© 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
[1] Boyett MR and Jewell BR. Analysis of the effects of changes in rate and rhythm upon electrical activity in the heart. Prog Biophys Molec Biol 1980; 36: 1–52.[Web of Science][Medline]
[2] Kligfield P, Lax KG, Okin PM. QT interval-heart rate relation during exercise in normal men and women: definition by linear regression analysis. J Am Coll Cardiol 1996; 28: 1547–1555.[Abstract]
[3] Ahnve S. Correction of the QT interval for heart rate: review of different formulas and the use of Bazett's formula in myocardial infarction. Am Heart J 1985; 109: 568–574.[CrossRef][Web of Science][Medline]
[4] Karjalainen J, Viitasalo M, Manttari M. Relation between QT intervals and heart rates from 40 to 120 beats/min in rest electrocardiograms of men and a simple method to adjust QT interval values. J Am Coll Cardiol 1994; 23: 1547–1553.[Abstract]
[5] Aytemir K, Maarouf N, Gallagher MM. Comparison of formulae for heart rate correction of QT interval in exercise electrocardiograms. Pacing Clin Electrophysiol 1999; 22: 1397–1401.[CrossRef][Medline]
[6] Merri M, Moss AJ, Benhorin J. Relation between ventricular repolarization duration and cardiac cycle length during 24-hour Holter recordings. Findings in normal patients and patients with long QT syndrome. Circulation 1992; 85: 1816–1821.
[7] Malik M. Problems of heart rate correction in assessment of drug-induced QT interval prolongation. J Cardiovasc Electrophysiol 2001; 12: 411–420.[CrossRef][Web of Science][Medline]
[8] Batchvarov V and Malik M. Individual pattern of QT/RR relationship. Cardiac Electro-Physiological Review 2002; 6: 282–288.[CrossRef]
[9] Elharrar V and Surawicz B. Cycle length effect on restitution of action potential duration in dog cardiac fibers. Am J Physiol 1983; 244: H782–H792.
[10] Zaza A, Malfatto G, Schwartz PJ. Sympathetic modulation of the relation between ventricular repolarization and cycle length. Circ Res 1991; 68: 1191–1203.
[11] Malfatto G, Zaza A, Schwartz PJ. Parasympathetic control of cycle length dependence of endocardial ventricular repolarisation in the intact feline heart during steady state conditions. Cardiovasc Res 1993; 27: 823–827.
[12] Malfatto G, Zaza A, Vanoli E, Schwartz PJ. Muscarinic effects on action potential duration and its rate dependence in canine Purkinje fibers. Pacing Clin Electrophysiol 1996; 19: 2023–2026.[CrossRef][Medline]
[13] Antzelevitch C, Sicouri S, Litovsky SH, Lukas A, Krishnan SC, Di Diego JM, Gintant GA, Liu DW. Heterogeneity within the ventricular wall. Electrophysiology and pharmacology of epicardial, endocardial, and M cells. Circ Res 1991; 69: 1427–1449.
[14] Burashnikov A and Antzelevitch C. Block of I(Ks) does not induce early after-depolarization activity but promotes beta-adrenergic agonist-induced delayed afterdepolarization activity. J Cardiovasc Electrophysiol 2000; 11: 458–465.[Web of Science][Medline]
[15] Stramba-Badiale M, Locati EH, Martinelli A, et al. Gender and the relationship between ventricular repolarization and cardiac cycle length during 24-h Holter recordings. Eur Heart J 1997; 18: 1000–1006.
[16] Drici MD, Burklow TR, Haridasse V, et al. Sex hormones prolong the QT interval and downregulate potassium channel expression in the rabbit heart. Circulation 1996; 94: 1471–1474.
[17] Lau CP, Freedman AR, Fleming S, Malik M, Camm AJ, Ward DE. Hysteresis of the ventricular paced QT interval in response to abrupt changes in pacing rate. Cardiovasc Res 1988; 22: 67–72.[Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. P. Imredy, J. R. Penniman, S. J. Dech, W. D. Irving, and J. J. Salata Modeling of the adrenergic response of the human IKs current (hKCNQ1/hKCNE1) stably expressed in HEK-293 cells Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H1867 - H1881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rocchetti, V. Freli, V. Perego, C. Altomare, G. Mostacciuolo, and A. Zaza Rate dependency of {beta}-adrenergic modulation of repolarizing currents in the guinea-pig ventricle J. Physiol., July 1, 2006; 574(1): 183 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fink, W. R Giles, and D. Noble Contributions of inwardly rectifying K+ currents to repolarization assessed using mathematical models of human ventricular myocytes Phil Trans R Soc A, May 15, 2006; 364(1842): 1207 - 1222. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||