Malignant Ventricular Arrhythmias Resulting From Drug-Induced QTc Prolongation: A Retrospective Study

BACKGROUND: Several drug classes (antiarrhythmics, antimicrobials, antidepressants, phenothiazines, opiates, prokinetics of digestive tract, etc.) have been related to ventricular hyperkinetic arrhythmias such as torsade de pointes (TdP). TdPs are usually heralded by an abnormal prolongation of heart rate-corrected QT interval on the electrocardiogram, so-called drug-induced long heart rate-corrected QT (diLQTc). We don’t know to what extent the drug-induced QTc prolongation is able to predict malignant arrhythmias. Thus we have retrospectively examined the clinical history of patients with diLQTc. METHODS: The case-record, concerning the period from January 2008 to December 2017, was collected from two hospitals. The diLQTc was defined as drug- induced heart rate-corrected QT of ≥ 450 ms or ≥ 470 ms, respectively in male or female patients. The primary purpose was to verify whether in diLQTc patients the length of this electrocardiographic segment was associated with the risk of symptoms or events (TdP, ventricular fibrillation). RESULTS: A total of 73 validated cases of diLQTc were gathered. Among them, the QTc duration was not able to predict the occurrence of symptoms or events (odds ratio: 0.998; 95% CI: 0.984 to 1.013; P = 0.8821). Likewise, a diQTc lasting longer than 500 ms compared to diQTc comprised between 450 and 500 ms was not associated with an increased risk of arrhythmic events. CONCLUSIONS: In some probably genetically predisposed subjects, the occurrence of symptoms (dizziness, lipothymia, syncope ) and/or documented arrhythmic events (TdP), is related to intake of certain drugs (antiarrhythmics, antimicrobials such as quinolones and macrolides, etc.). Nevertheless, in our diLQTc patients, QTc duration didn’t predict occurrence of symptoms, or arrhythmic events. Thus, other determinants should be postulated to clarify why sometimes diQTc prolongation propitiates ventricular malignant arrhythmias whereas in other cases this arrhythmogenic effect is lacking.