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https://www.readbyqxmd.com/read/29677462/ondansetron-blocks-wildtype-and-p-f503l-variant-small-conductance-calcium-activated-potassium-channels
#1
Jum-Suk Ko, Shuai Guo, Jonathan Hassel, Patricia Celestino-Soper, Ty C Lynnes, James E Tisdale, James J Zheng, Stanley E Taylor, Tatiana Foroud, Michael D Murray, Richard J Kovacs, Xiaochun Li, Shien-Fong Lin, Zhenhui Chen, Matteo Vatta, Peng-Sheng Chen, Michael Rubart
The apamin-sensitive, small conductance, calcium-activated potassium (SK) current ( IKAS ) is encoded by KCNN genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT (diLQT) syndrome, we (1) screened for KCNN variants among patients with diLQT, (2) determined the properties of heterologously expressed wildtype and variant KCNN channels, and (3) determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS ...
April 20, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29672935/electrocardiographic-effects-of-hawthorn-crataegus-oxyacantha-in-healthy-volunteers-a-randomized-controlled-trial
#2
Stephanie E Trexler, Elaine Nguyen, Samantha M Gromek, Marcy J Balunas, William L Baker
The objective of this study was to evaluate the electrocardiographic effects of hawthorn in healthy adult volunteers. It was double-blind cross-over trial randomized 20 healthy adult volunteers to receive either a single oral 160-mg dose of hawthorn or matching placebo. Triplicate 12-lead electrocardiograms were taken before treatment and at 1-, 2-, 4-, and 6-hr post-dose. Following at least a 7-day washout period, participants were crossed over to the opposing treatment arm and had the measurements repeated...
April 19, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29672845/drug-induced-proarrhythmia-and-torsade-de-pointes-a-primer-for-students-and-practitioners-of-medicine-and-pharmacy
#3
REVIEW
J Rick Turner, Ignacio Rodriguez, Emily Mantovani, Gary Gintant, Peter R Kowey, Ralph J Klotzbaugh, Krishna Prasad, Philip T Sager, Norman Stockbridge, Colette Strnadova
Multiple marketing withdrawals due to proarrhythmic concerns occurred in the United States, Canada, and the United Kingdom in the late 1980s to early 2000s. This primer reviews the clinical implications of a drug's identified proarrhythmic liability, the issues associated with these safety-related withdrawals, and the actions taken by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and by regulatory agencies in terms of changing drug development practices and introducing new nonclinical and clinical tests to asses proarrhythmic liability...
April 19, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29671888/whole-exome-sequencing-reveals-microsatellites-dna-markers-for-response-to-dofetilide-initiation-in-patients-with-persistent-atrial-fibrillation-a-pilot-study
#4
Nick Kinney, Timothy R Larsen, David M Kim, Robin T Varghese, Steven Poelzing, Harold R Garner, Soufian T AlMahameed
BACKGROUND: Dofetilide is a class III antiarrhythmic drug effective for the treatment of atrial fibrillation (AF). Dofetilide initiation (DI) associate with corrected QT (QTc) interval prolongation. Significant QTc prolongation during DI mandates dose adjustment or discontinuation of the drug. Microsatellite DNA are novel genetic markers associate with congenital and acquired health conditions. OBJECTIVE: The purpose of this study was to explore potential genetic markers for QTc prolongation in response to DI in patients with persistent AF METHODS: We performed Whole Exome sequencing in a cohort of patients with persistent AF undergoing DI...
April 19, 2018: Clinical Cardiology
https://www.readbyqxmd.com/read/29663451/association-of-prolonged-qtc-interval-with-takotsubo-cardiomyopathy-a-neurocardiac-syndrome-inside-the-mystery-of-the-insula-of-reil
#5
REVIEW
Vincenzo Marafioti, Giulia Turri, Vincenzo Carbone, Salvatore Monaco
The Takotsubo cardiomyopathy is often considered autochthonous to the heart, although the primary problem may be not in the heart muscle itself. Instead, similar to several Takotsubo-like cardiac pathologies seen in acute neurological diseases, it may reflect the capacity of the nervous system to injure the heart. Persuasive evidence exists that shocking emotional stress promotes direct heart injuries. Moreover, clinical and laboratory research shows that cardiac structural damage can occur in the presence of a normal heart, especially in the context of seizures, stroke, and traumatic brain injury or under conditions of psychological stress...
April 17, 2018: Clinical Cardiology
https://www.readbyqxmd.com/read/29659201/evaluation-of-eluxadoline-effect-on-cardiac-repolarization
#6
Laura Bonifacio, Thomas L Hunt, Gail McIntyre, Leonard S Dove, Paul S Covington
This study evaluated the effects of eluxadoline, a mixed μ-opioid receptor (OR) and κ-OR agonist and δ-OR antagonist, on cardiac repolarization. This evaluator-blinded, placebo- and positive-controlled, 4-period crossover study randomized healthy men and women to single oral doses of eluxadoline (therapeutic dose 100 mg or supratherapeutic dose 1000 mg), moxifloxacin 400 mg, or placebo. QT data were corrected using individual custom correction (QTcI). The primary endpoint was the change from baseline in QTcI intervals (ΔQTcI) between eluxadoline and placebo (ΔΔQTcI)...
April 16, 2018: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29652656/electrocardiogram-abnormalities-related-to-anti-malarials-in-systemic-lupus-erythematosus
#7
Taneisha K McGhie, Paula Harvey, Jiandong Su, Nicole Anderson, George Tomlinson, Zahi Touma
OBJECTIVES: Cardiotoxicity with potential conduction/structural abnormalities on electrocardiogram (ECG) have been reported with anti-malarial (AM). We aimed to study whether cumulative AM is associated with ECG abnormalities. METHODS: A standard resting supine ECG was performed on consecutive patients attending the Lupus Clinic since 2012. ECG abnormalities were grouped into structural [left ventricular hypertrophy or atrial enlargement] and conduction abnormalities [prolonged corrected QT interval (QTc), short PR interval, left bundle branch block (LBBB), right bundle branch block (RBBB) and atrioventricular block (AVB), bradycardia, tachycardia, premature atrial complex, ectopic atrial rhythm, atrial fibrillation, premature ventricular complex and ventricular bigeminy]...
April 13, 2018: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29651591/importance-of-qt-rr-hysteresis-correction-in-studies-of-drug-induced-qtc-interval-changes
#8
Marek Malik, Christine Garnett, Katerina Hnatkova, Lars Johannesen, Jose Vicente, Norman Stockbridge
QT/RR hysteresis and QT/RR adaptation are interlinked but separate physiological processes signifying how quickly and how much QT interval changes when heart rate changes, respectively. While QT interval duration is, as a rule, corrected for heart rate in terms of the QT/RR adaptation, the correction for QT/RR hysteresis is frequently omitted in studies of drug-induced QTc changes. This study used data from previously conducted thorough QT studies to investigate the extent of QTc errors caused by omitting the correction for QT/RR hysteresis, particularly in small clinical investigations...
April 12, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29651218/hypocalcemia-presenting-as-life-threatening-torsades-de-pointes-with-prolongation-of-qtc-interval
#9
Shibba Takkar Chhabra, Shivani Mehta, Sandeep Chhabra, Manikant Singla, Naved Aslam, Bishav Mohan, Gurpreet Singh Wander
Torsades de pointes with prolonged QTc interval is a form of ventricular tachycardia. Many predisposing factors have been identified and hypocalcemia is among the rare ones. Our case illustrates that though rare, hypocalcemia might manifest as torsades de pointes with prolongation of QTc interval. Early diagnosis and management of dyselectrolytemia can prevent these patients from catastrophic torsades de pointes.
April 2018: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/29650123/interplay-between-genetic-substrate-qtc-duration-and-arrhythmia-risk-in-patients-with-long-qt-syndrome
#10
Andrea Mazzanti, Riccardo Maragna, Gaetano Vacanti, Nicola Monteforte, Raffaella Bloise, Maira Marino, Lorenzo Braghieri, Patrick Gambelli, Mirella Memmi, Eleonora Pagan, Massimo Morini, Alberto Malovini, Martin Ortiz, Luciana Sacilotto, Riccardo Bellazzi, Lorenzo Monserrat, Carlo Napolitano, Vincenzo Bagnardi, Silvia G Priori
BACKGROUND: Long QT syndrome (LQTS) is a common inheritable arrhythmogenic disorder, often secondary to mutations in the KCNQ1, KCNH2, and SCN5A genes. The disease is characterized by a prolonged ventricular repolarization (QTc interval) that confers susceptibility to life-threatening arrhythmic events (LAEs). OBJECTIVES: This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS...
April 17, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29648704/abnormal-ventricular-repolarization-in-long-qt-syndrome-carriers-is-related-to-short-left-ventricular-filling-time-and-attenuated-stroke-volume-response-during-exercise
#11
Dafni Charisopoulou, George Koulaouzidis, Annika Rydberg, Michael Y Henein
BACKGROUND: Long QT syndrome (LQTS) carriers are characterized by abnormal ventricular repolarization, prolonged systole, and mechanical dispersion. Prolonged left ventricular (LV) systole has been shown to result in disproportionate shortening of LV filling in other conditions. The aim of this study was to assess LV filling, diastolic function, and stroke volume (SV) response to dynamic exercise, in a group of LQTS carriers. METHODS: Forty-seven LQTS carriers (45 ± 15 years, 20 symptomatic) and 35 healthy individuals underwent bicycle stress echocardiogram...
April 12, 2018: Echocardiography
https://www.readbyqxmd.com/read/29627227/effects-of-moxifloxacin-on-the-proarrhythmic-surrogate-markers-in-healthy-filipino-subjects-exposure-response-modeling-using-ecg-data-of-thorough-qt-qtc-study
#12
Suchitra Matsukura, Yuji Nakamura, Kiyotaka Hoshiai, Takashi Hayashi, Tadashi Koga, Ai Goto, Koki Chiba, Nur Jaharat Lubna, Mihoko Hagiwara-Nagasawa, Hiroko Izumi-Nakaseko, Kentaro Ando, Atsuhiko T Naito, Atsushi Sugiyama
Effects of moxifloxacin on QTc as well as proarrhythmic surrogate markers including J-Tpeak c, Tpeak -Tend and short-term variability (STV) of repolarization were examined by using both standard E14 time-based evaluation and exposure-response modeling. The study was conducted with a single-blind, randomized, single-dose, placebo-controlled and two-period cross-over design in healthy Filipino subjects. QT interval was corrected by Fridericia's formula (QTcF). In the E14 time-based evaluation of ECG data, the largest ΔΔQTcF with 90% confidence interval was 14...
March 27, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29625280/long-qt-syndrome-type-5-lite-defining-the-clinical-phenotype-associated-with-the-potentially-pro-arrhythmic-p-asp85asn-kcne1-common-genetic-variant
#13
Conor Lane, John R Giudicessi, Dan Ye, David J Tester, Ram K Rohatgi, J Martijn Bos, Michael J Ackerman
BACKGROUND: Long QT syndrome (LQTS) genetic test reports commonly exclude potentially pro-arrhythmic common variants such as p.Asp85Asn-KCNE1. OBJECTIVE: To determine if a discernible phenotype is associated with p.Asp85Asn-KCNE1 and if relatively common KCNE1 variants underlie transient QT prolongation pedigrees with negative commercial LQTS genetic tests. METHODS: Retrospective review was used to compare demographics, symptomatology, and QT parameters of individuals with p...
April 3, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29623481/effect-of-antazoline-on-electrophysiological-properties-of-atrial-muscle-and-conduction-system-of-the-heart
#14
Bartłomiej Jacek Bińkowski, Marcin Makowski, Paweł Kubiński, Andrzej Lubiński
PURPOSE: Antazoline is a first-generation antihistaminic agent with additional anticholinergic properties and antiarrhythmic potential. Recent data shows its high effectiveness in sinus rhythm restoration among patients with paroxysmal atrial fibrillation. The effect of antazoline on electrophysiological parameters of the heart in vivo has not yet been examined. The aim of this study was to evaluate changes in electrophysiological parameters of the heart muscle and conduction system as a response to increasing doses of antazoline...
April 6, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29622964/correlation-of-corrected-qt-dispersion-with-the-severity-of-coronary-artery-disease-detected-by-syntax-score-in-non-diabetic-patients-with-stemi
#15
Hatem Helmy, Ahmed Abdel-Galeel, Yehia Taha Kishk, Khaled Mohammed Sleem
Introduction: Determination of the QT interval dispersion by means of a standard ECG at rest has been widely used for cardiovascular risk assessment during the last 15 years as one of the recent explanations for the development of life threatening ventricular arrhythmias. However, little is known about the relation between QT dispersion and the severity of coronary artery atherosclerosis as defined by SYNTAX score. Aim of work: The present study was done to assess the correlation between QTc dispersion and the severity of coronary artery disease in acute ST elevation myocardial infarction (STEMI) detected by SYNTAX score...
June 2017: The Egyptian heart journal: (EHJ): official bulletin of the Egyptian Society of Cardiology
https://www.readbyqxmd.com/read/29622001/clinical-and-molecular-genetic-risk-determinants-in-adult-long-qt-syndrome-type-1-and-2-patients-koponen-et-al-follow-up-of-adult-lqts-patients
#16
Mikael Koponen, Aki S Havulinna, Annukka Marjamaa, Annukka M Tuiskula, Veikko Salomaa, Päivi J Laitinen-Forsblom, Kirsi Piippo, Lauri Toivonen, Kimmo Kontula, Matti Viitasalo, Heikki Swan
BACKGROUND: Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving β-blocker treatment. In addition, an attempt was made to associate risk of events to specific types of KCNQ1 and KCNH2 mutations. METHODS: A follow-up study covering a mean of 18.6 ± 6.1 years was conducted in 867 genetically confirmed LQT1 and LQT2 patients and 654 non-carrier relatives aged 18-40 years...
April 5, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29619337/prevalence-and-prognostic-significance-of-prolonged-qtc-interval-in-emergency-medical-patients-a-prospective-observational-study
#17
Chhagan Lal Birda, Susheel Kumar, Ashish Bhalla, Navneet Sharma, Savita Kumari
Introduction: QTc interval is affected by many factors and prolongation of same may have prognostic significance. A significant number of patients admitted in medical emergency are acutely ill, have multiple comorbidities and are on medications, all of these factors might affect QTc interval and prognosis. Materials and Methods: Single-center, prospective, observational study was carried out on 279 patients of different illnesses recruited from emergency medical services attached to the Department of Internal Medicine at Postgraduate Institute of Medical Education and Research, Chandigarh, India, a tertiary care hospital...
January 2018: International Journal of Critical Illness and Injury Science
https://www.readbyqxmd.com/read/29619160/clinical-features-and-electrocardiogram-parameters-in-parkinson-s-disease
#18
Hitoshi Mochizuki, Nobuyuki Ishii, Kazutaka Shiomi, Masamitsu Nakazato
We investigated the relation between clinical features and electrocardiogram (ECG) parameters in patients with Parkinson's disease (PD). One hundred and fifty-six PD patients were enrolled. Their clinical features [body mass index (BMI), age, disease duration, and disease stage] and ECG parameters [RR, PR, QRS, and QT intervals, and heart rate-corrected QT (QTc)] were analyzed. BMI was positively correlated with the PR and QRS intervals in patients with PD. The QRS interval was positively correlated with disease duration and Hoehn and Yahr stage, and the QT interval and QTc were positively correlated with age...
December 11, 2017: Neurology International
https://www.readbyqxmd.com/read/29616864/a-phase-1-study-of-dasatinib-plus-all-trans-retinoic-acid-in-acute-myeloid-leukemia
#19
Robert L Redner, Jan H Beumer, Patricia Kropf, Mounzer Agha, Michael Boyiadzis, Kathleen Dorritie, Rafic Farah, Jing-Zhao Hou, Annie Im, Seah H Lim, Anastasios Raptis, Alison Sehgal, Susan M Christner, Daniel Normolle, Daniel E Johnson
Src family kinases (SFKs) are hyperactivated in acute myeloid leukemia (AML). SFKs impede the retinoic acid receptor, and SFK inhibitors enhance all-trans retinoic acid (ATRA)-mediated cellular differentiation in AML cell lines and primary blasts. To translate these findings into the clinic, we undertook a phase-I dose-escalation study of the combination of the SFK inhibitor dasatinib and ATRA in patients with high-risk myeloid neoplasms. Nine subjects were enrolled: six received 70 mg dasatinib plus 45 mg/m2 ATRA daily, and three received 100 mg dasatinib plus 45 mg/m2 ATRA daily for 28 days...
April 4, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29611166/diagnostic-and-prognostic-value-of-qrs-duration-and-qtc-interval-in-patients-with-suspected-myocardial-infarction
#20
Janosch Cupa, Ivo Strebel, Patrick Badertscher, Roger Abächerli, Raphael Twerenbold, Lukas Schumacher, Jasper Boeddinghaus, Thomas Nestelberger, Patrick Maechler, Nikola Kozhuharov, Maria Rubini Giménez, Karin Wildi, Jeanne du Fay de Lavallaz, Zaid Sabti, Lorraine Sazgary, Christian Puelacher, Deborah Mueller, Chiara Bianci, Òscar Miró, Carolina Fuenzalida, Sofia Calderón, Javier Martin-Sanchez, Sergio Lopez Iglesias, Beata Morawiec, Damian Kawecki, Jiri Parenica, Dagmar I Keller, Nicolas Geigy, Stefan Osswald, Christian Mueller, Tobias Reichlin
BACKGROUND: While prolongation of QRS duration and QTc interval during acute myocardial infarction (AMI) has been reported in animals, limited data is available for these readily available electrocardiography (ECG) markers in humans. METHODS: Diagnostic and prognostic value of QRS duration and QTc interval in patients with suspected AMI in a prospective diagnostic multicentre study were prospectively assessed. Digital 12-lead ECGs were recorded at presentation. QRS duration and QTc interval were automatically calculated in a blinded fashion...
April 3, 2018: Cardiology Journal
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