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* From the University of Queensland, Brisbane, QLD, Australia.
Correspondence to: Thomas H. Marwick, MD, PhD, University of Queensland, Department of Medicine, Princess Alexandra Hospital, Ipswich Rd, Brisbane Q4102, QLD, Australia; e-mail: tmarwick{at}soms.uq.edu.au
Abstract
Objectives: The nongeometric nature of the right ventricle (RV) makes it difficult to measure. We sought to determine whether real-time three-dimensional echocardiography (RT3DE) is superior to two-dimensional echocardiography (2DE) for the follow-up of RV function by validation vs cardiac MRI.
Methods: RV volumes and ejection fraction (EF) were studied with 2DE (including area-length [A-L], the modified two-dimensional subtraction [2DS] method, and the Simpson method of discs), RT3DE, and MRI in 50 patients with left ventricular wall motion abnormalities, the results of which suggested possible RV infarction. Test-retest variation was performed by a complete restudy using a separate sonographer within 24 h without the alteration of hemodynamics or therapy. Interobserver and intraobserver variations were noted in a subgroup of 20 patients.
Results: EF estimations were similar using each technique. The mean (± SD) MRI end-diastolic volume (87 ± 22 mL) was only slightly underestimated by RT3DE (mean difference, –3 ± 10; p < 0.05), with a greater mean difference for 2DE A-L (–29 ± 10; p < 0.05), and the Simpson method of discs (–29 ± 23; p < 0.05), and was greatly overestimated by 2DS (mean difference, 26 ± 23; p < 0.05). Similarly, the mean MRI end-systolic volume (46 ± 17 mL) was only slightly underestimated by RT3DE (–4 ± 7; p < 0.05), compared with 2DE A-L (–16 ± 8; p < 0.05) and the Simpson method of discs (–16 ± 8; p < 0.05), and was overestimated by 2DS (14 ± 13; p < 0.05). RT3DE findings had a higher correlation with each parameter than any 2DE technique. There was also good intraobserver and interobserver correlation between RT3DE by two sonographers. RT3DE had less test-retest variation of RV volumes and EF than any 2DE measure.
Conclusions: RT3DE is more accurate than two-dimensional approaches and reduces the test-retest variation of RV volumes and EF measurements in follow-up RV assessment.
Key Words: ejection fraction • real-time three-dimensional echocardiography • right ventricle • two-dimensional echocardiography • volumes
The degree of right ventricular (RV) involvement is an important prognostic determinant after myocardial infarction.1 Moreover, sequential assessments of RV volumes and ejection fraction (EF) are potentially important in the follow-up of patients with congenital heart disease such as corrected tetralogy of Fallot,2 and the evaluation of RV systolic function is of value in assessing prognosis and treatment response in patients with pulmonary hypertension.3 A reliable noninvasive technique for RV evaluation would therefore be useful in patients with ischemic and other heart diseases. Two-dimensional echocardiography (2DE) remains the most widely available technique, but the nongeometric nature of the RV and its heavy trabeculations makes the measurement of RV volume difficult. Consequently, evaluation of the RV by 2DE is most commonly qualitative, rather than quantitative, and this is of limited value in the assessment of the RV over time.
Cardiac MRI is an alternative for RV volume and function assessment,4 but it is expensive, of limited availability, and cannot be performed in the increasing number of heart failure patients with implantable devices. Real-time three-dimensional echocardiography (RT3DE) has been validated5 as a reliable technique for the assessment of left ventricular (LV) size and function. Previous studies of RV volumes and EF with three-dimensional echocardiography (3DE) have been performed using three-dimensional (3D) reconstruction,6 sparse array transducers,789 and RT3DE,101112 but none have addressed test-retest reliability. We hypothesized that RT3DE would prove a reliable, reproducible technique for the follow-up of RV function, with results that would be comparable to those of cardiac MRI, and superior to those of 2DE. Therefore, the objectives of this study were as follows: (1) to compare RV volumes and EF by 2DE, RT3DE, and MRI; (2) to determine whether the test-retest variability of RT3DE; and (3) to compare the results of RT3DE to similar results from 2DE techniques.
Materials and Methods
Study Design
We prospectively recruited patients who had been referred to the echocardiography laboratory for the assessment of cardiac structure and function after experiencing an acute myocardial infarction, and who were scheduled to undergo 2DE, RT3DE, and MRI. In 54 patients (47 men; mean [± SD] age, 63 ± 10 years), RV involvement was suspected from standard imaging, and an additional medial RV view was obtained using RT3DE (see "RT3DE" section below). The investigations were approved by the Human Research Ethics Committee of Princess Alexandra Hospital, and all patients gave informed consent.
Data for test-retest variability were obtained by discharging patients from the laboratory and repeating their imaging within 24 h with no intervening therapy. A subgroup (n = 20) was studied for interobserver variability, which was determined by using the same set of 3D and two-dimensional images measured by two separate sonographers. The same group was tested for intraobserver variability, with volume measurements repeated on the same data set by the same sonographer. Intraobserver repeated measures were performed on average 1 week apart; repeated analysis was performed in random order.
2DE
An experienced sonographer acquired apical views of the RV, using harmonic imaging with a transthoracic 3-MHz phased array transducer (Sonos 7500; Philips Medical Systems; Andover, MA). Measurements of RV end-diastolic volume (EDV), RV end-systolic volume (ESV), and EF were obtained using the software installed on the ultrasound machine, with EDV measured at the time of tricuspid valve closure and ESV measured on the image with the smallest RV cavity. The papillary muscles were excluded from the volumes; however, the moderator band and trabeculations were included. The area-length (A-L) method used was the monoplane ellipsoid method, in which the RV volume is 3/8
{(Area-apical 4chr)2/Length-apical 4chr} (Fig 1
, top left, A).13 The Simpson method of discs is based on the division of the RV into a series of slices of equal thickness, the volume of each of which is calculated from the following formula: volume = area x length, so that the RV volume is calculated from the sum of these slices (Fig 1, center left, B). Both measurements were obtained from apical four-chamber views by tracing the endocardial border of the RV.14 The 2DE subtraction method15 was obtained from the apical four-chamber view by tracing the volume of the LV with the inclusion of the interventricular septum and subtracting it from the total volume of the LV and RV (Fig 1, bottom left, C).
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Measurements of RT3DE volumes and EF were performed off-line (4D Analysis; Tomtec Gmbh; Unterschlessheim, Germany). Frames for EDV and ESV measurements were identified by the same method as that for 2DE, and endocardial contours were marked in 12 slices (ie, 15° per slice). Contour tracing was performed with semiautomatic border detection; after first identifying the apex and tricuspid annulus on each slice, a preconfigured ellipse was fitted to the endocardial borders of each frame and was adjusted as required. The EDV and ESV were measured from the resulting 3D volume (Fig 1, top right, D). RV measurements were obtained by applying the LV model to fit the RV, with semiautomated border detection and manual editing of the borders to give a 3D model from which volumes can be measured without geometric assumptions. The mean scanning time for 3DE taken for one full volume was 50 ± 19 s; however, the acquisition time requiring a breathhold was approximately 10 s. The time required for the calculation of RV volumes ranged from 5 to 10 min.
MRI
MRI was performed using a 1.5-Tesla scanner (Sonata; Siemens; Erlangen, Germany). A true free induction, steady-state precession sequence (recovery time, 47.1 ms; echo time, 1.57 ms; flip angle, 60°; bandwidth, 930 Hz/pixel) was used to examine RV anatomy and function. Images were acquired during breath-hold in short-axis planes (voxel size, 1.8 x 1.3 x 10 mm) perpendicular to the tricuspid valve annulus. Between six and eight short-axis images of the RV were obtained with slice thicknesses of 8 mm. RV volumes were measured using offline software (Argus; Siemens). After the identification of the end-systolic and end-diastolic phases of the cardiac cycle, the semiautomated detection of endocardial borders was optimized with fine manual adjustment, and RV volumes and EF were calculated.
Statistical Analysis
The results for RV EDV, RV ESV, and EF are represented as the mean and SDs. Correlations were performed between echocardiography and MRI measurements, and agreement was expressed according to the method of Bland and Altman.161718 A p value of < 0.05 was considered to be significant. Z transformations were performed between each group to see whether there was any significant difference between correlations.19 Data analyses were performed using a statistical software package (SPSS, version 10; SPSS; Chicago, IL).
Results
Patient Characteristics
Of the 54 original patients, 2 were excluded from RT3DE as they were unable to hold their breath during acquisition, and another 2 were excluded from the MRI validation due to claustrophobia. Therefore, the results of the MRI, RT3DE, and 2DE were analyzed in 50 patients (43 men; mean age, 62 ± 11 years). All patients had LV regional wall motion abnormalities, with 70% of patients undergoing angiography. The majority had multivessel coronary artery disease (defined by > 70% stenosis in more than one major epicardial vessel). Interest in RV dysfunction was based on either inferior involvement in 41 patients (raising suspicions about RV infarction) or LV dysfunction (Table 1
). RV systolic dysfunction (RV EF, < 40%) was defined by the visual assessment of an experienced cardiologist. RT3DE slice planes showed that the greater the number of slices, the greater the possibility of capturing the entire structure, although there is a tradeoff with measurement time (Table 2
); hence, the use of 12 slices for RV volume measures.
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The results of this study of patients with ischemic LV dysfunction and suspicion of RV involvement indicate that RV volume measurements using RT3DE imaging are comparable with MRI. RT3DE also provides low test-retest variation and high reproducibility of RV measurements between observers.
RV Assessment by Echocardiography
Echocardiography is the most widely used technique for imaging the RV, but assessment can be challenging because of the location of the RV behind the sternum and its crescent shape, wrapped around the LV.20 Endocardial tracing and the calculation of volumes may be hindered by trabeculations and the presence of the moderator band within the volume. Geometric shapes are too simplistic to be applied as models for RV volume calculation; the Simpson method for the calculation of EFs is more accurate in patients with cor pulmonale.21 RV size and function may be difficult to assess in patients with pulmonary disease, but assessment plays an important role in clinical decision making for therapy and prognosis.
Because of these difficulties in RV volumetric assessment, other echocardiographic modalities have been used to assess RV function. These include tissue Doppler and strain rate imaging, which are sensitive and noninvasive, although the clinical experience with both is limited. Longitudinal strain rate imaging has been shown to be feasible in a clinical setting, but radial imaging is hindered by artifacts and has not been proven to be of clinical value.22 Pressure-volume loops are the "gold standard" approach to the load-independent assessment of RV systolic and diastolic function, but they require an invasive procedure.22
Measurements not only must be accurate but also reproducible. RT3DE has been found to be reproducible for the assessment of LV systolic function in the clinical laboratory523 and might, therefore, be useful for the assessment of RV function. Table 6 summarizes previous validation studies using 3DE of the RV that have used various techniques such as reconstructed array6 and sparse array,789 and, although some studies101112 used RT3DE, the method for analysis differs. Clearly, reproducibility is limited not only by measurement error but also by extrinsic variables such as preload, afterload, pericardial constraint, and medical therapy.24
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Previous studies of volumetric 3DE8 and reconstructed 3DE6 have shown that this technique exhibits higher reproducibility than 2DE. In this study, interobserver variation was optimized by the use of RT3DE, which could reflect the use of a semiautomated edge-detection technique. In contrast to the more widely reported parameters of intraobserver and interobserver variability, test-retest variation is not commonly reported but assumes particular importance in the use of a test in follow-up. RT3DE was found to have less variation and higher correlation to MRI than all 2DE techniques. The major contributor to the volume underestimation of 2DE is its single-plane approach to volumetric measurement. The large variation in the measurement is due to the multiplication of the error in the calculation of the volumes.
Limitations
The main limitation of this study was the relatively small population (n = 50) in whom interest in RV function pertained to ischemic heart disease. These changes are more subtle than those associated with more overt RV pathology such as tetralogy of Fallot, arrhythmogenic RV dysplasia, and pulmonary hypertension. The second limitation was the current shortcoming of RT3DE relating to the quality of images, which are compromised by both line density and frame rate. Difficulty in the discrimination of the endocardial border is an important potential contributor to inaccuracies in the measurement of RV volumes, and image quality was a predictor of discrepancy between 3D and MRI measurements of the change in RV volume. Both limitations of image quality and acquisition volume may be alleviated by technical improvements.
Finally, MRI may itself be imperfect for RV assessment. The failure to visualize the tricuspid valve may lead to the overestimation of RV volumes. Most MRI software derives volumes from serial short-axis slices of the RV, which may pose problems because of RV geometry, and gathering a 3D data set may be more effective in measuring such a nongeometric structure.
Conclusions
In this study, RT3DE was the most accurate echocardiographic technique used for the measurement of RV volumes in subjects with LV dysfunction. It also appears to be a feasible follow-up imaging tool for sequential measurements of the RV volumes and function.
Footnotes
Abbreviations: A-L = area-length; EDV = end-diastolic volume; EF = ejection fraction; ESV = end-systolic volume; LV = left ventricle, ventricular; RT3DE = real-time three-dimensional echocardiography; RV = right ventricle, ventricular; 3D = three-dimensional; 3DE = three-dimensional echocardiography; 2DE = two-dimensional echocardiography; 2DS = two-dimensional subtraction
Supported in part by a grant-in-aid from the National Health and Medical Research Council of Australia.
The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
Received for publication August 29, 2006. Accepted for publication January 28, 2007.
References
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