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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/29677051/electrocardiographic-predictors-of-atrial-fibrillation-in-nonhypertensive-and-hypertensive-individuals
#2
Arttu O Lehtonen, Ville L Langén, Kimmo Porthan, Mika Kähönen, Markku S Nieminen, Antti M Jula, Teemu J Niiranen
OBJECTIVE: The aim of this study was to compare the predictive value of ECG abnormalities for atrial fibrillation in nonhypertensive versus hypertensive individuals. METHODS: We recorded ECG and measured conventional cardiovascular risk factors in a nationwide population-based sample of 5813 Finns. We divided the participants into nonhypertensive (n = 3148) and hypertensive (n = 2665) individuals and followed the participants for incident atrial fibrillation events...
April 19, 2018: Journal of Hypertension
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/29669701/crizotinib-in-patients-with-advanced-inoperable-inflammatory-myofibroblastic-tumours-with-and-without-anaplastic-lymphoma-kinase-gene-alterations-european-organisation-for-research-and-treatment-of-cancer-90101-create-a-multicentre-single-drug-prospective-non
#5
Patrick Schöffski, Jozef Sufliarsky, Hans Gelderblom, Jean-Yves Blay, Sandra J Strauss, Silvia Stacchiotti, Piotr Rutkowski, Lars H Lindner, Michael G Leahy, Antoine Italiano, Nicolas Isambert, Maria Debiec-Rychter, Raf Sciot, Thomas Van Cann, Sandrine Marréaud, Axelle Nzokirantevye, Sandra Collette, Agnieszka Wozniak
BACKGROUND: An inflammatory myofibroblastic tumour (IMFT) is a rare mesenchymal neoplasm characterised by anaplastic lymphoma kinase (ALK) gene rearrangements. We assessed the activity and safety of crizotinib, a tyrosine kinase inhibitor, targeting ALK in patients with advanced IMFT either with or without ALK alterations. METHODS: We did a multicentre, biomarker-driven, single-drug, non-randomised, open-label, two-stage phase 2 trial (European Organisation for Research and Treatment of Cancer 90101 CREATE) at 13 study sites (five university hospitals and eight specialty clinics) in eight European countries (Belgium, France, Germany, Italy, Netherlands, Poland, Slovakia, and the UK)...
April 12, 2018: Lancet Respiratory Medicine
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/29657083/the-course-of-awake-breathing-disturbances-across-the-lifespan-in-rett-syndrome
#7
Daniel C Tarquinio, Wei Hou, Jeffrey L Neul, Gamze Kilic Berkmen, Jana Drummond, Elizabeth Aronoff, Jennifer Harris, Jane B Lane, Walter E Kaufmann, Kathleen J Motil, Daniel G Glaze, Steven A Skinner, Alan K Percy
Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder caused by mutations in MECP2, is associated with a peculiar breathing disturbance exclusively during wakefulness that is distressing, and can even prompt emergency resuscitation. Through the RTT Natural History Study, we characterized cross sectional and longitudinal characteristics of awake breathing abnormalities in RTT and identified associated clinical features. Participants were recruited from 2006 to 2015, and cumulative lifetime prevalence of breathing dysfunction was determined using the Kaplan-Meier estimator...
April 12, 2018: Brain & Development
https://www.readbyqxmd.com/read/29652656/electrocardiogram-abnormalities-related-to-anti-malarials-in-systemic-lupus-erythematosus
#8
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/29651961/the-benefit-of-prescribing-vitamin-d-as-add-on-therapy-on-the-electrocardiographic-changes-in-epileptic-patients
#9
Marwan S M Al-Nimer
BACKGROUND: Epileptic children and adolescent have a significantly low serum level of vitamin D due to the effect of antiepileptic drugs on the vitamin D metabolism. Those patients are at risk of cardiovascular events. OBJECTIVE: This study aimed to show that epileptic patients who treated with antiepileptic drugs supplemented with vitamin D are free from the electrocardiograph changes compared with those treated with antiepileptic drugs. METHOD: This cross-sectional study included, 121 epileptic patients aged < 18 years of both genders with a history of idiopathic generalized tonic clonic seizure...
April 12, 2018: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/29651591/importance-of-qt-rr-hysteresis-correction-in-studies-of-drug-induced-qtc-interval-changes
#10
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/29650123/interplay-between-genetic-substrate-qtc-duration-and-arrhythmia-risk-in-patients-with-long-qt-syndrome
#11
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
#12
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/29643708/evidence-based-review-and-appraisal-of-the-use-of-droperidol-in-the-emergency-department
#13
REVIEW
Pei-Chun Lai, Yen-Ta Huang
Droperidol is a short-acting, potent dopamine D2 antagonist that can pass through the blood-brain barrier. A black box warning was issued for droperidol by the United States Food and Drug Administration in 2001 because of a risk of development of torsades de pointes induced by QT prolongation. Many experts feel that the incidence of arrhythmia is overestimated, and low-dose droperidol is almost always used by anesthesiologists for postoperative nausea and vomiting. In this review, we used evidence-based analysis to appraise high-quality studies with a low risk of bias published after 2001 on the use of droperidol in the emergency department (ED)...
January 2018: Ci Ji Yi Xue za Zhi, Tzu-chi Medical Journal
https://www.readbyqxmd.com/read/29642718/psychotropic-pharmacotherapy-associated-with-qt-prolongation-among-veterans-with-posttraumatic-stress-disorder
#14
Eileen M Stock, John E Zeber, Catherine J McNeal, Javier E Banchs, Laurel A Copeland
BACKGROUND: In 2012, the Food and Drug Administration issued Drug Safety Communications on several drugs associated with QT prolongation and fatal ventricular arrhythmias. Among these was citalopram, a selective serotonin reuptake inhibitor (SSRI) approved for depression and commonly used for posttraumatic stress disorder (PTSD). Evaluation of the risk for QT prolongation among other psychotropic drugs for individuals with PTSD remains limited. OBJECTIVE: Explore psychotropic drugs associated with QT prolongation among veterans with PTSD...
April 1, 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29627768/mitochondrial-ca-2-influx-contributes-to-arrhythmic-risk-in-nonischemic-cardiomyopathy
#15
An Xie, Zhen Song, Hong Liu, Anyu Zhou, Guangbin Shi, Qiongying Wang, Lianzhi Gu, Man Liu, Lai-Hua Xie, Zhilin Qu, Samuel C Dudley
BACKGROUND: Heart failure (HF) is associated with increased arrhythmia risk and triggered activity. Abnormal Ca2+ handling is thought to underlie triggered activity, and mitochondria participate in Ca2+ homeostasis. METHODS AND RESULTS: A model of nonischemic HF was induced in C57BL/6 mice by hypertension. Computer simulations were performed using a mouse ventricular myocyte model of HF. Isoproterenol-induced premature ventricular contractions and ventricular fibrillation were more prevalent in nonischemic HF mice than sham controls...
April 7, 2018: Journal of the American Heart Association
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
#16
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
#17
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/29621539/molecular-determinants-of-kv7-1-kcne1-channel-inhibition-by-amitriptyline
#18
Kathya Villatoro-Gómez, David O Pacheco-Rojas, Eloy G Moreno-Galindo, Ricardo A Navarro-Polanco, Martin Tristani-Firouzi, Dimitris Gazgalis, Meng Cui, José A Sánchez-Chapula, Tania Ferrer
Amitriptyline (AMIT) is a compound widely prescribed for psychiatric and non- psychiatric conditions including depression, migraine, chronic pain, and anorexia. However, AMIT has been associated with risks of cardiac arrhythmia and sudden death since it can induce prolongation of the QT interval on the surface electrocardiogram and torsade de pointes ventricular arrhythmia. These complications have been attributed to the inhibition of the rapid delayed rectifier potassium current (IKr ). The slow delayed rectifier potassium current (IKs ) is the main repolarizing cardiac current when IKr is compromised and it has an important role in cardiac repolarization at fast heart rates induced by an elevated sympathetic tone...
April 2, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29616317/outcomes-of-patients-with-myelofibrosis-treated-with-compassionate-use-pacritinib-a-sponsor-independent-international-study
#19
J Mascarenhas, E Virtgaym, M Stal, H Blacklock, A T Gerds, R Mesa, P Ganly, D Snyder, I Tabbara, D Tremblay, E Moshier
Myelofibrosis (MF) is a chronic yet progressive myeloid neoplasm in which only a minority of patients undergo curative therapy, hematopoietic stem cell transplantation. Ruxolitinib, a JAK1/2 inhibitor, is the lone therapy approved for MF, offering a clear symptom and spleen benefit at the expense of treatment-related cytopenias. Pacritinib (PAC), a multi-kinase inhibitor with specificity for JAK2, FLT3, and IRAK1 but sparing JAK1, has demonstrated clinical activity in MF with minimal myelosuppression. Due to an FDA-mandated full clinical hold, the randomized phase 3 PERSIST trials were abruptly stopped and PAC was immediately discontinued for all patients...
April 3, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29608498/cardioprotection-in-the-modern-era-of-cancer-chemotherapy
#20
Anuradha Godishala, Shu Yang, Aarti Asnani
The current arsenal of cancer chemotherapy is broad and rapidly expanding and includes conventional cytotoxic agents and targeted and immune-based therapies. As cancer survival rates have improved, the acute and latent cardiotoxicities of chemotherapy have emerged as important contributors to morbidity and mortality in cancer survivors. All chemotherapeutic agents have the potential for cardiac complications, with manifestations ranging from subclinical left ventricular dysfunction and asymptomatic QT prolongation, to congestive heart failure, myocardial ischemia, myocarditis, arrhythmia, and sudden cardiac death...
May 2018: Cardiology in Review
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