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Torsades de Pointes

Sahan P Semasinghe Bandaralage, Selvanayagam Nirthanan, Selvanayagam Niranjan
Despite proven effectiveness in treating tachyarrhythmias, sotalol is proarrhythmic and can cause torsades de pointes. Given the emergence of studies that show no benefit from rhythm control strategies in managing atrial fibrillation, as well as the introduction of nonpharmacological approaches to treating arrhythmias, we felt it necessary to ascertain if there was any role for sotalol given its side effects. Review of the literature regarding sotalol use in the prevention and treatment of supraventricular and ventricular tachyarrhythmias seems to show that more effective and safer agents and nonpharmacological alternatives are currently available...
October 3, 2016: American Journal of Therapeutics
Altuğ Ösken, Nizamettin Selçuk Yelgeç, Regayip Zehir, Tuğba Kemaloğlu Öz, Selçuk Yaylacı, Ramazan Akdemir, Hüseyin Gündüz
Drug-induced torsades de pointes (TdP) is a rare but potentially fatal adverse effect of commonly prescribed medications including cardiac and noncardiac drugs. Importantly, many drugs have been reported to cause the characteristic Brugada syndrome-linked electrocardiography (ECG) abnormalities and/or (fatal) ventricular tachyarrhythmias. Chlorpheniramine and propranolol have the arrhythmogenic effects reported previously. A review of literature revealed a large number of case reports of chlorpheniramine or propranolol use resulting in QTc prolongation, TdP, or both...
July 2016: Indian Journal of Pharmacology
Yusuke Fujii, Hideki Itoh, Seiko Ohno, Takashi Murayama, Nagomi Kurebayashi, Hisaaki Aoki, Malorie Blancard, Yoshihisa Nakagawa, Satoshi Yamamoto, Yumie Matsui, Mari Ichikawa, Keiko Sonoda, Tomoya Ozawa, Kimie Ohkubo, Ichiro Watanabe, Pascale Guicheney, Minoru Horie
BACKGROUND: Ventricular fibrillation (VF) may be caused by premature ventricular contractions (PVCs) whose coupling intervals are under 300ms, a characteristic of scTdP. OBJECTIVE: The purpose of this study is to analyze the underlying RyR2 variants in patients with the short-coupled variant of torsade de pointes (scTdP). METHODS: Seven patients with scTdP (34±12 years old, 3 females) were enrolled in this study. The RyR2 gene was screened by targeted gene sequencing methods, and variant minor allele frequency (MAF) was confirmed in three databases, and the pathogenicity was investigated in multiple in silico tools...
October 15, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Zaid Altheeb, Moayyad Alziadat, Fayez Shamoon
No abstract text is available yet for this article.
October 12, 2016: American Journal of Therapeutics
Tiffany Healey, Clifford Buckley, Matthew Mollman
BACKGROUND: Brugada syndrome is a genetic disorder that increases an individual's risk for sudden cardiac death and ventricular dysrhythmias that was first described by the Brugada brothers in 1992. Brugada syndrome is characterized by an atypical electrocardiogram pattern that includes a bundle branch block and ST-segment elevation in the precordial leads. CASE REPORT: A 74-year-old man had a cardiac arrest at the time of a low-speed motor vehicle collision. When emergency medical services arrived, the patient was in torsades de pointes...
October 14, 2016: Journal of Emergency Medicine
Shegu Gilbert, Devender Singh, M Lawrance Jesuraj
Severe QT interval prolongation >500ms occurs in one quarter of cardiac surgical patients in the perioperative period while moderate prolongation occurs in most of them. Prolonged QT interval may be associated with torsades de pointes and lead to sudden cardiac death. Because of the high incidence of prolonged QT in cardiac surgery patients and its perioperative adverse outcomes, it is vital to identify it early and take necessary precautions. We report and discuss the catastrophic events and management of two patients with long QT syndrome complicating mitral valve replacement...
September 2016: Indian Heart Journal
Steven P Sears, Trevor W Getz, Christopher O Austin, William C Palmer, Evelyn A Boyd, Fernando F Stancampiano
BACKGROUND: Azithromycin has been associated with abnormalities of cardiac repolarization and development of torsades de pointes. Observational data suggest that the risk of death from cardiovascular causes is increased in patients taking azithromycin. Little is known regarding the risk of ventricular arrhythmia in patients with prolongation of the corrected QT interval who receive azithromycin. OBJECTIVE: The purpose of this study was to determine the incidence of sustained ventricular tachycardia in patients with prolonged corrected QT (QTc) who subsequently received azithromycin...
March 2016: Drugs—Real World Outcomes
Frank F Vincenzi, Philippe Lunetta
While SCUBA diving, a 44-year-old Caucasian patient had an abnormal cardiac rhythm, presumably Torsade de Pointes (TdP), during the initial descent to depth. Upon surfacing, she developed ventricular fibrillation and died. The patient had been treated for mild depression for nearly a year with citalopram 60 mg per day, a drug known to cause prolonged QT interval. She had also been treated with two potentially hepatotoxic drugs. Liver impairment causes selective loss of cytochrome P450 (CYP) 2C19 activity, the major pathway for metabolism of citalopram...
December 2015: Drug Saf Case Rep
Hiroko Izumi-Nakaseko, Yuji Nakamura, Xin Cao, Takeshi Wada, Kentaro Ando, Atsushi Sugiyama
Since an antipsychotic drug haloperidol has been clinically reported to induce QT interval prolongation and torsade de pointes, in this study its risk stratification for the onset of torsade de pointes was performed by using the chronic atrioventricular block canine model with a Holter electrocardiogram. Haloperidol in a dose of 3 mg kg(-1) p.o. prolonged the QT interval, but it did not induce torsade de pointes during the observation period of 21 h (n = 4), indicating that the dose would be safe. Meanwhile, haloperidol in a dose of 30 mg kg(-1) p...
October 13, 2016: Cardiovascular Toxicology
Yibo Wang, Jiqing Guo, Laura L Perissinotti, James Lees-Miller, Guoqi Teng, Serdar Durdagi, Henry J Duff, Sergei Yu Noskov
Mutations that reduce inactivation of the voltage-gated Kv11.1 potassium channel (hERG) reduce binding for a number of blockers. State specific block of the inactivated state of hERG block may increase risks of drug-induced Torsade de pointes. In this study, molecular simulations of dofetilide binding to the previously developed and experimentally validated models of the hERG channel in open and open-inactivated states were combined with voltage-clamp experiments to unravel the mechanism(s) of state-dependent blockade...
October 12, 2016: Scientific Reports
Sayaka Sasaoka, Toshinobu Matsui, Yuuki Hane, Junko Abe, Natsumi Ueda, Yumi Motooka, Haruna Hatahira, Akiho Fukuda, Misa Naganuma, Shiori Hasegawa, Yasutomi Kinosada, Mitsuhiro Nakamura
Long QT syndrome (LQTS) is a disorder of the heart's electrical activity that infrequently causes severe ventricular arrhythmias such as a type of ventricular tachycardia called torsade de pointes (TdP) and ventricular fibrillation, which can be fatal. There have been no previous reports on the time-to-onset for LQTS based on data from spontaneous reporting systems. The aim of this study was to assess the time-to-onset of LQTS according to drug treatment. We analyzed the association between 113 drugs in 37 therapeutic categories and LQTS including TdP using data obtained from the Japanese Adverse Drug Event Report database...
2016: PloS One
Barbara Wiśniowska, Sebastian Polak
This review aims to present and compare various Torsade de pointes propensity classification schemes of drugs that are publicly available from many scientific sources. We have also tracked and listed the compounds that were differently categorized. Additionally, we would like to draw attention to the need for establishing a general, standardized classification of a drug's proarrhythmic propensity. This is especially important in the current drug development process because of the changing paradigm of drug cardiac safety assessment...
October 4, 2016: Drug Discovery Today
Pietro Enea Lazzerini, Pier Leopoldo Capecchi, Iacopo Bertolozzi, Gabriella Morozzi, Sauro Lorenzini, Antonella Simpatico, Enrico Selvi, Maria Romana Bacarelli, Maurizio Acampa, Deana Lazaro, Nabil El-Sherif, Mohamed Boutjdir, Franco Laghi-Pasini
Mounting evidence indicates that in chronic inflammatory arthritis (CIA), QTc prolongation is frequent and correlates with systemic inflammatory activation. Notably, basic studies demonstrated that inflammatory cytokines induce profound changes in potassium and calcium channels resulting in a prolonging effect on cardiomyocyte action potential duration, thus on the QT interval on the electrocardiogram. Moreover, it has been demonstrated that in rheumatoid arthritis (RA) patients, the risk of sudden cardiac death is significantly increased when compared to non-RA subjects...
2016: Frontiers in Cardiovascular Medicine
Ksenia Blinova, Jayna Stohlman, Jose Vicente, Dulciana Chan, Lars Johannesen, Maria P Hortigon-Vinagre, Victor Zamora, Godfrey Smith, William J Crumb, Li Pang, Beverly Lyn-Cook, James Ross, Mathew Brock, Stacie Chvatal, Daniel Millard, Loriano Galeotti, Norman Stockbridge, David G Strauss
BACKGROUND: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) hold promise for assessment of drug-induced arrhythmias and are being considered for use under the Comprehensive in Vitro Proarrhythmia Assay (CiPA). METHODS AND RESULTS: We studied the effects of 26 drugs and 3 drug combinations on two commercially available iPSC-CM types using high-throughput voltage-sensitive dye (VSD) and microelectrode-array (MEA) assays being studied for the Comprehensive in Vitro Proarrhythmia Assessment (CiPA) initiative and compared the results to clinical QT prolongation and torsade de pointes (TdP) risk...
October 3, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
I Stankovic, B Putnikovic, A N Neskovic
No abstract text is available yet for this article.
2016: Acta Cardiologica
Trusha C Dhanani, Emily H Mantovani, J Rick Turner
All biologically active agents carry the potential to lead to adverse reactions in certain individuals, including serious cardiac adverse reactions. Since 2005, there has been an international regulatory landscape governing the investigation of a new drug's propensity to lead to the polymorphic ventricular tachycardia Torsades de Pointes (Torsades), a rare but potentially fatal occurrence. When a regulatory agency considers it appropriate, warning information is placed in a medicine's patient information leaflet (label) concerning drug-induced QT interval prolongation, a phenomenon associated with Torsades...
September 28, 2016: International Journal of Pharmacy Practice
Jaclyn R Moeller, David D Gummin, Tom J Nelson, Amy L Drendel, Breanne K Shah, Stuart Berger
OBJECTIVES: To evaluate the use of ondansetron in a tertiary care pediatric health system, assess the incidence of ventricular tachyarrhythmia within 24 hours of ondansetron, and identify the characteristics of children experiencing a ventricular tachyarrhythmia after ondansetron, to identify potential risk factors. STUDY DESIGN: This retrospective chart review identified children ≤18 years of age who received ondansetron within 24 hours prior to a ventricular tachyarrhythmia...
September 21, 2016: Journal of Pediatrics
Michelle Quinlan, Jocelyn Zhou, Eunju Hurh, Dalila Sellami
PURPOSE: Sonidegib prevents activation of the Hedgehog signal transduction pathway. This PK-QT analysis has been performed to test for potential prolongation of the QT/QTc interval during extended use, and to understand the exposure-QT relationship for sonidegib in patients and in healthy volunteers (HV). METHODS: A pooled analysis of the change in QT interval corrected for heart rate according to Fridericia's formula was conducted across four patient studies from a total of 341 patients (n = 211, 102, 21, and 7 from the phase II pivotal study A2201, study X2101, study X1101, and study B2209, respectively), and across four healthy volunteer studies from a total of 204 healthy volunteers (n = 146, 36, 16, and 6 from study A2114, study A1102, study A2108, and study A2110, respectively)...
September 23, 2016: European Journal of Clinical Pharmacology
Ehud Chorin, Aviram Hochstadt, Sami Viskin, Uri Rozovski, Ofer Havakuk, Adrian Baranchuk, Andres Enriquez, Boris Strasberg, Milton E Guevara-Valdivia, Manlio F Márquez, Héctor González-Pacheco, Can Hasdemir, Raphael Rosso
BACKGROUND: Female gender increases the risk of torsades de pointes (TdP) in the long QT syndrome, and this increased risk is assumed to be due to their longer QT interval. OBJECTIVE: The purpose of this study was to study the interplay between gender, duration of the QT interval, and risk of TdP during AV block. METHODS: We studied 250 patients (48% women) with AV block. QT interval was measured at the time of most severe bradycardia. We then constructed different receiver operating characteristic curves for the QTc of males and females for predicting TdP...
September 17, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Zhaokang Yang, Hannah Kirton, Moza Al-Owais, Jerôme Thireau, Sylvain Richard, Derek Steele, Chris Peers
AIMS: In the heart, β<sub>1</sub>-adrenergic signaling involves cyclic adenosine monophosphate (cAMP) acting via both protein kinase-A (PKA) and 'exchange protein directly activated by cAMP' (Epac): a guanine nucleotide exchange factor for the small GTPase Rap1. Inhibition of Epac-Rap1 signaling has been proposed as a therapeutic strategy for both cancer and cardiovascular disease. However, previous work suggests that impaired Rap1 signaling may have detrimental effects on cardiac function...
September 21, 2016: Antioxidants & Redox Signaling
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