Incidence of drug-induced torsades de pointes with intravenous amiodarone

Abstract

AimTo define the incidence, presentation, and outcomes of drug-induced Torsades de Pointes (TdP) with intravenous (IV) amiodarone.MethodsFrom January 2014 to August 2016 a total of 268 patients received IV amiodarone, 142 for ventricular tachycardia, 104 for atrial flutter/fibrillation, and 22 for incessant atrial tachycardia. A uniform dosing of amiodarone to yield 1 gm/day was used in all patients.ResultsFour of the 268 patients (M:F 1:3) with mean age of 51.25 + 9.17 years developed pause dependent TdP degenerating to VF, after a mean dose of 690 + 176.63 mg, infused over 12 + 5.88 h. The QTc that was 505 + 9.02 ms at the time of TdP normalized to 433.75 + 6.13 ms 48–72 h after stopping amiodarone. There was no immediate or late mortality, and patients are well at 5–10 months of follow-up. None of the patients tested positive for LQTS genes.ConclusionThe incidence of drug-induced TdP with IV amiodarone is about 1.5%. Risk factors include female sex, left ventricular dysfunction, electrolyte abnormalities, baseline prolonged QTc, concomitant beta-blocker, and digoxin therapy. Amiodarone induced TdP has favorable prognosis if recognized and treated promptly, and these patients should not receive amiodarone by any route in future.

Cardiolipotoxicity, Inflammation, and Arrhythmias: Role for Interleukin-6 Molecular Mechanisms

“…The molecular partners of I K , namely: I Kr and I Ks determine spatial and temporal activation and modulation of repolarization by I K (Sanguinetti and Jurkiewicz, 1991; Aromolaran et al, 2014). Thus, inactivation and/or downregulation of I K , either due to congenital mutations (Aromolaran et al, 2014; Puckerin et al, 2016), or secondary to pathological disease states including diabetes (Eranti et al, 2016), obesity (Papaioannou et al, 2003), or drugs (Shenthar et al, 2017; Grouthier et al, 2018), will delay repolarization leading to LQTS. Recently, we demonstrated that both gating and trafficking defects underlie pathological decreases in I Kr and I Ks in heart (Aromolaran et al, 2014; Puckerin et al, 2016).…”

Torsades de pointes after prolonged intravenous amiodarone therapy for atrial fibrillation

“…According to literature, amiodarone-induced TdP more commonly occurs within 24 hours after initiation of the therapy. 5 In our case, it occurred on day 3 of the maintenance infusion of amiodarone. On that morning the ECG revealed prolongation of QTc 488 msec as in comparison with ECG on admission (QTc 405 msec).…”

Torsade de pointes induced by intravenous amiodarone therapy accompanied by marked augmentation of the transmural dispersion of repolarization in a patient with tachycardia‐induced‐cardiomyopathy

“…Amiodarone is widely used for the treatment of malignant arrhythmias with a remarkably low frequency of proarrhythmia. The incidence of TdP associated with oral amiodarone is reported to be <1.0% (Hohnloser et al., 1994), while that with intravenous amiodarone is about 1.5% (Shenthar et al., 2017). Although both amiodarone and other antiarrhythmic drugs including class Ia and other class III prolong the QT interval, TdP is overwhelmingly rare during amiodarone therapy.…”

“…The case reports of amiodarone‐induced‐TdP so far were rare and have shown significant QT prolongation, but without Tp‐e prolongation (Belardinelli et al., 2003; Friedman & Stevenson, 1998; Hii et al., 1992; Hohnloser et al., 1994; Kotake et al., 2015; Shenthar et al., 2017). The increased TDR could provide a more accurate electrophysiologic marker of the risk for TdP than does the QT interval.…”