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https://www.readbyqxmd.com/read/28229241/acquired-prolongation-of-qt-interval-as-a-risk-factor-for-torsade-de-pointes-ventricular-tachycardia-a-narrative-review-for-the-anesthesiologist-and-intensivist
#1
REVIEW
Arsen Uvelin, Jasmina Pejaković, Vesna Mijatović
More than 70% of intensive care unit (ICU) patients experience heart rhythm disturbances, and these patients have correspondingly higher mortality rates. Consequently, one of the standards of care in ICUs is continuous electrocardiography monitoring. One of the potentially preventable dysrhythmic events is the occurrence of torsade de pointes ventricular tachycardia in the setting of acquired prolonged QT interval. This type of ventricular tachycardia can be malignant because it often progresses to ventricular fibrillation...
February 22, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/28223381/a-phase-i-randomized-double-blinded-placebo-and-moxifloxacin-controlled-4-period-crossover-study-to-evaluate-the-effect-of-gepotidacin-on-cardiac-conduction-as-assessed-by-12-lead-electrocardiogram-in-healthy-volunteers
#2
Mohammad Hossain, Meijian Zhou, Courtney Tiffany, Etienne Dumont, Borje Darpo
Gepotidacin is a novel, first in class triazaacenaphthylene antibiotic in development for treatment of conventional and biothreat infections. This was a single-dose, cross-over thorough QT study in healthy subjects who were administered an IV gepotidacin as a therapeutic (1000 mg), and supra-therapeutic (1800 mg) dose, placebo and 400 mg oral moxifloxacin in 4 separate treatment periods.Gepotidacin caused a mild effect on heart rate with a largest placebo-corrected change-from-baseline HR of 7 and 10 bpm at the end of the 1000 mg and 1800 mg infusion, respectively...
February 21, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28223296/cardiac-effects-of-sulfonylurea-related-hypoglycemia
#3
Timothy L Middleton, Jencia Wong, Lynda Molyneaux, Belinda A Brooks, Dennis K Yue, Stephen M Twigg, Ted Wu
OBJECTIVE: To determine the effect of sulfonylurea-related hypoglycemia on cardiac repolarization and ectopy in the setting of well-controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirty subjects with sulfonylurea-treated type 2 diabetes underwent 48 h of concurrent continuous glucose monitoring and ambulatory electrocardiography. Ventricular repolarization (QTc) and QT dynamicity were analyzed during periods of hypoglycemia (<3.5 mmol/L for >20 min) and compared with periods of euglycemia and hyperglycemia combined...
February 21, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28223123/proarrhythmia-liability-assessment-and-the-comprehensive-in-vitro-proarrhythmia-assay-cipa-an-industry-survey-on-current-practice
#4
Simon Authier, Michael K Pugsley, John E Koerner, Bernard Fermini, William S Redfern, Jean-Pierre Valentin, Hugo M Vargas, Derek J Leishman, Krystle Correll, Michael J Curtis
INTRODUCTION: The Safety Pharmacology Society (SPS) has conducted a survey of its membership to identify industry practices related to testing considered in the Comprehensive In vitro Proarrhythmia Assay (CiPA). METHODS: Survey topics included nonclinical approaches to address proarrhythmia issues, conduct of in silico studies, in vitro ion channel testing methods used, drugs used as positive controls during the conduct of cardiac ion channel studies, types of arrhythmias observed in non-clinical studies and use of the anticipated CiPA ion channel assay...
February 18, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28216052/interaction-among-herg-channel-blockers-is-a-potential-mechanism-of-death-in-caffeine-overdose
#5
Jifeng Zheng, Wei Zhao, Kai Xu, Qingmao Chen, Yingying Chen, Yueliang Shen, Liping Xiao, Liqin Jiang, Yuan Chen
Caffeine overdose death is due to cardiac arrest, but its mechanism has not been explored in detail. In this study, our data showed that caffeine significantly prolonged the heart rate-corrected QT interval (QTc) of rabbits in vivo (P < 0.05; n = 7). Caffeine was also found to be a hERG channel blocker with an IC50 of 5.04mM (n=5). Although these two findings likely link caffeine overdose death with hERG channel blockade, the amount of caffeine consumption needed to reach the IC50 is very high. Further study demonstrated that addition another hERG blocker could lower the consumption of caffeine significantly, no matter whether two hERG blockers share the same binding sites...
February 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28213753/electrophysiologic-studies-on-the-risks-and-potential-mechanism-underlying-the-proarrhythmic-nature-of-azithromycin
#6
Mengdan Zhang, Ming Xie, Sha Li, Ying Gao, Shuyin Xue, Huili Huang, Kesu Chen, Fuming Liu, Long Chen
The mechanisms underlying arrhythmia induced by the clinical use of azithromycin are poorly understood. We aimed to investigate the proarrhythmic effects of azithromycin using electrocardiogram (ECG) and ion channel models. In vivo and in vitro guinea pig ECG and current and voltage clamp recordings were carried out. Azithromycin at 114.6 mg/kg (three times the clinically relevant dose) reduced heart rate (HR) and prolonged the PR, QRS and rate-corrected QT (QTc) intervals of guinea pig ECG in vivo. In vitro technique revealed that azithromycin at 207...
February 17, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28213505/revealing-the-concealed-nature-of-long-qt-type-3-syndrome
#7
Amara Greer-Short, Sharon A George, Steven Poelzing, Seth H Weinberg
BACKGROUND: Gain-of-function mutations in the voltage-gated sodium channel (Nav1.5) are associated with the long-QT-3 (LQT3) syndrome. Nav1.5 is densely expressed at the intercalated disk, and narrow intercellular separation can modulate cell-to-cell coupling via extracellular electric fields and depletion of local sodium ion nanodomains. Models predict that significantly decreasing intercellular cleft widths slows conduction because of reduced sodium current driving force, termed "self-attenuation...
February 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28213480/a-common-genetic-variant-risk-score-is-associated-with-drug-induced-qt-prolongation-and-torsade-de-pointes-risk-a-pilot-study
#8
David G Strauss, Jose Vicente, Lars Johannesen, Ksenia Blinova, Jay W Mason, Peter Weeke, Elijah R Behr, Dan M Roden, Raymond Woosley, Gulum Kosova, Michael A Rosenberg, Christopher Newton-Cheh
Background -Drug-induced QT interval prolongation, a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications. The contribution of common genetic variants previously associated with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known. Methods -We tested the hypothesis that a weighted combination of common genetic variants contributing to QT interval at baseline, identified through genome-wide association studies, can predict individual response to multiple QT-prolonging drugs...
February 17, 2017: Circulation
https://www.readbyqxmd.com/read/28212739/individualized-corrected-qt-interval-is-superior-to-qt-interval-corrected-using-the-bazett-formula-in-predicting-mutation-carriage-in-families-with-long-qt-syndrome
#9
Tomas Robyns, Rik Willems, Bert Vandenberk, Joris Ector, Christophe Garweg, Cuno Kuiperi, Jeroen Breckpot, Anniek Corveleyn, Stefan Janssens, Hein Heidbuchel, Dieter Nuyens
BACKGROUND: Long QT syndrome (LQTS) is characterized by reduced penetrance and variable QT prolongation over time, resulting in an estimate of 25% carriers of a pathogenic mutation with a normal corrected QT (QTc) interval on the resting electrocardiogram (ECG). OBJECTIVE: The purpose of this study was to test the hypothesis that an individualized corrected QT interval derived from 24-hour Holter data more accurately predicts carriage of a pathogenic LQTS mutation than did QT derived from a standard 12-lead ECG and corrected using the Bazett formula (QTc interval)...
March 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28211989/timothy-syndrome-1-genotype-without-syndactyly-and-major-extracardiac-manifestations
#10
Róbert Sepp, Lidia Hategan, Attila Bácsi, Judit Cseklye, László Környei, János Borbás, Márta Széll, Tamás Forster, István Nagy, Zoltán Hegedűs
Timothy syndrome 1 (TS1) is a rare genetic disorder characterized by multisystem abnormalities including QT prolongation, congenital heart defects, facial dysmorphism, episodic hypoglycemia, and neurological symptoms. A morphological hallmark of TS1 is syndactyly, present in all cases. TS1 is caused by the canonical p.Gly406Arg mutation in the alternatively spliced exon 8A in the CACNA1C gene, encoding for the main cardiac L-type calcium channel. A variant case of TS1 is reported. The proband had intermittent fetal bradycardia with heart rate of 72 bpm...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28209348/effects-of-metabolically-healthy-and-unhealthy-obesity-on-prolongation-of-corrected-qt-interval
#11
Xiaofan Guo, Zhao Li, Liang Guo, Shasha Yu, Hongmei Yang, Liqiang Zheng, Guowei Pan, Yonghong Zhang, Yingxian Sun, Mark J Pletcher
Although obesity and the metabolic syndrome (MS) often co-occur, many obese (OB) subjects have a favorable metabolic profile. It is unclear whether these factors independently influence cardiac electrophysiology including prolongation of the QT interval. We examined associations among obesity, MS, and prolonged corrected QT (QTc) interval in a large sample of Chinese research participants aged ≥35 years recruited from rural areas of Liaoning Province during 2012 to 2013. Of the 11,209 participants, 6,364 (56...
January 25, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28202194/study-of-factors-affecting-the-progression-and-termination-of-drug-induced-torsade-de-pointes-in-two-dimensional-cardiac-tissue
#12
Ponnuraj Kirthi Priya, M Ramasubba Reddy
INTRODUCTION: To study the conditions leading to the initiation and termination of drug induced Torsade de pointes (TdP) along with QT prolongation. METHODS: A 2D anisotropic transmural section of the ventricular myocardium is modeled using the TP06 equations and the cells are interconnected with gap junction conductances (GJC). The tissue is remodeled by reducing the repolarization reserve (by increasing calcium current (ICaL)) of all cells thus making them vulnerable to development of early after depolarizations (EADs)...
February 2, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28197277/scoring-system-based-on-electrocardiogram-features-to-predict-the-type-of-heart-failure-in-patients-with-chronic-heart-failure
#13
Purnasidha Bagaswoto Hendry, Lucia Krisdinarti, Maharani Erika
BACKGROUND: Heart failure (HF) is divided into heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Mortality from HF is inversely related to left ventricular function. Additional studies are required to distinguish between these two types of HF. A previous study showed that HFrEF is less likely when electrocardiogram (ECG) findings are normal. This study aims to create a scoring system based on ECG findings that will predict the type of HF...
June 2016: Cardiology Research
https://www.readbyqxmd.com/read/28193647/piperaquine-population-pharmacokinetics-and-cardiac-safety-in-cambodia
#14
Pattaraporn Vanachayangkul, Chanthap Lon, Michele Spring, Sommethy Sok, Winita Ta-Aksorn, Chanikarn Kodchakorn, Sut-Thang Pann, Soklyda Chann, Mali Ittiverakul, Sabaithip Sriwichai, Nillawan Buathong, Worachet Kuntawunginn, Mary So, Theng Youdaline, Erin Milner, Mariusz Wojnarski, Charlotte Lanteri, Jessica Manning, Satharath Prom, Mark Haigney, Louis Cantilena, David Saunders
Despite rising resistance, dihydroartemisinin-piperaquine (DP) remains a first line therapy for uncomplicated malaria in many parts of Cambodia. While generally well-tolerated as a 3-day regimen, compressed 2-day regimens were associated with treatment-limiting cardiac repolarization effects in a recent clinical trial. To better estimate the risks of piperaquine concentration on QT interval prolongation, we pooled data from 3 randomized clinical trials between 2010 and 2014 in northern Cambodia. A population pharmacokinetic model was developed to compare exposure-response relationships between 2-day (2DP) and 3-day (3DP) regimens while accounting for differences in regimen and sample collection times between studies...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28193195/assessing-the-burden-of-treatment-emergent-adverse-events-associated-with-atypical-antipsychotic-medications
#15
Pierre-Michel Llorca, Christophe Lançon, Ann Hartry, T Michelle Brown, Dana B DiBenedetti, Siddhesh A Kamat, Clément François
BACKGROUND: Treatment of schizophrenia and major depressive disorder (MDD) with atypical antipsychotics (AAPs) show improved efficacy and reduced side effect burden compared with older antipsychotic medications. However, a risk of treatment-emergent adverse events (TEAEs) remains. TEAEs are hard to quantify and perspectives on the importance of TEAEs differ across patients and between patients and physicians. The current study is a qualitative assessment that investigates TEAEs of AAPs from both patient and physician perspectives to provide better understanding of the occurrence and burden of TEAEs associated with these medications...
February 13, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28186837/methadone-and-corrected-qt-prolongation-in-pain-and-palliative-care-patients-a-case-control-study
#16
Katherine M Juba, Tina M Khadem, David J Hutchinson, Jack E Brown
BACKGROUND: Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients. OBJECTIVE: Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool...
February 10, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28185059/severe-proarrhythmic-potential-of-the-antiemetic-agents-ondansetron-and-domperidone
#17
Gerrit Frommeyer, Christina Fischer, Christian Ellermann, Philipp S Lange, Dirk G Dechering, Simon Kochhäuser, Michael Fehr, Lars Eckardt
The potential of ondansetron and domperidone, both clinically established antiemetic agents, to increase the QT-interval has been described in several case reports. Therefore, the aim of the present study was to investigate whether these drugs may provoke polymorphic ventricular tachycardia in a sensitive experimental model of drug-induced proarrhythmia. In 10 female rabbits, ondansetron (1, 5 and 10 µM, n = 10) or domperidone (0.5, 1 and 2 µM, n = 8) was infused after obtaining baseline data. Eight endo- and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG reproduced the clinically observed QT-prolongation (ondansetron: 1 µM:+17 ms, 5 µM:+41 ms, 10 µM:+78 ms, p < 0...
February 9, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28182570/long-term-outcome-and-safety-of-prolonged-bedaquiline-treatment-for-multidrug-resistant-tuberculosis
#18
Lorenzo Guglielmetti, Marie Jaspard, Damien Le Dû, Marie Lachâtre, Dhiba Marigot-Outtandy, Christine Bernard, Nicolas Veziris, Jérôme Robert, Yazdan Yazdanpanah, Eric Caumes, Mathilde Fréchet-Jachym
Bedaquiline, a recently approved drug for the treatment of multidrug-resistant tuberculosis (MDR-TB), is recommended for a duration of 24 weeks. There are scarce data on patients treated with this drug outside clinical trials.All MDR-TB patients who started treatment from January 1, 2011 to December 31, 2013 and received ≥30 days of bedaquiline were included in a multicentre observational cohort.Among 45 MDR-TB patients, 53% harboured isolates resistant to both fluoroquinolones and second-line injectables, and 38% harboured isolates resistant to one of these drug classes...
December 22, 2016: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28174642/prolonged-qt-interval-and-cardiac-arrest-after-a-single-dose-of-amiodarone-in-a-woman-with-turner-s-syndrome
#19
Dorte Guldbrand Nielsen, Jens Cosedis Nielsen, Christian Trolle, Claus Højbjerg Gravholt, Niels Holmark Andersen
Low-dose QT-prolonging drugs may have detrimental effects on women with Turner's syndrome. Preventive measures would be to use potential QT-prolonging drugs with precaution and ensure that both before and during treatment, ECGs are evaluated and drug treatment stopped if the QT interval increases.
February 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28163191/csahi-study-detection-of-drug-induced-ion-channel-receptor-responses-qt-prolongation-and-arrhythmia-using-multi-electrode-arrays-in-combination-with-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#20
Takashi Kitaguchi, Yuta Moriyama, Tomohiko Taniguchi, Sanae Maeda, Hiroyuki Ando, Takaaki Uda, Koji Otabe, Masao Oguchi, Shigekazu Shimizu, Hiroyuki Saito, Atsushi Toratani, Mahoko Asayama, Wataru Yamamoto, Emi Matsumoto, Daisuke Saji, Hiroki Ohnaka, Norimasa Miyamoto
INTRODUCTION: The use of multi-electrode arrays (MEA) in combination with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provides a promising method to predict comprehensive cardiotoxicity, including drug-induced QT prolongation and arrhythmia. We previously demonstrated that MEA in combination with hiPSC-CMs could provide a generalizable platform by using 7 reference drugs at 10 testing facilities. Using this approach, we evaluated responses to reference drugs that modulate a range of cardiac ion currents and have a range of arrhythmogenic effects...
February 2, 2017: Journal of Pharmacological and Toxicological Methods
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