Drug Protocol Resolves Most Fetal Tachyarrhythmia

For fetal tachyarrhythmia, a standardized protocol of antiarrhythmic drugs given to the mother was tolerable and effective for most in a multicenter Japanese study.

Among the 50 pregnancies evaluated, fetal sinus rhythm was achieved in 89.8% of cases overall and in three of the four cases of fetal hydrops, reported Yasuki Maeno, MD, of Kurume University School of Medicine in Japan, and colleagues in the Journal of the American College of Cardiology.

Pre-term births were reported in 20.4% of the cohort and two fetal deaths occurred. Within a couple of weeks after birth, neonatal tachyarrhythmia reoccurred in 31.9% of neonates, the investigators found.

Notably, serious adverse events occurred in four fetuses and one mother. Maternal adverse events were reported in 78.0% of patients, they added.

Numerous retrospective investigations have backed the efficacy of transplacental therapy for fetal atrial flutter and supraventricular tachycardia, but the use of a first-line and second-line antiarrhythmic treatment is still not established, the researchers noted. “Because most studies are confounded by physician and institutional preferences, there are few data supporting specific treatment protocols.”

Their protocol-defined transplacental treatment involved rapid initial saturation and repeated doses of IV digoxin (Digitek) as first-line therapy (oral if IV wasn’t feasible) for fetuses with short ventriculoatrial supraventricular tachycardia or atrial flutter without hydrops. Treatment stepped up in 3 day increments if ineffective: Sotalol (Betapace) was added to second-line then dose increased if still ineffective. Then flecainide (Tambocor) was added to digoxin and could be dose increased. If the fetus hadn’t converted by day 3 of the higher dose third-line regimen, it was discontinued. Cases of hydrops went directly to the second-line strategy.

However, the authors cautioned about the fairly high occurrence of maternal adverse events, highlighting a possible underestimation in prior retrospective investigations. Half or more of the women had nausea or vomiting and elevated brain natriuretic peptide concentrations, while 38% had electrocardiographic abnormalities. The one serious event was a Mobitz type II AV block that resolved immediately after temporary discontinuation of digoxin and sotalol.

This study provides key information that will assist providers in making educated drug choices, wrote Janette Strasburger, MD, of the Medical College of Wisconsin in Milwaukee, in an accompanying editorial.

“As we counsel our pregnant patients at initiation of therapy, it is now possible to provide them with realistic estimates of the side effects that they may experience. In general, because pregnant women are usually healthy, these side effects are usually relatively benign,” she added, calling the protocol’s results “outstanding.”

Given the similar maternal digoxin concentrations between oral and IV dosing, Strasburger said her approach would change: “As a long-time IV digoxin advocate, I now will gladly embrace the oral route with the divided loading dosage of 1,500 μg/day. This should be both safer and easier to administer in a labor and delivery or a telemetry setting, without compromising time to achieve therapeutic serum concentration.”

The researchers evaluated 29 patients with atrial flutter, four with long ventriculoatrial supraventricular tachycardia, and 17 with short ventriculoatrial supraventricular tachycardia at 15 institutions in Japan. Median maternal age was 32 years.

Inclusion criteria were singleton pregnancy, ranging from 22 to 37 weeks of gestation, sustained fetal tachyarrhythmia greater than or equal to 180 beats per minute, with a diagnosis of atrial flutter or supraventricular tachycardia.

Patients were excluded if they had a:

• Fetal diagnosis of chaotic atrial tachycardia or multifocal atrial tachycardia
• Life-threatening, serious malformation diagnosed in the fetus
• Psychiatric or mental conditions that precluded safely participating in the trial
• Contraindication to the antiarrhythmic drugs used in the investigations
• Fetus or patient were not eligible for other reasons as determined by the researcher

Limitations of the study included its small sample size, single-arm design, and that the treatment protocol involved three antiarrhythmic agents, making it hard to assess the efficacy and safety of each agent separately.

“Further studies are needed to establish the safest and most effective antenatal treatment regimens for fetal supraventricular tachyarrhythmias,” the authors concluded.

last updated 08.13.2019