Answer: C. QT Prolongation
Discussion
This patient developed cardiac arrest secondary to Torsades de
Pointes (TdP), a polymorphic ventricular tachycardia associated with QT
interval prolongation that resulted from dofetilide. TdP is a
polymorphic ventricular tachycardia described and named for its
characteristic twisting of the QRS complex around a single isoelectric
point on electrocardiography. TdP is pathophysiologically dependent on
three conditions: prolongation of the QT interval (due to medications or
congenital abnormalities); development of an early after-depolarization
(a depolarization in the cell membrane that occurs prior to
repolarization of the membrane and prior to the refractory period); and
tissue heterogeneity that allows this early after-depolarization to
propagate as an action potential in a re-entrant pathway.
Prolongation of the QT interval most commonly occurs in the acquired
form due to medications that block the delayed potassium rectifier
channels that are responsible for ventricular repolarization.
Dofetilide is a class III anti-arrhythmic that functions by blocking
potassium rectifier channels. Dofetilide can induce Tdp via
prolongation of the repolarization interval as well as by slowing the
heart rate. Additionally, in patients with atrial fibrillation, after
restoration of sinus rhythm, there is increased risk for Tdp due to
bradycardia and heightened sensitivity to QT prolonging effects of
dofetilide.
Treatment of drug-induced Tdp centers on shortening the QT interval
and preventing early after-depolarizations by removing any reversible
causes. The precipitating drug should be stopped and electrolyte
abnormalities corrected including hypokalemia (to replete intracellular
potassium) and magnesium (to block calcium influx which prolongs phase
II of the action potential). As QT duration is inversely correlated
with heart rate, increasing the heart rate with beta-adrenergic
infusions or overdrive pacing can be therapeutic when bradycardia is
present.
References
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Yap, Y. G. Drug induced QT prolongation and torsades de pointes. Heart 2003; 89(11): 1363-1372.
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Brumberg et al. Frequency of toxicity with chemical cardioversion of
atrial fibrillation with dofetilide. Am J Cardiol 2013; 112(4): 505-8.
