What question did this study set out to answer?

To determine the maximum drug-induced heart rate change that allows fixed QT correction formulas to be used accurately compared to subject-specific corrections.

June 18, 2019Frontiers in PhysiologyOpen Access

Errors of Fixed QT Heart Rate Corrections Used in the Assessment of Drug-Induced QTc Changes

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Why the study?

The maximum heart rate change that permits the use of fixed QT heart rate corrections with reasonable accuracy had not been systematically investigated.

Do fixed QT heart rate corrections produce acceptable errors in ΔQTc assessment compared to subject-specific corrections during heart rate changes?

Key Points

To determine the maximum drug-induced heart rate change that allows fixed QT correction formulas to be used accurately compared to subject-specific corrections.
Analyzed complete QT and heart rate profiles from 751 healthy subjects (mean age 34.2 ± 9.6 years, range 18–61 years, 335 females) to evaluate six fixed corrections (Bazett, Fridericia, Framingham, Hodges, Rautaharju, and Sarma) against subject-specific corrections.
Conducted 10,000 statistical modeling iterations simulating clinical studies of N = 10 and N = 50 male or female cohorts across baseline heart rates of 40–120 bpm and heart rate changes of -20 to +20 bpm, assessing errors from spontaneous rate fluctuations and omitted QT/RR hysteresis.
Fridericia and Framingham formulas performed with acceptable accuracy (estimated ΔQTc error below 8 ms) in large cohorts (N = 50) only when heart rate changes remained within ±10 bpm.
Errors arising from fixed correction formulas and the omission of QT/RR hysteresis were additive, causing greater variability and impact in small studies (N = 10).
Bazett, Hodges, Rautaharju, and Sarma correction formulas produced substantially larger ΔQTc calculation errors than the Fridericia and Framingham formulas.

Structured PICO

Do fixed QT heart rate corrections produce acceptable errors in ΔQTc assessment compared to subject-specific corrections during heart rate changes?

Population

751 healthy subjects (mean age 34.2 ± 9.6, range 18-61 years, 335 females) used for statistical modeling experiments simulating clinical studies of N=10 or N=50 subjects.

Intervention

6 fixed QT heart rate corrections (Bazett, Fridericia, Framingham, Hodges, Rautaharju, and Sarma formulae)

Comparator

Subject-specific corrections established for each study participant

Outcome

Errors of ΔQTc intervals calculated as differences between QTc intervals at an initial heart rate (40-120 bpm) and after a heart rate change (-20 to +20 bpm)surrogate

Fixed QT corrections like Fridericia are only accurate for assessing drug-induced QTc changes when heart rate shifts are minimal (≤ ±10 bpm), emphasizing the need for subject-specific corrections in studies with larger heart rate fluctuations.

Discussion

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Implication

Fixed QTc corrections risk larger ΔQTc errors with HR fluctuations; leaves open subject-specific superiority in variable settings.

Cite This Study

Hnatkova et al. (2019) studied this question.

synapsesocial.com/papers/69dc2068796be608a2b650b0 https://doi.org/10.3389/fphys.2019.00635

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Errors of Fixed QT Heart Rate Corrections Used in the Assessment of Drug-Induced QTc Changes

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Errors of Fixed QT Heart Rate Corrections Used in the Assessment of Drug-Induced QTc Changes

Key Points

Structured PICO

Discussion

Implication

Cite This Study

Also Consider

Also Consider