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British Journal of Clinical Pharmacology Mar 2016Torsades de pointes (TdP) is a characteristic polymorphic ventricular arrhythmia associated with delayed ventricular repolarization as evidenced on the surface... (Review)
Review
Torsades de pointes (TdP) is a characteristic polymorphic ventricular arrhythmia associated with delayed ventricular repolarization as evidenced on the surface electrocardiogram by QT interval prolongation. It typically occurs in self-limiting bursts, causing dizziness and syncope, but may occasionally progress to ventricular fibrillation and sudden death. Acquired long QT syndromes are mainly caused by cardiac disease, electrolyte abnormalities or exposure to drugs that block rectifying potassium channels, especially IKr. Management of TdP or marked QT prolongation includes removal or correction of precipitants, including discontinuation of culprit drugs and institution of cardiac monitoring. Electrolyte abnormalities and hypoxia should be corrected, with potassium concentrations maintained in the high normal range. Immediate treatment of TdP is by intravenous administration of magnesium sulphate, terminating prolonged episodes using electrical cardioversion. In refractory cases of recurrent TdP, the arrhythmia can be suppressed by increasing the underlying heart rate using isoproterenol (isoprenaline) or transvenous pacing. Other interventions are rarely needed, but there are case reports of successful use of lidocaine or phenytoin. Anti-arrhythmic drugs that prolong ventricular repolarization should be avoided. Some episodes of TdP could be avoided by careful prescribing of QT prolonging drugs, including an individualized assessment of risks and benefits before use, performing baseline and periodic electrocardiograms and measurement of electrolytes, especially during acute illnesses, using the lowest effective dose for the shortest possible time and avoiding potential drug interactions. These steps are particularly important in those with underlying repolarization abnormalities and those who have previously experienced drug-induced TdP.
Topics: Anti-Arrhythmia Agents; Disease Management; Humans; Long QT Syndrome; Torsades de Pointes
PubMed: 26183037
DOI: 10.1111/bcp.12726 -
Annals of Noninvasive Electrocardiology... Nov 2017Since its initial description by Jervell and Lange-Nielsen in 1957, the congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. A... (Review)
Review
Since its initial description by Jervell and Lange-Nielsen in 1957, the congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. A prolonged QT interval in the surface electrocardiogram is the sine qua non of the LQTS and is a surrogate measure of the ventricular action potential duration (APD). Congenital as well as acquired alterations in certain cardiac ion channels can affect their currents in such a way as to increase the APD and hence the QT interval. The inhomogeneous lengthening of the APD across the ventricular wall results in dispersion of APD. This together with the tendency of prolonged APD to be associated with oscillations at the plateau level, termed early afterdepolarizations (EADs), provides the substrate of ventricular tachyarrhythmia associated with LQTS, usually referred to as torsade de pointes (TdP) VT. This review will discuss the genetic, molecular, and phenotype characteristics of congenital LQTS as well as current management strategies and future directions in the field.
Topics: Adrenergic beta-Antagonists; Electrocardiography; Humans; Long QT Syndrome; Torsades de Pointes
PubMed: 28670758
DOI: 10.1111/anec.12481 -
Indian Heart Journal 2014Dofetilide is an effective antiarrhythmic agent for conversion of atrial fibrillation and atrial flutter as well as maintenance of sinus rhythm in appropriately selected... (Review)
Review
Dofetilide is an effective antiarrhythmic agent for conversion of atrial fibrillation and atrial flutter as well as maintenance of sinus rhythm in appropriately selected patients. However, as with other antiarrhythmic agents, proarrhythmia is a known adverse effect. The risk of dofetilide induced torsade de pointes (Tdp) is low when used with strict dosing criteria guided by renal function, QT interval and concomitant drug therapy. Benefit from dofetilide use must be individualized and weighed against the side effects and the role of other available treatment options. In this review, we discuss the underlying mechanism, risk factors and precautionary measures to avoid dofetilide induced QT prolongation and ventricular tachycardia/Tdp. We suggest a scheme for the management of QT prolongation, ventricular arrhythmia and Tdp as well.
Topics: Anti-Arrhythmia Agents; Electrocardiography; Humans; Phenethylamines; Risk Factors; Sulfonamides; Torsades de Pointes
PubMed: 25634399
DOI: 10.1016/j.ihj.2013.12.021 -
European Journal of Clinical... Oct 2021To analyze the cases of torsade de pointes (TdP) and related symptoms reported in association with chloroquine (CQ), hydroxychloroquine (HCQ), and azithromycin (AZT) to...
PURPOSE
To analyze the cases of torsade de pointes (TdP) and related symptoms reported in association with chloroquine (CQ), hydroxychloroquine (HCQ), and azithromycin (AZT) to the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase) using qualitative and quantitative pharmacovigilance approaches.
METHODS
The main characteristics of the ICSRs reporting TdP with CQ, HCQ, and AZT have been summarized. Co-reported drugs with risk to cause QT prolongation have been described. Reporting odds ratios (RORs) as a measure of disproportionality for reported TdP and individual drugs have been calculated.
RESULTS
One hundred seventy ICSRs reporting TdP in association with the drugs of interest were identified (CQ: 11, HCQ: 31, CQ + HCQ: 1, HCQ + AZT: 27, AZT: 100). From these, 41 (24.3%) were received during the pandemic period (December 2019 to February 2021). The median age of the patients was 63, 53, and 63 years old for CQ, HCQ, and AZT, respectively. Reports included concomitant use of other QT-prolonging drugs (CQ 25.0%, HCQ 71.2%, AZT 64.6%). A proportion of the cases were fatal (CQ 25.0%, HCQ 8.6%, AZT 16.1%). Increased disproportionality has been found for the individual drugs and TdP: CQ (ROR: 7.41, 95% confidence interval (CI): 3.82, 12.96), HCQ (ROR: 8.49, 95% CI: 6.57, 10.98), azithromycin (ROR: 8.06, 95% CI: 6.76, 9.61). Disproportionality was also found for other related symptoms, Standardized MedDRA Query for torsade de pointes/QT prolongation (narrow): CQ (ROR: 11.95, 95% CI: 10.04-14.22); HCQ (ROR: 20.43, 95% CI: 19.13, 21.83), AZT (ROR: 7.78, 95% CI: 7.26, 8.34).
CONCLUSIONS
The prescription of CQ, HCQ, and AZT should be restricted to therapeutic indications with established positive benefit/risk profile. Doctors and patients should be aware of this potential adverse reaction especially when several risk factors are present.
Topics: Adult; Aged; Azithromycin; Chloroquine; Drug Therapy, Combination; Female; Humans; Hydroxychloroquine; Male; Middle Aged; Pharmacovigilance; Retrospective Studies; Torsades de Pointes
PubMed: 33938974
DOI: 10.1007/s00228-021-03133-w -
Circulation. Cardiovascular Quality and... Jul 2013Identifying hospitalized patients at risk for QT interval prolongation could lead to interventions to reduce the risk of torsades de pointes. Our objective was to... (Observational Study)
Observational Study
BACKGROUND
Identifying hospitalized patients at risk for QT interval prolongation could lead to interventions to reduce the risk of torsades de pointes. Our objective was to develop and validate a risk score for QT prolongation in hospitalized patients.
METHODS AND RESULTS
In this study, in a single tertiary care institution, consecutive patients (n=900) admitted to cardiac care units comprised the risk score development group. The score was then applied to 300 additional patients in a validation group. Corrected QT (QTc) interval prolongation (defined as QTc>500 ms or an increase of >60 ms from baseline) occurred in 274 (30.4%) and 90 (30.0%) patients in the development group and validation group, respectively. Independent predictors of QTc prolongation included the following: female (odds ratio, 1.5; 95% confidence interval, 1.1-2.0), diagnosis of myocardial infarction (2.4 [1.6-3.9]), septic shock (2.7 [1.5-4.8]), left ventricular dysfunction (2.7 [1.6-5.0]), administration of a QT-prolonging drug (2.8 [2.0-4.0]), ≥2 QT-prolonging drugs (2.6 [1.9-5.6]), or loop diuretic (1.4 [1.0-2.0]), age >68 years (1.3 [1.0-1.9]), serum K⁺ <3.5 mEq/L (2.1 [1.5-2.9]), and admitting QTc >450 ms (2.3; confidence interval [1.6-3.2]). Risk scores were developed by assigning points based on log odds ratios. Low-, moderate-, and high-risk ranges of 0 to 6, 7 to 10, and 11 to 21 points, respectively, best predicted QTc prolongation (C statistic=0.823). A high-risk score ≥11 was associated with sensitivity=0.74, specificity=0.77, positive predictive value=0.79, and negative predictive value=0.76. In the validation group, the incidences of QTc prolongation were 15% (low risk); 37% (moderate risk); and 73% (high risk).
CONCLUSIONS
A risk score using easily obtainable clinical variables predicts patients at highest risk for QTc interval prolongation and may be useful in guiding monitoring and treatment decisions.
Topics: Aged; Aged, 80 and over; Chi-Square Distribution; Coronary Care Units; Decision Support Techniques; Female; Hospitalization; Humans; Indiana; Logistic Models; Long QT Syndrome; Male; Middle Aged; Odds Ratio; Prospective Studies; Reproducibility of Results; Risk Assessment; Risk Factors; Tertiary Care Centers; Torsades de Pointes
PubMed: 23716032
DOI: 10.1161/CIRCOUTCOMES.113.000152 -
Cardiovascular Therapeutics Feb 2014This review aims to clarify the underlying risk of arrhythmia associated with the use of macrolides and fluoroquinolones antibiotics. Torsades de pointes (TdP) is a rare... (Review)
Review
This review aims to clarify the underlying risk of arrhythmia associated with the use of macrolides and fluoroquinolones antibiotics. Torsades de pointes (TdP) is a rare potential side effect of fluoroquinolones and macrolide antibiotics. However, the widespread use of these antibiotics compounds the problem. These antibiotics prolong the phase 3 of the action potential and cause early after depolarization and dispersion of repolarization that precipitate TdP. The potency of these drugs, as potassium channel blockers, is very low, and differences between them are minimal. Underlying impaired cardiac repolarization is a prerequisite for arrhythmia induction. Impaired cardiac repolarization can be congenital in the young or acquired in adults. The most important risk factors are a prolonged baseline QTc interval or a combination with class III antiarrhythmic drugs. Modifiable risk factors, including hypokalemia, hypomagnesemia, drug interactions, and bradycardia, should be corrected. In the absence of a major risk factor, the incidence of TdP is very low. The use of these drugs in the appropriate settings of infection should not be altered because of the rare risk of TdP, except among cases with high-risk factors.
Topics: Animals; Anti-Bacterial Agents; Drug Interactions; Electrocardiography; Fluoroquinolones; Humans; Macrolides; Torsades de Pointes
PubMed: 24428853
DOI: 10.1111/1755-5922.12054 -
In Vivo (Athens, Greece) 2023Torsade de pointes (TdP)/QT prolongation (QTP) is one of the most life-threatening adverse effects of antifungal triazoles. The aim of the present study was to evaluate...
BACKGROUND/AIM
Torsade de pointes (TdP)/QT prolongation (QTP) is one of the most life-threatening adverse effects of antifungal triazoles. The aim of the present study was to evaluate the association of antifungal triazoles with TdP/QTP by age group and the profile of the time of TdP/QTP onset by analyzing the spontaneous adverse event database for Japan.
PATIENTS AND METHODS
Data registered in the Japanese Adverse Drug Event Report database (JADER) from April 2004 to March 2022 were analyzed. The association between the administration of antifungal triazoles and TdP/QTP according to age was evaluated using an adjusted reporting odds ratio (aROR). In addition, the time-to-onset of TdP/QTP after antifungal triazole treatment was analyzed using the Weibull distribution according to the route of administration.
RESULTS
Antifungal triazole treatment was associated with TdP/QTP (aROR=1.77, 95% confidence interval=1.52-2.07). In the subgroup analyses by age group, antifungal triazole treatments in patients ≤29 years old and ≥50 (except ≥90) years old were associated with TdP/QTP. The medians (quartiles) of time-to-onset for intravenous and oral antifungal triazole treatment were 8 (6-12) and 23 (8-86) days, respectively. In addition, the shape parameter in the Weibull distribution analysis of oral triazole treatment revealed that the hazard exhibited an early failure profile.
CONCLUSION
TdP/QTP is associated with antifungal triazoles even in young patients, and patients should be monitored for the development of TdP/QTP, especially early after the initiation of treatment.
Topics: Humans; Adult; Aged, 80 and over; Torsades de Pointes; Antifungal Agents; Pharmacovigilance; Drug-Related Side Effects and Adverse Reactions; Long QT Syndrome; Triazoles; DNA-Binding Proteins; Electrocardiography
PubMed: 37905641
DOI: 10.21873/invivo.13382 -
Clinical Cardiology Sep 1993The polymorphic ventricular tachycardia torsade de pointes can occur in the congenital long QT syndromes or as a consequence of therapy with QT-prolonging drugs. The... (Review)
Review
The polymorphic ventricular tachycardia torsade de pointes can occur in the congenital long QT syndromes or as a consequence of therapy with QT-prolonging drugs. The latter can include not only antiarrhythmic drugs such as quinidine, but also a number of drugs which are not usually considered to have major cardiovascular effects: these include nonsedating antihistamines, such as terfenadine; antibiotics such as erythromycin; and neuroleptics such as thioridazine. The electrocardiographic hallmark of both the congenital and acquired forms of the long QT syndrome is marked QT(U) lability, particularly as a function of heart rate. The underlying mechanism is thought to be triggered activity arising as a consequence of early afterdepolarizations. An understanding of the basic mechanism has led to an understanding of the effective forms of therapy, which include maneuvers to include the heart rate (pacing, isoproterenol) as well as maneuvers which may not necessarily alter the QT interval but may prevent the arrhythmia (magnesium, beta blockers). Intensive study of the clinical features and basic mechanisms underlying torsade de pointes has led to the definition of a new mechanism for cardiac arrhythmias; understanding such mechanisms may ultimately lead to the development of safer antiarrhythmic therapy.
Topics: Adrenergic beta-Antagonists; Animals; Anti-Arrhythmia Agents; Antipsychotic Agents; Dogs; Electrocardiography; Erythromycin; Heart Rate; Histamine Antagonists; Humans; Long QT Syndrome; Torsades de Pointes
PubMed: 7902224
DOI: 10.1002/clc.4960160910 -
British Journal of Clinical Pharmacology Mar 2012
Topics: Anti-Arrhythmia Agents; Electrocardiography; Heart Rate; Humans; Long QT Syndrome; Torsades de Pointes
PubMed: 22329611
DOI: 10.1111/j.1365-2125.2012.04193.x -
Heart Rhythm Sep 2020There is no known effective therapy for patients with coronavirus disease 2019 (COVID-19). Initial reports suggesting the potential benefit of...
BACKGROUND
There is no known effective therapy for patients with coronavirus disease 2019 (COVID-19). Initial reports suggesting the potential benefit of hydroxychloroquine/azithromycin (HY/AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns about the potential risk of QT interval prolongation and induction of torsade de pointes (TdP).
OBJECTIVE
The purpose of this study was to assess the change in corrected QT (QTc) interval and arrhythmic events in patients with COVID-19 treated with HY/AZ.
METHODS
This is a retrospective study of 251 patients from 2 centers who were diagnosed with COVID-19 and treated with HY/AZ. We reviewed electrocardiographic tracings from baseline and until 3 days after the completion of therapy to determine the progression of QTc interval and the incidence of arrhythmia and mortality.
RESULTS
The QTc interval prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc interval prolongation to >500 ms, a known marker of high risk of TdP, had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc interval of patients exhibiting extreme QTc interval prolongation was normal.
CONCLUSION
The combination of HY/AZ significantly prolongs the QTc interval in patients with COVID-19. This prolongation may be responsible for life-threatening arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in light of its unproven efficacy. Strict QTc interval monitoring should be performed if the regimen is given.
Topics: Aged; Anti-Bacterial Agents; Antimalarials; Azithromycin; Betacoronavirus; COVID-19; Coronavirus Infections; Female; Humans; Hydroxychloroquine; Incidence; Long QT Syndrome; Male; Middle Aged; Pandemics; Pneumonia, Viral; Retrospective Studies; SARS-CoV-2; Torsades de Pointes; COVID-19 Drug Treatment
PubMed: 32407884
DOI: 10.1016/j.hrthm.2020.05.014