© 2003 by European Society of Cardiology
Characterization of the non-linear rate-dependency of QT interval in humans
1Divisione di Cardiologia, Ospedale San Luca, Istituto Auxologico Italiano IRCCS Milano, Italy; 2Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca Milano, Italy
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: APD=APDmax*CLS/(CL50S+CLS), where APDmax (APD extrapolated at infinite CL) is a rate-independent measure 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.
Key Words: Heart rate, QT interval, ventricular repolarization
Correspondence: Dott.ssa Gabriella Malfatto, Divisione di Cardiologia, Ospedale San Luca, Istituto Auxologico Italiano IRCCS, via Spagnoletto, 3-20149 Milano, Italy. Tel.: 39-02-582161; Fax: 39-02-58216712; E-mail: Malfi{at}Auxologico.it
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