QT Interval and Its Drug-Induced Prolongation

2003 ◽  
pp. 311-328 ◽  
Author(s):  
Wojciech Zareba ◽  
Arthur J. Moss
Keyword(s):  
Qt Interval ◽  
Drug Induced

scholarly journals Antipsychotics in routine treatment are minor contributors to QT prolongation compared to genetics and age

2021 ◽  
pp. 026988112110034
Author(s):  
Leif Hommers ◽  
Maike Scherf-Clavel ◽  
Roberta Stempel ◽  
Julian Roth ◽  
Matthias Falter ◽  
...  
Keyword(s):  
Qt Interval ◽  
Multivariate Regression Analysis ◽  
Cardiac Repolarization ◽  
Qtc Interval ◽  
Serum Concentrations ◽  
Drug Induced ◽  
Individual Level ◽  
Main Determinants ◽  
The Individual ◽  
Polygenic Variation

Background: Drug-induced prolongation of cardiac repolarization limits the treatment with many psychotropic drugs. Recently, the contribution of polygenic variation to the individual duration of the QT interval was identified. Aims: To explore the interaction between antipsychotic drugs and the individual polygenic influence on the QT interval. Methods: Retrospective analysis of clinical and genotype data of 804 psychiatric inpatients diagnosed with a psychotic disorder. The individual polygenic influence on the QT interval was calculated according to the method of Arking et al. Results: Linear regression modelling showed a significant association of the individual polygenic QT interval score (ßstd = 0.176, p < 0.001) and age (ßstd = 0.139, p < 0.001) with the QTc interval corrected according to Fridericia’s formula. Sex showed a nominal trend towards significance (ßstd = 0.064, p = 0.064). No association was observed for the number of QT prolonging drugs according to AZCERT taken. Subsample analysis ( n = 588) showed a significant association of potassium serum concentrations with the QTc interval (ßstd = −0.104, p = 0.010). Haloperidol serum concentrations were associated with the QTc interval only in single medication analysis ( n = 26, ßstd = 0.101, p = 0.004), but not in multivariate regression analysis. No association was observed for aripiprazole, clozapine, quetiapine and perazine, while olanzapine and the sum of risperidone and its metabolite showed a negative association. Conclusions: Individual genetic factors and age are main determinants of the QT interval. Antipsychotic drug serum concentrations within the therapeutic range contribute to QTc prolongation on an individual level.

scholarly journals Safety and effectiveness of drug therapy for the acutely agitated patient (Part I)

2013 ◽  
pp. 127-136
Author(s):  
Gianluca Airoldi
Keyword(s):  
Heart Rate ◽  
Qt Interval ◽  
Physical Restraint ◽  
Safety Data ◽  
Surrogate Marker ◽  
Diagnostic Procedures ◽  
Torsades De Pointes ◽  
Long Qt ◽  
Drug Induced ◽  
Qt Interval Prolongation

Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the first in a 2-part series) is to review the extensive safety data published on the antipsychotic medications currently available for managing situations of this type, including older neuroleptics like haloperidol, chlorpromazine, and pimozide as well as a number of the newer atypical antipsychotics (olanzapine, risperidone, ziprasidone). Particular attention is focused on the ability of these drugs to lengthen the QT interval in surface electrocardiograms. This adverse effect is of major concern, especially in light of the reported relation between QT interval and the risk of sudden death. In patients with the congenital long-QT syndrome, a long QT interval is associated with a fatal paroxysmal ventricular arrhythmia knownas torsades de pointes. Therefore, careful evaluation of the QT-prolonging properties and arrhythmogenic potential of antipsychotic drugs is urgently needed. Clinical assessment of drug-induced QT-interval prolongation is strictly dependent on the quality of electrocardiographic data and the appropriateness of electrocardiographic analyses. Unfortunately, measurement imprecision and natural variability preclude a simple use of the actually measured QT interval as a surrogate marker of drug-induced proarrhythmia. Because the QT interval changes with heart rate, a rate-corrected QT interval (QTc) is commonly used when evaluating a drug’s effect. In clinical settings, themost widely used formulas for rate-correction are those of Bazett (QTc=QT/RR^0.5) and Fridericia (QTc=QT/RR^0.33), both of which standardize themeasuredQTinterval to an RRinterval of 1 s (heart rate of 60 bpm).However, QT variability can also be influenced by other factors that are more difficult to measure, including body fat, meals, psycho-physical distress, and circadian and seasonal fluctuations.

scholarly journals Drug-induced long qt syndrome

2020 ◽  
Vol 27 (3) ◽  
pp. 42-52
Author(s):  
G. A. Golovina ◽  
K. V. Zaphiraki ◽  
E. D. Kosmacheva
Keyword(s):  
Long Qt Syndrome ◽  
Qt Interval ◽  
Diagnosis And Treatment ◽  
Fatal Complication ◽  
Long Qt ◽  
Drug Induced ◽  
Long Qt Interval ◽  
Qt Syndrome

In this review drug-induced long QT interval syndrome is described. The authors discuss approaches for the prevention, diagnosis, and treatment of this potentially fatal complication.

scholarly journals Drug-induced QT interval prolongation in cancer patients

2011 ◽  
Vol 4 (4) ◽  
pp. 223
Author(s):  
Torben K. Becker ◽  
Sai-Ching J. Yeung
Keyword(s):  
Cancer Patients ◽  
Qt Interval ◽  
Alkylating Agents ◽  
Torsade De Pointes ◽  
Interval Prolongation ◽  
Drug Induced ◽  
Vascular Disruption ◽  
Qt Interval Prolongation ◽  
Increased Risk ◽  
Multiple Drugs

Cancer patients are at an increased risk for QT interval prolongation and subsequent potentially fatal Torsade de pointes tachycardia due to the multiple drugs used for treatment of malignancies and the associated symptoms and complications. Based on a systematic review of the literature, this article analyzes the risk for prolongation of the QT interval with antineoplastic agents and commonly used concomitant drugs. This includes anthracyclines, fluorouracil, alkylating agents, and new molecularly targeted therapeutics, such as vascular disruption agents. Medications used in the supportive care can also prolong QT intervals, such as methadone, 5-HT3-antagonists and antihistamines, some antibiotics, antifungals, and antivirals. We describe the presumed mechanism of QT interval prolongation, drug-specific considerations, as well as important clinical interactions. Multiple risk factors and drug–drug interactions increase this risk for dangerous arrhythmias. We propose a systematic approach to evaluate cancer patients for the risk of QT interval prolongation and how to prevent adverse effects.

Abstract 211: Automated and Non-invasive Estimation of QT Interval from Microscopy Images of Stem Cell-Derived Cardiomyocytes

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Mahnaz Maddah ◽  
Kevin Loewke
Keyword(s):  
Drug Development ◽  
Qt Interval ◽  
Cellular Response ◽  
Cardiovascular Health ◽  
New Drugs ◽  
Patient Specific ◽  
Current Standard ◽  
Drug Induced ◽  
Safety Testing ◽  
Non Invasive

A promising application of induced pluripotent stem cells (iPSCs) is the generation of patient-specific cardiomyocytes (CMs), which can be used for drug development and safety testing related to cardiovascular health. iPSC-derived CMs can be used for preclinical testing of new drugs that may cause drug-induced arrhythmia or long QT syndrome, as well as post-market safety testing of existing drugs. The measurement of QT interval for iPSC-derived CMs is commonly analyzed using electrophysiological potentials captured by a micro-electrode array (MEA). While such systems are the current standard for characterization, they can be expensive and low-throughput, require high cell plating density, and due to the direct contact between cells and electrodes, may cause undesirable cellular response. Here, we present a new method to non-invasively measure the QT-interval in iPSC-derived CMs using video microscopy and computer vision analysis. Our algorithms can reliably and automatically extract beating signal characteristics such as frequency, irregularity, and duration through image analysis of cardiomyocyte motion. Through a correlative study with MEA, we demonstrate that a non-invasive measurement of QT interval can be derived from the duration of visible cellular motion that occurs during contraction and relaxation. We also show that our system can accurately characterize the cellular response from the addition of compounds known to modulate beating frequency and irregularity. Our measurement technique is robust, automated, and requires no physical or chemical contact with the cells, making it ideal for cardiovascular drug development and cardiotoxicity testing.

Abstract 15680: Validation of Remote Measurement of the Qtc Intervals Using an Apple Watch

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Carmen Spaccarotella ◽  
serena migliarino ◽  
annalisa mongiardo ◽  
Jolanda Sabatino ◽  
Giuseppe Santarpia ◽  
...  
Keyword(s):  
Qt Interval ◽  
Index Finger ◽  
Remote Measurement ◽  
Drug Induced ◽  
Left Wrist ◽  
Qt Interval Prolongation ◽  
The Right ◽  
Health Application ◽  
Pdf Format ◽  
E Mail

Introduction: In many circumstances, especially in the Covid-19 period, it could be necessary to measure the QT interval repeatedly even daily. Hypothesis: The aim of the study was to evaluate the feasibility of remote measuring LI-LII and V2 leads with using a commercially available Apple Watch Series 4. Methods: The accuracy of the QTc calculation with the smartwatch compared to the standard ECG was tested using di!erent formulae. One hundred patients admitted to our CCU were studied. LI-LII and V2 tracings were obtained immediately after the recording of the standard 12-lead ECG. The LI was recorded with the smartwatch on the left wrist and the right index finger on the crown; LII was obtained with the watch on the left lower abdomen and the right index finger on the crown; V2 lead was recorded with a smartwatch in the fourth intercostal space left parasternal with the right index finger on the crown. All recorded 30” ECGs were digitally stored using the health application of an iPhone Series 10 in the pdf format. The advantage of saving the ECG in pdf format is that it can be sent also via e-mail. Results: There was an agreement between the QTLI, QT-LII, QT-V2 and QT mean intervals of smartphone electrocardiography tracings and standard electrocardiography using Spearman’s correlation coefficient of 0.881; 0.885; 0.801; 0.911 respectively [p<0.001]. The reliability of the mean QTc measurements was tested with Bland-Altman analysis using Bazett’s, Friedericia’s, and Framingham’s formulas between standard ECG and smartwatch(Figure). Conclusions: These data demonstrated the feasibility to measure the QTc in LI, LII and V2 leads with a smartwatch with results comparable to that performed with the standard ECG. These data could have an important clinical impact both for the widespread di!usion of smartwatches and for the monitoring of drug-induced QT interval prolongation, especially in the Covid-19 era.

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