Recurrent vasovagal syncope: comparison between clomipramine and nitroglycerin as drug challenges during head-up tilt testing
Abstract
AIMS: To compare the responses between clomipramine, a centrally acting substance, and nitroglycerin, with mainly peripheral action, when each drug is used during tilt test for the induction of vasovagal syncope (VVS). METHODS AND RESULTS: Hundred patients with recurrent episodes of classical VVS underwent two tilt tests in a randomized sequence. One test included 20 min of tilt at 60 degrees with intravenous administration of 5 mg clomipramine (clomipramine tilt), whereas the other test included an initial 30 min period of passive 60 degrees tilt, followed by sublingual spray administration of 400 microg nitroglycerin (nitroglycerin tilt). Fifty asymptomatic subjects served as controls. Following clomipramine tilt, a positive response occurred in 73 patients (73%), a negative response in 23 (23%), and drug intolerance in 4 (4%). With nitroglycerin tilt, these percentages were 52, 48, and 0%, respectively. Significant differences were observed regarding positive responses (clomipramine vs. nitroglycerin: 73/100 vs. 52/100, P < 0.05), as well as negative responses (23/100 vs. 48/100, respectively, P < 0.05). A high concordance rate was observed in positive responses. CONCLUSION: In the evaluation of patients with recurrent classical VVS, clomipramine tilt is associated with an increased positive yield relative to nitroglycerin tilt. This suggests that central mechanisms may be more important than peripheral ones in VVS pathogenesis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Tilt testing has an acceptable sensitivity and specificity when calculated in patients with true VVS or without a history of syncope.
“Tilt testing has an acceptable sensitivity 124 and specificity 106,124,125 when these are calculated in patients with true VVS or without a history of syncope.”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [124]
Tilt testing was positive in 30-36% of patients with unexplained syncope after full investigation.
“in 30-36% with unexplained syncope after full investigation, 124,129”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [124]
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 [124]
Cites
Guidelines on management (diagnosis and treatment) of syncope
Brignole, M. (2001) · European Heart Journal · doi:10.1053/euhj.2001.2739 · Cited by 951 · see citing works
Linzer, M., Yang, E. H., Estes III, N. A. M., Wang, P., Vorperian, V. R., & Kapoor, W. N. (1997) · Annals of Internal Medicine · doi:10.7326/0003-4819-126-12-199706150-00012 · Cited by 437 · see citing works
Bartoletti, A. (2000) · Europace · doi:10.1053/eupc.2000.0125 · Cited by 315 · see citing works
Sympathetic and baroreceptor reflex function in neurally mediated syncope evoked by tilt
Mosqueda-Garcia, R., Furlan, R., Fernandez-Violante, R., Desai, T., Snell, M., Jarai, Z., Ananthram, V, Robertson, R. M., & Robertson, D. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119463 · Cited by 255 · see citing works
Brignole, M. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehl164 · Cited by 145 · see citing works
Cardiac Autonomic Patterns Preceding Occasional Vasovagal Reactions in Healthy Humans
Furlan, R., Piazza, S., Dell’Orto, S., Barbic, F., Bianchi, A. M., Mainardi, L. T., Cerutti, S., Pagani, M., & Malliani, A. (1998) · Circulation · doi:10.1161/01.cir.98.17.1756 · Cited by 142 · see citing works
Nitroglycerin infusion during upright tilt: A new test for the diagnosis of vasovagal syncope
Raviele, A., GASPARINI, G., Pede, F. D., Menozzi, C., Brignole, M., Dinelli, M., Alboni, P., & Piccolo, E. (1994) · American Heart Journal · doi:10.1016/0002-8703(94)90515-0 · Cited by 136 · see citing works
Pathophysiology, Diagnosis, and Treatment of Orthostatic Hypotension and Vasovagal Syncope
Medow, M. S., Stewart, J. M., Sanyal, S., Mumtaz, A., Sica, D. A., & Frishman, W. H. (2007) · Cardiology in Review · doi:10.1097/crd.0b013e31815c8032 · Cited by 112 · see citing works
An Implantable Loop Recorder Study of Highly Symptomatic Vasovagal Patients
Deharo, J.-C., Jego, C., Lanteaume, A., & Djiane, P. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.09.043 · Cited by 110 · see citing works
The effects on the central nervous system of nitroglycerin—putative mechanisms and mediators
Tassorelli, C., Joseph, S., Buzzi, M. G., & Nappi, G. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00071-9 · Cited by 84 · see citing works
Gisolf, J., Westerhof, B. E., van Dijk, N., Wesseling, K. H., Wieling, W., & Karemaker, J. M. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.04.038 · Cited by 59 · see citing works
Central Serotonergic Responsiveness in Neurocardiogenic Syncope
THEODORAKIS, G. N., Markianos, M., LIVANIS, E. G., Zarvalis, E., Flevari, P., & Kremastinos, D. T. (1998) · Circulation · doi:10.1161/01.cir.98.24.2724 · Cited by 48 · see citing works
Self-citationTilt testing for syncope: a reappraisal.
Sheldon, R. S. (2005) · PubMed · Cited by 46 · see citing works
Head-up tilt test with clomipramine challenge in vasovagal syndrome—a new tilt testing protocol
Theodorakis, G. (2003) · European Heart Journal · doi:10.1016/s0195-668x(02)00821-7 · Cited by 40 · see citing works
Self-citationNitrate stimulated tilt table testing: a review of the literature
AERTS, A. J. J., & DENDALE, P. (2003) · Pacing and Clinical Electrophysiology · doi:10.1046/j.1460-9592.2003.t01-1-00222.x · Cited by 35 · see citing works
Central 5-hydroxytryptamine (5-HT) receptors in blood pressure regulation.
Dabiré, H. (1992) · PubMed · Cited by 31 · see citing works
Baroreflexes in Vasovagal Syncope: Two Types of Abnormal Response
Flevari, P., LIVANIS, E. G., THEODORAKIS, G. N., et al. (2002) · Pacing and Clinical Electrophysiology · doi:10.1046/j.1460-9592.2002.01315.x · Cited by 19 · see citing works
Self-citationMitro, P., & Hijová, E. (2006) · Pacing and Clinical Electrophysiology · doi:10.1111/j.1540-8159.2006.00299.x · Cited by 17 · see citing works
The evaluation and treatment of syncope : a handbook for clinical practice
Benditt, D. G. (2006) · Medical Entomology and Zoology · Cited by 14 · see citing works
Overview of Recommended Diagnostic Strategies
Sutton, R. B., & Brignole, M. (2006) · doi:10.1002/9781444312812.ch6 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Sutton, R., & Brignole, M. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu255 · Cited by 127 · see citing works
Head-up tilt testing for diagnosing vasovagal syncope: a meta-analysis
Forleo, C., Guida, P., Iacoviello, M., Resta, M., Monitillo, F., Sorrentino, S., & Favale, S. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.09.023 · Cited by 112 · see citing works
Furukawa, T., Maggi, R., Solano, A., Croci, F., & Brignole, M. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2011.01.057 · Cited by 28 · see citing works
- Authors
- Flevari, P., Leftheriotis, D., Komborozos, C., Fountoulaki, K., Dagres, N., Theodorakis, G., & Kremastinos, D.
- Affiliations
- Onassis Cardiac Surgery Center (GR)
- Corresponding author
- Flevari, P.
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-06-25
- Volume
- 30
- Issue
- 18
- Pages
- 2249-2253
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W2006162449
- Cited by
- 38
- References
- 21
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 6 · 2017: 2 · 2016: 3 · 2014: 1 · 2013: 3 · 2012: 4
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- 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, clomipramine, nitroglycerin, head-up tilt, drug challenge, central mechanisms, peripheral mechanisms, diagnostic yield
- MeSH terms
- Administration, Inhalation, Adolescent, Adult, Central Nervous System Agents, Clomipramine, Female, Nitroglycerin, Humans, Injections, Intravenous, Male, Middle Aged, Random Allocation, Recurrence, Peripheral Nervous System Agents, Tilt-Table Test, Syncope, Vasovagal, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
