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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
#1
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a risk factor for life-threatening ventricular arrhythmias, is a potential side effect of many marketed and withdrawn medications.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/28185917/increment-of-late-sodium-currents-in-the-left-atrial-myocytes-and-its-potential-contribution-to-the-increased-susceptibility-of-atrial-fibrillation-in-castrated-male-mice
#2
Yang Zhang, Hui-Min Wang, Ying-Zhe Wang, Yi-Yuan Zhang, Xue-Xin Jin, Yue Zhao, Jin Wang, Yi-Lin Sun, Gen-Long Xue, Peng-Hui Li, Qi-He Huang, Bao-Feng Yang, Zhen-Wei Pan
BACKGROUND: The incidence of atrial fibrillation (AF) is correlated with the declined levels of testosterone in elder men. Late sodium current may exert a role in AF pathogenesis. OBJECTIVE: In this study we explored the effect of testosterone deficiency on AF susceptibility and the therapeutic effect of late sodium current inhibitors in mice. METHODS: Male ICR mice (5-week old) were castrated to establish testosterone deficiency model. One month after castration, dihydrotestosterone (5mg/kg) was administered subcutaneously for 2 months...
February 6, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28182279/ranolazine-added-to-amiodarone-facilitates-earlier-conversion-of-atrial-fibrillation-compared-to-amiodarone-only-therapy
#3
Nikos Tsanaxidis, Isaac Aidonidis, Apostolia Hatziefthimiou, Stella S Daskalopoulou, Grigorios Giamouzis, Filippos Triposkiadis, Ioannis Skoularigis
Amiodarone (AMIO) is for many years effectively used to control ventricular rate during atrial fibrillation (AF) and to convert it into sinus rhythm. However, due to its delayed onset of action, ranolazine (RAN), a new antianginal agent with atrial-selective electrophysiologic properties, has recently been attempted as add-on therapy with AMIO to facilitate AF conversion. To establish the role of this combination therapy, we enrolled 173 consecutive patients (68±10 years, 54% male) with recent-onset (< 48 h duration) AF who were eligible for pharmacologic cardioversion...
February 9, 2017: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/28178363/ranolazine-for-stable-angina-pectoris
#4
REVIEW
Carlos A Salazar, Juan E Basilio Flores, Liz E Veramendi Espinoza, Jhon W Mejia Dolores, Diego E Rey Rodriguez, César Loza Munárriz
BACKGROUND: Stable angina pectoris is a chronic medical condition with significant impact on mortality and quality of life; it can be macrovascular or microvascular in origin. Ranolazine is a second-line anti-anginal drug approved for use in people with stable angina. However, the effects of ranolazine for people with angina are considered to be modest, with uncertain clinical relevance. OBJECTIVES: To assess the effects of ranolazine on cardiovascular and non-cardiovascular mortality, all-cause mortality, quality of life, acute myocardial infarction incidence, angina episodes frequency and adverse events incidence in stable angina patients, used either as monotherapy or as add-on therapy, and compared to placebo or any other anti-anginal agent...
February 8, 2017: Cochrane Database of Systematic Reviews
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
#5
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
https://www.readbyqxmd.com/read/28155172/erratum-to-ranolazine-promotes-muscle-differentiation-and-reduces-oxidative-stress-in-c2c12-skeletal-muscle-cells
#6
Ileana Terruzzi, Anna Montesano, Pamela Senesi, Fernanda Vacante, Stefano Benedini, Livio Luzi
No abstract text is available yet for this article.
February 3, 2017: Endocrine
https://www.readbyqxmd.com/read/28105560/erratum-to-improvement-of-subjective-well-being-by-ranolazine-in-patients-with-chronic-angina-and-known-myocardial-ischemia-imwell-study
#7
Anthony A Bavry, Ki E Park, Calvin Y Choi, Ahmed N Mahmoud, Xuerong Wen, Islam Y Elgendy
No abstract text is available yet for this article.
January 19, 2017: Cardiology and Therapy
https://www.readbyqxmd.com/read/28101642/late-sodium-current-and-intracellular-ionic-homeostasis-in-acute-ischemia
#8
Carlotta Ronchi, Eleonora Torre, Riccardo Rizzetto, Joyce Bernardi, Marcella Rocchetti, Antonio Zaza
Blockade of the late Na(+) current (I NaL) protects from ischemia/reperfusion damage; nevertheless, information on changes in I NaL during acute ischemia and their effect on intracellular milieu is missing. I NaL, cytosolic Na(+) and Ca(2+) activities (Nacyt, Cacyt) were measured in isolated rat ventricular myocytes during 7 min of simulated ischemia (ISC); in all the conditions tested, effects consistently exerted by ranolazine (RAN) and tetrodotoxin (TTX) were interpreted as due to I NaL blockade. The results indicate that I NaL was enhanced during ISC in spite of changes in action potential (AP) contour; I NaL significantly contributed to Nacyt rise, but only marginally to Cacyt rise...
March 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28044265/improvement-of-subjective-well-being-by-ranolazine-in-patients-with-chronic-angina-and-known-myocardial-ischemia-imwell-study
#9
Anthony A Bavry, Ki E Park, Calvin Y Choi, Ahmed N Mahmoud, Xuerong Wen, Islam Y Elgendy
INTRODUCTION: We aimed to assess if ranolazine would improve angina symptoms among patients with documented myocardial ischemia. METHODS: Eligible subjects had chronic stable angina and at least one coronary stenosis with fractional flow reserve (FFR) ≤0.80 or at least one chronic total occlusion (CTO) without attempted revascularization. Subjects were randomized to oral ranolazine 500 mg twice daily for 1 week, then ranolazine 1000 mg twice daily for 15 weeks versus matching placebo...
January 2, 2017: Cardiology and Therapy
https://www.readbyqxmd.com/read/28024133/ranolazine-in-treatment-of-stable-angina-in-woman-with-atrial-fibrillation-and-intermittent-left-bundle-branch-block-a-case-report
#10
Natalia Yuriivna Osovska, Natalia Vitaliivna Kuzminova
Stable angina is the most frequent manifestation of ischemic heart disease (IHD) in women as compared to men (65% versus 37%). IHD in women has more favorable clinical course because myocardial infarction develops twice as rare as in men. Coronary angiography of angina patients demonstrates normal coronary arteries more frequently in women than in men. Microvascular angina (MVA) is found to be a rather common form of stable IHD as that particular diagnosis is made later in 20-30% of patients who previously underwent coronary angiography...
December 22, 2016: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28004395/myocardial-tissue-deformation-is-reduced-in-subjects-with-coronary-microvascular-dysfunction-but-not-rescued-by-treatment-with-ranolazine
#11
Michael D Nelson, Behzad Sharif, Jaime L Shaw, Galen Cook-Wiens, Janet Wei, Chrisandra Shufelt, Puja K Mehta, Louise E J Thomson, Daniel S Berman, Richard B Thompson, Eileen M Handberg, Carl J Pepine, Debiao Li, C Noel Bairey Merz
BACKGROUND: Patients with coronary microvascular dysfunction (CMD) often have diastolic dysfunction, representing an important therapeutic target. Ranolazine-a late sodium current inhibitor-improves diastolic function in animal models and subjects with obstructive coronary artery disease (CAD). HYPOTHESIS: We hypothesized that ranolazine would beneficially alter diastolic function in CMD. METHODS: To test this hypothesis, we performed retrospective tissue tracking analysis to evaluate systolic/diastolic strain, using cardiac magnetic resonance imaging cine images acquired in a recently completed, randomized, double-blind, placebo-controlled, crossover trial of short-term ranolazine in subjects with CMD and from 43 healthy reference controls...
December 22, 2016: Clinical Cardiology
https://www.readbyqxmd.com/read/27933435/ranolazine-promotes-muscle-differentiation-and-reduces-oxidative-stress-in-c2c12-skeletal-muscle-cells
#12
Terruzzi Ileana, Montesano Anna, Senesi Pamela, Vacante Fernanda, Benedini Stefano, Luzi Livio
PURPOSE: The purpose of this study is to investigate Ranolazine action on skeletal muscle differentiation and mitochondrial oxidative phenomena. Ranolazine, an antianginal drug, which acts blocking the late INaL current, was shown to lower hemoglobin A1c in patients with diabetes. In the present study, we hypothesized an action of Ranolazine on skeletal muscle cells regeneration and oxidative process, leading to a reduction of insulin resistance. METHODS: 10 μM Ranolazine was added to C2C12 murine myoblastic cells during proliferation, differentiation and newly formed myotubes...
December 8, 2016: Endocrine
https://www.readbyqxmd.com/read/27915058/larger-rate-dependence-of-late-sodium-current-in-cardiac-purkinje-cells-a-potential-link-to-arrhythmogenesis
#13
Wei Li, Ying Yu, Jian-Wen Hou, Zhi-Wen Zhou, Kai Guo, Peng-Pai Zhang, Zhi-Quan Wang, Jian-Hua Yan, Jian Sun, Qing Zhou, Yue-Peng Wang, Yi-Gang Li
BACKGROUND: Purkinje cells (PCs) have a steeper rate dependence of repolarization and are more susceptible to arrhythmic activity than do ventricular myocytes (VMs). Late sodium current (INaL) is rate dependent and contributes to rate dependence of repolarization. OBJECTIVE: This study sought to test our hypothesis that PCs have a larger rate dependence of INaL, contributing to their steeper rate dependence of repolarization and higher susceptibility to arrhythmic activity, than do VMs...
December 1, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27867290/ranolazine-is-an-effective-and-safe-treatment-of-adults-with-symptomatic-premature-ventricular-contractions-due-to-triggered-ectopy
#14
Gary L Murray
Early and delayed afterdepolarizations (EAD/DAD) cause triggered ventricular ectopy. Because ranolazine (RAN) suppresses EAD/DAD, we postulated that RAN might be effective in reducing premature ventricular contractions (PVCs). To assess the effect of RAN in patients with symptomatic PVCs due to triggered ectopy and its safety and tolerability. A total of 59 patients with symptomatic PVCs were identified from full-disclosure Holters. Doses of 500 and 1,000 mg offlabel RAN, daily, were given to 34 and 66% patients, respectively, and repeat Holters were performed prospectively during mean followup of 3...
December 2016: International Journal of Angiology: Official Publication of the International College of Angiology, Inc
https://www.readbyqxmd.com/read/27829006/hyperthermia-influences-the-effects-of-sodium-channel-blocking-drugs-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#15
Ibrahim El-Battrawy, Siegfried Lang, Zhihan Zhao, Ibrahim Akin, Gökhan Yücel, Sophie Meister, Bence Patocskai, Michael Behnes, Boris Rudic, Erol Tülümen, Volker Liebe, Malte Tiburcy, Jennifer Dworacek, Wolfram-Hubertus Zimmermann, Jochen Utikal, Thomas Wieland, Martin Borggrefe, Xiao-Bo Zhou
INTRODUCTION: Fever can increase the susceptibility to supraventricular and ventricular arrhythmias, in which sodium channel dysfunction has been implicated. Whether fever influences the efficacy of sodium channel blocking drugs is unknown. The current study was designed to investigate the temperature dependent effects of distinct sodium channel blocking drugs on the sodium currents in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). METHODS AND RESULTS: hiPSC-CMs were generated from human skin fibroblasts of a healthy donor...
2016: PloS One
https://www.readbyqxmd.com/read/27758968/the-novel-use-of-ranolazine-as-an-antiarrhythmic-agent-in-atrial-fibrillation
#16
REVIEW
C Michael White, Elaine Nguyen
OBJECTIVE: To review the limitations of current antiarrhythmic drugs in atrial fibrillation (AF) and discuss the rationale and clinical trials supporting the use of ranolazine in AF. DATA SOURCES: MEDLINE was searched from 1980 to September 2016 using the terms ranolazine, atrial fibrillation, coronary artery bypass grafting, and valve surgery STUDY SELECTION AND DATA EXTRACTION: English-language studies and reviews assessing antiarrhythmic drugs, including ranolazine, were incorporated...
October 6, 2016: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/27756767/ranolazine-reduces-atrial-fibrillatory-wave-frequency
#17
Eric W Black-Maier, Sean D Pokorney, Adam S Barnett, Peter Liu, Peter Shrader, Jason Ng, Jeffrey J Goldberger, Wojiech Zareba, James P Daubert, Augustus O Grant, Jonathan P Piccini
AIMS: Antiarrhythmic medications for the treatment of atrial fibrillation (AF) have limited efficacy and rare but potentially life-threatening side effects. Ranolazine is an antianginal agent that may have antiarrhythmic activity in AF. METHODS AND RESULTS: Using the Duke Enterprise Data Unified Content Explorer database, we analysed a cohort of AF patients on ranolazine. Patients served as their own historic control. Electrocardiograms (ECGs) were analysed before and after ranolazine initiation to determine the effect of ranolazine on dominant frequency (DF), f-wave amplitude, and organizational index (OI)...
October 17, 2016: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/27746384/role-of-ranolazine-in-the-prevention-and-treatment-of-atrial-fibrillation-a-meta-analysis-of-randomized-clinical-trials
#18
Mengqi Gong, Zhiwei Zhang, Nikolaos Fragakis, Panagiotis Korantzopoulos, Konstantinos P Letsas, Guangping Li, Gan-Xin Yan, Tong Liu
BACKGROUND: Randomized controlled trials (RCTs) on the use of ranolazine (RN) for prevention and cardioversion of atrial fibrillation (AF) have yielded conflicting results. OBJECTIVE: The purpose of this study was to conduct a meta-analysis of RCTs to examine the potential role of RN in the prevention and cardioversion of AF. METHODS: PubMed and EMBASE were searched until June 2016. Of 484 initially identified studies, 8 RCTs were finally analyzed...
January 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/27733495/ranolazine-for-congenital-long-qt-syndrome-type-iii-experimental-and-long-term-clinical-data
#19
Ehud Chorin, Dan Hu, Charles Antzelevitch, Aviram Hochstadt, Luiz Belardinelli, David Zeltser, Hector Barajas-Martinez, Uri Rozovski, Raphael Rosso, Arnon Adler, Jesaia Benhorin, Sami Viskin
BACKGROUND: The basic defect in long-QT syndrome type III (LQT3) is an excessive inflow of sodium current during phase 3 of the action potential caused by mutations in the SCN5A gene. Most sodium channel blockers reduce the early (peak) and late components of the sodium current (INa and INaL), but ranolazine preferentially reduces INaL. We, therefore, evaluated the effects of ranolazine in LQT3 caused by the D1790G mutation in SCN5A. METHODS AND RESULTS: We performed an experimental study of ranolazine in TSA201 cells expressing the D1790G mutation...
October 2016: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/27713141/fibroblast-growth-factor-23-dysregulates-late-sodium-current-and-calcium-homeostasis-with-enhanced-arrhythmogenesis-in-pulmonary-vein-cardiomyocytes
#20
Shih-Yu Huang, Yao-Chang Chen, Yu-Hsun Kao, Ming-Hsiung Hsieh, Yung-Kuo Lin, Cheng-Chih Chung, Ting-I Lee, Wen-Chin Tsai, Shih-Ann Chen, Yi-Jen Chen
Fibroblast growth factor 23 (FGF23), elevated in chronic renal failure, increases atrial arrhythmogenesis and dysregulates calcium homeostasis. Late sodium currents (INa-Late) critically induces ectopic activity of pulmoanry vein (the most important atrial fibrillation trigger). This study was to investigate whether FGF23 activates the INa-Late leading to calcium dysregulation and increases PV arrhythmogenesis. Patch clamp, western blot, and confocal microscopy were used to evaluate the electrical activities, calcium homeostasis, and mitochondrial reactive oxygen species (ROS) in PV cardiomyocytes with or without FGF23 (0...
October 4, 2016: Oncotarget
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