Multiple antiarrhythmic transplacental treatments for fetal supraventricular tachyarrhythmia: A protocol for systematic review and meta analysis.

BACKGROUND: Fetal supraventricular tachyarrhythmia is a common reason for referral to fetal cardiology. Multiple antiarrhythmic transplacental medications can be used to treat these diseases. Debates remain regarding the standardized therapy. METHODS: PubMed, EMBASE, Cochrane Library, Web of Science, Google Scholar, and ClinicalTrials.gov will be searched from inception to September 2020. A handsearching for gray literature, including unpublished conference articles, will be performed. The randomized control trials, case-control, and cohort studies will be accepted, no matter what the languages they were reported. We will first focus on the effectiveness of the therapy on fetal cardiac rhythm and/or heart rate. Then we will do further analysis of preterm delivery, fetal hydrops, intrauterine fetal demise, and maternal side effects. The Cochrane Risk of Bias Tool and the Newcastle-Ottawa scale will be used to assess the risk of bias of the randomized controlled trials, case-control, and cohort studies, respectively. Two independent reviewers will carry out literature identification, data collection, and study quality assessment. Discrepancies will be resolved by a third reviewer. Statistical analysis will be conducted using the STATA 13.0 software. RESULT: The results will provide helpful information about the effect of multiple antiarrhythmic transplacental therapies in pregnancies with supraventricular tachycardia or atrial flutter, and demonstrate which therapy is more effective. CONCLUSION: The conclusion drawn from this systematic review will benefit the patients with fetal supraventricular tachyarrhythmia.

Fetal supraventricular tachycardia at 12 weeks of gestation: diagnosis and follow up. A case report.

This report describes a case of fetal supraventricular tachycardia (SVT) diagnosed at 12 weeks of gestation in a pregnant woman with diabetes mellitus. Transplacental digoxin therapy administered orally to the mother was unsuccessful. Subsequently, sotalol was added to digoxin to achieve fetal heart rate (HR) control and the conversion to sinus rhythm was achieved. The fetal HR remained stable until term, and a healthy male baby was born. The newborn electrocardiogram showed sinus rhythm with normal PR and QTc intervals. When the newborn was stable, he was discharged with propanolol. Sustained SVT is extremely rare during the first trimester. The goal of treatment in utero is the conversion to sinus rhythm or reduction of the ventricular rate to tolerable levels, preventing or even reversing fetal hydrops.

Transplacental digoxin therapy for fetal tachyarrhythmia with multiple evaluation systems.

BACKGROUND: Sustained fetal tachyarrhythmia may result in congestive heart failure, hydrops fetalis, and fetal/neonatal death, which requires timely and appropriate therapy. AIM: To determine the value of transplacental digoxin therapy for fetal tachyarrhythmia with multiple evaluations. METHODS: Four cases of fetal tachyarrhythmia were diagnosed with fetal echocardiography and treated with transplacental digoxin therapy with an initial dosage of 0.25 mg qd. Fetal echocardiography and measurement of maternal serum digoxin concentrations were performed every 5-7 days. Echocardiographic information was further used for the calculation of three evaluation systems including, Tei index, cardiovascular profile score (CVPS), and umbilical artery resistance index (UARI). The dosage of digoxin was adjusted according to the serum concentration, as well as results from three evaluation systems. RESULTS: During the course of digoxin treatment, our patients show an increase of CVPS and decrease of Tei index and UARI, suggesting the recovery of heart function. Sinus rhythm was restored in 3-10 days in three cases and 42 days in one case. At the time of delivery, the placental transportation efficiency (neonate/mother ratio of serum digoxin concentration) was 76.45-84.31%. Following delivery, the general conditions of neonates were favorable. During the 4- to 14-month follow-up, reoccurrence of arrhythmia, neurological deficit, and retarded growth and development were not observed. CONCLUSIONS: Transplacental digoxin therapy with combined evaluation of Tei index, CVPS, and UARI systems is useful for treating fetal atrial flutter (AF) and supraventricular tachycardia (SVT).

Can digoxin and sotalol therapy for fetal supraventricular tachycardia and hydrops be successful? A case report.

BACKGROUND: Neonatal survival and prognosis are closely linked with development of hydrops in cases of sustained fetal tachycardia. Several antiarrhythmic medications are available for conversion to sinus rhythm. CASE: An 18-year-old woman had an audible fetal arrhythmia at 25 weeks' gestation. Fetal echocardiography revealed supraventricular tachycardia with worsening cardiac function at 28 weeks. Digoxin therapy was initiated and sotalol was later added for new-onset hydrops. The medications were then adjusted, and the fetus' heart rate converted to sinus rhythm with resolution of the hydrops. The patient was then managed as an outpatient with antenatal testing, serial laboratory studies and electrocardiograms until 39 weeks. CONCLUSION: Digoxin and sotalol therapy can be successful in blocking likely nodal reentry in sustained fetal supraventricular tachycardia, thus allowing resolution of hydrops with a favorable outcome.

[Combination therapy for fetal supraventricular tachycardia with flecainide and digoxin]. / Kombinationstherapie einer fetalen supraventrikulären Tachykardie mit Flecainid und Digoxin.

Persistent fetal supraventricular tachycardia (SVT) with more than 210 bpm frequently leads to congestive heart failure. We report on a case with SVT and congestive heart failure that converted into sinus rhythm within 19 days of therapy with flecainide and beta-acetyldigoxin. A 32-year-old II gravida I para (25 + 1 weeks of gestation) presented with fetal SVT of 267 bpm. A non-immunologic hydrops fetalis was diagnosed by ultrasound showing ascites, pleural and pericardial effusion and tricuspid regurgitation. Within 19 days of combination therapy with flecainide and digoxin, cardioversion was achieved. After 36 days of therapy no more signs of cardiac failure could be detected. A healthy boy was born at 38 + 6 weeks of gestation. Although cardioversion is expected after 72 h of therapy according to the literature, this fetus converted into sinus rhythm on day 19 of therapy. This indicates that patients should not be considered resistant to treatment within the first 3 - 4 days.

Characterization of fetal arrhythmias by means of fetal magnetocardiography in three cases of difficult ultrasonographic imaging.

Characterization of ultrasound detected fetal arrhythmias is generally performed by means of M-mode and pulsed Doppler echocardiography (fECHO), sonographic techniques that allow only indirect and approximate reconstruction of the true electrophysiological events that occur in the fetal heart. Several studies demonstrated the ability of fetal magnetocardiography (fMCG) to identify fetal arrhythmias. We report on three women, studied after the 32nd gestational week, who were referred for fMCG because of unsatisfying fetal cardiac visualization with fECHO due to maternal obesity, fetus in constant dorsal position hiding the fetal heart, intrauterine growth retardation, and oligohydramnios. Minor pericardial effusion was present in the third patient and digoxin therapy was given. FMCG were recorded with a 77-channel MCG system working in a shielded room. Independent Component Analysis (FastICA algorithm) was used to reconstruct fetal signals. The good quality of the retrieved fetal signals allowed real-time detection of arrhythmias and their classification as supraventricular extrasystoles (SVE), with/without aberrant ventricular conduction and/or atrioventricular block. The time course of the fetal cardiac rhythm was reconstructed for the entire recording duration; hence, fetal heart rate variability could be studied in time and frequency. Since isolated extrasystoles may progress to more hazardous supraventricular tachycardias, the noninvasive antenatal characterization of, even transient, fetal arrhythmias and their monitoring during pregnancy can be of great clinical impact.

Giant fetal magnetocardiogram P waves in congenital atrioventricular block: a marker of cardiovascular compensation?

BACKGROUND: Cardiogram signal amplitude is a key index of hypertrophy but has not been investigated extensively in utero. In this study, magnetocardiography was used to assess P and QRS amplitude in normal subjects and subjects with fetal arrhythmia. METHODS AND RESULTS: The study cohort consisted of 68 normal fetuses and 25 with various arrhythmias: 9 reentrant supraventricular tachycardia (SVT), 2 ventricular tachycardia (VT), 2 sinus tachycardia, 2 blocked atrial bigeminy, 2 congenital second-degree atrioventricular (AV) block, and 8 congenital complete AV block. Subjects with congenital AV block, all presenting with bradycardia, showed large QRS amplitude, exceedingly large P-wave amplitude, and long P-wave duration. The 2 subjects with VT, both with poor ventricular function, also exhibited large P waves. SVT was associated with only moderate signal amplitude elevation. CONCLUSIONS: The data imply that AV block in utero is accompanied by hypertrophy, which is more pronounced for the atria than the ventricles. We hypothesize that the hypertrophy results from a compensatory response associated with regulation of cardiac output and is likely to be observable in other arrhythmias and disease states. Magnetocardiography may be more sensitive than fetal echocardiography for detection of atrial hypertrophy in utero.

Role of amiodarone in the treatment of fetal supraventricular tachyarrhythmias and hydrops fetalis.

We report three consecutive hydropic fetuses with fetal tachyarrhythmias treated with amiodarone-two in combination with digoxin and one with digoxin, procainamide, and propranolol. Sinus rhythm was achieved in one case and ventricular rate control was achieved in two cases. All fetuses treated with amiodarone gradually improved. Observed side effects of amiodarone were a maternal rash in one mother and transient neonatal hypothyroidism in one infant. We conclude that amiodarone might be effective and safe for fetal tachyarrhythmias and impending hydrops. The small number of patients suggests that a multicenter cooperative approach is required in order to determine if this is correct.

Location of accessory connection in infants presenting with supraventricular tachycardia in utero: clinical correlations.

The most common mechanism of fetal tachycardia is orthodromic reciprocating tachycardia utilizing an accessory atrioventricular connection, however, data regarding accessory connection location in patients with fetal tachycardia is limited. To investigate the location of accessory connections in fetal tachycardia, postnatal transesophageal electrophysiology studies were performed at one institution over a 10-year period in 24 infants with documented fetal tachycardia. The 18 infants with inducible orthodromic reciprocating tachycardia were grouped according to accessory connection location, and groups were compared regarding prenatal presentation and clinical course. Left-sided connections were found in 13 (72%) patients, while accessory connection location could not be determined in the remaining 5 (28%) patients. The presence of a left-sided accessory connection was associated with sustained tachycardia, depressed ventricular function, and the need for antiarrhythmic therapy in utero. No other difference in clinical or electrophysiologic data was found between groups. Our findings indicate that a high proportion of patients with fetal tachycardia have left-sided accessory connections, and a left-sided connection may adversely affect fetal hemodynamics and cardiac output.

Fetoscopic transesophageal electrocardiography and stimulation in fetal sheep: a minimally invasive approach aimed at diagnosis and termination of therapy-refractory supraventricular tachycardias in human fetuses.

BACKGROUND: Therapy-refractory supraventricular tachycardia commonly results in hydrops and death in human fetuses. The purpose of this study in fetal sheep was to assess the feasibility of a minimally invasive fetoscopic approach for fetal transesophageal electrocardiography and stimulation aimed at diagnosis and termination of these tachycardias. METHODS AND RESULTS: We studied a total of 10 fetal sheep (87 to 103 days of gestation; term=145 days). We entered the amniotic cavity using a percutaneous fetoscopic approach and placed various electrophysiology catheters into the fetal esophagus. We recorded the number of animals in which fetoscopic transesophageal electrocardiography and stimulation were successful and assessed pacing success and thresholds for different catheters. In addition, we monitored for potential adverse effects from stimulation and for other complications of the operation. Recording of transesophageal electrocardiograms was successful in all fetal sheep. Capture during stimulation was successfully documented by additional fetal bipolar surface electrocardiograms in 7 fetuses. In fetuses in which fetal surface electrocardiograms were not recorded, pacing stimulus artifacts interfered with documentation of capture. Although stimulation thresholds were high, the maternal rhythm was not affected by fetal stimulation. CONCLUSIONS: Fetoscopic fetal transesophageal electrocardiography and stimulation are feasible in fetal sheep. This minimally invasive approach might have the potential to improve diagnosis and management of therapy-refractory supraventricular tachycardias in human fetuses.

Antiarrhythmic drug therapy in pregnancy and lactation.

Antiarrhythmic agents commonly used in clinical practice are reviewed with respect to their potential for teratogenic or other adverse fetal effects. Although most experience with antiarrhythmic drug therapy during pregnancy has accrued with digoxin, quinidine, and propranolol, other antiarrhythmic agents may also be used in the pregnant patient if indicated. The choice of antiarrhythmic drug depends on the specific arrhythmia being treated, the cardiac condition of the patient or fetus, and the known or anticipated actions of the antiarrhythmic drug being considered. The management of specific arrhythmias encountered in pregnant women are also discussed. For benign arrhythmias, a conservative approach starting first with preventive measures is appropriate. For more severe or symptomatic arrhythmias, pharmacologic therapy should be instituted using drugs with proven safety to the fetus, if possible. Electrical cardioversion of the patient may be performed with relative safety in more emergent situations.

[Fetal supraventricular tachycardia associated with anasarca: poor prognosis despite treatment. Apropos of two cases]. / Tachycardies supraventriculaires foetales avec anasarque: mauvais pronostic malgré le traitement. A propos de deux cas.

Two cases of foetal supraventricular tachycardia with hydrops with fatal outcomes illustrate the poor general prognosis of this condition. The absence of therapeutic consensus, of large series in the existing literature, does not prevent logical and reasonable management based on rhythmological, pharmacological and prognostic criteria. A combined approach associating antiarrhythmic therapy by the transplacental and intrafunicular approaches seems acceptable now that funicular puncture can be undertaken easily, and certain antiarrhythmic molecules suggest encouraging results. It is important to try to assess the haemodynamic tolerance by foetal Doppler echocardiography because the foetal prognosis depends on ischaemic cerebral lesions induced by anoxia, difficult to diagnose in utero: when observed, aggressive and occasionally dangerous therapies to foetus and mother may be justified in these extreme situations of foetoplacental hydrops.

Successful treatment of supraventricular tachycardia with flecainide acetate: a case report.

BACKGROUND: Efficacy of flecainide acetate for the treatment of fetal supraventricular tachycardia with cardiac failure was reported. CASE: For a case in which maternal digoxin therapy failed, flecainide acetate (400 mg/day) is used from 27 weeks. Cardioversion with improved cardiac function occurred 6 days after treatment. Fetal serum flecainide acetate level was 292 ng/ml which was 64% of the maternal level (453 ng/ml). No adverse maternal side effects were noted with 11 weeks of therapy. A vigorous male baby, weighing 3,610 g, Apgar 8/9, Ua-pH 7.24, was born. He is now 1 year of age and in good condition with medication of 5 mg/kg flecainide acetate. CONCLUSION: Flecainide acetate seemed to be safe for both mother and fetus, and effective for the treatment of fetal supraventricular tachycardia which is refractory to transplacental digoxin therapy.

[Successful treatment of fetal supraventricular tachycardia with a combination of digoxin and amiodarone]. / Magzati supraventricularis tachycardia sikeres kezelése digoxin és amiodaron kombinációjával.

The supraventricular tachycardia is a life threatening state in the intrauterine life. It can cause non-immune hydrops fetalis, intrauterine death or complications during the delivery. The unexplained tachycardia can cause fetal distress and premature delivery. Usually the digoxin is the first drug of choice for transplacental cardioversion. If digitalisation does not achieve cardioversion, the second line antiarrhythmic drugs should be instituted. Amiodarone has been suggested as a therapeutic alternative after failure of digoxin-verapamil combination. We give a drug in standard therapeutic doses for four-five days and after it we determine whether it is effective or not. We should determine the newer therapy or termination of pregnancy. The transplacental administration of amiodarone may be dangerous because of fetal cretinism. Our case is the first in Hungary-in our best knowledge- and we suggest the amiodarone for transplacental therapy.