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

Summary— 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. Holler 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 Holler recordings, the QTa (Q‐T apex) duration was linearly correlated with the heart rate over 24 hours. To specifically study day‐tonight 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. Using this technique, the two groups differed at baseline in terms of dynamicity of QTa: the QTa/RR regression line slope was steeper in normals, and the strongly significant day‐to‐night difference of QTa‐800 (P < 0.001) observed in them was absent in coronary patients. Bepridil, wliich did not significantly modify the 24‐hour heart rate, lengthened the QTa‐800 by 4–5%: although no more marked than with the QTc, this increase became significant at daytime (P = 0.04) and at night (P = 0.01) because of the inter‐individual consistency of the modifications. These results suggest that the approach of QT evaluation in strictly comparable conditions of environmental rate and time allowed by the Hotter technique is better adapted than the conventional QTc method to assess limited drug‐induced changes.