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Original Research |
1 Department of Radiology, Johns Hopkins University School of Medicine, Johns
Hopkins Hospital, Baltimore, MD.
2 Department of Epidemiology, Johns Hopkins University School of Medicine, Johns
Hopkins Hospital, Baltimore, MD.
3 Department of Radiology, UCLA School of Medicine, Los Angeles, CA.
4 Department of Radiology, Wake Forest University School of Medicine,
Winston-Salem, NC.
5 Department of Radiology, University of Minnesota, Minneapolis, MN.
6 Department of Radiology, College of Physicians and Surgeons of Columbia
University, New York, NY.
7 National Heart, Lung, and Blood Institute, National Institutes of Health,
Bethesda, MD.
8 Departments of Radiology and Medicine, Johns Hopkins University School of
Medicine, Johns Hopkins Hospital, 600 N Wolfe St., Baltimore, MD 21287.
Received December 8, 2004;
accepted after revision March 14, 2005.
Supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95168
from the National Heart, Lung, and Blood Institute.
Abstract
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SUBJECTS AND METHODS. Eight hundred participants (400 men, 400 women) in four age strata (45–54, 55–64, 65–74, 75–84 years) were chosen at random. Participants with the following known cardiovascular risk factors were excluded: current smoker, systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, fasting glucose > 110 mg/dL, total cholesterol > 240 mg/dL, and high-density lipoprotein (HDL) cholesterol < 40 mg/dL. Cardiac MR images were analyzed using MASS software (version 4.2). Mean values, SDs, and correlation coefficients in relationship to patient age were calculated.
RESULTS. There were significant differences in LV volumes and mass between men and women. LV volumes were inversely associated with age (p < 0.05) for both sexes except for the LV end-systolic volume index. For men, LV mass was inversely associated with age (slope = -0.72 g/year, p = 0.0021), but LV mass index was not associated with age (slope = -0.179 g/m2/year, p = 0.075). For women, LV mass (slope = -0.15 g/year, p = 0.30) and LV mass index (slope = 0.0044 g/m2/year, p = 0.95) were not associated with age. LV mass was the largest in the African-American group (men, 181.6 ± 35.8 [SD] g; women, 128.8 ± 28.1 g) and was smallest in the Asian-American group (men, 129.1 ± 20.0 g; women, 89.4 ± 13.3 g).
CONCLUSION. The normal LV differs in volume and mass between sexes and among certain ethnic groups. When indexed by body surface area, LV mass was independent of age for both sexes. Studies that assess cardiovascular risk factors in relationship to cardiac function and structure need to account for these normal variations in the population.
Keywords: atherosclerosis • cardiac function • cardiac imaging • ejection fraction • heart • left ventricle • left ventricle mass • MRI
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MRI acquires tomographic 2D or 3D images of the entire heart. Volumetric assessment of the LV is independent of geometric assumptions, noninvasive, and free of exposure to contrast agents or ionizing radiation. MRI is considered superior to other imaging techniques because of its capability for high-resolution measurements of anatomy and function of the LV. Cardiac MRI was implemented in the Multi-Ethnic Study of Atherosclerosis (MESA), sponsored by the National Heart, Lung, and Blood Institute of the National Institutes of Health. The purpose of MESA was to study the characteristics of subclinical cardiovascular disease and risk factors that predict progression to clinically overt cardiovascular disease and that predict progression of subclinical disease itself in an ethnically diverse population [18]. Participants included 6,814 asymptomatic men and women who ranged in age from 45 to 84 years and were free of clinical cardiovascular disease at baseline. Approximately 40% of the cohort were white Americans, 30% African-Americans, 20% Hispanics, and 10% Asian-Americans, predominantly of Chinese descent, recruited from six United States communities [18].
The purposes of this article are to describe the protocol for cardiac MRI for MESA and provide a set of normal reference values of LV mass and volumes with respect to sex, ethnicity, and age.
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MRI
MRI was performed at the six MESA field centers using 1.5-T magnets. The
following are the MR scanners that were used at each field center: Wake Forest
University, Signa CV/I (GE Healthcare); Columbia University, Signa LX (GE
Healthcare); Johns Hopkins University, Signa CV/I; University of Minnesota,
Vision or Sonata (Siemens Medical Solutions); Northwestern University, Sonata;
and University of California at Los Angeles, Signa LX or Vision. All imaging
examinations were performed with a four-element phased-array surface coil
placed anteriorly and posteriorly, ECG gating, and brachial artery blood
pressure monitoring.
MRI Protocol
Table 1 shows the outline of
the MESA MRI protocol. Cardiac MR examinations consisted of short- and
long-axis cine images, phase contrast images of the aorta, and black blood
aorta images. The protocol was accomplished within 30–45 min. All images
were acquired during short breath-holding (12–15 sec) at resting lung
volume.
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First, four midline ECG-gated sagittal scout images were acquired with a fast gradient-echo sequence (series 1). These images were used to confirm correct positioning of the phased-array surface coil. Second, the same sequence was used to acquire three axial scout views (series 2); these images were acquired beginning 2 cm above the diaphragm. Next, a pseudovertical long-axis scout image (series 3) was obtained using the largest LV image from series 2. This slice extended through the middle of the mitral valve plane and the LV apex. Four-chamber long-axis cine images (series 4) were next acquired using a cine ECG-gated fast gradient-echo pulse sequence. The imaging plane for the four-chamber view was prescribed along points intersecting the middle of the mitral valve plane and the LV apex. Short-axis cine images (series 5) were acquired from the end-diastolic image of the four-chamber acquisition, by prescribing 10–12 slices perpendicular to a line from the middle of the mitral valve plane to the cardiac apex. A two-chamber vertical long-axis cine sequence (series 6) was obtained by prescribing a single slice along a line extending from the LV apex to the middle of the mitral valve plane as viewed on the four-chamber view (series 4). The image prescription was designed to minimize variation among the MR field centers. Cine images were obtained with a temporal resolution of approximately 50 msec or less.
Additional pulse sequences were acquired, and those results will be reported separately. In brief, axial cine phase contrast images (series 7) were obtained through the ascending and descending aorta at the level of the right pulmonary artery. A blood-suppressed (black blood) double inversion recovery fast spin-echo image (series 8) was obtained in the sagittal oblique plane along a line intersecting the middle of the ascending and descending aorta as viewed on series 7. Series 9 consisted of blood-suppressed double inversion recovery fast spin-echo images prescribed at the level of the top of the pulmonary artery as seen on series 8 in the axial plane, vertical plane, and at 45° between the axial and vertical planes.
Image Analysis
Cardiac MR images were transmitted using DICOM transfer protocol to the
central cardiac MR review center in Baltimore, MD, at Johns Hopkins Hospital.
The cardiac MR images were transferred to a workstation (UNIX, Sun
Microsystems) for analysis. Image data were analyzed using MASS software
([version 4.2] Medis). Images were magnified to 250%. Image contrast was set
to 60; image brightness was set to 60; window width and level were set using
the Auto function in MASS, which sets the maximum and minimum pixel values in
the displayed image to values of 255 and 0, respectively.
Image analysts were trained technologists who received lectures in cardiac anatomy and function. Technologists were trained on a set of 40 training cases that were reviewed by an experienced cardiac MR physician. The training period examinations were accepted if LV function parameters were within 10% of the physician-determined values. The endocardial and epicardial borders were traced semiautomatically at both end-diastole and end-systole on short-axis cine images and were then corrected manually at the base of the heart. Corrections to other images were allowed if visual inspection revealed obviously incorrect borders. The papillary muscles were included in the LV end-diastolic volume and LV end-systolic volume and excluded from the LV mass. All image contours were checked by a cardiac MR physician after contouring was finished by the technologist.
LV end-diastolic volume and LV end-systolic volume were calculated using
Simpson's rule (the summation of areas on each separate slice multiplied by
the sum of slice thickness and image gap). LV mass was determined by the sum
of the myocardial area (the difference between endocardial and epicardial
contour) times slice thickness plus image gap in the end-diastolic phase
multiplied by the specific gravity of myocardium (1.05 g/mL). LV stroke volume
was calculated as the difference between LV end-diastolic volume and LV
end-systolic volume. LVEF was calculated as LV stroke volume divided by LV
end-diastolic volume multiplied by 100. Cardiac output was calculated as LV
stroke volume times heart rate. Body surface area (BSA) was calculated as
follows:
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Body mass index (BMI) was calculated as follows:
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Indexed parameters (e.g., LV mass index) were calculated by dividing each parameter (e.g., LV mass) by BSA.
Inter- and Intraobserver Variability
Technologist interobserver variability was measured in 79 MR readings
selected at random (3% of the entire cohort) by comparing the original MR
volumes and mass readings with results from a second review performed between
3 and 6 months later. Intraobserver variability was assessed in 75 MR readings
performed in the same manner. Reviewers were blinded to the results of the
initial reading at the time of the second and third readings.
Statistical Analysis
Data are presented as mean ± SD. Analysis of variance was used as
appropriate for statistical testing between groups. A multiple comparison
procedure, Dunnett's t test (two-sided), was used to compare the
differences among ethnic groups. A oneway analysis of variance with linear
contrasts (test for trend) was used for LV function parameters. Reliability
was assessed using intraclass correlation coefficient estimates, and
variability was assessed using technical error of measurement percentage of
the mean (TEM%).
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Age-Related Differences for LV Volumes and Mass
Figures 1A,
1B, and
1C shows the relationship
between LV functional parameters and age for men. LV mass showed an inverse
association with age (slope = -0.72 g/year, p = 0.0021), but LV mass
index (Fig. 1A) was not
associated with age (slope = -0.18 g/m2/year, p = 0.075).
LV end-diastolic volume (slope = -0.81 mL/year, p = 0.0003), LV
end-systolic volume (slope = -0.41 mL/year, p = 0.0014), and LV
volume indexes (Figs. 1B and
1C) were inversely associated
with age for men.
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0.0001), LV end-systolic volume (slope = -0.13 mL/year, p = 0.031),
and LV end-diastolic volume index (Fig.
2B) were inversely associated with age for women, but LV
end-systolic index showed only a small inverse association with age (slope =
-0.054 mL m2/year, p = 0.080)
(Fig. 2C).
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For men (Table 7), there were no significant differences for most LV parameters between white Americans, African-Americans, and Hispanics. However, LV end-diastolic volume, LV end-systolic volume, LV stroke volume, and LV mass were significantly different between Asians and other ethnic groups (all p < 0.05). Differences in LV end-diastolic volume, LV end-systolic volume, and LV mass remained significant between Asians and other ethnic groups after normalization by BSA (LV end-diastolic volume index, LV end-systolic volume index, and LV mass index).
For women (Table 8), there were no differences in most parameters between white Americans, African-Americans, and Hispanics. However, LV end-diastolic volume, LV stroke volume, and LV mass were significantly different between Asians and other ethnic groups (all p < 0.05). LV mass remained significantly different between Asians and other ethnic groups after normalization by BSA (LV mass index).
Inter- and Intraobserver Variability
Tables 9 and
10 show the results of
observer variability assessment. The interobserver TEM% for LV end-diastolic
mass, end-diastolic volume, and end-systolic volume were 6.0%, 4.4%, and
12.8%, respectively, and intraclass correlation coefficients were 0.98, 0.98
and 0.94, respectively. Intraobserver values are shown in
Table 10.
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MESA Study
The MESA study was initiated in July 2000 by the National Heart, Lung, and
Blood Institute to further understanding of the pathogenesis of
atherosclerosis and other cardiovascular diseases
[18]. A population-based
sample of 6,814 asymptomatic men and women who ranged in age from 45 to 84
years and were free of clinical cardiovascular disease at baseline were
evaluated. In addition to cardiac MRI, baseline measurements included
measurement of coronary calcium using CT; measurement of flow-mediated
brachial artery endothelial vasodilatation, carotid intimal–medial wall
thickness, and distensibility of the carotid arteries using sonography;
measurement of peripheral vascular disease using ankle and brachial blood
pressures; ECG; and assessments of microalbuminuria, standard cardiovascular
disease risk factors, sociodemographic factors, life habits, and psychosocial
factors. Blood samples have been obtained for putative biochemical risk
factors. Thus, MRI is one part of a rich imaging "phenotype" that
will be correlated with serologic and imaging risk factors for cardiovascular
disease.
The calculation of LV mass and volumes using MRI does not require assumptions to be made concerning an analytic model of LV shape. Unlike echocardiography and cineangiocardiography, cine MRI does not rely on geometric assumptions or calculations based on incomplete sampling of the cardiac volumes [19–21]. Furthermore, MRI is noninvasive and is free of exposure to contrast agents or ionizing radiation. These advantages over other imaging techniques have led to more widespread use of MRI for the assessment of cardiac function.
LV Parameters and Sex
Knowledge of the global structure and function of the normal LV underlies
current assessment of patients with cardiovascular disease. In this study,
normal volumes for the LV determined using MRI
(Table 2) are similar to those
of previous studies [20,
22,
23]. LV mass, however, in this
study is smaller than in other studies. The reason for this may include
exclusion of participants with cardiovascular risk factors such as smoking
[24], hypertension, diabetes,
and hyperlipemia. In addition, this study included individuals of different
ethnicity and this could account for lower LV mass values. Asian-Americans, in
particular, show lower mean values for LV mass than the other ethnic groups in
the MESA cohort.
In men, LV volumes and indexed volumes showed a small negative association with age (Figs. 1B and 1C). A similar pattern was seen for women (Figs. 2B and 2C), although LV end-systolic volume index showed only a trend toward negative association with age. For LV mass and LV mass index, there were also somewhat similar patterns for men and women; LV mass index showed no significant relationship to age (Figs. 1A and 2A). The absolute LV mass, however, was negatively associated with age for men and was not related to age for women.
Gerstenblith et al. [25] found age-associated LV hypertrophy using M-mode echocardiography. Shub et al. [26] reported an age-associated increase in LV mass in women, with no change in men. On autopsy findings, Olivetti et al. [27] described progressive LV myocyte loss, cellular hypertrophy, and multinucleation with decreased LV mass in men but not in women, similar to the results of this study. Also in agreement with the current study, Hees et al. [23] reported LV mass on MRI did not vary with age in women but that it decreased significantly in men. However, adjusting for body size (using BSA or LV mass index) reduced this age dependence in men in our study.
LV Parameters and Ethnicity
This study provides normal LV mass and volumes for white Americans,
African-Americans, Hispanics, and Asian-Americans. There are no previous
reports, to our knowledge, about LV parameters for different ethnic groups
described on MRI. The most notable finding is that Asian-Americans have lower
LV mass and volumes compared with other ethnic groups. LV volumes and mass in
African-Americans were largest for men, whereas LV volumes and LV mass were
smallest in Asian-American men. For women, African-Americans had similar LV
volumes compared with white Americans and Hispanics, whereas Asian-Americans
had smaller LV volumes and LV mass. These findings were significant after
normalization by BSA. Zabalgoitia et al.
[28] reported that LV mass
indexed to BSA of patients with mild to moderate high blood pressure was
similar among white Americans, African-Americans, and Hispanics using
echocardiography. Asian-Americans were not included in that study.
Limitations
There are several limitations in the current investigation. Risk factor
definition and cutoff values were based on prior studies that may have used
different characteristics than were used for participants in MESA. The reason
for LV mass and volume differences between ethnic groups may be related to
factors such as socioeconomic status or selection bias that has not been
evaluated. We expect to be able to analyze these factors further in subsequent
analyses involving cardiovascular risk factors in the MESA study.
The results we report in this study were obtained using a fast gradient-echo MR pulse sequence. More recently, the steady-state free precession (SSFP) pulse sequence became available. Early studies report slight differences in cardiac volume, mass, and EF obtained with fast gradient-echo versus SSFP images [29–32].
In conclusion, this article describes the relationship between sex and age and global measures of cardiac structure and function as defined by MRI in the MESA cohort for a population without traditional cardiovascular risk factors. Differences in cardiac structure and function among ethnic groups were present and need to be assessed in future studies in relationship to cardiovascular risk factors.
Acknowledgments
We thank the other investigators, the staff, and the participants of the
MESA study for their valuable contributions. A full list of participating MESA
investigators and institutions can be found at
www.mesa-nhlbi.org.
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