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Comparison of Transplacental Treatment of Fetal Supraventricular Tachyarrhythmias With Digoxin, Flecainide, and Sotalol: Results of a Nonrandomized Multicenter Study
Open accessAbstract
BACKGROUND: Fetal tachyarrhythmia may result in low cardiac output and death. Consequently, antiarrhythmic treatment is offered in most affected pregnancies. We compared 3 drugs commonly used to control supraventricular tachycardia (SVT) and atrial flutter (AF). METHODS AND RESULTS: We reviewed 159 consecutive referrals with fetal SVT (n=114) and AF (n=45). Of these, 75 fetuses with SVT and 36 with AF were treated nonrandomly with transplacental flecainide (n=35), sotalol (n=52), or digoxin (n=24) as a first-line agent. Prenatal treatment failure was associated with an incessant versus intermittent arrhythmia pattern (n=85; hazard ratio [HR]=3.1; P<0.001) and, for SVT, with fetal hydrops (n=28; HR=1.8; P=0.04). Atrial flutter had a lower rate of conversion to sinus rhythm before delivery than SVT (HR=2.0; P=0.005). Cardioversion at 5 and 10 days occurred in 50% and 63% of treated SVT cases, respectively, but in only 25% and 41% of treated AF cases. Sotalol was associated with higher rates of prenatal AF termination than digoxin (HR=5.4; P=0.05) or flecainide (HR=7.4; P=0.03). If incessant AF/SVT persisted to day 5 (n=45), median ventricular rates declined more with flecainide (-22%) and digoxin (-13%) than with sotalol (-5%; P<0.001). Flecainide (HR=2.1; P=0.02) and digoxin (HR=2.9; P=0.01) were also associated with a higher rate of conversion of fetal SVT to a normal rhythm over time. No serious drug-related adverse events were observed, but arrhythmia-related mortality was 5%. CONCLUSION: Flecainide and digoxin were superior to sotalol in converting SVT to a normal rhythm and in slowing both AF and SVT to better-tolerated ventricular rates and therefore might be considered first to treat significant fetal tachyarrhythmia.
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“Additional support for safety has been gained from treatment of foetal arrhythmias.407”
From European Heart Rhythm Association (EHRA) consensus document on the management of supraventricular arrhythmias, endorsed by Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLAECE) (2017) · cites this paper as [407]
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“Flecainide and sotalol can both be used for conversion of foetal arrhythmias without major adverse effects, 920”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [920]
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Fetal tachycardias: management and outcome of 127 consecutive cases
Simpson, J. M., & Sharland, G. K. (1998) · Heart · doi:10.1136/hrt.79.6.576 · Cited by 307
Allan, L. D., Hornberger, L. K., & Sharland, G. K. (2000) · Cited by 223
Management outcome and follow-up of fetal tachycardia
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Amiodarone Therapy for Drug-Refractory Fetal Tachycardia
Strasburger, J. F., Cuneo, B. F., Michon, M. M., Gotteiner, N. L., Deal, B. J., McGregor, S. N., Oudijk, M. A., Meijboom, E. J., Feinkind, L., Hussey, M. A., et al. (2004) · Circulation · doi:10.1161/01.cir.0000109494.05317.58 · Cited by 210
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Fetal tachycardia: Mechanisms and predictors of hydrops fetalis
Naheed, Z. J., Strasburger, J. F., Deal, B. J., Benson, D. W., & Gidding, S. S. (1996) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(96)00054-x · Cited by 193
Perinatal Outcome of Fetal Atrioventricular Block
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Sotalol in the Treatment of Fetal Dysrhythmias
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Atrial flutter in the perinatal age group: diagnosis, management and outcome
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2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P. F., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castellà, M., Diener, H., Heidbüchel, H., Hendriks, J., et al. (2016) · EP Europace · doi:10.1093/europace/euw295 · Cited by 6,438
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw210 · Cited by 6,418
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezw313 · Cited by 1,403
Donofrio, M. T., Moon-Grady, A. J., Hornberger, L. K., Copel, J. A., Sklansky, M. S., Abuhamad, A., Cuneo, B. F., Huhta, J. C., Jonas, R. A., Krishnan, A., et al. (2014) · Circulation · doi:10.1161/01.cir.0000437597.44550.5d · Cited by 1,275
“will benefit from the initiation of transplacental medical therapy.(449,491) Although data are limited, fetal autoimmune-mediated”
BackgroundBrugada, J., Katritsis, D. G., Arbelo, E., Arribas, F., Bax, J. J., Blomström‐Lundqvist, C., Calkins, H. G., Corrado, D., Deftereos, S. G., Diller, G., et al. (2019) · European Heart Journal · doi:10.1093/eurheartj/ehz467 · Cited by 1,312
Metadata
- Authors
- Jaeggi, E. T., Carvalho, J. S., De Groot, E., Api, O., Clur, S.-A. B., Rammeloo, L., McCrindle, B. W., Ryan, G., Manlhiot, C., & Blom, N. A.
- Affiliations
- Mount Sinai Hospital (CA)
- From the Hospital for Sick Children (E.T.J., B.W.M., C.M.) and Mount Sinai Hospital (G.R.), University of Toronto, Toronto, ON, Canada; Royal Brompton and St. George's Hospitals, London, UK (J.S.C., O.A.); Leiden University Medical Center, Leiden, the Netherlands (E.D.G., N.A.B.); Academic Medical Center, Amsterdam, the Netherlands (S.-A.B.C.); and Free University Medical Center, Amsterdam, the Netherlands (L.R.).
- ORCID
- Venue
- Circulation
- Published
- 2011-10-18
- Volume
- 124
- Issue
- 16
- Pages
- 1747-1754
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2096612114
- Cited by
- 237
- References
- 30
- Citations by year
- 2026: 16 · 2025: 16 · 2024: 11 · 2023: 19 · 2022: 15 · 2021: 15 · 2020: 12 · 2019: 11 · 2018: 15 · 2017: 18 · 2016: 16 · 2015: 18 · 2014: 17 · 2013: 19 · 2012: 18
- FWCI
- 12.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Congenital Heart Disease Studies
- Keywords
- fetal supraventricular tachycardia, fetal atrial flutter, digoxin, flecainide, sotalol, hydrops fetalis, ventricular rate control, drug safety in pregnancy
- MeSH terms
- Anti-Arrhythmia Agents, Digoxin, Drug Evaluation, Female, Fetal Diseases, Flecainide, Humans, Pregnancy, Retrospective Studies, Sotalol, Tachycardia, Supraventricular, Treatment Outcome, Fetal Therapies
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