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The Expectation Effect and Cardiac Pacing for Refractory Vasovagal Syncope
Abstract
Background Clinical trials of pacing for vasovagal syncope have shown conflicting results. We performed a meta-analysis to determine whether permanent pacemaker therapy prevents refractory vasovagal syncope.Methods Randomized trials comparing pacemaker therapy with medical therapy, usual care, placebo, or different pacing algorithms in the prevention of recurrent vasovagal syncope were considered. The primary endpoint was first recurrence of syncope.Results Nine randomized trials (2 double blind, 7 open label or single blind) were included. There was significant heterogeneity when all 9 trials were pooled (P=.0009 and I(2)=69.6%), reflecting methodological diversity in blinding and the nature of the control therapy. When pooled by trial methodology, heterogeneity was no longer apparent. Permanent pacing reduced the risk of recurrent syncope in unblinded studies (odds ratio [OR] 0.09, 95% confidence interval [CI], 0.04 to 0.22) and in studies comparing pacemaker algorithms (OR 0.04, 95% CI, 0.0 to 0.23). No effect was seen in double-blinded trials (OR 0.83, 95% CI, 0.41 to 1.70). Awareness that a permanent pacemaker was implanted and functional was associated with a significant 'expectation' effect, which itself reduced the risk of recurrent syncope (OR 0.16, 95% CI, 0.06 to 0.40, P=.0001). Results were similar when restricted to patients with a marked cardioinhibitory response on baseline tilt table testing.Conclusion The results of small, preliminary trials have overestimated the treatment effect of pacemakers due to a lack of blinding of physicians and patients. Blinded trials suggest that the apparent response is due to a strong expectation response to pacing.
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“A meta-analysis of all studies suggested a non-significant 17% reduction in syncope from the double-blind studies, and an 84% reduction in the studies where the control group did not receive a pacemaker. 301”
From 2018 ESC Guidelines for the diagnosis and management of syncope (2018) · cites this paper as [301]
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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
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
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 475
Brignole, M., Menozzi, C., Moya, A., Andresen, D., Blanc, J. J., Krahn, A. D., Wieling, W., Beiras, X., Deharo, J. C., Russo, V., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.082313 · Cited by 437
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
Metadata
- Authors
- Sud, S., Massel, D., Klein, G. J., Leong-Sit, P., Yee, R., Skanes, A. C., Gula, L. J., & Krahn, A. D.
- Affiliations
- Western University (CA)
- Corresponding author
- Krahn, Andrew D.
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 120
- Issue
- 1
- Pages
- 54-62
- ISSN
- 0002-9343 (ISSN-L)
- OpenAlex
- W1987480715
- Cited by
- 151
- References
- 50
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 5 · 2022: 7 · 2021: 8 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 15 · 2016: 8 · 2015: 9 · 2014: 10 · 2013: 15 · 2012: 15
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- vasovagal syncope, permanent pacemaker, cardiac pacing, expectancy effects, blinding, trial heterogeneity, syncope recurrence, cardioinhibitory response, tilt table test, pacing algorithms
- MeSH terms
- Cardiac Pacing, Artificial, Data Interpretation, Statistical, Female, Humans, Male, Middle Aged, Pacemaker, Artificial, Randomized Controlled Trials as Topic, Syncope, Vasovagal
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