Analysis of heart rate variability during head-up tilt-test in patients with vasovagal syncope
Languages of publication
Introduction Syncope is defined as transient loss of consciousness, due to decrease in brain perfusion. The most frequent mechanism is vasovagal syncope. In many patients, the cause of syncope remains unspecified, despite an extensive diagnostic work-up. Tilt-test (TT) is an acknowledged diagnostic tool for syncope. Currently, the so-called Italian protocol of TT is most widely used. Vasovagal syncope is caused by impaired circulatory regulation in response to orthostatic stress. One of the available tools to examine the influence of the nervous system on the circulation is the analysis of heart rate variability (HRV). Despite numerous publications concerning HRV parameters and autonomic regulation in patients with syncope, direct comparisons and metaanalysis of the results is impossible, due to variability of TT protocols and study group specifications. Aim of the study As there is no uniform model of HRV during TT, we aimed to analyze HRV parameters during TT (performed according to the Italian protocol) in patients with vasovagal syncope, in order to determine the possible application of HRV measurements in clinical practice in that group of patients. Detailed objectives were: (1) analysis and comparison of HRV in patients with and without the history of syncope; (2) analysis of HRV changes in consecutive stages of TT; (3) identification of possible HRV differences between patients with positive and negative TT results. Materials and methods Patients between 18 and 50 years of age were qualified for the study, if they had a history of at least 2 incidents of syncope or presyncope within the preceeding 6 months, and if signs and symptoms indicated the vasovagal mechanism. The study group included 150 patients: 100 consecutive patients with a postive TT result (POS), and 50 consecutive patients with a negative TT result (NEG). The control group (CG) comprised 50 volunteers with no history of syncope nor presyncope, matched according to age and sex to the study group. In all patients a TT was performed according to the Italian protocol, with paced breathing at a rate of 15/min. Time-domain (meanRR, SDNN, RMSSD, pNN50) and frequency-domain (abs_LF, abs_HF, rel_LF, rel_HF, norm_LF, norm_HF, LF/HF) HRV parameters were analyzed and compared at different stages of TT in the study groups as specified above. Results 100 patients at the age of 18-44 years were included in the POS group, 50 patients at the age of 18-39 years in the NEG group, and 50 volunteers at the age of 20-39 in the CG. Volunteers in the control group developed unexpectedly high percentage of positive TT (14 patients). For consistency of analysis, the CG was thus subdivided according to the result of the TT into CG_POS (positive result of TT) – 14 patients, and CG_NEG (negative result of TT) – 36 patients. Based on HRV analaysis, no significant differences in HRV values were noted between patients with a history of syncope and positive or negative result of TT. Upright tilt resulted in HRV changes of the same direction and value in syncopal patients in the POS and NEG goup, as well as in patients in the CG_NEG group. Conclusion HRV values and changes of those values at subsequent stages of TT were not different between syncopal patients with postive or negative TT result, or negative TT control group. The Italian protocol of TT may be associated with a surprisingly high percentage of false positive results.
- Moya A, Sutton R, Ammirati F, Blanc J-J, Brignole M, Dahm JB, et al. Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J. 2009;30(21):2631–2671.
- Blanc J-J, L’Her C, Touiza A, Garo B, L’Her E, Mansourati J. Prospective evaluation and outcome of patients admitted for syncope over a 1 year period. Eur Heart J. 2002;23(10):815–820.
- Colivicchi F, Ammirati F, Melina D, Guido V, Imperoli G, Santini M. Development and prospective validation of a risk stratification system for patients with syncope in the emergency department: the OESIL risk score. Eur Heart J. 2003;24(9):811–819.
- Disertori M, Brignole M, Menozzi C, Raviele A, Rizzon P, Santini M, et al. Management of patients with syncope referred urgently to general hospitals. Eur Eur pacing, arrhythmias, Card Electrophysiol J Work groups Card pacing, arrhythmias, Card Cell Electrophysiol Eur Soc Cardiol. 2003;5(3):283–291.
- Kapoor WN, Karpf M, Maher Y, Miller RA, Levey GS. Syncope of unknown origin. The need for a more cost-effective approach to its diagnosis evaluation. JAMA J Am Med Assoc. 1982;247(19):2687–2691.
- Sarasin FP, Louis-Simonet M, Carballo D, Slama S, Rajeswaran A, Metzger JT, et al. Prospective evaluation of patients with syncope: a population-based study. Am J Med. 2001;111(3):177–184.
- Calkins H, Byrne M, el-Atassi R, Kalbfleisch S, Langberg JJ, Morady F. The economic burden of unrecognized vasodepressor syncope. Am J Med. 1993;95(5):473–479.
- Kleinknecht RA, Lenz J. Blood/injury fear, fainting and avoidance of medically-related situations: a family correspondence study. Behav Res Ther. 1989;27(5):537–547.
- Camfield PR, Camfield CS. Syncope in childhood: a case control clinical study of the familial tendency to faint. Can J Neurol Sci. 1990;17(3): 306–308.
- Soteriades ES, Evans JC, Larson MG, Chen MH, Chen L, Benjamin EJ, et al. Incidence and prognosis of syncope. N Engl J Med. 2002;347(12): 878–885.
- Blanc J-J, Benditt DG. Vasovagal Syncope: Hypothesis Focusing on Its Being a Clinical Feature Unique to Humans. J Cardiovasc Electrophysiol. 2016 May;27(5):623–629.
- Barón-Esquivias G, Pedrote A, Cayuela A, Valle JI, Fernández JM, Arana E, et al. Long-term outcome of patients with asystole induced by head-up tilt test. Eur Heart J. 2002;23(6):483–489.
- Grimm W, Degenhardt M, Hoffman J, Menz V, Wirths A, Maisch B. Syncope recurrence can better be predicted by history than by head-up tilt testing in untreated patients with suspected neurally mediated syncope. Eur Heart J. 1997;18(9):1465–1469.
- Natale A, Geiger MJ, Maglio C, Newby KH, Dhala A, Akhtar M, et al. Recurrence of neurocardiogenic syncope without pharmacologic interventions. Am J Cardiol. 1996;77(11):1001–1003.
- Ruiz GA, Peralta A, Gonzalez-Zuelgaray J, Duce E. Evolution of patients with clinical neurocardiogenic (vasovagal) syncope not subjected to specific treatment. Am Heart J. 1995;130(2):345–350.
- Brignole M, Menozzi C, Del Rosso A, Costa S, Gaggioli G, Bottoni N, et al. New classification of haemodynamics of vasovagal syncope: beyond the VASIS classification. Analysis of the pre-syncopal phase of the tilt test without and with nitroglycerin challenge. Vasovagal Syncope International Study. Europace. 2000;2(1):66–76.
- Alboni P, Brignole M, Degli Uberti EC. Is vasovagal syncope a disease? Eur Eur pacing, arrhythmias, Card Electrophysiol J Work groups Card pacing, arrhythmias, Card Cell Electrophysiol Eur Soc Cardiol. 2007;9(2):83–87.
- Bartoletti A, Alboni P, Ammirati F, Brignole M, Del Rosso A, Foglia Manzillo G, et al. “The Italian Protocol”: a simplified head-up tilt testing potentiated with oral nitroglycerin to assess patients with unexplained syncope. Eur Eur pacing, arrhythmias, Card Electrophysiol J Work groups Card pacing, arrhythmias, Card Cell Electrophysiol Eur Soc Cardiol. 2000;2(4):339–342.
- 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(12):1694–1701.
- Sutton R. The Value of Tilt Testing and Autonomic Nervous System Assessment. Cardiol Clin. 2015;33(3):357–360.
- Kenny RA, Ingram A, Bayliss J, Sutton R. Head-up tilt: a useful test for investigating unexplained syncope. Lancet. 1986;1(8494):1352–1355.
- Zyśko D, Fedorowski A, Nilsson D, Rudnicki J, Gajek J, Melander O, et al. Tilt testing results are influenced by tilt protocol. Europace. 2016;18(7):1108–1112.
- Lee AKY, Krahn AD. Evaluation of syncope: focus on diagnosis and treatment of neurally mediated syncope. Expert Rev Cardiovasc Ther. 2016;14(6):725–736.
- Kim T-H, Jang H-J, Kim S, Cho SY, Song KS, Pickett C, et al. A new test for diagnosing vasovagal syncope: Standing after treadmill test with sublingual nitrate administration. Fukumoto Y, editor. PLoS One. 2017;12(6):e0179631.
- Chaddha A, Wenzke KE, Brignole M, Wasmund SL, Page RL, Hamdan MH. The Role of the Baroreflex in Tilt Table Testing. JACC Clin Electrophysiol. 2016;2(7):812–817.
- Brignole M, Alboni P, Benditt DG, Bergfeldt L, Blanc J-J, Bloch Thomsen PE, et al. Guidelines on management (diagnosis and treatment) of syncope--update 2004. Eur Eur pacing, arrhythmias, Card Electrophysiol J Work groups Card pacing, arrhythmias, Card Cell Electrophysiol Eur Soc Cardiol. 2004;6(6):467–537.
- Humm AM, Z’Graggen WJ. Venepuncture during head-up tilt testing in patients with suspected vasovagal syncope - implications for the test protocol. Eur J Neurol. 2015;22(2):389–394.
- Krauze T, Guzik P, Wysocki H. Zmienność rytmu serca: aspekty techniczne. Now Lek. 2001;70(9):973–984.
- Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J. 1996;17(3):354–381.
- Sneddon JF, Bashir Y, Murgatroyd FD, Ward DE, Camm AJ, Malik M. Do patients with neurally mediated syncope have augmented vagal tone? Am J Cardiol. 1993;72(17):1314–1315.
- Sneddon JF, Counihan PJ, Bashir Y, Haywood GA, Ward DE, Camm AJ. Assessment of autonomic function in patients with neurally mediated syncope: augmented cardiopulmonary baroreceptor responses to graded orthostatic stress. J Am Coll Cardiol. 1993;21(5):1193–1198.
- Kochiadakis GE, Orfanakis AE, Rombola AT, Chrysostomakis SI, Chlouverakis GI, Vardas PE. Reproducibility of time-domain indexes of heart rate variability in patients with vasovagal syncope. Am J Cardiol. 1997;79(2):160–165.
- Kochiadakis GE, Rombola AT, Kanoupakis EM, Simantirakis EN, Chlouverakis GI, Vardas PE. Assessment of autonomic function at rest and during tilt testing in patients with vasovagal syncope. Am Heart J. 1997;134(3):459–466.
- Hosaka H, Takase B, Katsushika S, Ohsuzu F, Kurita A. Altered fractal behavior and heart rate variability in daily life in neurally mediated syncope. Biomed Pharmacother. 2003;57 Suppl 1:77s–82s.
- Takase B, Akima T, Satomura K, Mastui T, Ohsuzu F, Ishihara M, et al. Assessment of autonomic activity during daily life of patients with head-up tilt-induced prolonged asystole. Biomed Pharmacother. 2004;58 Suppl 1:S40-44.
- Cintra F, Poyares D, DO Amaral A, DE Marchi G, Barreto S, Tufik S, et al. Heart rate variability during sleep in patients with vasovagal syncope. Pacing Clin Electrophysiol PACE. 2005;28(12):1310–1316.
- Pagani M, Lombardi F, Guzzetti S, Rimoldi O, Furlan R, Pizzinelli P, et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res. 1986;59(2):178–193.
- Vybiral T, Bryg RJ, Maddens ME, Boden WE. Effect of passive tilt on sympathetic and parasympathetic components of heart rate variability in normal subjects. Am J Cardiol. 1989;63(15):1117–1120.
- Furlan R, Piazza S, Dell’Orto S, Barbic F, Bianchi A, Mainardi L, et al. Cardiac autonomic patterns preceding occasional vasovagal reactions in healthy humans. Circulation. 1998;98(17):1756–1761.
- Lipsitz LA, Mietus J, Moody GB, Goldberger AL. Spectral characteristics of heart rate variability before and during postural tilt. Relations to aging and risk of syncope. Circulation. 1990;81(6):1803–1810.
- Morillo CA, Klein GJ, Jones DL, Yee R. Time and frequency domain analyses of heart rate variability during orthostatic stress in patients with neurally mediated syncope. Am J Cardiol. 1994;74(12):1258–1262.
- Vardas P, Kochiadakis G, Orfanakis A, Kalaitzakis M, Manios E. Intraindividual reproducibility of heart rate variability before and during postural tilt in patients with syncope of unknown origin. Pacing Clin Electrophysiol PACE. 1994;17(11 Pt 2):2207–2210.
- Baran I, Kaderli AA, Ozdemir B, Gemici K, Ekbul A, Güllülü S, et al. Lack of association of heart rate variability parameters with head-up tilt-test responses in patients with syncope. Indian Heart J. 2004;56(3):229–231.
- Pruvot E, Vesin JM, Schlaepfer J, Fromer M, Kappenberger L. Autonomic imbalance assessed by heart rate variability analysis in vasovagal syncope. Pacing Clin Electrophysiol PACE. 1994;17(11 Pt 2):2201–2206.
- Lippman N, Stein KM, Lerman BB. Failure to decrease parasympathetic tone during upright tilt predicts a positive tilt-table test. Am J Cardiol. 1995;75(8):591–595.
- Prinz-Zaiss M, Yeap AN, Moguilevski V, Trigg L, McGrath BP. Presyncopal sympathetic withdrawal is the same in patients with vasodepressor syncope and controls who faint on head-up tilting. Am Heart J. 1997;133(2):230–239.
- Kochiadakis GE, Orfanakis A, Chryssostomakis SI, Manios EG, Kounali DK, Vardas PE. Autonomic nervous system activity during tilt testing in syncopal patients, estimated by power spectral analysis of heart rate variability. Pacing Clin Electrophysiol PACE. 1997;20(5 Pt 1):1332–1341.
- Grimm W, Wirths A, Hoffmann J, Menz V, Maisch B. Heart rate variability during head-up tilt testing in patients with suspected neurally mediated syncope. Pacing Clin Electrophysiol PACE. 1998;21(11 Pt 2):2411–2415.
- Kochiadakis GE, Papadimitriou EA, Marketou ME, Chrysostomakis SI, Simantirakis EN, Vardas PE. Autonomic nervous system changes in vasovagal syncope: is there any difference between young and older patients? Pacing Clin Electrophysiol PACE. 2004;27(10):1371–1377.
- Kochiadakis GE, Kanoupakis EM, Igoumenidis NE, Marketou ME, Solomou MC, Vardas PE. Spectral analysis of heart rate variability during tilt-table testing in patients with vasovagal syncope. Int J Cardiol. 1998;64(2):185–194.
- Guzmán CE, Sánchez GM, Márquez MF, Hermosillo AG, Cárdenas M. Differences in heart rate variability between cardioinhibitory and vasodepressor responses to head-up tilt table testing. Arch Med Res. 1999;30(3):203–211.
- Kouakam C, Lacroix D, Zghal N, Logier R, Klug D, Le Franc P, et al. Inadequate sympathovagal balance in response to orthostatism in patients with unexplained syncope and a positive head up tilt test. Heart. 1999;82(3):312–318.
- Folino AF, Russo G, Porta A, Buja G, Cerutti S, Iliceto S. Modulations of autonomic activity leading to tilt-mediated syncope. Int J Cardiol. 2007;120(1):102–107.
- Freitas J, Pereira S, Lago P, Costa O, Carvalho MJ, Falcão de Freitas A. Impaired arterial baroreceptor sensitivity before tilt-induced syncope. Eur Eur pacing, arrhythmias, Card Electrophysiol J Work groups Card pacing, arrhythmias, Card Cell Electrophysiol Eur Soc Cardiol. 1999;1(4):258–265.
- Ruiz GA, Madoery C, Arnaldo F, Menéndez C, Tentori MC. Frequency-domain analysis of heart rate variability during positive and negative head-up tilt test: importance of age. Pacing Clin Electrophysiol PACE. 2000;23(3):325–332.
- Mangin L, Kobeissi A, Lelouche D, Dhérouville TY, Mansier P, Swynghedauw B, et al. Simultaneous analysis of heart rate variability and myocardial contractility during head-up tilt in patients with vasovagal syncope. J Cardiovasc Electrophysiol. 2001;12(6):639–644.
- Folino AF, Russo G, Porta A, Buja G, Cerutti S, Iliceto S. Autonomic modulation and cardiac contractility in vasovagal syncope. Int J Cardiol. 2010;139(3):248–253.
- Suzuki M, Hori S, Nakamura I, Nagata S, Tomita Y, Aikawa N. Role of vagal control in vasovagal syncope. Pacing Clin Electrophysiol PACE. 2003;26(2 Pt 1):571–578.
- Budrejko S. Analysis of heart rate variability during head-up tilt test in patients with vasovagal syncope. 15th Int Student Sci Conf Students Young Dr Gdańsk. 2007;S244.
- Klemenc M, Štrumbelj E. Predicting the outcome of head-up tilt test using heart rate variability and baroreflex sensitivity parameters in patients with vasovagal syncope. Clin Auton Res. 2015;25(6):391–398.
- Gursul E, Bayata S, Tuluce SY, Berilgen R, Safak O, Ozdemir E, et al. Parameters of Heart Rate Variability Can Predict Prolonged Asystole before Head-Up Tilt Table Test. Ann Noninvasive Electrocardiol. 2014 Sep;19(5):477–482.
- Duplyakov D, Golovina G, Sysuenkova E, Garkina S. Can the result of a tilt test be predicted in the first five minutes? Cardiol J. 2011;18(5): 521–526.
- Hainsworth R. Syncope: what is the trigger? Heart. 2003;89(2):123–124.
- Hainsworth R. Pathophysiology of syncope. Clin Auton Res Off J Clin Auton Res Soc. 2004;14 Suppl 1:18–24.
- Turk U, Alioglu E, Kirilmaz B, Duygu H, Tuzun N, Tengiz I, et al. Prediction of head-up tilt test result: is it possible? Pacing Clin Electrophysiol PACE. 2010;33(2):153–158.
- Virag N, Sutton R, Vetter R, Markowitz T, Erickson M. Prediction of vasovagal syncope from heart rate and blood pressure trend and variability: experience in 1,155 patients. Hear Rhythm Off J Hear Rhythm Soc. 2007;4(11):1375–1382.
- Aerts AJ, Dendale P. Nitrate-stimulated tilt test. Am Heart J. 1999;137(3):575–576.
- Kurbaan AS, Franzén AC, Bowker TJ, Williams TR, Kaddoura S, Petersen ME, et al. Usefulness of tilt test-induced patterns of heart rate and blood pressure using a two-stage protocol with glyceryl trinitrate provocation in patients with syncope of unknown origin. Am J Cardiol. 1999;84(6):665–670.
- Chen LY, Shen W-K, Mahoney DW, Jacobsen SJ, Rodeheffer RJ. Prevalence of syncope in a population aged more than 45 years. Am J Med. 2006;119(12):1088.e1-7.
- Piccirillo G, Naso C, Moisè A, Lionetti M, Nocco M, Di Carlo S, et al. Heart rate and blood pressure variability in subjects with vasovagal syncope. Clin Sci (London, Engl 1979). 2004;107(1):55–61.
Publication order reference