Arch Gynecol Obstet (2004) 269:244–253
DOI 10.1007/s00404-002-0461-x
O R I G I N A L A RT I C L E
Simone Ferrero · Barbara Maria Colombo
Nicola Ragni
Maternal arrhythmias during pregnancy
Received: 22 February 2002 / Accepted: 10 July 2002 / Published online: 16 January 2003
© Springer-Verlag 2003
Abstract Introduction: An increased incidence of ma-
ternal cardiac arrhythmias is observed during pregnancy
and they can range from clinically irrelevant isolated
premature beats to debilitating supraventricular and ven-
tricular tachycardias. Discussion: Management of ar-
rhythmias during pregnancy is similar to that in non-
pregnant patients. However, the presence of the foetus
and the risk of teratogenicity, the haemodynamic chang-
es, the effect of therapy on labour, delivery and lactation
must be evaluated. Antiarrhythmic drug selection de-
pends on the specific arrhythmia being treated and the
cardiac condition of the mother. Although no drug is
completely safe, most are well tolerated and can be given
with relatively low risk. Some antiarrhythmic agents,
such as propranolol, metoprolol, digoxin and quinidine,
have been extensively tested during pregnancy and have
proved to be safe; they should therefore, whenever possi-
ble, be used as a first-line. For supraventricular tachycar-
dia, intravenous adenosine may be used to terminate the
arrhythmia if vagal manoeuvres fail. If possible, drug
therapy should be avoided during the first trimester of
pregnancy. When drug treatment fails or is not indicated
because of the haemodynamic instability of the patient,
direct current cardioversion can be used. Conclusion:
Most patients with arrhythmias during pregnancy can be
treated with an excellent result.
S. Ferrero (✉) · N. Ragni
Dipartimento di Ostetricia e Ginecologia,
Università degli Studi di Genova,
Padiglione 1 Ospedale San Martino, Largo Rosanna Benzi 16132,
Genova, Italy
e-mail: simoneferrero@libero.it
Tel.: +39-010-511525, Fax: +39-010-511525
S. Ferrero
Department of Obstetrics and Gynaecology,
St. Bartholomew’s Hospital, West Smithfield, London, UK
B. M. Colombo
Dipartimento di Medicina Interna,
Università degli Studi di Genova,
Ospedale San Martino, Largo Rosanna Benzi 16132, Genova, Italy
Keywords Arrhythmias · Antiarrhythmic drugs ·
Pregnancy
Introduction
Normal physiologic changes, which occur during gesta-
tion, can aggravate underlying cardiac disease and lead to
the associated morbidity and mortality. Maternal adapta-
tion to pregnancy includes plasma volume changes with
an increase in total body water, vascular alteration with a
decrease in systemic resistance and modifications associ-
ated with hypercoagulability. These explain, in part, the
appearance of signs and symptoms, even in a normal
pregnant woman, that are difficult to distinguish from
those occurring in heart disease and why some cardiac
abnormalities are not well tolerated during pregnancy.
An increased incidence of maternal cardiac arrhyth-
mias is observed during pregnancy but life-threatening
rhythm disorders are relatively rare. The foetus may suf-
fer both haemodynamic alterations and adverse effects of
the treatment. Teratogenic risks are higher during orga-
nogenesis in the first 8 weeks of pregnancy, after this pe-
riod this risk is greatly reduced but drugs may affect foe-
tal growth and development. Moreover, most cardiolo-
gists do not have extensive experience in treating these
kinds of patients and the knowledge that therapy may af-
fect the foetus is sometimes intimidating.
Arrhythmias during pregnancy include a wide spec-
trum: the most common are simple ventricular and atrial
ectopy (reported in 50 to 60% of pregnant women) [77]
but also sinusal tachycardia in the gestation period is a
common find. Supraventricular tachycardia (SVT) oc-
curs more frequently during pregnancy. Others supraven-
tricular arrhythmias can occur especially in pregnant
women with congenital heart disease, ischaemic cardiop-
athy, cardiomyopathy, valvulopathy (such as prolapse of
mitral valve).
In this report we review the management of arrhyth-
mias during pregnancy showing that most patients can be
treated with an excellent result.

The database of the National Library of Medicine
(MEDLINE) was used to identify the cases, published in
all languages until December 2001. The following key
words were used: pregnancy, arrhythmias, antiarrhyth-
mic drugs (and the names of specific agents), cardiac ar-
rest, ventricular tachycardia, supraventricular tachycar-
dia, atrial flutter, atrial fibrillation, atrial tachycardia,
Wolff-Parkinson-White syndrome, supraventricular ec-
topic beats, ventricular ectopic beats and bradyarrhyth-
mias. The reference list of all journal articles and recent
book chapters was reviewed.
We will begin this review evaluating pathogenesis
and diagnosis of arrhythmias. Every antiarrhythmic drug
will be evaluated with special regard to risks related to
its use during pregnancy and lactation. At the end of this
paper we will review the treatment for every kind of ar-
rhythmias occurring during pregnancy.
Pathogenesis
The reasons for the increased incidence of arrhythmias
during pregnancy are unclear [90]. Gestation involves a
set of remarkable physiologic adjustments: haemody-
namic, hormonal, autonomic and emotional changes are
physiological during pregnancy. Increased blood volume
(by 40 to 50%) results in a rise in cardiac output (by 30
to 50%), in atrial stretch and increased end-diastolic vol-
umes. An increase of both the catecholamine level in
plasma and the adrenergic receptor sensitivity has been
reported [9, 12, 28]. These adjustments place increased
demands on the heart, respiratory system, arterial and
venous circulations.
Even if a healthy woman is able to meet these de-
mands without difficulty, the one with a compromised
cardiovascular condition may not. Increased ectopic ac-
tivity is common in both atrium and ventricle, this ectopy
is generally benign and well tolerated, but it can trigger a
recurrence in women with previously diagnosed tachyar-
rhythmias. The arrhythmias may be the first evidence in
women with organic illness of the heart for the physio-
logic adjustments that occur during pregnancy. Arrhyth-
mias may also be the initial presentation of a serious car-
diovascular condition that develops during pregnancy,
such as peripartum cardiomyopathy [47]. Moreover, ad-
vance in cardiac surgery have allowed an increased num-
ber of women with congenital cardiac malformations
(prone to arrhythmias) to reach reproductive age [64].
Evaluation of the symptoms
During pregnancy the monitoring of arrhythmia is of ut-
most importance. Severity, frequency and duration of the
symptoms will allow the physician to determine if the
treatment is necessary. Palpitation, fatigue, effort dys-
pnoea, dizziness, rest dyspnoea, chest oppression,
blurred vision, presyncope and syncope are the signs and
symptoms in patients with tachyarrhythmia.
245
The management of arrhythmias in pregnant women
is similar to that taken in patients who are not pregnant.
All patients with a sustained arrhythmia should have a
baseline electrocardiogram to determine whether the
rhythm abnormality originates from the atria or ventri-
cle. This is followed by search for an underlying
aetiology. It is important to detect factors worsening pre-
viously diagnosed arrhythmias and causing new arrhyth-
mias, such as tobacco, caffeine and illicit drug use. Pa-
tients should be evaluated for electrolytic imbalance,
anaemia and hyperthyroidism. If a contributing factor is
identified, behaviour modification is attempted and med-
ical conditions should be treated prior to conception.
Therapy
In the case of symptomatic arrhythmias, with haemody-
namic instability, medical treatment is advised. Many
factors must be evaluated: the presence of the foetus and
the risk of teratogenicity, the haemodynamic changes,
the effect of therapy on labour, delivery and lactation.
During pregnancy it may be more difficult to maintain
blood therapeutic drugs levels. Intravascular volume ex-
pansion can lead to an increase in the necessary effective
dose, but the reduction in serum proteins can decrease
the quantity of drug bound to proteins increasing the
amount of free bioactive drug. Because the effects of an-
tiarrhythmic drugs are related to the unbound drug, the
biologic activity of these agents in pregnant women may
be greater than suggested by serum drug assay that mea-
sure total drug level [59]. During pregnancy, both renal
perfusion is increased and liver metabolism is enhanced
causing an increase in the clearance of drugs. Gastric se-
cretion and intestinal motility are impaired in pregnant
women and this can affect gastrointestinal absorption.
Moreover, to use as few drugs at the lowest doses that
are effective is particularly important in pregnant pa-
tients to expose them to the least number of potential
toxins as is possible. Teratogenic risks are higher during
organogenesis in the first 8 weeks of pregnancy, after
this period this risk is greatly reduced, but drugs may af-
fect foetal growth and development. Table 1 describes a
foetal risk factor classification scheme, that is helpful
when choosing optimal medical therapy [62]. The major-
ity of antiarrhythmic drugs are United States Food and
Drug Administration category C, which means that there
are either animal studies suggesting risks but no confir-
matory human study or no controlled studies in either
humans or animals. Table 2 shows Vaughan Williams
classification dividing antiarrhythmic drugs into 5 cate-
gories [86].
The magnitude of physiologic changes occurring dur-
ing pregnancy varies in different trimesters: closer drug
monitoring and more frequent dose adjustments are nec-
essary in comparison to the no pregnant condition.
For acute treatment of narrow and wide tachycardias,
with few exceptions, antiarrhythmic medications appear
to be safe. Drug therapy may be attempted if the tachy-
246
Table 1 Food and Drug Administration Pregnancy Risk Classification (abbreviated) (Page 1995)

Category Risk

A Controlled studies show no risk

B No evidence of risk in pregnant women. Either animal studies show risk but human studies do not, or animal studies
do not show risk but no adequate studies in humans have been conducted
C Studies in pregnant women are lacking, and animal studies are either positive for foetal risk or lacking as well
D Positive evidence of risk. Investigational or post-marketing data show risk to the foetus, but the benefit from use
in pregnant women may be acceptable despite the risk
X Positive evidence of risk. Investigational or post-marketing data show risk to the foetus and the risk of use of the
drug in pregnant women clearly outweighs any possible benefits. The drug is contraindicated on women who are
or may become pregnant

Table 2 Classification of antiarrhythmic drugs (Vaughan Williams 1984)

Class Type Name

I Sodium channel blocking agents

IA Drugs that prolong the action potential duration Quinidine, procainamide, disopyramide
IB Drugs that cause shortening of the action potential duration Lidocaine, mexiletine, phenytoin
IC Drugs with little effect on action potential duration but that Flecainide, propafenone
cause profound slowing of conduction
II β adrenergic blocking agents Propranolol, metoprolol
III Potassium channel blocking agents Sotalol, amiodarone, ibutilide
IV Calcium channel blocking agents Verapamil, diltiazem
Other Digoxin, adenosine

cardia is haemodynamically well tolerated, but direct
current (DC) cardioversion should be performed if drug
treatment fails. Direct current cardioversion restores si-
nus rhythm for forms of sustained tachycardia, which are
haemodynamically not well tolerated by pregnant wom-
an and that cause foetal hypoperfusion. Direct current
cardioversion is safe at all stages of pregnancy [24, 46,
62, 73] and the risk of inducing foetal arrhythmias is
small, because the current reaching the foetus is insignif-
icant. However is necessary monitor foetal rhythm, be-
cause transient foetal arrhythmia has been reported dur-
ing DC cardioversion of pregnant woman.
Procainamide (class IA, category C)
Procainamide has been used frequently and no evidence
of teratogenicity has been reported even when used dur-
ing the first trimester of pregnancy [2, 24, 40]. Its chron-
ic use may be associated with a lupus-like syndrome, as
in non-pregnant patients [24]. Probably, procainamide
levels in breast milk are clinically insignificant [24],
however the experience with its use in pregnancy and
lactation is too limited to grant any recommendation re-
garding its use.

Disopyramide (class IA, category C)

Antiarrhythmic agents
Quinidine (class IA, category C)
Quinidine has been used during pregnancy since the
1930s. Although pregnancy-related adverse effects asso-
ciated with quinidine are uncommon [21, 22, 41, 57, 58],
some have been reported. It has been reported that quini-
dine can induce mild uterine contractions [58], prema-
ture labour [5] and neonatal thrombocytopenia [55]. At
toxic doses, quinidine has been reported to cause miscar-
riage [88] or possibly cranial nerve VIII injury [57]. In
general, quinidine is considered safe during pregnancy
and it is probably the class IA drug of choice. Quinidine
levels in breast milk are lower (70%) than in serum.
Even if reported experience with disopyramide during
pregnancy has not been associated with teratogenicity
[24], the experience is limited and caution is warranted.
Disopyramide can cause uterine contractions [51].
Lidocaine (class IB, category B)
Despite significant placental drug transfer [11], lidocaine
is not known to increase the risk of foetal malformations
[40]. However, it increases myometrial tone [38], de-
creases placental blood flow [78] and causes foetal bra-
dycardia [53]. Its administration during foetal acidosis
can cause heart and central nervous system toxicity in
the newborn [13]. Lidocaine is excreted in breast milk,
but the amount ingested by the infant is very small and
should not pose a hazard [24].

Mexiletine (class IB, category C)
Mexiletine is structurally similar to lidocaine and it free-
ly crosses the placenta [24]. Although teratogenicity has
not been reported, data in pregnant women is limited.
Flecainide (class IC, category C)
There is no wide experience about the use of flecainide
during pregnancy, but no evidence of teratogenicity or
adverse effects on the foetus has been reported [85, 87].
Flecainide passage through the placenta has been docu-
mented, especially during the third trimester of pregnan-
cy [1, 8, 44, 63, 87], but the level of the drug in plasma
is lower than in amniotic fluid, suggesting an effective
renal excretion. A reduction in the foetal heart rate vari-
ability has been observed, but it is reversible after deliv-
ery because of decreasing drug plasma levels [44, 85].
Flecainide is excreted in breast milk and there is limited
data regarding the safety of this drug during lactation
[24].
Propafenone (class IC, category C)
Although propafenone crosses the placental barrier [14],
no teratogenic or adverse effects have been reported.
Anyhow, use of this agent should be approached cau-
tiously, because it has not been studied extensively in
pregnant women. There is limited data regarding the
safety of this drug during lactation [24].
β-blockers (class II, category C)
β-blockers have been widely used during pregnancy to
treat hypertension [7, 29, 71, 72, 79], hypertrophic
cardiomyopathy [81], thyrotoxicosis [15, 45], mitral
stenosis [67] and foetal tachycardia [80]. No studies to
date implicate any β-blocker in foetal malformation and
they are considered reasonably safe during pregnancy
[76]. Anyhow, β-adrenergic blockade reduces umbilical
blood flow and increases uterine contractility (β2
effect).
Propranolol has been more extensively used and it ap-
pears to be well tolerated by the foetus; but it has been
reported to cause intrauterine growth delay [34], foetal
bradycardia [34], hypoglycaemia [34], polycythaemia
[48], prolonged labour [48] and transient respiratory de-
pression in infant at birth [23, 82]. One retrospective
study suggested an increase in foetal death due to pro-
pranolol use during pregnancy [52].
Atenolol, labetalol and metoprolol have been used
less extensively, but they were safe. It has been suggest-
ed than β1-selective β-blockers (metoprolol and atenol-
ol) might be preferable because they avoid β2 receptor
blockage (causing peripheral vasodilatation and uterine
relaxation) [24, 30, 33, 70].
247
If necessary, glucagons may be administered during
labour to counteract the bradycardic and hypoglycaemic
effects of β blockade [78].
Breast milk level of beta-blockers can be five times
higher than plasmatic level. Even if the amount ingested
by infants is low, it may cause side effects to breastfed
babies [68].
Sotalol (class III, category B)
Even if sotalol crosses the placenta, no studies implicat-
ed it in foetal malformations or severe side effects [62,
87]. It can be used in women with normal renal function.
Its use in pregnancy is safe, but some cases of bradycar-
dia in newborn babies are reported; even if they were of
no long-term consequence, some authors advocate foetal
monitoring [20]. There is a risk of torsade de points as-
sociated with prolongation of QT duration that is en-
hanced in female [50]. Sotalol is used to manage supra-
ventricular tachycardia (atrial fibrillation, atrial flutter,
atrial tachycardia, atrioventricular nodal re-entrant
tachycardia, atrioventricular reciprocating tachycardia)
and ventricular tachycardia. Although adverse effects to
nursing infants of mothers on sotalol therapy have not
yet been proven, it has been estimated that an infant may
be exposed to 20–23% of the maternal dose [37].
Ibutilide (class III, category C)
Because ibutilide is only prescribed for short-term use, it
is unlikely to have significant teratogenic effects. How-
ever, in laboratory rats, ibutilide administered in 4–16
times the maximum recommended human dose caused
adactyly, cleft palate, scoliosis, and foetal death [60]; no
adverse effects were noted when dosed at normal levels.
Considering the limited data, ibutilide is not recom-
mended during pregnancy. Although no data exist on ib-
utilide and lactation, this issue is probably not significant
because ibutilide is only prescribed for short-term use.
Amiodarone (class III, category D)
There is no wide experience of the use of amiodarone
during pregnancy. Amiodarone and its metabolite, des-
ethylamiodarone, have a limited ability to cross the pla-
centa, achieving foetal concentrations of only 9% and
14% respectively of the concentration in maternal serum
[24]. The drug has high iodine content: iodine crosses
the placenta freely and has an affinity for foetal thyroid
tissue. Some severe side effects have been described in
the foetus: foetal goitre and neonatal hypothyroidism
[12, 24]. Growth retardation may occur, which may be
partly due to impaired transplacental passage of nutrients
secondary to amiodarone accumulation in the placenta
[89]. Other reported adverse effects on the foetus associ-
ated with amiodarone included bradycardia, prolonged
248
QT interval, prematurity, miscarriage and death [89].
Amiodarone must be used only in life-threatening
arrhythmias resistant to other drugs [89]. Amiodarone
appears at a higher level in breast milk than in maternal
serum: a nursing infant may be exposed to the equivalent
of a low adult maintenance dose [56]. Even if adverse ef-
fects on nursing infants have not yet been proven, it is
recommended that patients on amiodarone therapy are
not currently or have within the past few months been,
breast-feeding.
Calcium antagonists (category C)
Calcium antagonists have been widely used in the treat-
ment of foetal supraventricular tachycardia [91], in the
prevention of preterm delivery [83] and pre-eclampsia
[74].
Verapamil is the preferred calcium antagonist to pre-
scribe during pregnancy. Verapamil is used for acute and
chronic treatment of supraventricular tachycardia, both
in the mother [90] and foetus [32, 91]. No evidence of
teratogenicity or severe adverse effects has been reported
with the use of verapamil during pregnancy [4, 24, 83].
However, maternal and/or foetal hypotension, bradycar-
dia, atrioventricular block and contractility reduction
have been described during the treatment of foetal ar-
rhythmias [62]. Intravenous administration of verapamil
carries a risk of maternal hypotension and blood uterine
flow reduction. Because of these reasons adenosine, if
disposable, must be preferred to verapamil.
Knowledge about the use of diltiazem during preg-
nancy is limited. Some animal studies suggest that, in
very large doses, it may cause skeletal abnormalities, de-
creased foetal weight and even foetal death [18, 24]. It
may also inhibit uterine contractions and delay delivery.
One retrospective analysis of 27 newborns exposed dur-
ing the first trimester to diltiazem suggests an associa-
tion with birth defects [10].
There is limited data regarding the safety of calcium
antagonists during lactation. Verapamil is excreted in
breast milk, with reported concentrations varying be-
tween 23% and 94% of those in maternal serum [24].
Digoxin (category C)
Digoxin has been widely used during pregnancy in the
treatment of foetal and maternal arrhythmias [24, 30]
and it can be considered the most secure anti arrhythmic
drug in pregnant woman on therapeutic doses. It is con-
sidered a preferred choice for acute and chronic treat-
ment of supraventricular tachycardias in the mother and
foetus [19, 32, 84], including atrial fibrillation, atrial
flutter, and atrial tachycardias. Digoxin crosses the pla-
centa freely and its serum levels are similar in the moth-
er and newborn [69]. Digitalis toxicity during pregnancy
has been associated with miscarriage and foetal death,
probably due to maternal cardiac instability, uterine hy-
poperfusion and foetal anoxia [65, 75]. Serum digoxin
levels may decrease by 50% during pregnancy due to in-
creased renal excretion [48]. This decrease is not likely
to be an artefact of reduced serum protein concentration,
because digoxin is not highly protein-bound [68]. Main-
tenance doses may require reduction in the presence of
decreased renal function or co-administration of quini-
dine, verapamil or amiodarone. Digoxin plasma levels
during the third trimester of pregnancy may be difficult
to evaluate, because some substances that interfere with
the radioimmunoassay are present in the blood of the
mother [59]. Because of this, a therapeutic dose can be
associated with toxic plasma level. On the contrary, in-
creased renal excretion during pregnancy can be associ-
ated with a reduction of the plasma level of the drug.
In women with therapeutic blood levels, digoxin ex-
cretion in the milk is less than 2 µg/die, but this amount
is not dangerous for the baby [6]. After delivery, digoxin
requirements may be decreased from the pregnant state
as pharmacokinetic parameters normalize.
Adenosine (category C)
Some authors advocate adenosine as the first choice
treatment of SVT during pregnancy [38, 54] because it
is an endogenous nucleoside, it has rapid action, its half-
life is very short (<10 s), and the passage through the
placenta is reduced by rapid excretion [54]. Adenosine
is effective and safe in the treatment of SVT, in which
the atrioventricular node is part of the re-entry circuit
[17, 26, 27, 31, 49, 54], i.e., atrioventricular nodal re-
entrant tachycardia and atrioventricular reciprocating
tachycardia involving an accessory pathway, as in
Wolff-Parkinson syndrome. However, clinical experi-
ence in pregnant women is relatively small. A retrospec-
tive study of adenosine use during the second and third
trimester suggests no teratogenicity and overall safety
and efficacy [31]. An important advantage compared
with verapamil (also used to terminate supraventricular
tachycardia) is that adenosine does not affect foetal
haemodynamics, while verapamil may reduce foetal
blood pressure [54]. Data on adenosine use in the first
trimester of pregnancy are lacking. Adenosine has been
used in the treatment of tachyarrhythmias during labour,
few temporary side effects have been described: in-
crease of uterine contractility, maternal hypotension and
foetal bradycardia. Monitoring foetal heart rate when at-
tempting to terminate maternal supraventricular tachy-
cardia is recommended. Even if the adenosine deami-
nase activity during pregnancy is reduced [42], the re-
quired adenosine dose for supraventricular tachycardia
termination in pregnant women is higher than in non-
pregnant women, this is probably due to the increased
plasma volume [31].
There is limited data regarding the use of adenosine
during lactation. However, because of its short half-life
and the fact that it terminates SVT in infants, it may be
safely used during breastfeeding.

Non-pharmacological treatment
The vagal manoeuvres (carotid sinus massage, Valsalva
manoeuvre, diving-reflex) are well tolerated during preg-
nancy and they must be the first treatment of tachycar-
dias, both with normal and large QRS. Performing ECG
during these manoeuvres may help in diagnosis [66].
Emergency and elective DC cardioversion is safe dur-
ing all phases of pregnancy [24, 46, 62]. Little electrical
current actually penetrates the uterus and the threshold to
provoke arrhythmias is higher in the foetal heart [24,
62]. Anyhow, it is preferable to perform the procedure
with foetal rhythm monitoring, because transient foetal
arrhythmias have been reported.
It was shown that pregnancy in patients with an im-
plantable cardioverter-defibrillator does not cause com-
plications or adverse events in the mother or foetus [61].
Thus, it was suggested that pregnancy should not be dis-
couraged merely because an implantable cardioverter-de-
fibrillator is present.
Use of pacemakers, permanent or temporary, is neces-
sary to alleviate symptoms caused by bradycardia or to
prevent severe symptoms in women who are likely to de-
velop symptomatic bradycardia. In the first trimester of
pregnancy the implantation of a pacemaker may be te-
ratogenic but it is possible to decrease the risks related to
radiation exposition with a protective device. In some
cases, during the last trimester of pregnancy, a temporary
pacemaker can be used in emergency conditions before
caesarean section.
Radio frequency catheter ablation is a percutaneous
catheter technique that can eliminate a variety of supra-
ventricular and ventricular arrhythmias. In patients with
frequent atrioventricular nodal re-entrant tachycardia,
atrioventricular reciprocating tachycardia episode, atrial
flutter and idiopathic ventricular tachycardia, RF abla-
tion prior to pregnancy should be considered (obviously,
RF ablation during pregnancy is highly undesirable be-
cause of the need for fluoroscopy). RF ablation for atrial
fibrillation has recently been reported in a patient in
whom this arrhythmia is induced by atrial tachycardia
episodes originating in or near the ostia of the pulmonary
veins [39].
There is not sufficient data about transcutaneous car-
diac stimulation during pregnancy.
Management of specific maternal arrhythmias during
pregnancy
Some general guidelines in managing arrhythmias during
pregnancy may be formulated.
Cardiac arrest
Cardiac arrest is a rare occurrence in pregnant women.
Its treatment involves special consideration especially in
the late stages of pregnancy. Standard cardiopulmonary
249
resuscitation (CPR), with the patient in the traditional su-
pine position, may fail, especially in the last trimester of
pregnancy. The gravid uterus acts like an abdominal
binding, increasing intra-thoracic pressure and reducing
both venous return and aortic flow [43, 46]. Successful
resuscitation may be obtained performing standard CPR
with the pregnant woman in a particular position: the pa-
tient is tilted on her side using either a wedge or another
rescuer’s knees for support [35]. Standard CPR protocol
must be followed because there is literature documenting
successful cardioversion with no adverse effect on the
mother or foetus discharging at 300 J. Emergency cae-
sarean section can make the resuscitation of the mother
easier [3].
Ventricular tachycardia
Ventricular tachycardia (VT) is uncommon in young
women, but its incidence may increase during pregnancy
and its symptoms may be severe [9, 12]. Ventricular
tachycardia may arise in young pregnant women with
structurally normal hearts, but these patients are at low
risk for subsequent mortality and morbidity. Ventricular
tachycardia may also be seen in patients with acquired or
congenital abnormalities and may have a more serious
prognosis than idiopathic VT. Women with hypertrophic
cardiomyopathy, right ventricular dysplasia, peripartum
cardiomyopathy and coronary artery disease have in-
creased risk of recurrent-paroxysmal VT.
Ventricular tachycardia can be haemodynamically un-
stable or stable. If it is stable and therapy is necessary, β-
blockers are the drug of choice [49]. Caution not to in-
duce maternal hypotension and subsequent foetal hypo-
perfusion is advised when administering these drugs.
When VT is unstable, immediate DC cardioversion is
appropriate and, in this case, lidocaine is the drug of
choice. Chronic antiarrhythmic therapy may be unavoid-
able in the face of sustained or recurrent VT: the drugs of
Category C (quinidine, procainamide, flecainide) and so-
talol are the drugs of choice [11].
Supraventricular tachycardia
Supraventricular tachycardias, in which the atrioventric-
ular node is part of the re-entry circuit, include atrioven-
tricular nodal re-entrant tachycardia and atrioventricular
reciprocating tachycardia involving an accessory path-
way, as in WPW syndrome. Also in these cases all anti-
arrhythmic drugs should be considered potentially toxic
to the foetus and, if is possible, non-pharmacologic or
preventive measures should be taken. Sustained tachy-
cardia in both forms may be terminated by vagal ma-
noeuvres, which transiently block atrioventricular nodal
conduction. If these measures fail, drug therapy is need-
ed, especially if haemodynamic instability and the symp-
toms are not bearable or there is a threat for the foetus or
pregnant woman. Intravenous adenosine is effective in
250

terminating re-entrant tachycardias that involve AV node

as a part of their re-entrant circuit (Fig. 1) [16]. If long-
term therapy is needed, verapamil, digoxin and β-block-
ers may be used. In atrioventricular reciprocating tachy-
cardia with an accessory pathway, class I antiarrhythmic
drugs (procainamide and quinidine) may be used to
blocking accessory pathway conduction. In patients with
an accessory pathway who have atrial fibrillation, the
therapy should not be aimed at suppression of atrioven-
tricular nodal conduction, because this may facilitate
conduction over the accessory pathway, thereby raising
the ventricular rate. In these patients effective drugs are
procainamide or quinidine (class I), which slow accesso-
ry pathway conduction and may prevent or terminate
atrial fibrillation. Patients with frequent atrioventricular
nodal re-entrant tachycardia or atrioventricular recipro-
cating tachycardia episodes need RF ablation prior to
pregnancy. In some cases electrical cardioversion is nec-
essary: 10–50 J of energy is usually sufficient.

Atrial flutter and atrial fibrillation

These rhythms are rare in women of childbearing age and
they are usually associated with structural heart disease.
If an obvious provoking factor is present (alcohol abuse,
thyroid dysfunction), the treatment should be aimed at
this factor. If spontaneous cardioversion to sinus rhythm
does not occur, early cardioversion should be performed
to avoid the need of anticoagulation. Quinidine is the
agent of choice for chemical cardioversion of atrial fibril-
lation and flutter. Procainamide is also safe for short term
use. There is no reported data on ibutilide use during
pregnancy. When cardioversion is impossible, adequate
rate control must be achieved to prevent haemodynamic
compromise of placental blood supply (ideally <90 bpm
at rest and <140 bpm with exercise) [3]. Rate control can
be obtained using verapamil, β-blockers (propranolol,
metoprolol) or digoxin. If the heart rate is not controlled
with these agents, the addition of verapamil would be a
reasonable step. In the event of haemodynamic embar-
rassment caused by rapid ventricular response, electrical
cardioversion is usually successful with 50–100 J for atri-
al fibrillation and 25–50 J for atrial flutter. In patients
with frequent atrial flutter episodes RF ablation prior to
pregnancy should be considered.
Pregnant patients with atrial fibrillation should be an-
ticoagulated with the subcutaneous adjusted-dose hepa-
rin regimen, if they meet the criteria accepted for non-
pregnant patients [36]. These include atrial fibrillation
with a history of thromboembolic complications, in the
presence of valvular disease, cardiomyopathy, or thyro-
toxic heart disease. Anticoagulation may also be consid-
ered in a patient with atrial fibrillation and congestive
heart failure. Risk factors are diabetes, hypertension,
previous stroke, rheumatic disease. Anticoagulation is
recommended for 3 weeks prior to cardioversion of atrial
fibrillation, and 4 weeks after conversion to a sinus
rhythm.
Fig. 1 Management of re-entrant supraventricular tachycardia in
pregnant patients [16]
Importantly, warfarin therapy is contraindicated dur-
ing the first trimester of pregnancy, because the drug
passes placental barrier and may lead to spontaneous
abortion, foetal haemorrhage, mental retardation and
birth malformations. High dose subcutaneous heparin is
recommended, particularly during the first trimester of
pregnancy, because its large molecular weight prevents
placental transfer. It should be discontinued at the onset
of labour or 24 h prior to the induction of labour. At
present, anticoagulation for chronic atrial flutter is not
recommended. Both warfarin and heparin are safe for
use in nursing mothers.
Atrial tachycardia
Occasionally, pregnant women develop primary atrial
tachycardia. Sustained atrial tachycardia may be termi-
nated by adenosine, which must be tried as a first choice.
Quinidine and procainamide are occasionally able to re-
store and maintain sinus rhythm. If cardioversion fails, it
is possible to slow the heart rate with β-blockers (pro-
pranolol or metoprolol), digoxin, verapamil, sotalol.
Chronic therapy may be necessary in patients in whom
drug cardioversion was unsuccessful.
Wolff-Parkinson-White syndrome
This syndrome is characterized by short PQ interval, δ
wave showing pre-excitation of a part of ventricle and

paroxysmal supraventricular tachycardias. These women
may have atrioventricular reciprocating tachycardia
treated as other SVT. Episodes of atrial fibrillation may
occur in patients with WPW syndrome, in which case
ventricular frequency increases and causes ventricular fi-
brillation. Procainamide is the drug of choice in women
presenting wide complex tachycardia, if it is of uncertain
origin and is haemodynamically stable. Cardioversion is
indicated in all unstable patients. Radio frequency abla-
tion should be considered in all patients with WPW syn-
drome before attempting pregnancy.
Supraventricular and ventricular ectopic beats
Ventricular or supraventricular ectopy in structurally
normal hearts has no clinical significance. The primary
goal in its management is reassurance. Exacerbating fac-
tors, such as chemical stimulating agents (caffeine,
smoking and alcohol) should be identified and eliminat-
ed. Drug therapy is not needed in the vast majority of
cases. If ectopy continues despite these measures and it
is very bothersome, β-blockers may be used. Propranolol
is very effective in reducing the frequency of palpitations
and alleviating anxiety. Metoprolol may be a better alter-
native in bronchospastic patients and its β1 selectivity
may confer additional benefits in terms of its safety pro-
file.
Bradyarrhythmias
Sinusal bradycardia is uncommon in pregnancy and it can
be associated with orthostatic hypotension; the enlarged
uterus compresses the inferior cava vein and it can make
this condition worse decreasing venous return. Vasovagal
syncope is one of the most common causes of symptomat-
ic bradycardia in women of childbearing age but it is rare
during pregnancy. In the case of congenital or acquired
cardiac bloc, in symptomatic pregnant women the therapy
of choice is an implantable pacemaker. In asymptomatic
pregnant women, Valsalva’s manoeuvre during delivery
causes decrease in cardiac frequency and may lead to syn-
cope or convulsion. In this case a temporary pacemaker is
necessary to sustain woman during delivery [25].
Intrapartum management
Labour and delivery are associated with significant
haemodynamic changes, as well as with pain and anxi-
ety, all of which could enhance arrhythmias. Pregnant
women with arrhythmias should undergo caesarean sec-
tion only for obstetrics indications. A caesarean may be
appropriate in the case when the blood pressure fluctua-
tions associated with labour are contraindicated and can-
not be controlled. Continuous cardiac monitoring may be
necessary intrapartum and postpartum for symptomatic
or complex arrhythmias.
251
Conclusion
Almost all kinds of ventricular and supraventricular ar-
rhythmias can occur during pregnancy. Medical care
must be initiated early, sometimes prior to conception,
but therapy should be provided only when the arrhyth-
mias cause severe symptoms or haemodynamic compro-
mise. Many factors must be evaluated in the administra-
tion of antiarrhythmic drugs: the presence of the foetus
and the risk of teratogenicity, the haemodynamic chang-
es, the effect of therapy on labour, delivery and lactation.
In general, arrhythmias during pregnancy can be safe-
ly managed and many of the currently available antiar-
rhythmic drugs are safe for the foetus. If possible, drug
therapy should be avoided during the first trimester of
pregnancy, because teratogenic risks are higher during
organogenesis. Drugs with the longest record of safe use
in pregnancy should be used as first-line therapy; the cli-
nician must use the least number of medications possible
and prescribe the lowest dose of drugs that is effective.
Drugs should be administered with close and frequent
monitoring.
When drug treatment fails or is not indicated because
of the haemodynamic instability of the patient, DC car-
dioversion can be used. Emergency and elective DC car-
dioversion has been proved to be safe during all phases
of pregnancy.
References
1. Allen LD, Shita SK, Sharland GK, Maxwell D, Priestley K
(1991) Flecainide in the treatment of fetal tachycardias. Br
Heart J 65:46–48
2. Allen NM, Page RL (1993) Administration of procainamide
during pregnancy. Clin Pharm 12:58–60
3. Anderson MH (1997) Heart disease in pregnancy. In: Oakley
C (ed) Heart disease in pregnancy. BMJ, London, p 248
4. Barrilon A, Grand A, Gerbaux A (1974) Treatment of the
heart during pregnancy. Ann Med Intern (Paris) 125:437–445
5. Bellet S (1972) Essentials of cardiac arrhythmias: diagno-
sis and management. In: Pregnancy. Saunders, Philadelphia,
p 257
6. Berlin CM (1981) Pharmacologic considerations of drug use
in the lactating mother. Obstet Gynecol 58 [Suppl]:17–23
7. Bott-Kanner G, Schweitzer A, Reisner SH, Joel-Cohen SJ,
Rosenfeld JB (1980) Propranolol and hydralazine in the man-
agement of essential hypertension in pregnancy. Br J Obstet
Gynaecol 87:110–114
8. Bourget P, Pons JC, Delouis C, Fermont L, Frydman R (1994)
Flecainide distribution, transplacental passage, and accumula-
tion in the amniotic fluid during the third trimester of pregnan-
cy. Ann Pharmacother 28:1031–1042
9. Braverman AC, Bromley BS, Rutherford JD (1991) New onset
ventricular tachycardia during pregnancy. Int J Cardiol
33:409–412
10. Briggs G, Freeman RK, Yaffe SJ (1994) Drugs in pregnancy
and lactation. A reference guide to fetal and neonatal risk, 4th
edn. Williams and Wilkins, Baltimore
11. Briggs G, Freeman RK, Yaffe SJ (1998) Drugs in pregnancy
and lactation. A reference guide to fetal and neonatal risk, 5th
edn. Williams and Wilkins, Baltimore
12. Brodsky M, Doria R, Allen B, Sato D, Thomas G, Sada M
(1992) New-onset ventricular tachycardia during pregnancy.
Am Heart J 123:933–941
252
13. Brown WW, Bell GG, Alper MH (1976) Acidosis, local anes-
thesia and newborn. Obstet Gynecol 48:23–30
14. Brunozzi T, Meniconi L, Chiocchi P, Liberati R, Zuanetti G,
Latini R (1988) Propafenone in the treatment of chronic ven-
tricular arrhythmias in a pregnant patient [letter]. Br J Clin
Pharmacol 26:489–490
15. Bullock JL, Harris RE, Young T (1975) Treatment of thyro-
toxicosis during pregnancy and propranolol. Am J Obstet
Gynecol 121:242–245
16. Burkart TA, Conti JB (1999) Arrhythmias in the pregnant pa-
tients: evaluation and management. Acc Curr J Rev 3:41–44
17. Camm JA, Garratt CJ (1991) Adenosine and supraventricular
tachycardia. N Engl J Med 325:1621–1629
18. Chaffman M, Brogden RN (1985) Diltiazem: a review of its
pharmacological properties and therapeutic efficacy. Drugs
29:387¯454
19. Chao RC, Ho ESC, Hsieh KS (1992) Fetal atrial flutter and fi-
brillation: prenatal echocardiographic detection and manage-
ment. Am Heart J 124:1095–1098
20. Chow T, Galvin J, McGovern B (1998) Antiarrhythmic drug
therapy in pregnancy and lactation. Am J Cardiol 82:581–621
21. Colin A, Lambotte R (1972) Influence tératogène des médica-
ments administrés à la femme enceinte. Rev Med Liege 27
[Suppl 1]:39–48
22. Conradsson TB, Werkö L (1974) Management of heart disease
in pregnancy. Prog Cardiovasc Dis 16:407–419
23. Cottrill M, McAllister RG, Gettes L Jr, Noonan JA (1977)
Propranolol therapy during pregnancy, labor, and delivery: ev-
idence for transplacental drug transfer and impaired neonatal
drug disposition. J Pediatr 91:812–814
24. Cox JL, Gardner MJ (1993) Treatment of cardiac arrhythmias
during pregnancy. Prog Cardiovasc Dis 36:137–178
25. Dalvi BV, Chaudhuri A, Kulkarni HL, Purushottam KA (1992)
Therapeutic guidelines for congenital complete heart block
presenting in pregnancy. Obstet Gynecol 79:802–804
26. Di Marco JP, Sellers TD, Berne RM, West GA, Belardinelli L
(1983) Adenosine: electrophysiologic effects and therapeutic
use for treating paroxysmal supraventricular tachycardia. Cir-
culation 68:1254–1263
27. Di Marco JP, Miles W, Akhtar M, Milstein S, Sharna AD,
Platia E et al (1990) Adenosine for paroxysmal supraventricular
tachycardia: dose ranging and comparison with verapamil.
Ann Intern Med 113:104–110
28. Doig JC, McComb JM, Reid DS (1992) Incessant atrial tachy-
cardia accelerated by pregnancy. Br Heart J 67:266–268
29. Eliahou HE, Silverberg DS, Reisin E, Romen I, Mashiach S,
Serr DM (1978) Propranolol for the treatment of hypertension
in pregnancy. Br J Obstet Gynaecol 85:431–436
30. Elkayam U (1992) Pregnancy and cardiovascular disease. In:
Braunwald E (ed) Heart disease. Saunders, Philadelphia, p 1790
31. Elkayam U, Goodwin TM (1995) Adenosine therapy for su-
praventricular tachycardia during pregnancy. Am J Cardiol
75:521–523
32. Engelhardt W, Grabitz RG, Funk A, von Bernuth G (1993) In-
trauterine treatment of fetal supraventricular tachycardia with
digoxin and verapamil. Z Geburtshilfe Perinatol 197:99–103
33. Frishman WH, Chesner M (1988) Beta-adrenergic blockers in
pregnancy. Am Heart J 115:147–152
34. Gladstone R, Hordof A, Gersony WM (1975) Propranolol ad-
ministration during pregnancy: effects on the fetus. J Pediatr
86:962–964
35. Goodwin AP, Pearce AJ (1992) The human wedge. A manoeu-
vre to relieve aortocaval compression during resuscitation in
late pregnancy. Anaesthesia 47:433–434
36. Greenspoon J (1987) Prosthetic valves, arrhythmias and anti-
coagulation in pregnancy. In: Clark SL (ed) Critical care ob-
stetrics. Oradell, New Jersey, p 114
37. Hackett LP, Wojnar-Horton RE, Dusci LH, Ilett KF, Roberts
MJ (1990) Excretion of sotalol in breast milk [letter]. Br J Clin
Pharmacol 29:277–278
38. Hagley MT, Cole PL (1994) Adenosine use in pregnancy
women with supraventricular tachycardia. Ann Pharmacother
28:1241–1242
39. Haissaguerre M, Jais P, Shah DC (1998) Spontaneous initia-
tion of atrial fibrillation by ectopic beats originating in the pul-
monary veins. N Engl J Med 339:659–666
40. Heinonen OP, Slone D, Shapiro S (1977) Birth defects and
drugs in pregnancy. Litteton, Massachusetts
41. Hill LM, Malkasian GD (1979) The use of quinidine sulfate
throughout pregnancy. Obstet Gynecol 54:366–368
42. Jaqueti J, Martinez-Hernandez D, Hernandez-Garcia R,
Navarro-Gallar F (1990) Adenosine deaminase in pregnant se-
rum. Clin Chem 36:2144
43. Kerr MG, Scott DB, Samuel E (1964) Studies of the inferior
vena cava in late pregnancy. BMJ 1:523–533
44. Kofinas AD, Simon NV, Sagel H, Lyttle E, Smith N, King K
(1991) Treatment of fetal supraventricular tachycardia with
flecainide acetate after dogixin failure. Am J Obstet Gynecol
165:630–631
45. Langer A, Hung CT, McAnulty JA, Harrigan JT, Washigton E
(1974) Adrenergic blockade: a new approach to hyperthyroid-
ism in pregnancy. Obstet Gynecol 44:181–186
46. Lee RV, Rodgers BD, White LM, Harvey RC (1986) Cardio-
pulmonary resuscitation of pregnant women. Am J Med
81:311–318
47. Lee W, Cotton D (1989) Peripartum cardiomyopathy: current
concepts and clinical managements. Clin Obstet Gynecol
32:54–67
48. Lees KR, Rubin PC (1987) Treatment of cardiovascular dis-
eases. BMJ 294:358–360
49. Leffler S, Johnson DR (1992) Adenosine use in pregnancy:
lack of effect on fetal heart rate. Am J Emerg Med 10:548–549
50. Lehmann MH, Hardy MS, Archibald D, Quart B, MacNeil DJ
(1996) Sex difference in risk of torsade de pointes with d,l-so-
talol. Circulation 94:2534–2541
51. Leonard RF, Braun TE, Levy AM (1978) Initiation of uterine
contractions by disopyramide during pregnancy. N Engl J Med
299:84–85
52. Lieberman BA, Stirrat GM, Cohen SL, Beard RW, Pinker GD,
Belsey E (1978) The possible adverse effect of propranolol on
the fetus in pregnancies complicated by severe hypertension.
Br J Obstet Gynaecol 85:678–683
53. Liston WA, Adjepon-Yamoah KK, Scott DB (1973) Foetal and
maternal lidocaine levels after paracervical block. Br J Anae-
sth 45:750–754
54. Mason BA, Ricci-Goodmann J, Koos BJ (1992) Adenosine in
the treatment of maternal paroxysmal supraventricular tachy-
cardia. Obstet Gynecol 80:478–480
55. Mauer A, Devaux L, Lakey M (1957) Neonatal and maternal
thrombocytopenic purpura due to quinidine. Pediatrics
19:84–87
56. McKenna WJ, Harris L, Rowland E, Whitelaw A, Storey G,
Holt D (1983) Amiodarone therapy during pregnancy. Am J
Cardiol 51:1231–1233
57. Mendelson CL (1956) Disorder of the heartbeat during preg-
nancy. Am J Obstet Gynecol 72:1268–1301
58. Meyer J, Lackner JE, Schochet SS (1930) Paroxysmal tachy-
cardia in pregnancy. JAMA 94:1901–1904
59. Mitani GM, Steinberg I, Lien EJ, Harrison EC, Elkayam U
(1987) The pharmacokinesis of antiarrhythmic agents in preg-
nancy and lactation. Clin Pharmacokinet 12:253–291
60. Mosby (1997) Mosby’s complete drug reference, 7th edn.
Mosby, St. Louis
61. Natale A, Davidson T, Geiger MY, Newby K (1997) Implanta-
ble cardioverters-defibrillators and pregnancy: a safe combina-
tion? Circulation 96:2808–2812
62. Page RL (1995) Treatment of arrhythmias during pregnancy.
Am Heart J 130:871–876
63. Palmer CM, Norris MC (1990) Placental transfer of flecainide.
Am J Dis Child 144:144
64. Perloff J (1991) Pregnancy and congenital heart disease. J Am
Coll Cardiol 18:340–342
65. Potondi A (1967) Congenital rhabdomyoma of the heart and
intrauterine digitalis poisoning. J Forensic Sci 11:81–88
66. Prystowsky EN (1988) Diagnosis and management of the pre-
excitation syndromes. Curr Probl Cardiol 13:225–310

67. Requena M, García-Cosío F, Fernández-Yáñez J, García-
Alarilla M, Bajo J (1985) Tratamiento de la estenosis mitral
con propranolol durante el embarazo y el puerperio. Med Clin
(Barc) 85:412–414
68. Rotmensch HH, Elkayam U, Frishman W (1983) Antiarrhythmic
drug therapy during pregnancy. Ann Intern Med 98:487–497
69. Rotmensch HH, Rotmensch S, Elkayam U (1987) Management
of cardiac arrhythmias during pregnancy. Drugs 33:623–633
70. Rubin PC, Butters L, Clark D, Sumner D, Belfield A, Pledger
D et al (1984) Obstetric aspects of the use in pregnancy-asso-
ciated hypertension of the beta-adrenoceptor agonist atenolol.
Am J Obstet Gynecol 150:389–392
71. Sandström B (1978) Antihypertensive treatment with the ad-
renergic beta-receptor blocker metoprolol during pregnancy.
Gynecol Obstet Invest 9:195–204
72. Sandström B (1982) Adrenergic beta-receptor blockers in hy-
pertension of pregnancy. Clin Exp Hypertens 1:127–141
73. Schroeder JS, Harrison DC (1971) Repeated cardioversion
during pregnancy. Am J Cardiol 27:445–449
74. Serafini PC, Petracco A, Vicosa HM, Costa PL (1979) Arterial
hyposensitive effect of verapamil in severe pre-eclampsia: pre-
liminary study. Arq Bras Cardiol 32:57–61
75. Sherman JL, Locke RV (1960) Transplacental neonatal digital-
is intoxication. Am J Cardiol 6:834–837
76. Shnider SM, Way EL (1968) Plasma levels of lidocaine (Xylo-
caine) in mother and newborn following obstetrical conduction
anesthesia: clinical applications. Anesthesiology 29:951–958
77. Sholan A, Ostzega E, Mehra A, Johnson JV, Elkayam U
(1997) Incidence of arrhythmias in normal pregnancy and rela-
tion to palpitations, dizziness, and syncope. Am J Cardiol
79:1061–1064
78. Tamari I, Eldar M, Rabinowitz B, Neufeld HN (1982) Medical
treatment of cardiovascular disorders during pregnancy. Am
Heart J 104:1357–1363
79. Tcherdakoff PH, Colliard M, Berrard E, Kreft C, Dupay A,
Bernaille JM (1978) Propranolol in hypertension during preg-
nancy. Br Med J 2:670
253
80. Teuscher A, Bossi E, Imhof P (1978) Effect of propranolol on fe-
tal tachycardia in diabetic pregnancy. Am J Cardiol 42:304–307
81. Turner GM, Oakley CM, Dixon HG (1968) Management of
pregnancy complicated by hypertrophic obstructive cardiomy-
opathy. Br Med J 4:281–284
82. Turnstall ME (1969) The effect of propranolol on the onset of
breathing at birth [abstract]. Br J Anaesth 41:792
83. Ulmsten U (1979) Inhibition of myometrial hyperactivity by
Ca antagonist. Dan Med Bull 26:125
84. Van Engelen AD, Weijtens O, Brenner JI, Kleinman CS, Copel
JA, Stoutenbeek P et al (1994) Management outcome and fol-
low-up of fetal tachycardia. J Am Coll Cardiol 24:1371–1375
85. Van Gelder-Hasker MR, De Jong CL, De Vries JI, Van Geijn
HP (1995) The effect of flecainide acetate for fetal tachycardia
and fetal hydrops. J Pediatr 126:988–990
86. Vaughan Williams EM (1984) A classification of antiarrhyth-
mic actions reassessed after a decade of new drugs. J Clin
Pharmacol 24:129–147
87. Wagner X, Jouglar J, Moulin M, Miller AM, Petitjean J,
Pisapia A (1990) Coadministration of flecainide acetate and
sotalol during pregnancy: lack of teratogenic effects, passage
across the placenta, and excretion in human breast milk. Am
Heart J 119:700–702
88. Webster LJ (1990) Drugs used in the chemotherapy of proto-
zoal infections—malaria. In: Gilman AG, Rall TW, Nies AS,
Taylor P (eds) Goodman and Gillman’s the pharmacological
basis of therapeutics, 8th edn. Pergamon, New York, p 978
89. Widerhorn J, Bhandari AK, Bughi S, Rahimtoola SH, Elkayam
U (1991) Fetal and neonatal adverse effects profile of amioda-
rone treatment during pregnancy. Am Heart J 122:1162–1166
90. Widerhorn J, Widerhorn ALM, Rahimtoola SH, Elkayam U
(1992) WPW syndrome during pregnancy: increased incidence
of supraventricular arrhythmias. Am Heart J 123:796–798
91. Wolff F, Breuker KH, Schlensker KH, Bolte A (1980) Prenatal
diagnosis and therapy of fetal heart rate anomalies: with a con-
tribution on placental transfer of verapamil. J Perinatal Med
8:203–208