Download Amiodarone in treatment of fetal

Fetal Diagn Ther 2006;21:72–76
DOI: 10.1159/000089052
Received: July 13, 2004
Accepted after revision: December 14, 2004
Amiodarone in Treatment of Fetal
Supraventricular Tachycardia
A Case Report and Review of Literature
Mandakini Pradhana Manishaa Renu Singha Aditya Kapoorb
Departments of a Medical Genetics and b Cardiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences,
Lucknow, U.P., India
Key Words
Fetal supraventricular tachycardia Amiodarone Hydrops fetalis
Abstract
We report a case of nonimmune hydrops fetalis detected
at 32 weeks of gestation. Fetal heart rate was 300 beats
per minute. Ultrasound and fetal Doppler echocardiography showed it to be due to supraventricular tachycardia (SVT). Following failed maternal therapy with digoxin alone, amiodarone with digoxin was used. Conversion
to sinus rhythm and resolution of hydrops followed this
treatment. Since there is no ideal treatment protocol for
these cases at present, we reviewed reports of transplacental treatment of SVT.
Copyright © 2006 S. Karger AG, Basel
Introduction
Nonimmune hydrops accounts for 80% of cases of hydrops fetalis. Cardiac causes are seen in more than 25%
cases after 28 weeks’ gestation. Fetal tachyarrhythmia is
associated with a significant perinatal morbidity and
mortality when hydrops occurs. Although the natural his-
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tory remains poorly understood, it seems that half of the
fetuses with supraventricular tachycardia (SVT) develop
hydrops and of these the majority will develop clinical
hydramnios. Perinatal mortality ranges from 40 to 90%
in untreated hydrops. A number of drugs like digoxin,
propranolol, flecainide, procainamide, verapamil, and
amiodarone have been used with varying success in these
cases. Here, we report a case of fetal SVT complicated
with heart failure; transplacental therapy with amiodarone and digoxin could achieve a sinus rhythm after failure with digoxin alone.
Case Report
A 28-year-old G3 P2 was referred to our clinic for investigation
and treatment of polyhydramnios, observed at 32 weeks of gestation. Her investigations for gestational diabetes (glucose tolerance
test), intrauterine infection (antibody titers for toxoplasmosis, cytomegalovirus, rubella, parvovirus B19) were normal. The previous
ultrasound done at 20 weeks did not show any abnormality. On
ultrasonography, a single live fetus with ascites, pleural and pericardial effusion, and skin edema was seen. The fetal heart rate
(FHR) was 300 beats per minute, with a 1:1 atrioventricular conduction. There was no structural cardiac defect. Amniotic fluid
index was increased (30 cm) with increased placental thickness
(9 cm). The diagnosis of heart failure secondary to SVT was made.
Transplacental treatment with digoxin was initiated at the dose of
Dr. Mandakini Pradhan
Department of Medical Genetics
Sanjay Gandhi Postgraduate Institute of Medical Sciences
Rae Bareli Road, Lucknow, U.P (India)
Tel. +91 522 2668700 2335, Fax +91 522 26680172, E-Mail [email protected]
0.25 mg 6 hourly for 24 h, then once daily. The maternal plasma
digoxin levels measured before the subsequent dose was between
1.7 and 2 g/l. Though initially the tachycardia responded to digoxin with reversion to sinus rhythm after 48 h, the tachycardia
recurred again within next 24 h. Subsequently, amiodarone at the
dose of 1,000 mg/day for 2 days followed by 400 mg/day in two
divided doses was added to the existing digoxin therapy of 0.25 mg/
day. FHR reverted to sinus rhythm after 24 h of starting amiodarone. Regular ultrasonography showed FHR in the normal range
and there was gradual decrease in fetal ascites and pericardial and
pleural effusion until it resolved completely by 35 weeks. The same
treatment was continued up to 37 weeks; she delivered a baby girl
weighing 2.7 kg by cesarean section in view of transverse lie. The
baby had sinus rhythm with no evidence of pre-excitation or signs
of cardiac failure at birth, and therefore did not require any treatment. Echocardiography and thyroid profile on 1st, 3rd, and 7th
day were normal. The child is now 6 months of age and has not had
any recurrence of tachyarrhythmia.
Apart from amiodarone, flecainide is another widely used antiarrhythmic drug. Hence, we have analyzed all published data retrieved through PubMed to compare their effectiveness and side
effects in treatment of fetal SVT. For the articles which were published in languages other than English, the abstract of the articles
were used for analysis.
Discussion
Identification of the type of arrhythmia is essential before starting transplacental therapy. A tachycardia is defined as FHR in excess of 200 beats/min. SVT is diag-
nosed if there is 1:1 atrioventricular conduction, and atrial flutter when the atrial rate is in excess of ventricular
rate [1]. In particular, ventricular tachycardia must be
excluded, as it contraindicates treatment with digoxin [2].
The earliest gestation at which the SVT has been diagnosed is at 13 weeks [3]. As it is difficult to predict which
fetus with tachycardia will eventually develop hydrops,
most centers initiate treatment as soon as the diagnosis
of fetal tachycardia is established [4]. Most authorities
recommend that the fetus should be in SVT more than
50% of the time to initiate treatment. The primary form
of pharmacological intervention is maternal transplacental therapy. Other routes of treatment are intravascular
and intramuscular treatment of fetus, which is mainly
used in refractory cases.
Digoxin is the most common drug used to treat fetal
tachycardia [4]. Transplacental digoxin has been found
to be effective in treating SVT complicated by fetal hydrops in a small percentage, but there has been no consensus regarding antiarrhythmic treatment if digoxin
therapy fails. Sotalol was earlier thought to be drug of
choice for fetal SVT because it is efficient in treating arrhythmia in infants [5]. However, there has been report
of 4 sudden fetal deaths in 21 fetuses treated with sotalol,
3 of which occurred just after initiation of treatment. This
suggested a proarrhythmic affect of this drug [4]. Verapamil is also not recommended as it has been associated
Table 1. Outcome of transplacental treatment of SVT: literature review
S. Authors
no.
1 Belhassan et al. [12]
Total no.
of cases
1
Diagnosis
1st-line
therapy
Outcome
2nd-line
therapy
Outcome/side effects
NM
D
failed
A
SR
2 Valhot et al. [13]
1
H
D
failed
A
SR
3 Owen et al. [6]
1
H
D+V
failed
–
Fetus died
4 Kofinas et al. [14]
1
H
D
failed
F
SR
14
H
F
SR
IUD
failed
5 Allan [8]
11
1
2
6 Amiel et al. [15]
2
H
D+A+S
SR
2
7 De Catte et al. [9]
1
H
A
SR
1
1
NH
A
SR
1
NH 22
D
SR
12
H 13
D6
SR
IUD
SR
Del
NND
8 Chen et al. [16]
9 Frohn-Mulder et al. [17]
35
F7
Amiodarone in Treatment of Fetal
Supraventricular Tachycardia
1
3
3
3*
1
D
2
SR
1
Hypothyroidism in fetus
F
Del
V/P
4
6*
2
SR
4
NND
2
Fetal Diagn Ther 2006;21:72–76
73
Table 1 (continued)
S. Authors
no.
Total no.
of cases
Diagnosis
1st-line
therapy
Outcome
10 Vanderhal et al. [18]
1
H
F
SR
11 Van Gelder et al. [19]
1
H
D
failed
1
2nd-line
therapy
Outcome/side effects
–
Conjugated hyperbilirubinemia in fetus
F
SR
12 Hajdu et al. [20]
1
H
D
failed
A
SR
13 Amano et al. [21]
1
H
D
failed
F
SR
14 Hamel et al. [22]
1
H
F
SR
1
15 Chang et al. [23]
1
H
D
SR
1
NH 63
D
SR
SVT
–
Alive
IUD
SR
SVT
5
2
10
4
16 Simpson and Sharland [1] 110
39
24
V
H 47
D6
D+V 14
SR
IUD
Alive
SVT
SR
IUD
SVT
F 27
SR
IUD
NND
1
1
3
1
7
1
4*
15
4
2
17 Edwards et al. [24]
1
H* *
F
SR
1
18 Vautier et al. [11]
3
H
F
SR
IUD
2
1
NH 28
D
H9
D
SR
SVT
SR
15
5*
2
19 Ebenroth et al. [25]
37
20 Krapp et al. [26]
20
H
F+D
SR
21 Jouannic et al [7]
25
H 25
D7
SVT
Del
SVT
SVT
SR
SVT
IUD
TOP
SR
SVT
TOP
5
1*
1
2
7
2
2
1
2
1*
1
1
D+S 2
F 12
A4
22 Nakata et al. [27]
23 Porat et al. [3]
24 Strasburger et al. [10]
1
H
F
SR
1
H
D+F
SR
15
H
D
Failed
14
F
3
SR
3
A (DFT)
V
1
1
1
F
1
SR
Neonatal
death
SR
D+V
D
S+A
D+V+A
3
1
1
1
SR 2 + NND 1
SR but NND
SR
IUD
F
8
P
P+V
F
1
1
5
SR
SVT
SR
SVT*
F
A
5
A
2
A
2
A
15
Alive 3
Neonatal
death 1
1
1
7
1
P+A (3rd line) -SR
5
20
SR 5
TSH elevated in 2
cases
SR 1 + IUD 1
SR
1
15
2
Fetal SVT treated at 13 weeks
Transient hypothyroidism in 5 fetuses
A = Amiodarone; D = digoxin; F = flecainide; V = verapamil; S = sotalol; P = propranolol; SR = sinus rhythm; H = hydropic fetus; NH = nonhydropic fetus;
IUD = intrauterine death; NM = not mentioned in the abstract (article not in English language); TOP = termination of pregnancy; Del = delivery; NND = neonatal death; TSH = thyroid-stimulating hormone; DFT = direct fetal therapy.
* Treated after delivery.
** Twin pregnancy, one fetus with SVT and hydrops.
74
Fetal Diagn Ther 2006;21:72–76
Pradhan/Manisha/Singh/Kapoor
with neonatal death owing to its negative inotropic effects [6].
Flecainide is a potent class 1c antiarrhythmic drug that
is available for treatment of atrial, junctional, and ventricular arrhythmias. It acts on fast sodium channel and
slows conduction throughout the conduction system; its
greatest effect is on bundle of His. Up to 30–40% of the
fetuses do not respond to this therapy [1]. Amiodarone
belongs to class III drugs and acts by prolonging action
potential, thus lengthening the refractory period. Amiodarone is effective against a wide variety of atrial and
ventricular arrhythmias [7]. It has been found to be safe
in pediatric patients also.
A review of all published experience with transplacental flecainide and amiodarone was done to evaluate which
of the two is more effective in controlling SVT and at the
same time has fewer side effects (table 1). Amiodarone as
transplacental therapy used alone or in combination with
digoxin and/or sotalol in 37 cases (nine studies) was successful in 33 (89.2%) of them. The side effect in the form
of fetal hypothyroidism was seen in 8 cases; all of which
were transient, were treated, and had no long-term sequel.
Flecainide was used transplacentally in 108 cases (fifteen studies). It successfully controlled arrhythmia in 85
(78.7%) of them. There were 8 (7.4%) cases of sudden fetal death in four reports [1, 7, 8, 11].
Though there have been more studies done on flecainide than on amiodarone on transplacental fetal therapy, there have been reports about sudden intrauterine
death with flecainide, which has limited its use. On the
other hand, there has been no death reported while using
amiodarone alone. The main side effect seen is fetal hypothyroidism, as it contains 37% iodine by weight; this
fetal iodine overload may be responsible for fetal hypothyroidism [7]. The hypothyroidism that was observed in
three reports (total 8 cases); 2 presented elevated thyroid
stimulating hormone at day 3–4 and required thyroid
hormone substitution therapy for 2–6 months with normal outcome [7], and in another case intra-amniotic instillation of L-thyroxine was done weekly for 3 weeks;
thyroid levels on treatment normalized quickly and baby
was normal at the time of birth [9]. In the remaining
5 cases the hypothyroidism was transient [10].
Amiodarone was successful in reverting SVT in patients who were not responding to flecainide treatment as
well [7], but there were no reports showing tachycardia
refractory to amiodarone being controlled by flecainide.
Hence, we conclude that amiodarone is an attractive
therapeutic modality for management of fetal SVT.
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