Characterization of the non-linear rate-dependency of QT interval in humans

Alms Repolarization has rate-dependent and rate-independent components. A function considering such components separately was validated in canine Purkinje fibres and applied to the QT/RR relation in humans. Methods and Results Action potential duration (APD) was measured in Purkinje fibres during steady-state pacing at different cycle lengths (CL) and after prolonged quiescence (APD,). The APD/CL relationship was expressed by this function: APD = APD(max)(*)CL(S)/(CL50S + CLS), where APD(max) (APD extrapolated at infinite CL) is a rate-independent measure of repolarization, CL50 (CL at which 50% of APD(max) is achieved) and S evaluates the rate dependency of APD. The same function was used to fit the QT/RR relation in 46 normal subjects (20 males. 26 females) and in 7 amiodarone-treated subjects undergoing a bicycle stress test. RR and QT (V-5) were measured at the end of each load step: QT, (Bazett*s formula) was obtained at rest. The APD/CL and QT/RR relations were equally well expressed by the function with high correlation coefficients (R greater than or equal to 0.90). In Purkinje fibres, APD(max) was 461 +/- 37 ms, CL50 was 394 +/- 54 ms and S was 0.98 +/- 0.11. APD(max) and APD, correlated (R=0.96) and were similar. The corresponding values in humans were: QT(max) 432 +/- 63 ms. RR50 345 +/- 60 ms and S 2.6 +/- 0.8. While QT(c) and QT(max) were longer in females. RR50 and S were similar between genders. Amiodarone increased QT(c). QT(max) and RR50 and decreased S. In QT(max) and QT, distributions generated by pooling data from treated and untreated subjects. 86% of treated subjects were correctly identified by QT(max) and 28% by QT(c). Conclusions Canine and human repolarization showed a saturating dependency on cycle length. described by the proposed function, Gender and amiodarone independently affected QT(max), RR50 and S: therefore they might reflect specific ionic mechanisms. Finally. QT(max) identified drug-induced repolarization abnormalities in individual subjects better than QT(c).