Europace Advance Access originally published online on November 15, 2007
Europace 2008 10(1):112-113; doi:10.1093/europace/eum252
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org.
ELECTROCARDIOGRAPHY
Amiodarone-associated macroscopic T-wave alternans and torsade de pointes unmasking the inherited long QT syndrome
Florian T. Wegener,
Joachim R. Ehrlich and
Stefan H. Hohnloser*
Division of Cardiology, Section of Clinical Electrophysiology, J.W. Goethe-University, Theodor-Stern-Kai 7, D 60590 Frankfurt, Germany
Manuscript submitted 4 September 2007. Accepted after revision 20 October 2007.
* Corresponding author: Tel: +49 69 6301 7404; fax: +49 69 6301 7017; E-mail address: hohnloser{at}em.uni-frankfurt.de
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Introduction
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The congenital form of the long QT syndrome (LQTS) results from
mutations in cardiac ion channels with a high degree of genetic
heterogeneity. Ten different genes and >400 mutations with
varying penetrance have been identified to date. Drug-induced
acquired LQTS with torsade de pointes tachycardia as its most
relevant clinical manifestation has been described as a result
of previously unsuspected congenital LQTS. Only rarely, macroscopic
T-wave alternans (TWA) is documented before the onset of torsade
de pointes.
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Case report
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A 62-year-old male patient without previously documented QT
prolongation or ventricular tachyarrhythmias presented with
new-onset atrial fibrillation and a rapid ventricular response
(
Figure 1A). The patient was started on intravenous therapy
with amiodarone. Following 48 h of drug exposure (total dose
of 3.0 g amiodarone), sinus rhythm could be re-established.
However, the patient developed massive QT
c prolongation from
baseline value of 401 ms to 592 ms. Moreover, there was prominent
TWA visible on the surface ECG (
Figure 1B). This TWA preceded
the development of torsade de pointes degenerating in ventricular
fibrillation (
Figure 1C). Amiodarone plasma concentration
was 0.87 mg/l at that time (therapeutic range, 0.59–2.5
mg/l). The patient was resuscitated and taken off amiodarone.
He recovered completely and at the time of discharge, the QT
interval had normalized (QT
c, 416 ms). Subsequent genetic testing
revealed a previously unpublished mutation at the
KCNE2 gene
(exon 1, position A269G), leading to a glycine substitution
for glutamine within the C-terminus of this potassium channel
β-subunit corresponding to the LQTS VI entity.
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Discussion
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This case illustrates that previously unsuspected congenital
LQTS may become clinically manifest when additional risk factors
(such as therapy with antiarrhythmic drugs) may synergistically
challenge reduced repolarization reserve. In a Finnish population,
19% of patients with drug-induced torsade de pointes carried
one of the four common Finnish founder mutations of LQTS. Besides
the culprit drug, one or more additional risk factors such as
female sex, congestive heart failure, or atrial fibrillation
were present. Our patient is a particularly exceptional example
of how clinically inapparent congenital LQTS may manifest itself
during exposure to repolarization prolonging antiarrhythmic
drugs. Whereas the QT interval was within normal limits prior
to treatment, it prolonged significantly and—most interestingly
and only rarely observed—was associated with macroscopic
TWA. This highly arrhythmogenic milieu gave then rise to the
development of torsade de pointes and ventricular fibrillation.
This case highlights that normal baseline electrocardiogram
does not exclude a risk for proarrhythmic events during antiarrhythmic
therapy.
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Introduction
Case report