Clinical characteristics of patients with drug-induced QT interval prolongation and torsade de pointes: identification of risk factors

• Published in: Clinical research in cardiology 2009-04, Vol.98 (4), p.208-212
• Main Authors: Letsas, Konstantinos P. MD, Efremidis, Michalis, Kounas, Stavros P, Pappas, Loukas K, Gavrielatos, Gerasimos, Alexanian, Ioannis P, Dimopoulos, Nikolaos P, Filippatos, Gerasimos S, Sideris, Antonios, Kardaras, Fotis
• Format: Article
• Language: English
• Subjects: Adult; Age Factors; Aged; Aged, 80 and over; Anti-Arrhythmia Agents - adverse effects; Anti-Bacterial Agents - adverse effects; Antipsychotic Agents - adverse effects; Cardiology; Cardiovascular disease; Cytochrome P-450 Enzyme System - drug effects; Cytochrome P-450 Enzyme System - metabolism; Drug Interactions; Echocardiography; Female; Heart Arrest - etiology; Humans; Hypertension; Hypertension - complications; Long QT Syndrome - chemically induced; Male; Medicine; Medicine & Public Health; Middle Aged; Original Paper; Prognosis; Risk Factors; Sex Factors; Tachycardia, Paroxysmal - complications; Torsades de Pointes - chemically induced
• ISSN: 1861-0684; 1861-0692
• DOI: 10.1007/s00392-008-0741-y

The present study aimed to investigate the causative medications and underlying risk factors that predispose to drug-induced QT interval prolongation. Twenty-one patients with drug-induced long QT (90% females, mean age 64.3 ± 14.1 years) were included in the study. Transthoracic echocardiography as well as continuous or ambulatory 48-h electrocardiographic monitoring was carried out in all patients during their hospitalization. The mean corrected QT (QTc) interval was 542 ± 56.8 ms. Known cardiac agents (mainly class III antiarrhythmics) were implicated in 13/21 (62%), antipsychotics in 8/21 (38%), and antibiotics in 5/21 patients (24%). Potential drug-interactions through inhibition of cytochrome P450 isoenzymes were considered responsible in 5/21 cases (24%). The underlying cardiovascular diseases included hypertension (57%) with left ventricular hypertrophy (29%), paroxysmal atrial tachyarrhytmias (48%), heart failure (14%), valvular heart disease (10%), and coronary artery disease (5%). Torsade de pointes (TdP) was recorded in 6/21 of patients, and cardiac arrest necessitating resuscitation occurred in five of them. A significant correlation was observed between administration of cardiac agents and TdP events (P < 0.05). TdP and cardiac arrest events were both associated with a QTc interval >510 ms (P < 0.05). Advanced age (>60 years), female gender, hypertension and paroxysmal atrial tachyarrhytmias were the most common identifiable pre-existing factors for drug-induced long QT in our patient cohort. Marked QTc interval prolongation should be considered of prognostic significance for TdP and cardiac arrest events.