CLINICAL STUDY: NEW METHODS
Contrast echocardiography improves the accuracy and reproducibility of left ventricular remodeling measurements
A prospective, randomly assigned, blinded study
Helen L. Thomson, MD, PhD*,
Arsene-Joseph Basmadjian, MD*,
Andrew J. Rainbird, MD*,
Mehdi Razavi, MD*,
Jean-Francois Avierinos, MD*,
Patricia A. Pellikka, MD, FACC*,
Kent R. Bailey, PhD ,
Jerome F. Breen, MD* and
Maurice Enriquez-Sarano, MD, FACC*
* Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA
Section of Biostatistics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA
Manuscript received December 20, 2000;
revised manuscript received April 16, 2001,
accepted May 15, 2001.
Reprint requests and correspondence: Dr. Maurice Enriquez-Sarano, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
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Abstract
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OBJECTIVES
We sought to assess the impact of contrast injection and harmonic imaging, on the measure by echocardiography of left ventricular (LV) remodeling.
BACKGROUND
Left ventricular remodeling is a precursor of LV dysfunction, but the impact of contrast injection and harmonic imaging on the accuracy or reproducibility of echocardiography is unclear.
METHODS
We prospectively collected LV images by using simultaneous methods. Then, LV volumes were measured off-line, in blinded manner and in random order. The accuracy of echocardiography was determined in comparison to electron beam computed tomography (EBCT) in 26 patients. The reproducibility of echocardiography was assessed by three blinded observers with different training levels in 32 patients.
RESULTS
End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF), as measured by EBCT (195 ± 55, 58 ± 24 and 137 ± 35 ml and 71 ± 5%, respectively) and echocardiography with harmonic imaging and contrast injection (194 ± 51, 55 ± 20 and 140 ± 35 ml and 72 ± 4%, respectively), showed no differences (all p > 0.15) and excellent correlations (all r > 0.87). In contrast, echocardiography using harmonic imaging without contrast injection underestimated the EBCT results (all p < 0.01). Reproducibility was superior with rather than without contrast injection for intraobserver and interobserver variabilities (all p < 0.001). Values measured by different observers were different without contrast injection, but were similar with contrast injection (all p > 0.18). Consequently, intrinsic patient differences represented a larger and almost exclusive proportion of global variability with contrast injection for EDV (94 vs. 79%), ESV (93 vs. 82%), SV (87 vs. 53%) and EF (84 vs. 41%), as compared with harmonic imaging without contrast injection (all p < 0.005).
CONCLUSIONS
For assessment of LV remodeling, echocardiography with harmonic imaging and contrast injection improved the accuracy and reproducibility, as compared with imaging without contrast injection. With contrast injection, variability was almost exclusively due to intrinsic patient differences. Therefore, when evaluation of LV remodeling is deemed important, assessment after contrast injection should be the preferred echocardiographic approach.
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Abbreviations and Acronyms
| | ANOVA | = analysis of variance | | EBCT | = electron beam computed tomography | | EDV | = end-diastolic volume | | EF | = ejection fraction | | ESV | = end-systolic volume | | LV | = left ventricular | | SV | = stroke volume |
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Cardiac remodeling is defined clinically as changes in the size, shape and function of the heart, resulting from cardiac load or injury (1). Uncontrolled left ventricular (LV) remodeling is part of a vicious cycle associated with progression of LV dysfunction, with a poor prognosis, regardless of the symptoms or cause (2–7). Therefore, accurate assessment of the degree and progression of LV remodeling is integral to the clinical evaluation of patients with LV overload or dysfunction.
Measurement of LV size (end-diastolic volume [EDV] and end-systolic volume [ESV]) and ejection phase indexes (stroke volume [SV] and ejection fraction [EF]) is essential to monitor LV remodeling. Because relatively small increases in ventricular volume are associated with major independent increases in the mortality risk of coronary disease (6,8,9), valvular disease (2–5) or idiopathic heart failure (7), accurate and reproducible assessment of LV volume is crucial. Left ventricular diameters are used as surrogates for LV volumes, but their measurement is fraught with wide uncertainty regarding the assessment of LV size, especially for enlarged ventricles (10).
Although selective angiography was the initial method for measurement of LV volumes (6,8), its small but definite risk makes it unsuitable for serial assessment. Thus, echocardiography is used for serial assessment of LV remodeling in routine clinical practice. However, previous studies suggest that echocardiography may underestimate LV volume (11) and may be poorly reproducible (12,13). High-resolution imaging and advanced expertise may overcome these limitations in selected centers with experienced observers (14). Nevertheless, echocardiographic LV volumes are rarely measured in routine practice, and because of their uncertain accuracy and reproducibility, they have rarely been used as end points in major LV remodeling clinical trials such as Survival And Ventricular Enlargement (15) or Studies Of Left Ventricular Dysfunction (16).
Recent imaging advances may improve echocardiographic assessment of LV remodeling (17). Harmonic imaging improves LV visualization (18) and injection of contrast agents, although more costly and time-consuming, may improve assessment of LV border and size (19). The respective impacts of these technical improvements on the accuracy and reproducibility of LV remodeling assessment have not been evaluated, partly because of the lack of an accurate reference method. However, electron beam computed tomography (EBCT) provides an accurate reference measurement of LV volumes and allows testing of the hypothesis that the accuracy and reproducibility of echocardiographic assessment of LV volumes are improved by adding contrast injection to harmonic imaging.
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Methods
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General study design.
The study was institutionally funded and approved by the Institutional Review Board. After the patients gave written, informed consent, a peripheral intravenous catheter was inserted, and LV echocardiographic imaging was performed before and after intravenous injection of a contrast agent and digitally stored. After completion of the study, the saved cardiac cycles were retrieved, assigned a predefined random number and then analyzed in blinded, random order in duplicate. Inclusion criteria were: 1) patients with LV remodeling due to isolated mitral regurgitation (at least mild) or LV dysfunction, or both; and 2) imaging of the LV from apical views, possible but of any quality. Exclusion criteria were: 1) previous valve replacement or repair; 2) mitral stenosis; 3) ruptured papillary muscles; 4) aortic valve disease; 5) allergy to blood products or to contrast material; 6) religious or other beliefs precluding the use of human albumin products; 7) pregnancy or breast-feeding; and 8) no venous access.
No patient was excluded on the basis of age, gender, race, heart rate or rhythm or image quality. The study, because of its time-consuming nature, was conducted in two parts—accuracy and reproducibility—and patients participated in either part, but not in both of these parts, according to availability.
Two-dimensional Doppler echocardiographic methods.
A complete two-dimensional Doppler echocardiographic examination was performed. The LV was imaged in the orthogonal apical views using harmonic imaging (1.7 MHz to transmit, 3.5 MHz to receive), without and then with contrast injection (Optison). The apical views of the LV (four-chamber and either two-chamber or long-axis views) were acquired and stored digitally (Acuson Sequoia, Mountain View, California). After completion of all echocardiograms, the images with and without contrast injection were assigned random numbers and analyzed by observers who had no knowledge of the patients’ identification, clinical data and previous results. Each observer computed EDV, ESV, SV and EF by tracing the LV contours where they visualized the endocardial border, as recommended by the American Society of Echocardiography (20). Tracing of LV contour left the papillary muscles and trabeculations within the LV cavity, but otherwise was performed where the blood-myocardial interface was seen (20). The LV volumes were then calculated using the biplane Simpson’s rule (method of disks) (20). Measurements were then entered in the study data base by data-entry personnel not involved in the study.
To define the reproducibility of echocardiography in 32 patients, LV contours were traced off-line from the digitally retrieved cycles in random order by observers who had no knowledge of the previous results and the patients’ identification. Three observers, with training levels 1, 2 and 3 (21,22), independently performed all measurements, which were repeated a second time in a different random order by each observer. To determine the accuracy of echocardiography in 26 patients, LV echocardiographic images were recorded and saved within 1 h before performance of an EBCT of the heart. The LV contour tracings of the echocardiographic images were performed in a blinded and randomly ordered fashion after completion of the study.
Quantitation of mitral regurgitation was performed using the quantitative Doppler (23) and proximal isovelocity surface area (24) methods. Regurgitant volume and effective regurgitant orifice were calculated (24,25).
Optison was administered intravenously in doses of 0.5 ml, followed by a saline flush. Additional doses, up to a maximal dose of 3.0 ml, were given until the LV was opacified with the contrast agent. Contrast injection images were acquired using second-order harmonic imaging with settings adjusted to reduce the mechanical index to 0.5 to 0.6 and with displacement of the transmit zone to the level of the tips of the mitral valve leaflets.
Electron beam computed tomography.
Electron beam computed tomography (Imatron C-150, South San Francisco, California) was performed using electrocardiographic triggering for acquisition of polytomographic images at 17 frames/s. The subjects were positioned to acquire parallel tomographic images in the short axis from the LV apex through the left atrial roof. Infusion of a nonionic contrast agent (iopamidol [Isovue-370]) was administered using a power injector. With suspended respiration, an eight-level ECG-triggered cine sequence with 8-mm-thick slices was obtained. The identical sequence was repeated after repositioning to obtain a total of 16 levels covering the entire cardiac span. Cross-sectional tomographic images (360 x 360 matrix) were reconstructed using a filtered back-projection algorithm and stored on optical disk. The LV epicardial and endocardial surfaces were identified during contrast enhancement (26) and traced for each slice, with LV volumes calculated using the modified Simpson’s rule (27).
Statistical analysis.
The results are expressed as the mean value ± SD or percentages, as appropriate. Comparison of echocardiography and EBCT was based on paired t tests. Comparison of the relative accuracy of the methods (echocardiography vs. EBCT) was done using paired t tests with unsigned differences (absolute and relative) between echocardiography and EBCT.
Intraobserver variability of the echocardiographic methods was compared by submitting unsigned differences (absolute and relative) between replicate readings for each observer for each modality to three-way analysis of variance (ANOVA) (patient by modality by observer) and by estimating and testing the main effects of each patient, observer and modality on intraobserver differences. To analyze interobserver variability, replications for each observer were averaged, and the sample variance (s2) of these averages within each patient across modalities was calculated. The s values were then submitted to two-way ANOVA (patient by modality), and the main effects of each patient and modality were estimated and tested. Analysis was repeated on a relative standard deviation, defined as standard deviation divided by the mean value. Finally, to estimate the components of global variability, the original data of each modality were submitted to three-level nested ANOVA, with replication nested within observer, nested within patient. A formal comparison was carried out on the basis of ratios between patient variance and intraobserver or interobserver variance. The difference of the logarithm of the ratio of mean square values was calculated, with standard error based on an asymptotic calculation using the chi-square distribution, and assumed independence between all mean square values. Because mean square values are almost certainly positively correlated between modalities, this procedure is conservative, but all pairwise comparisons turned out to be significant (p < 0.05).
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Results
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Baseline characteristics.
The baseline characteristics were similar for patients participating in the accuracy (n = 26, 58% male, 68 ± 14 years old) and reproducibility (n = 32, 66% male, 66 ± 14 years old) parts of the study. In the accuracy and reproducibility subsets, New York Heart Association functional class was I or II in 100% and 88%, respectively. The LV end-diastolic and end-systolic diameters and EF by M-mode echocardiography were 58 ± 6 mm, 34 ± 5 mm and 68 ± 6%, respectively, in the accuracy subset and 56 ± 7 mm, 39 ± 10 mm and 58 ± 11%, respectively, in the reproducibility subset. Trivial aortic regurgitation was present in 8% and 6% of the accuracy and reproducibility subsets, respectively. The mean regurgitant volume and effective regurgitant orifice showed notable mitral regurgitation in the accuracy (71 ± 21 ml and 35 ± 11 mm2) and reproducibility (32 ± 42 ml and 24 ± 27 mm2) subsets. The systolic and diastolic blood pressure and heart rate were within the normal range in the accuracy (142 ± 19 mm Hg and 75 ± 12 mm Hg and 64 ± 10 beats/min) and reproducibility (138 ± 28 mm Hg and 80 ± 12 mm Hg and 71 ±12 beats/min) subsets. No side effects from contrast injection were observed in any of the patients.
Accuracy of absolute LV volumes.
Compared with EBCT, echocardiography without contrast injection leads to marked underestimation of EDV, ESV and SV (all p < 0.0001) (Table 1). The magnitude of underestimation was 76 ± 30 ml, 18 ± 17 ml and 58 ± 20 ml, respectively, for EDV, ESV and SV, or 39%, 31% and 42% in relative terms. There was no significant underestimation for EDV, ESV or SV measured with contrast injection (all p > 0.17) (Table 1), with the regression line almost superimposed on the identity line (all r > 0.87) (Figs. 1A, 2A and 3A). The systematic difference in accuracy of EDV, ESV and SV by echocardiography with and without contrast injection was confirmed by Bland-Altman plots (Figs. 1B, 2B and 3B). The unsigned (absolute value) differences between echocardiography and EBCT (expressed in original units or as a percentage of EBCT values) were significantly lower with than without contrast injection for EDV, ESV and SV (all p < 0.001), confirming the superiority of the results obtained by using contrast injection.
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Figure 1 The impact of contrast injection on the assessment of left ventricular remodeling. (A) Scatterplot of end-diastolic volume (EDV) measured with electron beam computed tomography (EBCT) (x axis) and echocardiography (Echo) (y axis) with (solid circles) and without (open triangles) contrast injection. The solid lines represent the regression lines between each echocardiographic modality and EBCT. The dashed line represents the identity line. (B) Scatterplot of the differences (y axis) in EDV between EBCT and echocardiography with contrast injection (solid circle) and between EBCT and echocardiography without contrast injection (open triangles). The thick solid line and the two thin lines indicate the mean value and 95% confidence interval of the difference between EBCT and echocardiography with contrast injection. Note the wide scatter of differences without contrast injection.
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Figure 2 The impact of contrast injection on the assessment of left ventricular remodeling. (A) Scatterplot of end-systolic volume (ESV) measured with electron beam computed tomography (EBCT) (x axis) and echocardiography (Echo) (y axis) with (solid circles) and without (open triangles) contrast injection. The solid lines represent the regression lines between each echocardiographic modality and EBCT. The dashed line represents the identity line. (B) Scatterplot of differences (y axis) in ESV between EBCT and echocardiography with contrast injection (solid circles) and between EBCT and echocardiography without contrast injection (open triangles). The thick solid line and the two thin lines indicate the mean value and 95% confidence interval of the difference between EBCT and echocardiography with contrast injection.
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Figure 3 The impact of contrast injection on the assessment of left ventricular remodeling. (A) Scatterplot of stroke volume (SV) measured with electron beam computed tomography (EBCT) (x axis) and echocardiography (Echo) (y axis) with (solid circles) and without (open triangles) contrast injection. The solid lines represent the regression lines between each echocardiographic modality and EBCT. The dashed line represents the identity line. (B) Scatterplot of differences (y axis) in SV between EBCT and echocardiography with contrast injection (solid circles) and between EBCT and echocardiography without contrast injection (open triangles). The thick solid line and the two thin lines indicate the mean value and 95% confidence interval of the difference between EBCT and echocardiography with contrast injection. Note the wide scatter of differences without contrast injection.
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The EF obtained by echocardiography without contrast injection was lower than that obtained by EBCT (68 ± 7% vs. 71 ± 5%, p = 0.011)—an underestimation by 3 ± 6 points, or 4% in relative terms—whereas the EF by echocardiography with contrast injection was not different from that by EBCT (72 ± 4%, p = 0.15). Unsigned differences between echocardiography and EBCT for EF were lower with than without contrast injection (both p < 0.03).
Compared with the total SV measured by Doppler, the LV SV showed marked underestimation when measured without contrast injection (–69 ± 26 ml, p < 0.0001), but no significant difference with contrast injection (–8 ± 25 ml, p = 0.12).
Reproducibility.
Intraobserver variability (Table 2, upper rows) decreased by measuring LV volumes after contrast injection, whether expressed in absolute (p < 0.004 for EDV, ESV and SV; p = 0.1 for EF) or relative (p < 0.05 for EDV, SV and EF) values. The other components of ANOVA showed significant patient effects (p < 0.005 for EDV, ESV and SV; p = 0.3 for EF) and mostly nonsignificant observer effects (p > 0.07 for EDV, SV and EF; p = 0.03 for ESV). There was no interaction between the experience of the observer and the decline in intraobserver variability (all p > 0.10). When harmonic imaging was compared with fundamental imaging, there was a trend toward lower intraobserver variability for EDV (15 vs.19 ml, p = 0.10) and ESV (13 vs.16 ml, p = 0.09), but no significant difference for SV (16 vs. 14 ml, p = 0.43) or EF (6% vs. 6%, p = 0.99).
Interobserver variability (Table 2, lower rows) decreased by measuring LV volumes after contrast injection, whether expressed in absolute (all p < 0.001) or relative (p < 0.01 for EDV, SV and EF) values. The other component of ANOVA showed mostly nonsignificant patient effects (p > 0.20 for EDV, SV and EF; p = 0.05 for ESV). Of note, the EDV, SV and EF values obtained by the three observers were significantly different when using harmonic imaging alone (all p < 0.002) (with a trend toward a difference in ESV, p = 0.10), whereas all values obtained with contrast injection were not different (all p > 0.18). When harmonic imaging was compared with fundamental imaging, interobserver variability was not different for EDV (22 vs. 24 ml, p = 0.53) or SV (22 vs. 25 ml, p = 0.24), but was reduced for ESV (14 vs. 21 ml, p = 0.0001) and EF (8% vs. 11%, p = 0.02).
Global variability.
The distribution of global variability of the dependent variables (EDV, ESV, SV and EF) is composed of variability due to observers (intraobserver and interobserver), variability due to intrinsic differences between patients (reflecting the breadth of values between patients) and variability due to random error. A perfect method results in 100% of variability related to intrinsic patient differences. Nested ANOVA, used to analyze components of global variability, showed highly significant components for patient variability (all p < 0.0001) and observer variability (all p < 0.006). Compared with measurements without contrast injection, variability components due to observer and random error were significantly reduced with contrast injection (Table 3). Of note, measurement of LV volumes with contrast injection was associated with global variability due almost entirely to intrinsic patient differences (94% for EDV, 93% for ESV, 87% for SV and 84% for EF).
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Table 3 Components of Global Variability*: Impact of Adding Contrast Injection on the Relative Distribution of Sources of Variability
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Discussion
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The present study shows that the addition of intravenous contrast injection results in improved accuracy and reproducibility of assessment of LV remodeling when compared with state-of-the-art echocardiography using harmonic imaging. In comparison to simultaneous EBCT, the accuracy of echocardiography for assessment of LV volumes is markedly improved, without underestimation. With the random-assignment design of the present study, the use of contrast injection results in a marked decrease in intraobserver and interobserver variabilities for measurement of LV volume, SV and EF. Therefore, postcontrast injection measures of LV remodeling show no significant difference between observers with different levels of training and experience. These improvements resulted in significant changes in the distribution of variability, which, after contrast injection, was due almost entirely due to intrinsic patient differences.
LV remodeling: importance of accurate assessment.
Left ventricular remodeling predicts a poor prognosis in the context of coronary disease (6,8,9), dilated cardiomyopathy (7) and valvular heart disease (2–5). Regardless of the causal disease, progression of LV remodeling leads to congestive cardiac failure and increased mortality (2–9). In coronary disease, LV remodeling may be influenced by medical treatment, and nonresponders usually display a poor prognosis (15). Similarly, in valvular disease, indications for surgical repair are dependent on the degree and progression of LV remodeling (2–5).
Clinically, assessment of LV remodeling requires at least an accurate and reproducible measurement of size (EDV and ESV) and systolic indexes (SV and EF). These simple variables represent a minimal requirement before more complex indexes can even be considered (28). Calculation of EF by simplified methods is usually appropriate (10,13,29), and measurement of LV volumes for that purpose is rarely required, although it may be necessary with complex regional wall motion abnormalities (20,30) or for detection of small changes. However, measurement of LV volumes to assess the degree and progression of LV remodeling is indispensable. Insidious remodeling with LV dilation, which usually precedes a decline in EF (7,31), has led to the concept of aggressive and early treatment of LV remodeling (3,31). This concept is applicable only if accurate detection of mild LV remodeling is feasible. Small increases in LV size are associated with a notable, independent increase in mortality (2–9). Therefore, sensitive, accurate and reproducible assessment of LV size is crucial in risk stratification and clinical decision-making. M-mode LV diameters are easy to measure as surrogates for LV volumes and have a narrow range of error in estimating LV volumes when LV size is close to normal. However, with increasing LV size, a considerable range of error makes LV diameters of little use for prediction of LV volume (10). Furthermore, the curvilinear relationship between diameter and volume means that small increases in diameter may correspond to large increases in volume in dilated ventricles (10). Therefore, with a remodeled LV, it is essential to directly measure LV volumes, rather than using imprecise and potentially misleading surrogates.
Rationale for use of contrast injection for assessment of LV volumes.
Echocardiography has been used to assess LV volume, but its accuracy and reproducibility have been challenged (11), especially with poor image quality. Technological advances that improve endocardial definition, second-order harmonic imaging and intravenous contrast injection (32,33) have the potential to improve the accuracy and reproducibility of assessment of LV volumes. Contrast injection improves measurement of LV volumes, compared with fundamental imaging alone (19). However, the current state-of-the-art imaging using harmonic imaging decreases side lobes and improves lateral resolution and endocardial definition (18). Whether contrast injection provides any further improvement may be questionable. Harmonic imaging may improve visualization of endocardial borders to such an extent that the use of contrast agents, which is costly, and inconvenient venous line placement may not be required for accurate quantification of LV function.
The present study shows that, despite the use of state-of-the-art harmonic imaging as a comparison standard, contrast enhancement results in improved accuracy and reduced intraobserver and interobserver variability for measurement of LV volumes and EF. This improvement allows observers with different levels of training to obtain similar results, not different from the results obtained by the reference method of EBCT, and decreases overall variability to the point that it is essentially due to intrinsic patient differences. Therefore, contrast enhancement is crucial for assessment of LV remodeling and has important clinical implications. The mechanism for this improvement with contrast injection is directly related to ventricular anatomy. The LV endocardial border is obscured by true myocardial structures, trabeculations, irregularities and papillary muscles (34), which, unlike artifacts and side lobes, are not eliminated by harmonic imaging. Echocardiographic contrast agents that traverse the pulmonary circulation enhance all blood-filled parts of the LV cavity and not only improve LV imaging quality (35,36) but also delimit the true cavity to the endocardial boundary (17).
Clinical implications.
With contrast injection, observers of all levels of expertise obtained similar and highly reproducible assessment of LV remodeling. Therefore, reproducible and accurate LV volume measurement, which in the past could be obtained using standard imaging in the hands of experts (14,19), can now be achieved by nonexperts using contrast injection and has the potential to result in more frequent assessment of LV remodeling in routine practice.
The accurate assessment of LV remodeling using contrast injection, in comparison to EBCT, is an essential improvement over the shortcomings of M-mode echocardiographic methods. The use of intravenous contrast injection is essential for initial or serial assessment of LV volumes in patients with an abnormal or dilated LV. In contrast, in normal ventricles, assessment of LV size and function using M-mode echocardiography is adequate (10). Therefore, contrast injection is not necessary in all patients undergoing echocardiography, but it is an important addition for the appropriate measurement of LV volumes in patients in whom LV dilation or remodeling is suspected, such as in patients with cardiomyopathy, previous myocardial infarction or valvular heart disease.
Study limitations.
The choice of the reference method can be disputed. Measurements of LV volume and mass by EBCT have been validated both in vivo and in vitro and show very low interobserver and intraobserver variabilities (26,27,37), allowing for follow-up of patients to detect LV remodeling (38). Because EBCT assessment of LV volumes is three-dimensional, noninvasive, accurate and reproducible, it serves as an ideal reference method for this study.
Measurements by experts may provide accurate LV volumes without injection of contrast (14), but are not widely applicable. The present study, by using observers who were not experts and who had different levels of experience, is widely applicable to routine echocardiography practice. Importantly, the present study shows, under its stringent methodology, that nonexperts of various levels can obtain accurate, highly reproducible measures of LV remodeling, and that the advantages provided by contrast injection are widely applicable.
It is impossible to blind observers to the presence of contrast agents on echocardiographic images, and this may potentially introduce bias. However, as the observers were totally blinded to each patient’s other results and to the patients’ identity, with tracings done in totally random order, the probability of bias is very low. Hence, the low variability and high accuracy of LV volumes measured with contrast injection underscore the value of this approach in assessing LV remodeling.
Conclusions.
The present study documents the improved accuracy and reproducibility of LV volume measurements when contrast injection is added to state-of-the-art second-order harmonic imaging. With contrast injection, observers with different levels of training and experience obtain similar LV remodeling measurements, and the global variability of measurements is almost exclusively due to intrinsic patient differences. Therefore, when evaluation of LV remodeling is deemed important, assessment after contrast injection should be the preferred echocardiographic approach and has the potential to be widely applicable in routine clinical practice.
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Footnotes
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Dr. Thomson was supported by a Research Fellowship Grant from the Royal Australian College of Physicians. Dr. Basmadjian was supported by a grant of the American Society of Echocardiography. The study was supported by a grant from the Mayo Foundation, Rochester, Minnesota. This study was also supported in part by the grants HL64928 and RR00585 of the National Institutes of Health.
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Abstract
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