CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 5, June 2013
AFRICA
e13
With transthoracic echocardiography, the ejection fraction of
the left ventricle was measured at 60% and medium tricuspid
valve insufficiency was detected. Additionally, a detailed family
history of the patient, particularly with regard to sudden
cardiac death, was taken. Cardiological examination including
echocardiography and ECG analysis of first-degree relatives of
the patient was also done.
Acquired long QT syndrome associated with ibandronate was
the primary consideration. Acetylsalicylic acid, subcutaneous
enaxoparine and bisoprolol were administered to the patient, and
ibandronic acid was discontinued. Amiodarone therapy had also
been stopped at the first admission to our hospital due to the
termination of the patient’s VT attack.
ECG monitoring was performed regularly on the patient for
two weeks after the discontinuation of ibandronic acid. It was
observed that ventricular extrasystoles disappeared and the QTc
interval returned to normal, measured at 0.42 seconds (Fig.
3). Finally, no VT was induced with programmed ventricular
stimulation during a diagnostic electrophysiological study after
the normalisation of the QTc interval.
Discussion
The top limit for the duration of the QTc interval according to
heart rate is usually given as 0.44 seconds, however, it can be
0.46 seconds in men and 0.47 seconds in women.
1
Prolongation
of the duration of the ventricular action potential is recognised
as prolongation of the QT interval on superficial ECG and can
cause torsades de pointes, a life-threatening arrhythmia.
2
Acquired long QT syndrome can be induced by anti-
arrhythmic agents, such as quinidine, procainamide, sotalol,
amiodarone and disopyramide; tricyclic antidepressant drugs;
non-sedative antihistamines, such as astemizol and terfenedine;
and antibiotics, such as erythromycin and pentamidine. Acquired
long QTc may also be caused by electrolyte abnormalities such
as hypokalaemia, hypocalcaemia and hypomagnesaemia; fasting;
lesions on the central nervous system; apparent bradyarrhythmias;
cardiac ganglionitis; and mitral valve prolapse.
1
In our case, there was no previously known structural cardiac
disease, and no electrolyte abnormalitywas detected on admission.
Acute ischaemia was not considered because the patient’s cardiac
enzymes were within normal limits, and no lesions had been
detected in a recent coronary angiography. Based on the history
of taking ibandronate for two weeks and no other drug that
prolongs the QT interval except for amiodarone, whose half-life
may be up to 100 days,
4
we diagnosed the patient with VT-based
acquired long QT syndrome associated with ibandronate.
Bisphosphonate agents are widely used in the treatment
of osteoporosis, Paget’s disease and hypercalcaemia.
3-5
They are inorganic pyrophosphate analogues that act as
endogenous regulators of calcium metabolism. Ibandronate is a
bisphosphonate derivative preferred primarily for the treatment
of hypercalcaemia and osteolytic bone disease.
5
The wide use of
bisphosphonates necessitates investigation of their relationship
with cardiovascular diseases.
6
Much research related to the cardiovascular safety of
bisphosphonates has been conducted. A published analysis
stated that zoledronic acid, which is a bisphosphonate derivative,
increased the incidence of atrial fibrillation and that no
significant difference in arrhythmia potential was found between
other bisphosphonate derivatives and placebos. Furthermore,
no increase was established in cases of death, stroke and other
non-arrhythmic cardiovascular events.
7
In another study in which ibandronate was administered to
6 830 patients and a placebo to 1 924 patients, no increased
incidence in atrial fibrillation or other serious cardiovascular
disease was observed after either oral or intravenous
administration of ibandronate.
8
Bisphosphonates may induce
abnormalities of electrolytes, and ibandronate is more potent
than other bisphosphonates in promoting the development of
hypocalcaemia. Clinical findings may be associated with the
development of hypocalcaemia and electrocardiographically
long QT.
9
No serious cardiovascular cases associated with ibandronate
use have been reported in the literature. However, pathologies
such as abnormalities of electrolytes, ischaemia and structural
heart disease that may cause acquired long QT syndrome
were not detected in our case. The patient was thought to
have acquired long QT syndrome and accordingly, ventricular
tachycardia associated with ibandronate use, even though the
serum calcium level was normal.
Intravenous magnesium, atrial or ventricular pacing control
and cardioversion are among the first methods to select for
patients who have developed acquired long QT syndrome and
VT. It is necessary to avoid any agents that cause long QT.
1
Since ventricular arrhythmia is associated with reversible causes,
there are no indications for implantable cardioverter-defibrillator
(ICD).
10
In our case, after medical cardioversion with amiodarone,
ibandronate therapy, which can cause long QT syndrome, was
discontinued and electrolytes were monitored frequently to
prevent an imbalance that could induce ventricular arrhythmias.
No temporary pacing or repeated cardioversion was required
for our patient due to haemodynamic stabilisation throughout
hospitalisation.
During follow up, the patient’s QTc interval returned to the
normal range and no symptoms developed. In addition, VT was
not induced with programmed ventricular stimulation during
diagnostic electrophysiological study after the normalisation of
the QTc interval.
Conclusion
ECG monitoring should be performed regularly on patients
treated with bisphosphonates such as ibandronic acid. As in our
case, ibandronic acid may cause VT after prolongation of the
QT interval, even without the development of any electrolyte
abnormality.
References
1.
Braunwald E, Bonow RO, Libby P, Zipes DP. Long QT syndrome
.
Braunwald’s Heart Disease. A Textbook of Cardiovascular Medicine.
8th edn. USA: Natasha Andjelkovic, 2008: 901.
2.
Darbar D, Kimbrough J, Jawaid A, McCray R. Persistent atrial fibrilla-
tion ıs asssociated with reduced risk of torsades de pointes in patients
with drug-induced long QT syndrome
. J Am Coll Cardiol
2008;
51
(8):
836–842.
3.
Brunch TJ, Anderson JL, May HT, Muhlestein JB. Relation of bispho-
sphonate therapies and risk of developing atrial fibrillation.
Am J
Cardiol
2009;
103
(6): 824–828.
4.
Latini R, Tognoni G, Kates RE. Clinical pharmacokinetics of amiodar-
