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Torsade de pointes
Beware of drugs that induce this
condition
BY Abdelwahab Arrazaghi, MB
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Torsade de pointes is a low frequency event but a potentially life-threatening
condition. It's an arrhythmia with ventricular tachycardia and long
QT interval. The name "twisting of points" was given by F. Dessertenne
in 1966 to refer to the undulating pattern of QRS complexes along
the isoelectric line of the electrocardiogram (ECG). The condition
is either congenital or acquired mainly as an iatrogenic disease.
In the presence of secondary risk factors, certain drugs inhibit
the potassium rapidly activating rectifier outward current (IKr)
in the cardiac action potential, prolonging the QT interval. The
incidence appears to be 3-15% for a wide range of products. To prevent
unnecessary exposure to risk, doctors need to be aware of these
interactions and of the typical features of torsade, its diagnosis
and management. Choosing the lowest effective dosage and close clinical
and electrocardiographic monitoring of the QT interval would be
prudent during treatment.
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Etiology of QT prolongation
- based on clinical findings and response
to therapy
- congenital, or idiopathic
- acquired
- pause-dependent
- most frequently induced by drug
effects/interactions or electrolyte disturbances
- more than 2 agents that prolong QT
behave synergistically on repolarization
- interaction of torsadogenic drug
with agent that inhibits cytochrome P-450 metabolism, especially
CYP3A4
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Predisposing factors
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Symptoms
- may be asymptomatic
- otherwise, low cardiac output leading
to syncope, palpitations, dizziness, exertional dyspnea,
fatigue, angina, signs and symptoms of congestive heart
failure
- if attack was prolonged or in rapid
succession, seizures, syncope, death
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ECG
The following features distinguish
torsade de pointes from other ventricular tachycardias
- heart rate -- 200-240 beats/min,
range 160-280 beats/min
- rhythm -- irregular
- R-R interval -- variable, with
a long/short cycle often seen before torsade begins
- QRS complex -- wide (> 0.12
secs) and bizarre in appearance with varying amplitude and
axis
- torsade -- clusters over runs
of 5-20 beats
- AV-dissociation -- if the P
waves are visible
- QT interval -- delay in repolarization
-- long QT and often the ap--pearance of a U wave. This
should be measured in several leads and the longest QT (QT-max)
should be used. Prolonged QT interval is at least 500 msecs
or QTc 440 msecs.
- T wave -- distorted or broad
- end of torsade -- arrhythmia
is non-sustained -- either terminates spontaneously or degenerates
to ventricular fibrillation and sudden death
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Abdelwahab Arrazaghi, MB, BCH, DABIM, FRCPC has obtained
specialization in internal medicine and cardiovascular diseases
from the University of Toronto. He is Director of the Toronto Heart
and Women's Health Clinic and medical director of the Kennedy and
Sheppard Diagnostic Centre.
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Dangerous drugs
Some agents with risk for torsade
de pointes
- class 1A antiarrhythmics -- quinidine,
disopyramide, procainamide
- class 1C -- encainide
- class III -- potassium channel blockers
-- sotalol, amiodarone, N-acetyl procainamide, dofetilide, ibutilide
- class IV -- calcium channel blockers, e.g.
bepridil
- class V -- adenosine
- psychotropic drugs -- phenothiazines (thioridazine,
chlorpromazine), haloperidol, tricyclic and tetracyclic antidepressants
- antimicrobials -- macrolides (e.g. erythromycin,
tacrolimus), quinolones (e.g. chloroquine), amantadine, trimethoprim-sulfamethoxazole
- histamine receptor H1 antagonists -- astemizole,
terfenadine
- lipid-lowering agents -- probucol
- prokinetic medications -- cisapride
- toxins -- zinc, organophosphates
- tamoxifen, arsenic trioxide, methadone,
domperidone
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Congenital long QT
- dynamic long QT or QTU segments during
1 adrenergic stimulation -- e.g. exercise, pain/emotion and provocation
with beta-adrenergic agents
- Romano-Ward syndrome
- Jervell and Lange-Nielsen syndrome
- six mutations identified so far -- LQT1
to LQT6 -- in genes encoding ion channels
- reduced potassium outflow current prolongs
action potential and QT interval
- mutations may correlate with specific therapies
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Emergency therapy
- do not confuse with other ventricular tachycardias
-- class IA antidysrhythmic drugs can be disastrous
- if degenerates to ventricular fibrillation
-- current cardio-ver-sion (DC shock) for termination
- urgent measures to prevent immediate
recurrence
- removal of any potentially torsadogenic
agents
- magnesium infusion
- supplemental potassium to increase
serum levels to 4.5 mmol/L -- this will accelerate repolarization
- transvenous cardiac pacing to 100-140
beats/min -- may be life-saving; the inverse relationship
between basic heart rate and repolarization time means faster
pacing will result in shorter QT interval.
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