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QT prolongation was perceived as a major antiarrhythmic mechanism, but soon became a surrogate for torsades de pointes (TdP) instead. Drugs that prolong the QT interval range from having potent torsadogenic activity to no proarrhythmic action and even antiarrhythmic effects. Blockade of hERG channels is the primary cause of TdP, but blockade/activation of other channels can also be torsadogenic. TdP is primarily caused by disturbances of TRIaD, but disturbance of wavelength can also contribute to TdP (where TRIaD is triangulation, reverse use dependence, instability and dispersion, and wavelength equals conduction velocity times effective refractory period). The above proarrhythmic parameters do not only result in TdP, but can also lead to ventricular tachycardia (VT) and ventricular fibrillation (VF). Note that QT prolongation (not listed as a causal factor) yields many false positives (potentially depriving patients from much needed drugs) and false negatives (potentially exposing patients to lethal arrhythmias). Thus, drug-induced QT prolongation is a bad surrogate for TdP, VT or VF; it is high time to move away from an oversimplified and erroneous surrogate. [ABSTRACT FROM AUTHOR]

Long QT syndrome is a genetic disorder associated with life threatening ventricular arrhythmias and sudden death. This inherited arrhythmic disorder exhibits genetic heterogeneity, incomplete penetrance, and variable expressivity. During the past two decades there have been major advancements in understanding the genotype-phenotype correlations in LQTS. This genotype-phenotype relationship can lead to improved management of LQTS. However, development of genotype-specific or mutation-specific management strategies is very challenging. This review describes the pathophysiology of LQTS, genotype-phenotype correlations, and focuses on the management of LQTS. In general, the treatment of LQTS consists of lifestyle modifications, medical therapy with beta-blockers, device and surgical therapy. We further summarize current data on the efficacy of pharmacological treatment options for the three most prevalent LQTS variants including beta-blockers in LQT1, LQT2 and LQT3, sodium channel blockers and ranolazine for LQT3, potassium supplementation and spironolactone for LQT2, and possibly sex hormone-based therapy for LQT2. [ABSTRACT FROM AUTHOR]

Objective: To develop guidelines for the management of QT prolongation after citalopram overdose, including decontamination with single-dose activated charcoal (SDAC) and cardiac monitoring.Design: Simulation study using a previously developed pharmacokinetic-pharmacodynamic (PKPD) model which predicted the time-course of QT prolongation and the effect of citalopram dose and use of SDAC on QT prolongation.Main Measures and Results: The previously developed PKPD model was used to address the following in patients following citalopram overdose: (1) Above what dose should patients be decontaminated? (2) Above what dose should patients have cardiac monitoring? (3) For what period of time should patients be monitored? The primary outcome was QT,RR combinations above an abnormal threshold as a surrogate predictor of torsades de pointes. Simulations were performed using MATLAB for an overdose patient with typical demographics: 30-year-old female with a heart rate of 79 bpm taking citalopram therapeutically. The simulations showed: (1) There was significant benefit associated with the administration of SDAC to patients following citalopram overdose ingesting >600 mg; (2) With citalopram overdoses >1,000mg it was advisable to give SDAC and cardiac monitor the patient; (3) The risk of developing future abnormal QT,RR combinations was less than 1% in patients with normal QT,RR combinations up to 13 h post-dose, so the minimum monitoring time for citalopram overdoses >1,000mg should be 13h. Recommended dose levels for intervention should be lowered in older patients and patients with tachycardia, while men are less sensitive to QT prolongation.Conclusions: Guidelines for the management of QT prolongation after citalopram overdose were developed. We believe the model will help clinicians to decide which patients to decontaminate and monitor. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine the effects of the interaction between intravenous anesthetics and desflurane on the QT interval.Methods: Fifty patients who underwent lumbar spine surgery were included. The patients received 3 μg/kg fentanyl and were randomly divided into two groups: group P patients received 1.5 mg/kg propofol and group T patients received 5 mg/kg thiamylal 2 min after fentanyl injection. All patients received rocuronium and desflurane (6% inhaled concentration) after loss of consciousness. Tracheal intubation was performed 3 min after rocuronium injection. Heart rate (HR), mean arterial pressure (MAP), bispectral index score (BIS), and the heart rate-corrected QT (QTc) interval on a 12-lead electrocardiograms were recorded before fentanyl injection (T1), 2 min after fentanyl injection (T2), 1 min after propofol or thiamylal injection (T3), immediately before intubation (T4), and 2 min after intubation (T5).Results: There were no significant intergroup differences in patient characteristics. BIS and MAP decreased after anesthesia induction in both groups. MAP values at T3, T4, and T5 in group T were higher than those in group P. HR did not change over time or differ between the groups. The QTc intervals at T4 and T5 in group T were longer than those at T1. In group P, the QTc interval at T3 was significantly shorter than that at T1. The QTc intervals at T3, T4, and T5 in group T were significantly longer than those in group P.Conclusions: A propofol injection could counteract the QTc interval prolongation during desflurane anesthesia induction.Trial registration: UMIN Clinical Trials Registry database reference number: UMIN000023707. This study was registered on August 21, 2016. [ABSTRACT FROM AUTHOR]