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https://www.readbyqxmd.com/read/29219167/quantitative-understanding-of-qtc-prolongation-and-gender-as-risk-factors-for-torsade-de-pointes
#1
Lars Johannesen, Christine Garnett, Man Luo, Shari Targum, Jens Stampe Sørensen, Nitin Mehrotra
Several risk factors for development of a potentially fatal ventricular arrhythmia, torsade de pointes, have been observed, including female gender. However, in most investigations, only few torsade events were included and/or rarely were postdose heart rate corrected QT (QTc) measurements included, as a surrogate of drug exposure. We developed a multivariate logistic regression model using data from 22,214 patients (33% women) with 84 torsade events (56% women) to evaluate the relationship between risk factors for torsade using data from four anti-arrhythmic drug development programs...
December 8, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29217664/incidence-diagnosis-and-management-of-qt-prolongation-induced-by-cancer-therapies-a-systematic-review
#2
REVIEW
Andreu Porta-Sánchez, Cameron Gilbert, Danna Spears, Eitan Amir, Joyce Chan, Kumaraswamy Nanthakumar, Paaladinesh Thavendiranathan
BACKGROUND: The cardiovascular complications of cancer therapeutics are the focus of the burgeoning field of cardio-oncology. A common challenge in this field is the impact of cancer drugs on cardiac repolarization (ie, QT prolongation) and the potential risk for the life-threatening arrhythmia torsades de pointes. Although QT prolongation is not a perfect marker of arrhythmia risk, this has become a primary safety metric among oncologists. Cardiologists caring for patients receiving cancer treatment should become familiar with the drugs associated with QT prolongation, its incidence, and appropriate management strategies to provide meaningful consultation in this complex clinical scenario...
December 7, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29209226/uncertainty-quantification-reveals-the-importance-of-data-variability-and-experimental-design-considerations-for-in-silico-proarrhythmia-risk-assessment
#3
Kelly C Chang, Sara Dutta, Gary R Mirams, Kylie A Beattie, Jiansong Sheng, Phu N Tran, Min Wu, Wendy W Wu, Thomas Colatsky, David G Strauss, Zhihua Li
The Comprehensive in vitro Proarrhythmia Assay (CiPA) is a global initiative intended to improve drug proarrhythmia risk assessment using a new paradigm of mechanistic assays. Under the CiPA paradigm, the relative risk of drug-induced Torsade de Pointes (TdP) is assessed using an in silico model of the human ventricular action potential (AP) that integrates in vitro pharmacology data from multiple ion channels. Thus, modeling predictions of cardiac risk liability will depend critically on the variability in pharmacology data, and uncertainty quantification (UQ) must comprise an essential component of the in silico assay...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29201009/in-vitro-and-in-silico-risk-assessment-in-acquired-long-qt-syndrome-the-devil-is-in-the-details
#4
REVIEW
William Lee, Monique J Windley, Jamie I Vandenberg, Adam P Hill
Acquired long QT syndrome, mostly as a result of drug block of the Kv11. 1 potassium channel in the heart, is characterized by delayed cardiac myocyte repolarization, prolongation of the T interval on the ECG, syncope and sudden cardiac death due to the polymorphic ventricular arrhythmia Torsade de Pointes (TdP). In recent years, efforts are underway through the Comprehensive in vitro proarrhythmic assay (CiPA) initiative, to develop better tests for this drug induced arrhythmia based in part on in silico simulations of pharmacological disruption of repolarization...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29197146/is-myocardial-repolarization-duration-associated-with-repolarization-heterogeneity
#5
Keith A Marill, Pat Dorsey, Anthony Holmes, Ketaki Muthal, Emily S Miller, Joel Xue
BACKGROUND: Dispersion of repolarization is theorized as one mechanism by which myocardial repolarization prolongation causes lethal torsades de pointes, (TdP). Our primary purpose was to determine whether prolongation of myocardial repolarization as measured by the heart rate-corrected J-to-T peak interval (JTpkc), is associated with repolarization heterogeneity as measured by transmural dispersion, defined as the median duration from the peak to the end of the T wave (TpTe). METHODS: A retrospective cohort study was performed at a single urban tertiary ED from July 2011-September 2012...
December 2, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/29194874/late-onset-severe-long-qt-syndrome
#6
Babken Asatryan, André Schaller, Deborah Bartholdi, Argelia Medeiros-Domingo
We report a case of torsades de pointes arrhythmia as the first manifestation of congenital Long QT syndrome in a 77-year-old man with family history of sudden unexplained death. This case illustrates the importance of vigilant clinical assessment and genetic counseling in families with sudden death in order to identify properly asymptomatic relatives at risk for cardiac events. It also demonstrates that Long QT syndrome can still manifest with potentially fatal arrhythmias late in life in previously asymptomatic elderly patients...
November 30, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/29194862/a-case-report-is-mexiletine-usage-effective-in-the-shortening-of-qtc-interval-and-improving-the-t-wave-alternans-in-timothy-syndrome
#7
Gulhan Tunca Sahin, Yakup Ergul
Timothy syndrome (TS) is a multisystemic disease that occurs because of a mutation in CACN1C gene and is characterized by prolonged QT interval. Mexiletine is a Class 1B antiarrhythmic drug that causes the disappearance of T-wave alternans by shortening QTc and peak-to-end of the T wave. It may block the development of torsades de pointes in a prolonged QT. This study presented the case of a patient diagnosed with TS and had a cardiac arrest history, prolonged QT, and T-wave alternans. After mexiletine treatment, the QTc interval shortened and T-wave alternans disappeared...
November 30, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/29194447/sevoflurane-causes-greater-qtc-interval-prolongation-in-chronically-hyperglycemic-patients-than-in-normoglycemic-patients
#8
Seishi Kimura, Shinichi Nakao, Atsuhiro Kitaura, Tatushige Iwamoto, Kei Houri, Mayuka Matsushima, Shinichi Hamasaki
QTc interval prolongation is a serious diabetic complication and increases mortality rate. Hyperglycemia inhibits the rapid component of delayed rectifier potassium channel currents (Ikr) and prolongs the QTc interval on electrocardiograms. Sevoflurane also inhibits the Ikr and causes QTc interval prolongation. In fact, torsade de pointes occurred in a patient with poorly controlled diabetes mellitus during sevoflurane anesthesia. We enrolled 74 patients, including 37 normoglycemic patients (glycated hemoglobin [HbA1c]: <6...
2017: PloS One
https://www.readbyqxmd.com/read/29192591/torsades-de-pointes-associated-with-qt-prolongation-after-catheter-ablation-of-paroxysmal-atrial-fibrillation
#9
Yae Min Park, Mi Suk Cha, Woong Chol Kang, Mi-Seung Shin, Young-Hoon Kim, In Suck Choi, Eak Kyun Shin
A 79-year-old woman who underwent catheter ablation for paroxysmal atrial fibrillation presented with Torsades de Pointes (TdP). Aggravation of prolonged QT interval which is most likely due to neural modulation by catheter ablation, played major role in the initiation of TdP. The patient was successfully treated with isoproterenol during acute stage and discharged after stabilization without implantation of permanent pacemaker or implantable cardioverter defibrillator.
September 2017: Indian Pacing and Electrophysiology Journal
https://www.readbyqxmd.com/read/29191244/frequency-characteristics-and-risk-factors-of-qt-interval-prolonging-drugs-and-drug-drug-interactions-in-cancer-patients-a-multicenter-study
#10
Qasim Khan, Mohammad Ismail, Sehrash Khan
BACKGROUND: Cancer patients may receive a high number of medications with the potential to prolong QT interval and subsequent TdP (torsades de pointes). This study aimed to identify the prevalence of QT prolonging drugs, their TdP risk, QT prolonging drug-drug interactions (QT-DDIs), levels, predictors, and TdP risk of drugs involved in QT-DDIs. METHODS: This multicenter study included cancer patients from three major tertiary care hospitals of Khyber-Pakhtunkhwa, Pakistan...
December 1, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29189312/hypoglycemia-and-sudden-death-during-treatment-with-methadone-for-opiate-detoxification
#11
Christopher J Plescia, Peter Manu
CLINICAL FEATURES: We present a case of a middle-aged man admitted to an inpatient detoxification facility for withdrawal of intranasal heroin, alprazolam, and ethanol. The patient was placed on methadone and chlordiazepoxide tapers. Ondansetron and trazodone were prescribed as needed for symptom control. On the third hospital day, the patient was found unresponsive with blood glucose of 40 mg/dL. He had no history of glucose dysregulation. The patient was pronounced dead shortly thereafter...
November 14, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/29184497/novel-two-step-classifier-for-torsades-de-pointes-risk-stratification-from-direct-features
#12
Jaimit Parikh, Viatcheslav Gurev, John J Rice
While pre-clinical Torsades de Pointes (TdP) risk classifiers had initially been based on drug-induced block of hERG potassium channels, it is now well established that improved risk prediction can be achieved by considering block of non-hERG ion channels. The current multi-channel TdP classifiers can be categorized into two classes. First, the classifiers that take as input the values of drug-induced block of ion channels (direct features). Second, the classifiers that are built on features extracted from output of the drug-induced multi-channel blockage simulations in the in-silico models (derived features)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29181850/can-nonclinical-repolarization-assays-predict-the-results-of-clinical-thorough-qt-studies-results-from-a-research-consortium
#13
Eunjung Park, Gary A Gintant, Daoqin Bi, Devi Kozeli, Syril D Pettit, Jennifer B Pierson, Matthew Skinner, James Willard, Todd Wisialowski, John Koerner, Jean-Pierre Valentin
BACKGROUND AND PURPOSE: Translation of nonclinical markers of delayed ventricular repolarization to clinical QTc prolongation (a biomarker for Torsades de Pointes proarrhythmia) remains an issue in drug discovery and regulatory evaluations. A retrospective analysis of 150 submitted drug applications in a US-FDA database was conducted to determine the utility of established nonclinical in vitro iKr current (hERG), action potential duration (APD) and in vivo (QTc) repolarization assays to detect and predict clinical QTc prolongation...
November 27, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29174490/risk-of-cardiac-events-associated-with-antidepressant-therapy-in-patients-with-long-qt-syndrome
#14
Meng Wang, Barbara Szepietowska, Bronislava Polonsky, Scott McNitt, Arthur J Moss, Wojciech Zareba, David S Auerbach
Patients with long QT syndrome (LQTS) are at a high risk of cardiac events. Many patients with LQTS are treated with antidepressant drugs (ADs). We investigated the LQTS genotype-specific risk of recurrent cardiac arrhythmic events (CAEs) associated with AD therapy. The study included 59 LQT1 and 72 LQT2 patients from the Rochester-based LQTS Registry with corrected QT (QTc) prolongation and a history of AD therapy. Using multivariate Anderson-Gill models, we estimated the LQTS genotype-specific risk of recurrent CAEs (ventricular tachyarrhythmias, aborted cardiac arrest, or sudden cardiac death) associated with time-dependent ADs...
November 13, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/29174246/incidence-of-drug-induced-torsades-de-pointes-with-intravenous-amiodarone
#15
Jayaprakash Shenthar, Jayasheelan Mambally Rachaiah, Vivek Pillai, Siva Sankara Chakali, Vidhyakar Balasubramanian, Manjunath Chollenhalli Nanjappa
AIM: To define the incidence, presentation, and outcomes of drug-induced Torsades de Pointes (TdP) with intravenous (IV) amiodarone. METHODS: From January 2014 to August 2016 a total of 268 patients received IV amiodarone, 142 for ventricular tachycardia, 104 for atrial flutter/fibrillation, and 22 for incessant atrial tachycardia. A uniform dosing of amiodarone to yield 1gm/day was used in all patients. RESULTS: Four of the 268 patients (M:F 1:3) with mean age of 51...
November 2017: Indian Heart Journal
https://www.readbyqxmd.com/read/29167918/risk-factors-for-qtc-interval-prolongation
#16
Charlotte P M Heemskerk, Marieke Pereboom, Karlijn van Stralen, Florine A Berger, Patricia M L A van den Bemt, Aaf F M Kuijper, Ruud T M van der Hoeven, Aukje K Mantel-Teeuwisse, Matthijs L Becker
PURPOSE: Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In this study, we quantified the effect of these risk factors on the length of the QTc interval. METHODS: We analyzed all ECGs that were taken during routine practice between January 2013 and October 2016 in the Spaarne Gasthuis, a general teaching hospital in the Netherlands...
November 22, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29162767/an-increasing-electromechanical-window-is-a-predictive-marker-of-ventricular-fibrillation-in-anesthetized-rabbit-with-ischemic-heart
#17
Vudhiporn Limprasutr, Prapawadee Pirintr, Anusak Kijtawornrat, Robert L Hamlin
The QTc interval is widely used in Safety Pharmacological studies to predict arrhythmia risk, and the electromechanical window (EMW) and short-term variability of QT intervals (STVQT) have been studied as new biomarkers for drug-induced Torsades de Pointes (TdP). However, the use of EMW and STVQT to predict ventricular fibrillation (VF) has not been elucidated. This study aimed to evaluate EMW and STVQT to predict VF in anesthetized rabbit model of VF. VF was induced by ligation of the left anterior descending and a descending branch of the left circumflex coronary arteries in a sample population of rabbits (n=18)...
November 21, 2017: Experimental Animals
https://www.readbyqxmd.com/read/29157021/gastroparesis-pharmacotherapy-and-cardiac-risk
#18
Per M Hellström, Ahmad Al-Saffar
BACKGROUND: Gastroparesis is characterized by abnormal gastric motility and delayed emptying with symptoms of early satiety, postprandial fullness, bloating, nausea, vomiting and abdominal pain. Pharmacological discovery has been lagging because potential drugs often are associated with abnormalities of electrical conduction of the myocardium due to interaction with cardiac ion channels leading to limited pharmaceutical options for development of new drugs. OBJECTIVE: Addresses the safety of drugs for gastroparesis in terms of cardiotoxicity related to the clinical use of prokinetics and antiemetics...
November 20, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/29151524/atrioventricular-block-induced-torsades-de-pointes-associated-with-kcnq1-g269s
#19
Tadashi Nakajima, Takashi Sugawara, Yoshiaki Kaneko, Masahiko Kurabayashi
No abstract text is available yet for this article.
November 20, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29147476/sudden-cardiac-arrest-as-a-rare-presentation-of-myxedema-coma-case-report
#20
Divya Salhan, Deepak Sapkota, Prakash Verma, Saroj Kandel, Omar Abdulfattah, Antony Lixon, Deribe Zwenge, Frances Schmidt
Myxedema coma is a decompensated hypothyroidism which occurs due to long-standing, undiagnosed, or untreated hypothyroidism. Untreated hypothyroidism is known to affect almost all organs including the heart. It is associated with a decrease in cardiac output, stroke volume due to decreased myocardial contractility, and an increase in systemic vascular resistance. It can cause cardiac arrhythmias and the most commonly seen conduction abnormalities are sinus bradycardia, heart block, ventricular tachycardia, and torsade de pointes...
2017: Journal of Community Hospital Internal Medicine Perspectives
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