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https://www.readbyqxmd.com/read/28089740/early-remodeling-of-repolarizing-k-currents-in-the-%C3%AE-mhc-403-mouse-model-of-familial-hypertrophic-cardiomyopathy
#1
Rocco Hueneke, Adam Adenwala, Rebecca L Mellor, Jonathan G Seidman, Christine E Seidman, Jeanne M Nerbonne
Familial hypertrophic cardiomyopathy (HCM), linked to mutations in myosin, myosin-binding proteins and other sarcolemmal proteins, is associated with increased risk of life threatening ventricular arrhythmias, and a number of animal models have been developed to facilitate analysis of disease progression and mechanisms. In the experiments here, we use the αMHC(403/+) mouse line in which one αMHC allele harbors a common HCM mutation (in βMHC, Arg403 Gln). Here, we demonstrate marked prolongation of QT intervals in young adult (10-12week) male αMHC(403/+) mice, well in advance of the onset of measurable left ventricular hypertrophy...
January 12, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28087566/application-of-whole-exome-sequencing-in-the-clinical-diagnosis-and-management-of-inherited-cardiovascular-diseases-in-adults
#2
Sara B Seidelmann, Emily Smith, Lakshman Subrahmanyan, Daniel Dykas, Maen D Abou Ziki, Bani Azari, Fady Hannah-Shmouni, Yuexin Jiang, Joseph G Akar, Mark Marieb, Daniel Jacoby, Allen E Bale, Richard P Lifton, Arya Mani
BACKGROUND: With the advent of high throughput sequencing, the identification of genetic causes of cardiovascular disease (CVD) has become an integral part of medical diagnosis and management and at the forefront of personalized medicine in this field. The use of whole exome sequencing for clinical diagnosis, risk stratification, and management of inherited CVD has not been previously evaluated. METHODS AND RESULTS: We analyzed the results of whole exome sequencing in first 200 adult patients with inherited CVD, who underwent genetic testing at the Yale Program for Cardiovascular Genetics...
February 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28073690/citrate-pathophysiology-and-metabolism
#3
REVIEW
Mehran Monchi
By chelating ionized calcium, citrate allows extracorporeal circuit anticoagulation without a bleeding risk for the patient. Citrate anticoagulation is also associated with a reduced activation of leucocytes and platelets. Citrate clearance by citric acid cycle (Krebs cycle) is not modified by renal failure, but is reduced by about 50% in patients with cirrhosis. Toxic effects of citrate result from a decrease in plasma ionized calcium of the patient. The first side effect is a prolongation of the QT interval...
December 30, 2016: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28073687/adverse-event-detection-using-the-fda-post-marketing-drug-safety-surveillance-system-cardiotoxicity-associated-with-loperamide-abuse-and-misuse
#4
Kimberley A Swank, Eileen Wu, Cindy Kortepeter, Jana McAninch, Robert L Levin
OBJECTIVE: The purpose of this investigation was to identify and characterize post-marketing reports of cardiotoxicity, including torsades de pointes (TdP), associated with loperamide use. METHODS: We searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database for post-marketing reports of serious cardiac adverse events associated with loperamide use from December 28, 1976 (U.S. drug approval date), through December 14, 2015. We also conducted a Pubmed and Google Scholar search to identify additional published reports of cardiotoxicity associated with loperamide in the medical literature through February 11, 2016...
January 7, 2017: Journal of the American Pharmacists Association: JAPhA
https://www.readbyqxmd.com/read/28071178/psychotropic-drugs-and-ventricular-repolarisation-the-effects-on-qt-interval-t-peak-to-t-end-interval-and-qt-dispersion
#5
Tiziano Acciavatti, Giovanni Martinotti, Mariangela Corbo, Eduardo Cinosi, Matteo Lupi, Fabrizio Ricci, Rosa Di Scala, Emilia D'Ugo, Viola De Francesco, Raffaele De Caterina, Massimo di Giannantonio
OBJECTIVE: We aimed to investigate in a clinical setting, the effects of different classes of psychotropic drugs on cardiac electrophysiological measures linked with an increased risk of sudden cardiac death. METHODS: We conducted a cross-sectional study in a population of 1059 psychiatric inpatients studying the effects of various psychotropic drugs on the T-peak to T-end (TpTe) interval, QT dispersion and QT interval. RESULTS: Methadone use showed a strong association with TpTe prolongation (odds ratio (OR)=12...
January 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28070113/pharmacological-characterization-of-microminipig-as-a-model-to-assess-the-drug-induced-cardiovascular-responses-for-non-clinical-toxicity-and-or-safety-pharmacology-studies
#6
Hirofumi Yokoyama, Yuji Nakamura, Hiroyuki Saito, Yukitoshi Nagayama, Kiyotaka Hoshiai, Takeshi Wada, Hiroko Izumi-Nakaseko, Kentaro Ando, Yasuki Akie, Atsushi Sugiyama
We tried to establish the halothane-anesthetized microminipigs as an alternative animal model for non-clinical toxicity and/or safety pharmacology studies. In order to characterize the halothane-anesthetized microminipigs, we firstly clarified the effects of halothane anesthesia on their cardiovascular system (n = 5). Then, we examined the cardiovascular effects of dl-sotalol in doses of 0.1, 0.3 and 1 mg/kg, i.v. on the halothane-anesthetized microminipigs (n = 6). Induction of the halothane anesthesia by itself prolonged the QT interval as well as QTcF, suggesting that the halothane anesthesia can reduce the cardiac repolarization reserve in microminipigs like in dogs...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28062938/mineral-metabolism-and-cardiovascular-disease-in-ckd
#7
REVIEW
Hideki Fujii, Nobuhiko Joki
The mineral bone disorder of CKD, called Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), has a major role in the etiology and progression of cardiovascular disease in CKD patients. Since the main emphasis in CKD-MBD is on three categories (bone abnormalities, laboratory abnormalities, and vascular calcifications), we have routinely accepted ectopic cardiovascular calcifications as a central risk factor in the pathophysiology of CKD-MBD for cardiac events. However, recent compelling evidence suggests that some CKD-MBD-specific factors other than vascular calcification might contribute to the onset of cardiovascular disease...
January 6, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28052945/ecg-changes-in-hyperemesis-gravidarum
#8
Sophie Jessica Mitchell, Patricia Cox
This is a case report of a 30-year-old patient presenting at advanced gestation with hyperemesis, who developed a prolonged QT interval secondary to electrolyte imbalance during recovery. This potentially fatal complication should be considered in all patients with hyperemesis gravidarum, especially after a prolonged period of starvation. We hope to highlight the importance of ECG monitoring and careful prescribing in such cases, something that is not considered in current guidelines.
January 4, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28043860/differential-heart-rate-variability-and-physiological-responses-associated-with-accumulated-short-and-long-term-stress-in-rodents
#9
Sunghee E Park, Dajeong Park, Kang-Il Song, Joon-Kyung Seong, Seok Chung, Inchan Youn
In this study, we tested the hypothesis that chronic stress has cumulative effects over time on heart rate variability (HRV) and physiological responses in a rodent model of chronic mild stress. Rats were exposed to either short-term (2weeks) or long-term (4weeks) stress, followed by a 1-week recovery period. Controls were normally housed rats that did not undergo the stress procedure. For electrocardiogram recordings, transmitters were implanted in all rats 10days before the onset of the experiment to allow recovery from surgery...
December 30, 2016: Physiology & Behavior
https://www.readbyqxmd.com/read/28043059/determining-factors-of-electrocardiographic-abnormalities-in-patients-with-epilepsy-a-case-control-study
#10
Jorge Murilo Barbosa de Sousa, Guilherme Loureiro Fialho, Peter Wolf, Roger Walz, Katia Lin
Sudden unexpected death in epilepsy (SUDEP) is a major cause of mortality in young patients with epilepsy (PWE). Although its mechanisms are still poorly understood, they may include cardiorespiratory dysfunction. Standard 12-lead electrocardiograms (ECGs) were obtained from 62 consecutive patients (aged 18-66y) with a definite diagnosis of epilepsy, without seizures at the day of ECG, and 57 healthy controls matched for sex, age and body mass index (BMI). All ECGs were evaluated by a blinded board-certified cardiologist...
December 20, 2016: Epilepsy Research
https://www.readbyqxmd.com/read/28039329/a-genome-wide-interaction-analysis-of-tricyclic-tetracyclic-antidepressants-and-rr-and-qt-intervals-a-pharmacogenomics-study-from-the-cohorts-for-heart-and-aging-research-in-genomic-epidemiology-charge-consortium
#11
Raymond Noordam, Colleen M Sitlani, Christy L Avery, James D Stewart, Stephanie M Gogarten, Kerri L Wiggins, Stella Trompet, Helen R Warren, Fangui Sun, Daniel S Evans, Xiaohui Li, Jin Li, Albert V Smith, Joshua C Bis, Jennifer A Brody, Evan L Busch, Mark J Caulfield, Yii-Der I Chen, Steven R Cummings, L Adrienne Cupples, Qing Duan, Oscar H Franco, Rául Méndez-Giráldez, Tamara B Harris, Susan R Heckbert, Diana van Heemst, Albert Hofman, James S Floyd, Jan A Kors, Lenore J Launer, Yun Li, Ruifang Li-Gao, Leslie A Lange, Henry J Lin, Renée de Mutsert, Melanie D Napier, Christopher Newton-Cheh, Neil Poulter, Alexander P Reiner, Kenneth M Rice, Jeffrey Roach, Carlos J Rodriguez, Frits R Rosendaal, Naveed Sattar, Peter Sever, Amanda A Seyerle, P Eline Slagboom, Elsayed Z Soliman, Nona Sotoodehnia, David J Stott, Til Stürmer, Kent D Taylor, Timothy A Thornton, André G Uitterlinden, Kirk C Wilhelmsen, James G Wilson, Vilmundur Gudnason, J Wouter Jukema, Cathy C Laurie, Yongmei Liu, Dennis O Mook-Kanamori, Patricia B Munroe, Jerome I Rotter, Ramachandran S Vasan, Bruce M Psaty, Bruno H Stricker, Eric A Whitsel
BACKGROUND: Increased heart rate and a prolonged QT interval are important risk factors for cardiovascular morbidity and mortality, and can be influenced by the use of various medications, including tricyclic/tetracyclic antidepressants (TCAs). We aim to identify genetic loci that modify the association between TCA use and RR and QT intervals. METHODS AND RESULTS: We conducted race/ethnic-specific genome-wide interaction analyses (with HapMap phase II imputed reference panel imputation) of TCAs and resting RR and QT intervals in cohorts of European (n=45 706; n=1417 TCA users), African (n=10 235; n=296 TCA users) and Hispanic/Latino (n=13 808; n=147 TCA users) ancestry, adjusted for clinical covariates...
December 30, 2016: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28033168/is-cardiovascular-risk-a-concern-when-prescribing-azithromycin
#12
S Scott Sutton
The FDA has updated azithromycin package labeling to include the risk of prolonged cardiac repolarization and QT prolongation, which increase the possibility of cardiac dysrhythmias and torsades de pointes, especially in older adults. The update was initiated by a study that found an increased risk of death in patients taking azithromycin compared with those taking amoxicillin. However, cardiovascular results of other azithromycin studies have demonstrated discordant results, and more research is needed. In the meantime, providers should recognize that azithromycin has a role in the management of bacterial infections and should prescribe the antibiotic when warranted...
January 2017: JAAPA: Official Journal of the American Academy of Physician Assistants
https://www.readbyqxmd.com/read/28024277/qt-prolongation-caused-by-insulin-induced-hypoglycaemia-an-interventional-study-in-119-individuals
#13
Stella Kacheva, Beate Karges, Katrin Göller, Nikolaus Marx, Karl Mischke, Wolfram Karges
AIMS: Hypoglycaemia is associated with increased risk of cardiovascular events and mortality in patients with diabetes, but the extent and mechanisms of this link are ill defined. We here prospectively studied cardiac repolarization abnormalities during insulin-induced hypoglycaemia in humans. METHODS: 119 individuals (69 males, age 47.5±13.4years, range 18-82years) were assessed during hypoglycaemia after the injection of 0.1-0.25units/kg human insulin. Corrected QT intervals (QTc) and QT dispersion (QTd) were calculated from serially recorded twelve lead electrocardiograms, and plasma glucose and other endocrine markers were studied...
December 3, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28012712/unintended-consequences-of-adjusting-citalopram-prescriptions-following-the-2011-fda-warning
#14
Lauren B Gerlach, Helen C Kales, Donovan T Maust, Claire Chiang, Claire Stano, Hae Mi Choe, Kara Zivin
OBJECTIVES: In 2011, the U.S. Food and Drug Administration (FDA) issued a safety announcement cautioning providers against prescribing citalopram above 40 mg per day given concerns for QT prolongation. We assessed the impact of a health system quality improvement initiative to identify patients taking higher than the recommended dose of citalopram. DESIGN: Retrospective cohort study. SETTING: Nine primary care clinics within the University of Michigan from March 2012 to February 2013...
November 18, 2016: American Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28011953/hyperventilation-assists-proarrhythmia-development-during-delayed-repolarization-in-clofilium-treated-anaesthetized-mechanically-ventilated-rabbits
#15
H Papp, A Sarusi, A S Farkas, H Takacs, P Kui, D Vincze, E Ivany, A Varro, J G Papp, T Forster, A Farkas
Hyperventilation reduces partial pressure of CO2 (PCO2) in the blood, which results in hypokalaemia. Hypokalaemia helps the development of the life-threatening torsades de pointes type ventricular arrhythmia (TdP) evoked by repolarization delaying drugs. This implies that hyperventilation may assist the development of proarrhythmic events. Therefore, this study experimentally investigated the effect of hyperventilation on proarrhythmia development during delayed repolarization. Phenylephrine (an α1-adrenoceptor agonist) and clofilium (as a representative repolarization delaying agent inhibiting the rapid component of the delayed rectifier potassium current, IKr) were administered intravenously to pentobarbital-anaesthetized, mechanically ventilated, open chest rabbits...
October 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28009315/differences-in-ecg-characteristics-and-co-morbidities-among-patients-who-underwent-elective-surgical-repair
#16
I Botchorishvili, N Sharashidze, N Pargalava, Z Pagava, G Saatashvili
The aim of the study was to assess differences in ECG features and prevalence of comorbidies between two groups of patiens: with Abdominal Aortic Aneurism (AAA) and Aorto-Iliac Occlusive Desieses-Lerish Syndrome (LS). Data was collected for all consecutive adult patients who underwent elective surgical repair of AAA (fusiform aneurysm) or LS at "The Center of Vascular and Heart Diseases" (Tbilisi, Georgia) between 2010 and 2014. We studied a prevalence of Arterial Hypertension (AHT); Diabetes mellitus (DM); Renal Failure (RF),Peripheral Artery Disease (PAD), Coronary Artery Disease (CAD) and rate of coronary revascularization in these patients; We also, investigate some of the electrocariographic characteristics: Corrected QT interval(QTC),QT dispersion(QTD)...
November 2016: Georgian Medical News
https://www.readbyqxmd.com/read/28007405/ephedrine-treatment-for-autoimmune-myasthenia-gravis
#17
Alexander F Lipka, Charlotte Vrinten, Erik W van Zwet, Kirsten J M Schimmel, Martina C Cornel, Marja R Kuijpers, Yechiel A Hekster, Stephanie S Weinreich, Jan J G M Verschuuren
We studied the effect and safety of ephedrine as add-on treatment for patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG), who do not sufficiently respond to standard treatment. Four patients with AChR MG were included in a placebo-controlled, double-blind, and randomised, multiple crossover series of n-of-1 trials. Each n-of-1 trial consisted of 3 cycles, in which two 5-day intervention periods were followed by 2 days washout. In each cycle, ephedrine 50 mg daily in 2 doses was compared with placebo in the alternate treatment period...
November 18, 2016: Neuromuscular Disorders: NMD
https://www.readbyqxmd.com/read/28007118/rapidly-progressive-cataract-formation-associated-with-non-small-cell-lung-cancer-therapy
#18
Erica Liu, Kamden Kopani
: We report 6 patients who developed rapidly progressive hypermature cataracts after starting treatment with rociletinib, a non-small-cell lung cancer therapy with known side effects of hyperglycemia, fatigue, and prolonged QT. Early cataract detection and surgery may prevent complications during future cataract removal. Although rociletinib development has been suspended, there are patients who have been treated and will continue to be treated with this medication based on their physician's judgment...
December 2016: Journal of Cataract and Refractive Surgery
https://www.readbyqxmd.com/read/28003052/population-pharmacokinetic-pharmacodynamic-analysis-to-compare-the-effect-of-moxifloxacin-on-qt-interval-prolongation-between-healthy-korean-and-japanese-subjects
#19
Hyang-Ki Choi, Jin Ah Jung, Tomoe Fujita, Hideki Amano, Jong-Lyul Ghim, Dong-Hwan Lee, Kenichi Tabata, Il-Dae Song, Mika Maeda, Yuji Kumagai, Boaz Mendzelevski, Jae-Gook Shin
PURPOSE: The goal of this study was to evaluate the moxifloxacin-induced QT interval prolongation in healthy male and female Korean and Japanese volunteers to investigate interethnic differences. METHODS: This multicenter, randomized, double-blind, placebo-controlled, 2-way crossover study was conducted in healthy male and female Korean and Japanese volunteers. In each period, a single dose of moxifloxacin or placebo 400 mg was administered orally under fasting conditions...
December 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/28000393/prediction-of-herg-liability-using-svm-classification-bootstrapping-and-jackknifing
#20
Hongmao Sun, Ruili Huang, Menghang Xia, Sampada Shahane, Noel Southall, Yuhong Wang
Drug-induced QT prolongation leads to life-threatening cardiotoxicity, mostly through blockage of the human ether-à-go-go-related gene (hERG) encoded potassium ion (K(+) ) channels. The hERG channel is one of the most important antitargets to be addressed in the early stage of drug discovery process, in order to avoid more costly failures in the development phase. Using a thallium flux assay, 4,323 molecules were screened for hERG channel inhibition in a quantitative high throughput screening (qHTS) format...
December 21, 2016: Molecular Informatics
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