Ventricular gradient and nondipolar repolarization components increase at higher heart rate.

Differences in action potential duration reflect differences in ion channel properties. These properties also determine rate dependence of action potential duration, and transmural dispersion was confirmed experimentally to increase with cycle length. While several electrocardiographic indexes characterizing repolarization abnormalities have been proposed, studies of their heart rate dependence are missing. This study therefore investigated rate relationship of two repolarization descriptors, namely, the so-called total cosine of the QRS-T angle (TCRT), proposed to characterize global repolarization heterogeneity, and the so-called relative T wave residuum (TWR), linked to regional repolarization dispersion. During 24-h holter recordings in 60 healthy subjects (27 males), a 12-lead ECG was obtained every 30 s. RR intervals, QT intervals, and TCRT and TWR were calculated in each ECG and averaged over RR interval bins ranging from 550 to 1,150 ms in 10-ms steps. Women had uniformly greater TCRT and TWR values than men did over the entire range of investigated RR intervals. Whereas the TCRT in both sexes showed marked rate dependence with higher values at long RR intervals (550 vs. 1,150 ms: women, 0.46 +/- 0.31 vs. 0.76 +/- 0.18, P = 9 x 10(-7); men, 0.08 +/- 0.45 vs. 0.49 +/- 0.35, P = 9 x 10(-8)), the rate dependence of TWR was more marked in women than in men, showing higher values at shorter RR intervals (550 ms vs. 1,150 ms: women: 0.29 +/- 0.14% vs. 0.08 +/- 0.06%, P = 2 x 10(-8); men: 0.14 +/- 0.12% vs. 0.04 +/- 0.02%, P = 2 x 10(-15)). This suggests that both global and regional repolarization heterogeneity are increased at faster heart rates. Whereas in women at all heart rates the sequence of repolarization more closely replicates the sequence of depolarization, localized repolarization is more heterogeneous than in men especially at fast heart rates.

[1]  Gan-XinYan,et al.  Cellular Basis for the Normal T Wave and the Electrocardiographic Manifestations of the Long-QT Syndrome , 1998 .

[2]  Y. Rudy,et al.  Imaging Dispersion of Myocardial Repolarization, I: Comparison of Body-Surface and Epicardial Measures , 2001, Circulation.

[3]  M. Rosen,et al.  Effects of gonadal steroids on gender-related differences in transmural dispersion of L-type calcium current. , 2002, Cardiovascular research.

[4]  D. Rosenbaum,et al.  Modulated dispersion explains changes in arrhythmia vulnerability during premature stimulation of the heart. , 1998, Circulation.

[5]  S. Priori,et al.  Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: findings from the International LQTS Registry. , 1998, Circulation.

[6]  D. Rosenbaum,et al.  Role of Structural Barriers in the Mechanism of Alternans-Induced Reentry , 2000, Circulation research.

[7]  C Antzelevitch,et al.  Distribution of M Cells in the Canine Ventricle , 1994, Journal of cardiovascular electrophysiology.

[8]  Katerina Hnatkova,et al.  Sex differences in the rate dependence of the T wave descending limb. , 2003, Cardiovascular research.

[9]  M. Nash,et al.  Imaging Electrocardiographic Dispersion of Depolarization and Repolarization During Ischemia: Simultaneous Body Surface and Epicardial Mapping , 2003, Circulation.

[10]  Katerina Hnatkova,et al.  Sex differences in repolarization homogeneity and its circadian pattern. , 2002, American journal of physiology. Heart and circulatory physiology.

[11]  T Heeren,et al.  Sudden death in the Framingham Heart Study. Differences in incidence and risk factors by sex and coronary disease status. , 1984, American journal of epidemiology.

[12]  D. Rosenbaum,et al.  Mechanism linking T-wave alternans to the genesis of cardiac fibrillation. , 1999, Circulation.

[13]  B. Surawicz,et al.  Primary T wave abnormalities caused by uniform and regional shortening of ventricular monophasic action potential in dog. , 1975, Circulation.

[14]  C. Antzelevitch,et al.  Transient Outward Current Prominent in Canine Ventricular Epicardium but Not Endocardium , 1988, Circulation research.

[15]  K. Kamiya,et al.  Heterogeneous distribution of the two components of delayed rectifier K+ current: a potential mechanism of the proarrhythmic effects of methanesulfonanilideclass III agents. , 1999, Cardiovascular research.

[16]  H V Huikuri,et al.  Sex-related differences in autonomic modulation of heart rate in middle-aged subjects. , 1996, Circulation.

[17]  D. T. Kaplan,et al.  Repolarization Inhomogeneities in Ventricular Myocardium Change Dynamically With Abrupt Cycle Length Shortening , 1991, Circulation.

[18]  C. Antzelevitch,et al.  Unique Topographical Distribution of M Cells Underlies Reentrant Mechanism of Torsade de Pointes in the Long-QT Syndrome , 2002, Circulation.

[19]  M. Franz,et al.  Monophasic action potential mapping in human subjects with normal electrocardiograms: direct evidence for the genesis of the T wave. , 1987, Circulation.

[20]  M. Malik,et al.  Spatial, temporal and wavefront direction characteristics of 12-lead T-wave morphology , 1999, Medical & Biological Engineering & Computing.

[21]  D. Rosenbaum,et al.  Modulation of ventricular repolarization by a premature stimulus. Role of epicardial dispersion of repolarization kinetics demonstrated by optical mapping of the intact guinea pig heart. , 1996, Circulation research.

[22]  B. Hoffman,et al.  Effect of heart rate on cardiac membrane potentials and the unipolar electrogram. , 1954, The American journal of physiology.

[23]  C. Antzelevitch,et al.  Transmural Heterogeneity of Ventricular Repolarization Under Baseline and Long QT Conditions in the Canine Heart In Vivo: Torsades de Pointes Develops with Halothane but not Pentobarbital Anesthesia , 2000, Journal of cardiovascular electrophysiology.

[24]  D. Noble,et al.  The interpretation of the T wave of the electrocardiogram. , 1978, Cardiovascular research.

[25]  M. Rosen,et al.  Impact of Sex and Gonadal Steroids on Prolongation of Ventricular Repolarization and Arrhythmias Induced by IK-Blocking Drugs , 2001, Circulation.

[26]  C. Fiset,et al.  Gender-Based Differences in Cardiac Repolarization in Mouse Ventricle , 2001, Circulation research.

[27]  Y. Rudy,et al.  Imaging Dispersion of Myocardial Repolarization, II: Noninvasive Reconstruction of Epicardial Measures , 2001, Circulation.

[28]  Katerina Hnatkova,et al.  Analysis of T-Wave Morphology From the 12-Lead Electrocardiogram for Prediction of Long-Term Prognosis in Male US Veterans , 2002, Circulation.

[29]  C. Antzelevitch,et al.  Characteristics of the delayed rectifier current (IKr and IKs) in canine ventricular epicardial, midmyocardial, and endocardial myocytes. A weaker IKs contributes to the longer action potential of the M cell. , 1995, Circulation research.

[30]  C Antzelevitch,et al.  A subpopulation of cells with unique electrophysiological properties in the deep subepicardium of the canine ventricle. The M cell. , 1991, Circulation research.

[31]  E. R. Smith,et al.  Vulnerability to ventricular arrhythmia: assessment by mapping of body surface potential. , 1986, Circulation.

[32]  G. Helguera,et al.  Remodeling of Kv4.3 Potassium Channel Gene Expression under the Control of Sex Hormones* , 2001, The Journal of Biological Chemistry.

[33]  M. Lehmann,et al.  Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. , 1993, JAMA.

[34]  P. Schwartz,et al.  Gender and the relationship between ventricular repolarization and cardiac cycle length during 24-h Holter recordings. , 1997, European heart journal.

[35]  M Malik,et al.  Analysis of 12-Lead T-Wave Morphology for Risk Stratification After Myocardial Infarction , 2000, Circulation.

[36]  M. Morad,et al.  Gender difference in the cycle length-dependent QT and potassium currents in rabbits. , 1998, The Journal of pharmacology and experimental therapeutics.

[37]  CHARLES ANTZELEVITCH,et al.  The M Cell: , 1999, Journal of cardiovascular electrophysiology.

[38]  P. C. Viswanathan,et al.  Effects of IKr and IKs heterogeneity on action potential duration and its rate dependence: a simulation study. , 1999, Circulation.

[39]  A. Katz,et al.  Cardiac Ion Channels , 1993 .

[40]  M. Nieminen,et al.  Relation of twelve-lead electrocardiographic T-wave morphology descriptors to left ventricular mass. , 2002, The American journal of cardiology.

[41]  E. Rowland,et al.  Dispersion of monophasic action potential duration: demonstrable in humans after premature ventricular extrastimulation but not in steady state. , 1992, Journal of the American College of Cardiology.

[42]  Franklin D. Johnston,et al.  The determination and the significance of the areas of the ventricular deflections of the electrocardiogram , 1934 .

[43]  M. Lehmann,et al.  Increased Propensity of Women to Develop Torsades de Pointes During Complete Heart Block , 1995, Journal of cardiovascular electrophysiology.

[44]  M. Franz,et al.  Is Dispersion of Ventricular Repolarization Rate Dependent? , 1997, Pacing and clinical electrophysiology : PACE.

[45]  C Antzelevitch,et al.  I(to) and action potential notch are smaller in left vs. right canine ventricular epicardium. , 1996, The American journal of physiology.

[46]  A J Camm,et al.  QT Dispersion Does Not Represent Electrocardiographic Interlead Heterogeneity of Ventricular Repolarization , 2000, Journal of cardiovascular electrophysiology.

[47]  Richard B. Devereux,et al.  Principal Component Analysis of the T Wave and Prediction of Cardiovascular Mortality in American Indians: The Strong Heart Study , 2002, Circulation.

[48]  S. Priori,et al.  Evaluation of the spatial aspects of T-wave complexity in the long-QT syndrome. , 1997, Circulation.