Nitrate-potentiated head-up tilt testing (HUT) has a low diagnostic yield in patients with likely vasovagal syncope
Abstract
BACKGROUND: Vasovagal syncope (VVS) is characterized by a wide spectrum of clinical presentations, but the relationship between clinical presentation and response to head-up tilt testing (HUT) has not yet been evaluated in detail. The aim of this study was to assess the relationship between the clinical presentation of VVS and HUT and clinical outcome at long-term follow-up. METHODS: Out of 671 consecutive subjects undergoing nitroglycerin-potentiated HUT for suspected VVS, 369 patients with normal electrocardiogram and no structural heart disease were included in our study. RESULTS: A history suggestive of typical or atypical VVS was obtained in 198 and 171 patients, respectively. The positivity rate of HUT was 65% and 36% in patients with established and likely VVS, respectively (P < 0.0001). In patients with established VVS, a time interval of ≤28 days between the last syncope and HUT was the only independent predictor of a positive test. In patients with likely VVS, no variable was predictive of a positive HUT. At a mean follow-up of 43 ± 27 months, the rate of adverse events (all-cause mortality, syncope recurrence, and major diagnostic and/or therapeutic procedures) was similar in patients of both groups, independent of HUT results. CONCLUSION: In patients with likely VVS, HUT has a low-diagnostic yield and may be inadequate to establish a reliable diagnosis. Similar long-term outcomes were observed in patients with positive or negative test results, suggesting that HUT is of limited value in the management of patients with suspected neurally mediated syncope.
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Tilt testing was positive in 51-56% of patients with atypical clinical features suggesting a reflex mechanism.
“Indeed, tilt testing was positive in 51-56% of patients with atypical clinical features suggesting a reflex mechanism, 106,124-128”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [127]
Cites
Developed in collaboration with, European Heart Rhythm Association (EHRA), Heart Failure Association (HFA), and Heart Rhythm Society (HRS), societies, E. B. T. F., European Society of Emergency Medicine (EuSEM), European Federation of Internal Medicine (EFIM), European Union Geriatric Medicine Society (EUGMS), American Geriatrics Society (AGS), European Neurological Society (ENS), et al. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp298 · Cited by 2,040 · see citing works
Mark, A. L. (1983) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(83)80014-x · Cited by 721 · see citing works
Lipsitz, L. A., Mietus, J. E., Moody, G. B., & Goldberger, A. L. (1990) · Circulation · doi:10.1161/01.cir.81.6.1803 · Cited by 519 · see citing works
Differential changes of autonomic nervous system function with age in man
Pfeifer, M. A., Weinberg, C. R., Cook, D., Best, J. D., Reenan, A., & Halter, J. B. (1983) · The American Journal of Medicine · doi:10.1016/0002-9343(83)91201-9 · Cited by 453 · see citing works
Diagnostic value of history in patients with syncope with or without heart disease
Alboni, P., Brignole, M., Menozzi, C., Raviele, A., Del Rosso, A., Dinelli, M., Solano, A., & Bottoni, N. (2001) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(01)01241-4 · Cited by 444 · see citing works
The elusive pathophysiology of neurally mediated syncope
Mosqueda-Garcia, R., Furlan, R., MD, J. T., & Fernandez-Violante, R. (2000) · Circulation · doi:10.1161/01.cir.102.23.2898 · Cited by 383 · see citing works
Self-citationMechanism of Syncope in Patients With Isolated Syncope and in Patients With Tilt-Positive Syncope
Moya, A., Brignole, M., Menozzi, C., Garcia-Civera, R., Tognarini, S., Mont, L., Botto, G., Giada, F., Cornacchia, D., & on behalf of the International Study on Syncope of Uncertain Etiology (ISSUE) Investigators (2001) · Circulation · doi:10.1161/hc3601.095708 · Cited by 378 · see citing works
Brignole, M., Sutton, R., Menozzi, C., Garcia-Civera, R., Moya, A., Wieling, W., Andresen, D., Benditt, D. G., & Vardas, P. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehi842 · Cited by 376 · see citing works
Brignole, M., Menozzi, C., Bartoletti, A., Giada, F., Lagi, A., Ungar, A., Ponassi, I., Mussi, C., Maggi, R., Re, G., et al. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehi647 · Cited by 332 · see citing works
Bartoletti, A. (2000) · Europace · doi:10.1053/eupc.2000.0125 · Cited by 315 · see citing works
Syncope prevalence in the ED compared to general practice and population: a strong selection process
Olde Nordkamp, L. R. A., van Dijk, N., Ganzeboom, K. S., Reitsma, J. B., Luitse, J. S. K., Dekker, L. R. C., Shen, W.-K., & Wieling, W. (2009) · The American Journal of Emergency Medicine · doi:10.1016/j.ajem.2008.02.022 · Cited by 158 · see citing works
Age-related changes of baroreflex function, plasma norepinephrine, and blood pressure.
Shimada, K., Kitazumi, T., Sadakane, N., Ogura, H., & Ozawa, T. (1985) · Hypertension · doi:10.1161/01.hyp.7.1.113 · Cited by 156 · see citing works
Relation of clinical presentation of syncope to the age of patients
Del Rosso, A., Alboni, P., Brignole, M., Menozzi, C., & Raviele, A. (2005) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2005.07.047 · Cited by 138 · see citing works
Age of First Faint in Patients with Vasovagal Syncope
SHELDON, R. S., SHELDON, A. G., CONNOLLY, S. J., MORILLO, C. A., KLINGENHEBEN, T., KRAHN, A. D., KOSHMAN, M., RITCHIE, D., & for the Investigators of the Syncope Symptom Study and the Prevention of Syncope Trial (2006) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2005.00267.x · Cited by 134 · see citing works
Brignole, M., Ungar, A., Casagranda, I., Gulizia, M., Lunati, M., Ammirati, F., Del Rosso, A., Sasdelli, M., Santini, M., Maggi, R., et al. (2010) · Europace · doi:10.1093/europace/eup370 · Cited by 133 · see citing works
Ungar, A., Rosso, A. D., Giada, F., Bartoletti, A., Furlan, R., Quartieri, F., Lagi, A., Morrione, A., Mussi, C., Lunati, M., et al. (2010) · European Heart Journal · doi:10.1093/eurheartj/ehq017 · Cited by 112 · see citing works
DIFFERENTIAL DIAGNOSIS OF CARDIOGENIC SYNCOPE AND SEIZURE DISORDERS
Bergfeldt, L. (2003) · Heart · doi:10.1136/heart.89.3.353 · Cited by 110 · see citing works
Is vasovagal syncope a disease?
Alboni, P., Brignole, M., & Uberti, E. C. D. (2007) · EP Europace · doi:10.1093/europace/eul179 · Cited by 81 · see citing works
SUMNER, G. L., ROSE, M. S., KOSHMAN, M. L., RITCHIE, D., SHELDON, R. S., & for the Prevention of Syncope Trial Investigators (2010) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2010.01848.x · Cited by 80 · see citing works
Comparison of Patients With Syncope of Unknown Cause Having Negative or Positive Tilt-Table Tests
Sheldon, R. S., Rose, S., & Koshman, M. L. (1997) · The American Journal of Cardiology · doi:10.1016/s0002-9149(97)00425-6 · Cited by 56 · see citing works
Predicting the cause of syncope from clinical history in patients undergoing prolonged monitoring
Sud, S., Klein, G. J., Skanes, A. C., Gula, L. J., Yee, R., & Krahn, A. D. (2009) · Heart Rhythm · doi:10.1016/j.hrthm.2008.10.035 · Cited by 43 · see citing works
Ebert, T. J., Hughes, C. V., Tristani, F. E., Barney, J. A., & Smith, J. (1982) · Cardiovascular Research · doi:10.1093/cvr/16.11.663 · Cited by 41 · see citing works
Head-up Tilt Table Testing: A state-of-the-art review
Tan, M.-S., Duncan, G. W., & Parry, S. W. (2009) · PubMed · doi:10.25405/ncl.34139748 · Cited by 16 · see citing works
Oh, J. H., Kim, J. S., Gwon, H. C., Hong, K. P., Park, J. R., Seo, J. D., & LEE, W. R. (2003) · Pacing and Clinical Electrophysiology · doi:10.1046/j.1460-9592.2003.00099.x · Cited by 10 · see citing works
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2018 ESC Guidelines for the diagnosis and management of syncope
Brignole, M., Moya, A., de Lange, F. J., Deharo, J.-C., Elliott, P. M., Fanciulli, A., Fedorowski, A., Furlan, R., Kenny, R. A., Martín, A., et al. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy037 · Cited by 1,951 · see citing works
2018 ESC Guidelines for the diagnosis and management of syncope
Brignole, M., Moya‐Mitjans, À., de Lange, F. J., Deharo, J., Elliot, P. M., Fanciulli, A., Fedorowski, A., Furlan, R., Kenny, R. A., Martiın, A., et al. (2018) · Kardiologia Polska · doi:10.5603/kp.2018.0161 · Cited by 474 · see citing works
Sutton, R., & Brignole, M. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu255 · Cited by 127 · see citing works
The Diagnostic Value of Cardiac Deceleration Capacity in Vasovagal Syncope
Zheng, L., Sun, W., Liu, S., Liang, E., Du, Z., Guo, J., Wu, L., Asirvatham, S. J., & Yao, Y. (2020) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.120.008659 · Cited by 46 · see citing works
Zou, R., Wang, S., Zhu, L., Wu, L., Lin, P., Li, F., Xie, Z., Li, X., & Wang, C. (2016) · Neurological Sciences · doi:10.1007/s10072-016-2740-5 · Cited by 30 · see citing works
Are women really more affected by vasovagal syncope than men?
Alboni, P., Messop, A. C., Lauri, A., & Furlan, R. (2020) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0000000000001009 · Cited by 22 · see citing works
Heart rate variability analysis during head-up tilt test predicts nitroglycerine-induced syncope
Efremov, K., Brisinda, D., Venuti, A., Iantorno, E., Cataldi, C., Fioravanti, F., & Fenici, R. (2014) · Open Heart · doi:10.1136/openhrt-2014-000063 · Cited by 18 · see citing works
The clinical presentation of syncope influences the head-up tilt test responses
Russo, V., Parente, E., Comune, A., Laezza, N., Rago, A., Golino, P., Nigro, G., & Brignole, M. (2023) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2023.01.001 · Cited by 17 · see citing works
Head-up tilt test diagnostic yield in syncope diagnosis
Barón‐Esquivias, G., Martín, A. J., Castillo, A. M. D., Quintanilla, M., Barón-Solís, C., & Morillo, C. A. (2020) · Journal of Electrocardiology · doi:10.1016/j.jelectrocard.2020.09.016 · Cited by 13 · see citing works
Xu, L., Cao, X., Wang, R., Duan, Y., Ye, Y., Hou, J., Wang, J., Chen, B., Xue, X., Zhang, B., et al. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.781157 · Cited by 11 · see citing works
Treatment of Neurocardiogenic Syncope: From Conservative to Cutting-edge
Gampa, A., & Upadhyay, G. A. (2018) · Journal of Innovations in Cardiac Rhythm Management · doi:10.19102/icrm.2018.090702 · Cited by 10 · see citing works
The pathophysiologic mechanisms associated with hypotensive susceptibility
Chaddha, A., Rafanelli, M., Brignole, M., Sutton, R., WENZKE, K. E., Wasmund, S. L., Page, R. L., & Hamdan, M. H. (2016) · Clinical Autonomic Research · doi:10.1007/s10286-016-0362-x · Cited by 8 · see citing works
Usefulness of Tilt Testing and Carotid Sinus Massage for Evaluating Reflex Syncope
Rivasi, G., Rafanelli, M., & Ungar, A. (2018) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2018.04.033 · Cited by 7 · see citing works
Symptom Score: A New Instrument to Assess Orthostatic Intolerance in Children and Adolescents
Cai, H., Wang, S., Zou, R., Liu, P., Yang, H., Wang, Y., & Wang, C. (2020) · Journal of Child Neurology · doi:10.1177/0883073820936025 · Cited by 6 · see citing works
Guo, Y., Lin, T., Lin, N., & Lin, H. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1333684 · Cited by 5 · see citing works
A contemporary review of the head-up tilt test: Utility and limitations
Udyavar, A. R., Shenthar, J., Naik, A. M., Khanra, D., Ramalingam, V., Singhal, R., Choudhary, D., Gupta, P. N., Rao, B. H., Mehrotra, S., et al. (2025) · Indian Heart Journal · doi:10.1016/j.ihj.2025.03.014 · Cited by 9 · see citing works
Isoprenaline versus nitroglycerine in head-up tilt test
Bilagi, U. R., Shenthar, J., & Cholenahally, M. N. (2016) · Indian Heart Journal · doi:10.1016/j.ihj.2016.06.007 · Cited by 3 · see citing works
Gemein, C., Roos, M., Wolf, A., Hermann, N., Kelava, A., Chasan, R., Weipert, K. F., Helmig, I., Bogossian, H., Hamm, C. W., et al. (2018) · International Journal of Cardiology · doi:10.1016/j.ijcard.2018.01.102 · Cited by 3 · see citing works
Ray, J. C., Kusumoto, F. M., & Goldschlager, N. (2014) · Journal of Intensive Care Medicine · doi:10.1177/0885066614552988 · Cited by 3 · see citing works
Russo, V., Comune, A., Nardo, G. D., Parente, E., Marco, G. M. D., Nigris, A. D., Russo, M. G., Sarubbi, B., Nigro, G., & Brignole, M. (2025) · Clinical Autonomic Research · doi:10.1007/s10286-025-01145-5 · Cited by 2 · see citing works
Tilt test in paced patients: Is it worth the effort?
Bhargava, K. (2015) · Indian Pacing and Electrophysiology Journal · doi:10.1016/j.ipej.2015.10.009 · Cited by 2 · see citing works
Sunkak, S., & Argun, M. (2022) · Trends in Pediatrics · doi:10.4274/tp.2022.49469 · Cited by 2 · see citing works
Diagnostic efficacy of transcranial Doppler combined with upright tilt test in vasovagal syncope
Wang, J., Li, H., & Cao, L. (2025) · Journal of Neurology · doi:10.1007/s00415-025-13154-5 · Cited by 1 · see citing works
2018 KHRS guideline for the evaluation and management of syncope-Part 1
Park, J., Cha, M.-J., Kim, D. H., Kim, Y. R., Mun, H. S., Bae, E. J., Seo, D. W., Song, M. K., Ahn, J., Yoon, H. D., et al. (2018) · International Journal of Arrhythmia · doi:10.18501/arrhythmia.2018.009 · Cited by 1 · see citing works
2018 KHRS guideline for the evaluation and management of syncope-Part 2
Kim, Y. R., Chun, K. J., Kim, J. S., Mun, H. S., Park, J., Seo, D. W., Song, M. K., Ahn, J. H., Yoon, H. J., Lee, D. I., et al. (2018) · International Journal of Arrhythmia · doi:10.18501/arrhythmia.2018.010 · Cited by 1 · see citing works
Rocha, E. A., Kubrusly, B. S., Gurgel, A. D. A. A., Pinho, L. G. B., Farias, A. G. P., Coimbra, V. O., Gondim, P. S. P., Rocha, M. C. T., Rocha, M. E. Q. A., Pereira, F. T. M., et al. (2024) · Journal of Cardiac Arrhythmias · doi:10.24207/jca.v37i1.3490 · Cited by 1 · see citing works
Sutton, R. (2016) · International Journal of Heart Rhythm · doi:10.4103/2352-4197.191478 · Cited by 1 · see citing works
- Authors
- PETIX, N. R., DEL ROSSO, A., FURLAN, R., GUARNACCIA, V., & ZIPOLI, A.
- Affiliations
- Ospedale San Giuseppe (IT)
- Arrhythmology Section – Cardiology Department San Giuseppe Hospital Empoli (FI) Italy
- Humanitas University (IT)
- ORCID
- FURLAN, RAFFAELLO
- Venue
- Pacing and Clinical Electrophysiology
- Publisher
- Wiley
- Published
- 2013-08-30
- Volume
- 37
- Issue
- 2
- Pages
- 164-172
- ISSN
- 0147-8389 (ISSN-L)
- 1540-8159
- OpenAlex
- W2106035499
- Cited by
- 27
- References
- 26
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2022: 2 · 2020: 4 · 2018: 7 · 2016: 4 · 2015: 1 · 2014: 3
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pacing and Clinical Electrophysiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Life Sciences › Neuroscience › Neurology › Vestibular and auditory disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- vasovagal syncope, head-up tilt, neurally mediated syncope, diagnostic yield, syncope recurrence, long-term outcomes
- MeSH terms
- Electrocardiography, Female, Nitroglycerin, Humans, Italy, Male, Middle Aged, Sensitivity and Specificity, Vasodilator Agents, Reproducibility of Results, Incidence, Survival Rate, Tilt-Table Test, Syncope, Vasovagal
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