Risk of torsades de pointes depending on drug-induced QT prolongation
Torsade de pointes (TdP) can be associated with drug-induced prolongation of the QT interval. This model indicates the relationship between the magnitude of QT prolongation and the risk of TdP.
Research authors: Joy JP, Coulter CV, Duffulll SB, and Isbister GK.
Details Formula Study characteristics Files & References
★★★
Model author
Model ID
1417
Version
1.9
Revision date
2018-07-17
MeSH terms
  • Long QT Syndrome
  • Torsades de Pointes
  • Cardiac Arrhythmias
  • Model type
    Logistic regression (Calculation)
    Status
    public
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    Formula

    Additional information

    Study population:
    457 electrocardiograms (ECGs) were analyzed arising from 86 cases of amisulpride overdose in 66 patients. Data were prospectively collected as part of an observational clinical study of the effects of amisulpride. The minimum QT interval associated with TdP events in the study group was 560 ms.

    ECG analysis:
    All 12-lead ECGs were read manually by one investigator using a standardized approach, as previously described. The QT interval was measured in three chest leads and three limb leads from the beginning of the Q wave up to the point where the T wave returns to baseline (isoelectric line), and the median was calculated. The HR value used was the one taken as an automated measurement by the ECG machine.

    Statistical analysis:
    A logistic regression analysis was carried out using NONMEM VI (GloboMax, Hanover, MD) to assess for the influence of the various QT and corrected QT descriptors as well as HR interval and dose. Dose and HR were included for comparison. Model comparisons were made on the basis of the value –2LL, where lower values represent better predictive performance of the factor.

    Study Population

    Total population size: 86
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    Continuous characteristics

    Name Mean SD Unit
    Age 31 6 years
    Name LL Q1 Median Q3 UL Unit
    Dose 3 6 12 gram
    RR 722 816 923 ms
    QT 423 485 560 ms
    QTcB 486 544 605 ms
    QTcF 465 525 583 ms

    Probability of torsades de pointes (TdP) based on uncorrected QT interval:
    ...

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    Result
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    Probability of torsades de pointes (TdP) based on uncorrected QT interval:

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    Outcome stratification

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    Conditional information

    Result interpretation

    Context information:
    Measures of the magnitude of (uncorrected) QT interval predicted the risk of TdP significantly better than dose, heart rate, or the mere presence of a prolonged QT. Moreover, the magnitude of the QT prolongation was a better predictor of TdP than the mere presence or absence of an abnormal QT, highlighting the problematic nature of using a single cutoff value for risk assessment.

    Source:
    Joy JP, Coulter CV, Duffull SB, Isbister GK. Prediction of torsade de pointes from the QT interval: analysis of a case series of amisulpride overdoses. Clin Pharmacol Ther. 2011;90(2):243-5.

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    Calculations alone should never dictate patient care, and are no substitute for professional judgement. See our full disclaimer.

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