QT prolongation and the antiarrhythmic efficacy of amiodarone

Abstract

Amiodarone is an antiarrhythmic agent known to cause prolongation of action potential duration which is reflected in the electrocardiogram as a prolongation of the QT interval. Prolongation of the QT interval in patients dying suddenly was compared with that in patients who remained alive to determine whether a difference existed between these two groups. The electrocardiogram and amiodarone levels were evaluated in 33 patients who presented with cardiac arrest and symptomatic ventricular tachycardia in whom no other antiarrhythmic agent was found effective in preventing induction of ventricular tachycardia during electrophysiologic studies. There were 30 men and 3 women (mean age 52 +/- 10 years). Twenty-three are alive after a mean follow-up period of 12 +/- 7 months. Ten died: six suddenly, three of non-cardiac causes and one of congestive heart failure. Using a two-way analysis of variance, the percent change in QT, QTc, JT and JTc intervals before and after amiodarone therapy was analyzed. Marked prolongation in the QT interval was present in patients who remained alive with amiodarone therapy. A significant difference in percent QT prolongation was seen between the latter patients and those who died suddenly (p less than 0.005). No difference was observed in the percent change in QRS interval between the two groups. The levels of amiodarone (2.5 versus 3.2 micrograms/ml) and its metabolite (desethylamiodarone) were not significantly different between the living patients and those who died suddenly. These findings suggest that a prolongation of the QT interval may be a marker for the therapeutic antiarrhythmic effect of amiodarone.

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: A potential anti-arrhythmic agent

“…Its electrophysiologic effects as to other class 3 anti-arrhythmic drugs, through inhibition of potassium channels, are to prolong the action potential duration and effective refractory periods (Miller & Zipes, 2001) and hence prolongation of QT interval (Chabner & Knollman, 2011). Moreover, similar to class 4 anti-arrhythmic drugs, through inhibition of calcium channels, amiodarone can decrease the slope of pacemaker potential, reduction of HR and increase the PR interval (Torres et al, 1986;Winslow et al, 1990). Consistent with previous reports in our study amiodarone induced the PR and QTc interval prolongation that explains its anti-arrhythmic effect.…”

Dramatic inhibition of amiodarone metabolism induced by grapefruit juice

“…Since the gut wall contains CYP3A4, it is highly probable that these inhibitors act, at least in part, on the prehepatic amiodarone biotransformation [2–7]. These induced alterations of amiodarone metabolism could have clinical consequences: like amiodarone, N‐DEA has class III antiarrhythmic properties, but it also has some electrophysiological properties which differ from the parent drug, notably by a higher fast sodium channel blockade and lower class IV effects [38–43]. Experimental data have shown a correlation between N‐DEA plasma concentration and antiarrhythmic properties of amioda‐rone [18, 19].…”

Efficacy, Safety, and Determinants of Conversion of Atrial Fibrillation and Flutter With Oral Amiodarone

“…14,15 Several investigators have demonstrated only a weak or even an absent concentrationeffect relation. [16][17][18][19][20] Others found a clear concentration-related effect of amiodarone on QT-interval prolongation, slowing of heart rate, and suppression of ventricular arrhythmias. [21][22][23] The present study showed that for conversion of atrial fibrillation, plasma concentrations of desethylamiodarone were more important than those of the parent compound.…”