The present retrospective analysis comprised 80 healthy adult volunteers with a mean age of 28.1 $\pm$ 6.3 years (33 males) with normally directed LV rotational mechanics. All participants underwent physical examination, laboratory testing, standard 12-lead electrocardiography (ECG) and two-dimensional (2D) Doppler echocardiography with a negative result. None of the participants were taking any medication, none were smokers or obese, and none had a known disorder or any pathological state. 3DSTE-derived data acquisition was performed directly after the 2D echocardiographic examination in accordance with recent practices and detailed 3DSTE-derived analysis was performed at a later date offline. The present retrospective cohort study is part of the ‘Motion Analysis of the heart and Great vessels bY three-dimensionAl speckle-tRacking echocardiography in Healthy subjects’ (MAGYAR-Healthy) Study. This study was organized to examine the physiologic relationship between different volumetric and functional parameters including 3DSTE-derived variables in healthy circumstances (‘Magyar’ means ‘Hungarian’ in Hungarian language). The study was approved by the Institutional and Regional Human Biomedical Research Committee of University of Szeged, Hungary (No.: 71/2011) and all healthy volunteers gave informed consent. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

Professional guidelines and accepted practices were followed for 2D Doppler cardiac ultrasound measurements. A Toshiba Artida${}^{\text{TM}}$ cardiac ultrasound tool (Toshiba Medical Systems, Tokyo, Japan) attached to a 1–5 MHz PST-30BT phased-array transducer was used for all measurements. Subjects were lying on their left side, and then, the transducer was placed on the chest and measurements were made from the typical parasternal and apical views. Doppler echocardiography was used to exclude any significant degree of valvular stenosis and regurgitation on any valves, and transmitral E and transmitral A flow velocities and E/A were determined to evaluate the diastolic function of the LV. Chamber quantifications including left atrial and LV measurements were also performed with the measurement of the LV ejection fraction (EF) according to the Simpson’s method [12]. TAPSE, systolic longitudinal TA motion as a representation of RV longitudinal shortening was assessed in apical long-axis view as a movement of the lateral edge of the TA toward the apex in systole [6, 7, 8, 9, 10] (Fig. 1).

Fig. 1.

M-mode echocardiography-derived measurement of tricuspid annular plane systolic excursion (TAPSE). Abbreviations: TAPSE, tricuspid annular plane systolic excursion; RA, right atrium; RV, right ventricle; LA, left atrium; LV, left ventricle.

During 3DSTE studies, the same Toshiba Artida${}^{\text{TM}}$ cardiac ultrasound tool (Toshiba Medical Systems, Tokyo, Japan) was used by the same observer (ÁK), and a PST-25SX matrix-array transducer was attached to the ultrasound tool. For 3DSTE, all subjects had to be in sinus rhythm and the subjects were lying in the left lateral position. Six 3D echocardiographic subvolumes (datasets) were then acquired within 6 cardiac cycles with respiratory retention from the apical window, the subvolumes were merged together automatically for a full-volume dataset. At a later date, data analysis was performed with a 3D Wall Motion Tracking software version 2.7 (Ultra Extend, Toshiba Medical Systems, Tokyo, Japan) [13, 14, 15, 16].

Apical longitudinal 4-chamber (AP4CH) and 2-chamber (AP2CH) views and apical, midventricular and basal cross-sectional planes were automatically selected by the software during analysis. Mitral annular (MA)-LV lateral and septal edges and the endocardial surface of the LV apex were defined. Then a sequential analysis was started to create a virtual 3D cast of the LV helping to determine the following LV rotational parameters using a 3D cast of the LV [17] (Fig. 2):

Fig. 2.

Analysis of the rotational mechanics of the left ventricle (LV) by three-dimensional (3D) speckle-tracking echocardiography. Apical longitudinal four-chamber (A) and two-chamber views (B) and short-axis views at apical (C3), midventricular (C5) and basal LV levels (C7) are shown together with a 3D model of the LV (D) and calculated LV volumetric data (E). Time - LV apical (yellow arrows) and basal (dashed yellow arrows) rotation curves are shown together with time - LV volume change curve during the cardiac cycle (F). Abbreviations: EDV, end-diastolic volume; ESV, end-systolic volume; EF, ejection fraction; RA, right atrium; RV, right ventricle; LA, left atrium; LV, left ventricle.

- clockwise basal LV rotation (in degrees).

- counterclockwise apical LV rotation (in degrees).

- LV twist (net difference of LV apical and basal rotations in degrees).

- time-to-peak LV twist (in milliseconds).

There is a special form of LV rotational mechanics when the direction of LV apical and basal rotations are in the same clockwise/counterclockwise direction, therefore LV twist cannot be measured, and only an LV apico-basal gradient is present (so-called LV ‘rigid body rotation’, RBR). Subjects with LV-RBR were not involved in this study [18].

In RA-focused images, similarly to the images focusing on the LV, data were displayed in selected apical longitudinal two- (AP2CH) and four-chamber (AP4CH) views and 3 short-axis views at basal, midatrial and superior levels at end-diastole. A 3D model of the RA was created following the definition of septal and lateral RA-TA edges and RA apex in AP2CH and AP4CH views at end-diastole, then the endocardial RA surface was reconstructed with sequential analysis. The following RA volumes were obtained [19] (Fig. 3):

Fig. 3.

Assessment of the right atrium by three-dimensional (3D) speckle-tracking echocardiography. Apical four-chamber (A) and two-chamber views (B) and short-axis views at basal (C3), midatrial (C5) and superior RA levels (C7) are demonstrated together with a 3D RA cast (D) and calculated RA volumes (E). Time - RA volume changes curve represented by a white dashed line is also shown (F). Abbreviations: LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; EDV, end-diastolic volume; ESV, end-systolic volume; EF, ejection fraction; V${}_{\text{max}}$, maximum RA volume; V${}_{\text{preA}}$, pre-atrial contraction RA volume; V${}_{\text{min}}$, minimum RA volume.

- maximum RA volume, measured at end-systole, just before the opening of the tricuspid valve (V${}_{\text{max}}$).

- RA volume before atrial contraction, measured at early-diastole at the time of the P wave on the ECG (V${}_{\text{preA}}$).

- minimum RA volume measured at end-diastole, just before the closure of the mitral valve (V${}_{\text{min}}$).

Mean $\pm$ standard deviation (SD) (for continuous variables) and n (%) format (for categorical variables) were used for data presentations. Statistical significance was considered to be present when p 0.05. Pearson’s coefficients were measured to characterize correlations between variables. Analysis of variance (ANOVA) and independent sample t-test were used for the comparison of groups. SPSS software analyses (SPSS Inc. version 22, Chicago, IL, USA) were performed.

Normal clinical and routine 2D Doppler echocardiographic parameters were found in all cases as presented in Table 1.

According to guidelines, TAPSE is considered to be normal if $\ge$17 mm, while the average TAPSE proved to be approximately 21.5 mm in healthy individuals in a recent study [8, 10]. Therefore, the group of healthy subjects was divided into 2 subgroups: subjects with TAPSE between 17 and 21 mm were compared with subjects with TAPSE $\ge$22 mm. For another comparison, subjects were divided into subgroups according to the mean $\pm$ SD of basal and apical LV rotations as assessed by 3DSTE as well, the values were –4.10 $\pm$ 2.31° and 9.37 $\pm$ 4.04°, respectively. The healthy subjects were classified into subgroups based on the lower (–1.79° and 5.33°, respectively) and upper (–6.41° and 13.41°, respectively) values of these parameters.

No difference was found in the case of LV volumes and the rotational parameters in healthy cases with TAPSE 18–21 mm vs. TAPSE $>$22 mm. Similarly, RA volumetric parameters did not differ either (Table 2).

TAPSE showed no association with the degree of basal LV rotation. A tendentious increase of LV-ESV and a decrease of LV-EF could be detected with higher basal LV rotation. Moreover, RA volumes showed a slight increase as well (Table 3).

Similar to basal LV rotation, TAPSE did not change with the degree of apical LV rotation. While LV-EDV and basal LV rotation did not show any changes with increasing apical LV rotation, a tendentious increase of LV-EF could be detected. Similar to basal LV rotation, a tendentious increase in RA volumes could be demonstrated with increasing apical LV rotation (Table 3).

No correlations were found between apical and basal LV rotations and TAPSE.

We consider it to be important to mention the following limitations:

- Image quality is a significant limitation of 3DSTE, which is worse than that of 2DE [13, 14, 15, 16].

- Although detailed global and segmental LV strain measurements could be performed using the same 3D LV casts, our study did not aim to determine them.

- 3DSTE-derived characterization of the TA function was not aimed either.

- Moreover, volumetric and functional characterization of other cardiac chambers was not performed either.

- We did not plan to validate 3DSTE-derived LV rotational parameters [20, 21, 22] and TAPSE measurement [9] due to their validated nature.

- A one-dimensional parameter (TAPSE) does not sufficiently express the characteristics of a particular RV function. Characterizing the function of the RV with a more appropriate parameter would be much more worthy.

- Healthy volunteers were included in the study, however, neither special laboratory tests nor imaging tests were performed to rule out possible subclinical abnormalities.