Real-time 3-dimensional echocardiography early after acute myocardial infarction: Incremental value of echo-contrast for assessment of left ventricular function
Article Outline
Background
Accurate and reproducible assessment of left ventricular (LV) systolic function is important in patients with acute myocardial infarction (AMI). Real-time 3-dimensional echocardiography (RT3DE) is an accurate technique, but it relies heavily on good image quality. The aim of the present study was to evaluate the incremental value of contrast-enhanced RT3DE.
Methods
A total of 140 consecutive patients (58 ± 11 years, 78% men) with ST-elevation AMI clinically underwent nonenhanced and contrast-enhanced RT3DE within 24 hours from AMI to evaluate global and regional LV systolic function. Endocardial border definition was graded for each of the 16 LV segments as follows: 0 = border invisible, 1 = border visualized only partially, and 2 = complete visualization of the border. Three image-quality groups (good, fair, and uninterpretable) were identified. Left ventricular volumes and ejection fraction were measured off-line. Wall motion was graded for each visible segment as follows: 1 = normal, 2 = hypokinetic, 3 = akinetic, and 4 = dyskinetic.
Results
During contrast-enhanced RT3DE, as compared with nonenhanced RT3DE, the number of segments with complete visualization of the endocardial border increased from 66% to 84% (P < .001); and the number of patients with a good-quality echocardiogram increased from 59% to 94% (P < .001). Intra- and interobserver agreement for assessment of global and regional LV systolic function improved during contrast-enhanced RT3DE, as compared with nonenhanced RT3DE.
Conclusions
Assessment of LV systolic function in AMI patients with RT3DE is frequently hampered by suboptimal echocardiographic quality. Contrast-enhanced RT3DE is of incremental value, improving the endocardial border visualization and the reproducibility of LV function assessment.
The assessment of global and regional left ventricular (LV) systolic function is extremely important among patients with acute myocardial infarction (AMI) because it carries significant therapeutic and prognostic implications.1, 2, 3, 4, 5, 6 Recently, real-time 3-dimensional echocardiography (RT3DE) has been introduced for assessment of LV function and volumes. Real-time 3D echocardiography has been validated against magnetic resonance imaging and found to be more accurate and reproducible as compared with 2-dimensional echocardiography (2DE).7, 8, 9, 10, 11, 12, 13
However, even more than 2DE, RT3DE relies heavily on the presence of good image quality.14, 15
The use of intravenous contrast agents during 2DE has been shown to be of incremental value, improving LV endocardial border visualization among patients with suboptimal image quality and increasing the accuracy and reproducibility of LV systolic function measurements.16, 17, 18, 19, 20, 21, 22 In contrast, data regarding the use of echo-contrast during RT3DE are scarce.14,23, 24, 25 In particular, no specific data exist about the efficacy of contrast-enhanced RT3DE performed early after AMI; the safety of contrast-enhanced echocardiography early after AMI was recently reported.26 The aim of the present study was therefore to investigate, in a large cohort of consecutive patients with AMI, the potential incremental value of contrast-enhanced RT3DE over nonenhanced RT3DE for assessment of LV function and volumes.
Methods
Study population
The study population consisted of 140 patients admitted to the coronary care unit because of ST-elevation AMI. The diagnosis of ST-elevation AMI was made on the basis of typical electrocardiographic changes and/or ischemic chest pain associated with elevation of cardiac biomarkers.27
All patients underwent immediate coronary angiography and primary percutaneous coronary intervention. As part of the clinical workup, RT3DE (with echo-contrast) was performed in the coronary care unit within 24 hours from patients' admission to accurately evaluate global and regional LV systolic function. Of note, the safety profile of echo-contrast infusion in 115 of these patients has been recently reported using conventional 2DE.26
Echocardiography
Patients were imaged in left lateral decubitus position with a commercially available system (Vivid 7; GE Healthcare, Horten, Norway) equipped with a 3-V phased array transducer (2.5 MHz). First, apical full-volume 3D data sets were acquired in harmonic mode, integrating, during a brief breath hold, 8 R wave–triggered subvolumes into a larger pyramidal volume (90° by 90°) with a complete capture of the LV. Thereafter, the same acquisition was repeated during echo-contrast administration (Luminity; Bristol-Myers Squibb Pharma, Bruxelles, Belgium) to optimize LV border delineation. Each patient received an intravenous infusion of 1.3 mL of echo-contrast diluted in 50 mL of 0.9% NaCl solution; the rate of infusion was initially set at 4.0 mL/min and then titrated to achieve optimal LV chamber opacification and endocardial border delineation.28 Contrast-enhanced RT3DE was performed in harmonic mode at low mechanical index (0.26), and care was taken to record the images at a phase when echo-contrast flow was relatively stable with absent or minimal swirling in the apex.
The 3D data sets were digitally stored for the off-line analysis.
Echocardiographic analysis
The 3D data sets were analyzed online for the analysis of LV chamber opacification and off-line for the analysis of LV endocardial border definition and LV volumes and function. The off-line analysis was performed using a dedicated software (4D LV-Analysis; TomTec, Munich, Germany) by an observer who had no knowledge of the patient's identity, medical history, and symptom status. As described elsewhere,29 the software automatically displays in a quad screen the 4-chamber view, as a reference view; the 2- and 3- chamber views with default interplane angles at 60°; and a short-axis view (Figure 1). The interplane angles can be manually modified to obtain adequate orientation of the 3 apical views, and their meeting point can be adjusted in the middle of the LV cavity to avoid LV foreshortening. This procedure can also be used to evaluate regions between the 3 adjacent conventional apical views.
Figure 1.
A, Example of fair-quality echocardiogram during nonenhanced RT3DE. B, Optimal LV chamber opacification and improved endocardial border definition during contrast-enhanced RT3DE in the same patient. The 3 apical views are shown with the 4-chamber view as a reference view in the top right and the 2- and 3-chamber views in the bottom left and bottom right, respectively. Top left: short-axis view.
The degree of LV chamber opacification during echo-contrast administration was graded according to 5-point rating scale17, 28: 0 = no contrast enhancement, 1 = weak or little contrast enhancement, 2 = adequate contrast enhancement that facilitates image interpretation, 3 = full contrast enhancement that definitely aids image interpretation, and 4 = excessive contrast enhancement that hampers interpretation. The percentage of patients with adequate-to-full contrast enhancement was calculated. The mean time needed to achieve adequate-to-full contrast enhancement was measured.
LV endocardial border definitionQualitative assessment of the endocardial border was performed in both nonenhanced and contrast-enhanced images. A standard 16-segment model was used.30 Adequacy of LV endocardial border definition was graded for each of the 16 cardiac segments as follows22: 0 = border invisible, 1 = border visualized only partially throughout the cardiac cycle and/or incomplete segment length, and 2 = complete visualization of the border. A global endocardial visualization score was calculated as the sum of each LV segment's score.
On basis of the global score, 3 image-quality groups were defined: good (score 25-32), fair (score 17-24), and uninterpretable (score ≤16).15, 22 Uninterpretable echocardiograms were deemed nondiagnostic, and further analyses of LV volumes and global and regional LV functions were considered not feasible.
LV volumes and global systolic functionThe algorithm used by the software to calculate LV end-diastolic volume (EDV), LV end-systolic volume (ESV), and LV ejection fraction (EF) is described in detail elsewhere.29 Briefly, the endocardial border is manually traced in the 3 apical views (including LV trabeculations and papillary muscles within the cavity) in both the end-diastolic and end-systolic frames. Subsequently, the software automatically identifies the endocardial border in the entire 3D data set; further manual adjustments are possible in approximately 30 coronal and sagittal planes. Finally, a reconstruction of the LV model is generated; and LV volumes and LVEF are obtained.
LV regional functionQualitative assessment of the regional wall motion was performed in both nonenhanced and contrast-enhanced images, according to the same 16-segment model used for the evaluation of LV endocardial border definition.30 Segments with invisible endocardial border were excluded from this analysis. Wall motion was graded for each of the visualized segments as follows: 1 = normal, 2 = hypokinetic, 3 = akinetic, and 4 = dyskinetic. A global wall motion score index (WMSI) was calculated as the sum of each LV segment's score divided by the number of visualized segments.
Reproducibility of RT3DE measurementsThe data sets of 20 patients with a good-quality echocardiogram and 20 patients with a fair-quality echocardiogram during nonenhanced RT3DE were randomly selected and analyzed again 1 month later by the original observer and by a second observer who was blinded to the results of the previous analysis. Intra- and interobserver agreement was assessed for the measurements of LV volumes and LVEF and the grading of regional wall motion.
Statistical analysis
Continues variables are expressed as mean and SD. Categorical data are presented as absolute numbers and percentages. The global endocardial visualization score and the measurements of LV volumes, LVEF, and WMSI were compared between the 2 imaging techniques with the paired t test. To determine whether there was a statistically significant difference in the comparison between categorical variables, the McNemar test was performed for binary data and the marginal homogeneity test for multinomial response data.
Intra- and interobserver agreement in the measurements of LV volumes and LVEF were assessed using Bland-Altman analysis and expressed as the mean difference between the 2 measurements ± 2 SDs. To evaluate intra- and interobserver agreement in the grading of regional wall motion, weighted κ test was used; and the level of agreement was interpreted as follows : 0 to 0.2 = poor to slight, 0.21 to 0.4 = fair, 0.41 to 0.6 = moderate, 0.61 to 0.8 = substantial, and 0.81 to 1.0 = nearly perfect. A P value < .05 was considered statistically significant. Statistical analysis was performed using the SPSS software package (SPSS 15.0, Chicago, IL).
The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents. No extramural funding was used to support this work.
Results
Study population
The baseline characteristics of the study population are summarized in Table I. Mean age of the patients was 58 ± 11 years; 109 (78%) were male. The infarct-related artery was the left anterior descending coronary artery in 60 (43%) patients, the left circumflex coronary artery in 19 (13%), and the right coronary artery in 61 (44%). Obstructive multivessel disease (ie, >1 vessel with a luminal narrowing ≥70%) was present in 51 (36%) patients.
Table I. Clinical and echocardiographic patient characteristics (N = 140)
| Age (y) | 58 ± 11 |
| Gender (male/female) | 109/31 |
| Diabetes | 16 (11%) |
| Family history of coronary artery disease | 54 (39%) |
| Hypercholesterolemia | 26 (19%) |
| Hypertension | 50 (36%) |
| Current or previous smoking | 85 (61%) |
| Previous myocardial infarction | 15 (11%) |
| Previous myocardial revascularization | 12 (9%) |
| Body mass index (kg/m2) | 27 ± 4 |
| Current anterior myocardial infarction | 60 (43%) |
| Current infarct-related artery | |
 Left anterior descending coronary artery | 60 (43%) |
| Left circumflex coronary artery | 19 (13%) |
| Right coronary artery | 61 (44%) |
| Multivessel coronary artery disease | 51 (36%) |
Echocardiography
The mean infusion rate of echo-contrast was 3.0 ± 0.6 mL/min, and the total infusion dose was on average 16 μL/kg.
LV chamber opacificationAdequate-to-full enhancement during echo-contrast infusion was noted in 130 (93%) patients. Weak or little contrast enhancement was observed in 9 (6%) patients and excessive contrast enhancement in 1 (1%) patient. The mean time needed to achieve adequate-to-full LV contrast enhancement was 65 ± 20 seconds.
LV endocardial border definitionDuring nonenhanced RT3DE, from the total number of 2,240 LV segments, the endocardial border was invisible in 243 (11%) and visualized only partially in 509 (23%). A complete visualization of the border was possible in 1,488 (66%) segments (Table II). The mean global endocardial visualization score was 25 ± 6. A total of 82 (59%) patients had a good-quality echocardiogram, whereas 44 (31%) and 14 (10%) had a fair-quality and uninterpretable echocardiogram, respectively (Figure 2).
Table II. Left ventricular endocardial border definition with nonenhanced and contrast-enhanced RT3DE
| Nonenhanced RT3DE | Contrast-enhanced RT3DE | P value | |
|---|---|---|---|
| Overall segments (N = 2240) | <.001 | ||
| Border invisible | 243 (11%) | 16 (1%) | |
| Border visualized only partially | 509 (23%) | 334 (15%) | |
| Complete visualization of the border | 1488 (66%) | 1890 (84%) | |
| Anterior wall segments (n = 420) | <.001 | ||
| Border invisible | 118 (28%) | 4 (1%) | |
| Border visualized only partially | 145 (35%) | 139 (33%) | |
| Complete visualization of the border | 157 (37%) | 277 (66%) | |
| Anterolateral wall segments (n = 420) | <.001 | ||
| Border invisible | 40 (10%) | 1 (0%) | |
| Border visualized only partially | 151 (36%) | 46 (11%) | |
| Complete visualization of the border | 229 (54%) | 373 (89%) | |
| Anterior septum segments (n = 280) | <.001 | ||
| Border invisible | 55 (20%) | 5 (2%) | |
| Border visualized only partially | 64 (23%) | 57 (20%) | |
| Complete visualization of the border | 161 (57%) | 218 (78%) | |
| Inferior wall segments (n = 420) | .04 | ||
| Border invisible | 13 (3%) | 2 (1%) | |
| Border visualized only partially | 52 (12%) | 52 (12%) | |
| Complete visualization of the border | 355 (85%) | 366 (87%) | |
| Inferolateral wall segments (n = 280) | <.001 | ||
| Border invisible | 7 (2%) | 2 (1%) | |
| Border visualized only partially | 67 (24%) | 29 (10%) | |
| Complete visualization of the border | 206 (74%) | 249 (89%) | |
| Inferior septum segments (n = 420) | <.001 | ||
| Border invisible | 10 (2%) | 2 (1%) | |
| Border visualized only partially | 30 (7%) | 11 (2%) | |
| Complete visualization of the border | 380 (91%) | 407 (97%) |
Figure 2.
Image quality during nonenhanced and contrast-enhanced RT3DE. P < .001 for comparison between the 2 imaging techniques.
During contrast-enhanced RT3DE, a complete visualization of the border was possible in 1,890 (84%) segments (P < .001 vs nonenhanced RT3DE) (Table II). The LV endocardial border definition significantly improved in the segments of each LV wall (Table II). As compared with nonenhanced RT3DE, the mean global endocardial visualization score improved to 29 ± 3 (P < .001). A total of 131 (94%) patients had a good-quality echocardiogram, whereas 7 (5%) and 2 (1%) had a fair-quality and uninterpretable echocardiogram, respectively (P < .001 vs nonenhanced RT3DE) (Figure 2).
An example of LV chamber opacification and improved endocardial border definition during contrast-enhanced RT3DE, as compared with nonenhanced RT3DE, is displayed in Figure 1.
LV volumes and global systolic functionNonenhanced RT3DE provided significantly lower values of LV EDV as compared with contrast-enhanced RT3DE (107 ± 28 vs 113 ± 27 mL, P < .001). The values of LV ESV were not statistically different between the 2 techniques (59 ± 21 vs 61 ± 20 mL, P = not significant). Accordingly, nonenhanced RT3DE provided slightly but significantly lower values of LVEF (45% ± 9% [median 46%, interquartile range 39%-51%] vs 47% ± 9% [median 47%, interquartile range 39%-53%], P = .003).
LV regional systolic functionWall motion score index assessed on nonenhanced and contrast-enhanced images was 1.8 ± 0.4 and 1.7 ± 0.4, respectively (P = .04).
Reproducibility of RT3DE measurementsIntra- and interobserver agreement for the measurements of LV volumes and LVEF and the grading of regional wall motion obtained with the 2 techniques is shown in Table III, Table IV. The weakest agreements were observed among patients with a fair-quality echocardiogram. Contrast-enhanced RT3DE improved intra- and interobserver agreement in both good and fair echocardiograms.
Table III. Intra- and interobserver agreements for the measurements of LV volumes and LV global function in relation to image quality during nonenhanced RT3DE
| Good-quality echocardiogram during nonenhanced RT3DE | Fair-quality echocardiogram during nonenhanced RT3DE | |||
|---|---|---|---|---|
| Intraobserver agreement | ||||
| Nonenhanced | Contrast enhanced | Nonenhanced | Contrast enhanced | |
| LV EDV | −1.5 ± 28.0 | −0.7 ± 6.8 | −4.5 ± 42 | 4.0 ± 12.8 |
| LV ESV | −1.0 ± 17.0 | 0.2 ± 5.4 | −2.7 ± 24.8 | 3.1 ± 5.6 |
| LVEF | −0.1 ± 10.0 | −0.4 ± 4.6 | 1.7 ± 14.8 | −0.8 ± 5.0 |
| Interobserver agreement | ||||
| LV EDV | −6.1 ± 36.2 | −0.6 ± 13.8 | −6.6 ± 44.2 | 4.8 ± 17.4 |
| LV ESV | −4.2 ± 20.2 | 0.5 ± 9.2 | −6.4 ± 36.2 | 3.8 ± 12.6 |
| LVEF | 1.0 ± 12.8 | −0.7 ± 7.4 | 2.2 ± 22.4 | −1.4 ± 8.8 |
Table IV. Intra- and interobserver agreements for the grading of LV regional wall motion in relation to image quality during nonenhanced RT3DE
| Good-quality echocardiogram during nonenhanced RT3DE | Fair-quality echocardiogram during nonenhanced RT3DE | |||
|---|---|---|---|---|
| Intraobserver agreement | ||||
| Nonenhanced | Contrast enhanced | Nonenhanced | Contrast enhanced | |
| LV RWM | 0.77 | 0.95 | 0.69 | 0.92 |
| Interobserver agreement | ||||
| LV RWM | 0.65 | 0.87 | 0.54 | 0.85 |
Discussion
The current results show that, among unselected patients in the early stage of AMI, contrast-enhanced RT3DE has a high feasibility (93%) and is of incremental value for the assessment of LV systolic function. Specifically, as compared with nonenhanced RT3DE, (1) it significantly increased the number of LV segments with a complete visualization of the endocardial border (from 66% to 84%); (2) it increased the number of good-quality echocardiograms (from 59% to 94%); and (3) it reduced the number of fair-quality and uninterpretable echocardiograms (from 41% to 6%). Moreover, intra- and interobserver agreement for the measurements of global and regional LV systolic function improved during contrast-enhanced RT3DE, particularly among patients with fair-quality echocardiogram during nonenhanced RT3DE.
Advantages and limitations of RT3DE
The most commonly used imaging modality for the evaluation of global and regional LV systolic function is 2DE. However, 2DE relies on significant geometric assumptions, resulting in modest agreement with reference methods and fair reproducibility.17, 31
More recently, RT3DE has been proposed to overcome the above-mentioned limitations of 2DE; RT3DE correlated well with magnetic resonance imaging for assessment of LV volumes and LVEF.8, 9, 10, 11 In addition, it has been suggested that RT3DE has potential advantages for the evaluation of regional LV function in regions/planes that could not be adequately visualized with 2DE.7, 13
Because of its higher accuracy and reproducibility, RT3DE could be extremely useful for serial assessment of systolic function.32 Real-time 3D echocardiography would be particularly useful in AMI patients, in whom accurate assessment of LV function and volumes is important for prediction of future adverse events.2, 3
However, RT3DE still has several limitations; particularly, RT3DE image quality is highly dependent on the acoustic window because of a lower spatial and temporal resolution as compared with 2DE.11, 24 Accordingly, adequate endocardial border delineation may be difficult on RT3DE still frames, even in the presence of relatively good-quality 2DE.33 Because of this limitation, most of the previous RT3DE studies included only patients with an optimal acoustic window.8, 9, 10 Few studies explored the feasibility of RT3DE, in relation to the image quality, for the assessment of LV systolic function in unselected population and reported a prevalence of uninterpretable or poor-quality RT3DE images in the range of 35%.15, 24 This issue may be even more prominent in patients with AMI, in whom adequate assessment of LV function and volumes is important for prognosis, but in whom RT3DE data acquisition may be hampered by reduced patient mobility.12, 34 In the present study, 41% of 140 consecutive patients referred to RT3DE within 24 hours from AMI had a fair-quality or uninterpretable echocardiogram. This percentage is in line with previous studies15, 24 and may also be related to technical limitations associated to the performance of RT3DE in the coronary care unit, as well as the high body mass index of our study population.
Incremental value of contrast-enhanced RT3DE
In the subset of patients with inadequate RT3DE images, contrast agents could improve LV endocardial border visualization, increasing the feasibility, accuracy, and reproducibility of LV function assessment as previously reported with 2DE.16, 17, 18, 19, 20, 21, 22
Thus far, few small studies14,23, 24, 25 (16, 20, 39, and 50 patients, respectively) previously assessed the accuracy of contrast-enhanced RT3DE, reporting a good agreement between contrast-enhanced RT3DE and magnetic resonance imaging for assessment of LV function and volumes.
However, data regarding the feasibility of contrast-enhanced RT3DE and its incremental value over nonenhanced RT3DE (in terms of improved image quality) have not been shown. In the present study, we reported our experience on the feasibility and efficacy of contrast-enhanced RT3DE in a large, unselected cohort of patients in the early stage of AMI. Echo-contrast infusion ensured optimal LV opacification in 93% of the patients. Moreover, the definition of the endocardial border significantly increased with the use of echo-contrast, allowing more reliable and reproducible assessment of regional wall motion abnormalities. Of note, visualization of the anterior and anterolateral walls particularly improved with the use of echo-contrast.
Overall, the prevalence of good-quality echocardiograms increased from 59% to 94% with the intravenous contrast. The prevalence of fair image quality and uninterpretable echocardiograms decreased from 31% to 5% and from 10% to 1%, respectively.
Taking into account these data, the use of echo-contrast should therefore be advocated whenever a confident and reproducible assessment of LV systolic function is not possible because of suboptimal RT3DE images to increase the number of patients who could benefit from an RT3DE assessment of LV systolic function.
Study limitations
The present study has some limitations that should be acknowledged. First, the semiautomated algorithm used for LV volume analysis requires manual tracing of the endocardial border in the 3 apical planes, which is a subjective procedure that could alter the reproducibility of the technique. Second, an independent criterion standard (eg, magnetic resonance imaging) was not performed; and therefore, data about accuracy of contrast-enhanced RT3DE could not be provided.
Disclosures
Gaetano Nucifora is financially supported by the Research Fellowship of the European Association of Percutaneous Cardiovascular Interventions (Sophia Antipolis, France). Nina Ajmone Marsan is financially supported by the Research Fellowship of the European Society of Cardiology (Sophia Antipolis, France). Jacob M. van Werkhoven is financially supported by The Netherlands Society of Cardiology (Utrecht, the Netherlands). Martin J. Schalij has research grants from Biotronik (Berlin, Germany), Boston Scientific (Natick, MA), and Medtronic. Jeroen J. Bax has research grants from Biotronik, BMS Medical Imaging (North Billerica, MA), Boston Scientific, Edwards Lifesciences (Irvine, CA), GE Healthcare (Buckinghamshire, United Kingdom), Medtronic (Minneapolis, MN), and St. Jude Medical (St. Paul, MN).
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PII: S0002-8703(09)00126-4
doi:10.1016/j.ahj.2009.02.002
© 2009 Mosby, Inc. All rights reserved.
