Academic Editor: Vasileios Panoulas
Background: Three-dimensional (3D) speckle-tracking echocardiography
(3DSTE) is one of the newest development in non-invasive imaging offering
simultaneous 3D evaluation of atria and valvular annuli. 3DSTE was used to
analyze correlations between left atrial (LA) volume changes and mitral annular
(MA) dimensions and functional properties in healthy adult subjects.
Methods: A total of 297 healthy subjects were enrolled
in this retrospective cohort study, from which insufficient quality of images was
responsible for the exclusion of 98 cases (33%). The remaining study population
consisted of 199 healthy adults without valvular regurgitation/stenosis in sinus
rhythm (mean age: 33.5
Both left atrium (LA) and mitral annulus (MA) have cyclic changes in dimensions during the heart cycle [1, 2]. Three-dimensional (3D) speckle-tracking echocardiography (3DSTE) is one of the newest development in cardiac imaging offering simultaneous 3D examination of atria and valvular annuli [3, 4, 5]. There are limited number of studies assessing physiologic connections between LA and MA in healthy subjects, therefore each study assessing their relationship could increase our knowledge in this field [2, 6]. Therefore, in the present study, correlations between MA and LA volume changes were analyzed by 3DSTE in healthy adults.
Hundreds of healthy adult volunteers were recruited as part of the screening
between 2011–2015 and were examined at the outpatient cardiology clinic at the
University of Szeged, Hungary. Screening involved physical examination, standard
12-lead electrocardiography (ECG), two-dimensional Doppler echocardiography (2DE)
and 3DSTE. This retrospective cohort study comprised 297 healthy cases, from
which insufficient quality of images was responsible for the exclusion of 98
cases (33%). The remaining study population consisted of 199 healthy adults in
sinus rhythm (mean age: 33.5
All the 2DE images were acquired by a Toshiba Artida
As a first step, separate LA- and left ventricle (LV)-focused 3D
echocardiographic datasets were acquired digitally by the same Toshiba
Artida
Following optimalisations on LA-focused images, apical two- (AP2CH) and AP4CH views and 3 short-axis views at basal, midatrial and superior LA levels at end-diastole helped creation of virtual 3D cast of the LA, from which LA volumes were calculated (Fig. 1) [8]:
- maximum LA volume (V
- LA volume at the onset of atrial systole (V
- minimum LA volume (V
Three-dimensional (3D) speckle tracking echocardiography-derived full-volume dataset from which the 3D cast of the left atrium (LA) is extracted in a healthy subject. (A) Apical four-chamber view. (B) Apical two-chamber view. (C3) Short-axis view at basal LA level, (C5) short-axis view at midatrial LA level and (C7) short-axis view at superior LA level are presented (D) with a 3D virtual model of the LA. (E) Time–global LA volume change (dashed line) and time–global LA area change ratio (strain) curves (white line) with (F) calculated volumetric LA data are also shown. Abbreviations: EDV, LA volume at end-diastole; ESV, LA volume at end-systole; EF, LA ejection fraction; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
The following LA functional properties were calculated:
- LA total stroke (emptying) volume (TASV) = (V
- LA total emptying fraction (TAEF) = TASV/V
- LA passive stroke (emptying) volume (PASV) = V
- LA passive emptying fraction (PAEF) = PASV/V
- LA active stroke (emptying) volume (AASV) = V
- LA active emptying fraction (AAEF) = AASV/V
Healthy subjects were classified into 3 groups according to the normal maximum
end-systolic LA volume as presented in a recent study. Estimated mean
Using the LV-focused datasets, image planes were optimized on lateral and septal MA-LV edges/endpoints on AP2CH and AP4CH views [6, 10]. MA dimensions were assessed on the C7 short-axis view as demonstrated on Fig. 2. Several MA parameters featuring 2D-projected MA dimensions were measured with respect to the cardiac cycle [11]:
- MA diameter (MAD) was measured as a perpendicular line drawn from the peak of the MA curvature to the middle of the straight MA border, and it was measured both at end-diastole (MAD-D) and end-systole (MAD-S),
- MA area (MAA) was measured by planimetry both at end-diastole (MAA-D) and end-systole (MAA-S),
- MA perimeter (MAP) was measured by planimetry both at end-diastole (MAP-D) and end-systole (MAP-S).
MA diameter and MA area data were used for calculation of MA functional properties:
- MA fractional shortening (MAFS) was measured as [MAD-D – MAD-S]/MAD-D
- MA fractional area change (MAFAC) was measured as [MAA-D – MAA-S]/MAA-D
Three-dimensional speckle tracking echocardiography-derived three-dimensional dataset from which the mitral annulus is extracted. (A) Apical four-chamber view, (B) apical two-chamber view and a cross sectional view at the level of the mitral annulus (C7) following optimizations in apical four- and two-chamber views. The mitral annular plane is shown by a white arrow on long- (A, B) and short-axis (C7) images. Abbreviations: LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; Area, MA area, Circ, MA perimeter, Dist, MA diameter.
Categorical variables were presented as absolute values (percentages) and
continuous variables were presented as mean
LV end-diastolic and end-systolic diameters (48.4
LA and MA features measured by 3DSTE are presented in Table 1. The subject group
was divided into three subgroups according to their V
Parameters | Measures | |
Left atrial volumes | ||
Maximum LA volume (V |
40.9 | |
Maximum LA volume-indexed (mL) | 22.2 | |
Pre-atrial contraction LA volume (V |
27.9 | |
Pre-atrial contraction LA volume-indexed (mL) | 15.2 | |
Minimum LA volume (V |
19.6 | |
Minimum LA volume-indexed (mL) | 10.7 | |
Left atrial stroke volumes | ||
Total atrial stroke volume (TASV) (mL) | 21.3 | |
Total atrial stroke volume-indexed (mL) | 11.6 | |
Passive atrial stroke volume (PASV) (mL) | 13.0 | |
Passive atrial stroke volume-indexed (mL) | 7.1 | |
Active atrial stroke volume (AASV) (mL) | 8.3 | |
Active atrial stroke volume-indexed (mL) | 4.5 | |
Let atrial emptying fractions | ||
Total atrial emptying fraction (TAEF) (%) | 52.3 | |
Passive atrial emptying fraction (PAEF) (%) | 32.8 | |
Active atrial emptying fraction (AAEF) (%) | 29.0 | |
Mitral annular end-diastolic data | ||
Mitral annular diameter (MAD-D) (mm) | 2.42 | |
Mitral annular area (MAA-D) (mm |
7.25 | |
Mitral annular perimeter (MAP-D) (mm) | 10.18 | |
Mitral annular end-systolic data | ||
Mitral annular diameter (MAD-S) (mm) | 1.58 | |
Mitral annular area (MAA-S) (mm |
3.41 | |
Mitral annular perimeter (MAP-S) (mm) | 7.06 | |
Mitral annular functional properties | ||
Mitral annular fractional area change (MAFAC) (%) | 51.5 | |
Mitral annular fractional shortening (MAFS) (%) | 33.9 | |
Abbreviations: LA, left atrial; D, end-diastolic; S, end-systolic. |
V |
30 mL |
V | |
(n = 42) | (n = 120) | (n = 37) | |
V |
25.4 |
39.6 |
62.0 |
V |
14.9 |
21.8 |
33.1 |
V |
16.8 |
26.3 |
45.4 |
V |
9.4 |
14.5 |
24.1 |
V |
12.2 |
18.7 |
30.5 |
V |
7.1 |
10.2 |
16.2 |
TASV (mL) | 13.3 |
20.8 |
31.5 |
TASV-indexed (mL) | 7.7 |
11.5 |
16.9 |
PASV (mL) | 8.6 |
13.3 |
16.6 |
PASV-indexed (mL) | 5.2 |
7.2 |
8.9 |
AASV (mL) | 4.7 |
7.6 |
14.9 |
AASV-indexed (mL) | 2.7 |
4.3 |
7.9 |
TAEF (%) | 52.1 |
52.8 |
51.2 |
PAEF (%) | 33.9 |
34.0 |
27.3 |
AAEF (%) | 27.4 |
28.6 |
32.3 |
MAD-D (cm) | 2.26 |
2.45 |
2.53 |
MAA-D (cm |
6.37 |
7.40 |
7.75 |
MAP-D (cm) | 9.61 |
10.26 |
10.59 |
MAD-S (cm) | 1.44 |
1.58 |
1.73 |
MAA-S (cm |
2.79 |
3.43 |
4.02 |
MAP-S (cm) | 6.44 |
7.09 |
7.62 |
MAFAC (%) | 53.8 |
52.3 |
45.8 |
MAFS (%) | 35.5 |
34.4 |
31.0 |
Abbreviations: AAEF, active atrial emptying fraction; AASV, active atrial stroke
volume; PAEF, passive atrial emptying fraction; PASV, passive atrial stroke
volume; TAEF, total atrial emptying fraction; TASV, total atrial stroke volume;
V |
Some MA morphological parameters and MAFAC were found to be associated with
V
Prognostic value of mitral annular dimensions and mitral annular fractional area change to predict larger than 50 mL maximum left atrial volume. Abbreviations: MAD-D, end-diastolic mitral annular diameter; MAD-S, end-systolic mitral annular diameter; MAA-S, end-systolic mitral annular area; MAP-D, end-diastolic mitral annular perimeter; MAP-S, end-systolic mitral annular perimeter; MAFAC, mitral annular fractional area change; AUC, area under curve.
All LA volumes were elevated with dilated MAD-D and MAD-S, only increased
V
MAD-D |
MAD-D |
MAD-S |
MAD-S |
MAFAC |
MAFAC | |
(n = 76) | (n = 123) | (n = 101) | (n = 98) | (n = 88) | (n = 111) | |
V |
37.7 |
42.7 |
38.3 |
43.5 |
42.3 |
39.7 |
V |
21.9 |
23.0 |
21.2 |
23.5 |
23.5 |
22.3 |
V |
25.5 |
29.4 |
24.8 |
31.1 |
30.3 |
26.1 |
V |
14.2 |
15.9 |
13.8 |
16.8 |
16.8 |
14.2 |
V |
18.5 |
20.2 |
16.8 |
22.5 |
22.0 |
17.7 |
V |
11.3 |
10.9 |
9.3 |
12.3 |
12.0 |
9.5 |
TASV (mL) | 19.2 |
22.5 |
21.5 |
21.1 |
20.3 |
22.1 |
TASV-indexed (mL) | 10.6 |
12.2 |
11.6 |
11.2 |
11.3 |
11.5 |
PASV (mL) | 12.3 |
13.4 |
13.5 |
12.4 |
12.1 |
13.6 |
PASV-indexed (mL) | 6.6 |
7.3 |
7.6 |
6.7 |
6.8 |
7.3 |
AASV (mL) | 7.0 |
9.1 |
8.0 |
8.7 |
8.2 |
8.5 |
AASV-indexed (mL) | 3.8 |
4.9 |
4.4 |
4.6 |
4.6 |
4.7 |
TAEF (%) | 51.3 |
53.0 |
55.8 |
48.8 |
48.3 |
55.5 |
PAEF (%) | 33.8 |
32.2 |
36.3 |
29.3 |
29.4 |
35.3 |
AAEF (%) | 26.2 |
30.7 |
30.5 |
27.4 |
26.5 |
31.0 |
MAD-D (cm) | 2.00 |
2.67 |
2.27 |
2.56 |
2.35 |
2.47 |
MAA-D (cm |
5.48 |
8.34 |
6.49 |
8.02 |
6.60 |
7.76 |
MAP-D (cm) | 9.10 |
10.85 |
9.73 |
10.65 |
9.74 |
10.54 |
MAD-S (cm) | 1.40 |
1.70 |
1.28 |
1.89 |
1.77 |
1.44 |
MAA-S (cm |
2.74 |
3.83 |
2.56 |
4.27 |
4.09 |
2.88 |
MAP-S (cm) | 6.43 |
7.45 |
6.30 |
7.82 |
7.71 |
6.55 |
MAFAC (%) | 48.3 |
53.3 |
58.2 |
44.6 |
37.3 |
62.8 |
MAFS (%) | 29.9 |
36.2 |
42.6 |
25.1 |
24.3 |
41.6 |
Abbreviations: AAEF, active atrial emptying fraction; AASV, active atrial stroke
volume; PAEF, passive atrial emptying fraction; PASV, passive atrial stroke
volume; TAEF, total atrial emptying fraction; TASV, total atrial stroke volume;
V |
The average
Intraobserver agreement | Interobserver agreement | |||
Average |
Pearson’s coefficient | Average |
Pearson’s coefficient | |
V |
0.4 |
0.95 (p |
0.5 |
0.97 (p |
V |
0.4 |
0.96 (p |
0.3 |
0.97 (p |
V |
–1.0 |
0.88 (p |
–0.9 |
0.86 (p |
MAD-D | 0.00 |
0.95 (p |
0.02 |
0.96 (p |
MAA-D | 0.02 |
0.96 (p |
0.00 |
0.97 (p |
MAP-D | –0.07 |
0.93 (p |
–0.10 |
0.92 (p |
MAD-S | 0.00 |
0.96 (p |
0.00 |
0.97 (p |
MAA-S | 0.00 |
0.98 (p |
–0.01 |
0.97 (p |
MAP-S | 0.06 |
0.98 (p |
0.03 |
0.98 (p |
Abbreviations: V |
In a recent work, correlations could be confirmed between LA volumes and
volume-based functional properties and MA dimensions and calculated functional
parameters in healthy adults [6]. While V
The present study aimed to provide further detailed exploration of the relationship between MA and LA volume changes in healthy adults by 3DSTE. Larger LA was found to be associated with more dilated MA dimensions and its reduced function in otherwise healthy subjects without mitral regurgitation. Moreover, it was also verified that dilated MA was associated with dilated LA volumes with respect to the cardiac cycle. Interestingly, elevated LA stroke volumes could be detected only in systole and end-diastole, while increased LA emptying fraction was present only in end-diastole. Reduced MA fractional area change was associated with larger diastolic LA volumes, smaller early diastolic LA stroke volume and all LA emptying fractions were reduced as well. These results suggest fine cooperation between LA volumes and volume-based functional properties and MA dimensions even in healthy subjects.
The LA is located on the left side of the heart and is connected to the LV via the MA. The LA has a dynamic motion with respect to the heart cycle working as a reservoir during LV systole, being a conduit during early diastole forwarding blood to the LV from the pulmonary veins and an actively contracting pump during late diastole [1]. The saddle-shaped left-sided atrio-ventricular mitral valve includes MA, leaflets, papillary muscles and chordae [12]. Although MA is a fibrous ring, it is affected by the contractility of the adjacent LA and LV areas, therefore it works like a “sphincter” [2]. Pre-systolic contraction of the MA is related to LA contraction, and minimal MA area during early LV systole, suggesting that complete MA contraction requires both and properly timed LA and LV systole [13]. Contrariwise, changes in dimensions and function of the MA are accompanied with different disorders (cardiomyopathies, cardiac amyloidosis, ischaemic heart disease, etc.), which could influence LA and LV alone or via consecutive mitral regurgitation, as well [14]. Moreover, severe aortic valve stenosis is mostly accompanied with different remodeling patterns including concentric, mixed and dilated hypertrophy in response to pressure overload leading to MA abnormalities as well [15].
3DSTE seems to be an optimal imaging tool for simultaneous evaluation of LA volumes and two-dimensionally projected MA dimensions on a certain plane with respect to the cardiac cycle. Moreover, using (end-)systolic and (end-)diastolic data, several LA and MA functional properties could be calculated at the same time allowing evaluation of their relationship on each other [6]. 3DSTE is based on ‘block-matching algorhythm’, it was found to be suitable not only for chamber quantifications [4], but also for the assessment of valvular annular dimensions [9, 10].
The strong relationship between LA and MA dimensions and functions even in cases without known pathological states should highlight our attention on the fact, that any changes in LA volumes are accompanied with changes in MA dimensions possibly proceeding into functional valvular regurgitation.
Recent echocardiographic methods including measurement of strains offer significant potentials in the evaluation of LA function. Clinical usefulness and relevance of adding LA strain to LA volume index in the detection of LV diastolic dysfunction were found in patients with preserved LV-EF [16]. Moreover, LA function was found to be correlated with LV deformation [17]. These facts could highlight our attention on the relationship between LA strains and MA parameters, which could be a topic of future publications.
- 2DE still have better image quality as compared to that of recently available 3DSTE systems, which could affect results [18]. The 3DSTE-derived acquisition allows 3D pyramidal echocardiographic full volume, but requires 4–6 cardiac cycles and gated capture to reconstruct the 3D image creating an opportunity for stitching artifacts. Moreover, rhythm disturbances and respiratory motion are also making imaging difficult. These facts could explain higher ratio of subjects who were excluded due to suboptimal image quality [19].
- Not the 3D saddle-shape of the MA, but its two-dimensionally projected image was assessed by 3DSTE analysis.
- Comparison of different echocardiographic modalities in the assessment of LA and MA dimensions was not aimed.
- Furthermore, validation of echocardiographic techniques was not purposed either due to their validated nature.
- No strain parameters featuring MA functionality was determined during the study.
- LA strains were not purposed to be determined [20].
- No volumetric or functional parameters including strains of both ventricles or the right atrium were assessed in this study.
- Fluid state of subjects were not controlled which could affect results.
- Differences could be demonstrated between published normal reference values of volumetric 3D echocardiography-derived LA volumetric data and 3DSTE-derived ones due to methodological differences.
3DSTE is suitable not only for chamber quantifications, but also for the assessment of valvular annular dimensions. Strong relationship exists between LA volumes and MA dimensions and functional properties in healthy subjects. With increasing LA volumes MA dilates and becomes functionally impaired which could explain developing functional mitral regurgitation in later stages.
AN: conceptualization, writing original draft; ÁK: methodology, software, investigation, data curation; NA: writing review, editing; CL: writing review, editing. All authors read and approved the final manuscript.
All subjects gave their informed consent for inclusion before they participated in the MAGYAR-Healthy Study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of University of Szeged (approval number: 71/2011).
We would like to express our gratitude to all those who helped us during the writing of this manuscript.
This research received no external funding.
The authors declare no conflict of interest. AN is serving as one of the Editorial Board members of this journal. We declare that AN had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Vasileios Panoulas.