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J Am Coll Cardiol, 2002; 39:1055-1060 © 2002 by the American College of Cardiology Foundation |






,*
* Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory of the Department of Medicine, Boston, Massachusetts, USA
Department of Radiology, Beth Israel Deaconess Medical Center; Department of Medicine, Boston, Massachusetts, USA
Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
NHLBIs Framingham Heart Study, Framingham, Massachusetts, USA
Manuscript received July 11, 2001; revised manuscript received November 12, 2001, accepted December 19, 2001.
* Reprint requests and correspondence: Dr. Warren J. Manning, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
wmanning{at}caregroup.harvard.edu
| Abstract |
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BACKGROUND: Cardiovascular magnetic resonance imaging is increasingly applied in the clinical setting, but age-relevant, gender-specific normative values are currently unavailable.
METHODS: A representative sample of 318 Framingham Heart Study (FHS) Offspring participants free of clinically overt cardiovascular disease underwent CMR examination to determine LV end-diastolic and end-systolic volume (EDV and ESV, respectively), mass, ejection fraction (EF) and linear dimensions (wall thickness, cavity length). Subjects with a clinical history of hypertension or those with a systolic blood pressure
140 mm Hg or diastolic pressure
90 mm Hg at any FHS cycle examination were excluded, leaving 142 subjects (63 men, 79 women; age 57 ± 9 years).
RESULTS: All volumetric (EDV, ESV, mass) and unidimensional measures were significantly greater (p < 0.001) in men than in women and remained greater (p < 0.02) after adjustment for subject height. Volumetric measures were greater (p < 0.001) in men than in women after adjustment for body surface area (BSA), but there were increased linear dimensions in women after adjustment for BSA. In particular, end-diastolic dimension indexed to BSA was greater in women (p < 0.001) than in men. There were no gender differences in global LVEF (men = 0.69; women = 0.70).
CONCLUSIONS: Cardiovascular magnetic resonance measures of LV volumes, mass and linear dimensions differ significantly according to gender and body size. This study provides gender-specific normal CMR reference values, uniquely derived from a population-based sample of persons free of cardiovascular disease and clinical hypertension. These data may serve as a reference to identify LV pathology in the adult population.
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| Methods |
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140 mm Hg or diastolic blood pressure
90 mm Hg (14) during any FHS examination. The study was approved by human study committees of both the Boston University School of Medicine and Beth Israel Deaconess Medical Center. Written informed consent was obtained from all participants. Imaging. Cardiovascular magnetic resonance imaging was performed with subjects positioned supine in a 1.5-T scanner using a 5-element cardiac array coil for radiofrequency signal detection (Gyroscan ACS/NT, Philips Medical Systems, Best, The Netherlands). Following scout images to determine the position and orientation of the heart within the thorax, images were acquired using a prospective, electrocardiogram (ECG)-triggered K-space segmented hybrid gradient-echo echo-planar breath-hold cine sequence (15). A stack of 10-mm thick contiguous slices encompassing the left ventricle from base to apex in the cardiac short-axis orientation was acquired during a series of end-tidal breath-holds. Imaging parameters included the following: repetition time = R-R interval, echo time = 9 ms, flip angle = 30°, effective temporal resolution of 39 ms. In-plane spatial resolution was 1.25 x 2.0 mm2.
Image analysis. All image analysis was performed by an observer blinded to all clinical history (including age and gender) using a commercially available EasyScil workstation (Philips Medical Systems). Endocardial LV borders were manually traced at end-diastole (the first image in the ECG-gated cine dataset) and at end-systole (the cardiac phase with minimal cross-sectional area) (Fig. 1). In the tracing convention used, the papillary muscles were included as part of LV cavity volume. Left ventricular end-diastolic volume (EDV) and end-systolic volume (ESV) were determined using a summation of disks ("Simpsons Rule") method. Ejection fraction (EF) was computed as EF = (EDV ESV)/EDV. Left ventricular epicardial borders were also traced on the end-diastolic images with LV mass computed as the end-diastolic myocardial volume (i.e., epicardial endocardial volumes) multiplied by myocardial density (1.05 g/ml). Intraobserver and interobserver reproducibility for LV volumetric measures by our group have been previously reported (16). In addition to volumetric measurements, one-dimensional measurements of LV end-diastolic dimension (EDD), posterior wall thickness (PWT) and anterior interventricular septum thickness (IVS) were measured from an end-diastolic short-axis slice immediately basal to the tips of the papillary muscles. Finally, end-diastolic LV long-axis lengths, from the apical endocardial border to the mitral valve plane, were measured from both the two-chamber and four-chamber data sets.
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| Results |
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| Discussion |
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Gender differences and impact of adjustment for height and BSA. As has been described for both echocardiographic and smaller CMR series, absolute LV mass, EDV, ESV and linear dimensions were significantly greater in men than in women. This emphasizes the need for gender-specific reference values, as use of gender-indifferent threshold values for LV hypertrophy or chamber dilation would lead to reduced sensitivity for women and reduced specificity for men. Data from the present study, as well as previous work by others and us, indicate that LV mass, volume and linear dimensions are significantly correlated with body habitus, so that adjustment is warranted to account for differences in body size (8,9,18,19). As in these prior reports, we reported adjustment with respect to body height and to BSA; these measures are commonly used to index cardiac data with other imaging modalities. Height is simple to determine and is strongly associated with lean body mass (19), may best reflect metabolic demands on the heart (20), and does not make allowance for obesity. Direct measurement of lean body mass is difficult to acquire in the clinical setting. Obesity is associated with LV hypertrophy (21,22); indexing LV measurements by weight thus might fail to detect pathologic levels of LV mass and, accordingly, was not developed in this report. Body surface area makes partial allowance for obesity, as weight is used in conjunction with height to determine BSA. In the present study, gender differences persisted after adjustment for height, except in the case of EDD, which was similar in men and women. Adjustment for BSA resulted in a tendency toward "cross-over" with greater linear dimensions in women compared with men. The physiologic or prognostic implications of this gender-differential effect of adjustment for BSA are unknown and await further study with a larger cohort.
Comparison with previous CMR studies. Several investigators have reported normal CMR indexes for cardiac anatomy and function based on findings from relatively young cohorts. In the two largest series to date, Lorenz et al. (8) reported normal LV CMR values in 75 healthy subjects (28 women, 47 men; age 28 ± 9 years), and Marcus et al. (9) described LV parameters in 61 healthy young adults (32 men, 29 women; mean age 22 ± 2 years). Consistent with the findings of the present study, both investigators reported greater LV volume and mass in men, before and after adjustment for height and BSA. Compared with our results, however, both Lorenz and Marcus reported greater EDV values, regardless of gender or adjustment method. This may be due in part to the younger age of their participants, or population differences in habitual physical activity. With respect to LV mass, mean values in the Marcus study were lower than corresponding values in our study. This may reflect differences in body habitus, as well as age; the greatest proportional difference was observed after adjustment for height, which does not make allowance for obesity or overweight. Subjects in the Marcus study were substantially taller (men: 1.83 ± 0.07 m, women: 1.71 ± 0.07 m) and leaner (men: body mass index [BMI] = 23.1 ± 2.7 kg/m2; women: BMI = 21.6 ± 2.5 kg/m2) than participants in our study (Table 1). The above studies should be viewed as complementary to the present study, as the subjects were principally drawn from a young-adult age group not represented in this report.
Comparison with echocardiographic studies. Although two-dimensional (2D) and three-dimensional (3D) echocardiography are available for measurement of LV anatomy and systolic function, M-mode echocardiography, because of its ease of acquisition and measurement, remains the most widely used method for determination of LV dimension and mass, both in clinical practice and in many research studies. Cardiovascular magnetic resonance imaging-derived LV EDD and wall thickness in the present study were similar to corresponding M-mode derived values obtained from 914 clinically healthy FHS subjects in a separate study (23). In the present study, however, gender-specific values for normal CMR LV mass are lower than previously reported M-mode-derived values obtained from 864 healthy adults drawn from the same FHS Offspring cohort (24) and likely reflect differences between CMR and M-mode echocardiographic derived volumes and mass. In support of this hypothesis, another study of 111 healthy, normotensive adults (25) found that M-mode echocardiographically derived mass was greater than volumetric CMR mass. In a third series of healthy normotensive subjects (19), M-mode values for LV mass are more comparable to our data, although mean M-mode mass still exceeded the CMR mass values of the present study. Notably, the proposed upper 95th percentile "limits of normal" for LV mass in each of the echocardiographic studies (men: 259 g, 143 g/m, 261 g; women: 166 g, 123 g/m, 191 g, respectively, for the three studies) are substantially greater than the corresponding upper 95th percentile values in the present CMR study (Table 2). Although not widely available, 3D echocardiography yields excellent agreement with CMR imaging for LV volume (16) and mass. Analogous to our findings, M-mode derived mass is significantly greater than 3D echo mass in the same subjects (26).
Rationale for CMR imaging. Cardiovascular magnetic resonance imaging is highly reproducible (16,27) and may be particularly advantageous in traditionally difficult-to-image patients with obese body habitus or pulmonary disease, as CMR is not dependent on adequate acoustic windows for imaging (28) and does not suffer from attenuation artifacts associated with radionuclide imaging. In the present study, adequate or better quality images suitable for analysis were obtained in 137 (96.5%) of 142 subjects. Use of recently developed non-breath-hold real-time CMR techniques (29,30) may have allowed acquisition of analyzable images in the remaining five subjects, but we did not pursue this option, in the interest of methodological consistency. In the context of clinical studies, use of CMR imaging may minimize selection bias associated with echocardiography (31), which disproportionally excludes obese and elderly subjects (10). Furthermore, the excellent reproducibility of CMR may allow dramatic reductions in sample size needed to observe response to experimental treatments (7,27).
Study limitations. This study was not designed or powered to address possible age-related changes in LV parameters. However, the FHS study sample represents a clinically relevant adult population, about which CMR normative data were previously unknown. This closely followed cohort allowed us to more carefully screen for hypertension and other potential confounders. The FHS sample was overwhelmingly caucasian. The results of the present study may not be generalized to non-caucasian populations. Finally, we did not control for physical activity, which is known to increase both EDV and LV mass, although such changes are generally considered "physiologic" and are not believed to be indicative of disease (32).
Conclusions. Cardiovascular magnetic resonance imaging determined that LV volume, mass and linear dimensions in a normal adult population free of clinically overt cardiovascular disease are affected by gender and body size. Left ventricular EDV, ESV and mass are all greater in men than in women, regardless of adjustment for height or BSA. This study provides gender-specific CMR reference values for a clinically relevant population in whom cardiovascular disease and hypertension were rigorously excluded, and may serve as normative reference data for this population.
| Footnotes |
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| References |
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