Antenatal Antiarrhythmic Treatment for Fetal Tachyarrhythmias: A Prospective Multicentre Trial

Abstract

Background: Standardized treatment of fetal supraventricular tachycardia (SVT) and atrial flutter (AFL) has not been established. The aim of this study was to evaluate the safety and efficacy of protocol-defined transplacental treatment for fetal SVT and AFL. Methods: In this multicentre single-arm trial (UMIN Clinical Trials Registry number 000004270), protocol-defined transplacental treatment using digoxin, sotalol, and flecainide was performed for singletons from 22 to <37 weeks of gestation with sustained fetal SVT or AFL ≥180 beats per minute. The primary endpoint was resolution of fetal tachyarrhythmia. Secondary endpoints were fetal death, preterm birth, neonatal arrhythmia, and neonatal survival. Maternal, fetal, and neonatal adverse events (AEs) were evaluated. Findings: A total of 50 participants were enrolled and treated at 15 institutions in Japan from October 2010 to January 2017. They had short VA SVT (n=17), long VA SVT (n=4), and AFL (n=29). One participant with AFL was excluded due to withdrawal of consent. Fetal tachyarrhythmia resolved in 89·8% (44 of 49) of cases overall and 75·0% (3 of 4) of cases with fetal hydrops. Preterm births occurred in 20·4% (10 of 49) of participants. Maternal AEs were observed in 78·0% (39 of 50) of pregnant women. Severe AEs occurred in one mother and four fetuses, resulting in discontinuation of protocol treatment in four participants. Two fetal deaths occurred, mainly due to heart failure. No neonatal deaths occurred. Neonatal tachyarrhythmia was observed in 31·9% (15 of 47) of participants within 2 weeks after birth, except for one neonate with SVT. Interpretation: Protocol-defined transplacental treatment for fetal SVT and AFL was effective and tolerable in 90% of participants. However, it should be kept in mind that severe AEs may take place in fetuses and that recurrence of tachyarrhythmias may happen within 2 weeks after birth. Clinical Trials Number: UMIN Clinical Trials Registry number 000004270 Funding Statement: This work was supported by a grant from the Ministry of Health, Labor and Welfare of Japan (Health and Labour Science Research Grants for Clinical Research for New Medicine) (H19-009, H23-004), and in part by a grant from the Takeda Science Foundation (J042) and Tsuchiya Foundation (J151). Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The Institutional Review Board of the National Cerebral and Cardiovascular Center of Japan.