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QTc prolongation

Abdunoor M Kabanywanyi, Rita Baiden, Ali M Ali, Muhidin K Mahende, Bernhards R Ogutu, Abraham Oduro, Halidou Tinto, Margaret Gyapong, Ali Sie, Esperanca Sevene, Eusebio Macete, Seth Owusu-Agyei, Alex Adjei, Guillaume Compaoré, Innocent Valea, Isaac Osei, Abena Yawson, Martin Adjuik, Raymond Akparibo, Mwaka A Kakolwa, Salim Abdulla, Fred Binka
The antimalarial drug piperaquine is associated with delayed ventricular depolarization, causing prolonged QT interval (time taken for ventricular de-polarisation and re-polarisation). There is a lack of safety data regarding dihydroartemisinin/piperaquine (DHA/PPQ) for the treatment of uncomplicated malaria, which has limited its use. We created a platform where electrocardiograms (ECG) were performed in public hospitals for the safety assessment of DHA/PPQ, at baseline before the use of dihydroartemisinin/piperaquine (Eurartesim®), and on day 3 (before and after administration of the final dose) and day 7 post-administration...
2016: PloS One
Altuğ Ösken, Nizamettin Selçuk Yelgeç, Regayip Zehir, Tuğba Kemaloğlu Öz, Selçuk Yaylacı, Ramazan Akdemir, Hüseyin Gündüz
Drug-induced torsades de pointes (TdP) is a rare but potentially fatal adverse effect of commonly prescribed medications including cardiac and noncardiac drugs. Importantly, many drugs have been reported to cause the characteristic Brugada syndrome-linked electrocardiography (ECG) abnormalities and/or (fatal) ventricular tachyarrhythmias. Chlorpheniramine and propranolol have the arrhythmogenic effects reported previously. A review of literature revealed a large number of case reports of chlorpheniramine or propranolol use resulting in QTc prolongation, TdP, or both...
July 2016: Indian Journal of Pharmacology
Ning Ma, Xiao-Yan Wu, Chang-Sheng Ma, Nian Liu, Rong Bai, Xin Du, Yan-Fei Ruan, Jian-Zeng Dong
Catheter ablation has been recommended as a treatment option for paroxysmal atrial fibrillation (PAF) patients complicated with type 2 diabetes mellitus (T2DM). PAF patients with T2DM have a higher recurrence rate after catheter ablation. Prolongation of corrected QT (QTc) interval has been linked to poor outcomes in T2DM patients. Whether the abnormal QTc interval is associated with the ablation outcome in the PAF patients with T2DM remains unknown. In this study, 134 PAF patients with T2DM undergoing primary catheter ablation were retrospectively enrolled...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Steven P Sears, Trevor W Getz, Christopher O Austin, William C Palmer, Evelyn A Boyd, Fernando F Stancampiano
BACKGROUND: Azithromycin has been associated with abnormalities of cardiac repolarization and development of torsades de pointes. Observational data suggest that the risk of death from cardiovascular causes is increased in patients taking azithromycin. Little is known regarding the risk of ventricular arrhythmia in patients with prolongation of the corrected QT interval who receive azithromycin. OBJECTIVE: The purpose of this study was to determine the incidence of sustained ventricular tachycardia in patients with prolonged corrected QT (QTc) who subsequently received azithromycin...
March 2016: Drugs—Real World Outcomes
Harmke Nijboer, Geert Lefeber, Alidair McLullich, Barbara van Munster
BACKGROUND: Haloperidol, frequently used for delirium, can lead to serious side effects, of which QTc prolongation is the most worrisome since it is associated with an increased risk of fatal cardiac arrhythmia. OBJECTIVES: The aim of this study was to measure the frequency of haloperidol use after procedures in patients aged ≥65 years in a hospital in the Netherlands. METHODS: This was a retrospective study among patients hospitalized in the Netherlands who were aged ≥65 years and who underwent a procedure between January 2008 and January 2009...
March 2016: Drugs—Real World Outcomes
S Gibiino, A Trappoli, B Balzarro, A R Atti, D De Ronchi
A 71-year-old man developed coma with severe respiratory failure, hypotension, and tachycardia induced by the intentional ingestion of quetiapine fumarate extended release (XR) 20 g. At the time, he had been treated for bipolar depression with venlafaxine 75 mg/day, lamotrigine 100 mg/day, pregabalin 75 mg/day, and quetiapine XR 400 mg/day for approximately 1 year. Comorbidities were hypertension treated with metoprolol, diabetes mellitus type 2 treated with metformin, and benign prostatic hyperplasia treated with silodosin...
December 2015: Drug Saf Case Rep
Tal Lorberbaum, Kevin J Sampson, Jeremy B Chang, Vivek Iyer, Raymond L Woosley, Robert S Kass, Nicholas P Tatonetti
BACKGROUND: QT interval-prolonging drug-drug interactions (QT-DDIs) may increase the risk of life-threatening arrhythmia. Despite guidelines for testing from regulatory agencies, these interactions are usually discovered after drugs are marketed and may go undiscovered for years. OBJECTIVES: Using a combination of adverse event reports, electronic health records (EHR), and laboratory experiments, the goal of this study was to develop a data-driven pipeline for discovering QT-DDIs...
October 18, 2016: Journal of the American College of Cardiology
Julia H Indik, Vineet Nair, Ruslan Rafikov, Iwan S Nyotowidjojo, Jaskanwal Bisla, Mayank Kansal, Devang S Parikh, Melissa Robinson, Anand Desai, Megha Oberoi, Akash Gupta, Taimur Abbasi, Zain Khalpey, Amit R Patel, Roberto M Lang, Samuel C Dudley, Bum-Rak Choi, Joe G N Garcia, Roberto F Machado, Ankit A Desai
Sudden death is a leading cause of mortality in sickle cell disease, implicating ventricular tachyarrhythmias. Prolonged QTc on an electrocardiogram (ECG), commonly seen with myocardial ischemia, is a known risk for polymorphic ventricular tachycardia (VT). We hypothesized that prolonged QTc is associated with mortality in sickle cell disease. ECG were analyzed from a cohort of 224 sickle patients (University of Illinois at Chicago, UIC) along with available laboratory, and echocardiographic findings, and from another cohort of 38 patients (University of Chicago, UC) for which cardiac MRI and free heme values were also measured...
2016: PloS One
Damodhar Reddy Gouni, Gandiah P, Venkateshwarlu Nandyala P
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Desheng Zhai, Yan Lang, Gaopan Dong, Yijun Liu, Xin Wang, Dushuang Zhou, Taizhen Cui, Yuxin Yang, Wenxi Zhang, Ying Zhao, Ruiling Zhang
Antipsychotic use is reported to be associated with a higher risk of sudden cardiac death and new users are especially susceptible to that risk. In this study, we focused on the ability of antipsychotics to prolong the QTc interval at the earliest stages of antipsychotic use. We employed a retrospective cohort study design in a naturalistic setting where having three ECG measurements over time (at baseline and after drug exposure) in antipsychotic-naïve, first-episode schizophrenia (FES) inpatients. The results revealed, in this relatively homogeneous, drug naïve FES patient sample, that QTc intervals were statistically significantly prolongated after a relatively short term (2-4weeks) of antipsychotic treatments, compared with baseline...
October 7, 2016: Schizophrenia Research
Wijith Munasinghe, Sven Stodtmann, Anthony Tolcher, Emiliano Calvo, Michael Gordon, Mathilde Jalving, Judith de Vos-Geelen, Diane Medina, Dennis Bergau, Silpa Nuthalapati, David Hoffman, Stacie Shepherd, Hao Xiong
PURPOSE: Veliparib (ABT-888) is an orally bioavailable potent inhibitor of poly(ADP-ribose) polymerase (PARP)-1 and PARP-2. This phase 1 study evaluated the effect of veliparib on corrected QT interval using Fridericia's formula (QTcF). METHODS: Eligible patients with advanced solid tumors received single-dose oral veliparib (200 mg or 400 mg) or placebo in a 6-sequence, 3-period crossover design. The primary endpoint was the difference in the mean baseline-adjusted QTcF between 400 mg veliparib and placebo (∆∆QTcF) at six post-dose time points...
October 5, 2016: Cancer Chemotherapy and Pharmacology
Pietro Enea Lazzerini, Pier Leopoldo Capecchi, Iacopo Bertolozzi, Gabriella Morozzi, Sauro Lorenzini, Antonella Simpatico, Enrico Selvi, Maria Romana Bacarelli, Maurizio Acampa, Deana Lazaro, Nabil El-Sherif, Mohamed Boutjdir, Franco Laghi-Pasini
Mounting evidence indicates that in chronic inflammatory arthritis (CIA), QTc prolongation is frequent and correlates with systemic inflammatory activation. Notably, basic studies demonstrated that inflammatory cytokines induce profound changes in potassium and calcium channels resulting in a prolonging effect on cardiomyocyte action potential duration, thus on the QT interval on the electrocardiogram. Moreover, it has been demonstrated that in rheumatoid arthritis (RA) patients, the risk of sudden cardiac death is significantly increased when compared to non-RA subjects...
2016: Frontiers in Cardiovascular Medicine
Ksenia Blinova, Jayna Stohlman, Jose Vicente, Dulciana Chan, Lars Johannesen, Maria P Hortigon-Vinagre, Victor Zamora, Godfrey Smith, William J Crumb, Li Pang, Beverly Lyn-Cook, James Ross, Mathew Brock, Stacie Chvatal, Daniel Millard, Loriano Galeotti, Norman Stockbridge, David G Strauss
BACKGROUND: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) hold promise for assessment of drug-induced arrhythmias and are being considered for use under the Comprehensive in Vitro Proarrhythmia Assay (CiPA). METHODS AND RESULTS: We studied the effects of 26 drugs and 3 drug combinations on two commercially available iPSC-CM types using high-throughput voltage-sensitive dye (VSD) and microelectrode-array (MEA) assays being studied for the Comprehensive in Vitro Proarrhythmia Assessment (CiPA) initiative and compared the results to clinical QT prolongation and torsade de pointes (TdP) risk...
October 3, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Justin A Green, Khadeeja Mohamed, Navin Goyal, Samia Bouhired, Azra Hussaini, Siôn W Jones, Gavin C K W Koh, Ivan Kostov, Maxine Taylor, Allen Wolstenholm, Stephan Duparc
Tafenoquine is in development as a single-dose treatment for relapse prevention in Plasmodium vivax malaria. Tafenoquine must be co-administered with a blood schizonticide; either chloroquine or artemisinin-based combination therapy (ACT). This open-label, randomized, parallel-group study evaluated potential drug interactions between tafenoquine and two ACTs: dihydroartemisinin-piperaquine or artemether-lumefantrine. Healthy volunteers of either sex, aged 18-65 years, without glucose-6-phosphate dehydrogenase deficiency, were randomized into five cohorts (n=24 per cohort) to receive tafenoquine on day 1 (300 mg) plus: once daily dihydroartemisinin-piperaquine on days 1, 2 and 3 (120:960 mg for 36-<75 kg bodyweight; 160:1280 mg for ≥75-100 kg bodyweight); or artemether-lumefantrine (80:480 mg) two doses 8 h apart on day 1, then twice daily on days 2 and 3; or each drug given alone...
October 3, 2016: Antimicrobial Agents and Chemotherapy
Eric C Landsness, Leo H Wang, Robert C Bucelli
Migraine headache is among the most prevalent neurologic disorders. Status migrainosus often leads to hospitalization, and multiple medications are sometimes required for symptomatic relief. In 2008, neurologists at our institution started using the atypical antipsychotic ziprasidone as an abortive medication for status migrainosus. The Clinical Investigation Data Exploration Repository was used to search for patients admitted to the Barnes-Jewish Hospital inpatient neurology service with diagnoses of "headache" or "migraine...
October 2016: Neurohospitalist
Foroogh Sabzghabaei, Seyed Alireza Heydariezade, Rashin S Joodat
INTRODUCTION: Hemodialysis (HD) has impact on the cardiovascular system by inducing changes in the characteristics of body fluids such as PH, temperature and electrolyte concentrations. In the previous studies, prolongation of the QT interval and increase of QT dispersion have been reported during HD sessions. These changes were more significant while using solutions with less potassium and higher bicarbonate during dialysis. OBJECTIVES: The aim of our study was to investigate the effects of different potassium and bicarbonate concentrations on electrocardiography (ECG) parameters and the electrochemical balance of cell membranes...
2016: Journal of Renal Injury Prevention
Jani Pirinen, Jukka Putaala, Karoliina Aarnio, Aapo L Aro, Juha Sinisalo, Markku Kaste, Elena Haapaniemi, Turgut Tatlisumak, Mika Lehto
INTRODUCTION: Ischemic stroke (IS) in a young patient is a disaster and recurrent cardiovascular events could add further impairment. Identifying patients with high risk of such events is therefore important. The prognostic relevance of ECG for this population is unknown. MATERIALS AND METHODS: A total of 690 IS patients aged 15-49 years were included. A 12-lead ECG was obtained 1-14 d after the onset of stroke. We adjusted for demographic factors, comorbidities, and stroke characteristics, Cox regression models were used to identify independent ECG parameters associated with long-term risks of (1) any cardiovascular event, (2) cardiac events, and (3) recurrent stroke...
September 29, 2016: Annals of Medicine
Yan Li, Leonidas N Carayannopoulos, Michael Thomas, Maria Palmisano, Simon Zhou
CC-122 hydrochloride is a novel pleiotropic pathway modifier compound that binds cereblon, a substrate receptor of the Cullin 4 RING E3 ubiquitin ligase complex. CC-122 has multiple activities including modulation of immune cells, antiproliferative activity of multiple myeloma and lymphoma cells, and antiangiogenic activity. CC-122 is being developed as an oncology treatment for hematologic malignancies and advanced solid tumors. Cardiovascular and vital sign assessments of CC-122 have been conducted in hERG assays in vitro and in a 28-day good laboratory practice monkey study with negative signals...
2016: Clinical Pharmacology: Advances and Applications
Salman Waheed, Buddhadeb Dawn, Kamal Gupta
BACKGROUND: Both QT interval and body mass index (BMI) are independently associated with mortality. Those with higher BMI have longer QT, although evidence is inconsistent. The joint association of QT and BMI with mortality merits investigation. OBJECTIVE: To examine the association of QT with BMI, and to examine the joint association of QT and BMI with all-cause and cardiovascular mortality. METHODS: We followed 4036 participants from NHANES III for a median of 14...
September 23, 2016: Obesity Research & Clinical Practice
Michelle Quinlan, Jocelyn Zhou, Eunju Hurh, Dalila Sellami
PURPOSE: Sonidegib prevents activation of the Hedgehog signal transduction pathway. This PK-QT analysis has been performed to test for potential prolongation of the QT/QTc interval during extended use, and to understand the exposure-QT relationship for sonidegib in patients and in healthy volunteers (HV). METHODS: A pooled analysis of the change in QT interval corrected for heart rate according to Fridericia's formula was conducted across four patient studies from a total of 341 patients (n = 211, 102, 21, and 7 from the phase II pivotal study A2201, study X2101, study X1101, and study B2209, respectively), and across four healthy volunteer studies from a total of 204 healthy volunteers (n = 146, 36, 16, and 6 from study A2114, study A1102, study A2108, and study A2110, respectively)...
September 23, 2016: European Journal of Clinical Pharmacology
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