Of the 29 fetuses with sustained tachycardia, 14 initially presented with mild-to-moderate congestive heart failure and hydrops (Table 4). Sustained cardio-version with transplacental therapy was successful in eight patients; three responded to digoxin alone and five to the additional transplacental antiarrhythmic agents quinidine (n = 1), verapamil (n = 3), and amiodarone (n = 1). Tachycardia persisted but at a lower rate after combination transplacental treatment in fetus 26, and hydrops did not develop. This fetus was delivered electively at 36 weeks. Time to conversion or progression in group 3 was 1 to 18 (mean 5.4) days.
Two fetuses with mild to moderate congestive heart failure initially did not convert to sustained sinus rhythm or rate control despite combination transplacental therapy. Fetuses 28 and 29 developed severe heart failure after 2 weeks of unsuccessful treatment, necessitating direct fetal treatment and reassignment to group 3. The remaining three fetuses (20, 25, and 27) presented at or near term and were delivered electively by cesarean at the parents' request without antenatal treatment. All three were cardioverted successfully within 12 hours of delivery.
In 17 fetuses (15 fetuses at initial presentation and fetuses 28 and 29), heart failure was severe, with or without an abnormal biophysical profile (excluding heart rate) (Table 5). Fetuses presenting with severe heart failure were significantly less mature than those in group 1 (P = .02). These fetuses were treated with direct intramuscular injections of digoxin (n = 16). Fetus 43 was given intramuscular procainamide in addition to intramuscular digoxin because of advanced hydrops, an abnormal biophysical profile, and severe ventricular dysfunction. We were not confident at this early point in our experience that only one agent given directly would cardiovert a compromised fetus receiving transplacental antiarrhythmic medications.
With direct plus transplacental therapy, 15 fetuses converted to sinus rhythm in 0.25–21 days (mean 4.3 days). In six fetuses, cardioversion occurred 3–24 hours after intramuscular therapy was initiated. Time to resolution of hydrops was 2–56 days. Two immature fetuses were delivered at 33 weeks after spontaneous rupture of membranes. Fetus 44 had partial sinus rhythm with resolving hydrops, and fetus 33 had sustained sinus rhythm with resolved hydrops. Neither required intubation or oxygen therapy.
There was no difference in mean gestational age at delivery among groups. In addition to the two fetuses delivered at 33 weeks after ruptured membranes, six were delivered before 36 weeks (five for obstetric reasons and one because of a restrictive patent foramen ovale and persistent ascites). No fetus required intubation after 24 hours; none had central nervous system or respiratory sequelae of prematurity.
Atrioventricular-reciprocating tachycardia with rates of 220–300 beats per minute was the sole mechanism in 30 fetuses. Ten fetuses had atrial flutter with predominantly 2:1 conduction, one had ventricular tachycardia, and three had more than one type of tachycardia (two atrial flutter plus atrioventricular-reciprocating tachycardia, one atrial flutter plus ventricular tachycardia).
One death occurred for a mortality rate of 2.2% (95% CI 0.06%, 12.0%). A severely hydropic 34-week-old fetus died 80 hours after successful transplacental and direct fetal digoxin therapy. Even with sinus rhythm, this fetus had poor heart rate variability with decreased fetal movement and tone. In contrast to the surviving fetuses that had normal hepatic venous flow pattern within hours of cardioversion, this fetus continued to have reversal of hepatic vein Doppler flow for several days despite sinus rhythm. Maternal viral titers and AF cultures were negative, but postmortem examination of the fetal heart showed lymphocytic infiltrates suggestive of myocarditis. A second major adverse reaction occurred during flecainide treatment, when a slower but incessant fetal tachycardia developed (160–180 beats per minute) and persisted for 3 weeks with progression of hydrops. This condition resolved after flecainide was discontinued.
Minor fetal and maternal adverse reactions resolved after medication reduction or discontinuation. One complication unrelated to treatment occurred in fetus 36, which was delivered at 36 weeks because of persistent ascites despite sustained cardioversion. Necrotizing enterocolitis developed at 1 week of age, but the infant recovered after a prolonged hospitalization and is currently doing well. One mother with normal thyroid function throughout treatment and for 6 months postpartum subsequently developed clinical hypothyroidism. It is not known whether such delayed onset of thyroid dysfunction was attributable to amiodarone therapy. Two fetuses had transient elevation in TSH postnatally without hypothyroidism.
The safe delivery of a full-term, nonhydropic infant with sinus rhythm is the desired outcome of a pregnancy complicated by fetal tachycardia. To achieve this outcome, our management strategy has the following goals: to limit exposure to potent antiarrhythmic agents to fetuses that have or are likely to develop heart failure and, in fetuses with heart failure, to distinguish those for which the risk of direct treatment outweighs the need from those that risk significant morbidity and mortality without direct treatment.
For the compromised fetus with severe heart failure and hydrops, the mortality rate is high (8%–27%).1–8,10 The alternative—delivery of an immature, hydropic infant—has equally unacceptable morbidity and mortality. The combination of direct intramuscular digoxin therapy and short-term transplacental treatment with amiodarone achieved cardioversion or rate control and averted preterm delivery. Because transplacental drug delivery is markedly impaired in the presence of hydrops, direct intramuscular therapy achieves therapeutic drug effect more rapidly, often resulting in short-term cardioversion.6,15 The use of intramuscular digoxin for treatment of supraventricular tachycardia in hydropic fetuses is well established.6,18,19 Other investigators have used intracordal digoxin,7 amiodarone,20 verapamil,7 adenosine (Blanch G, Walkinshaw SA, Walsch K. Cardioversion of fetal tachyarrhythmia with adenosine [letter]. Lancet 1994;44:1646), but there is an inherent risk of fetal death.21,22 Brief conversion of fetal tachycardia can be achieved after cordal drug administration, but recurrence of tachycardia because of atrial ectopy is frequent.4 We, therefore, recommend intramuscular administration of digoxin in conjunction with maternal digoxin because of its safety and superior efficacy in eliminating recurrences when used alone or in tandem with maternal amiodarone therapy.
Amiodarone is highly effective in achieving rapid and sustained conversion (Strasburger JF, Cuneo BF, Naheed Z, Gotteiner N, Duffy E, Deal S, et al. Cardiovascular disease in the young: Short-term amiodarone for refractory fetal tachycardia with hydrops fetalis [abstract]. Circulation 1995;92(Suppl 1)I-764.),23–26 but clinical and biochemical fetal hypothyroidism and possible growth restriction have been reported after long-term exposure during the second and third trimesters.27–29 These consequences have led some investigators to use other transplacental second-line agents, such as verapamil,1,7 quinidine,30 flecainide,31 or sotalol (Eric J. Meijboom, MD, PhD, University Medical Center, Utrecht, The Netherlands, personal communication). However, those agents are not without risk. Fetal death has been reported with flecainide12,14; in addition, concerns about proarrhythmias in other studies32 and in this series have led us to abandon flecainide in favor of amiodarone. Reports of fetal death with verapamil11 and the negative inotropic effects of calcium channel blocking agents in severe congestive heart failure have prompted us to restrict its use to fetuses with no or mild congestive heart failure. We know of no reports of fetal death after transplacental amiodarone therapy. Because these are potent antiarrhythmic agents, however, close supervision by an electrophysiologist is advised for both mother and fetus.
Approximately 75–85% of fetuses with sustained tachycardia and mild heart failure respond to transplacental antiarrhythmic therapy.6,8,10 It is difficult to predict which fetuses will progress to severe heart failure. We have found that it does not depend on tachycardia mechanism or rate but appears to be related to sustained duration of tachycardia and young gestational age.18 Fetal myocardial reserve, status of the placental vascular bed, and other factors might have contributory effects. Most fetuses that cardioverted did so within 24 hours of maternal drug effect, measured either by high serum concentrations (digoxin, procainamide, quinidine, flecainide) or maternal electrocardiographic effects (verapamil, amiodarone, sotalol). Therapeutic options when initial transplacental therapy fails include direct intramuscular digoxin therapy, alternate transplacental drug therapy, or combination transplacental drug therapy. However, if conversion is delayed beyond 1 week, heart failure is likely to progress and hydrops to worsen.
Our results support the findings that fetuses with intermittent tachycardia are at low risk for progression to sustained tachycardia and development of heart failure.8,10,16 However, heart failure has been reported in three of 16 fetuses and in one of nine fetuses with intermittent tachycardia.10,16 There might be a relationship between gestational age and duration of tachycardia. Similar to those in other reports, fetuses with intermittent tachycardia in our series were more mature than those with sustained tachycardia.16 Further investigation is necessary to determine whether the less mature fetus is at greater risk for arrhythmia progression. For this reason, we recommend vigilant fetal heart rate and ultrasound monitoring to allow for early intervention should tachycardia progress and heart failure develop.
Vigilant monitoring must be continued for the remainder of the pregnancy, even after sustained conversion. Phasic forward flow has been seen in the hepatic vein almost immediately after cardioversion even in severe congestive heart failure.33,34 The findings of significant reversed flow many hours after sustained sinus rhythm and persistently poor fetal movement are poor prognostic signs, as seen in the fetus that died in our series. Although this strategy resulted in low morbidity and mortality rates, the study was limited by a small sample size.
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© 2000 The American College of Obstetricians and Gynecologists
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