Sample Size Calculation in Other Areas
Shein-Chung Chow, Jun Shao, Hansheng Wang, Yuliya Lokhnygina in Sample Size Calculations in Clinical Research: Third Edition, 2017
In clinical trials, a 12-lead electrocardiogram (ECG) is usually conducted for the assessment of potential cardiotoxicity induced by the treatment under study. On an ECG tracing, the QT interval is measured from the beginning of the Q wave to the end of the T wave. QT interval is often used to indirectly assess the delay in cardiac repolarization, which can predispose to the development of life-threatening cardiac arrhythmias such as torsade de pointes (Moss, 1993). QTc interval is referred to as the QT interval corrected by heart rate. In clinical practice, it is recognized that the prolongation of the QT/QTc interval is related to increased risk of cardiotoxicity such as a life-threatening arrhythmia (Temple, 2003). Thus, it is suggested that a careful evaluation of potential QT/QTc prolongation be assessed for potential drug-induced cardiotoxicity.
Paper 3 Answers
James Day, Amy Thomson, Tamsin McAllister, Nawal Bahal in Get Through, 2014
The QT interval is a measure of the time taken for a cycle of ventricular depolarization and repolarization, and is measured as the time between the beginning of the electrocardiogram Q wave and the end of the T wave. It varies with heart rate and is therefore corrected to give the QTc. Prolongation of the QT interval can be due to genetic or acquired causes but is often due to a combination of a genetic predisposition and acquired factors. Prolongation of QT interval leads to impairment of ventricular repolarization, which can predispose to polymorphic ventricular tachycardia (torsade de pointes). Drugs that prolong QT interval include most volatile anaesthetic agents, amiodarone, flecainide, thiazides, phenothiazines, tricyclic antidepressants and suxamethonium. In addition, excessive stress can trigger torsades de pointes in patients with prolonged QT interval. Care must therefore be taken in administering general anaesthesia in such patients.
Medicinal poisons
Jason Payne-James, Richard Jones in Simpson's Forensic Medicine, 2019
Since the 1990s, the concept of primary ‘inherited’ arrhythmia syndromes, or ion channelopathies, has developed from advances in molecular genetics. Alterations in genes coding for membrane proteins, such as ion channels or their associated proteins responsible for the generation of cardiac action potentials (AP), cause specific malfunctions which eventually lead to cardiac arrhythmias. These arrhythmic disorders include a wide variety of conditions. Among these, long QT, and Brugada, syndromes are the most extensively studied, and drugs cause a phenocopy of these two diseases. More than 10 different genes have been reported to be responsible for each syndrome. Individuals with long QT syndrome (LQTS) experience abnormal prolongation of the QT interval – the portion of the electrocardiogram (ECG) that represents repolarisation of cardiomyocytes (Figure 25.1). The QT interval extends from the onset of the Q wave to the end of the T wave. The normal rate-adjusted length for the QT interval is less than 440 milliseconds. A prolonged QT interval favours the occurrence of a lethal form of ventricular tachycardia known as torsades des pointes. The QT prolongation may be caused by genetic aberration or it may be acquired. Even those with the genetic form of the disease may have a perfectly normal-appearing electrocardiogram until some event causes the QT interval to lengthen, become pathologically long and produce an arrhythmia. The diagnosis is made by DNA resequencing.
A pharmacological profile of intravenous amisulpride for the treatment of postoperative nausea and vomiting
Published in Expert Review of Clinical Pharmacology, 2020
Several unwanted, ‘off-target’ effects of dopamine-antagonist antiemetics have limited their clinical use, the most important being a prolongation of the QT interval of the electrocardiogram, mediated by binding to the potassium ion channel known as the hERG channel, after the human ether-à-go-go-related gene (hERG) which codes for its alpha subunit. The QT interval represents the electrical repolarization of the heart in preparation for a new beat. QT prolongation can, therefore, lead to rhythm disturbances, including the potentially fatal torsade de pointes. Numerous dopaminergic antiemetics have been shown to bind hERG with high affinity, including droperidol (half-maximal inhibitory concentration [IC50] = 0.6–0.9 µM), haloperidol (~1 µM) and prochlorperazine (0.7–0.9 µM) [28–30]. These agents are also associated with a significant prolongation of the QT interval and cases of torsade de pointes in clinical practice [31–33].
Prolonged QTc Interval in Nigerian Children with Sickle Cell Anemia
Published in Hemoglobin, 2021
Maxwell U. Anah, Anthony C. Nlemadim, Chigozie I. Uzomba, Egorp O. Ineji, Friday A. Odey
There are other established causes of prolonged QTc interval, the majority of which have been excluded in the subjects of this study [8]. One of them is hypocalcemia, which appears to be a constant factor in sickle cell anemia, and together with myocardial ischemia, may be the fundamental reason for the occurrence of prolonged QTc interval in sickle cell anemia unlike in non sickle cell anemia patients with anemia due to other hematological diseases [3,4,21]. Hypomagnesemia also causes prolonged QTc interval by impairing release of parathormone and tissue response to parathormone that leads to secondary hypocalcemia [22]. Therefore, if serum calcium levels were measured in this study, one may have found hypocalcemia in both clinical states similar to that obtained in previous studies [3–7].
Prevalence and Risk Factors of QTc Prolongation in Prostate Cancer Patients Undergoing Brachytherapy
Published in Cancer Investigation, 2022
Simon Saad, Guila Delouya, Carole Lambert, Maroie Barkati, Charles Dariane, Mikhael Laskine, Daniel Taussky
Ninety-five patients were excluded from the analysis because of the ECG selection criteria. The median age of the study population (n = 754) was 64 years (IQR 60–69). Forty-five patients (6.0%) had a prolonged QTc interval (≥450ms) and among them six with a QTC >470ms. Fifty-four patients (7.2%) had a QTc interval between 439 and 449 ms, considered borderline elevated. No patient had a QTc of ≥500ms. One hundred-twenty-nine patients (17.1%) had a CAPRA score between 6 and 10, indicating high-risk prostate cancer. Sixty-eight (9.0%) patients were using at least one potential QTc prolongating drug at the time the ECG was performed. None of the patients with a QTC ≥450ms were taking drugs known to increase QTc interval and 3 patients with QTC ≥450ms (4.4%) were taking a drug with a possible risk of QTc prolongation. Seven percent of patients who had HDR brachytherapy and 9% of patients who received ADT had a QTc ≥450ms. Baseline characteristics of the study population are indicated in Table 1.
Related Knowledge Centers
- Arrhythmia
- Cardiac Arrest
- T Wave
- Ventricle
- Heart
- Electrocardiography
- Qrs Complex
- Genetics
- Long Qt Syndrome
- Sotalol