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The Israel Medical Association Journal... Mar 2005Torsade de pointes is rarely associated with chronic amiodarone treatment, despite the effect of amiodarone on QT interval prolongation. (Review)
Review
BACKGROUND
Torsade de pointes is rarely associated with chronic amiodarone treatment, despite the effect of amiodarone on QT interval prolongation.
OBJECTIVE
To identify risk factors and associated conditions that may cause TdP in patients on chronic amiodarone treatment.
METHODS
We reviewed the data of six consecutive patients on chronic amiodarone treatment who were admitted to the intensive cardiac care unit due to syncope and TdP.
RESULTS
The patients' median age was 73.5 years, and five were women. Concomitantly, loratadine was given to two patients and trazodone to one patient. Associated and attributing conditions to the development of TdP were hypokalemia in three patients, drug-induced bradycardia in one and reduced left ventricular function in four.
CONCLUSIONS
TdP associated with chronic amiodarone treatment may occur when amiodarone is co-administered with drugs that may potentially prolong QT interval. Additional risk factors for amiodarone-associated TdP include female gender, hypokalemia, reduced left ventricular function and bradycardia.
Topics: Aged; Amiodarone; Drug Interactions; Female; Humans; Male; Retrospective Studies; Torsades de Pointes
PubMed: 15792261
DOI: No ID Found -
Clinical Research in Cardiology :... May 2022The short-coupled variant of torsade de pointes (sc-TdP) is a malignant arrhythmia that frequently presents with ventricular fibrillation (VF) electrical storm....
BACKGROUND
The short-coupled variant of torsade de pointes (sc-TdP) is a malignant arrhythmia that frequently presents with ventricular fibrillation (VF) electrical storm. Verapamil is considered the first-line therapy of sc-TdP while catheter ablation is not widely adopted. The aim of this study was to determine the origin of sc-TdP and to assess the outcome of catheter ablation using 3D-mapping.
METHODS AND RESULTS
We retrospectively analyzed five patients with sc-TdP who underwent 3D-mapping and ablation of sc-TdP at five different institutions. Four patients initially presented with sudden cardiac arrest, one patient experienced recurrent syncope as the first manifestation. All patients demonstrated a monomorphic premature ventricular contraction (PVC) with late transition left bundle branch block pattern, superior axis, and a coupling interval of less than 300 ms. triggering recurrent TdP and VF. In four patients, the culprit PVC was mapped to the free wall insertion of the moderator band (MB) with a preceding Purkinje potential in two patients. Catheter ablation using 3D-mapping and intracardiac echocardiography eliminated sc-TdP in all patients, with no recurrence at mean 2.7 years (range 6 months to 8 years) of follow-up.
CONCLUSION
3D-mapping and intracardiac echocardiography demonstrate that sc-TdP predominantly originates from the MB free wall insertion and its Purkinje network. Catheter ablation of the culprit PVC at the MB free wall junction leads to excellent short- and long-term results and should be considered as first-line therapy in recurrent sc-TdP or electrical storm.
Topics: Humans; Catheter Ablation; DNA-Binding Proteins; Electrocardiography; Retrospective Studies; Torsades de Pointes; Ventricular Fibrillation; Ventricular Premature Complexes
PubMed: 33770204
DOI: 10.1007/s00392-021-01840-z -
Circulation Journal : Official Journal... 2011
Topics: Action Potentials; Anti-Arrhythmia Agents; Computer Simulation; Heart Conduction System; Heart Ventricles; Humans; Imaging, Three-Dimensional; Kinetics; Models, Cardiovascular; Myocytes, Cardiac; Potassium; Potassium Channels; Tachycardia, Ventricular; Torsades de Pointes; Ventricular Fibrillation
PubMed: 21173506
DOI: 10.1253/circj.cj-10-0914 -
Emergency Medicine Journal : EMJ Sep 2002A case is described of torsade de pointes in a 41 year old woman with pre-existing QTc prolongation, potentially exacerbated by treatment with sotalol. Previous cardiac...
A case is described of torsade de pointes in a 41 year old woman with pre-existing QTc prolongation, potentially exacerbated by treatment with sotalol. Previous cardiac investigations had been normal and after a second episode of ventricular fibrillation the patient was referred for electrophysiological studies. The authors review the physiology, causes, and treatment of QTc prolongation and torsade de pointes.
Topics: Adult; Electrocardiography; Female; Heart Conduction System; Humans; Torsades de Pointes
PubMed: 12205024
DOI: 10.1136/emj.19.5.485 -
Clinical Pharmacology and Therapeutics Aug 2021Torsade de Pointes (TdP), a rare but lethal ventricular arrhythmia, is a toxic side effect of many drugs. To assess TdP risk, safety regulatory guidelines require...
Torsade de Pointes (TdP), a rare but lethal ventricular arrhythmia, is a toxic side effect of many drugs. To assess TdP risk, safety regulatory guidelines require quantification of hERG channel block in vitro and QT interval prolongation in vivo for all new therapeutic compounds. Unfortunately, these have proven to be poor predictors of torsadogenic risk, and are likely to have prevented safe compounds from reaching clinical phases. Although this has stimulated numerous efforts to define new paradigms for cardiac safety, none of the recently developed strategies accounts for patient conditions. In particular, despite being a well-established independent risk factor for TdP, female sex is vastly under-represented in both basic research and clinical studies, and thus current TdP metrics are likely biased toward the male sex. Here, we apply statistical learning to synthetic data, generated by simulating drug effects on cardiac myocyte models capturing male and female electrophysiology, to develop new sex-specific classification frameworks for TdP risk. We show that (i) TdP classifiers require different features in females vs. males; (ii) male-based classifiers perform more poorly when applied to female data; and (iii) female-based classifier performance is largely unaffected by acute effects of hormones (i.e., during various phases of the menstrual cycle). Notably, when predicting TdP risk of intermediate drugs on female simulated data, male-biased predictive models consistently underestimate TdP risk in women. Therefore, we conclude that pipelines for preclinical cardiotoxicity risk assessment should consider sex as a key variable to avoid potentially life-threatening consequences for the female population.
Topics: Calcium Isotopes; Computer Simulation; Female; Humans; Machine Learning; Male; Models, Biological; Myocytes, Cardiac; Risk Assessment; Risk Factors; Sex Factors; Torsades de Pointes
PubMed: 33772748
DOI: 10.1002/cpt.2240 -
European Journal of Medical Research Nov 2022Sex differences exist in the structure and function of human heart. The patterns of ventricular repolarization in normal electrocardiograms (ECG) differ in men and... (Review)
Review
Sex differences exist in the structure and function of human heart. The patterns of ventricular repolarization in normal electrocardiograms (ECG) differ in men and women: men ECG pattern displays higher T-wave amplitude and increased ST angle. Generally, women have longer QT duration because of reduced repolarization reserve, and thus, women are more susceptible for the occurrence of torsades de pointes associated with drugs prolonging ventricular repolarization. Sex differences are also observed in the prevalence, penetrance and symptom severity, and also in the prognosis of cardiovascular disease. Generally, women live longer, have less clinical symptoms of cardiac diseases, and later onset of symptoms than men. Sex hormones also play an important role in regulating ventricular repolarization, suggesting that hormones directly influence various cellular functions and adrenergic regulation. From the clinical perspective, sex-based differences in heart physiology are widely recognized, but in daily practice, cardiac diseases are often underdiagnosed and untreated in the women. The underlying mechanisms of sex differences are, however, poorly understood. Here, we summarize sex-dependent differences in normal cardiac physiology, role of sex hormones, and differences in drug responses. Furthermore, we also discuss the importance of human induced pluripotent stem cell-derived cardiomyocytes in further understanding the mechanism of differences in women and men.
Topics: Humans; Female; Male; Sex Characteristics; Induced Pluripotent Stem Cells; Torsades de Pointes; Gonadal Steroid Hormones; Heart Diseases; Electrocardiography
PubMed: 36352432
DOI: 10.1186/s40001-022-00880-z -
Europace : European Pacing,... Sep 2007Torsade de pointes (TdP) is a life-threatening arrhythmia that develops as a consequence of a reduction in the repolarization reserve of cardiac cells leading to... (Review)
Review
Torsade de pointes (TdP) is a life-threatening arrhythmia that develops as a consequence of a reduction in the repolarization reserve of cardiac cells leading to amplification of electrical heterogeneities in the ventricular myocardium as well as to the development of early after depolarization-induced triggered activity. Electrical heterogeneities within the ventricles are due to differences in the time course of repolarization of the three predominant cell types that make up the ventricular myocardium, giving rise to transmural voltage gradients and a dispersion of repolarization that contributes to the inscription of the electrocardiographic T wave. A number of non-antiarrhythmic drugs and antiarrhythmic agents with class III actions and/or the various mutations and cardiomyopathies associated with the long QT syndrome reduce net repolarizing current and amplify spatial dispersion of repolarization, thus creating the substrate for re-entry. This results in a prolongation of the QT interval, abnormal T waves, and development of TdP. Agents that prolong the QT interval but do not cause an increase in transmural dispersion of repolarization (TDR) do not induce TdP, suggesting that QT prolongation is not the sole or optimal determinant for arrhythmogenesis. This article reviews recent advances in our understanding of these mechanisms, particularly the role of TDR in the genesis of drug-induced TdP, and examines how these may guide us towards development of safer drugs.
Topics: Action Potentials; Heart Conduction System; Humans; Ion Channels; Long QT Syndrome; Myocytes, Cardiac; Torsades de Pointes
PubMed: 17766323
DOI: 10.1093/europace/eum166 -
Journal of the American College of... Apr 2016Drug-induced long QT syndrome (diLQTS) and congenital LQTS (cLQTS) share many features, and both syndromes can result in life-threatening torsades de pointes (TdP). Our... (Review)
Review
Drug-induced long QT syndrome (diLQTS) and congenital LQTS (cLQTS) share many features, and both syndromes can result in life-threatening torsades de pointes (TdP). Our understanding of their mechanistic and genetic similarities has led to their improved clinical management. However, our inability to prevent diLQTS has resulted in removal of many medicines from the market and from development. Genetic and clinical risk factors for diLQTS and TdP are well known and raise the possibility of TdP prevention. Clinical decision support systems (CDSS) can scan the patient's electronic health records for clinical risk factors predictive of diLQTS and warn when a drug that can cause TdP is prescribed. CDSS have reduced prescriptions of QT-prolonging drugs, but these relatively small changes lack the power to reduce TdP. The growing genetic evidence linking diLQTS to cLQTS suggests that prevention of TdP in the future may require inclusion of both genetic and clinical predictors into CDSS.
Topics: Adverse Drug Reaction Reporting Systems; Decision Support Systems, Clinical; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Genomics; Humans; Internet; Long QT Syndrome; Risk Factors; Torsades de Pointes
PubMed: 27150690
DOI: 10.1016/j.jacc.2015.12.063 -
European Heart Journal Jan 2013Drug-induced Torsades de Pointes is a rare, unpredictable, and life-threatening serious adverse event. It can be caused by both cardiac and non-cardiac drugs and has... (Review)
Review
Drug-induced Torsades de Pointes is a rare, unpredictable, and life-threatening serious adverse event. It can be caused by both cardiac and non-cardiac drugs and has become a major issue in novel drug development and for the regulatory authorities. This review describes the problem, predisposing factors, and the underlying genetic predisposition as it is understood currently. The future potential for pharmacogenomic-guided and personalized prescription to prevent drug-induced Torsades de Pointes is discussed. Database searches utilized reports from www.qtdrugs.org up to January 2012, case reports and articles from www.pubmed.com up to January 2012, and the British National Formulary edition at www.bnf.org.
Topics: Anti-Arrhythmia Agents; Electrocardiography; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Ion Channels; Long QT Syndrome; Polymorphism, Genetic; Risk Factors; Torsades de Pointes
PubMed: 23091201
DOI: 10.1093/eurheartj/ehs351 -
International Journal of Clinical... Jul 2021There are some data showing that repurposed drugs used for the Coronavirus disease-19 (COVID-19) have potential to increase the risk of QTc prolongation and torsade de...
BACKGROUND
There are some data showing that repurposed drugs used for the Coronavirus disease-19 (COVID-19) have potential to increase the risk of QTc prolongation and torsade de pointes (TdP), and these arrhythmic side effects have not been adequately addressed in COVID-19 patients treated with these repurposed medications.
METHODS
This is the prospective study of 2403 patients hospitalised at 13 hospitals within the COVID-19 epicentres of the Iran. These patients were treated with chloroquine, hydroxychloroquine, lopinavir/ritonavir, atazanavir/ritonavir, oseltamivir, favipiravir and remdesivir alone or in combination with azithromycin. The primary outcome of the study was incidence of critical QTc prolongation, and secondary outcomes were incidences of TdP and death.
RESULTS
Of the 2403 patients, 2365 met inclusion criteria. The primary outcome of QTc ≥ 500 ms and ∆QTc ≥ 60 ms was observed in 11.2% and 17.6% of the patients, respectively. The secondary outcomes of TdP and death were reported in 0.38% and 9.8% of the patients, respectively. The risk of critical QT prolongation increased in the presence of female gender, history of heart failure, treatment with hydroxychloroquine, azithromycin combination therapy, simultaneous furosemide or beta-blocker therapy and acute renal or hepatic dysfunction. However, the risk of TdP was predicted by treatment with lopinavir-ritonavir, simultaneous amiodarone or furosemide administration and hypokalaemia during treatment.
CONCLUSION
This cohort showed significant QTc prolongation with all COVID-19 medications studied, however, life-threatening arrhythmia of TdP occurred rarely. Among the repurposed drugs studied, hydroxychloroquine or lopinavir-ritonavir alone or in combination with azithromycin clearly demonstrated to increase the risk of critical QT prolongation and/or TdP.
Topics: COVID-19; Electrocardiography; Female; Humans; Iran; Pharmaceutical Preparations; Prospective Studies; SARS-CoV-2; Torsades de Pointes
PubMed: 33759318
DOI: 10.1111/ijcp.14182