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https://www.readbyqxmd.com/read/29321131/efficacy-of-ranolazine-in-patients-with-symptomatic-hypertrophic-cardiomyopathy-the-restyle-hcm-randomized-double-blind-placebo-controlled-study
#1
Iacopo Olivotto, Paolo G Camici, Piera Angelica Merlini, Claudio Rapezzi, Monica Patten, Vicent Climent, Gianfranco Sinagra, Benedetta Tomberli, Francisco Marin, Philipp Ehlermann, Lars S Maier, Alessandra Fornaro, Claudius Jacobshagen, Antonello Ganau, Luciano Moretti, Antonio Hernandez Madrid, Raffaele Coppini, Giorgio Reggiardo, Corrado Poggesi, Francesco Fattirolli, Luiz Belardinelli, Gianfranco Gensini, Alessandro Mugelli
BACKGROUND: The late sodium current inhibitor ranolazine reverses the main electrophysiological and mechanical abnormalities of human hypertrophic cardiomyopathy (HCM) cardiomyocytes in vitro, suggesting potential clinical benefit. We aimed to assess the effect of ranolazine on functional capacity, symptomatic status, diastolic function, and arrhythmias in HCM. METHODS AND RESULTS: In this multicenter, double-blind, phase 2 study, 80 adult patients with nonobstructive HCM (age 53±14 years, 34 women) were randomly assigned to placebo (n=40) or ranolazine 1000 mg bid (n=40) for 5 months...
January 2018: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29306026/differential-regulation-of-tefluthrin-and-telmisartan-on-the-gating-charges-of-ina-activation-and-inactivation-as-well-as-on-resurgent-and-persistent-ina-in-a-pituitary-cell-line-gh3
#2
Edmund Cheung So, Sheng-Nan Wu, Yi-Ching Lo, Kevin Su
Voltage-gated Na+ currents (INa), known to contain many components (e.g., transient, resurgent and persistent INa) with unique gating properties, are involved in the generation and propagation of action potentials in excitable cells. In this study, how tefluthrin (Tef), a synthetic pyrethoid, and telmisartan (TEL), blocker of angiotensin II receptors can perturb those components of INa was investigated. The presence of either Tef or TEL increased the values of the gating charges of INa involved in the activation (za) and inactivation (za)...
January 3, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29274809/antihyperglycemic-and-metabolic-effects-of-ranolazine-in-patients-with-diabetes-mellitus
#3
REVIEW
Brian W Gilbert, Max Sherard, Lindsey Little, Joshua Branstetter, Amber Meister, Joel Huffman
The antianginal drug ranolazine, because of its unique mechanism of action, has been shown to have antihyperglycemic effects. Here, we review the reports on the antihyperglycemic and metabolic effects of ranolazine. MEDLINE was searched from 2000 to October 1, 2016 using the terms ranolazine, antihyperglycemic, diabetes, cardiology, and antianginal. Studies and reviews were included if they were in English and provided relevant data to inform practicing clinicians. Ranolazine has been shown to be effective as an antihyperglycemic while utilized as monotherapy or in combination with traditional diabetic regimens...
November 28, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/29231052/efficacy-and-safety-of-ranolazine-in-diabetic-patients-a-systematic-review-and-meta-analysis
#4
Xiaofang Zeng, Yinyin Zhang, Jianhui Lin, Haikuo Zheng, Jie Peng, Wei Huang
BACKGROUND: Recent studies have discovered that the antiangina agent ranolazine exerts a glucometabolic effect. OBJECTIVE: This systematic review and meta-analysis aimed to further understand the efficacy and safety profile of ranolazine in patients with diabetes. METHODS: Randomized controlled trials (RCTs) were searched in PubMed, Cochrane, and EMBASE databases and in ClinicalTrials.gov up to July 2017. Efficacy end points were defined as the change in hemoglobin A1C (A1C) and fasting serum glucose (FSG) levels...
December 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29188487/sodium-metabisulfite-effects-on-ionic-currents-and-excitotoxicity
#5
Ming-Chi Lai, Te-Yu Hung, Kao-Min Lin, Pi-Shan Sung, Shyh-Jong Wu, Chih-Sheng Yang, Yi-Jen Wu, Jing-Jane Tsai, Sheng-Nan Wu, Chin-Wei Huang
How sodium metabisulfite (SMB; Na2S2O5), a popular food preservative and antioxidant, interacts with excitable membrane and induces excitotoxicity is incompletely understood. In this study, the patch-clamp technique was used to investigate and record the electrophysiological effect of SMB on electrically excitable HL-1 cardiomyocytes and NSC-34 neurons, as well as its relationship to pilocarpine-induced seizures and neuronal excitotoxicity in rats. We used Western blotting, to analyze sodium channel expression on hippocampi after chronic SMB treatment...
November 29, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29157949/non-pci-cabg-therapies-for-refractory-angina
#6
REVIEW
Ki E Park, C Richard Conti
Angina persists for many patients despite modern medical therapy and/or revascularization, and this is referred to as refractory angina. All patients with refractory angina must be treated with aggressive risk factor modification plus optimized medical management. β-Blockers and nitrates are usually first-line agents; however most patients require multiple medications for refractory symptom control. Novel agents, such as ranolazine and ivabradine, as well as non-pharmacologic therapies, such as enhanced external counterpulsation and cardiac rehabilitation, may provide relief or reduction of angina...
October 20, 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29127703/comparison-of-two-highly-automated-ecg-algorithms-for-detection-of-drug-induced-cardiac-ion-channel-block
#7
M Brockway, A A Fossa, J W Mason
FDA investigators recently demonstrated in a crossover study that early (J-Tpeak c) and late (Tpeak -Tend ) repolarization duration can differentiate selective potassium block with a high arrhythmia risk from multichannel block with lower risk in subjects receiving dofetilide, verapamil, quinidine or ranolazine. The purpose of this study was to determine if findings by FDA using their published software algorithm could be corroborated using an alternative software algorithm for the same metrics and to determine if methodological differences resulted in clinically meaningful differences in interpretation...
November 11, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29127493/late-sodium-current-associated-cardiac-electrophysiological-and-mechanical-dysfunction
#8
REVIEW
Shandong Yu, Gang Li, Christopher L-H Huang, Ming Lei, Lin Wu
Late sodium current (INaL) is a small sustained inward current observed during the cardiac action potential plateau phase following decay of the early peak INa. The endogenous INaL is relatively small in normal hearts but exerts functionally significant effects on cardiomyocyte repolarization with potentially pro-arrhythmic effects in hearts with reduced repolarization reserve. Enhanced INa,L occurs in long QT syndrome 3 (LQTS 3) patients, and under a number of pathological and pharmacological cardiovascular conditions, including bradycardia, myocardial ischemia, reperfusion injury, and heart failure...
November 10, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29079674/myocardial-bridge-bridging-the-differential-diagnosis
#9
Mayur Patel, Brenen Swofford, Edward Distler
A 50-year-old man with a history of vasospastic angina diagnosed 3 months prior presented with recurrent episodes of substernal chest pain. His chest pain was characterised as 'squeezing', lasting 10 min and typically occurred on awakening. Medications included isosorbide, nitroglycerin and ranolazine; however, due to lack of insurance he was unable to obtain these medications. On admission, patient was given a full-dose aspirin and nitroglycerin, which acutely worsened his chest pain. ECG did not reveal ischaemic changes and initial troponin was negative...
October 27, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29068807/antiarrhythmic-effects-of-combining-dofetilide-and-ranolazine-in-a-model-of-acutely-induced-atrial-fibrillation-in-horses
#10
Helena Carstensen, Line Kjær, Maria Mathilde Haugaard, Mette Flethøj, Eva Zander Hesselkilde, Jørgen K Kanters, Steen Pehrson, Rikke Buhl, Thomas Jespersen
BACKGROUND: Antiarrhythmic compounds against atrial fibrillation (AF) often have reduced efficacy and may display cardiac and/or non-cardiac toxicity. Efficacy can be improved by combining two compounds with distinct mechanisms, and it may be possible to use lower doses of each compound, thereby reducing the likelihood of adverse side-effects. The purpose of this study was to investigate whether the effective doses of dofetilide and ranolazine can be reduced if the drugs are combined...
October 25, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29046002/-optimal-diagnostics-and-therapy-for-microvascular-angina-pectoris
#11
Peter Ong, Udo Sechtem
Patients with microvascular angina are characterized by angina pectoris with proof of myocardial ischemia in the absence of any relevant epicardial stenosis and without myocardial disease (type 1 coronary microvascular dysfunction according to Crea and Camici). Structural and functional alterations of the coronary microvessels (diameter < 500 µm) are the reason for this phenomenon. Frequently such alterations are associated with cardiovascular risk factors. Patients with angina pectoris without epicardial stenoses represent for 10 - 50 % of all patients undergoing coronary angiography depending on the clinical presentation...
October 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29033611/stable-ischemic-heart-disease-in-women-current-perspectives
#12
REVIEW
Fatima Samad, Anushree Agarwal, Zainab Samad
Cardiovascular disease is the leading cause of death in women accounting for 1 in every 4 female deaths. Pathophysiology of ischemic heart disease in women includes epicardial coronary artery, endothelial dysfunction, coronary vasospasm, plaque erosion and spontaneous coronary artery dissection. Angina is the most common presentation of stable ischemic heart disease (SIHD) in women. Risk factors for SIHD include traditional risks such as older age, obesity (body mass index [BMI] >25 kg/m2), smoking, hypertension, dyslipidemia, cerebrovascular and peripheral vascular disease, sedentary lifestyle, family history of premature coronary artery disease, metabolic syndrome and diabetes mellitus, and nontraditional risk factors, such as gestational diabetes, insulin resistance/polycystic ovarian disease, pregnancy-induced hypertension, pre-eclampsia, eclampsia, menopause, mental stress and autoimmune diseases...
2017: International Journal of Women's Health
https://www.readbyqxmd.com/read/29021091/an-evaluation-of-multiple-algorithms-for-the-measurement-of-the-heart-rate-corrected-jtpeak-interval
#13
Jean-Philippe Couderc, Shiyang Ma, Alex Page, Connor Besaw, Jean Xia, W Brian Chiu, Johan de Bie, Jose Vicente, Martino Vaglio, Fabio Badilini, Saeed Babaeizadeh, Cheng-Hao Simon Chien, Mathias Baumert
Interest in the effects of drugs on the heart rate-corrected JTpeak (JTpc) interval from the body-surface ECG has spawned an increasing number of scientific investigations in the field of regulatory sciences, and more specifically in the context of the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. We conducted a novel initiative to evaluate the role of automatic JTpc measurement technologies by comparing their ability to distinguish multi- from single-channel blocking drugs. A set of 5232 ECGs was shared by the FDA (through the Telemetric and Holter ECG Warehouse) with 3 ECG device companies (AMPS, Mortara, and Philips)...
November 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/29017927/eleclazine-exhibits-enhanced-selectivity-for-long-qt-syndrome-type-3-associated-late-na-current
#14
Nesrine El-Bizri, Cheng Xie, Lynda Liu, James Limberis, Michael Krause, Ryoko Hirakawa, Steven Nguyen, Dennis R Tabuena, Luiz Belardinelli, Kristopher M Kahlig
BACKGROUND: Eleclazine (GS-6615) is a sodium channel blocker designed to improve the selectivity for cardiac late Na+ current (INa) over peak INa. OBJECTIVES: The goals of this study were to investigate the inhibition of late INa by eleclazine using a sample of long QT syndrome type 3 (LQT3) and overlap LQT3/Brugada syndrome mutant channels; to compare the apparent binding rates for eleclazine with those for other class 1 antiarrhythmic agents; and to investigate the binding site...
October 7, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28949056/marked-exercise-induced-t-wave-heterogeneity-in-symptomatic-diabetic-patients-with-nonflow-limiting-coronary%C3%A2-artery-stenosis
#15
Fernando G Stocco, Ederson Evaristo, Nishant R Shah, Michael K Cheezum, Jon Hainer, Courtney Foster, Bruce D Nearing, Ernest Gervino, Richard L Verrier
BACKGROUND: T-wave heterogeneity (TWH) independently predicted cardiovascular mortality in Health Survey 2000 based on 12-lead ECGs recorded at rest. We investigated whether TWH is elevated during exercise tolerance testing (ETT) in symptomatic diabetic patients with nonflow-limiting coronary artery stenosis compared to control subjects without diabetes. METHODS: Cases were all patients (n = 20) with analyzable ECG recordings during both rest and ETT who were enrolled in the Effects of Ranolazine on Coronary Flow Reserve (CFR) in Symptomatic Patients with Diabetes and Suspected or Known Coronary Artery Disease (RAND-CFR) study (NCT01754259); median CFR was 1...
September 26, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/28942951/the-algorithmic-performance-of-j-tpeak-for-drug-safety-clinical-trial
#16
Simon C Chien, Richard E Gregg
INTRODUCTION: The interval from J-point to T-wave peak (JTp) in ECG is a new biomarker able to identify drugs that prolong the QT interval but have different ion channel effects. If JTp is not prolonged, the prolonged QT may be associated with multi ion channel block that may have low torsade de pointes risk. From the automatic ECG measurement perspective, accurate and repeatable measurement of JTp involves different challenges than QT. We evaluated algorithm performance and JTp challenges using the Philips DXL diagnostic 12/16/18-lead algorithm...
August 15, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28941606/new-developments-in-hypertrophic-cardiomyopathy
#17
REVIEW
Robert M Cooper, Claire E Raphael, Max Liebregts, Nandan S Anavekar, Josef Veselka
Hypertrophic cardiomyopathy is the leading cause of sudden death in young individuals and an important cause of heart failure at any age. In this review we discuss advances in investigation and management of this heterogenous disease. Improved cardiac imaging has allowed us to detail many of the structural abnormalities whereas the use of new techniques, predominantly in cardiac magnetic resonance imaging, has given us a greater insight in to tissue architecture, mechanism of contractile abnormalities, and function...
October 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28933367/targeting-metabolic-modulation-and-mitochondrial-dysfunction-in-the-treatment-of-heart-failure
#18
REVIEW
Abbey Steggall, Ify R Mordi, Chim C Lang
Despite significant improvements in morbidity and mortality with current evidence-based pharmaceutical-based treatment of heart failure (HF) over the previous decades, the burden of HF remains high. An alternative approach is currently being developed, which targets myocardial energy efficiency and the dysfunction of the cardiac mitochondria. Emerging evidence suggests that the insufficient availability of ATP to the failing myocardium can be attributed to abnormalities in the myocardial utilisation of its substrates rather than an overall lack of substrate availability...
May 10, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28915573/lipid-catabolism-inhibition-sensitizes-prostate-cancer-cells-to-antiandrogen-blockade
#19
Thomas W Flaig, Maren Salzmann-Sullivan, Lih-Jen Su, Zhiyong Zhang, Molishree Joshi, Miguel A Gijón, Jihye Kim, John J Arcaroli, Adrie Van Bokhoven, M Scott Lucia, Francisco G La Rosa, Isabel R Schlaepfer
Prostate cancer (PCa) is the most common malignancy among Western men and the second leading-cause of cancer related deaths. For men who develop metastatic castration resistant PCa (mCRPC), survival is limited, making the identification of novel therapies for mCRPC critical. We have found that deficient lipid oxidation via carnitine palmitoyltransferase (CPT1) results in decreased growth and invasion, underscoring the role of lipid oxidation to fuel PCa growth. Using immunohistochemistry we have found that the CPT1A isoform is abundant in PCa compared to benign tissue (n=39, p<0...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28904076/residual-angina-after-elective-percutaneous-coronary-intervention-in-patients-with-diabetes-mellitus
#20
Anna Grodzinsky, Mikhail Kosiborod, Fengming Tang, Philip G Jones, Darren K McGuire, John A Spertus, John F Beltrame, Jae-Sik Jang, Abhinav Goyal, Neel M Butala, Robert W Yeh, Suzanne V Arnold
BACKGROUND: Previous studies suggest that among patients with stable coronary artery disease, patients with diabetes mellitus (DM) have less angina and more silent ischemia when compared with those without DM. However, the burden of angina in diabetic versus nondiabetic patients after elective percutaneous coronary intervention (PCI) has not been recently examined. METHODS AND RESULTS: In a 10-site US PCI registry, we assessed angina before and at 1, 6, and 12 months after elective PCI with the Seattle Angina Questionnaire angina frequency score (range, 0-100, higher=better)...
September 2017: Circulation. Cardiovascular Quality and Outcomes
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