Differences in left ventricular functional properties in healthy adults with greater end-diastolic versus end-systolic aortic valve annular area—detailed analysis from the three-dimensional speckle-tracking echocardiographic MAGYAR-Healthy Study

Introduction

The aortic valve (AV), located between the left ventricle (LV) and the ascending aorta, plays an important role in one-way blood flow. The AV is made up of the three semilunar leaflets, with a circular/oval-shaped annulus (AVA) (1,2). The AVA is considered to be a key element of the aortic root, and given the frequent pathological abnormalities of the valve, such as stenosis or regurgitation, accurate assessment of its dimensions respecting the cardiac cycle is essential in clinical practice (1-4). There is a close relationship between the AV and the surrounding LV, its leaflets are attached in a crescent shape from the sinotubular junction to the basal LV junction. Two out of three leaflets are supported by the LV muscle, while the third one is supported by a fibrous attachment (2). This strong relationship may partially explain the previously described associations between AVA and LV volumes and functions (1,2,5,6). It is well-known that the atrioventricular valves have completely different structures, characterized by larger end-diastolic versus end-systolic annuli (7). In case of the AV, the situation is less clear. According to the literature, in 35% of the cases, the AV is greater in end-diastole than in end-systole in aortic stenosis patients, although the clinical and pathological significance remains uncertain (8).

Three-dimensional (3D) echocardiography has all the beneficial properties for the accurate assessment of valvular annuli, including the AVA, with confirmed feasibility and accuracy (5,6,9,10). The main advantage of three-dimensional speckle-tracking echocardiography (3DSTE) is its capability to perform volumetric and functional analyses of any cardiac chamber, such as segmental, regional and global measurements of deformation and rotational mechanics of the LV, while allowing detailed AVA assessment simultaneously from the same digitally acquired 3D echocardiographic database (5,6,11-18). 3DSTE has been validated for LV volumetric, strain and rotational measurements (19-25), with defined normal reference values (16-18). Due to its easy-to-perform, easy-to-learn and non-invasive nature, 3DSTE seems to be ideal for such analyses, however, limitations in imaging quality and test feasibility still exist (12-26).

The significance of whether the end-diastolic or end-systolic AVA is greater remains inadequately explored, as does its potential association with any LV functional properties. Therefore, the present study was designed to investigate which differences in LV volumes and functional properties can be demonstrated in healthy individuals, depending on whether the end-systolic or end-diastolic AVA area is greater. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1354/rc).

Methods

Population of healthy individuals

The present cohort study comprised 254 Caucasian healthy adults, of whom 142 subjects were excluded due to inferior image quality (56%). Thus, the remaining population consisted of 112 individuals [mean age: 33.7±11.1 years, 69 males, body mass index (BMI): 18.5±0.19 kg/m²], with no known disorders or pathologies that could affect the findings. Electrocardiography (ECG) and routine two-dimensional (2D) Doppler echocardiography showed no abnormalities in any case. None of the participants were professional athletes, yoga practitioners, regular smokers, drug users, obese or pregnant at the time of the enrollment. At the time of the 2D echocardiography, data acquisition by 3DSTE was also performed. The acquired 3D echocardiographic datasets were analyzed by a single observer (A.N.) using a vendor-derived dedicated software at a later date. Together with routine 2D Doppler echocardiographic assessments, AVA dimensions and LV volumes, deformation and rotational mechanics were evaluated by 3DSTE. Based on the findings, several subgroups of healthy subjects were created:

• Subjects with a greater end-systolic than end-diastolic AVA area (n=70, mean age: 33.7±11.1 years, 48 males, BMI: 18.4±0.21 kg/m²);
• Subjects with equal-sized end-diastolic and end-systolic AVA areas (n=8, mean age: 34.9±15.1 years, 3 males, BMI: 18.2±0.24 kg/m²);
• Subjects with a greater end-diastolic than end-systolic AVA area (n=34, mean age: 37.6±12.3 years, 18 males, BMI: 18.6±0.18 kg/m²).

This investigation was part of the ‘Motion Analysis of the heart and Great vessels bY three-dimensionAl speckle-tRacking echocardiography in Healthy subjects’ (MAGYAR-Healthy) Study, which partly aims to analyze the physiological aspects of parameters as assessed by 3DSTE in healthy adult individuals (‘Magyar’ means ‘Hungarian’ in Hungarian) (2,5,6,16,17). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Institutional and Regional Biomedical Research Committee of the University of Szeged (No. 71/2011) and informed consent was obtained from all individual participants.

Two-dimensional Doppler echocardiography

A Toshiba Artida^TM echocardiography equipment (Toshiba Medical Systems, Tokyo, Japan) was used for standard 2D Doppler echocardiographic studies, equipped with a PST-30BT phased-array transducer (1–5 MHz). Left atrial and LV dimensions were measured together with Simpson’s LV ejection fraction (EF). On one hand, significant valvular regurgitations and stenoses were excluded by Doppler, on the other hand, early (E) and late (A) transmitral flow velocities were measured, and E/A ratio was calculated to assess diastolic function of the LV (27).

3DSTE

All 3DSTE studies were conducted in two steps using the same Toshiba Artida^TM cardiac ultrasound tool: as a first step, 3D echocardiographic datasets (volumes) were acquired after changing the transducer to a PST-25SX matrix-array one (11-15). Images were acquired from the apical window following image optimization (gain, magnitude, etc.). Six subvolumes were acquired during 6 cardiac cycles for optimal images, then the software automatically stitched them together to reconstruct a 3D full-volume dataset.

As a second step, datasets were analyzed using a vendor-derived 3D Wall Motion Tracking software version 2.7 (Toshiba Medical Systems, Tokyo, Japan). Firstly, a 3D model/cast of the LV was created for the simultaneous assessment of LV volumes, strains, and rotational parameters. During the analysis, apical 2-chamber (AP2CH) and 4-chamber (AP4CH) long-axis views and cross-sectional basal, midventricular and apical views were determined by the software. For the 3D LV model, LV - lateral and septal mitral annular edges and apical endocardial LV surface were defined by the observer, followed by a sequential analysis. The following LV parameters were assessed (Figure 1) (11-26):

• End-diastolic and end-systolic LV volumes, LV-EF and LV mass;
• Basal and apical LV rotations and LV twist;
• LV radial strain (RS) for characterizing thickening/thinning of the myocardial tissue;
• LV longitudinal strain (LS) for characterizing lengthening/shortening of the myocardial tissue;
• LV circumferential strain (CS) for characterizing widening/narrowing of the myocardial tissue;
• LV 3D strain (3DS), which is the combination of RS, CS and LS;
• LV area strain (AS), which is the combination of CS and LS.

Figure 1 3D speckle-tracking echocardiographic assessment of the LV parameters. After 3D echocardiographic dataset acquisitions, apical 4-chamber (A) and two-chamber (B) long-axis views and short axis views at apical (C1), midventricular (C2) and basal (C3) LV levels are created using 3D Wall Motion Tracking software. Together with a 3D virtual model of the LV (D), calculated LV volumetric data and LV ejection fraction (E) and apical (white arrow) and basal (dashed white arrow) LV rotations (F) together with curves representing time—LV global (white curve) and segmental (coloured curves) longitudinal (G), circumferential (H), radial (I), area (J) and 3D (K) strain curves with curves representing time—LV volume changes (dashed white curve) are presented. 3D, three-dimensional; EDV, end-diastolic volume; EF, ejection fraction; ESV, end-systolic volume; LA, left atrial/atrium; LV, left ventricle; RV, right ventricle.

In all cases, global, mean segmental, and basal, midventricular and apical regional LV strains were calculated.

Following optimization of LV longitudinal planes on AP2CH and AP4CH views, dimensions of the AVA were measured (5,6). The aorta and the aortic valve were visualized by tilting and optimizing the longitudinal planes in AP4CH and AP2CH long-axis views. Then the planes were aligned parallel to the centerline of the aortic root. The cross-sectional view on C7, perpendicular to the longitudinal plane, was aligned to the AVA to ensure that the plane C7 is perpendicular, and that the actual AVA was measured, not the Valsalva or the outflow tract. All AVA dimensions—including minimum and maximum AVA diameters, AVA area, and AVA perimeter—were measured in both end-systole and end-diastole using planimetric analysis (5,6) (Figure 2).

Figure 2 3D speckle-tracking echocardiographic assessment of the AVA in end-diastole and end-systole. Following optimization of the LV longitudinal planes on apical 4-chamber (A) and 2-chamber (B) long-axis views, and visualization of the AVA/aorta by tilting and optimizing the longitudinal planes in these long-axis views. The planes were positioned parallel with the aortic root centerline. The C3 served as the AVA cross-sectional view, which was perpendicular to the longitudinal plane. The white arrow represents the AVA, while dashed white arrow represents the ascending aorta. Area A, AVA area; AVA, aortic valve annulus; Circ A, AVA perimeter; Dist B and C, minimum and maximum AVA diameters; LV, left ventricle; RV, right ventricle.

Statistical analysis

Continuous variables were demonstrated as mean ± standard deviation, while categorical variables were presented as n (%). Statistical significance was defined in the presence of P<0.05. For comparisons of continuous variables between three groups, analysis of variance (ANOVA) or Kruskal-Wallis tests were used, where appropriate. For categorical variables, Fisher’s exact test was used. The Bland-Altman method was applied for intraobserver and interobserver agreements. The reproducibility of AVA measurements by 3DSTE was assessed by two observers (interobserver agreement) and twice by the same observer (intraobserver agreement) in 30 healthy subjects, together with their respective interclass correlation coefficients (ICCs). All statistics were performed using an SPSS software (version 22, SPSS Inc., Chicago, IL, USA).

Results

Left ventricular sizes and EF

No differences in routine 2D echocardiographic data or LV volumes as assessed by 3DSTE could be demonstrated between the groups (Table 1). No healthy individuals had grade 1 or larger valvular regurgitations or showed a significant valvular stenosis. Although LV-EF, measured by 2D echocardiography was reduced in subjects having greater end-diastolic AVA area compared with those with a greater end-systolic AVA area, LV-EF measured by 3DSTE was similar between these groups (Table 1).

AVA dimensions

Subjects having greater end-diastolic AVA area showed larger end-diastolic AVA dimensions, as well as smaller end-systolic AVA area and perimeter, compared with those with a greater end-systolic AVA area (Table 2).

Left ventricular deformation

No differences in mean segmental and global LV strain between the groups examined were present (Table 3). However, basal LV-LS and LV-RS proved to be significantly reduced in subjects with a greater end-diastolic AVA area compared with those with a greater end-systolic AVA area. Subjects with equal end-diastolic and end-systolic AVA areas also showed significantly reduced basal LV-LS compared with subjects with a greater end-systolic AVA area (Table 4).

Left ventricular rotational mechanics

Five out of 70 subjects (7%) showed counterclockwise LV-RBR (basal LV rotation: 0.73±0.31 degrees and apical LV rotation: 6.81±3.06 degrees), while 2 cases (3%) demonstrated clockwise LV-RBR (basal LV rotation: −2.00±0.14 degrees and apical LV rotation: −1.11±0.57 degrees) in individuals with a greater end-systolic AVA area. In the remaining 63 subjects, rotational mechanics of the LV were directed normally with greater end-systolic AVA area, basal and apical LV rotations and LV twist were measured to be −4.50±2.33, 9.57±3.45 and 14.07±3.59 degrees, respectively. Among the 34 individuals who had greater end-diastolic AVA area, all 3 cases (9%) had clockwise LV-RBR (basal LV rotation: −4.76±1.00 degrees and apical LV rotation: −0.82±0.65 degrees). In the remaining 31 subjects with normally directed LV rotational mechanics and a greater end-diastolic AVA, basal and apical rotations and LV twist were −3.43±1.49, 10.91±3.47 and 14.34±4.08 degrees, respectively. Basal rotation of the LV was significantly lower in subjects with a greater end-diastolic AVA area compared with those with a greater end-systolic AVA area, without significant differences in apical rotation and twist of the LV.

Reproducibility of 3DSTE-derived AVA measurements

Interobserver and intraobserver agreements of end-diastolic and end-systolic AVA diameters, areas, and perimeters are demonstrated with their respective ICCs in Table 5. No discrepancy was observed between observers regarding the timing of maximum AVA during the cardiac cycle.

Discussion

The AVA serves as the gateway between the LV and the aorta, with which it is closely connected (1,2,5,6). The LV functions as a pump during the cardiac cycle and exhibits a complex motion pattern (28,29). Due to the interdependence of LV deformation and rotational mechanics, the LV can maximize its emptying during systole (30-34). Epicardial and endocardial LV muscle fibers move perpendicularly, the basal and apical LV regions rotate clockwise and counterclockwise during systole, respectively, while simultaneously undergoing longitudinal shortening (represented by LV-LS), circumferential narrowing (represented by LV-CS), and radial thickening (represented by LV-RS). These parameters, however, are not uniform, exhibiting characteristic regional variations (16,30-34).

Based on the findings presented above, it could be established that 30% of healthy adult individuals have a greater end-diastolic AVA area with reduction of basal LV rotation, basal LV-RS and LV-LS compared with subjects with a greater end-systolic AVA. Although 2D echocardiographic Simpson’s assessment of LV-EF was found to be reduced, 3DSTE did not confirm this finding. According to the guidelines, 3D echocardiographic measurement of LV-EF is suggested, when available, due to its significantly superior accuracy (27).

These findings suggest several implications. First, they demonstrate that LV strains, rotational parameters, and AVA dimensions can be assessed simultaneously using the same echocardiographic datasets for physiologic evaluations during a 3DSTE-derived analysis within the framework of the MAGYAR-Healthy Study. Such an analysis has not been performed previously, therefore it is a novel finding (5,6). Secondly, differences in basal LV functional properties could be demonstrated between certain subsets of healthy subjects. In a recent study, smaller basal LV rotation was demonstrated to be associated with greater end-diastolic AVA area at a healthy population level (6). The present study extends this finding demonstrating a complex functional deterioration of the basal LV region, characterized by reduced basal LV strains and rotation in the presence of a greater end-diastolic AVA area. Thirdly, this raises the question of causality, which came first, the chicken or the egg? Could differences in myocardial morphology and consequential function lead to differences in AVA dimensions, or vice versa? Finally, what is the significance and relevance of these findings? How can the result of this study be used in the clinical setting? Its clinical relevance is not clear, but in a recent study examining AVA in LV non-compaction, higher ratio of patients showed greater end-diastolic AVA area than greater end-systolic AVA area (35). However, the prognostic impact of the presence of a larger end-diastolic AVA area has not yet been confirmed either, and its role in the development on cardiac dysfunction or aortic valve regurgitation/stenosis remains to be clarified in future investigations. It is therefore recommended that similar physiological studies be conducted both in healthy individuals and in patients with specific pathologies, to confirm the presented findings and to determine their long-term significance.

Limitation section

• Although healthy individuals were involved in this study, it cannot be ruled out with 100% certainty that some subjects have a subclinical abnormality.
• There was an exclusion of a significant portion (56%) of the initial cohort which may introduce the potential for selection bias. This fact should be considered when interpreting the findings.
• According to the presented findings, healthy individuals, who have same size end-systolic and end-diastolic AVA areas seems to be rare. This subgroup with a small sample size (n=8) can raise serious concerns about statistical power and type I/II error risk, which fact should be mentioned when interpreting the results.
• One of the most important technical issues regarding 3DSTE is its low temporal and spatial resolution. Moreover, the footprint of the transducer for 3DSTE is greater than that of the transducer used for 2D echocardiography. In addition, the fact that more than 1 subvolume is necessary to be acquired for optimal images makes an opportunity for stitching and motion artifacts and consequential deterioration of image quality (11-17).
• Although 3DSTE is capable of performing not only chamber quantifications, but also of determining mitral and tricuspid annular dimensions (7,16,17). Moreover, the aorta is a complex 3D structure with Valsalva sinuses and the sinotubular junction (1,2). However, it was not aimed to assess these structures.
• 2D Doppler echocardiography and AVA dimensions measured by 3DSTE were not aimed to be compared either (36).

Conclusions

Although the majority of healthy adults have greater end-systolic than end-diastolic AVA area, 30% of the cases show greater end-diastolic AVA area. Healthy subjects with a greater end-diastolic versus end-systolic AVA area have reduced basal radial and longitudinal LV strains, as well as lower basal LV rotation.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1354/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1354/dss

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1354/coif). A.N. serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by Institutional and Regional Biomedical Research Committee of the University of Szeged (No. 71/2011) and informed consent was obtained from all individual participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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