Atrial and Ventricular Rate Response and Patterns of Heart Rate Acceleration during Maternal–Fetal Terbutaline Treatment of Fetal Complete Heart Block

Abstract

Terbutaline is used to treat fetal bradycardia in the setting of complete heart block (CHB); however, little is known of its effects on atrial and ventricular beat rates or patterns of heart rate (HR) acceleration. Fetal atrial and ventricular beat rates were compared before and after transplacental terbutaline treatment (10 to 30 mg/day) by fetal echocardiography in 17 fetuses with CHB caused by immune-mediated damage to a normal conduction system (isoimmune, n = 8) or a congenitally malformed conduction system associated with left atrial isomerism (LAI, n = 9). While receiving terbutaline, 9 of the 17 fetuses underwent fetal magnetocardiography (fMCG) to assess maternal HR and rhythm, patterns of fetal HR acceleration, and correlation between fetal atrial and ventricular accelerations (i.e., AV correlation). Maternal HR and fetal atrial and ventricular beat rates increased with terbutaline. However, terbutaline's effects were greater on the atrial pacemaker(s) in fetuses with isoimmune CHB and greater on the ventricular pacemaker(s) in those with LAI-associated CHB. Patterns of fetal HR acceleration also differed between isoimmune and LAI CHB. Finally, despite increasing HR, terbutaline did not restore the normal coordinated response between atrial and ventricular accelerations in isoimmune or LAI CHB. In conclusion, the pathophysiologic heterogeneity of CHB is reflected in the differing effect of terbutaline on the atrial and ventricular pacemaker(s) and varying patterns of HR acceleration. However, regardless of the cause of CHB, terbutaline augments HR but not AV correlation, suggesting that its effects are determined by the conduction system defect rather than the autonomic control of the developing heart. Fetal complete heart block (CHB) is a rare condition, occurring in approximately 1 of 15,000 pregnancies. Fetal CHB that occurs in association with maternal immunoglobulin-G Sjögren antibodies (i.e., isoimmune CHB) is believed to be a result of immune-mediated fibrosis disrupting continuity between the atrium and the atrioventricular (AV) bundle relatively late in cardiogenesis, 1-3 whereas CHB associated with congenital cardiac malformations such as left atrial isomerism (LAI) is believed to result from maldevelopment of the conduction system early in cardiogenesis, probably during pattern formation of the specialized versus working myocardium. 4 heterogeneity, it might be expected that the electrophysiologic characteristics of the atrial and ventricular pacemakers in fetuses with CHB would differ in response to pharmacologic heart rate (HR) augmentation with a β agonist such as terbutaline. [8][9][10] Using the technique of fetal magnetocardiography (fMCG)-the only high-resolution fetal electrocardiography technique with the capacity for beat-to-beat analysis over many hours-we observed patterns of HR accelerations, the atrial and ventricular pacemaker response, and the ventricular rate response to atrial accelerations (i.e., AV correlation) during terbutaline treatment in fetuses with isoimmun...

Diagnosis and Treatment of Fetal Cardiac Disease

“…351,352 fMCG has led to modifications in medical therapy of arrhythmias in some cases. [329][330][331]353 Unlike fetal electrocardiography, fMCG allows raw signal analysis even in the presence of an irregular rhythm. fMCG holds an inherent advantage over fetal electrocardiography in signalto-noise ratios because the conductance properties of magnetic signals are not affected by poor conductivity of fetal and maternal tissues.…”

“…Regardless of the origin (immune mediated or structural CHB), the use of β-sympathomimetics (terbutaline, salbutamol, isoprenaline) to augment fetal ventricular rates when <55 bpm has been reported. 353 β-Sympathomimetics are reasonable to use in fetuses with heart rates <55 bpm or in fetuses with higher heart rates if there is underlying severe CHD or symptoms of fetal heart failure or hydrops. Terbutaline appears to be well tolerated, although maternal resting heart rates of 100 to 120 bpm and benign ectopy are commonly encountered.…”

Evaluation of Transplacental Treatment for Fetal Congenital Bradyarrhythmia

“…13- 19 Jaeggi et al reported a significant improvement in the outcome of fetal CAVB simultaneously with the introduction of routine perinatal treatment guidelines in 1997. 9 Hutter et al obtained an improved survival rate of >90% by initiation of maternal high-dose dexamethasone at the time of CAVB detection and maintenance of this dose during pregnancy, with addition of β-sympathomimetics to keep the fetal heart rate above 55 beats/min.…”

“…2,7-9,11, 12 There is limited evidence for the clinical efficacy of transplacental treatment of congenital AVB. [13][14][15][16][17][18][19] Steroids and i.v. immunoglobulins are given as anti-inflammatory treatment, while β-sympathomimetics are used for fetal pacing.…”

Isolated Atrioventricular Block in the Fetus

“…Maternal betamimetic therapy for fetuses with ventricular rates Ͻ55 bpm has also been given, with minimal benefit in most reports. 6,[12][13][14] …”