Literature DB >> 12633641

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

G Malfatto1, M Facchini, A Zaza.   

Abstract

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 (APD(0)). The APD/CL relationship was expressed by this function: APD=APD(max)(*)CL(S)/(CL(50)(S)+CL(S)), where APD(max) (APD extrapolated at infinite CL) is a rate-independent measure of repolarization, CL(50) (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(c) (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>or=0.90). In Purkinje fibres, APD(max) was 461+/-37 ms, CL(50) was 394+/-54 ms and S was 0.98+/-0.11. APD(max) and APD(0) correlated (R=0.96) and were similar. The corresponding values in humans were: QT(max) 432+/-63 ms, RR(50) 345+/-60 ms and S 2.6+/-0.8. While QT(c) and QT(max) were longer in females, RR(50) and S were similar between genders. Amiodarone increased QT(c), QT(max) and RR(50) and decreased S. In QT(max) and QT(c) 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), RR(50) and S: therefore they might reflect specific ionic mechanisms. Finally, QT(max) identified drug-induced repolarization abnormalities in individual subjects better than QT(c). Copyright 2003 The European Society of Cardiology. Published by Elsevier Science Ltd.

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Year:  2003        PMID: 12633641     DOI: 10.1053/eupc.2002.0297

Source DB:  PubMed          Journal:  Europace        ISSN: 1099-5129            Impact factor:   5.214


  3 in total

1.  A novel method for patient-specific QTc--modeling QT-RR hysteresis.

Authors:  David M Hadley; Victor F Froelicher; Paul J Wang
Journal:  Ann Noninvasive Electrocardiol       Date:  2011-01       Impact factor: 1.468

2.  Integrated TK-TD modeling for drug-induced concurrent tachycardia and QT changes in beagle dogs.

Authors:  Fan Wu; Tycho Heimbach; Panos Hatsis; Hai-Ming Tang; Raviprakash Dugyala; Qin Yue; Tao Wang; Handan He
Journal:  J Pharmacokinet Pharmacodyn       Date:  2017-06-22       Impact factor: 2.745

3.  Rate dependency of beta-adrenergic modulation of repolarizing currents in the guinea-pig ventricle.

Authors:  M Rocchetti; V Freli; V Perego; C Altomare; G Mostacciuolo; A Zaza
Journal:  J Physiol       Date:  2006-02-16       Impact factor: 5.182

  3 in total

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