Evaluation of drug-induced QT interval modifications in dynamic electrocardiography: the case of bepridil

Abstract

Drug-induced modifications of QT interval are usually assessed through formulae defining the corrected QT interval "QTc". They are all based on the assumption that the correction is adequate, and that drug-induced heart rate variations and rate-dependent QT changes are proportional. Holter ECG allows to study the repolarization in selected RR cycles while controlling environmental rate-related and circadian influences. Repolarization duration was evaluated in 15 normal individuals and 13 patients with stable coronary artery disease and no heart failure who did not differ in terms of 24-hour heart rate, age and sex. The effects of a 3-month treatment with bepridil were assessed in the latter. Using the conventional evaluation through the corrected QT (Bazett formula), no difference was found between the two groups at baseline, and bepridil induced a non-significant 5% prolongation of QTc. At Holter recordings, the QTa (Q-T apex) duration was linearly correlated with the heart rate over 24 hours. To specifically study day-to-night variations and to exclude the rate-dependent and short-term autonomic influences. QTa was studied in populations of averaged QRS-T selected according to i) the last RR cycle length and ii) an identical mean RR interval during the preceding minute. Both RR values were fixed at 800 ms to obtain the "QTa-800" measured directly or extrapolated from linearly correlated, other RR values.(ABSTRACT TRUNCATED AT 250 WORDS)