CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 2, March/April 2010
AFRICA
111
electrolytes, the patient had another episode of ventricular fibril-
lation, which required external defibrillation. Subsequent ECGs
demonstrated normalised QT intervals.
Cardiac function, assessed by transthoracic two-dimension-
al echocardiography was normal, and a coronary angiogram
demonstrated normal coronary arteries without angiographic
evidence of any obstructive disease, coronary spasm or embolus.
Right ventricular endomyocardial biopsies did not reveal any
signs of acute cellular or humoral rejection.
We hypothesise that amiodarone given to the recipient for a
prolonged time prior to transplantation, followed by re-exposure
to intravenous amiodarone with increased bioavailability due to
concomitant tacrolimus therapy after transplantation might have
caused prolonged QT interval in the donor heart with subsequent
ventricular arrhythmia.
After considering a watch-and-wait approach versus a tempo-
rary wearable defibrillator vest (which was rejected by the patient)
it was decided to proceed with implantation of a single-chamber
ICD as primary prevention of sudden death 14 days after cardiac
transplantation. The patient was discharged in a stable condition
and so far, has had no further arrhythmic events.
Discussion
We report recurrent ventricular fibrillation in a patient soon after
cardiac transplantation without evidence of electrolyte abnor-
malities, myocardial ischaemia, humoral or cellular rejection or
graft dysfunction. ECG revealed a prolonged QT interval, which
occurred after a brief re-exposure to intravenous amiodarone
after the recipient had had prolonged IV and oral amiodarone in
the days prior to transplantation.
Even though not proven without doubt, it is likely that previ-
ous amiodarone therapy induced QT prolongation in the trans-
planted donor heart due to its long half-life, even after the drug
was stopped.
9,10
The brief intravenous re-exposure might have
boosted amiodarone levels, however, unlike oral amiodarone,
IV amiodarone alone is rarely associated with significant QT
prolongation and even more rarely with torsade de pointes.
Other potential reasons for the QT prolongation cannot be
ruled out completely. A cross check of drugs known to prolong
QT intervals, such as albuterol, alfuzosin, amantadine, amitriptyl-
ine, amphetamines, arsenic, astemizole, atazanavir, atomoxetine,
azythromycin, chloroquine, clomipramine, dolasetron, metapro-
terenol, moxifloxacin, phentermine, and phenylpropanolamine
revealed that none of those had been reported to be taken by the
recipient or the donor in the past.
There was no significant bradycardia and no relevant elec-
trolyte abnormalities that could have caused either QT prolon-
gation or ventricular arrhythmia. No evidence for myocardial
ischaemia, graft dysfunction or rejection was evident. The donor
had no known history of long QT syndrome or any cardiovas-
cular disorder and had died of non-cardiac reasons. Therefore,
we believe that the QT-prolonging and pro-arrhythmic potential
of extended amiodarone therapy prior to transplant caused the
events in the case described here.
In general, the occurrence of QT prolongation with subse-
quent ventricular fibrillation in the absence of ischaemia or
graft rejection is extremely rare early after cardiac transplanta-
tion, and in fact, has not been reported so far, to the best of our
knowledge. Also, we did not find any reports in the literature of
either ventricular fibrillation or ICD implantation in the early
postoperative period after heart transplantation or on potential
anti-arrhythmia-induced QT prolongation.
Serum levels of amiodarone, even though not measured,
could have been increased by a potential drug interaction with
tacrolimus,
11
which was given as part of the immunosuppressive
regime after transplantation. Similarly, this has been described
with cyclosporine,
12
and both drugs can contribute to higher
bioavailability of amiodarone.
MacDonald
et al
. demonstrated that patients who received
amiodarone before transplantation had significantly lower heart
rates at one and four weeks after transplantation and required
prolonged atrial pacing (7.3
±
1.4 versus 3.4
±
0.8 days,
p
<
0.02). In a relatively small study of 19 patients on amiodar-
one compared to 31 controls, no effect of prior amiodarone
therapy on early allograft function or on clinical outcome was
detected.
13
Even though some authors in the past have recommended
continuing amiodarone after cardiac transplantation because of
serious side effects after discontinuation of the drug,
14
this is
not recommended anymore. Moreover, there is also controversy
about the use of beta-adrenergic blockers (early) after trans-
plantation,
15
but there are no data from controlled large-scale
studies.
Since we believed that the arrhythmia was most likely caused
by amiodarone, we recommended waiting until the drug was
completely cleared, as demonstrated by continuous monitoring.
Also, a wearable defibrillator vest was discussed, but neither was
accepted by the patient and therefore, a single-chamber ICD was
implanted for the prevention of sudden death. This has not been
reported that early after transplantation before.
In contrast, ventricular arrhythmias and the need for anti-
arrhythmic therapy, including ICD implantation has been
described late after cardiac transplantation. Arrhythmic events
in the post-transplant population are most often associated with
graft dysfunction secondary to chronic allograft vasculopathy
and subsequent myocardial ischaemia, with an increased risk
of sudden death years after transplant.
16
The usefulness of ICD
implantation has been described in 10 out of 493 heart transplant
recipients,
17
which is not as common as ICD implantation in
heart failure patients awaiting cardiac transplantation.
18-20
Conclusion
The potential arrhythmogenic effects of anti-arrhythmic drugs
such as amiodarone should be considered, even after cessation
of the drug, and even in the transplanted donor heart. Because of
the potential drug interactions with immunosuppressive agents
such as tacrolimus, the QT interval in the transplanted heart
should be monitored closely in patients who had received amio-
darone prior to transplantation.
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1.
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1999;
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Cohn WE, Gregoric ID, Radovancevic B, Wolf RK, Frazier OH
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