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https://www.readbyqxmd.com/read/27920831/assessment-of-drug-induced-proarrhythmias-due-to-pilsicainide-in-patients-with-atrial-tachyarrhythmias
#1
Hideki Koike, Tadashi Fujino, Makiko Koike, Shintaro Yao, Masaya Shinohara, Ken Kitahara, Toshio Kinoshita, Hitomi Yuzawa, Takeya Suzuki, Hideyuki Sato, Shunji Fukunaga, Kenzaburo Kobayashi, Takanori Ikeda
BACKGROUND: Pilsicainide, a pure Na(+) channel blocker, is a popular antiarrhythmic drug for the management of atrial tachyarrhythmias (AT), in Japan. However, serious drug-induced proarrhythmias (DIPs) may unexpectedly occur. We assessed the clinical background of AT patients presenting with DIPs caused by pilsicainide. METHODS: This study retrospectively enrolled 874 consecutive patients (543 men, 63.6±15.3 years old, and 57.9±16.5 kg of body weight), who were orally administered pilsicainide for AT management...
December 2016: Journal of Arrhythmia
https://www.readbyqxmd.com/read/27917367/the-role-of-interaction-model-in-simulation-of-drug-interactions-and-qt-prolongation
#2
REVIEW
Barbara Wiśniowska, Sebastian Polak
Computational modelling is a cornerstone of Comprehensive In Vitro Proarrhythmia Assay and is re-increasingly being used in drug development. Electrophysiological effects of drug-drug interactions can be predicted in silico, e.g. with the use of in vitro cardiac ion channel data, PK profiles and human ventricular cardiomyocyte models. There are, however, several approaches with different assumptions used to assess the combined effect of multiple drugs, and there is no agreed standard interaction model. The aim of this study was to assess whether the choice of the drug-drug interaction (DDI) model (Bliss independence, Loewe additivity, or simple sum) influences the results of QT interval simulation trial...
2016: Current Pharmacology Reports
https://www.readbyqxmd.com/read/27915266/systematic-ajmaline-challenge-in-patients-with-long-qt-3-syndrome-caused-by-the-most-common-mutation-a-multicentre-study
#3
Stephan Hohmann, Boris Rudic, Torsten Konrad, David Duncker, Thorben König, Erol Tülümen, Thomas Rostock, Martin Borggrefe, Christian Veltmann
AIMS: Overlap syndromes of long QT 3 syndrome (LQT3) and the Brugada syndrome (BrS) have been reported. Identification of patients with an overlapping phenotype is crucial before initiation of Class I antiarrhythmic drugs for LQT3. Aim of the present study was to elucidate the yield of ajmaline challenge in unmasking the Brugada phenotype in patients with LQT3 caused by the most common mutation, SCN5A-E1784K. METHODS AND RESULTS: Consecutive families in tertiary referral centres diagnosed with LQT3 caused by SCN5A-E1784K were included in the study...
December 2, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/27914889/ventricular-tachycardia-and-prolonged-qt-interval-presenting-as-seizure-like-activity-a-case-report
#4
Max Wentlandt, Stephen C Morris, Steven H Mitchell
Seizures can be difficult to distinguish from other causes of transient cerebral hypoxia in the emergency room. We present a case of seizure activity in a woman in whom EKG led to a diagnosis of intermittent monomorphic and polymorphic ventricular tachycardia (torsades de pointes), highlighting the need for careful consideration of alternative causes of seizures, even in patients with known epilepsy.
November 22, 2016: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27913272/the-northeast-regional-sps-meeting-update-safety-pharmacology-innovations-and-applications
#5
REVIEW
Malar Pannirselvam, Tiffini Brabham, Alfred W Botchway, Donald B Hodges, Martin Traebert, Michael K Pugsley
The Safety Pharmacology Society (SPS) held a Northeast (NE) regional meeting in Boston, MA on May 13, 2016 at the Vertex Pharmaceuticals Incorporated site. There were 103 attendees from the pharmaceutical industry, contract research organizations (CROs), academia, and global regulatory agencies. An assortment of scientific topics were presented by 7 speakers that included broad topics in the cardiovascular (organ on chip, statistical power and translation of rat cardiovascular telemetry data and dual inhibition of IKr and IKs on QT interval prolongation) and central nervous system (in vitro platform for neurotoxicity, an integrated risk assessment of suicidal ideation and behavior, and EEG advances in safety pharmacology) and a novel topic discussing preclinical challenges faced in the development of a novel gene therapy...
November 29, 2016: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/27908913/comfrey-herbal-remedy-causing-second-degree-heart-block-do-not-be-outfoxed-by-digitalis
#6
Mathew Kurian Vithayathil, Matthew Edwards
A previously well woman aged 63 years presents to the emergency department with vomiting, palpitations and 3 presyncopal episodes. She had no previous medical or cardiac history, with the patient stating that she tried a herbal remedy of boiled comfrey leaves for insomnia 18 hours before arrival to the department. Her ECG showed multiple abnormalities, including bradycardia, second-degree atrioventricular node block, Mobitz Type 2, a shortened QT interval, downsloping ST depression and presence of U waves...
December 1, 2016: BMJ Case Reports
https://www.readbyqxmd.com/read/27904744/qt-interval-prolongation-and-torsades-de-pointes-with-oxaliplatin
#7
Jules C Hancox, Rachel E Caves, Stéphanie C M Choisy, Andrew F James
No abstract text is available yet for this article.
December 2016: Therapeutic Advances in Drug Safety
https://www.readbyqxmd.com/read/27904512/evaluation-of-inhomogeneities-of-repolarization-in-patients-with-psoriasis-vulgaris
#8
Korhan Soylu, Sinan İnci, Gökhan Aksan, Gökay Nar, Esra Pancar Yüksel, Hande Serra Ocal, Mustafa Çapraz, Serkan Yüksel, Mahmut Şahin
INTRODUCTION: The arrhythmia potential has not been investigated adequately in psoriatic patients. In this study, we assessed the ventricular repolarization dispersion, using the Tp-e interval and the Tp-e/QT ratio, and investigated the association with inflammation. MATERIAL AND METHODS: Seventy-one psoriasis vulgaris patients and 70 age- and gender-matched healthy individuals were enrolled in the study. The severity of the disease was calculated using Psoriasis Area and Severity Index scoring...
December 1, 2016: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/27903879/the-analysis-of-qt-interval-and-repolarization-morphology-of-the-heart-in-chronic-exposure-to-lead
#9
J Kiełtucki, M Dobrakowski, N Pawlas, B Średniawa, M Boroń, S Kasperczyk
There are no common recommendations regarding electrocardiographic monitoring in occupationally exposed workers. Therefore, the present study was designed to investigate whether exposure to lead results in an increase of selected electrocardiography (ECG) pathologies, such as QT interval prolongation and repolarization disorders, in occupationally exposed workers. The study group included 180 workers occupationally exposed to lead compounds. The exposed group was divided according to the median of the mean blood lead level (PbBmean) calculated based on a series of measurements performed during 5-year observation period (35 µg/dl) into two subgroups: low exposure (LE, PbBmean = 20...
November 30, 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/27899938/detailed-analysis-of-the-impact-of-age-on-the-qt-interval
#10
Simon W Rabkin, Xin-Bo Justin Cheng, Darby Js Thompson
OBJECTIVE: To analyze the effect of age on the ECG QT interval, an important predictor of cardiovascular mortality and drug-induced cardiac arrhythmias, and determine whether QT-heart rate correction formulae (QTc) have differential relationships with age and sex. METHODS: Data were examined from the US National Health and Nutrition Examination Survey (NHANES) II and III, civilian population aged 25 to 90 years. QT weighted means and standard deviations were calculated for all ages...
September 2016: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/27899087/paradoxical-physiological-responses-to-propranolol-in-a-rett-syndrome-patient-a-case-report
#11
P J Santosh, L Bell, K Lievesley, J Singh, F Fiori
BACKGROUND: Rett Syndrome (RTT), caused by a loss-of-function in the epigenetic modulator: X-linked methyl-CpG binding protein 2 (MeCP2), is a pervasive neurological disorder characterized by compromised brain functions, anxiety, severe mental retardation, language and learning disabilities, repetitive stereotyped hand movements and developmental regression. An imbalance in the sympathetic and the parasympathetic nervous system (dysautonomia) and the resulting autonomic storms is a frequent occurrence in patients with RTT...
November 29, 2016: BMC Pediatrics
https://www.readbyqxmd.com/read/27896662/investigating-the-additive-interaction-of-qt-prolonging-drugs-in-older-people-using-claims-data
#12
Andreas D Meid, Anna von Medem, Dirk Heider, Jürgen-Bernhard Adler, Christian Günster, Hanna M Seidling, Renate Quinzler, Hans-Helmut König, Walter E Haefeli
INTRODUCTION: Drugs that potentially prolong the QT interval carry the risk of life-threatening Torsades de pointes (TdP) ventricular arrhythmia. OBJECTIVE: The objective of this study was to investigate the potential additive risk for ventricular arrhythmia with concomitant prescriptions of QT-prolonging drugs. METHODS: Claims data for persons aged ≥65 years between 2010 and 2012 in Germany were analyzed and all cases hospitalized for ventricular arrhythmia were selected...
November 29, 2016: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/27891661/synergistic-effects-of-polydatin-and-vitamin-c-in-inhibiting-cardiotoxicity-induced-by-doxorubicin-in-rats
#13
Hui-Lin Wang, Xiao-Hua Cui, Hai-Lun Yu, Rong Wu, Xu Xu, Jian-Ping Gao
The purpose of this study was to assess the synergistic effect of polydatin and vitamin C on attenuating cardiotoxicity induced by doxorubicin (DOX) in rats. Polydatin could significantly increase the activity of SOD and the heart rate, attenuate myocardial pathological damage, decrease MDA content, slightly increase arterial pressure and GSH-Px activity, reduce intervals of QRS, QT and ST, and lower FFA content. The combination of polydatin and vitamin C could significantly increase arterial pressure and heart rate, decrease QRS interval and slightly reduce ST and QT intervals, significantly attenuate myocardial pathological damage, increase the activities of GSH-Px,T-SOD, Na(+) K(+) -ATPase and Ca(2+) Mg(2+) -ATPase, and elevate PCr and ATP contents, slightly increase ADP and TAN contents and PCr/ATP, and significantly decrease the contents of MDA and FFA, when compared with those in the DOX group...
November 28, 2016: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/27886373/clemizole-hydrochloride-blocks-cardiac-potassium-currents-stably-expressed-in-hek-293-cells
#14
Ling-Jun Jie, Wei-Yin Wu, Gang Li, Guo-Sheng Xiao, Shetuan Zhang, Gui-Rong Li, Yan Wang
BACKGROUND AND PURPOSE: Recent studies showed that clemizole has a potential therapeutic effect for hepatitis C infection and also potently inhibits TRPC5 channels. The aim of the present study was to investigate whether clemizole blocks cardiac K(+) currents and affects cardiac repolarization. EXPERIMENTAL APPROACH: Whole-cell patch technique was employed to examine the effects of clemizole on hERG channel current, IKs and Kv1.5 current in HEK 293 cell expression systems as well as on ventricular action potentials of guinea pig hearts...
November 25, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27882731/reproducibility-of-corrected-qt-interval-in-pediatric-genotyped-long-qt-syndrome
#15
Yoshiharu Ogawa, Toshikatsu Tanaka, Sachiko Kido
Reproducibility of corrected QT interval (QTc), especially QTc after exercise, has not been thoroughly investigated. We reviewed charts of pediatric patients who underwent treadmill-exercise stress testing without medication multiple times within 1 year. In patients with long-QT syndrome (LQTS; n = 22), the discrepancy in QTc between two treadmill exercise stress tests using Fridericia's formula was 14 ± 12 ms at rest, 13 ± 12 ms 4 min after exercise, with a maximum of 14 ± 12 ms after exercise. There was no statistically significant difference in QTc between the two tests...
November 2016: Pediatrics International: Official Journal of the Japan Pediatric Society
https://www.readbyqxmd.com/read/27878411/reckless-administration-of-qt-interval-prolonging-agents-in-elderly-patients-with-drug-induced-torsade-de-pointes
#16
Galia Jackobson, Narin Nard Carmel, Dor Lotan, Anjelika Kremer, Dan Justo
A systematic review was conducted for all published case reports on drug-induced torsade de pointes (TdP) in elderly (≥80 years) patients to study if the administration of the offending agent was reckless. Overall, 61 reports on drug-induced TdP in patients aged 80-97 years were included in the analysis. Non-modifiable risk factors for drug-induced TdP (e.g. acute coronary syndrome, female gender and congestive heart failure), modifiable risk factors (e.g. hypokalemia, severe hypomagnesemia and digitalis toxicity) and reckless administration of a QT interval-prolonging agent (e...
November 22, 2016: Zeitschrift Für Gerontologie und Geriatrie
https://www.readbyqxmd.com/read/27877193/a-combined-linkage-and-exome-sequencing-analysis-for-electrocardiogram-parameters-in-the-erasmus-rucphen-family-study
#17
Claudia T Silva, Irina V Zorkoltseva, Najaf Amin, Ayşe Demirkan, Elisabeth M van Leeuwen, Jan A Kors, Marten van den Berg, Bruno H Stricker, André G Uitterlinden, Anatoly V Kirichenko, Jacqueline C M Witteman, Rob Willemsen, Ben A Oostra, Tatiana I Axenovich, Cornelia M van Duijn, Aaron Isaacs
Electrocardiogram (ECG) measurements play a key role in the diagnosis and prediction of cardiac arrhythmias and sudden cardiac death. ECG parameters, such as the PR, QRS, and QT intervals, are known to be heritable and genome-wide association studies of these phenotypes have been successful in identifying common variants; however, a large proportion of the genetic variability of these traits remains to be elucidated. The aim of this study was to discover loci potentially harboring rare variants utilizing variance component linkage analysis in 1547 individuals from a large family-based study, the Erasmus Rucphen Family Study (ERF)...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27875737/experimental-evidence-for-a-severe-proarrhythmic-potential-of-levosimendan
#18
Gerrit Frommeyer, Anja Kohnke, Christian Ellermann, Dirk G Dechering, Simon Kochhäuser, Christian Pott, Michael Fehr, Lars Eckardt
BACKGROUND: The calcium sensitizer levosimendan is established for therapy of acutely decompensated congestive heart failure. Clinical experience suggests a possible proarrhythmic potential. The aim of the present study was to assess possible proarrhythmic effects and underlying electrophysiological mechanisms. METHODS AND RESULTS: Ten rabbit hearts were isolated and Langendorff-perfused. Thereafter, levosimendan was infused in 3 concentrations (0.5, 1, and 2μM)...
November 14, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27871843/considerations-when-using-next-generation-sequencing-for-genetic-diagnosis-of-long-qt-syndrome-in-the-clinical-testing-laboratory
#19
Hyojin Chae, Jiyeon Kim, Gun Dong Lee, Woori Jang, Joonhong Park, Dong Wook Jekarl, Yong Seog Oh, Myungshin Kim, Yonggoo Kim
BACKGROUND: Congenital long-QT syndrome (LQTS) is a potentially lethal cardiac electrophysiologic disorder characterized by QT interval prolongation and T-wave abnormalities. At least 13 LQTS-associated genes have been reported, but the high cost and low throughput of conventional Sanger sequencing has hampered the multi-gene-based LQTS diagnosis in clinical laboratories. METHODS: We developed an NGS (next-generation sequencing)-based targeted gene panel for 13 LQTS genes using the Ion PGM platform, and a cohort of 36 LQTS patients were studied for characterization of analytical performance specifications...
November 18, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27868338/incomplete-timothy-syndrome-secondary-to-a-mosaic-mutation-of-the-cacna1c-gene-diagnosed-using-next-generation-sequencing
#20
Amandine Baurand, Sylvie Falcon-Eicher, Gabriel Laurent, Elisabeth Villain, Caroline Bonnet, Christel Thauvin-Robinet, Caroline Jacquot, Jean-Christophe Eicher, Jean-Baptiste Gourraud, Sébastien Schmitt, Stéphane Bézieau, Mathilde Giraud, Solenne Dumont, Paul Kuentz, Vincent Probst, Antoine Burguet, Florence Kyndt, Laurence Faivre
Autosomal dominant genetic diseases can occur de novo and in the form of somatic mosaicism, which can give rise to a less severe phenotype, and make diagnosis more difficult given the sensitivity limits of the methods used. We report the case of female child with a history of surgery for syndactyly of the hands and feet, who was admitted at 6 years of age to a pediatric intensive care unit following cardiac arrest. The electrocardiogram (ECG) showed a long QT interval that on occasions reached 500 ms. Despite the absence of facial dysmorphism and the presence of normal psychomotor development, a diagnosis of Timothy syndrome was made given the association of syndactyly and the ECG features...
November 21, 2016: American Journal of Medical Genetics. Part A
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