated syncope. VVS results from acute orthostatic intolerance and recurrent syncopal attacks, which can seriously affect an individual’s quality of life. In addition, some children even experience trauma during attacks. Therefore, it is particularly important to clarify the pathogenesis of VVS. The aim of our study is to reveal the latest research progress of VVS.

Data sources

Literature that involved the pathogenesis of VVS were selected from Cochrane Library (1990–2019), EMBASE (1991–2019) and PubMed (1968–2019) databases.


Hypovolemia, autonomic dysfunction, vasomotor dysfunction, baroreceptor reflex abnormalities, endothelial dysfunction, serotonin surges, and gut microbiota were involved in the underlying mechanism of VVS.


VVS is not always a benign prognosis. Various aspects were involved in its pathogenesis. Bezold–Jarish reflex, dysfunction of the autonomic nervous system, genetic factors and so on played important roles in VVS; however, the mechanism remains unclear.

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  1. 1.

    Li H, Liao Y, Han Z, Wang Y, Liu P, Zhang C, et al. Head-up tilt test provokes dynamic alterations in total peripheral resistance and cardiac output in children with vasovagal syncope. Acta Paediatr. 2018;107:1786–91.

    Article  Google Scholar 

  2. 2.

    Yang J, Li H, Ochs T, Zhao J, Zhang Q, Du S, et al. Erythrocytic hydrogen sulfide production is increased in children with vasovagal syncope. J Pediatr. 2015;166:965–9.

    CAS  Article  Google Scholar 

  3. 3.

    Sutton R. Should we treat severe vasovagal syncope with a pacemaker? J Intern Med. 2017;281:554–61.

    CAS  Article  Google Scholar 

  4. 4.

    Kruit MC, Thijs RD, Ferrari MD, Launer LJ, van Buchem MA, van Dijk JG. Syncope and orthostatic intolerance increase risk of brain lesions in migraineurs and controls. Neurology. 2013;80:1958–65.

    Article  Google Scholar 

  5. 5.

    Stewart JM, Medow MS, Sutton R, Visintainer P, Jardine DL, Wieling W. Mechanisms of vasovagal syncope in the young: reduced systemic vascular resistance versus reduced cardiac output. J Am Heart Assoc. 2017;6:e004417.

    PubMed  PubMed Central  Google Scholar 

  6. 6.

    Zygmunt A, Stanczyk J. Heart rate variability in children with neurocardiogenic syncope. Clin Auton Res. 2004;14:99–106.

    Article  Google Scholar 

  7. 7.

    Evrengul H, Tavli V, Evrengul H, Tavli T, Dursunoglu D. Spectral and time-domain analyses of heart-rate variability during head-upright tilt-table testing in children with neurally mediated syncope. Pediatr Cardiol. 2006;27:670–8.

    Article  Google Scholar 

  8. 8.

    Akçaboy M, Atalay S, Uçar T, Tutar E. Heart rate variability during asymptomatic periods in children with recurrent neurocardiogenic syncope. Turk J Pediatr. 2011;53:59–66.

    PubMed  Google Scholar 

  9. 9.

    Köse MD, Bağ Ö, Güven B, Meşe T, Öztürk A, Tavlı V. P-wave dispersion: an indicator of cardiac autonomic dysfunction in children with neurocardiogenic syncope. Pediatr Cardiol. 2014;35:596–600.

    Article  Google Scholar 

  10. 10.

    Zhang QY, Du JB, Wang C, Du ZD, Wang L, Tang CS. The diagnostic protocol in children and adolescents with syncope: a multi-centre prospective study. Acta Paediatr. 2009;98:879–84.

    Article  Google Scholar 

  11. 11.

    Kong Q, Yang X, Cai Z, Pan Y, Wang M, Liu M, et al. Twenty-four-hour urine NE level as a predictor of the therapeutic response to metoprolol in children with recurrent vasovagal syncope. Ir J Med Sci. 2019;188:1279–87.

    CAS  Article  Google Scholar 

  12. 12.

    Chan WL, Lu TM, Wang JJ, Jiau SS, Kong CW. Haemodynamic significance of heart rate in neurally mediated syncope. Clin Cardiol. 2004;27:635–40.

    Article  Google Scholar 

  13. 13.

    Bondanelli M, Alboni P, Margutti A, Franceschetti P, Dinelli M, Gruppillo P, et al. Plasma galanin response to head-up tilt in normal subjects and patients with recurrent vasovagal syncope. Metabolism. 2003;52:315–21.

    CAS  Article  Google Scholar 

  14. 14.

    Alboni P, Dinelli M, Gruppillo P, Bondanelli M, Bettiol K, Marchi P, et al. Haemodynamic changes early in prodromal symptoms of vasovagal syncope. Europace. 2002;4:333–8.

    CAS  Article  Google Scholar 

  15. 15.

    Lin J, Jin H, Du J. Assessment of therapeutic biomarkers in the treatment of children with postural tachycardia syndrome and vasovagal syncope. Cardiol Young. 2014;24:792–6.

    Article  Google Scholar 

  16. 16.

    Benditt DG, Ermis C, Padanilam B, Samniah N, Sakaguchi S. Catecholamine response during haemodynamically stable upright posture in individuals with and without tilt-table induced vasovagal syncope. Europace. 2003;5:65–70.

    CAS  Article  Google Scholar 

  17. 17.

    Liao Y, Chen S, Liu X, Zhang Q, Ai Y, Wang Y, et al. Flow-mediated vasodilation and endothelium function in children with postural orthostatic tachycardia syndrome. Am J Cardiol. 2010;106:378–82.

    Article  Google Scholar 

  18. 18.

    Gallegos A, Márquez-Velasco R, Allende R, Gómez-Flores JR, Cázares-Campos I, González-Hermosillo A. Serum concentrations of nitric oxide and soluble tumor necrosis factor receptor 1 (sTNFR1) in vasovagal syncope: effect of orthostatic challenge. Int J Cardiol. 2013;167:2321–2.

    Article  Google Scholar 

  19. 19.

    Li H, Liao Y, Han Z, Du J, Jin H. The change of c-type natriuretic peptide of vasovagal syncope children in head-up tilt test. Chin J Appl Clin Pediatr. 2017;32:133–6 (in Chinese).

    Google Scholar 

  20. 20.

    Yamashita T, Fujii T, Yamauchi I, Ueda Y, Hirota K, Kanai Y, et al. C-type natriuretic peptide restores growth impairment under enzyme replacement in mice with mucopolysaccharidosis VII. Endocrinology. 2020;161:bqaa008.

    Article  Google Scholar 

  21. 21.

    Hinson JP, Kapas S, Smith DM. Adrenomedullin, a multifunctional regulatory peptide. Endocr Rev. 2000;21:138–67.

    CAS  PubMed  Google Scholar 

  22. 22.

    Abassi Z, Karram T, Ellaham S, Winaver J, Hoffman A. Implications of the natriuretic peptide system in the pathogenesis of heart failure: diagnostic and therapeutic importance. Pharmacol Ther. 2004;102:223–41.

    CAS  Article  Google Scholar 

  23. 23.

    Liao Y, Xu WR, Li HX, Tang CS, Jin HF, Du JB. Plasma neuropeptide Y levels in vasovagal syncope in children. Chin Med J (Engl). 2017;130:2778–844.

    CAS  Article  Google Scholar 

  24. 24.

    Hartl J, Dietrich P, Moleda L, Müller-Schilling M, Wiest R. Neuropeptide Y restores non-receptor-mediated vasoconstrictive action in superior mesenteric arteries in portal hypertension. Liver Int. 2015;35:2556–633.

    CAS  Article  Google Scholar 

  25. 25.

    Morris MJ, Tortelli CF, Hart DP, Delbridge LM. Vascular and brain neuropeptide Y in banded and spontaneously hypertensive rats. Peptides. 2004;25:1313–9.

    CAS  Article  Google Scholar 

  26. 26.

    Jin L, Huang XM, Wang C, Wu L, Lin P. Changes of serum iron and serum ferritin in children with vasovagal syncope. Chin J Appl Clin Pediatr. 2013;28:987–8 (in Chinese).

    Google Scholar 

  27. 27.

    Guven B, Oner T, Tavli V, Yilmazer MM, Demirpence S, Mese T. Low iron storage in children with tilt positive neurally mediated syncope. World J Pediatr. 2013;9:146–51.

    CAS  Article  Google Scholar 

  28. 28.

    Coupal KE, Heeney ND, Hockin BCD, Ronsley R, Armstrong K, Sanatani S, et al. Pubertal hormonal changes and the autonomic nervous system: potential role in pediatric orthostatic intolerance. Front Neurosci. 2019;13:1197.

    Article  Google Scholar 

  29. 29.

    Fu Q, Levine BD. Pathophysiology of neurally mediated syncope: role of cardiac output and total peripheral resistance. Auton Neurosci. 2014;184:24–6.

    CAS  Article  Google Scholar 

  30. 30.

    Fu Q, Verheyden B, Wieling W, Levine BD. Cardiac output and sympathetic vasoconstrictor responses during upright tilt to presyncope in healthy humans. J Physiol. 2012;590:1839–48.

    CAS  Article  Google Scholar 

  31. 31.

    Verheyden B, Liu J, van Dijk N, Westerhof BE, Reybrouck T, Aubert AE, et al. Steep fall in cardiac output is main determinant of hypotension during drug-free and nitroglycerine-induced orthostatic vasovagal syncope. Heart Rhythm. 2008;5:1695–701.

    Article  Google Scholar 

  32. 32.

    Shinohara T, Ebata Y, Ayabe R, Fukui A, Okada N, Yufu K, et al. Cardiac autonomic dysfunction in patients with head-up tilt test-induced vasovagal syncope. Pacing Clin Electrophysiol. 2014;37:1694–701.

    Article  Google Scholar 

  33. 33.

    Huang YJ, Huang M. Research progress of the correlation between genetic polymorphism of candidate genes and vasovagal syncope. Chin J Med. 2015;50:17–20 (in Chinese).

    CAS  Google Scholar 

  34. 34.

    Huang YJ, Zhou ZW, Xu M, Ma QW, Yan JB, Wang JY, et al. Alteration of gene expression profiling including GPR174 and GNG2 is associated with vasovagal syncope. Pediatr Cardiol. 2015;36:475–80.

    Article  Google Scholar 

  35. 35.

    Bai W, Chen S, Tang CS, Qi JG, Cui QH, Xu M, et al. Gut microbiota analysis and its significance in vasovagal syncope in children. Chin Med J (Engl). 2019;132:411–9.

    Article  Google Scholar 

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Author information




LHX has finished the retrieval of literatures and wrote the first draft. GL revised the the first draft. YY analyzed the literatures and revised the first draft. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Yue Yuan.

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Li, HX., Gao, L. & Yuan, Y. Advance in the understanding of vasovagal syncope in children and adolescents. World J Pediatr 17, 58–62 (2021).

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  • Autonomic nervous system
  • Bezold–Jarish reflex
  • Children
  • Genetic pathogenesis
  • Vasovagal syncope