Study Population

A retrospective cohort of 41 adult patients with HCM (defined as a maximal septal thickness ≥13 mm and a ratio of septal to posterior wall thickness ≥1.3, in the absence of another cardiac or systemic disease that could cause LV hypertrophy) was included in the study. All patients had undergone comprehensive transthoracic echocardiography and CMR <24 hours apart. In a subset of five patients, either complete longitudinal or circumferential strain was not available, because of incomplete data sets or suboptimal echocardiographic image quality, resulting in a final patient population of 36 patients for longitudinal and circumferential strain, respectively, and 34 patients for assessment of rotation parameters.

Clinical and 2D Echocardiographic Data

A retrospective chart review was performed to obtain demographic data for the patient cohort. Standard 2D echocardiographic data were obtained from the study performed on the same day as CMR. All studies were performed on a Toshiba Artida 4D System (Toshiba America Medical Systems, Tustin, CA) with a PST-30SBT transducer, according to the standards of the American Society of Echocardiography. Two-dimensional data sets for speckle-tracking analysis included three short-axis views (basal, midventricular, and apical) and three apical longitudinal views (four, two, and three chamber). Special care was taken to ensure the acquisition of optimal circumferential cross-sectional slabs at the basal (mitral leaflets visible without presence of papillary muscles), midventricular (papillary muscles visible without presence of mitral leaflets), and apical (toward the LV apex, absence of papillary muscles) levels. Adjustments in sector depth and angle yielded a temporal resolution of 80 to 100 frames/sec. A minimum of 40 frames/cycle was required for offline analysis (with a range of 40–82 frames/cycle achieved). LV outflow tract obstruction was defined by continuous-wave Doppler echocardiography as a peak instantaneous systolic gradient ≥30 mm Hg under resting conditions due to marked systolic anterior movement of the mitral valve leaflets. The study was approved by the Investigational Review Board at Tufts Medical Center and the Research Ethics Board of the Toronto General Hospital.

CMR Protocol

At Tufts Medical Center, CMR imaging was performed using a Philips Gyroscan ACS-NT 1.5 scanner (Philips Medical Systems, Best, The Netherlands). Cine steady-state free precession (SSFP) images were acquired in short axis (sequential 10-mm slices from the atrioventricular ring to the apex) and two-chamber, three-chamber, and four-chamber long axes. Scan parameters were as follows (1) retrospective electrocardiographic triggering; (2) spatial resolution, 1.6 × 1.6 mm/pixel; (3) field of view, 32 to 36 cm; and (4) temporal resolution, 35 msec. LV volumes, mass, and ejection fraction were measured using standard volumetric techniques and analyzed using commercially available software (MASS version 6.1.6; MEDIS Medical Imaging, Inc., Leiden, The Netherlands). Maximal end-diastolic LV wall thickness measurements for each of the 16 segments were provided automatically by the commercially available software. LV mass data were indexed to body surface area.

VVI

VVI is an angle-independent feature-tracking method that incorporates speckle-tracking and endocardial and epicardial contour-tracking. VVI quantifies myocardial motion from B-mode clips by automatically tracking user-defined endocardial and epicardial contours to define the inward and outward myocardial motion. On the basis of the motion of the tracked points between the frames and the knowledge of the time interval between frames, 2D tissue velocity is computed. Strain and strain rate are computed by the change in the relative distance between localized tracked trace points, combined with the difference in the relative displacement of the tissue motion behind the tracked points. Strain was defined as the instantaneous local trace lengthening or shortening and strain rate as the rate of lengthening or shortening. In the long-axis images, the software calculates longitudinal (systolic shortening) and radial (systolic thickening) velocity, strain, strain rate. In the short-axis images, it calculates circumferential and radial strain and strain rate, as well as radial and rotational velocities and angles relative to the ventricular centroid (center of the LV cavity).

The speckle-tracking program, VVI version 3.0.0, was applied to the echocardiographic and CMR cine SSFP images from archived studies, allowing endocardial, myocardial, and epicardial strain parameter assessment.

Cine SSFP data derived from CMR images were converted from Digital Imaging and Communications in Medicine to audio-video interleaved format, creating 30 cardiac phases. Archived echocardiographic images in Digital Imaging and Communications in Medicine format were used for analysis. Subsequently, myocardial motion was quantified by automatic tracking of user-defined points in both subendocardial and subepicardial regions, as previously described, to derive both endocardial and full-thickness strain. Default software settings were used with tracking of both endocardial and epicardial borders for analysis of both echocardiographic and CMR-derived images.

Myocardial Mechanics

Longitudinal strain was measured from the horizontal long-axis/four-chamber, vertical long-axis/two-chamber, and three-chamber/LV outflow tract views on CMR and from apical four-chamber, apical two-chamber, and apical three-chamber views on echocardiography. Circumferential strain was measured in three short-axis views. The basal level was selected as a short-axis view of the mitral valve (LV outflow tract no longer visible, papillary muscles not visible), the midventricular level at the level of the papillary muscles (mitral leaflets not visible), and the apical level at the true LV apex (papillary muscles not visible). In addition, radial strain was assessed from the short-axis views (global radial strain). Global longitudinal strain and strain rate values were obtained by averaging the segmental strain values (six segments in each of the four-chamber, two-chamber, and three-chamber views, for a total of 18 segments). Global circumferential strain and strain rate values were obtained by averaging the segmental strain values (six segments in the basal and midventricular short-axis views and four segments in the apical short-axis view, for a total of 16 segments). For each view, endocardial borders were manually traced in the end-diastolic frame, with the system automatically identifying the epicardial border. Manual adjustment of each border independently of the other could be performed before analysis and processing. The version of VVI used in the present study measures strain in three layers, with the myocardial layer automatically assigned midway between the endocardial and epicardial layers by the software program. Strain parameters were recorded after visual confirmation of best endocardial and epicardial motion tracking (by operator subjective visual assessment). Segments with poor tracking were excluded from further analysis. If more than two segments demonstrated poor tracking, the view was excluded from further analysis.

Averaged myocardial rotation angles (measured from the short-axis views) were used to calculate twist. Twist was defined as the maximal instantaneous basal-to-apical angle difference. To standardize the temporal evaluation of twist, all twist and untwist times were normalized and presented as a percentage of the R-R cycle length.

All echocardiographic images were analyzed in a random order by a single reader. CMR images were analyzed in a random order by a second independent reader who was blinded to the results of analysis of the echocardiographic images.

Intraobserver and Interobserver Variability

For intraobserver variability, 10 randomly assigned patients were reanalyzed by the same observer on both echocardiographic and CMR data sets. For interobserver variability, the same patients were analyzed by a second observer. We assessed the variability of global longitudinal and global circumferential strain, as well as total twist.

Statistical Analyses

Continuous data are reported as mean ± SD. Comparison of the values obtained from the two imaging modalities was made by means of Pearson’s correlation and Bland-Altman analysis. Intraobserver and interobserver variability was assessed using Bland-Altman analysis. All statistical analyses were performed using MedCalc version 11.6.0.0 (MedCalc Software, Mariakerke, Belgium). Statistical significance was defined as a P value < .05.

Patient Demographics and Clinical Data

Clinical and demographic findings as well as basic echocardiographic and CMR characteristics are shown in Table 1 . All patients had LV ejection fractions ≥55%, with 46% of the cohort having evidence of either resting or provocable LV outflow tract gradients of ≥30 mm Hg.

Myocardial Mechanics

Longitudinal Strain

Representative longitudinal strain curves obtained from four-chamber, two-chamber, and three-chamber views are shown in Figure 1 . The values for global longitudinal strain derived from CMR and echocardiography and their correlations are shown in Table 2 . Overall the mean differences in global longitudinal systolic strain for the two imaging modalities (CMR − echocardiography) were −1.1 ± 3.3% for endocardial strain and −2.2 ± 3.6% for full-thickness strain ( Figure 2 ), with CMR consistently resulting in higher strain values than echocardiography.

Representative endocardial longitudinal strain curves and average strain values from echocardiography ( left ) and CMR imaging ( right ) demonstrating assessment in the four-chamber view ( top ), two-chamber view ( middle ), and three-chamber/LV outflow tract view ( bottom ). Endocardial and epicardial tracings are demonstrated. The figure demonstrates that similar global values and curves were obtained by both techniques.

Table 2

GLS parameters

	Echocardiography	CMR
Parameter	( n = 36)	( n = 36)	Correlation	P	Bias ± LOA (Bland-Altman)	Percentage difference
Endocardial GLS	−16.3 ± 4	−17.4 ± 3	0.87	<.0001	−1.1 ± 3.3	6.8
Myocardial GLS	−11.9 ± 3	−14.4 ± 3	0.81	<.0001	−2.5 ± 3.4	19.3
Epicardial GLS	−8.1 ± 3	−10.9 ± 4	0.52	.001	−2.8 ± 6.0	29.1
Full-thickness GLS	−12.1 ± 3	−14.2 ± 3	0.81	<.0001	−2.2 ± 3.6	16.2

GLS , Global longitudinal strain; LOA , limits of agreement.

Bland-Altman plots show agreement between endocardial longitudinal strain ( top left ) and full-thickness longitudinal strain ( top right ) measurements made by VVI applied to CMR and echocardiographic images. On each plot, the solid middle line represents the overall bias, and the top and bottom dashed lines represent the limits of agreement between methods. The correlations between strain measurements made by VVI applied to CMR and echocardiographic images are demonstrated for endocardial longitudinal strain ( bottom left ) and full-thickness longitudinal strain ( bottom right ).

Circumferential Strain

Representative circumferential strain curves obtained from short-axis views at the level of the base, midventricle, and apex are shown in Figure 3 . The values for global circumferential strain derived from CMR and echocardiography and their correlations are shown in Table 3 . Overall, the mean differences in global circumferential systolic strain for the two imaging modalities (CMR − echocardiography) were −4.7 ± 5.3% for endocardial strain and −3.4 ± 3.8% for full-thickness strain ( Figure 4 ), with CMR consistently resulting in higher strain values than echocardiography.

Representative endocardial circumferential strain curves and average strain values from echocardiography ( left ) and CMR imaging ( right ) demonstrating assessment at the basal level ( top ), midventricle/papillary muscle level ( middle ), and apical level ( bottom ). Endocardial and epicardial tracings are demonstrated. The figure demonstrates that similar global values and curves were obtained by both techniques.

Table 3

GCS parameters

	Echocardiography	CMR
Parameter	( n = 36)	( n = 36)	Correlation	P	Bias ± LOA (Bland-Altman)	Percentage difference
Endocardial GCS	−29.4 ± 4	−34.1 ± 4	0.80	<.0001	−4.7 ± 5.3	15.3
Myocardial GCS	−16.3 ± 3	−20.4 ± 3	0.68	<.0001	−4.1 ± 4.3	22.7
Epicardial GCS	−10.1 ± 2	−11.3 ± 2	0.42	.01	−1.3 ± 4.6	11.7
Full-thickness GCS	−18.6 ± 3	−21.9 ± 3	0.76	<.0001	−3.4 ± 3.8	16.7
Global radial strain	33.2 ± 10	64.2 ± 24	0.52	.001	30.9 ± 40.1	60.3
Basal endocardial CS	−24.9 ± 4	−29.6 ± 5	0.73	<.0001	−4.7 ± 7.1	17.1
Mid endocardial CS	−29.3 ± 5	−32.5 ± 6	0.73	<.0001	−3.2 ± 7.9	10.3
Apical endocardial CS	−31.5 ± 7	−40.3 ± 6	0.39	.03	−8.9 ± 14.8	12.9

CS , Circumferential strain; GCS , global circumferential strain; LOA , limits of agreement.

Bland-Altman plots show agreement between endocardial circumferential strain ( top left ) and full-thickness circumferential strain ( top right ) measurements made by VVI applied to CMR and echocardiographic images. On each plot, the solid middle line represents the overall bias, and the top and bottom dashed lines represent the limits of agreement between methods. The correlations between strain measurements made by VVI applied to CMR and echocardiographic images are demonstrated for endocardial circumferential strain ( bottom left ) and full-thickness circumferential strain ( bottom right ).

Circumferential strain data by short-axis levels were also analyzed ( Table 3 ). The mean difference in global circumferential systolic strain at the basal level for the two imaging modalities (CMR − echocardiography) was −4.7 ± 7.1%, with a correlation of 0.73. At the level of the midventricle, the mean difference was −3.2 ± 7.9%, with a correlation of 0.73. There was a poor correlation (0.39) at the apical level, with a mean difference of −8.9 ± 14.8%.

Global radial strain values derived from CMR and echocardiography and their correlations are shown in Table 3 . CMR consistently resulted in higher radial strain values than echocardiography.

Rotation Parameters

The values for rotation at the three short-axis planes, total twist, as well as twist and untwist times derived from CMR and echocardiography and their correlations are shown in Table 4 .

Table 4

Rotation parameters

	Echocardiography	CMR
Parameter	( n = 34)	( n = 34)	Correlation	P	Bias ± LOA (Bland-Altman)	Percentage difference
Basal endocardial rotation (°)	−7.7 ± 2	−7.1 ± 3	0.63	.0001	0.6 ± 4.2	23.5
Basal full-thickness rotation (°)	−5.9 ± 2	−6.0 ± 2	0.41	.01	−0.1 ± 4.1	28.7
Mid endocardial rotation (°)	0.03 ± 6	−0.6 ± 5	0.24	NS	−0.6 ± 12.8	—
Mid full-thickness rotation (°)	0.3 ± 4	−0.9 ± 3	0.29	NS	−1.1 ± 8.5	—
Apical endocardial rotation (°)	8.6 ± 4	8.5 ± 4	0.70	<.0001	−0.1 ± 5.9	27.4
Apical full-thickness rotation (°)	6.6 ± 3	6.5 ± 3	0.71	<.0001	−0.1 ± 4.2	27.5
Endocardial twist (°)	14.7 ± 4	14.5 ± 4	0.73	<.0001	−0.2 ± 5.6	15.9
Full-thickness twist (°)	11.4 ± 3	11.6 ± 3	0.56	.001	0.1 ± 5.8	21.1
TTPT (%CL)	37.6 ± 8	38.7 ± 9	0.67	<.0001	1.0 ± 13.4	15.2
TRRT (%CL)	62.3 ± 8	61.3 ± 9	0.67	<.0001	−1.0 ± 13.5	9.7

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