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https://www.readbyqxmd.com/read/28756098/phenotypic-variability-in-lqt3-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-and-their-response-to-antiarrhythmic-pharmacologic-therapy-an-in-silico-approach
#1
Michelangelo Paci, Elisa Passini, Stefano Severi, Jari Hyttinen, Blanca Rodriguez
BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are in vitro models with the clear advantages of their human origin and suitability for human disease investigations. However, limitations include their incomplete characterization and variability reported in different cell lines and laboratories. OBJECTIVE: The purpose of this study was to investigate in silico ionic mechanisms potentially explaining the phenotypic variability of hiPSC-CMs in long QT syndrome type 3 (LQT3) and their response to antiarrhythmic drugs...
July 27, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28751012/the-j-to-t-peak-interval-as-a-biomarker-in-drug-safety-studies-a-method-of-accuracy-assessment-applied-to-two-algorithms
#2
W Brian Chiu, Johan de Bie, David W Mortara
OBJECTIVES: To evaluate performance of J-to-T-peak (JTP) measurements of 12-lead ECGs, in a five-arm study using drugs with various levels of electrolyte channel block. METHODS: The novel evaluation method distinguishes between different aspects of measurement. "Random noise" is the variability among repeated measurements made without changing the conditions. "Context noise" is the variability of changes in context of the measurement, e.g. T-wave morphology, autonomic nervous system state...
July 12, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28710329/open-label-trial-of-ranolazine-for-the-treatment-of-myotonia-congenita
#3
W David Arnold, David Kline, Alan Sanderson, Ahmed A Hawash, Amy Bartlett, Kevin R Novak, Mark M Rich, John T Kissel
OBJECTIVE: To determine open-label, pilot study whether ranolazine could improve signs and symptoms of myotonia and muscle stiffness in patients with myotonia congenita (MC). METHODS: Thirteen participants were assessed at baseline and 2, 4, and 5 weeks. Ranolazine was started after baseline assessment (500 mg twice daily), increased as tolerated after week 2 (1,000 mg twice daily), and maintained until week 4. Outcomes included change from baseline to week 4 in self-reported severity of symptoms (stiffness, weakness, and pain), Timed Up and Go (TUG), hand grip and eyelid myotonia, and myotonia on EMG...
August 15, 2017: Neurology
https://www.readbyqxmd.com/read/28692548/comparison-of-vernakalant-and-ranolazine-in-atrial-fibrillation
#4
Gerrit Frommeyer, Magdalena Sterneberg, Dirk G Dechering, Simon Kochhäuser, Nils Bögeholz, Michael Fehr, Lars Eckardt
BACKGROUND: Current guidelines recommend vernakalant for pharmacologic cardioversion of recent-onset atrial fibrillation. However, this drug is not established as chronic therapy. METHODS AND RESULTS: In total, 15 rabbit hearts were Langendorff-perfused. A burst pacing protocol-induced atrial fibrillation in 7 of 15 hearts at baseline (10 episodes). Subsequently, a combination of acetylcholine and isoproterenol (ACH/ISO) has been administered to increase occurrence of atrial fibrillation resulting in a reduction of atrial action potential duration (-25 ms, P < 0...
September 2017: Journal of Cardiovascular Medicine
https://www.readbyqxmd.com/read/28680620/ranolazine-safe-and-effective-in-a-patient-with-hypertensive-cardiomyopathy-and-multiple-episodes-of-electrical-storm
#5
Panagiotis Margos, Nikolaos Margos, Nadiya Mokadem, Ilias Patsiotis, Athanasios Kranidis
Among implantable cardioverter-defibrillator (ICD) recipients, there are patients with recurrent episodes of electrical storm (ES), retractable to the optimal antiarrhythmic drug therapy or invasive ablation procedures. A relatively novel anti-ischemic drug with also antiarrhythmic properties, ranolazine, may effectively suppress ventricular arrhythmias in such patients for a long period of time.
July 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28656516/targeting-mitochondrial-calcium-handling-and-reactive-oxygen-species-in-heart-failure
#6
REVIEW
Alexander Dietl, Christoph Maack
PURPOSE OF REVIEW: In highly prevalent cardiac diseases, new therapeutic approaches are needed. Since the first description of oxidative stress in heart failure, reactive oxygen species (ROS) have been considered as attractive drug targets. Though clinical trials evaluating antioxidant vitamins as ROS-scavenging agents yielded neutral results in patients at cardiovascular risk, the knowledge of ROS as pathophysiological factors has considerably advanced in the past few years and led to novel treatment approaches...
August 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28653394/ranolazine-reduces-repolarization-heterogeneity-in%C3%A2-symptomatic-patients-with-diabetes-and-non-flow-limiting-coronary-artery-stenosis
#7
Ederson Evaristo, Fernando G Stocco, Nishant R Shah, Michael K Cheezum, Jon Hainer, Courtney Foster, Bruce D Nearing, Marcelo Di Carli, Richard L Verrier
BACKGROUND: Experimental evidence suggests that ranolazine decreases susceptibility to ischemia-induced arrhythmias independent of effects on coronary artery blood flow. OBJECTIVE: In symptomatic diabetic patients with non-flow-limiting coronary artery stenosis with diffuse atherosclerosis and/or microvascular dysfunction, we explored whether ranolazine reduces T-wave heterogeneity (TWH), an electrocardiographic (ECG) marker of arrhythmogenic repolarization abnormalities shown to predict sudden cardiac death...
June 27, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/28648439/modulation-of-myocardial-energetics-an-important-category-of-agents-in-the-multimodal-treatment-of-coronary-artery-disease-and-heart-failure
#8
REVIEW
Jamshed J Dalal, Sundeep Mishra
The combined and relative contribution of glucose and fatty acid oxidation generates myocardial energy, which regulates the cardiac function and efficiency. Any dysregulation in this metabolic homeostasis can adversely affect the function of heart and contribute to cardiac conditions such as angina and heart failure. Metabolic agents ameliorate this internal metabolic anomaly, by shifting the energy production pathway from free fatty acids to glucose, resulting in a better performance of the heart. Metabolic therapy is relatively a new modality, which functions through optimization of cardiac substrate metabolism...
May 2017: Indian Heart Journal
https://www.readbyqxmd.com/read/28610990/atrial-ventricular-differences-in-rabbit-cardiac-voltage-gated-na-currents-basis-for-atrial-selective-block-by-ranolazine
#9
Rachel E Caves, Hongwei Cheng, Stéphanie C Choisy, Hanne C Gadeberg, Simon M Bryant, Jules C Hancox, Andrew F James
BACKGROUND: Class 1 antiarrhythmic drugs are highly effective in restoring and maintaining sinus rhythm in atrial fibrillation patients but carry a risk of ventricular tachyarrhythmia. The antianginal agent ranolazine is a prototypic atrial-selective voltage-gated Na(+) channel blocker but the mechanisms underlying its atrial-selective action remain unclear. OBJECTIVE: The present study examined the mechanisms underlying the atrial-selective action of ranolazine...
June 10, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28607609/efficacy-of-ranolazine-in-preventing-atrial-fibrillation-following-cardiac-surgery-results-from-a-meta-analysis
#10
REVIEW
Chintan Trivedi, Ankit Upadhyay, Kinjal Solanki
BACKGROUND: Atrial fibrillation (AF) is a common complication after cardiac surgery. Ranolazine is a Food and Drug Administration approved anti-ischemic drug, which also has anti-arrhythmic properties. Recent studies have demonstrated the benefit of ranolazine in preventing post-operative AF (POAF) in patients undergoing cardiac surgery. Hence, we performed a meta-analysis of published studies comparing ranolazine plus standard therapy versus standard therapy for POAF prevention in patients undergoing cardiac surgery...
June 2017: Journal of Arrhythmia
https://www.readbyqxmd.com/read/28601914/left-ventricular-ejection-fraction-as-therapeutic-target-is-it-the-ideal-marker
#11
REVIEW
V Katsi, G Georgiopoulos, A Laina, E Koutli, J Parissis, C Tsioufis, P Nihoyannopoulos, D Tousoulis
Heart failure (HF) consists the fastest growing clinical cardiac disease. HF patients are categorized on the basis of underlying left ventricular ejection fraction (LVEF) into HF with preserved EF (HFpEF), reduced LVEF (HFrEF), and mid-range LVEF (HFmrEF). While LVEF is the most commonly used surrogate marker of left ventricular (LV) systolic function, the implementation of two-dimensional echocardiography in estimating this parameter imposes certain caveats on current HF classification. Most importantly, LVEF could fluctuate in repeated measurements or even recover after treatment, thus blunting the borders between proposed categories of HF and enabling upward classification of patients...
June 10, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28576663/impact-of-ranolazine-on-coronary-microvascular-dysfunction-micro-study
#12
Bina Ahmed, Judith Mondragon, Mark Sheldon, Stacey Clegg
BACKGROUND: Patients with angina and coronary microvascular dysfunction, without evidence of structural or epicardial coronary disease (Type I CMVD) remain without evidence based treatment options. Previous work has demonstrated that ranolazine can improve angina frequency and stability among patients with Type 1 CMVD; however, the mechanism remains unclear. Therefore, the objective of this pilot project was to assess the impact of ranolazine on Type I CMVD as measured using an invasive tool to measure global resistance (index of microcirculatory resistance (IMR))...
April 22, 2017: Cardiovascular Revascularization Medicine: Including Molecular Interventions
https://www.readbyqxmd.com/read/28571183/effect-of-ranolazine-in-patients-with-chest-pain-and-normal-coronaries-a-hospital-based-study
#13
Swapan Saha, Tony Ete, Manish Kapoor, Pravin Kumar Jha, Rinchin Dorjee Megeji, Gaurav Kavi, Synrang Batngen Warjri, Animesh Mishra
INTRODUCTION: There is an important role of coronary microcirculation in the clinical presentation and prognosis of patients who have typical chest pain despite normal epicardial coronary arteries (microvascular angina). Treatment of these patients is empirical because of the incomplete knowledge of its cause. Limited data has shown that ranolazine reduces angina and improves exercise performance in such patients with frequent angina. AIM: To evaluate the effect of ranolazine in patients with chest pain and normal epicardial coronaries (micro-vascular angina)...
April 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28552884/ranolazine-facilitates-termination-of-ventricular-tachyarrhythmia-associated-with-acute-myocardial-ischemia-through-suppression-of-late-ina-mediated-focal-activity
#14
Takashi Ogawa, Haruo Honjo, Masatoshi Yamazaki, Yasunori Kushiyama, Ichiro Sakuma, Itsuo Kodama, Kaichiro Kamiya
BACKGROUND: Ventricular tachycardia/fibrillation (VT/VF) associated with acute myocardial ischemia is the most common cause of sudden cardiac death, but its underlying mechanisms are incompletely understood. It is hypothesized that late Na(+)current (INa) contributes to arrhythmogenic activity in ischemic myocardium.Methods and Results:Langendorff-perfused rabbit hearts with regional ischemia in ventricles were optically mapped. Perfusion with ranolazine (10 μmol/L), a selective inhibitor of lateINa, significantly reduced excitation frequency and facilitated termination of VT/VF induced after occlusion of the left main coronary trunk...
May 26, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28521025/mechanism-of-as2o3-induced-action-potential-prolongation-and-using-hips-cms-to-evaluate-the-rescue-efficacy-of-drugs-with-different-rescue-mechanism
#15
Meng Yan, Lifang Feng, Yanhui Shi, Junnan Wang, Yan Liu, Fengmei Li, Baoxin Li
Arsenic trioxide (As2O3) has been verified as a breakthrough in the management of acute promyelocytic leukemia in recent decades. However, cardiotoxicity, especially long QT syndrome (LQTS) has become the most important issue during As2O3 treatment. The characterized mechanisms behind this adverse effect are inhibition of cardiac hERG channel trafficking and increase of cardiac calcium currents. In our study, we found a new pathway underlying As2O3-induced cardiotoxicity that As2O3 accelerates lysosomal degradation of hERG on plasma membrane after using brefeldin A (BFA) to block protein trafficking...
May 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28497941/antiarrhythmic-effects-of-ranolazine-used-both-alone-for-prevention-of-atrial-fibrillation-and-as-an-add-on-to-intravenous-amiodarone-for-its-pharmacological-cardioversion-a-meta-analysis
#16
Renato DE Vecchis, Carmelina Ariano, Anna Giasi, Carmela Cioppa
BACKGROUND: Recent evidence from relatively small randomized controlled trials would seem to support a useful role of ranolazine for the prevention and treatment of atrial fibrillation (AF). The present study is aimed at providing information about the possible beneficial anti-arrhythmic properties of ranolazine. In particular, the meta-analysis carried out in this study focuses on the application of ranolazine to prophylaxis and treatment of atrial fibrillation. METHODS: Both randomized controlled trials (RCTs) and non randomized observational studies concerning the effects of ranolazine on AF were included in the meta-analysis...
May 10, 2017: Minerva Cardioangiologica
https://www.readbyqxmd.com/read/28491780/complexity-of-ranolazine-and-phenytoin-use-in-an-infant-with-long-qt-syndrome-type-3
#17
Reina Bianca Tan, Sujata Chakravarti, Melissa Busovsky-McNeal, Abigail Walsh, Frank Cecchin
No abstract text is available yet for this article.
January 2017: HeartRhythm Case Reports
https://www.readbyqxmd.com/read/28473655/lipid-catabolism-inhibition-sensitizes-prostate-cancer-cells-to-antiandrogen-blockade
#18
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...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28473401/ranolazine-in-symptomatic-diabetic-patients-without-obstructive-coronary-artery-disease-impact-on-microvascular-and-diastolic-function
#19
Nishant R Shah, Michael K Cheezum, Vikas Veeranna, Stephen J Horgan, Viviany R Taqueti, Venkatesh L Murthy, Courtney Foster, Jon Hainer, Karla M Daniels, Jose Rivero, Amil M Shah, Peter H Stone, David A Morrow, Michael L Steigner, Sharmila Dorbala, Ron Blankstein, Marcelo F Di Carli
BACKGROUND: Treatments for patients with myocardial ischemia in the absence of angiographic obstructive coronary artery disease are limited. In these patients, particularly those with diabetes mellitus, diffuse coronary atherosclerosis and microvascular dysfunction is a common phenotype and may be accompanied by diastolic dysfunction. Our primary aim was to determine whether ranolazine would quantitatively improve exercise-stimulated myocardial blood flow and cardiac function in symptomatic diabetic patients without obstructive coronary artery disease...
May 4, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28473137/ranolazine-in-diabetics-with-stable%C3%A2-ischemic-heart-disease-greatest-efficacy-related-to-greatest-metabolic-stress
#20
EDITORIAL
Peter H Stone
No abstract text is available yet for this article.
May 9, 2017: Journal of the American College of Cardiology
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