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(Hypertension. 1996;27:251-258.)
© 1996 American Heart Association, Inc.
Articles |
Time-Voltage Area of the QRS for the Identification of Left Ventricular Hypertrophy
From The Division of Cardiology, Department of Medicine, The New York Hospital–Cornell Medical Center, New York.
Correspondence to Peter M. Okin, MD, The New York Hospital–Cornell Medical Center, 525 E 68th St, New York, NY 10021.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Abstract Standard electrocardiographic criteria have exhibited poor sensitivity for left ventricular hypertrophy at acceptable levels of specificity and perform less well in women than men, even when sex-specific criteria are used. The time-voltage integral of the horizontal plane vector QRS complex can improve identification of hypertrophy in men, but performance of this approach in women and the effect of sex-specific criteria on accuracy have not been examined. To evaluate the accuracy of the time-voltage integral of the QRS complex for the identification of left ventricular hypertrophy in women and to examine the effect of sex- and non–sex-specific criteria on test performance, we obtained standard 12-lead and orthogonal-lead signal-averaged electrocardiograms and echocardiograms in 175 control subjects without hypertrophy (43 women and 132 men) and 75 patients with hypertrophy (26 women and 49 men) defined by echocardiographic criteria (indexed left ventricular mass >110 g/m2 in women and >125 g/m2 in men). Voltage of the QRS complex was integrated over the total QRS duration in leads X and Z for calculation of the time-voltage integral of the horizontal plane vector complex. With the use of a partition of 99.2 µV·s with a specificity of 98% in the entire normal group, sensitivity of the horizontal plane vector integral was significantly lower in women than men (31% versus 71%, P<.001). In contrast, use of sex-specific partitions of 75.4 µV·s in women and 99.2 µV·s in men with matched 98% specificity significantly improved sensitivity in women to 81% (P<.001), with no change in sensitivity in men (71%). Comparison of receiver operating characteristic curves with the use of sex-specific criteria demonstrated no significant difference in overall performance of the horizontal plane vector integral between men and women. The 81% and 71% sensitivities of the sex-specific horizontal plane vector integral were significantly greater than the 27% to 58% sensitivities of sex-specific 12-lead electrocardiographic criteria in this population. Thus, sex-specific criteria significantly improve performance of the time-voltage integral of the QRS for the identification of left ventricular hypertrophy in women, with no loss of accuracy in men. Use of the time-voltage integral can improve the accuracy of the electrocardiogram for the identification of left ventricular hypertrophy in both women and men.
Key Words: echocardiography • electrocardiography • gender • hypertrophy
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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The standard 12-lead ECG remains the most widely used initial diagnostic test in the screening process for LVH. However, both simple voltage criteria based on measured QRS amplitudes1 2 3 4 5 6 and more complex ECG criteria that incorporate QRS voltages, QRS duration, P wave amplitudes, repolarization abnormalities, and demographic variables in linear scores5 6 7 8 9 10 have exhibited relatively poor sensitivity at high levels of specificity, limiting the clinical utility and cost-effectiveness of the ECG for the detection of hypertrophy.11 In addition, although information is limited regarding the relative performance of ECG criteria in men and women,4 12 13 recent observations suggest that even when ECG criteria are adjusted for known sex differences in QRS duration and amplitudes,14 15 16 17 18 19 standard ECG criteria appear to have lower accuracy in women than men.20 21
Accuracy of the ECG for the detection of LVH can be improved based on observations that relate increased LV mass to increases in the time-voltage area of the QRS complex.22 23 24 25 26 27 For example, the simple product of QRS voltage and duration, as an approximation of the time-voltage area of the QRS, can improve the ECG identification of hypertrophy as defined at autopsy25 and by echocardiography.26 However, test performance of these simple voltage-duration products is significantly lower in women than men.21 More precise quantification of QRS area by measurement of the time-voltage integral of the horizontal plane vector can further improve the ECG identification of LVH in men.27 However, performance of this approach in women and the effect of sex-specific criteria on test accuracy have not been examined. Therefore, we conducted the present study to evaluate the accuracy of the time-voltage integral of the QRS complex for the identification of LVH in women and to examine the effect of sex- and non–sex-specific criteria on test performance.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Study Population
Signal-averaged and 12-lead ECGs were obtained in 250 subjects who underwent echocardiography at The New York Hospital–Cornell Medical Center as part of several ongoing longitudinal studies. Group 1 consisted of 175 normotensive or mildly hypertensive subjects (132 men and 43 women; mean age, 48±10 [SD] years) with normal LV mass indexed to body surface area as defined below. Group 2 consisted of 75 subjects (49 men and 26 women; mean age, 51±16 years) with chronic regurgitant valvular heart disease and LVH. Because of the absence of any subjects with right or left bundle-branch block in group 1, subjects with bundle branch blocks were excluded from group 2. All subjects gave informed consent to participation in the study, which was performed in accordance with protocols approved by the Committee on Human Rights in Research of Cornell University Medical College. Data on signal-averaged ECG performance in a large proportion of the men in this study were included in a prior report of the performance of the time-voltage integral in men.27
Electrocardiography
Standard 12-lead ECGs were recorded at 25
mm/s and 1 mV/cm
standardization with equipment (Marquette Electronics Inc) whose
frequency response characteristics met recommendations of the American
Heart Association.28 All ECGs were digitized at 250 or 500
Hz, and all measurements were performed by computer from median
complexes with visual verification by a single investigator who had no
knowledge of the echocardiographic findings; QRS
duration was measured to the nearest millisecond and QRS amplitudes to
the nearest microvolt.
Several widely used ECG criteria for the detection of LVH were examined. These include QRS duration; Sokolow-Lyon voltage (sum of the amplitude of the S wave in lead V1 and the R wave in lead V5 or V6)10 ; Cornell voltage (sum of the amplitude of the R wave in lead aVL and the amplitude of the S wave in lead V3)6 ; the sum of QRS voltage in all 12 leads29 ; and the Romhilt-Estes point score,30 a complex ECG criterion for hypertrophy based on a weighted score that incorporates QRS duration, QRS voltages, repolarization changes, and P-wave abnormalities. On the basis of the observation that the product of QRS duration and voltage, as an approximation of the time-voltage area under the QRS, improves ECG identification of LVH,25 26 a voltage-duration product was calculated for Cornell voltage, Sokolow-Lyon voltage, and the 12-lead sum of QRS voltage.
Signal-Averaged
Electrocardiography
After careful skin preparation with the patient
lying quietly in
the supine position, three orthogonal X, Y, and Z leads were acquired
(Predictor Signal Averaging ECG, Arrhythmia Research
Technology, Inc) with an operator-selected template at a sampling
frequency of 2000 Hz. Signal averaging was terminated when the residual
root mean square noise in the ST segment was no more than 1 µV and in
the majority of cases when the residual noise reached 0.3 µV. Digital
filtering was performed on averaged, orthogonal-lead complexes with
a standard-frequency (0 to 100 Hz), low-pass filter. Vector
magnitudes were calculated for each filtered orthogonal lead as
(X2)1/2,
(Y2)1/2, and
(Z2)1/2, which were then combined into a
maximal spatial vector magnitude,
(X2+Y2+Z2)1/2.
Additional vector magnitudes were calculated separately for the
horizontal plane (X2+Z2)1/2,
frontal plane (X2+Y2)1/2,
and sagittal plane (Y2+Z2)1/2.
Vector QRS complex onset and offset were determined by a computer
algorithm that determined the first and last points at which voltage
exceeded the mean of the baseline noise level plus three times the SD
to the nearest 0.5 millisecond. Time-voltage integrals of each
vector QRS magnitude were measured over the duration of the QRS to the
nearest 0.01 µV·s.27 In addition, the peak amplitude
of the maximal spatial vector was measured to the nearest microvolt to
replicate previous vector
studies.27 31 32
Echocardiography
All subjects underwent standard M-mode and
two-dimensional
echocardiography performed by a skilled research
technician using a commercially available
echocardiograph equipped with 2.5- and 3.5-MHz
imaging transducers. LV dimensions were obtained from
two-dimensionally guided M-mode tracings according to the
recommendations of the American Society of
Echocardiography.33 Measurements were
performed on multiple cardiac cycles by use of a digitizing tablet and
were averaged. If M-mode tracings were technically inadequate, LV wall
thicknesses and internal dimensions were measured from the
two-dimensional study by the method recommended by the American
Society of Echocardiography.34 LV mass
was calculated according to an anatomically validated
formula,35 and LVH was considered present if the LV
mass indexed to body surface area exceeded 110 g/m2 in
women and 125 g/m2 in men, partition values chosen based on
the distribution of values in employed normotensive and hypertensive
adults36 and subsequently shown to be related to
prognosis.37 38
Data Analysis and Statistical Methods
Mean and SD values are
reported for each variable by group
and sex. Comparison of mean demographic,
echocardiographic, and signal-averaged ECG values
between men and women was performed after first adjusting for the
presence or absence of LVH by either parametric or
Kruskal-Wallis two-way ANOVA, as appropriate, with inclusion of an
interaction term between sex and hypertrophy. Sex
differences in mean values of signal-averaged ECG
variables were also compared by ANCOVA to adjust for baseline
differences between men and women in LV mass and body surface area.
Comparison of subgroup proportions was performed by
2 analysis with correction for continuity
or by a two-tailed Fisher's exact test. Sex differences in the
distribution of the horizontal plane vector integral were assessed
separately in patients with and without hypertrophy by the
Kolmogorov-Smirnov test.39 The strength of the relation
between signal-averaged ECG variables and LV mass index was
assessed by Pearson correlation coefficients. Differences in
correlation coefficients between men and women were compared
statistically by two-tailed tests after application of Fisher's Z
transformation.
Definitions of test sensitivity and specificity conform
to standard
use.40 Test specificity of each ECG and
signal-averaged ECG method for the identification of LVH was
assessed in all 175 subjects without hypertrophy and also
separately in the 132 men and 43 women without LVH to produce
sex-specific test criteria. The sensitivity of each criterion in
men and women was compared with the use of partitions with matched
specificity of 98% and a two-tailed Fisher's exact test.
Comparisons of test sensitivity of the horizontal plane vector integral
with the other signal-averaged and standard ECG criteria among men
and separately among women were performed with McNemar's modification
of the 2 method for paired proportions. Because
the sensitivity and specificity of a test depend on the partition
values chosen for test positivity, test accuracy of the horizontal
plane vector integral was also compared with ECG and
vectorcardiographic criteria with the use of ROC curve
analysis. ROC curves compare the sensitivity and specificity of
different tests over a wide range of possible partition values and can
be used to compare differences between methods independent of
empirically derived criteria, with a greater area under a
performance curve of a method indicative of superior test
performance.41 ROC curves were compared
statistically by means of a univariate z score
test of the difference between the partial areas under two
performance curves at specificities between 80% and
100%,42 which is a clinically relevant range of
specificity for the identification of LVH. For all comparisons, a value
of P<.05 was required for rejection of the null
hypothesis.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Relation of Clinical and Echocardiographic Variables to Sex
Sex differences in demographic and echocardiographic variables in relation to the presence or absence of LVH are examined in Table 1
. Men
and women with and without hypertrophy were similar with
respect to mean age, but women had significantly lower body surface
area, lower septal wall thickness, smaller LV internal dimension during
diastole, and lower LV mass. Mean posterior wall thickness
and LV mass index were similar in men and women with
hypertrophy but were significantly lower in women without
LVH. Sex-specific indexed LV mass partitions showed there to be no
significant difference in the prevalence of LVH in women and men (38%
versus 27%, P=NS).
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Relation of Signal-Averaged Electrocardiographic Variables
to Sex
Mean values of the maximal spatial vector amplitude;
single-lead QRS integrals; maximal spatial vector integral; and
vector integrals of the horizontal, sagittal, and frontal planes in men
and women according to the presence or absence of LVH are
presented in Table 2. Women with and without
hypertrophy had significantly lower vector amplitudes and
time-voltage integrals than did men. Differences in
signal-averaged ECG measurements between women and men persisted
after baseline sex differences in LV mass and body surface area were
adjusted for by ANCOVA.
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Because differences of mean values may not
necessarily reflect
differences in the overall distribution of the same
values,39 sex differences in the distribution of
signal-averaged ECG criteria were compared separately in the
subjects with and without LVH. In both subjects without
hypertrophy and patients with LVH there were significant
differences between men and women in the frequency distributions of all
of the signal-averaged ECG variables (P<.01 to
P<.0001). Sex differences in the frequency distribution for
the horizontal plane vector integral are shown in Fig 1;
similar patterns were observed for the other variables, with a
greater proportion of women with and without LVH having lower test
values than men.
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Univariate linear correlations of signal-averaged ECG
variables with indexed LV mass are shown according to sex in Table
3. There were highly significant correlations between LV
mass index and signal-averaged ECG criteria in both men and women,
with no significant differences in correlation between the sexes.
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Sex and the Electrocardiographic Identification of
LVH
The sensitivity and overall performance of the horizontal
plane vector integral and the other signal-averaged ECG criteria
were highly dependent on whether test specificity was defined in the
overall group of subjects without hypertrophy or separately
in men and women with normal indexed LV mass values (Tables 4
and 5,
Fig 2). When specificity
was defined in all 175 normal subjects, using single,
non–sex-specific partitions with matched specificities of
98%, the sensitivity of the horizontal plane vector integral was
significantly lower in women than men (31% versus 71%,
P<.001, Table 4). In addition, sensitivity was
significantly lower in women than men for the lead Z integral, the
horizontal and sagittal plane vector integrals, and the maximal spatial
vector integral, with trends toward lower sensitivity in women for the
maximal spatial vector amplitude, the lead X and lead Y integrals, and
the frontal plane vector integral (Table 4).
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The use of
sex-specific test partitions significantly improved
sensitivity in women, with no loss of sensitivity in men (Table
5
).
When test specificity was defined separately in the 43 women and 132
men without LVH, use of partitions of 75.4 and 99.2 µV·s,
respectively, significantly improved the sensitivity of the horizontal
plane vector integral in women to 81% (95% confidence interval, 64%
to 98%; P<.001), with no change in sensitivity in men
(71%; 95% confidence interval, 58% to 84%). Similar increases in
sensitivity in women were observed for the lead X and lead Z integrals
and the sagittal plane and maximal spatial vector integrals with the
use of sex-specific criteria (P<.05 to
P<.001), with no significant change in the sensitivity of
any of the signal-averaged ECG criteria in men. As a consequence,
there were no significant differences in the sensitivity of the
signal-averaged ECG criteria between men and women when
sex-specific test partitions were used (Table 5). Comparison of
ROC
curves for the horizontal plane and maximal spatial vector integrals
further highlights the effect of using sex-specific partitions and
defining test performance separately in men and women (Fig 2).
For both criteria, overall test performance was lower when
tested and defined in the overall population than when assessed
separately in each sex.
The effect of using sex-specific criteria as
opposed to criteria
derived in the overall population on the sensitivity of
time-voltage area criteria in the total study population is
examined in Table 6. At a matched specificity of 98%,
use of sex-specific partitions significantly improved the
sensitivity of the lead Z integral, the horizontal and sagittal plane
integrals, and the maximal spatial vector integral compared with
partitions derived in the overall population of subjects without
hypertrophy, with nonsignificant increases in sensitivity
found for the other time-voltage area criteria.
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Identification of LVH by the Time-Voltage Area of the
QRS
Improved performance of the time-voltage area of the
QRS in the horizontal plane for the identification of LVH relative to
other signal-averaged ECG criteria is examined according to sex in
Table 5. Among women, at a matched specificity of 98%, the 81%
sensitivity of the horizontal plane vector integral was significantly
greater than the 46% sensitivity of the maximal spatial vector
amplitude, the 35% sensitivity of the lead Y integral, and the 54%
sensitivity of the lead Z integral. As a consequence of the poor
performance of the lead Y integral, calculation of the
time-voltage area of the QRS in the frontal or sagittal plane
resulted in lower sensitivities than found for the horizontal plane
vector integral. Similarly, incorporation of all three orthogonal leads
into a maximal spatial vector QRS complex did not improve the
sensitivity of the time-voltage integral for LVH in women (62%,
P<.05 versus the horizontal plane integral). Of note, the
81% sensitivity of the horizontal plane vector integral was
significantly greater than the 35% to 54% sensitivity of standard ECG
criteria in these women (P<.01 to P<.001).
Comparison of ROC curves confirmed that the superior
performance of the horizontal plane vector integral relative to
other ECG and signal-averaged ECG criteria for the identification
of LVH in women was independent of partition value selection over the
clinically relevant range of specificities from 80% to 100% (Figs 3 through
6),
with differences generally greatest at high specificities. As
previously reported,27 a similar improvement in
sensitivity and overall performance was observed in men for the
horizontal plane vector integral. Importantly, comparison of ROC curves
demonstrated no significant difference in the overall
performance of the horizontal plane vector integral or other
signal-averaged criteria between men and women. Of note, when
sensitivity was examined in the total group of 75 men and women with
hypertrophy with the use of sex-specific partitions
(Table 6), the 75% sensitivity of the horizontal plane vector
integral
was significantly greater than the 28% to 65% sensitivity of the
other vector criteria.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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These data demonstrate that the use of sex-specific partitions improves the performance of the time-voltage integral of the vector QRS complex for the identification of LVH in women compared with the use of non–sex-specific criteria, with no loss of test accuracy in men. These findings highlight the importance of defining the test performance of ECG criteria separately in men and women rather than in the entire population of men and women together. These results further demonstrate that similar to previous findings in men,27 the use of the horizontal plane vector integral provides increased accuracy of ECG methods for the identification of hypertrophy in women and support the use of the time-voltage area of the QRS for optimal ECG detection of LVH.
Sex Differences in the Electrocardiographic Identification of
LVH
Although differences in QRS duration and voltage between men and
women have been recognized for some
time,14 15 16 17 18 19
most
standard ECG criteria for the detection of LVH do not use
sex-specific
partitions.10 25 26 29 30
ECG methods
that do use sex-specific criteria5 6 or otherwise
adjust for sex5 6 8 9 have
been reported to improve the
accuracy of the ECG for the identification of hypertrophy
in populations that include both men and
women.5 6 8 9
However, sex differences in the test performance of 12-lead ECG
criteria have only recently been
examined.9 20 21
With respect to standard 12-lead ECG criteria, a recent study from our laboratory21 found that significant differences in ECG measurements between men and women persisted even when baseline sex differences in LV mass and body size were taken into account. Furthermore, the overall accuracy of QRS duration, Cornell voltage, Sokolow-Lyon voltage, the 12-lead sum of voltage, and their respective voltage-duration products was significantly lower in women than men even when sex-specific criteria were used.21 In a study of 923 hypertensive subjects, Schillaci et al20 demonstrated higher sensitivity at matched specificity and greater overall performance by ROC curve analysis for Cornell voltage in men than women. In contrast, Norman et al9 found no significant sex differences in the sensitivity of Cornell voltage criteria at specificities of 85% or greater.
The current study extends these observations to time-voltage integral criteria. When non–sex-specific criteria were used, the test sensitivity of the horizontal plane vector integral was significantly lower in women than men. The use of sex-specific test partitions significantly increased test sensitivity in women, with no loss of sensitivity in men. As a result, in contrast to standard ECG criteria,21 there were no significant differences in the sensitivity or overall performance of the time-voltage integral of the horizontal plane between men and women when sex-specific partitions based on sex differences in normal time-voltage areas were used. The comparable performance of sex-specific, signal-averaged ECG criteria in women and men in the current study was not a consequence of sex differences in the severity of hypertrophy or in the relative severity of indexed LV mass in the subjects without hypertrophy: The mean ratios of LV mass index to the sex-specific partitions for LVH (125 g/m2 in men and 110 g/m2 in women) were nearly identical in the men and women with hypertrophy (1.28±0.27 versus 1.38±0.29, P=NS) and those without hypertrophy (0.66±0.13 versus 0.63±0.13, P=NS). However, in contrast to our findings for 12-lead ECG criteria,21 the time-voltage integrals had equally close linear relations with indexed LV mass in women and men, a possible explanation for the similar performance of sex-specific partitions in this population.
Time-Voltage Area of the QRS and LVH
Previous observations
that the time-voltage integral of the
vectorcardiographic QRS complex improves ECG correlation with LV
mass31 32 suggest that increases in LV mass may be
paralleled by subtle increases in both QRS voltage and duration
that together produce a proportionally greater increase in the area
under the QRS complex than in either QRS duration or maximal amplitude
alone. Indeed, the use of the simple product of QRS duration and
voltages, as an approximation of the area under the QRS, has been found
to improve the accuracy of the ECG for the identification of LVH
relative to criteria based on QRS voltages or duration alone or in
combinations of linear weighted sums.25 26 The
present
study extends our previous observations in men27 by
showing that the time-voltage integral of the QRS more accurately
reflects the presence of LVH in women than either standard 12-lead ECG
criteria or simple voltage-duration products that crudely
approximate the area under the QRS.25 26
Implications and Limitations
The increased morbidity and
mortality associated with
echocardiographically detected
LVH38 43 44 45 46
make its detection by simple, accurate, and cost-effective
screening methods a clinical priority.11 As a consequence,
improvement in the well-recognized low sensitivity of the widely
used and inexpensive ECG is of great importance. The current findings
suggest that analysis of the ECG time-voltage integral
using separate sex-specific partitions in men and women improves
the diagnostic ability of the ECG to identify LVH. Although
the present study used specialized signal-averaged ECG
equipment, some current computerized 12-lead ECG systems can make
measurements from the standard 12 leads that should allow synthesis or
close approximation of the horizontal plane QRS vector, facilitating
both large-scale testing and ultimate clinical application of this
approach.
Our patients with LVH had underlying valvular regurgitation, and findings may vary in populations with concentric forms of hypertrophy, including those composed purely of patients with hypertension. Validation or adjustment of these partition values therefore is required before these methods are applied to hypertensive men and women. Further validation of this approach also will be necessary in larger and more heterogeneous groups of normal subjects and in patients with LVH who have bundle branch blocks. However, the nearly identical sensitivities and specificities of the simple voltage-duration products in patients with and without bundle branch blocks25 suggest that the time-voltage integral may also be useful in these patients. Furthermore, analysis of characteristics of the relation between the QRS time-voltage integral and LV mass in black and white subjects may clarify the basis for the apparently lower specificity of standard ECG criteria for LVH in black subjects.47
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Selected Abbreviations and Acronyms |
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Received March 31, 1995; first decision August 2, 1995; accepted October 5, 1995.
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