Clinical and Genetic Determinants of Torsade de Pointes Risk

Sauer, Andrew J.; Newton‐Cheh, Christopher

doi:10.1161/circulationaha.111.080887

Cited by 78 publications

(65 citation statements)

References 134 publications

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“…1). Other Twave parameters, notably the Tpeak-Tend interval that has been suggested previously as a marker of TdP risk in several studies [7], might reflect similar electrophysiological concepts, but failed to distinguish cases from controls in the present study [11]. Sugrue et al suggest that difficulty determining the precise end of the T-wave in the presence of class III AADs might prevent adequate discrimination based on Tpeak-Tend in this small cohort [11].…”

supporting

confidence: 63%

“…Excessive prolongation of the QTc interval is currently employed as the standard parameter in this process. However, QT-interval prolonging drugs show marked differences in their torsadogenic potency, indicating that QTc-interval prolongation alone is an imperfect measure for the risk of drug-induced TdP [5,7,8]. Substantial research efforts have been directed to identify other ECG parameters that can support risk assessment for both ventricular and atrial arrhythmias [7][8][9][10].…”

mentioning

confidence: 99%

“…The susceptibility can be assessed non-invasively through changes in the ECG morphology, including QT-interval duration and T-wave right-slope, as shown in the work by Sugrue et al [11] the repolarization of the AP [14]. Because of this redundancy, genetic and/or acquired modulation of other ion channels, which have no or limited effect on the baseline ECG, can modulate the response to class III AADs and the likelihood of TdP [7,14]. In accordance with this concept, several genetic modifiers of drug-induced TdP have been determined [14].…”

mentioning

confidence: 99%

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T-wave Right Slope Provides a New Angle in the Prediction of Drug-Induced Ventricular Arrhythmias

Heijman

Crijns

2015

Cardiovasc Drugs Ther

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supporting

confidence: 63%

mentioning

confidence: 99%

mentioning

confidence: 99%

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T-wave Right Slope Provides a New Angle in the Prediction of Drug-Induced Ventricular Arrhythmias

Heijman

Crijns

2015

Cardiovasc Drugs Ther

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“…They may result from EADs occurring above a certain threshold required to cause triggered activity that can induce arrhythmia. The arrhythmia is more likely to develop if there is instability of repolarization as reflected on the ECG by T/U wave variability, such as T wave alternans or short term variations in the QT interval [9,12]. TdP is more common in those with structural heart diseases, including heart failure, myocardial infarction and left ventricular hypertrophy, as well as those with cLQTS, which may be concealed.…”

mentioning

confidence: 99%

Pharmacological treatment of acquired QT prolongation and torsades de pointes

Thomas

Behr

2015

Brit J Clinical Pharma

117

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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.

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“…-current, the clinical phenotype was extremely diverse [1]. Thus, other risk factors including a genetic predisposition, disease-related remodeling, neurohumoral factors, and drug effects can importantly influence the development and maintenance of cardiac arrhythmias [5,7,18]. This complexity also highlights the urgent need for novel integrative cardiac safety assays that can bridge the gap between available in vitro and in vivo systems and can provide a reliable assessment of potential proarrhythmic consequences of novel pharmacological compounds.…”

mentioning

confidence: 99%