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torsade de pointes

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https://www.readbyqxmd.com/read/29330129/estradiol-up-regulates-l-type-ca2-channels-via-membrane-bound-estrogen-receptor-phosphoinositide-3kinase-akt-camp-response-element-binding-protein-signaling-pathway
#1
Xiaoyan Yang, Xiaofang Mao, Gao Xu, Shasha Xing, Ansuman Chattopadhyay, Si Jin, Guy Salama
BACKGROUND: In long QT type-2 (LQT2), women are more prone to lethal arrhythmias called Torsade de Pointes (TdP) than men. We previously reported that 17-β-estradiol (E2) upregulates L-type Ca2+-channels and current (ICa,L) (∼30%) in rabbit ventricular myocytes by a classical genomic-mechanism mediated by estrogen-receptor-α (ER)α. In LQT2 ( IKr-blockade or bradycardia), the higher Ca2+ influx via ICa,L, causes Ca2+-overload, spontaneous sarcoplasmic reticulum Ca2+-release, and re-activation of ICa,L that trigger early afterdepolarizations (EADs) and TdP...
January 9, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/29317399/effect-of-a-single-dose-of-i-v-ondansetron-on-qtc-interval-in-emergency-department-patients
#2
Kai Li, Kathy Vo, Byron K Lee, Newton Addo, Zlatan Coralic
PURPOSE: Results of a study to determine whether i.v. administration of a single dose of 4 mg of ondansetron was associated with QT interval prolongation in emergency department (ED) patients are reported. METHODS: In a prospective observational study conducted at an urban academic medical center ED, a convenience sample of adult ED patients treated with ondansetron 4 mg i.v. were enrolled. A 12-lead electrocardiogram (ECG) was obtained immediately before and 5 minutes after ondansetron administration...
January 9, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29298624/approach-to-initiating-qt-prolonging-oncology-drugs-in-the-ambulatory-setting
#3
Mário L de Lemos, Carrie Kung, Victoria Kletas, Nadine Badry, Isabell Kang
Since the introduction of regulatory drug approval guidance on the evaluation of QT interval prolongation, an increasing number of drug monographs has included cautions on the risk of QT prolongation. For example, QT prolongation is mentioned in the Canadian product monographs of 29 drugs commonly seen in oncology practice. This presents two major challenges. First, most guidelines and risk predictive tools for QT prolongation have been developed for hospitalized patients in acute care settings. In contrast, most QT-prolonging oncology drugs are used in medically stable patients in the ambulatory setting...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29297274/development-of-models-for-predicting-torsade-de-pointes-cardiac-arrhythmias-using-perceptron-neural-networks
#4
Mohsen Sharifi, Dan Buzatu, Stephen Harris, Jon Wilkes
BACKGROUND: Blockage of some ion channels and in particular, the hERG (human Ether-a'-go-go-Related Gene) cardiac potassium channel delays cardiac repolarization and can induce arrhythmia. In some cases it leads to a potentially life-threatening arrhythmia known as Torsade de Pointes (TdP). Therefore recognizing drugs with TdP risk is essential. Candidate drugs that are determined not to cause cardiac ion channel blockage are more likely to pass successfully through clinical phases II and III trials (and preclinical work) and not be withdrawn even later from the marketplace due to cardiotoxic effects...
December 28, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29283067/safety-limits-of-antidepressant-use-plus-combinations-focus-on-cardiovascular-function
#5
Florindo Stella, Julia C Loureiro, Marcos V Pais, Paulo R Canineu, Orestes V Florenza
BACKGROUND: Antidepressants have been widely prescribed for depression, anxiety, sleep disorders, and in the management of behavioural symptoms of adult-old patients. Although generally safe, newer generation antidepressants are not devoid of the risk of inducing clinically relevant adverse events. OBJECTIVES: To investigate the association between newer generation antidepressants and the occurrence of cardiovascular adverse events and electrocardiogram (ECG) abnormalities...
December 27, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29275963/qt-prolongation-torsades-de-pointes-and-psychotropic-medications-a-5-year-update
#6
REVIEW
Scott R Beach, Christopher M Celano, Alan M Sugrue, Caitlin Adams, Michael J Ackerman, Peter A Noseworthy, Jeff C Huffman
BACKGROUND: Some psychotropic medications have been associated with prolongation of the QT interval and QT prolongation, especially in those with medical illness, and are linked to lethal ventricular arrhythmias, such as Torsades de Pointes (TdP). In 2013, we published a review of QT prolongation, TdP, and psychotropic medications. OBJECTIVE: We provide an update over the past 5 years on the specific concerns most relevant to clinicians who see medically ill patients...
November 3, 2017: Psychosomatics
https://www.readbyqxmd.com/read/29274816/molecular-determinants-of-loperamide-and-n-desmethyl-loperamide-binding-in-the-herg-cardiac-k-channel
#7
Roy J Vaz, Jiesheng Kang, Yongyi Luo, David Rampe
Abuse of the common anti-diarrheal loperamide is associated with QT interval prolongation as well as development of the potentially fatal arrhythmia torsades de pointes. The mechanism underlying this cardiotoxicity is high affinity inhibition of the human ether-a-go-go-related gene (hERG) cardiac K+ channel. N-Desmethyl loperamide is the major metabolite of loperamide and is a close structural relative of the parent molecule. To date no information is available regarding the affinity of N-desmethyl loperamide for human cardiac ion channels...
December 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29259786/necessity-to-evaluate-pi3k-akt-signalling-pathway-in-proarrhythmia
#8
REVIEW
Martin Ezeani, Sunday Elom
The incidence of QT prolongation and torsades de pointes is on the rise due to the use of cardiovascular and non-cardiovascular drugs. Robust efforts have been made and are still ongoing to understand the underlying mechanisms that can enhance or prevent the development of drug-induced proarrhythmia. A caveat in the use of antiarrhythmic drugs is the ability to obtain safe action potential prolongation therapeutic effects, through IKr blockade. This remains as yet completely unachievable, as blockers of the potassium channel have not provided complete safe measures...
2017: Open Heart
https://www.readbyqxmd.com/read/29259513/torsades-de-pointes-after-ondansetron-infusion-in-2-patients
#9
Danny Y Lee, Tri Trinh, Sion K Roy
Drugs that prolong the electrocardiographic QT interval increase the risk of ventricular arrhythmias, particularly torsades de pointes. Ondansetron, a 5-hydroxytryptamine type 3 receptor antagonist antiemetic, is one such drug. We present the cases of 2 patients who were given intravenous ondansetron and subsequently developed torsades de pointes. Both had normal QT intervals at baseline but were discovered to have risk factors that predisposed them to drug-induced QT prolongation and ventricular arrhythmias...
October 2017: Texas Heart Institute Journal
https://www.readbyqxmd.com/read/29258620/refractory-ventricular-fibrillations-after-surgical-repair-of-atrial-septal-defects-in-a-patient-with-cacna1c-gene-mutation-case-report
#10
Ai Kojima, Fumiaki Shikata, Toru Okamura, Takashi Higaki, Seiko Ohno, Minoru Horie, Shunji Uchita, Yujiro Kawanishi, Kenji Namiguchi, Takumi Yasugi, Hironori Izutani
BACKGROUND: Congenital long QT syndrome (LQTS) can cause ventricular arrhythmic events with syncope and sudden death resulting from malignant torsades de pointes (TdP) followed by ventricular fibrillations (VFs). However, the syndrome is often overlooked prior to the development of arrhythmic events in patients with congenital heart diseases demonstrating right bundle branch block on electrocardiogram (ECG). We present a case of an adult patient with congenital heart disease who developed VFs postoperatively, potentially due to his mutation in a LQTS related gene, which was not identified on preoperative assessment due to incomplete evaluation of his family history...
December 19, 2017: Journal of Cardiothoracic Surgery
https://www.readbyqxmd.com/read/29245320/qtc-prolongation-and-torsades-de-pointes-due-to-a-coadministration-of-fluoxetine-and-amiodarone-in-a-patient-with-implantable-cardioverter-defibrillator-case-report-and-review-of-the-literature
#11
Anhua Wei, Jinlan Peng, Zhichun Gu, Juan Li
RATIONALE: Drug-induced prolongation of the corrected QT interval (QTc) may lead to serious and potentially life-threatening ventricular tachyarrhythmia, such as torsades de pointes (Tdp), which is worthy of clinical attention. Here, we report 1 case of Tdp after a coadministration of fluoxetine and amiodarone. PATIENT CONCERNS: A 62-year-old Chinese male who placed with the implanted cardioverter-defibrillator (ICD) appeared the QTc prolongation and Tdp after the concurrent administration of fluoxetine and amiodarone...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29219167/quantitative-understanding-of-qtc-prolongation-and-gender-as-risk-factors-for-torsade-de-pointes
#12
Lars Johannesen, Christine Garnett, Man Luo, Shari Targum, Jens Stampe Sørensen, Nitin Mehrotra
Several risk factors for development of a potentially fatal ventricular arrhythmia, torsade de pointes, have been observed, including female gender. However, in most investigations, only few torsade events were included and/or rarely were postdose heart rate corrected QT (QTc) measurements included, as a surrogate of drug exposure. We developed a multivariate logistic regression model using data from 22,214 patients (33% women) with 84 torsade events (56% women) to evaluate the relationship between risk factors for torsade using data from four anti-arrhythmic drug development programs...
February 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29217664/incidence-diagnosis-and-management-of-qt-prolongation-induced-by-cancer-therapies-a-systematic-review
#13
REVIEW
Andreu Porta-Sánchez, Cameron Gilbert, Danna Spears, Eitan Amir, Joyce Chan, Kumaraswamy Nanthakumar, Paaladinesh Thavendiranathan
BACKGROUND: The cardiovascular complications of cancer therapeutics are the focus of the burgeoning field of cardio-oncology. A common challenge in this field is the impact of cancer drugs on cardiac repolarization (ie, QT prolongation) and the potential risk for the life-threatening arrhythmia torsades de pointes. Although QT prolongation is not a perfect marker of arrhythmia risk, this has become a primary safety metric among oncologists. Cardiologists caring for patients receiving cancer treatment should become familiar with the drugs associated with QT prolongation, its incidence, and appropriate management strategies to provide meaningful consultation in this complex clinical scenario...
December 7, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29209226/uncertainty-quantification-reveals-the-importance-of-data-variability-and-experimental-design-considerations-for-in-silico-proarrhythmia-risk-assessment
#14
Kelly C Chang, Sara Dutta, Gary R Mirams, Kylie A Beattie, Jiansong Sheng, Phu N Tran, Min Wu, Wendy W Wu, Thomas Colatsky, David G Strauss, Zhihua Li
The Comprehensive in vitro Proarrhythmia Assay (CiPA) is a global initiative intended to improve drug proarrhythmia risk assessment using a new paradigm of mechanistic assays. Under the CiPA paradigm, the relative risk of drug-induced Torsade de Pointes (TdP) is assessed using an in silico model of the human ventricular action potential (AP) that integrates in vitro pharmacology data from multiple ion channels. Thus, modeling predictions of cardiac risk liability will depend critically on the variability in pharmacology data, and uncertainty quantification (UQ) must comprise an essential component of the in silico assay...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29201009/in-vitro-and-in-silico-risk-assessment-in-acquired-long-qt-syndrome-the-devil-is-in-the-details
#15
REVIEW
William Lee, Monique J Windley, Jamie I Vandenberg, Adam P Hill
Acquired long QT syndrome, mostly as a result of drug block of the Kv11. 1 potassium channel in the heart, is characterized by delayed cardiac myocyte repolarization, prolongation of the T interval on the ECG, syncope and sudden cardiac death due to the polymorphic ventricular arrhythmia Torsade de Pointes (TdP). In recent years, efforts are underway through the Comprehensive in vitro proarrhythmic assay (CiPA) initiative, to develop better tests for this drug induced arrhythmia based in part on in silico simulations of pharmacological disruption of repolarization...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29197146/is-myocardial-repolarization-duration-associated-with-repolarization-heterogeneity
#16
Keith A Marill, Pat Dorsey, Anthony Holmes, Ketaki Muthal, Emily S Miller, Joel Xue
BACKGROUND: Dispersion of repolarization is theorized as one mechanism by which myocardial repolarization prolongation causes lethal torsades de pointes, (TdP). Our primary purpose was to determine whether prolongation of myocardial repolarization as measured by the heart rate-corrected J-to-T peak interval (JTpkc), is associated with repolarization heterogeneity as measured by transmural dispersion, defined as the median duration from the peak to the end of the T wave (TpTe). METHODS: A retrospective cohort study was performed at a single urban tertiary ED from July 2011-September 2012...
December 2, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/29194874/late-onset-severe-long-qt-syndrome
#17
Babken Asatryan, André Schaller, Deborah Bartholdi, Argelia Medeiros-Domingo
We report a case of torsades de pointes arrhythmia as the first manifestation of congenital Long QT syndrome in a 77-year-old man with family history of sudden unexplained death. This case illustrates the importance of vigilant clinical assessment and genetic counseling in families with sudden death in order to identify properly asymptomatic relatives at risk for cardiac events. It also demonstrates that Long QT syndrome can still manifest with potentially fatal arrhythmias late in life in previously asymptomatic elderly patients...
November 30, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/29194862/a-case-report-is-mexiletine-usage-effective-in-the-shortening-of-qtc-interval-and-improving-the-t-wave-alternans-in-timothy-syndrome
#18
Gulhan Tunca Sahin, Yakup Ergul
Timothy syndrome (TS) is a multisystemic disease that occurs because of a mutation in CACN1C gene and is characterized by prolonged QT interval. Mexiletine is a Class 1B antiarrhythmic drug that causes the disappearance of T-wave alternans by shortening QTc and peak-to-end of the T wave. It may block the development of torsades de pointes in a prolonged QT. This study presented the case of a patient diagnosed with TS and had a cardiac arrest history, prolonged QT, and T-wave alternans. After mexiletine treatment, the QTc interval shortened and T-wave alternans disappeared...
November 30, 2017: Annals of Noninvasive Electrocardiology
https://www.readbyqxmd.com/read/29194447/sevoflurane-causes-greater-qtc-interval-prolongation-in-chronically-hyperglycemic-patients-than-in-normoglycemic-patients
#19
Seishi Kimura, Shinichi Nakao, Atsuhiro Kitaura, Tatushige Iwamoto, Kei Houri, Mayuka Matsushima, Shinichi Hamasaki
QTc interval prolongation is a serious diabetic complication and increases mortality rate. Hyperglycemia inhibits the rapid component of delayed rectifier potassium channel currents (Ikr) and prolongs the QTc interval on electrocardiograms. Sevoflurane also inhibits the Ikr and causes QTc interval prolongation. In fact, torsade de pointes occurred in a patient with poorly controlled diabetes mellitus during sevoflurane anesthesia. We enrolled 74 patients, including 37 normoglycemic patients (glycated hemoglobin [HbA1c]: <6...
2017: PloS One
https://www.readbyqxmd.com/read/29192591/torsades-de-pointes-associated-with-qt-prolongation-after-catheter-ablation-of-paroxysmal-atrial-fibrillation
#20
Yae Min Park, Mi Suk Cha, Woong Chol Kang, Mi-Seung Shin, Young-Hoon Kim, In Suck Choi, Eak Kyun Shin
A 79-year-old woman who underwent catheter ablation for paroxysmal atrial fibrillation presented with Torsades de Pointes (TdP). Aggravation of prolonged QT interval which is most likely due to neural modulation by catheter ablation, played major role in the initiation of TdP. The patient was successfully treated with isoproterenol during acute stage and discharged after stabilization without implantation of permanent pacemaker or implantable cardioverter defibrillator.
September 2017: Indian Pacing and Electrophysiology Journal
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