Abnormal repolarization pattern resulting from prolongation of QT interval or abnormal morphology of the T-wave can result in TdP [
1,
2]. Congenital and acquired causes of long QT syndrome (LQTS) can predispose to TdP. Apart from a prolonged QT, the presence of bradycardia and beat-to-beat variability [
3,
4] in QT are other known risk factors for TdP. Medications that affect cardiac repolarization are a common cause of acquired LQTS. In the acquired variant, a typical sequence of events has been described in the EKG [
2]. It starts with a ventricular premature complex or an ectopic beat that results in a compensatory pause. This is followed by a sinus beat that usually has a long QTc, terminating in a ventricular extrasystole that usually starts the TdP. It may be self-limiting, in which case it can cause syncope, or if sustained, it can degenerate into ventricular fibrillation resulting in a cardiac arrest. The EKG strip in our patient (
Figure 1A) shows the variability in QT interval and prolongation of QT before the onset of TdP.
Drug-induced LQTS that can potentially lead to TdP and ventricular fibrillation arrest is a well-known but underestimated problem. Antiarrhythmics, psychiatric medications, antihistaminics, antibiotics, antifungals and antiemetics are some of the common classes of drugs that can cause prolongation of QTc. All these drugs are commonly used in the emergency department and inpatient setting [
5]. There are reports of metoclopramide associated TdP [
6,
7], mostly in patients with underlying heart disease or renal failure. Cocaine [
8,
9] and methadone [
10] are also associated with LQTS. Other cardiac effects of methadone predisposing to TdP include bradycardia and QT dispersion [
11]. Opioids vary in their tendency to predispose to cardiac arrhythmias. Methadone has been identified as a higher risk agent that can increase the risk of long QT related arrhythmias even in lower doses [
12], and hence, a close monitoring of these individuals is recommended. Methadone is metabolized in the liver, primarily by CYP3A4, with CYP 2D6 and CYP1A2 also being involved [
13]. Metronidazole is an inhibitor of CYP2C9 and CYP3A4 isoenzymes and can interact with drugs [
14] causing LQTS and TdP. Older age, female sex, underlying structural heart disease, recent myocardial infarction and family history of sudden cardiac death are known risk factors [
1,
15]. Simultaneous use of drugs that can prolong QT interval is a significant risk factor. Use of these drugs in patients on enzyme (cytochrome P450) inhibitors or those with electrolyte abnormalities (hypokalemia, hypocalcemia and hypomagnesemia) can also predispose to TdP. Judicious use of these drugs in recommended doses, minimizing use in patients with pre-existing prolonged QT interval or other cardiac risk factors can help in reducing this life-threatening iatrogenic adverse event. There are several online tools such as RxList, WebMD and Medscape that are available to health care professionals to check interactions between medications. CredibleMeds [
16] is a website with a free smartphone app that offers information on general drug interactions and a dedicated section on QTc interactions.
TdP with hemodynamic instability is treated with defibrillation. IV magnesium sulfate is the first-line therapy [
17,
18] and is effective in patients with normal serum magnesium levels as well. Other interventions include identification and discontinuation of the culprit medications and correction of electrolyte abnormalities, especially hypokalemia [
18]. Cardiac pacing and isoproterenol are reserved for refractory cases [
17,
18].