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Mechanisms of exercise-related neurocardiogenic syncope and the relationship between resting and dynamic cardiac testing

Published online by Cambridge University Press:  09 January 2025

Bradley J. Conant ,
Kristian C. Becker ,
Garick D. Hill Open the ORCID record for Garick D. Hill [Opens in a new window] ,
Camden L. Hebson ,
Jeffrey B. Anderson ,
Christopher J. Statile ,
Sean M. Lang ,
Kristin Schneider ,
Cameron Thomas  and
Martha W. Willis
...Show all authors
Bradley J. Conant
Affiliation:
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Kristian C. Becker
Affiliation:
Cincinnati Children’s Hospital Medical Center, The Heart Institute, Cincinnati, OH, USA
Garick D. Hill
Affiliation:
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA Cincinnati Children’s Hospital Medical Center, The Heart Institute, Cincinnati, OH, USA
Camden L. Hebson
Affiliation:
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA
Jeffrey B. Anderson
Affiliation:
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA Cincinnati Children’s Hospital Medical Center, The Heart Institute, Cincinnati, OH, USA
Christopher J. Statile
Affiliation:
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA Cincinnati Children’s Hospital Medical Center, The Heart Institute, Cincinnati, OH, USA
Sean M. Lang
Affiliation:
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA Cincinnati Children’s Hospital Medical Center, The Heart Institute, Cincinnati, OH, USA
Kristin Schneider
Affiliation:
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA Cincinnati Children’s Hospital Medical Center, The Heart Institute, Cincinnati, OH, USA
Cameron Thomas
Affiliation:
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Martha W. Willis
Affiliation:
Cincinnati Children’s Hospital Medical Center, The Heart Institute, Cincinnati, OH, USA
Adam W. Powell*
Affiliation:
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA Cincinnati Children’s Hospital Medical Center, The Heart Institute, Cincinnati, OH, USA
*
Corresponding author: Adam W. Powell; Email: [email protected]
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Abstract

Objective:

Syncope is common among pediatric patients and is rarely pathologic. The mechanisms for symptoms during exercise are less well understood than the resting mechanisms. Additionally, inert gas rebreathing analysis, a non-invasive examination of haemodynamics including cardiac output, has not previously been studied in youth with neurocardiogenic syncope.

Methods:

This was a retrospective (2017–2023), single-center cohort study in pediatric patients ≤ 21 years with prior peri-exertional syncope evaluated with echocardiography and cardiopulmonary exercise testing with inert gas rebreathing analysis performed on the same day. Patients with and without symptoms during or immediately following exercise were noted.

Results:

Of the 101 patients (15.2 ± 2.3 years; 31% male), there were 22 patients with symptoms during exercise testing or recovery. Resting echocardiography stroke volume correlated with resting (r = 0.53, p < 0.0001) and peak stroke volume (r = 0.32, p = 0.009) by inert gas rebreathing and with peak oxygen pulse (r = 0.61, p < 0.0001). Patients with syncopal symptoms peri-exercise had lower left ventricular end-diastolic volume (Z-score –1.2 ± 1.3 vs. –0.36 ± 1.3, p = 0.01) and end-systolic volume (Z-score –1.0 ± 1.4 vs. −0.1 ± 1.1, p = 0.001) by echocardiography, lower percent predicted peak oxygen pulse during exercise (95.5 ± 14.0 vs. 104.6 ± 18.5%, p = 0.04), and slower post-exercise heart rate recovery (31.0 ± 12.7 vs. 37.8 ± 13.2 bpm, p = 0.03).

Discussion:

Among youth with a history of peri-exertional syncope, those who become syncopal with exercise testing have lower left ventricular volumes at rest, decreased peak oxygen pulse, and slower heart rate recovery after exercise than those who remain asymptomatic. Peak oxygen pulse and resting stroke volume on inert gas rebreathing are associated with stroke volume on echocardiogram.

Keywords

Cardiopulmonary exercise testingsyncopeinert gas rebreathingechocardiography
Type
Original Article
Information
Cardiology in the Young , First View , pp. 1 - 8
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Copyright
© The Author(s), 2025. Published by Cambridge University Press

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References

Massin, MM, Bourguignont, A, Coremans, C, Comté, L, Lepage, P, Gérard, P. Syncope in pediatric patients presenting to an emergency department. J Pediatr 2004; 145: 223–228. DOI: 10.1016/j.jpeds.2004.01.048.CrossRefGoogle ScholarPubMed
Zavala, R, Metais, B, Tuckfield, L, DelVecchio, M, Aronoff, S. Pediatric syncope: a systematic review. Pediatr Emerg Care 2020; 36: 442–445. DOI: 10.1097/PEC.0000000000002149.CrossRefGoogle ScholarPubMed
Winder, MM, Marietta, J, Kerr, LM et al. Reducing unnecessary diagnostic testing in pediatric syncope: a quality improvement initiative. Pediatr Cardiol 2021; 42: 942–950. DOI: 10.1007/s00246-021-02567-4.CrossRefGoogle ScholarPubMed
Anderson, JB, Willis, M, Lancaster, H, Leonard, K, Thomas, C. The evaluation and management of pediatric syncope. Pediatr Neurol 2016; 55: 6–13. DOI: 10.1016/j.pediatrneurol.2015.10.018.CrossRefGoogle ScholarPubMed
Freeman, R, Wieling, W, Axelrod, FB et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 2011; 21: 69–72. DOI: 10.1007/s10286-011-0119-5.CrossRefGoogle ScholarPubMed
Raj, SR, Biaggioni, I, Yamhure, PC et al. Renin-aldosterone paradox and perturbed blood volume regulation underlying postural tachycardia intolerance. Circulation 2005; 111: 1574–1582. DOI: 10.1161/01.CIR.0000160356.97313.5D.CrossRefGoogle Scholar
Jacob, G, Biaggioni, I, Mosqueda-Garcia, R, Robertson, RM, Robertson, D. Relation of blood volume and blood pressure in orthostatic intolerance. Am J Med Sci 1998; 315: 95–100. DOI: 10.1097/00000441-199802000-00005.Google ScholarPubMed
Hebson, CL, McConnell, ME, Hannon, DW. Pediatric dysautonomia: much-maligned, often overmedicated, but not as complex as you think. Congenit Heart Dis 2019; 14: 156–161. DOI: 10.1111/chd.12720.CrossRefGoogle ScholarPubMed
Jardine, DL, Wieling, W, Brignole, M, Lenders, JWM, Sutton, R, Stewart, J. The pathophysiology of the vasovagal response. Heart Rhythm 2018; 15: 921–929. DOI: 10.1016/j.hrthm.2017.12.013.CrossRefGoogle ScholarPubMed
Fu, Q, Levine, BD. Pathophysiology of neurally mediated syncope: role of cardiac output and total peripheral resistance. Autonom Neurosci 2014; 184: 24–26. DOI: 10.1016/j.autneu.2014.07.004.CrossRefGoogle ScholarPubMed
DiVasta, AD, Alexander, ME. Fainting freshmen and sinking sophomores: cardiovascular issues of the adolescent. Curr Opin Pediatr 2004; 16: 350–356. DOI: 10.1097/01.mop.0000133079.40007.62.CrossRefGoogle ScholarPubMed
Okwose, N, Zhang, J, Chowdhury, S et al. Reproducibility of inert gas rebreathing method to estimate cardiac output at rest and during cardiopulmonary exercise stress testing. Int J Sports Med 2019; 40 : 125–132. DOI: 10.1055/a-0809-5408.Google ScholarPubMed
Fontana, P, Boutellier, U, Toigo, M. Reliability of measurements with innocor during exercise. Int J Sports Med 2009; 30: 747–753. DOI: 10.1055/s-0029-1225340.CrossRefGoogle ScholarPubMed
Sheth, SS, Maxey, DM, Drain, AE, Feinstein, JA. Validation of the innocor device for noninvasive measurement of oxygen consumption in children and adults. Pediatr Cardiol 2013; 34: 847–852. DOI: 10.1007/s00246-012-0555-6.CrossRefGoogle ScholarPubMed
Chwiedź, A, Minarowski, Ł., Mróz, RM, Razak Hady, H. Non-invasive cardiac output measurement using inert gas rebreathing method during cardiopulmonary exercise testing—A systematic review. J Clin Med 2023; 12: 7154. DOI: 10.3390/jcm12227154.CrossRefGoogle ScholarPubMed
Lopez, L, Saurers, DL, Barker, PCA et al. Guidelines for performing a comprehensive pediatric transthoracic echocardiogram: recommendations from the American society of echocardiography. JASE 2024; 37: 119–170. DOI: 10.1016/j.echo.2023.11.015.Google ScholarPubMed
Lopez, L, Colan, SD, Frommelt, PC et al. Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the pediatric measurements writing group of the American society of echocardiography pediatric and congenital heart disease council. JASE 2010; 23: 465–495. DOI: 10.1016/j.echo.2010.03.019.Google ScholarPubMed
Lopez, L, Colan, S, Stylianou, M et al. Relationship of echocardiographic Z scores adjusted for body surface area to age, sex, race, and ethnicity. Circ Cardiovasc Imaging 2017; 10: e006979. DOI: 10.1161/circimaging.117.006979.CrossRefGoogle ScholarPubMed
Powell, AW, Wittekind, SG, Alsaied, T et al. Body composition and exercise performance in youth with a fontan circulation: a bio-impedance based study. J Am Heart Assoc 2020; 9: e018345. DOI: 10.1161/jaha.120.018345.CrossRefGoogle ScholarPubMed
Borg, G. Borg’s Perceived Exertion and Pain Scales. Human Kinetics, 1998.Google Scholar
Cooper, DM, Weiler-Ravell, D, Whipp, BJ, Wasserman, K. Aerobic parameters of exercise as a function of body size during growth in children. J Appl Physiol Respir Environ Exerc Physiol 1984; 56 : 628–634.Google ScholarPubMed
Wasserman, K, Hansen, JE, Sue, DY, Casaburi, R, Whipp, BJ. Principles of Exercise Testing and Interpretation: Including Pathophysiology and Clinical Applications. 3rd edn. Williams & Wilkins, Lippincott, 1999.Google Scholar
Perak, AM, Opotowsky, AR, Walsh, BK et al. Noninvasive cardiac output estimation by inert gas rebreathing in mechanically ventilated pediatric patients. J Pediatr 2016; 177: 184–190.e3. DOI: 10.1016/j.jpeds.2016.07.007.CrossRefGoogle ScholarPubMed
Kakavand, B, Maul, TM, Madueme, P, Dadlani, GH. The effect of cardiac mass and venous return in children with postural orthostatic tachycardia syndrome: a prospective, observational study. Pediatr Cardiol 2023; 44 : 1358–1366. DOI: 10.1007/s00246-023-03113-0.CrossRefGoogle ScholarPubMed
Lavie, CJ, Arena, R, Swift, DL et al. Exercise and the cardiovascular system: clinical science and cardiovascular outcomes. Circ Res 2015; 117: 207–219. DOI: 10.1161/CIRCRESAHA.117.305205.CrossRefGoogle ScholarPubMed
Cole, CR, Blackstone, EH, Pashkow, FJ, Snader, CE, Lauer, MS. Heart-rate recovery immediately after exercise as a predictor of mortality. N Engl J Med 1999; 341; 1351–1357. DOI: 10.1056/NEJM199910283411804.CrossRefGoogle ScholarPubMed
Diller, GP, Dimopoulos, K, Okonko, D et al. Heart rate response during exercise predicts survival in adults with congenital heart disease. J Am Coll Cardiol 2006; 48; 1250–1256. DOI: 10.1016/j.jacc.2006.05.051.CrossRefGoogle ScholarPubMed
Choi, YJ, Kang, KW, Jang, SH, Kim, JG, Lee, SJ, Jung, KT. Heart rate recovery and diastolic blood pressure ratio on the treadmill test predict an induction and recurrence of vasovagal syncope. Korean J Intern Med 2019; 34: 315–323. DOI: 10.3904/kjim.2017.180.CrossRefGoogle ScholarPubMed
Kocabaş, U, Kaya, EB, Aytemir, K et al. A novel method for the diagnosis of neurocardiogenic syncope: heart rate recovery index. Cardiology 2009; 114: 50–55. DOI: 10.1159/000212079.CrossRefGoogle ScholarPubMed
Borresen, J, Lambert, MI. Changes in heart rate recovery in response to acute changes in training load. Eur J Appl Physiol 2007; 101: 503–511. DOI: 10.1007/s00421-007-0516-6.CrossRefGoogle ScholarPubMed
Djaoui, L, Haddad, M, Chamari, K, Dellal, A. Monitoring training load and fatigue in soccer players with physiological markers. Physiol Behav 2017; 181: 86–94. DOI: 10.1016/j.physbeh.2017.09.004.CrossRefGoogle ScholarPubMed
Longin, E, Reinhard, J, von Buch, C, Gerstner, T, Lenz, T, König, S. Autonomic function in children and adolescents with neurocardiogenic syncope. Pediatr Cardiol 2008; 29: 763–770. DOI: 10.1007/s00246-008-9198-z.CrossRefGoogle ScholarPubMed
Tao, C, Tang, C, Chen, S, Jin, H, Du, J. Autonomic nervous function in vasovagal syncope of children and adolescents. Neurosci Bull 2019; 35: 937–940. DOI: 10.1007/s12264-019-00383-8.CrossRefGoogle ScholarPubMed
Reynolds, E, Curry, K, Barton, G, Chandra, A, Crandall, CG, Berry, JD. Impact of the insoluble gas concentration on measured stroke volume at rest and submaximal exercise using the innocor device. Med Sci Sports Exerc 2023; 55: 601–606. DOI: 10.1249/MSS.0000000000003073.CrossRefGoogle ScholarPubMed
Corte, TJ, Wells, AU, Gatzoulis, MA et al. Non-invasive assessment of pulmonary blood flow using an inert gas rebreathing device in fibrotic lung disease. Thorax 2010; 65: 341–345. DOI: 10.1136/thx.2009.121129.CrossRefGoogle ScholarPubMed
Kuhn, M, Hornung, A, Ulmer, H, Schlensak, C, Hofbeck, M, Wiegand, G. Comparative noninvasive measurement of cardiac output based on the inert gas rebreathing method (Innocor®) and MRI in patients with univentricular hearts. Pediatr Cardiol 2018; 39: 810–817. DOI: 10.1007/s00246-018-1824-9.CrossRefGoogle ScholarPubMed
Fu, Q, Verheyden, B, Wieling, W, Levine, BD. Cardiac output and sympathetic vasoconstrictor responses during upright tilt to presyncope in healthy humans. J Physiol, Apr 2012; 590:1839–1848. DOI: 10.1113/jphysiol.2011.224998.CrossRefGoogle ScholarPubMed
Aghajani, F, Tavolinejad, H, Sadeghian, S et al. Implementation of supervised physical training to reduce vasovagal syncope recurrence: a randomized controlled trial. J Cardiovasc Electrophysiol 2022; 33: 1863–1870. DOI: 10.1111/jce.15578.CrossRefGoogle ScholarPubMed
Winker, R, Barth, A, Bidmon, D et al. Endurance exercise training in orthostatic intolerance: a randomized, controlled trial. Hypertension 2005; 45: 391–398. DOI: 10.1161/01.HYP.0000156540.25707.af.CrossRefGoogle ScholarPubMed
George, SA, Bivens, TB, Howden, EJ et al. The international POTS registry: evaluating the efficacy of an exercise training intervention in a community setting. Heart Rhythm 2016; 13: 943–950. DOI: 10.1016/j.hrthm.2015.12.012.CrossRefGoogle Scholar
Fu, Q, Vangundy, TB, Shibata, S, Auchus, RJ, Williams, GH, Levine, BD. Exercise training versus propranolol in the treatment of the postural orthostatic tachycardia syndrome. Hypertension 2011; 58: 167–175. DOI: 10.1161/HYPERTENSIONAHA.111.172262.CrossRefGoogle ScholarPubMed
Galbreath, MM, Shibata, S, VanGundy, TB, Okazaki, K, Fu, Q, Levine, BD. Effects of exercise training on arterial-cardiac baroreflex function in POTS. Clin Auton Res 2011; 21: 73–80. DOI: 10.1007/s10286-010-0091-5.CrossRefGoogle ScholarPubMed
Gibbons, CH, Silva, G, Freeman, R. Cardiovascular exercise as a treatment of postural orthostatic tachycardia syndrome: a pragmatic treatment trial. Heart Rhythm 2021; 18: 1361–1368. DOI: 10.1016/j.hrthm.2021.01.017.CrossRefGoogle ScholarPubMed
Wheatley-Guy, CM, Shea, MG, Parks, JK et al. Semi-supervised exercise training program more effective for individuals with postural orthostatic tachycardia syndrome in randomized controlled trial. Clin Auton Res 2023; 33: 659–672. DOI: 10.1007/s10286-023-00970-w.CrossRefGoogle ScholarPubMed
Teson, KM, Watson, JS, Mays, WA et al. Practices and procedures in clinical pediatric exercise laboratories in North America. Pediatr Exerc Sci 2022; 34: 202–209. DOI: 10.1123/pes.2021-0149.CrossRefGoogle ScholarPubMed
Sajnach-Menke, MA, Walpole, SC. What is the diagnostic value of the paediatric exercise tolerance test? Results from a UK centre. Cardiol Young 2017; 27: 1336–1340. DOI: 10.1017/S1047951117000233.CrossRefGoogle Scholar
Vanbrabant, P, Van Ouytsel, V, Knockaert, D, Gillet, JB. Diagnostic yield of syncope investigation (initiated) in the emergency department: a pilot study. Acta Clin Belg 2011; 66: 110–115. DOI: 10.2143/ACB.66.2.2062528.Google ScholarPubMed
Anderson, JB, Czosek, RJ, Knilans, TK, Marino, BS. The effect of paediatric syncope on health-related quality of life. Cardiol Young 2012; 22: 583–588. DOI: 10.1017/S1047951112000133.CrossRefGoogle ScholarPubMed
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