Effect of verapamil in infants with paroxysmal supraventricular tachycardia.
J Soler-Soler, J Sagristá-Sauleda, A Cabrera, J Sauleda-Parés, J Iglesias-Berengué, G
Permanyer-Miralda and J Roca-Llop
Circulation. 1979;59:876-879
doi: 10.1161/01.CIR.59.5.876
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Effect of Verapamil in Infants
with Paroxysmal Supraventricular Tachycardia
J. SOLER-SOLER, M.D., J. SAGRISTA-SAULEDA, M.D., ALBERTO CABRERA, M.D.,
J. SAULEDA-PARES, M.D., J. IGLESIAS-BERENGUE, M.D., G. PERMANYER-MIRALDA, M.D.,
AND J. ROCA-LLOP, M.D.
SUMMARY Twenty-nine consecutive spontaneous attacks of paroxysmal supraventricular tachycardia
(PSVT) in 14 infants (mean age 4.4 months) were treated with verapamil. No infant had associated heart disease. Verapamil 1-2 mg i.v. was administered over 30 seconds. The dosage varied according to the weight of the
infant. Within 60 seconds sinus rhythm was obtained in 28 instances (96.5%). No significant complications
were observed. The high effectiveness, rapid action and lack of undesirable side effects observed in this series
suggest that verapamil is the drug of choice in the treatment of PSVT in infants without underlying heart disease.
VERAPAMIL is considered by many authors1-7 to
be the drug of choice in the treatment of paroxysmal
supraventricular tachycardia (PSVT) in adults. It has
been particularly effective in reciprocating junctional
tachycardias with6' 8 or without6 8 an associated extranodal pathway. The rapid action of verapamil and
its quick elimination contribute to its clinical
usefulness. This antiarrhythmic drug must be used
with caution in patients with acute myocardial infarction,9 sick sinus syndrome'0 and obstructive bronchopulmonary disease.8' 11 Verapamil is contraindicated
in patients with high-degree atrioventricular (AV)
block'2 and in patients receiving A-blocking agents;4 it
is probably contraindicated as well in patients with
severe primary heart failure.5' 13, 14
Digitalis is considered the drug of choice in the
treatment of PSVT in infants.'5 -1 However, as
Lubbers et al.20 have stated, "the value of newer antiarrhythmic drugs remains to be fully evaluated" in
this age group. Bein et al.22' 23 reported excellent
results with verapamil in the treatment of PSVT in infants and children. The present paper reports our
results with verapamil in the treatment of PSVT in infants.
atrial echoes were observed after termination of
tachycardia. Underlying heart disease could not be
demonstrated in any infant by noninvasive methods.
Only two infants had an acute intercurrent illness
(pneumonia).
Before the administration of verapamil, we
attempted to terminate tachycardia in all cases with
vagal maneuvers or with a precordial blow. Attacks
had begun 15 minutes to 2 days (possibly 5 days in one
case) before verapamil was administered. In 18 attacks congestive heart failure was present; in five of
them it was severe (pulmonary edema and/or physical
signs of shock). In two patients 0.03 mg/kg digoxin
i.v. had been administered 3 hours and 5 hours
previously. Another patient had received procainamide 1 hour before receiving verapamil.
Verapamil was given intravenously over 30 seconds,
at a dosage of 1 mg in infants weighing < 5 kg, 1.5 mg
in infants weighing 5-10 kg, and 2 mg in infants
weighing > 10 kg. The dosage schedule was derived
from that used in adults, according to the equivalent
table of Talbot et al.24 This dosage schedule was
successful in our first series of treated infants.25 In one
case we administered an additional 0.5 mg because the
usual dose failed (1 mg in an infant weighing 4.5 kg);
in another case a higher dose (2 mg in a 5.6 kg infant)
was required for the same reason; and in a third infant, a dose three times greater than scheduled (4.5 mg
in a 5.8 kg infant) was inadvertently administered. In
all cases administration of verapamil was carried out
under continuous electrocardiographic monitoring.
Materials and Methods
We treated 29 consecutive, spontaneous attacks of
PSVT in 14 infants ages 5 days to 18 months (mean
age 4.4 months) with verapamil. All attacks corresponded to supraventricular tachycardia (regular
tachycardia with narrow QRS in a 12-lead ECG) of
the paroxysmal type. Heart rate ranged from 214-330
beats/min. In seven infants (13 attacks) the ECG
between attacks showed a Wolff-Parkinson-White
syndrome, and in two other infants (three attacks)
Results
Stable sinus rhythm was obtained in 28 of 29
treated attacks. The only failure occurred in an infant
in whom a higher-than-usual dose (2 mg in a 5.6 kg infant) did not abolish the tachycardia. This attack was
terminated with a precordial blow, the same maneuver
that was repeatedly ineffective before administration
of verapamil. All attacks ceased immediately or
within 60 seconds after administration of the drug.
The heart rate usually slowed before the tachycardia
stopped. In four instances there were atrial echoes or
From the Servicio de Cardiologia y Hospital Infantil, Ciudad
Sanitaria Seguridad Social, Paseo Valle de Hebr6n, Barcelona, and
the Hospital Infantil de Cruces, Bilbao, Spain.
Address for reprints: Dr. J. Soler-Soler, Departamento de
Medicina, Servicio de Cardiologia, Ciudad Sanitaria de la
Seguridad Social, Paseo Valle de Hebr6n, s/n, Barcelona (35),
Spain.
Received May 10, 1978; revision accepted December 8, 1978.
Circulation 59, No. 5, 1979.
876
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VERAPAMIL IN INFANTS WITH PSVT/Soler-Soler et al.
877
A.L.F. 2M 1MGR
D ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
FIGURE 1. A) Control tracing of a paroxysmal supraventricular tachycardia (PSVT) in a 2-month-old
infant with a heart rate oF315 beats/mmi B) PSVTstops 48 seconds after the administration of 1 mg of
verapamil. Three sinus beats are followed by severe depression of sinus automaticity and atrioventricular
(A V) junctional escape rhythm at a frequency of 68-75 beats/min. C) A run of sinus beats interrulpts a more
rapid A V junctional escape rhythm. This tracing was obtained 13 seconds after strip B. D) Stable sinus
rhythm registered 17 seconds after strip C.
short, self-limited runs of paroxysmal tachycardia.
We observed transient depression of sinus automaticity (fig. 1) requiring no treatment in the only infant who had received procainamide 1 hour before.
When present, heart failure disappeared a few hours
after termination of tachycardia.
The only complication (severe hypotension with
shock) was seen in the infant who inadvertently
received a dose three times greater than recommended. This complication was successfully treated
with isoproterenol.
Discussion
PSVT in infants is often a cardiac emergency. In
this age group, correct diagnosis is often delayed
because the initial symptoms (pallor, feeding troubles,
vomiting) are vague. The degree of heart failure
depends on the duration of the attack, on the heart
rate and on any associated cardiac anomaly. Although
prognosis is usually good,'6' 20, 25 isolated fatal cases
have been reported.26'2,27 In some series 16,282 mortality iis
2-11%, and death is related to heart failure or to complications of therapy.
Digitalis, considered to be the first-choice drug in
the treatment of PSVT in infants,'5-21 abolishes more
than 90% of attacks. Usually, sinus rhythm is obtained
within 10 hours.16 This delay is distressingly long in
patients who do not tolerate PSVT, which may require
the administration of other antiarrhythmic drugs, with
unpredictable combined effects.
Verapamil involves neither blockade of the ,Badrenoreceptors of the heart nor quinidine-like activity. Vaughan Williams29 considers verapamil to be a
new, fourth type of antiarrhythmic drug. Specifically,
verapamil blocks the slow calcium inward channel,30
but does not significantly modify the transmembrane
sodium influx through the fast inward channel.3' The
sinus node and the AV node are particularly sensitive
to verapamil because normal impulse formation in the
sinus node and conduction in the AV node appear to
be maintained by slow channel-dependent mechanisms. The effect exerted by verapamil on AV conduction may explain its effectiveness in treating
tachyarrhythmias.33 3
Our results with verapamil are dramatic: Within 60
seconds sinus rhythm was obtained in 28 of 29 instances (96.5%). The only refractory attack was
observed in a patient in whom verapamil had been
successful in two previous episodes of tachycardia during his first admission. Interestingly, this refractory
tachycardia was abolished with a precordial blow
shortly after administration of verapamil. As this
maneuver had been unsuccessful before verapamil we
assume the the drug had some influence in the interruption of the tachycardia. Our results are similar
to those reported by Bein et al.,22 who obtained sinus
rhythm in all the 70 attacks of PSVT in patients aged
4 days to 14 years.
Since some PSVTs are short-lived, the purist may
argue that the termination of tachycardia is not
always related to verapamil, but may be a spontaneous event. However, the very short interval between
administration of the drug and termination of the
tachycardia observed in this and other series3 5 6, 22
strongly suggests that termination of tachycardia is
due to the action of verapamil.
The following points should be emphasized:
Quick Action of Verapamil
All attacks but one ceased immediately after the
administration of verapamil or within 60 seconds. We
stress that after 3-5 minutes of its administration,
verapamil cannot be assumed to have stopped the
tachycardia.5 In case of failure of the drug, another
therapeutic approach can be safely undertaken after
this interval.
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878
CIRCULATION
Stable Sinus Rhythm
The arrhythmia relapsed within 24 hours after its
termination in only two infants. This frequency is
similar to that reported with digitalis.16 18, 20
Verapamil and Heart Failure
In spite of the negative inotropic effect of
verapamil,'2' 13, 35 the signs of heart failure quickly
subsided after termination of tachycardia. In our
series heart failure was secondary to PSVT, and no infant had underlying heart disease. In the series of Bein
et al,22 two infants with severe congenital heart disease
developed PSVT during heart catheterization; in both
cases verapamil administration was followed by complete AV block with spontaneous return to sinus
rhythm. Apitz et al.36 reported a fatal case after administration of verapamil in a 9-year-old child with
primary cardiomyopathy and chronic heart failure.
Singh et al.35 studied the effects of verapamil on
hemodynamics in patients with heart failure and conclude that "the intrinsic negative inotropic action of
verapamil is minimized by its effects on afterload so
that cardiac index is not reduced by the drug in
patients with cardiac disease." However, in their
series no patient was in functional class IV and all had
basal left ventricular end-diastolic pressure < 20 mm
Hg and ejection fraction > 40%. These authors were
probably aware that their patients represented a
selected heart disease population because at the end of
the paper, in spite of the above-mentioned conclusions, they state: "caution should nevertheless be
exercised in the use of verapamil in patients with
severe myocardial decompensation." All these data,
along with the experimental studies of Nayler et al.,'3
the clinical observations of Witchitz et al.'4 and our
own experience in the adult5 suggest that verapamil is
probably contraindicated in patients with severe heart
failure secondary to or coincident with severe heart
disease.
Absence of Complications
The important bradycardia and shock observed in
one case must be related to the overdose administered
by mistake. The effects of a dose three times greater
than standard, however, were readily controlled by administration of isoproterenol, as has been reported in
VOL 59, No 5, MAY 1979
interrupted all instances of PSVT: directly in 28 cases
and indirectly in one. Contrary to what has been
reported in comparable series,'5 2 administration of
antiarrhythmic drugs or cardioversion were not
needed. It is possible to use other drugs (personal experience in adults, unpublished data) or electrical cardioversion7 shortly after administration of verapamil
if this drug has been unsuccessful. Previous administration of digitalis does not contraindicate the
use of verapamil, but concurrent use of A-blocking
agents does.4 The high effectiveness, rapid action and
lack of undesirable side effects observed in our series
suggest that verapamil is the drug of choice in the
treatment of PSVT in infants without underlying
heart disease.
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Dosage
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16.
Summary
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27. Kimball JL, Burch G: Prognosis of the Wolff-Parkinson-White
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28. Keith JD, Rowe RD, Vlad P: Heart disease in infancy and
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1971
The Cardiac Conduction System in Situs Ambiguus
DAVID F. DICKINSON, M.B., M.R.C.P., D.C.H., JAMES L. WILKINSON, M.B., M.R.C.P.,
KENNETH R. ANDERSON, M.B., M.R.C.P., AUDREY SMITH, F.I.M.L.S.,
SIEN YEN Ho, M. PHIL., AND ROBERT H. ANDERSON, M.D., M.R.C. PATH.
SUMMARY The cardiac specialized conduction tissue was studied by serial sectioning in 13 cases of situs
ambiguus. In four cases of right isomerism, we found paired sinus nodes in relation to a crista terminalis, and
in each case a sling of conduction tissue between two atrioventricular nodes was present regardless of the ventricular morphology or cardiac position. In the cases with left isomerism, the sinus node was hypoplastic and
abnormally located. We saw two types of atrioventricular conduction systems. In the three cases in which the
morphologically right ventricle lay to the right of the morphologically left ventricle (presumed d-loop), a single
atrioventricular bundle arose from a normally located atrioventricular node. In the five cases in which the
morphologically right ventricle lay to the left of the morphologically left ventricle (presumed 1-loop) and in the
one case with a univentricular heart, paired atrioventricular nodes were present, linked or potentially linked by
a sling of conduction tissue.
visceral configuration with duplication of either left-
FAILURE OF LATERALIZATION of thoracic and
abdominal viscera into the pattern of either situs
solitus or situs inversus results in the symmetrical
or right-sided structures termed situs ambiguus.' This
frequently results in major malformations in the cardiovascular system. In situs ambiguus with right
isomerism, duplication of right-sided structures, such
as the crista terminalis, is associated with duplication
of the sinus node.2 In the left isomeric form, where the
crista terminalis is absent, atrial depolarization is
known to be abnormal as judged from the surface
ECG.3 The sinus node has been reported to be abnormally located in two cases studied by Bharati and
Lev,4 one with multiple spleens and the other with a
From the Department of Child Health, University of Liverpool,
and the Department of Paediatrics, Cardiothoracic Institute,
Brompton Hospital, London, England.
Supported by grants from the Endowment Fund, Royal Liverpool Children's Hospital, and the National Heart Research Fund.
Dr. Kenneth Anderson was a New Zealand Heart Foundation
Travelling Fellow; present address: Department of Pathology,
University of Otago, Dunedin, New Zealand.
Dr. Robert Anderson is supported by the Joseph Levy Foundation and the British Heart Foundation.
Address for reprints: Dr. James L. Wilkinson, Cardiac Department, Royal Liverpool Children's Hospital, Myrtle Street, Liverpool L7 7DG, United Kingdom.
Received September 22, 1978; accepted November 14, 1978.
Circulation 59, No. 5, 1979.
single bilobed spleen.
The atrioventricular conduction system has not
been studied extensively in hearts with situs ambiguus.
We have previously observed5 a sling of ventricular
conduction tissue connecting paired atrioventricular
879
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