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https://www.readbyqxmd.com/read/28814790/in-silico-investigation-of-a-kcnq1-mutation-associated-with-short-qt-syndrome
#1
Ismail Adeniran, Dominic G Whittaker, Aziza El Harchi, Jules C Hancox, Henggui Zhang
Short QT syndrome (SQTS) is a rare condition characterized by abnormally 'short' QT intervals on the ECG and increased susceptibility to cardiac arrhythmias and sudden death. This simulation study investigated arrhythmia dynamics in multi-scale human ventricle models associated with the SQT2-related V307L KCNQ1 'gain-of-function' mutation, which increases slow-delayed rectifier potassium current (IKs). A Markov chain (MC) model recapitulating wild type (WT) and V307L mutant IKs kinetics was incorporated into a model of the human ventricular action potential (AP) for investigation of QT interval changes and arrhythmia substrates...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28813535/modeling-hypothermia-induced-effects-for-the-heterogeneous-ventricular-tissue-from-cellular-level-to-the-impact-on-the-ecg
#2
Roland Kienast, Michael Handler, Markus Stöger, Daniel Baumgarten, Friedrich Hanser, Christian Baumgartner
Hypothermia has a profound impact on the electrophysiological mechanisms of the heart. Experimental investigations provide a better understanding of electrophysiological alterations associated with cooling. However, there is a lack of computer models suitable for simulating the effects of hypothermia in cardio-electrophysiology. In this work, we propose a model that describes the cooling-induced electrophysiological alterations in ventricular tissue in a temperature range from 27°C to 37°C. To model the electrophysiological conditions in a 3D left ventricular tissue block it was essential to consider the following anatomical and physiological parameters in the model: the different cell types (endocardial, M, epicardial), the heterogeneous conductivities in longitudinal, transversal and transmural direction depending on the prevailing temperature, the distinct fiber orientations and the transmural repolarization sequences...
2017: PloS One
https://www.readbyqxmd.com/read/28812984/modelling-the-effects-of-quinidine-disopyramide-and-e-4031-on-short-qt-syndrome-variant-3-in-the-human-ventricles
#3
Cunjin Luo, Kuanquan Wang, Henggui Zhang
Short QT syndrome (SQTS) is an inherited cardiac channelopathy, but at present little information is available on its pharmacological treatment. SQT3 variant (linked to the inward rectifier potassium current IK1) of SQTS, results from a gain-of-function mutation (Kir2.1 D172N) in the KCNJ2-encoded channels, which is associated with ventricular fibrillation (VF). Using biophysically-detailed human ventricular computer models, this study investigated the potential effects of quinidine, disopyramide, and E-4031 on SQT3...
August 16, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28808933/cardiovascular-disease-in-clozapine-treated-patients-evidence-mechanisms-and-management
#4
REVIEW
Kathlyn J Ronaldson
Myocarditis occurs in about 3% of those initiated on clozapine but monitoring reduces the risk of serious outcome. Cardiomyopathy may develop after myocarditis, or from prolonged tachycardia. Monitoring using echocardiography is not deemed cost effective. Tachycardia, orthostatic hypotension and reduced heart rate variability are a group of clozapine-related adverse effects associated with autonomic dysfunction and may have serious consequences in the long term. Elevated heart rate and poor heart rate variability can be treated with a β-blocker or a non-dihydropyridine calcium channel blocker, while orthostatic hypotension can be alleviated by increased fluid intake and abdominal binding, but may require pharmacological intervention...
August 14, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28804970/arrhythmogenic-gene-remodelling-in-elderly-patients-with-type-2-diabetes-with-aortic-stenosis-and-normal-left-ventricular-ejection-fraction
#5
R Ashrafi, P Modi, A Y Oo, D M Pullan, K Jian, H Zhang, J Yanni Gerges, G Hart, M R Boyett, G K Davis, J P H Wilding
Type 2 diabetes is associated with higher rate of ventricular arrhythmias and this is hypothesised to be independent of coronary artery disease or hypertension. To investigate further we compared changes in left ventricular myocardial gene expression in Type 2 diabetes to patients in a control group with left ventricular hypertrophy. 9 control patients and 7 patients with type 2 diabetes with aortic stenosis undergoing aortic valve replacement had standard ECGs, signal averaged ECGs and echocardiograms prior to surgery...
August 14, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28804248/effect-of-chronic-hepatitis-c-virus-treatment-by-combination-therapy-on-cardiovascular-system
#6
Reda Biomy, Mohamed Abdelshafy, Ahmed Abdelmonem, Hesham Abu-Elenin, George Ghaly
BACKGROUND: The prevalence of hepatitis C virus (HCV) in Egypt is quite high, and the combined oral direct-acting antiviral agents (DAAs) may have impressive results. OBJECTIVE: To assess the cardiovascular effects of DAAs in patients with HCV. METHODS: A total of 170 patients with HCV were divided into 2 groups: first group (100 patients) received triple combination therapy (pegylated interferon alfa, sofosbuvir, and ribavirin, whereas the second group (70 patients) received dual combination therapy (sofosbuvir and simeprevir)...
2017: Clinical Medicine Insights. Cardiology
https://www.readbyqxmd.com/read/28803378/qt-interval-prolongation-in-hospitalized-patients-on-cardiology-wards-a-prospective-observational-study
#7
Qasim Khan, Mohammad Ismail, Iqbal Haider, Inam Ul Haq, Sidra Noor
PURPOSE: Prolonged QT interval may lead to a lethal form of arrhythmia, torsades de pointes (TdP), which is associated with cardiovascular mortality. Therefore, we aimed to identify prevalence of QT interval prolongation, compare clinical characteristics of patients with normal and prolonged QT interval, and identify predictors of QT interval prolongation. METHODS: A prospective observational study was conducted in cardiology wards of two teaching hospitals in Pakistan...
August 12, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28801207/crediblemeds-org-what-does-it-offer
#8
REVIEW
Raymond L Woosley, Kristin Black, C William Heise, Klaus Romero
Since the 1990s, when numerous non-cardiac drugs were first recognized to have the potential to prolong the QT interval and cause torsades de pointes (TdP), clinicians, drug regulators, drug developers, and clinical investigators have become aware of the complexities of assessing evidence and determining TdP causality for the many drugs being marketed or under development. To facilitate better understanding, the Arizona Center for Education and Research on Therapeutics, known as AZCERT, has developed the CredibleMeds...
August 1, 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28800275/polyphenol-rich-fraction-of-parquetina-nigrescens-mitigates-dichlorvos-induced-cardiorenal-dysfunction-through-reduction-in-cardiac-nitrotyrosine-and-renal-p38-expressions-in-wistar-rats
#9
Ademola A Oyagbemi, Temidayo O Omobowale, Grace O Ochigbo, Ebunoluwa R Asenuga, Olufunke Eunice Ola-Davies, Temitayo O Ajibade, Adebowale B Saba, Adeolu A Adedapo
Parquetina nigrescens is commonly used to treat diseases in humans and animals in developing countries, including Nigeria. This study evaluates the effects of its polyphenol-rich fraction (prf) on dichlorvos-induced cardio- and renal toxicity. There were several factors assessed during this study, including cardiac and renal markers, serum myeloperoxidase and xanthine oxidase, and electrocardiograph (ECG) changes. The changes in electrocardiograph (ECG) were recorded. Immunohistochemistry of cardiac and renal p38 and nitrotyrosine was determined...
August 11, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28799823/lack-of-qt-prolongation-for-2-o-methoxyethyl-modified-antisense-oligonucleotides-based-on-retrospective-exposure-response-analysis-of-ten-phase-1-dose-escalation-placebo-controlled-studies-in-healthy-subjects
#10
Rosie Z Yu, Rudy Gunawan, Richard S Geary, Steven G Hughes, Scott P Henry, Yanfeng Wang
The potential of QT prolongation of ten 2'-O-methoxyethyl-modified (2'-MOE) antisense oligonucleotides (ASOs) was evaluated retrospectively via exposure/response (ER) analysis using data from Phase 1 clinical studies in healthy subjects. All Phase 1 studies were double-blind, placebo-controlled, single and multiple ascending dose studies designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of the ASOs in healthy subjects. The active doses in these studies ranged from 50 to 450 mg administered by subcutaneous (SC) injection in single and multiple ascending dose cohorts...
August 11, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28798290/bradycardia-and-hypothermia-complicating-azithromycin-treatment
#11
Kerri Benn, Sam Salman, Madhu Page-Sharp, Timothy M E Davis, Jim P Buttery
BACKGROUND Azithromycin is a macrolide antibiotic widely used to treat respiratory, urogenital, and other infections. Gastrointestinal upset, headache, and dizziness are common adverse effects, and prolongation of the rate-corrected electrocardiographic QT interval and malignant arrhythmias have been reported. There are rare reports of bradycardia and hypothermia but not in the same patient. CASE REPORT A 4-year-old boy given intravenous azithromycin as part of treatment for febrile neutropenia complicating leukemia chemotherapy developed hypothermia (rectal temperature 35...
August 11, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28797793/bpc-157-counteracts-qtc-prolongation-induced-by-haloperidol-fluphenazine-clozapine-olanzapine-quetiapine-sulpiride-and-metoclopramide-in-rats
#12
Dean Strinic, Zeljka Belosic Halle, Kresimir Luetic, Ana Nedic, Igor Petrovic, Mario Sucic, Gordana Zivanovic Posilovic, Dijana Balenovic, Sanja Strbe, Mario Udovicic, Domagoj Drmic, Mirjana Stupnisek, Martina Lovric Bencic, Sven Seiwerth, Predrag Sikiric
AIM: Commonly, neuroleptics and prokinetics induce a prolonged QTc interval. In this study, stable gastric pentadecapeptide BPC 157 counteracts the prolongation of the QTc interval in Wistar rats that underwent daily administration of dopamine neuroleptics or prokinetics. Previously, in rats and mice, BPC 157 counteracted neuroleptic-induced catalepsy and gastric ulcers. MAIN METHODS: To counteract neuroleptic- or prokinetic-induced prolongation of the QTc interval, rats were given a BPC 157 regimen once daily over seven days (10μg, 10ng/kg ip) immediately after each administrations of haloperidol (0...
August 7, 2017: Life Sciences
https://www.readbyqxmd.com/read/28797161/masked-inherited-primary-arrhythmia-syndromes-in-sudden-cardiac-death-patients-accompanied-by-coronary-vasospasm
#13
Ki Hong Lee, Hyung Wook Park, Jeong Nam Eun, Jeong Gwan Cho, Nam Sik Yoon, Mi Ran Kim, Yo Han Ku, Hyukjin Park, Seung Hun Lee, Jeong Han Kim, Min Chul Kim, Woo Jin Kim, Hyun Kuk Kim, Jae Yeong Cho, Keun-Ho Park, Doo Sun Sim, Hyun Ju Yoon, Kye Hun Kim, Young Joon Hong, Ju Han Kim, Youngkeun Ahn, Myung Ho Jeong, Jong Chun Park
Background/Aims: Coronary vasospasms are one of the important causes of sudden cardiac death (SCD). Provocation of coronary vasospasms can be useful, though some results may lead to false positives, with patients potentially experiencing recurrent SCD despite appropriate medical treatments. We hypothesized that it is not coronary vasospasms but inherited primary arrhythmia syndromes (IPAS) that underlie the development of SCD. Methods: We analyzed 74 consecutive patients (3...
August 11, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28793999/association-of-qt-prolonging-medication-use-in-ckd-with-electrocardiographic-manifestations
#14
Soren Snitker, Rebecca M Doerfler, Elsayed Z Soliman, Rajat Deo, Wendy L St Peter, Susan Kramlik, Michael J Fischer, Sankar Navaneethan, Patrice Delafontaine, Bernard G Jaar, Akinlolu Ojo, Gail K Makos, Anne Slaven, Matthew R Weir, Min Zhan, Jeffrey C Fink
BACKGROUND AND OBJECTIVES: Several drugs used in CKD can prolong electrocardiographic conduction. We examined the use of electrocardiogram QT-prolonging medications in predialysis CKD and their association with QT duration. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 3252 Chronic Renal Insufficiency Cohort participants with at least one study electrocardiogram between 2003 and 2011 were included. QT-prolonging medications used in 100 or more visits (n=16,451 visits) along with diuretics and proton pump inhibitors, given their potential for electrolyte disturbances, were examined for QT interval prolongation...
August 9, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28793044/reproducibility-and-reliability-of-qtc-and-qtcd-measurements-and-their-relationships-with-left-ventricular-hypertrophy-in-hemodialysis-patients
#15
Maria Angélica Gonçalves Alonso, Valentine de Almeida Costa de Castro Lima, Maria Angela Magalhães de Queiroz Carreira, Jocemir Ronaldo Lugon
Background: Left ventricular hypertrophy (LVH) is very common in hemodialysis patients and an independent risk factor for mortality in this population. The myocardial remodeling underlying the LVH can affect ventricular repolarization causing abnormalities in QT interval. Objective: to evaluate the reproducibility and reliability of measurements of corrected QT interval (QTc) and its dispersion (QTcd) and correlate these parameters with LVH in hemodialysis patients...
August 7, 2017: Arquivos Brasileiros de Cardiologia
https://www.readbyqxmd.com/read/28791627/influence-of-intravenous-administration-of-the-antipsychotic-drug-benperidol-on-the-qt-interval
#16
Alexander Schmidt, Peter Fischer, Beate Wally, Joachim Scharfetter
A group effect is generally assumed regarding the prolongation of the QT interval through butyrophenone antipsychotics like haloperidol. Consequently intravenous administration of benperidol is seen critically notwithstanding sparse evidence; thus benperidol and haloperidol were compared regarding their cardiac risk of prolonging the QT interval when administered intravenously for acute sedation of psychotic patients. The QT interval was measured by a 12-lead ECG. For the correction of QT values Bazett's formula was used...
August 8, 2017: Neuropsychiatrie: Klinik, Diagnostik, Therapie und Rehabilitation
https://www.readbyqxmd.com/read/28783871/cardiac-safety-of-ozanimod-a-novel-sphingosine-1-phosphate-receptor-modulator-results-of-a-thorough-qt-qtc-study
#17
Jonathan Q Tran, Jeffrey P Hartung, Allan D Olson, Boaz Mendzelevski, Gregg A Timony, Marcus F Boehm, Robert J Peach, Sheila Gujrathi, Paul A Frohna
Ozanimod is a novel, selective, oral sphingosine-1-phosphate (1 and 5) receptor modulator in development for multiple sclerosis and inflammatory bowel disease. This randomized, double-blind, placebo-controlled, positive-controlled, parallel-group thorough QT study characterized the effects of ozanimod on cardiac repolarization in healthy subjects. Eligible subjects were randomized to 1 of 2 groups: ozanimod (escalated from 0.25 to 2 mg over 14 days) or placebo (for 14 days). A single dose of moxifloxacin 400 mg or placebo was administered on days 2 and 17...
August 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28782696/heritability-in-a-scn5a-mutation-founder-population-with-increased-female-susceptibility-to-non-nocturnal-ventricular-tachyarrhythmia-and-sudden-cardiac-death
#18
Rachel M A Ter Bekke, Aaron Isaacs, Andrei Barysenka, Marije B Hoos, Jan D H Jongbloed, Jan C A Hoorntje, Alfons S M Patelski, Apollonia T J M Helderman-van den Enden, Arthur van den Wijngaard, Monika Stoll, Paul G A Volders
BACKGROUND: Heritable cardiac sodium-channel dysfunction is associated with various arrhythmia syndromes, some predisposing to ventricular fibrillation. Phenotypic diversity among carriers of identical-by-descent mutations is often remarkable, suggesting influences of genetic modifiers. OBJECTIVE: We identified a unique SCN5A-mutation founder population with mixed clinical phenotypes and sudden cardiac death, and investigated the heritability of electromechanical traits besides the SCN5A-mutation effect...
August 3, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28782310/ecg-changes-in-young-healthy-smokers-a-simple-and-cost-effective-method-to-assess-cardiovascular-risk-according-to-pack-years-of-smoking
#19
Nirmal Kumar Sharma, Kapil Kumar Jaiswal, S R Meena, Rahul Chandel, Saurabh Chittora, Prem Singh Goga, H B Harish, Rajesh Sagar
OBJECTIVE: To document the prevalence of ECG abnormalities in young healthy smokers and compare ECG changes in smokers, young healthy non-smokers and amongst smokers with different pack years. METHODS: This was a prospective case-control study consisting of 200 young healthy male and female individuals, 150 smokers and 50 non-smokers between ages 25-40 years, further categorized and compared according to age, sex and pack years of smoking. The ECG recordings were analyzed for different ECG parameters like heart rate, P-wave duration, P-wave amplitude, PR interval, QRS duration, RR-interval, ST-segment duration, QT interval and QTc interval...
June 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28780600/the-anti-influenza-drug-oseltamivir-reduces-atrial-fibrillation-in-an-experimental-whole-heart-model
#20
Gerrit Frommeyer, André Mittelstedt, Julian Wolfes, Christian Ellermann, Simon Kochhäuser, Patrick Leitz, Dirk G Dechering, Lars Eckardt
Recent experimental studies suggested direct effects of the anti-influenza drug oseltamivir on cardiac electrophysiology. We therefore aimed at analyzing potential antiarrhythmic effects of oseltamivir on atrial fibrillation (AF) in an experimental whole-heart model. Twelve rabbit hearts were isolated and Langendorff perfused. Thereafter, hearts were paced at cycle lengths of 350, 250, and 200 ms in the atrium. A standardized protocol employing atrial burst pacing induced AF in 4 of 12 hearts under baseline conditions (33%, 11 episodes)...
August 6, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
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