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Torsades de Pointes

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https://www.readbyqxmd.com/read/28527921/drug-induced-fatal-arrhythmias-acquired-long-qt-and-brugada-syndromes
#1
REVIEW
Isik Turker, Tomohiko Ai, Hideki Itoh, Minoru Horie
Since the early 1990s, the concept of primary "inherited" arrhythmia syndromes or ion channelopathies has evolved rapidly as a result of revolutionary progresses made in molecular genetics. Alterations in genes coding for membrane proteins such as ion channels or their associated proteins responsible for the generation of cardiac action potentials (AP) have been shown to cause specific malfunctions which eventually lead to cardiac arrhythmias. These arrhythmic disorders include congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, progressive cardiac conduction disease, etc...
May 17, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28525920/torsade-de-pointes-arrhythmias-arise-at-the-site-of-maximal-heterogeneity-of-repolarization-in-the-chronic-complete-atrioventricular-block-dog
#2
Albert Dunnink, Thom R G Stams, Alexandre Bossu, Veronique M F Meijborg, Jet D M Beekman, Sofieke C Wijers, Jacques M T De Bakker, Marc A Vos
Aims: The chronic complete atrioventricular block (CAVB) dog is highly sensitive for drug-induced torsade de pointes (TdP) arrhythmias. Focal mechanisms have been suggested as trigger for TdP onset; however, its exact mechanism remains unclear. In this study, detailed mapping of the ventricles was performed to assess intraventricular heterogeneity of repolarization in relation to the initiation of TdP. Methods and results: In 8 CAVB animals, 56 needles, each containing 4 electrodes, were inserted in the ventricles...
May 1, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28522677/synergistic-effect-of-dofetilide-and-mexiletine-on-prevention-of-atrial-fibrillation
#3
Guizhi Liu, Xiaolin Xue, Chuanyu Gao, Jiaqi Huang, Datun Qi, Yanzhou Zhang, Jian-Zeng Dong, Chang-Sheng Ma, Gan-Xin Yan
BACKGROUND: Although atrial fibrillation (AF) is the most common abnormal heart rhythm and its prevalence continues to rise, there is a marked paucity of effective and safe antiarrhythmic drugs for AF. This study was done to test whether combined use of dofetilide and mexiletine exhibits not only a synergistic effect on AF suppression but also a safer profile in drug-induced ventricular proarrhythmias. METHODS AND RESULTS: The effects of dofetilide plus mexiletine on atrial effective refractory period (ERP), AF inducibility, QT, and QT-related ventricular arrhythmias were studied using the isolated arterially perfused rabbit atrial and ventricular wedge preparations...
May 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28516454/a-multiscale-computational-modelling-approach-predicts-mechanisms-of-female-sex-risk-in-the-setting-of-arousal-induced-arrhythmias
#4
Pei-Chi Yang, Laura L Perissinotti, Fernando López-Redondo, Yibo Wang, Kevin R DeMarco, Mao-Tsuen Jeng, Igor Vorobyov, Robert D Harvey, Junko Kurokawa, Sergei Y Noskov, Colleen E Clancy
Female sex is a risk factor for inherited and acquired Long-QT associated Torsade de Pointes (TdP) arrhythmias, and sympathetic discharge is a major factor in triggering TdP in female Long-QT syndrome patients. We used a combined experimental and computational approach to predict 'the perfect storm' of hormone concentration, IKr block, and sympathetic stimulation that induces arrhythmia in females with inherited and acquired Long-QT. More specifically, we developed mathematical models of acquired and inherited Long-QT syndrome in male and female ventricular human myocytes by combining effects of a hormone and a hERG blocker dofetilide or hERG mutations...
May 18, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28511997/thorough-qt-tqt-studies-concordance-with-torsadogenesis-and-an-evolving-cardiac-safety-testing-paradigm
#5
Barbara Wiśniowska, Zofia Tylutki, Sebastian Polak
Since 2005, when the International Conference on Harmonisation (ICH) E14 guideline was adopted, no drug has been withdrawn because of QTc prolongation or torsade de pointes arrhythmia. There are, however, costs associated with this success. In addition to the time and money invested, thorough QT (TQT) studies have limited the efficiency of the drug development pipeline. In this paper, we discuss the relevance of TQT trials as a tool for proarrhythmic risk prediction as a part of the debate regarding their usefulness...
May 13, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28507587/an-unusual-etiology-of-torsade-de-pointes-induced-syncope
#6
Marco Morosin, Ermanno Dametto, Federica Del Bianco, Marco Brieda, Gian L Nicolosi
No abstract text is available yet for this article.
April 1, 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28496937/amiodarone-induced-third-degree-atrioventricular-block-and-extreme-qt-prolongation-generating-torsade-des-pointes-in-paroxysmal-atrial-fibrillation
#7
Orlando Robert Sequeira, Nelson Javier Aquino, Nancy Beatriz Gómez, Laura Beatriz García, Cristina Cáceres, Oscar A Lovera, Osmar Antonio Centurión
Amiodarone is still the most potent antiarrhythmic drug in the prevention of life threatening ventricular arrhythmias and demonstrates a very low incidence of torsade de pointes. An unusual case of an 81-year-old woman who developed serious abnormalities of the conduction system of the heart and torsade des pointes during intravenous infusion of amiodarone for the treatment of paroxysmal atrial fibrillation is described. To the best of our knowledge, this is the first case showing an association of intravenous amiodarone-induced third degree atrioventricular block and extreme QT interval prolongation generating torsade des pointes in a patient with paroxysmal atrial fibrillation who required an implantable cardioverter-defibrillator...
October 2016: Journal of Atrial Fibrillation
https://www.readbyqxmd.com/read/28494415/studies-on-curative-efficacy-of-monoterpene-eugenol-on-anti-leukemic-drug-arsenic-trioxide-induced-cardiotoxicity
#8
Prakash Binu, Nellikunnath Priya, Surendran Abhilash, Radhakrishnan Chandraprabha Vineetha, Raveendran Harikumaran Nair
BACKGROUND: Arsenic trioxide (As2O3) is emerging as a frontline agent for the treatment of acute promyelocytic leukemia (APL) but the therapeutic application is limited by its toxicity. QT prolongation, torsades de pointes and sudden cardiac death have been implicated in the As2O3 therapy. So eugenol is a monoterpene compound is well known for its antioxidant properties and protective effect on the cardiovascular system. OBJECTIVE: In this study, the cardioprotective effect of eugenol on cardiac electrical conductivity, tissue electrolytes, myocardial markers, antioxidant system, lipid peroxidation and nitric oxide production was investigated in male Wistar rats treated with arsenic trioxide...
May 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28491783/atrioventricular-block-and-pause-dependent-torsade-de-pointes
#9
Mustafa Dohadwala, Fayak Kamili, Na Mark Estes, Munther Homoud
No abstract text is available yet for this article.
February 2017: HeartRhythm Case Reports
https://www.readbyqxmd.com/read/28491728/a-case-of-takotsubo-cardiomyopathy-showing-two-modes-of-initiation-for-ventricular-fibrillation-augmented-j-wave-and-torsade-de-pointes-with-qt-prolongation
#10
Masato Shimizu, Mitsuhiro Nishizaki, Noriyoshi Yamawake, Hiroyuki Fujii, Harumizu Sakudara, Masayasu Hiraoka
No abstract text is available yet for this article.
September 2016: HeartRhythm Case Reports
https://www.readbyqxmd.com/read/28490617/systemic-inflammation-as-a-novel-qt-prolonging-risk-factor-in-patients-with-torsades-de-pointes
#11
Pietro Enea Lazzerini, Franco Laghi-Pasini, Iacopo Bertolozzi, Gabriella Morozzi, Sauro Lorenzini, Antonella Simpatico, Enrico Selvi, Maria Romana Bacarelli, Francesco Finizola, Francesca Vanni, Deana Lazaro, Ademuyiwa Aromolaran, Nabil El Sherif, Mohamed Boutjdir, Pier Leopoldo Capecchi
OBJECTIVE: Increasing evidence indicates systemic inflammation as a new potential cause of acquired long QT syndrome (LQTS), via cytokine-mediated changes in cardiomyocyte ion channels. Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia occurring in patients with LQTS, usually when multiple QT-prolonging factors are simultaneously present. Since classical risk factors cannot fully explain TdP events in a number of patients, we hypothesised that systemic inflammation may represent a currently overlooked risk factor contributing to TdP development in the general population...
May 10, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28486375/domperidone-for-lactation-what-health-care-providers-need-to-know
#12
Catherine A Sewell, Christina Y Chang, Miriam M Chehab, Christine P Nguyen
This commentary serves to raise health care provider awareness about the regulatory status and available evidence regarding domperidone for insufficient lactation. Breastfeeding provides significant health benefits for mothers and infants, and insufficient milk production remains the most common reason for early weaning. Domperidone, a dopamine receptor antagonist that may increase milk production, is not approved for any human use in the United States. It is approved in some countries for certain gastrointestinal disorders, but is not approved in any country for lactation enhancement...
May 5, 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28480041/risk-of-qt-prolongation-and-torsade-de-pointes-associated-with-exposure-to-hydroxyzine-re-evaluation-of-an-established-drug
#13
Anne-Françoise Schlit, Annie Delaunois, Aurore Colomar, Branderley Claudio, Luca Cariolato, Rossen Boev, Jean-Pierre Valentin, Christopher Peters, Victor S Sloan, Jürgen W G Bentz
Several noncardiac drugs have been linked to cardiac safety concerns, highlighting the importance of post-marketing surveillance and continued evaluation of the benefit-risk of long-established drugs. Here, we examine the risk of QT prolongation and/or torsade de pointes (TdP) associated with the use of hydroxyzine, a first generation sedating antihistamine. We have used a combined methodological approach to re-evaluate the cardiac safety profile of hydroxyzine, including: (1) a full review of the sponsor pharmacovigilance safety database to examine real-world data on the risk of QT prolongation and/or TdP associated with hydroxyzine use and (2) nonclinical electrophysiological studies to examine concentration-dependent effects of hydroxyzine on a range of human cardiac ion channels...
June 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28431243/cryo-em-structure-of-the-open-human-ether-%C3%A3-go-go-related-k-channel-herg
#14
Weiwei Wang, Roderick MacKinnon
The human ether-à-go-go-related potassium channel (hERG, Kv11.1) is a voltage-dependent channel known for its role in repolarizing the cardiac action potential. hERG alteration by mutation or pharmacological inhibition produces Long QT syndrome and the lethal cardiac arrhythmia torsade de pointes. We have determined the molecular structure of hERG to 3.8 Å using cryo-electron microscopy. In this structure, the voltage sensors adopt a depolarized conformation, and the pore is open. The central cavity has an atypically small central volume surrounded by four deep hydrophobic pockets, which may explain hERG's unusual sensitivity to many drugs...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28405995/recurrent-ventricular-tachycardia-due-to-long-qt-syndrome
#15
Rambabu Singh, Kshitiz Nath, Archana
Long QT syndrome (LQTS) is a rare inherited heart condition in which delayed repolarization of the heart following a heartbeat, increases the risk of episodes of Torsades de pointes (TdP, a form of irregular heartbeat that originates from the ventricles). These episodes may lead to palpitations, fainting, and sudden death due to ventricular fibrillation. Episodes may be provoked by various stimuli, depending on the subtype of the condition. We are reporting a case of 37 years old male whom we diagnosed to have long QT syndrome on the basis of clinical and ECG findings...
December 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28383310/short-term-variability-of-repolarization-is-superior-to-other-repolarization-parameters-in-the-evaluation-of-diverse-antiarrhythmic-interventions-in-the-chronic-av-block-dog
#16
A Bossu, R Varkevisser, Hdm Beekman, Mjc Houtman, Mag van der Heyden, M A Vos
Short-term variability (STV), to quantify beat-to-beat variability of repolarization (BVR), is a surrogate parameter that reliably identifies proarrhythmic risk in preclinical models. Examples include not only the use in the chronic atrioventricular block (CAVB) dog model whereby it was developed, but also in vulnerable patients with heart failure or drug-induced long QT syndrome. In the CAVB dog model, STV can specifically distinguish between safe and unsafe drugs in proarrhythmic screening. Conversely, this dog model also offers the possibility to evaluate antiarrhythmic strategies in a setting of Torsades de Pointes (TdP) induction with a standard IKr inhibitor...
March 31, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28364778/clinical-and-molecular-findings-in-a-moroccan-family-with-jervell-and-lange-nielsen-syndrome-a-case-report
#17
N Adadi, N Lahrouchi, R Bouhouch, I Fellat, R Amri, M Alders, A Sefiani, C Bezzina, I Ratbi
BACKGROUND: Jervell and Lange-Nielsen syndrome (Online Mendelian Inheritance in Man 220400) is a rare autosomal recessive cardioauditory ion channel disorder that affects 1/200,000 to 1/1,000,000 children. It is characterized by congenital profound bilateral sensorineural hearing loss, a long QT interval, ventricular tachyarrhythmias, and episodes of torsade de pointes on an electrocardiogram. Cardiac symptoms arise mostly in early childhood and consist of syncopal episodes during periods of stress, exercise, or fright and are associated with a high risk of sudden cardiac death...
April 2, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28363206/recent-developments-in-the-science-of-proarrhythmic-cardiac-safety-of-new-drugs
#18
J Rick Turner, Dilip R Karnad, Christopher H Cabell, Snehal Kothari
Following marketing withdrawals of several drugs due to proarrhythmic safety concerns, the ICH Guidelines S7B and E14 were released in 2005 and have guided pre-approval cardiac safety assessments in multiple regulatory jurisdictions. While this S7B-E14 paradigm has successfully prevented drugs with unanticipated potential for inducing Torsades de Pointes entering the market, it has unintentionally resulted in the termination of development programs for potentially important compounds that could have exhibited a favourable benefit-risk balance...
April 1, 2017: European Heart Journal. Cardiovascular Pharmacotherapy
https://www.readbyqxmd.com/read/28359306/clinicians-adherence-to-clinical-practice-guidelines-for-cardiac-function-monitoring-during-antipsychotic-treatment-a-retrospective-report-on-434-patients-with-severe-mental-illness
#19
Mirko Manchia, Giorgio Firinu, Bernardo Carpiniello, Federica Pinna
BACKGROUND: Severe mental illness (SMI) has considerable excess morbidity and mortality, a proportion of which is explained by cardiovascular diseases, caused in part by antipsychotic (AP) induced QT-related arrhythmias and sudden death by Torsade de Point (TdP). The implementation of evidence-based recommendations for cardiac function monitoring might reduce the incidence of these AP-related adverse events. To investigate clinicians' adherence to cardiac function monitoring before and after starting AP, we performed a retrospective assessment of 434 AP-treated SMI patients longitudinally followed-up for 5 years at an academic community mental health center...
March 31, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28335691/cases-of-drug-induced-torsade-de-pointes-a-review-of-belgian-cases-in-the-eudravigilance-database
#20
Eline Vandael, Bert Vandenberk, Joris Vandenberghe, Rik Willems, Veerle Foulon
OBJECTIVES: Post-marketing surveillance is very important, especially for rare adverse drug reactions like QTc-prolongation and Torsade de Pointes (TdP). The objective of this study was to investigate the characteristics of Belgian cases of drug-related TdP reported in the EudraVigilance database. METHODS: The EudraVigilance database was searched for Belgian post-marketing cases of TdP reported between December 2001-April 2015. These cases were identified with MedDRA preferred terms...
March 24, 2017: Acta Clinica Belgica
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