Study Design

Subjects 5 to 18 years of age who underwent clinically indicated echocardiographic examinations were prospectively recruited in an outpatient setting. Control subjects with normal intracardiac anatomy and function and study patients with diagnoses of DCM were enrolled after informed consent was obtained. Patients who were pacemaker dependent, and those with underlying structural lesions were excluded. This study was approved by the Stanford Medical School Committee on Clinical Investigation.

Echocardiographic Imaging

Images were acquired using a standard protocol by two cardiologists (T.A.T. and S.B.) with expertise in both 2D and 3D echocardiographic imaging, using the Acuson SC2000 ultrasound system (Siemens Medical Solutions, Mountain View, CA).

Two-dimensional images were acquired using 8V3c or 4V1c transducers with the subject in the lateral decubitus position. For each view, images were acquired over two or three heartbeats, and one cardiac cycle was analyzed. Machine settings were selected to provide sharp endocardial definition and a frame rate of approximately 80 Hz. Images were acquired in the apical four-chamber view focused for visualization of the left ventricle and the parasternal short-axis view at the mitral valve, mid papillary muscle, and LV apex. Ejection fraction was calculated using the 5/6 area-length method.

Three-dimensional RTFV data sets were obtained using the 4Z1c transducer for each patient. To ensure the inclusion of the entire left ventricle, orientation was adjusted to visualize the LV apex in both the four-chamber and two-chamber planes. All 3D echocardiographic images were full-volume reconstructed from a single beat. Image depth and width were adjusted to achieve a volume rate of approximately 40 volumes/sec.

LV Mechanics Analysis Using 2D Echocardiography

Postprocessing of 2D echocardiographic images was performed using the eSie VVI technology 2D speckle-tracking software version 3.0 (Siemens Medical Solutions). The endocardial and epicardial layers were manually traced. Global strain analysis included the standard 16-segment model, with the global values derived from the average of all segments, and the peak systolic strain values were recorded. Circumferential and radial strain were acquired at the mid papillary muscle level, and longitudinal strain was analyzed from the four-chamber view. LV torsion (degrees per centimeter) was calculated as the difference in rotation (degrees) between the LV apex and the base, divided by the end-diastolic length of the left ventricle measured from the four-chamber view.

LV Mechanics Analysis Using 3D Echocardiography

Postprocessing of 3DE images was performed with a dedicated voxel (3D) tracking software with automated ventricular contouring capabilities, previously described. The new application, eSie Mechanics, leverages the knowledge-based, expert-trained, automated contouring solution provided whereby the endocardium is detected in the first frame of the heart cycle. The left ventricle is automatically segmented. Deformation was analyzed in the circumferential, longitudinal, and radial directions; global strain and rotation indices were analyzed. Two or three cardiac cycle clips were acquired, and then all analysis results were averaged. A representative analysis of a volume set and the related output is shown in Figure 1 .

Box-and-whisker plot showing comparisons of longitudinal (A) , circumferential (B) , and radial (C) strain in healthy control subjects ( red bars ) and patients with DCM ( blue bars ) as analyzed by 2D and 3D image analysis. Paired t tests were used for 2D versus 3D image analysis, and the nonparametric Mann-Whitney U test was for comparison between disease and control groups.

Statistical Analysis

The paired t test was used to compare differences in 2D and 3D measurements. The nonparametric Mann-Whitney U test was used to compare differences in indices of mechanics between patients with DCM and control subjects. Correlations between ventricular ejection fraction and deformation indices and between 2D and 3D deformation indices were analyzed using the Spearman correlation coefficient ( r ).

Receiver operating characteristic curves were generated to evaluate strain indices as potential measures associated with LV dysfunction defined as an LV ejection fraction < 55%.

Reproducibility

At least two sets of images were obtained in 10 subjects, which included both control subjects and patients. Intra- and interobserver variability was evaluated on a single volume set obtained and analyzed by two investigators (S.B. and S.N.S.). Test-retest analysis was performed by obtaining and analyzing two separate volume sets on a single patient by two independent investigators (S.B. and T.A.T.), allowing complete independence of these measures. Volume sets for test-retest reliability were obtained using the same equipment and location and within a short period of time (<5 min). All investigators were blinded to the results of the second data set. Reproducibility results are reported as intraclass correlation coefficients and coefficients of variation (calculated as the absolute difference divided by the mean of the repeated observations and expressed as percentages).

Patient Characteristics

The baseline clinical characteristics are summarized in Table 1 . Of the 32 patients recruited, 15 had histories of DCM, with varying degrees of remodeling, and were being followed in an outpatient setting. Of these patients, the etiologies of DCM included familial ( n = 5), metabolic ( n = 1), infectious ( n = 1), LV noncompaction ( n = 3), and other ( n = 5). Three of the 15 patients with DCM had recovered ventricular function at the time of recruitment.

Comparison of Cardiac Mechanics Analysis Using 2D and 3D Speckle-Tracking Echocardiography

Two-dimensional echocardiographic frame rates were significantly higher than the volume rates achieved with 3D echocardiography ( Table 2 ). Despite this observation, 2D and 3D strain analysis produced similar differences when comparing healthy control subjects and patients with DCM ( Table 2 , Figures 1 A–1C).

In contrast, notable differences in the magnitudes of twist and torsion indices were present between 2D and 3D echocardiography. By 3D analysis, both parameters were significantly higher in comparison with 2D analysis ( Table 2 , Figure 2 ). This magnitude of difference was preserved both in healthy control subjects and in patients with DCM ( Figure 2 ).

Bar graph showing comparisons of ventricular torsion derived from 2D ( red bars ) and 3D ( blue bars ) image analysis in healthy control subjects and in patients with DCM.

Two-dimensional and 3D global longitudinal and circumferential strain exhibited a fair correlation, whereas radial strain and torsion did not ( Figure 3 ).

Scatterplots show no correlation between 2D and 3D torsion ( top left ) and radial strain ( bottom left ) and good correlation between 2D and 3D circumferential ( top right ) and longitudinal strain ( bottom right ). Control subjects are shown in blue and patients with DCM in red .

Distinguishing between Control Subjects and Patients with DCM

As expected, there were significant differences in ejection fraction, global longitudinal strain ( Figure 1 A), and circumferential strain ( Figure 1 B) between healthy control subjects and patients with DCM in both the 2D and 3D analyses. In contrast, radial strain was not different between control subjects and patients with DCM in the 2D analysis ( Figure 1 C). Furthermore, no appreciable differences were noted in global twist and torsion ( Figure 2 ) values between the control and disease groups. A separate analysis that dichotomized the cohort by manifest systolic dysfunction using an ejection fraction < 55% also did not demonstrate appreciable difference in twist or torsion. However, significant differences were seen in global longitudinal, circumferential, and radial strain in both 2D and 3D analyses (data not shown).

Global circumferential, longitudinal, and radial strain were correlated with ventricular systolic function as measured by ejection fraction ( Figures 4 A–4C). This correlation was present in both 2D and 3D analysis. In contrast, no significant association was noted between torsion and twist indices and ventricular systolic function either by 2D or 3D analysis ( Figure 5 ).

Scatterplots showing significant correlation between circumferential strain (A) , longitudinal strain (B) , and radial strain (C) and ventricular ejection fraction; control subjects are shown in blue and patients with DCM in red . Similar trends are seen with 2D ( right ) and 3D ( left ) image analysis.

Scatterplots showing no correlation between twist by 2D ( top left ) and 3D ( top right ) analysis and ventricular ejection fraction and torsion by 2D ( bottom left ) and 3D ( bottom right ) analysis and ventricular ejection fraction. Control subjects are shown in blue and patients with DCM in red .

Receiver operating characteristic curve analysis demonstrated strong associations between 3D global circumferential (area under the curve [AUC] = 0.87, P = .001) and longitudinal strain (AUC = 0.87, P < .001) and LV dysfunction. Similar associations were seen between LV dysfunction and 2D-derived circumferential strain (AUC = 0.95, P < .0001) and longitudinal strain (AUC = 0.93, P < .0001).

Reproducibility of Mechanics Derived from 2D versus 3D Echocardiography

Intraobserver, interobserver, and test-retest reliability were all superior for 3D versus 2D analysis, with an average intraclass correlation coefficient of 0.93 and a coefficient of variation <10% for 3D echocardiography compared with 0.71 and 10% to 48%, respectively, for 2D echocardiography.

Comparison of reproducibility for 2D and 3D analyses is summarized in Table 3 . With the exception of 3D circumferential strain, all other comparisons yielded excellent test-retest reliability and coefficients of variation <15%.

Table 3

Inter- and intrarater variability for 2D and 3D deformational indices

	Intrarater ( n = 10)		Interrater ( n = 10)		Test-retest ( n = 10)
	ICC	CoV (%)	ICC	CoV (%)	ICC	CoV (%)
2D echocardiography
Circumferential strain	0.70 (−0.10 to 0.92)	19.4	0.69 (−0.78 to 0.92)	26.0	0.94 (0.77 to 0.99)	10.9
Longitudinal strain	0.86 (0.46 to 0.96)	17.8	0.93 (0.74 to 0.98)	10.4	0.92 (0.68 to 0.98)	12.8
Radial strain	0.64 (−0.23 to 0.91)	21.9	−0.42 (−7.9 to 0.68)	31.5	0.34 (−0.45 to 0.72)	41.9
Apex-base torsion	0.60 (−0.30 to 0.89)	48.3	0.80 (0.26 to 0.95)	30.0	0.72 (0.13 to 0.93)	31.9
3D echocardiography
Circumferential strain	0.99 (0.96 to 0.998)	6.6	0.98 (0.49 to 0.997)	7.0	0.45 (−0.38 to 0.76)	13.6
Longitudinal strain	1.00 (0.98 to 0.999)	2.6	0.99 (0.96 to 0.998)	3.0	0.93 (0.72 to 0.98)	9.9
Radial strain	0.97 (0.87 to 0.99)	6.6	0.98 (0.77 to 0.995)	7.0	0.75 (0.02 to 0.94)	13.4
Apex-base torsion	1.00 (0.98 to 0.999)	3.5	0.98 (0.93 to 0.995)	4.0	0.84 (0.36 to 0.96)	15.0

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