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

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Aims. 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 (APD0). The APD/CL relationship was expressed by this function: of repolarization, CL50 (CL at which 50% of APDmax 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 (V5) were measured at the end of each load step; QTc (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≥0.90). In Purkinje fibres, APDmax was 461 ± 37 ms, CL50 was 394 ± 54 ms and S was 0.98 ± 0.11. APDmax and APD0 correlated (R=0.96) and were similar. The corresponding values in humans were: QTmax 432 ± 63 ms, RR50 345 ± 60 ms and S 2.6 ± 0.8. While QTc and QTmax were longer in females, RR50 and S were similar between genders. Amiodarone increased QTc, QTmax and RR50 and decreased S. In QTmax and QTc distributions generated by pooling data from treated and untreated subjects, 86% of treated subjects were correctly identified by QTmax and 28% by QTc. Conclusions. Canine and human repolarization showed a saturating dependency on cycle length, described by the proposed function. Gender and amiodarone independently affected QTmax, RR50 and S: therefore they might reflect specific ionic mechanisms. Finally, QTmax identified drug-induced repolarization abnormalities in individual subjects better than QTc.

Original languageEnglish
Pages (from-to)163-170
Number of pages8
Issue number2
Publication statusPublished - Apr 2003


  • Heart rate
  • QT interval
  • Ventricular repolarization

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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