doi: 10.1161/hc2601.091738
(Circulation. 2001;104:32.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Sexual Dimorphism in the Electrocardiographic Dynamics of Human Ventricular Repolarization
Characterization in True Time Domain
From the Department of Internal Medicine (M.H.L.), Division of Cardiology, University of Michigan and Veterans Administration Medical Center, Ann Arbor, Mich, and Sinai Hospital (M.H.L., H.Y.), Detroit, Mich.
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Abstract |
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Background—Previous characterizations of sex differences in ST-T waveform voltages have largely focused on amplitudes at selected time points during repolarization, subject to potential distortions from variations in heart rate (HR) or reliance on a JT-normalized time scale.
Methods and Results—Using digitized 12-lead ECGs from 553 normal adults (426 males) with HRs confined to 60±1, 70±1, or 80±1 bpm, we derived X, Y, and Z lead voltages and then generated, for each HR category by sex, summary (population mean) resultant spatial vector amplitudes (ST-TXYZ) and instantaneous slopes (dV/dtXYZ) at successive 4-ms intervals following the J point. Within each HR category, there was an early intersex divergence of ST-TXYZ trajectories (95% CIs nonoverlapping), with men exhibiting 2- to 3-fold greater dV/dtXYZ values during the ST segment and achieving greater maximum TXYZ and dV/dtXYZ values than women; descending TXYZ limbs were relatively more concordant between sexes but still steeper in men. The early sex differences in repolarization dynamics persisted in multiple regression analyses that took into account age and a morphometric index of left ventricular mass. In men, absolute values of extrema of TXYZ and dV/dtXYZ varied inversely with HR.
Conclusions—At physiological resting HRs, the spatial ST-T vector voltage time trajectory is steeper in men than in women, beginning virtually from the J point. In addition to its mechanistic implications, the demonstration of marked sensitivity of ST-TXYZ and especially dV/dtXYZ to sex raises the possibility that these time-based, ECG-derived parameters might be informative in pathophysiological studies of ventricular repolarization.
Key Words: electrocardiography • sex • heart rate
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Introduction |
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Recent awareness of an increased susceptibility of women to development of torsade de pointes ventricular tachycardia1 has highlighted the need to understand better the nature and extent of sex modulation of normal human ventricular repolarization. The existence of quantitative sex differences in the ECG manifestations of myocardial repolarization has been appreciated since the early 20th century, when Bazett2 reported that women have a longer average rate-corrected QT interval (QTc) than men. Such a sex disparity has since been confirmed repeatedly and found to apply to various ECG indices of repolarization duration.3 4 5 6 7 8
Over the years, investigators have also described differences between the sexes with respect to selected ST- and T-wave amplitudes, ie, typically higher mean values in men.3 4 9 10 11 These studies, however, did not correct for variations in heart rate (HR), a deficiency that other researchers attempted to remedy by reliance on a JT-normalized time scale.12 13 14 Thus, to date, a systematic comparison of the ST-T voltage trajectory and its dynamics, as a true function of time, in men and women has not been accomplished.
In the present study, we circumvented rate-related or temporal distortions inherent in previous methodologies by utilizing ECG data obtained at uniform HRs. This enabled us, for the first time, to compare by sex successive (4 ms) ST-T spatial vector voltages and first derivatives of those voltages in true time domain.
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Methods |
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We used a database of ECGs recorded on a MAC-12 System (Marquette Electronics Inc) in normal adults, as described previously.5 8 In brief, subjects contributing to the database had normal histories and physical examinations and were not taking any cardioactive medication. None had ECG evidence of ventricular hypertrophy, intraventricular conduction disturbance, or myocardial infarction. The study subset was limited to individuals in the database whose resting HR by ECG fell into 1 of 3 narrow ranges: 60±1, 70±1, and 80±1 bpm, hereafter designated as HR 60, HR 70, and HR 80, respectively.
The 12-lead ECG signals were digitized and recorded at 250 Hz (4-ms sampling intervals). HRs, as well as markings of P onset, QRS onset and offset (ie, J point), and T offset, based on the median beat, were calculated by the MAC-12 software (12SL program) as previously described and validated15 ; however, QRS onset and offset were the only predetermined fiducial points we used.
Exclusions
Of 618 subjects (482 men and 136 women) in the ECG
database who met the inclusion criteria described above, 34 (29 men and
5 women) had to be excluded because of incomplete ECG data files. An
additional 31 subjects (27 men and 4 women) were excluded because of
the absence of height or weight data needed for estimation of body
surface area (described below). ECGs for the remaining 553 subjects
formed the basis of the present study.
Study Population Characteristics
Of the 553 study subjects, 426 (77%) were men and
127 (23%) were women. These individuals hailed from across the United
States and had the following racial profile: 416 (75.2%) were white,
40 (7.2%) were black, 40 (7.2%) were Hispanic, 13 (2.4%) were
Oriental, 12 (2.2%) were Native American, and 32 (5.8%) were of
unknown race. Mean age of the men was 34.0±12.1 years (range 15 to 74
years), and mean age of the women was 40.9±16.5 years (range 17 to 81
years).
Computed ECG Parameters
Digitized and MAC-12–preprocessed 12-lead ECG
signals were stored and processed on a personal
computer.8 For purposes of
the present study, we confined our analysis primarily to
the ST-T waveform, ie, ECG voltages recorded during the JT
interval, at successive 4-ms intervals, with t=0 ms defined at the J
point. Various ECG-derived parameters were calculated for
distinct population subsets within the database, stratified by HR
category and sex. Our analysis was based on ST-T vector
voltages in the 3 orthogonal Frank X, Y, and Z leads
(ST-Tx, ST-Ty, and
ST-Tz, respectively), which were mathematically
synthesized (at each successive sample time) from linear combinations
of standard ECG leads V1 through
V6 and leads I and
II.16
Instantaneous Voltages of Reconstructed Spatial
ST-T Vectors as a Function of Time
For each subject, the voltage magnitude of the
reconstructed instantaneous spatial ST-T vector was calculated as the
3D resultant, ST-Txyz, of the 3 orthogonal
components ST-Tx, ST-Ty,
and ST-Tz. Thus, at any given sample time
ti:
 | (1) |
For a population of
n subjects, we could then
calculate at each sample time a summary (population mean) instantaneous resultant
spatial ST-T voltage as follows:
 | (2) |
Instantaneous Slopes (dV/dt) of ST-T
Waveform
For any given sequence of
ST-T(ti) voltages, the raw instantaneous slope
(change in voltage, or dV/dt) of
the ST-T(t) curve at t=ti is approximated by
[ST-T(ti)-ST-T(ti-1)]/[ti-ti-1],
provided ti-ti-1 is
sufficiently small (4 ms in our study). Owing to the jagged nature of
the resulting dV/dt of ST-T
waveform, we used a 7-point moving average of this raw
dV/dt (centered at each
ti) to generate a smoothed
dV/dt of ST-T
waveform,8 beginning at 16 ms
after the J point. Throughout the remainder of this article,
dV/dt is assumed to refer to
smoothed dV/dt.
Using the dV/dt values
for each ST-Txyz curve, designated
dV/dtxyz, it was then possible to
calculate for the n-sized population of
interest, at any sample time ti (beginning 16 ms
after the J point), a summary (population mean) instantaneous slope of
the spatial ST-T voltage vector magnitude waveform, as
follows:
 | (3) |
A more mathematically precise notation for this parameter is d(VXYZ)/dt, but we have opted for dV/dtXYZ as a simpler linear notation, with the understanding that the spatial subscript (XYZ) actually applies to the ST-T voltage (V) rather than time (t).
Feature Extraction
Specific parameters were extracted from
the summary (not individual) ST-TXYZ and
dV/dtXYZ curves. Three extrema were derived: Max
TXYZ, the peak value of
TXYZ, and Max (or Min)
dV/dtXYZ, the peak positive (or peak negative)
value of dV/dtXYZ. Two duration
parameters were extracted: J-to-Max
TXYZ, the time from the J point to the peak of
TXYZ, and J-to-End TXYZ,
the time from the J point to the nadir between
TXYZ and
UXYZ.
Statistical Analysis
Summary values of a given parameter with
corresponding 95% CIs were plotted on a graph to depict quantitative
differences in summary waveforms between the sexes. Inasmuch as age is
known to affect various ECG parameters of depolarization
and
repolarization,4 6 9 10 14
we repeated our sex comparisons within HR categories dichotomized by a
40-year age cut point. ST-TXYZ and
dV/dtXYZ were also recalculated as
parameters normalized for each subject’s height (in
meters) to the 2.7 power and, alternatively, body surface area
estimated17 from height and
weight to the 1.5 power. These morphometric indices (especially the
former) have been shown to largely adjust for sex differences in
echocardiographically measured left
ventricular
mass.18
Intersex and intrasex comparisons of mean age, height2.7, and QRS duration for the 3 HR categories were performed initially with ANOVA, followed where appropriate by Student’s unpaired t test. Within each HR category, multiple regression analysis was used to assess the potential influence of sex, age (as a continuous variable), and height2.7 on both ST-TXYZ and dV/dtXYZ at 40, 80, and 120 ms after the J point and on the extrema Max TXYZ, Max dV/dtXYZ, and Min dV/dtXYZ. Analogous multiple regression analyses were performed to analyze the potential influence of HR on these extrema of TXYZ and dV/dtXYZ for each sex. Statistical significance in these analyses was defined as P<0.05.
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Results |
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Table 1
provides age, morphometric, and QRS duration data
for study subjects by HR category. Within each HR category, men
were younger, with greater mean height2.7
and QRS duration. For each sex, there were no significant differences
across HR categories with respect to any of the 3
parameters except for age in men, at HR 60 versus HR 80
(P<0.03).
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ST-TXYZ and
dV/dtXYZ in Men vs Women
Figure 1 shows, for each HR category, a comparison by sex of
summary ST-TXYZ voltages (top panels) and
summary dV/dtXYZ values (bottom panels) as a
function of time (referenced to the J point). At each HR, the
ST-TXYZ mean voltages, from the J point through
the entire ascending limb of TXYZ, achieved
greater values and peaked 28 to 32 ms sooner in men. The 95% CIs for
these mean voltages, at each 4-ms sample time, were nonoverlapping
between the sexes from the J point (or just beyond) through their
respective TXYZ peak amplitudes. Although the
J-to-End TXYZ interval was also shorter in men
(by 20 to 36 ms), mean spatial vector voltages were relatively more
concordant between sexes over the course of the descending limb of
TXYZ after transient overlap of 95% CIs, with
mean voltages declining more rapidly in men. The
UXYZ peak also occurred earlier (by 32 to 52 ms)
in men than in women.
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) at 3 common HRs. Upper panels show ST-TXYZ waveforms and lower panels dV/dtXYZ waveforms, with left, middle, and right vertical panel pairs corresponding to HR 60, HR 70, and HR 80 bpm, respectively. Time scale is absolute (nonnormalized), referenced to J point (0 ms). Vertical bars extending above and below data points demarcate 95% CIs for depicted summary values; when these bars are not shown for particular data points, size of corresponding 95% CI is actually smaller than diameter of plotted symbol. ST-TXYZ waveform plots consist of contiguous STXYZ and TXYZ portions, followed by low-amplitude UXYZ. Plots of dV/dtXYZ begin at 16 ms after J point (see Methods); mV/s units are equivalent to µV/ms. Format similar in subsequent figures, except as indicated.
As evident from the dV/dtXYZ curves
in
Figure 1
, for each HR category, early values of
dV/dtXYZ, as well as absolute maximum and
minimum values, were consistently greater in men. At each HR,
the 95% CIs for mean instantaneous slopes of the spatial vector
voltage time function were nonoverlapping between men and women, from
the first plotted value (at 16 ms after the J point) through the timing
of Max dV/dtXYZ in men. After the initial
crossing of the male and female dV/dtXYZ curves
(near Max dV/dtXYZ in women), the 95% CIs were
again nonoverlapping through the timing of Min
dV/dtXYZ in men. Subsequently, in their terminal
portions, these dV/dtXYZ curve pairs exhibited
somewhat greater concordance. Max dV/dtXYZ was
attained 28 to 40 ms and Min dV/dtXYZ 24 to 36
ms sooner in men than in women.
Even at the 40- and 80-ms points of the ST segment, the male
to female ratios for summary parameters
ST-TXYZ and dV/dtXYZ
ranged approximately from 1.2 to 2.5 and from 2.3 to 3.6, respectively,
at each HR, with nonoverlap of even 99% CIs between the sexes for
ST-TXYZ and dV/dtXYZ
values
(Table 2). In all 3 HR categories, the sex ratios for these
ST-related parameters (especially
dV/dtXYZ) typically exceeded the female to male
ratios (range 1.1 to 1.2) for either of the repolarization duration
indices, J-to-Max TXYZ or J-to-End
TXYZ.
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ST-T Voltages in ECG-Derived Orthogonal
Leads
Figure 2 shows summary ST-T voltages at successive 4-ms
intervals in each of the 3 mathematically synthesized orthogonal
component leads that were used to reconstruct successive
ST-TXYZ vectors, at HR 70. Although mean ST-T
voltages until the T-wave peak were of greater absolute magnitude in
men for each of the 3 orthogonal leads (but most apparent in leads X
and Z), the algebraic signs of these components from the J point onward
were similar in both sexes (ie, positive in X, positive in Y, and
negative in Z), yielding a spatial orientation of each instantaneous
resultant vector that was grossly comparable (directed leftward,
inferiorly, and anteriorly) in men and women. Similar
results were obtained at HR 60 and HR 80 (data not
shown).
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Adjustment for Age and Body Size
The sexual dimorphism in ST-TXYZ
voltages and dV/dtXYZ observed at HR 70
(Figure 1) was maintained when ECGs were dichotomized with a
40-year age cut point
(Figure 3; more evident in the younger age group) or when the
analysis was performed with ST-T voltages normalized by
height2.7
(Figure 4). Qualitatively similar results were obtained at HR
60 and HR 80 (data not shown). For all 3 HR categories, the described
sex differences also persisted when morphometric normalization was
performed with body surface area1.5 rather
than height2.7 (data not shown).
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40 years of age.
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Within HR groups, multiple regression analysis was performed to assess the possible predictive effects of sex, age, and height2.7, specifically on early spatial vector amplitudes and slopes, at 40, 80, and 120 ms after the J point. Sex was found to be a highly significant independent predictor of the 3 early ST-TXYZ parameters (P<0.0001 at HR 60 and HR 70, P<0.004 at HR 80) and the 3 early dV/dt XYZ parameters (P<0.0001 at HR 60 and HR 70, P<0.001 at HR 80). Age was also a significant independent (inversely related) predictor of these various parameters at HR 60 and HR 70 (P<0.0001) but not at HR 80. Height2.7, however, was virtually never an independent predictor of any of the 6 parameters (exception mainly at 40 ms).
When extrema of TXYZ and dV/dtXYZ were similarly analyzed by multiple regression analysis, within HR categories, sex was independently predictive of Max TXYZ at all 3 HRs (P<0.001), Max dV/dtXYZ at HR 60 and HR 80 (P<0.02), and Min dV/dtXYZ at HR 60 and HR 70 (P<0.05). For all 3 HRs, age, but not height2.7, was a significant (inverse) predictor of Max TXYZ (P<0.02) and absolute values of Max (P<0.03) and Min (P<0.01) dV/dtXYZ.
Effect of HR on ST-TXYZ
and dV/dtXYZ
Superimposed HR plots of
ST-TXYZ and dV/dtXYZ for
men and women are shown in
Figure 5. When extrema of TXYZ and
dV/dtXYZ were compared by HR, within each sex,
multiple regression analysis (incorporating age and
height2.7) revealed a statistically
significant HR effect in men such that the absolute values for Max
TXYZ, Max dV/dtXYZ, and
Min dV/dtXYZ varied inversely with HR
(P<0.0001, HR 70 and HR 80
versus HR 60 for Max TXYZ;
P<0.02, HR 80 versus HR 60 for
Max dV/dtXYZ; and
P<0.0001, HR 80 versus HR 60,
and P<0.01, HR 70 versus HR
60, for Min dV/dtXYZ). There were no
statistically significant differences among values of these
parameters in women, however, when compared by HR. In both
sexes, the multiple regression analysis also showed age, but
not height2.7, to be a significant
(inversely related) predictor of the absolute values of Max
TXYZ, Max dV/dtXYZ, and
Min dV/dtXYZ
(P<0.0001 for men,
P<0.02 for
women).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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The present study is the first to compare at common HRs in men and women successive mean ECG-derived spatial vectorcardiographic voltages (ST-TXYZ) and concomitant mean instantaneous slopes (dV/dtXYZ) at high temporal resolution during ventricular repolarization. At each of the 3 physiological resting rates studied (HR 60, HR 70, and HR 80), our findings attest to clear quantitative sex differences in the ECG dynamics of repolarization, with more brisk dynamics of ST-T–wave generation seen in men. This sex difference largely persisted after adjustment for age and body size.
Conventional3 4 9 10 and orthogonal11 lead scalar ECG studies have demonstrated in men greater peak T-wave amplitudes (especially anteriorly), select ST-segment voltages, and precordial mean ST angles.19 Limiting these prior investigations, however, was the fact that measured ST-T parameters were averaged within study groups regardless of intersubject variations in HR. In contrast, Green et al14 used a time-normalization procedure on digitized body-surface potential maps in normal subjects and reported "slightly" larger average ST potentials and greater average early and mid T-wave potentials in men than in women. Analogous observations were made in previous scalar orthogonal lead ECG studies in which intersex time-normalized repolarization voltages were compared at successive 1/8 time divisions of the JT interval.12 13 More recently, Macfarlane20 found men to have greater average ST angles, as measured between the J point and 3/8 of the JT interval (P.W. Macfarlane, PhD, personal communication, 1999), in selected conventional ECG leads. The time-normalization approach, however, is acknowledged to introduce some distortions of its own, potentially affecting intergroup comparisons.14
The present study design was intended to overcome
limitations of the earlier methodologies by focusing on ECGs at common
HRs, thereby permitting direct and comprehensive comparisons of derived
3D vectorcardiographic voltages as a true function of time (at 4-ms
intervals) during ventricular repolarization. We
demonstrated greater and more rapidly attained absolute values of
maximal instantaneous slopes of the ascending and descending limbs of
the spatial T vector waveform in men, extending our findings in lead
V5.8
Importantly, the present study enabled us to trace systematically
the temporal origin of these more brisk male dynamics of T-wave
generation back to the ST segment
(Figure 1), where dV/dtXYZ values were
already some 2- to 3-fold greater in men
(Table 2). Thus, at each study HR, a steeper
ST-TXYZ voltage time trajectory was found in men
relative to women, essentially from the ECG inception of
ventricular repolarization. Moreover, sex differences in
early ST-T amplitudes and slopes persisted in multiple regression
analyses that included age and
height2.7.
We found expected sex differences in repolarization
duration5 to be of relatively
smaller magnitude than the sex disparity in early
dV/dtXYZ values. Whereas J-to-Max
TXYZ and J-to-End TXYZ
were shorter (by 
20 to 40 ms) in men, the female to male ratios were
just slightly >1 for both parameters.
Mechanistic Considerations
The ST-T waveform is primarily a manifestation of
successive, instantaneous net transmural ventricular
voltage gradients during repolarization, with superimposed effects of
regional, ie, "geographic," differences in electrical recovery
properties (especially within the more rapidly repolarizing epicardial
layer).21 The general
concordance in orthogonal lead distribution of early ST-T voltages in
men and women
(Figure 2), however, argues against a gross sex disparity in
geographic sequence of repolarization as the basis for the observed
sexual dimorphism in ST-TXYZ
dynamics.
More tenable is the hypothesis that during repolarization, there are sex-related quantitative differences in the action potential voltage time course of 1 or more ventricular transmural cell types that may have an effect on the morphology of the ST-T waveform. This conjecture is motivated by experimental data implying that the aggregate ventricular repolarization gradient reflected in the ST-T waveform until the peak of the T wave is driven largely by the voltage time dynamics of phases 2 and 3 of action potentials in the epicardium relative to those of deeper myocardial cell layers.22
Sex steroids (especially androgens) appear likely mediators23 of the peripubertal shortening of QTc6 and the lower propensity to JTc prolongation24 and torsade de pointes1 exhibited by men versus women. By extension, these hormones, which are capable of affecting repolarizing currents,25 26 also could have a modulating influence on the transmural voltage gradients that contribute to the genesis and dynamics of the ST-T waveform. This hypothesis is supported by a recent report describing differences in precordial lead T-wave amplitudes and average ST angles under altered androgenic states.27
Influence of HR and Age
Our findings, at least in men, of a decrease in Max
TXYZ as resting HR increases
(Figure 5) confirm definitively earlier scalar ECG
impressions.3 Such behavior,
implying the need for "rate correction" of maximum T-wave amplitude
measurements, is consistent with observations in the perfused
left ventricular wedge
preparation.28 We further
documented a similar inverse relationship in men between absolute value
of Max (and Min) dV/dtXYZ and HR.
In both men and women, age was found to be an independent (inverse) predictor of the absolute values of the extrema of TXYZ and dV/dt XYZ (at all 3 HRs), as well as the values of these parameters during the ST segment (at HR 60 and HR 70). Although of unclear mechanistic origin, these observations at controlled HRs extend traditional ECG analyses showing age-related declines in ST-T parameters, especially in men, during adulthood.4 9 10
Study Limitations
Conceivably, differences in resting HR among the study
population may have reflected, in part, variations in other
physiological parameters, eg,
sympathetic and parasympathetic tone. Such an HR selection artifact
could have had a confounding influence on the quantitative comparison
of repolarization dynamics among the HR categories we studied but would
not be expected to negate the highly consistent sex difference
we documented within each HR group. We recognize that the onset of
detectable ventricular repolarization actually precedes the
J point (our operational "time zero") by an average of 5 to 12
ms.29 However, slight
interindividual differences in true t0 would not
explain the consistent early upward displacement of the
dV/dtXYZ curves and steeper
STXYZ trajectory in men relative to women. The
relative paucity of women in our study population (<1:3 female:male
ratio) may have limited our ability to precisely define the
relationship between HR and Max TXYZ, Max
dV/dtXYZ, and Min
dV/dtXYZ in women
(Figure 5). Expanded studies are needed to address this issue
and to explore ST-T dynamics in nonwhite populations, older subjects,
and groups with defined levels of physical
activity.
Implications
The present findings add to accumulating evidence
for the existence of fundamental differences between the sexes in the
physiology of ventricular repolarization. Our observations
of the marked sex sensitivity of instantaneous ST-T spatial vector
amplitudes, and particularly slopes, raise the possibility that these
time-based parameters may convey information regarding a
variety of processes capable of modulating
repolarization.30
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Acknowledgments |
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The authors thank Gregor Altvater, BSEE, for reviewing the data calculations; Dan Montgomery, BS, for assistance with statistical analysis and preparation of the figures; and Michael R. Rosen, MD, and Janice M. Jenkins, PhD, for their critical reviews of the manuscript.
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Footnotes |
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Reprint requests to Michael H. Lehmann, MD, University of Michigan Medical Center, Women’s Hospital Room L3119, Box 0273, 1500 E Medical Center Dr, Ann Arbor, MI 48109-0273.
Received January 26, 2001; revision received April 4, 2001; accepted April 11, 2001.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Makkar RR, Fromm BS, Steinman RT, et al. Female gender as a risk factor for torsade de pointes associated with cardiovascular drugs. JAMA. 1993;270:2590–2597.
2. Bazett H. An analysis of the time relations of electrocardiogram. Heart. 1920;7:353–370.
3. Ashman R, Hull E. Essentials of Electrocardiography. New York, NY: Macmillan Co; 1941:145–167.
4. Macfarlane PW, Lawrie TDV. The normal electrocardiogram and vectorcardiogram. In: MacFarlane PW, Lawrie TDV, eds. Comprehensive Electrocardiology: Theory and Practice in Health and Disease. New York, NY: Pergamon Press; 1989;1:407–445.
5. Merri M, Benhorin J, Alberti M, et al. Electrocardiographic quantitation of ventricular repolarization. Circulation. 1989;80:1301–1308.
6. Rautaharju PM, Zhou SH, Wong S, et al. Sex differences in the evolution of the electrocardiographic QT interval with age. Can J Cardiol. 1992;8:690–695.
7. Lepeschkin E, Surawicz B. The duration of the Q-U interval and its components in electrocardiograms of normal persons. Am Heart J. 1953;46:9–20.
8. Yang H, Elko P, Fromm BS, et al. Maximal ascending and descending slopes of the T wave in men and women. J Electrocardiol. 1997;30:267–276. (Correction. 2001;34:183)
9. Simonson E. Differentiation between normal and abnormal in electrocardiography. St Louis, Mo: Mosby Co; 1961:99–101.
10. Gambill CL, Wilkins ML, Haisty WK, et al. T wave amplitudes in normal populations. J Electrocardiol. 1995;28:191–197.
11. Sotobata I, Richman H, Simonson E. Sex differences in the vectorcardiogram. Circulation. 1968;37:438–448.
12. Nemati M, Doyle JT, McCaughan D, et al. The orthogonal electrocardiogram in normal women: implications of sex differences in diagnostic electrocardiography. Am Heart J. 1978;95:12–21.
13. Ishikawa K. Correlation coefficients for electrocardiographic and constitutional variables. Am Heart J. 1976;92:152–161.
14. Green LS, Lux RL, Haws CW, et al. Effects of age, sex, and body habitus on QRS and ST-T potential maps of 1100 normal subjects. Circulation. 1985;71:244–253.
15. 12SL ECG Analysis Program Physician’s Guide. Milwaukee, Wis: GE Marquette Medical Systems Inc; 1999.
16. Edenbrandt L, Pahlm O. Vectorcardiogram synthesized from a 12-lead ECG: superiority of the inverse Dower matrix. J Electrocardiol. 1988;21:361–367.
17. Mosteller R. Simplified calculation of body-surface area. N Engl J Med. 1987;317:1098. Letter.
18. de Simone G, Daniels SR, Devereux RB, et al. Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight. J Am Coll Cardiol. 1992;20:1251–1260.
19. Bidoggia H, Maciel JP, Capalozza N, et al. Sex-dependent electrocardiographic pattern of cardiac repolarization. Am Heart J. 2000;140:430–436.
20. Macfarlane PW, Lawrie TDV, eds. Comprehensive Electrocardiology: Theory and Practice in Health and Disease. New York, NY: Pergamon Press; 1989;3:1459.
21. Surawicz B. ST-T abnormalities. In: MacFarlane PW, Lawrie TDV, eds. Comprehensive Electrocardiology: Theory and Practice in Health and Disease. New York, NY: Pergamon Press; 1989;3:511–563.
22. Antzelevitch C, Yan GX, Shimizu W, et al. Electrical heterogeneity, the ECG and cardiac arrhythmias. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology: From Cell to Bedside. 3rd ed. Philadelphia, Pa; WB Saunders Co; 2000:222–238.
23. 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.
24. Lehmann MH, Hardy S, Archibald D, et al. JTc prolongation with d,l-sotalol in women versus men. Am J Cardiol. 1999;83:354–359.
25. Liu XK, Katchman A, Drici MD, et al. Gender difference in the cycle length-dependent QT and potassium currents in rabbits. J Pharmacol Exp Ther. 1998;285:672–679.
26. Hara M, Danilo P Jr, Rosen MR. Effects of gonadal steroids on ventricular repolarization and on the response to E4031. J Pharmacol Exp Ther. 1998;285:1068–1072.
27. Bidoggia H, Maciel JP, Capalozza N, et al. Sex differences on the electrocardiographic pattern of repolarization: possible role of testosterone. Am Heart J. 2000;140:678–683.
28. Shimizu W, Antzelevitch C. Sodium channel block with mexiletine is effective in reducing dispersion of repolarization and preventing torsade des pointes in LQT2 and LQT3 models of the long-QT syndrome. Circulation. 1997;96:2038–2047.
29. Spach MS, Barr RC, Benson W, et al. Body surface low-level potentials during ventricular repolarization with analysis of the ST segment: variability in normals. Circulation. 1979;59:822–836.
30. Sasaki A, Takimiya A, Arai T, et al. Abnormalities of T waves in effort angina pectoris patients at rest evaluated by spatial velocity electrocardiogram. Jpn Heart J. 1996;37:879–889.
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