Syndromes of orthostatic intolerance and syncope in young adults
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Objective: To explore the clinical and neuroendocrine characteristics of syndromes of orthostatic intolerance and syncope in young adults. Methods: Two hundred and thirty-six patients aged 18–40 years with orthostatic intolerance and/or syncope were examined by head-up tilt test (HUT). Plasma levels of epinephrine, norepinephrine, renin, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal-endothelin-1 and mid-regional-fragment of pro-atrial-natriuretic-peptide (MR-proANP) were analysed. Patients’ history, haemodynamic parameters and plasma biomarkers were related to main diagnoses such as vasovagal syncope (VVS), postural tachycardia syndrome (POTS), orthostatic hypotension (OH) and negative HUT. Results: No self-reported symptom of orthostatic intolerance was highly specific for any diagnosis. Patients with VVS (n=103) were more likely to be men (p=0.011) and had lower resting heart rate (HR; 66±11) compared with POTS (73±11; n=72; p=0.001) and negative HUT (74±11; n=39; p=0.001). Patients with POTS demonstrated greater rise in norepinephrine (p=0.008) and CT-proAVP (p=0.033) on standing compared with negative HUT, and lower resting MR-proANP compared with VVS (p=0.04) and OH (p=0.03). Patients with OH had lower resting renin (p=0.03). Subjects with a resting HR <70 and MR-proANP >45 pm/L had an OR of 3.99 (95 % CI 1.68 to 9.52; p=0.002) for VVS compared with subjects without any of these criteria; if male sex was added the OR was 21.8 (95% CI 3.99 to 119; p<0.001). Conclusions: Syndromes of orthostatic intolerance and syncope share many characteristics in younger persons. However, patients with VVS are more likely to be men, have lower HR and higher MR-proANP at rest compared with POTS, which might be taken into account at an early stage of evaluation.
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In a specialized syncope unit, nearly one-third of patients aged 18-40 with unexplained syncope and pronounced orthostatic intolerance may satisfy POTS diagnostic criteria.
“In a specialized syncope unit, almost one-third of patients aged 18-40 years with a history of unexplained syncope and pronounced orthostatic intolerance may meet the diagnostic POTS criteria [22].”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [22]
Orthostatic intolerance symptoms and syncopal event counts do not reliably separate POTS from other syncope-related dysautonomic conditions, orthostatic hypotension, or recurrent vasovagal syncope.
“Importantly, symptoms of orthostatic intolerance and number of syncopal events do not well discriminate between POTS and other syncope-related dysautonomic conditions, orthostatic hypotension and recurrent vasovagal syncope [22].”
From Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management (2019) · cites this paper as [22]
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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
Self-citationSheldon, R. S., Grubb, B. P., Olshansky, B., Shen, W.-K., Calkins, H., Brignole, M., Raj, S. R., Krahn, A. D., Morillo, C. A., Stewart, J. M., et al. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.03.029 · Cited by 1,013 · cited 1× · see citing works
“The fact that the proportion of men is higher among patients with VVS than among patients with POTS is consistent with the well-known fact that POTS is more often diagnosed in women.(6) Among other observations, lower renin in OH is supported by earlier studies in diabetic patients with OH,(25) but has not been recent…”
ResultSelf-citationRicci, F., De Caterina, R., & Fedorowski, A. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.06.1084 · Cited by 472 · see citing works
Self-citationGANZEBOOM, K. S., MAIRUHU, G., REITSMA, J. B., LINZER, M., WIELING, W., & VAN DIJK, N. (2006) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2006.00595.x · Cited by 375 · see citing works
Fedorowski, A., Stavenow, L., Hedblad, B., Berglund, G., Nilsson, P. M., & Melander, O. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp329 · Cited by 350 · see citing works
Self-citationBartoletti, A. (2000) · Europace · doi:10.1053/eupc.2000.0125 · Cited by 315 · see citing works
Guía de práctica clínica para el diagnóstico y manejo del síncope (versión 2009)
Moya‐Mitjans, À., Sutton, R., Ammirati, F., Blanc, J., Brignole, M., Dahm, J. B., Deharo, J., Gajek, J. J., Gjesdal, K., Krahn, A. D., et al. (2009) · Revista Española de Cardiología (English Edition) · doi:10.1016/s1885-5857(09)73541-8 · Cited by 277 · see citing works
Self-citationDiagnostic criteria for vasovagal syncope based on a quantitative history
Sheldon, R., Rose, S., Connolly, S., Ritchie, D., Koshman, M.-L., & Frenneaux, M. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehi584 · Cited by 252 · see citing works
van der Hoorn, F. A. J., Boomsma, F., VELD, A. J. M. I., & Schalekamp, M. A. D. H. (1989) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(00)83003-0 · Cited by 224 · see citing works
Nexfin Noninvasive Continuous Blood Pressure Validated Against Riva-Rocci/Korotkoff
Schattenkerk, D. W. E., LIESHOUT, J. J. V., van den Meiracker, A. H., Wesseling, K. H., Blanc, S., Wieling, W., van Montfrans, G. A., Settels, J. J., Wesseling, K. H., & Westerhof, B. E. (2009) · American Journal of Hypertension · doi:10.1038/ajh.2008.368 · Cited by 222 · see citing works
Finucane, C., O’Connell, M. D. L., Fan, C. W., Savva, G. M., Soraghan, C. J., Nolan, H., Cronin, H., & Kenny, R. A. (2014) · Circulation · doi:10.1161/circulationaha.114.009831 · Cited by 219 · see citing works
Mechanisms of atrial natriuretic peptide secretion from the atrium
Dietz, J. R. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2005.06.008 · Cited by 180 · see citing works
VAN DIJK, N., BOER, K. R., COLMAN, N., BAKKER, A., STAM, J., VAN GRIEKEN, J. J. M., WILDE, A. A. M., LINZER, M., REITSMA, J. B., & WIELING, W. (2008) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2007.00984.x · Cited by 164 · see citing works
The hemodynamic and neurohumoral phenotype of postural tachycardia syndrome
Garland, E. M., Raj, S. R., Black, B. K., Harris, P. A., & Robertson, D. (2007) · Neurology · doi:10.1212/01.wnl.0000267663.05398.40 · Cited by 159 · see citing works
Syndromes of orthostatic intolerance: a hidden danger
Fedorowski, A., & Melander, O. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12021 · Cited by 151 · see citing works
Self-citationAntiadrenergic autoimmunity in postural tachycardia syndrome
Fedorowski, A., Li, H., Yu, X., Koelsch, K. A., Harris, V. M., Liles, C., Murphy, T. A., Quadri, S. M. S., Scofield, R. H., Sutton, R., et al. (2017) · EP Europace · doi:10.1093/europace/euw154 · Cited by 151 · see citing works
Self-citationSutton, R., & Brignole, M. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu255 · Cited by 127 · see citing works
Self-citationInfluence of age and gender on the occurrence and presentation of reflex syncope
Romme, J. J. C. M., van Dijk, N., Boer, K. R., Dekker, L. R. C., Stam, J., Reitsma, J. B., & Wieling, W. (2008) · Clinical Autonomic Research · doi:10.1007/s10286-008-0465-0 · Cited by 115 · see citing works
Christlieb, A. R., MUNICHOODAPPA, C. S., & Braaten, J. T. (1974) · Diabetes · doi:10.2337/diab.23.10.835 · Cited by 92 · see citing works
Novel cardiovascular biomarkers in unexplained syncopal attacks: the <scp>SYSTEMA</scp> cohort
Fedorowski, A., Burri, P., Struck, J., Juul‐Möller, S., & Melander, O. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12043 · Cited by 62 · see citing works
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Wieling, W., van Dijk, N., de Lange, F. J., Nordkamp, L. R. A. O., Thijs, R. D., van Dijk, J. G., Linzer, M., & Sutton, R. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu478 · Cited by 57 · see citing works
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Nilsson, D., Sutton, R., Tas, W., Burri, P., Melander, O., & Fedorowski, A. (2015) · PLOS ONE · doi:10.1371/journal.pone.0128962 · Cited by 54 · see citing works
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Li, H., Kem, D. C., Reim, S., Khan, M., Vanderlinde-Wood, M., Zillner, C., Collier, D., Liles, C., Hill, M. A., Cunningham, M. W., et al. (2012) · Hypertension · doi:10.1161/hypertensionaha.111.184937 · Cited by 51 · see citing works
Zhao, J., Du, S., Yang, J., Lin, J., Tang, C., Du, J., & Jin, H. (2014) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2014.05.039 · Cited by 41 · see citing works
Clinical history in management of suspected syncope: A powerful diagnostic tool
Sutton, R., van Dijk, N., & Wieling, W. (2014) · Cardiology Journal · doi:10.5603/cj.2014.0097 · Cited by 39 · see citing works
Self-citationTheuns, D. A. M. J., Szili‐Törok, T., & Jordaens, L. J. L. M. (2008) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2008.01215.x · Cited by 38 · see citing works
Zhao, J., Tang, C., Jin, H., & Du, J. (2014) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2014.04.032 · Cited by 27 · see citing works
Role of atrial pressure and rate in release of atrial natriuretic peptide
Walsh, K. P., Williams, T. D. M., Spiteri, C., Pitts, E., Lightman, S. L., & Sutton, R. (1988) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1988.254.4.r607 · Cited by 27 · see citing works
Self-citationWagoner, A. L., Shaltout, H. A., Fortunato, J. E., & Diz, D. I. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00583.2015 · Cited by 22 · see citing works
Krishnan, B., Patarroyo-Aponte, M., Duprez, D., Pritzker, M., Missov, E., & Benditt, D. G. (2015) · Heart Rhythm · doi:10.1016/j.hrthm.2015.02.015 · Cited by 13 · see citing works
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Medic Spahic, J., Ricci, F., Aung, N., Hallengren, E., Axelsson, J., Hamrefors, V., Melander, O., Sutton, R., & Fedorowski, A. (2020) · Figshare · doi:10.6084/m9.figshare.12177873
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- Authors
- Hamrefors, V., Spahic, J. M., Nilsson, D., Senneby, M., Sutton, R., Melander, O., & Fedorowski, A.
- Affiliations
- Lund University (SE)
- Hammersmith Hospital (GB)
- Corresponding author
- Hamrefors, Viktor
- Venue
- Open Heart
- Publisher
- BMJ
- Published
- 2017-05
- Volume
- 4
- Issue
- 1
- Pages
- e000585
- ISSN
- 2053-3624 (ISSN-L)
- PMC
- PMC5471871
- OpenAlex
- W2614254939
- Cited by
- 23
- References
- 30
- Citations by year
- 2024: 6 · 2022: 5 · 2021: 1 · 2020: 5 · 2019: 4 · 2018: 2
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Open Heart (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- The Albert Phlsson Research Foundation
- Skne University Hospital
- The Medical Faculty of Lund University
- The Ernhold Lundstrms Research Foundation
- The Crafoord Foundation
- The Swedish Heart and Lung Foundation
- Swedish Medical Research Council
- European Research Council
- The King Gustaf V and Queen Victoria Foundation
- The Wallenberg Foundation
- ALF-funds
- The Region Skne
- The Hulda and Conrad Mossfelt Foundation
- The Lennart Hanssons Memorial Foundation
- The Anna Lisa and Sven-Erik Lundgrens Foundation
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Neurology › Vestibular and auditory disorders
- Keywords
- orthostatic intolerance, syncope, vasovagal syncope, postural orthostatic tachycardia syndrome, orthostatic hypotension, head-up tilt, neuroendocrine markers, norepinephrine, vasopressin, MR-proANP, endothelin-1, renin, heart rate, young adults, diagnostic criteria, sex differences
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