Abstract
Purpose
We aimed to evaluate left atrial appendage functions (LAA) derived by speckle tracking echocardiography in patients with mild to severe mitral regurgitation (MR) and assess the relation between MR severity and LAA’s anatomical, structural, and physiological functions.
Methods
Ninety-seven patients with mild, moderate, or severe MR admitted to our department for transesophageal echocardiography were included. In addition to conventional echocardiographic measurements, LAA functions were assessed by speckle tracking echocardiography. Patients were divided into three groups according to MR grades: mild MR, moderate MR, and severe MR.
Results
The LAA reservoir, conduit, and contractile phase strain were lower in patients with moderate and severe MR than in those with mild MR. (10.0 ± 3.7 vs. 8.2 ± 3.5 vs. 16.7 ± 6.7, p < 0.001; 6.4 ± 3.0 vs. 4.9 ± 3.0 vs. 10.6 ± 4.9, p < 0.001; 3.6 ± 2.8 vs. 3.3 ± 2.1 vs. 6.1 ± 3, p < 0.001, respectively).
Also, the LAA volume and area were significantly higher in the severe MR group. Spontaneous echo contrast was another factor associated with lower LAA strain parameters.
Conclusion
Hemodynamically important MR was associated with reduced LAA functions detected by speckle-tracking echocardiography. LAA strain may be used to predict the unfavorable effects of MR on LAA.
Keywords: Left atrial appendage, Mitral regurgitation, Strain
Introduction
One of the most common and clinically significant valvular heart diseases in the world, mitral regurgitation (MR) significantly impairs cardiovascular health [1]. Its prevalence increases with age and affects more than 2% of the general population [2]. MR causes volume overload and pressure elevation in the left atrium (LA). The LA enlargement and remodeling association is related to early cardiac outcomes and can occur due to MR [3]. Although LA expansion is a compensatory mechanism for volume overload to prevent pulmonary edema in MR, it is shown that patients with enlarged LA have a poor prognosis after successful MR surgery [4]. Atrial fibrillation (AF) is one of the worst consequences of LA expansion and remodeling, and it increases stroke risk, cardiac mortality, and morbidity [5]. Previous studies showed that severe primary MR with enlarged LA and sinus rhythm has an increased risk of mortality and postoperative morbidity [3]. Transthoracic echocardiography (TTE) is the main diagnostic tool for classifying and determining the etiology of MR. There are several echocardiographic methods, including vena contracta width, pulmonary vein flow, mitral inflow, regurgitant volume (RV), and effective regurgitant orifice area (EROA) to grade MR severity. Although RV and EROA are the quantitative methods of which use recommended mostly, the decision of MR severity should not be made on a single parameter [6].
Left atrial appendage (LAA) has contractile functions; thus, it is important to compensate for LA hemodynamics. LAA distension capacity and quantity of atrial natriuretic peptide excretion are higher than those of the LA [7]. There is limited data in the literature about the assessment of LAA functions. Transesophageal echocardiography (TOE) provides better visualization of the LAA. LAA peak flow velocity is the main determinant of LAA functions; however, it has limitations. Strain imaging evaluates myocardial deformation, is independent of volume overload, and has many other advantages. Although strain imaging with speckle-tracking echocardiography is widely used to assess the LA, left ventricle (LV), and right ventricle, insufficient data support its use in LAA imaging [8]. In a previous study, global longitudinal strain—defined as the peak strain value of the left atrial appendage (LAA) segments—was utilized to assess LAA function in patients with ischemic stroke history [9]. On the other hand, some studies evaluate LAA strain similar to the LA strain as reservoir, conduit, and contractile phase strain for patients without AF.
Numerous studies in the literature have evaluated the relationship between the LAA strain and thrombus formation. However, there is limited data about the effect of MR on LAA mechanics. Our study aimed to evaluate LAA functions assessed by speckle-tracking echocardiography in MR.
Methods
One hundred and fifty-one patients who underwent TOE in our department between August 2024 and February 2025 were included in our study.
Patients with MR as an indication for TOE and those with mild MR who underwent TOE for patent foramen ovale or bicuspid aorta pre-diagnosis without any pathology were included in the study. 28 patients with AF were excluded from the moderate-severe MR group. Patients with cardioversion or AF ablation indications for TOE were not initially included in the study. Also, patients with rheumatic mitral valve stenosis, history of valve surgery or LAA occlusion, aortic stenosis or moderate-severe aortic regurgitation, atrial or ventricular septal defect, restrictive cardiomyopathy, poor image quality, intracardiac thrombus, extreme tachycardia, or high blood pressure were excluded from the study (Fig. 1). Chronic diseases regarding hypertension, diabetes mellitus, chronic kidney disease, and coronary artery disease were noted.
Fig. 1.
A flow chart figure of the study population
Patients were divided into three groups according to MR grades: mild MR (group 1), moderate MR (group 2), and severe MR (group 3).
The local Ethical Committee approved the study, and all patients provided written informed consent.
Clinical trial number: not applicable.
Transthoracic echocardiography
TTE was performed in the left lateral decubitus position using commercially available echocardiography systems Philips Affiniti CVx (Philips Medical Systems, Andover, MA). TTE imaging is commented according to the guidelines of the American Society of Echocardiography and the European Association of Cardiovascular Imaging [10]. Standard echocardiographic measurements such as LV end-diastolic diameter, end-systolic diameter, and LA diameter were taken from the parasternal long-axis view. LV ejection fraction (EF) by the biplane Modified Simpson method was measured from apical four-chamber and apical two-chamber views.
Transesophageal echocardiography
TOE was performed with Philips Affiniti CVx (Philips Medical Systems, Andover, MA) in all subjects by the two experienced operators. All TOE evaluations were performed after at least four hours of fasting. In our routine procedure, lidocaine spray was used for local anesthesia of the posterior pharynx, and 1–2 mg midazolam was used for sedation. Blood pressure, oxygen saturation, and pulse rates were recorded. After the TOE probe was positioned to the mid-esophagus, LAA was visualized at 45–90 degrees in the long axis with the left upper pulmonary vein, LA, mitral valve, and LV. LAA early peak flow velocity was measured from the inflow with pulsed-wave Doppler. The presence of spontaneous echo contrast (SEC) or thrombus was determined from multiplane LAA views. Also, the LAA type was decided from multiplane views, which were classified as cactus, windsock, Chicken Wings, and cauliflower. The mitral valve was evaluated from 0, 60, 90, and 120 degree views. Mitral valve scallops were examined from a bicommissural view. 3D views were used to determine MR etiology and valve complications. Vena contracta, EROA, and RV were the quantitative parameters of MR. Mitral annulus diameter was measured from a 0-degree four-chamber view. Also, the aortic valve, interatrial septum, and tricuspid valve were evaluated in our routine TOE procedure.
SEC was defined as smoke-like blood flow in LA or LAA, which was classified into mild or dense/severe (also known as sludge) [6]. In statistical analysis, patients were divided into two groups: SEC (+) or SEC (-).
Speckle tracking echocardiography
Two-dimensional speckle tracking echocardiography views were taken with a frame rate of 60–100 frames/s in order to obtain high temporal resolution with acceptable spatial definition in the light of ESC/EACVI recommendations [6]. Three consecutive beats were recorded in cine-loop format and analyzed with offline dedicated software (Tomtec, Phillips Medical Systems, offline analysis software, version 2.51.00). The global longitudinal strain (GLS) of LA was measured to express the deformation in all segments in the TTE apical 4 C view. The region of interest (ROI), defined as the inner endocardial contour of the myocardium, was obtained, and the LA endocardial border was tracked manually. LA longitudinal strain (LAS) was measured in three left atrial phases. EACVI/ASE/Industry task force consensus document nomenclature was used for the defining LAS. LAS is defined according to three LA cycles: LAS during the reservoir phase (LASr), LAS during the conduit phase (LAScd), and LAS during the contraction phase (LASct). LAA long-axis images obtained from mid-esophageal TOE 45 to 90 degree views were used for LAA strain measurements. The LA strain modality was used since there was no specific program for the LAA strain. ROI was chosen, and the endocardial border was tracked manually. ROI width is adjusted to cover wall thickness completely. LAA longitudinal strain (LAAS) was obtained similarly with three LA phases (Fig. 2). EACVI/ASE/Industry task force consensus document nomenclature was used to define LAS. LAAS was defined according to three LAA cycles: LAAS during the reservoir phase (LAASr), LAAS during the conduit phase (LAAScd), and LAAS during the contraction phase (LAASct) [10].
Fig. 2.
Left atrial appendage strain in the patient with moderate mitral regurgitation
The two operators-experienced strain imaging-performing LAA strain analysis were unaware of the patients’ clinical conditions and the degree of MR. The LAA strain analysis was repeated three times by the same operator, average value was calculated.
Statistical analysis
All statistical analyses were performed using SPSS software version 22.0 (SPSS Inc., Chicago, IL). Interobserver variability was assessed using the Bland-Altman method. Continuous parametric data were summarized as means ± standard deviation (SD) and compared using a one-way analysis of variance (ANOVA). Nonparametric data were summarized as medians ± interquartile range (IQR) and compared using the Kruskal-Wallis test. We utilized the Pearson chi-square to analyze categorical data. Continuous variables, including LAA volume, area, pulse wave velocity, and LAA, were presented as means ± standard deviation (SD) and compared between the SEC (+) and SEC (-) groups by t-test analysis. The receiver operating characteristic (ROC) curve was used to explore the association between LAA strain parameters and moderate-to-severe MR. Multivariable logistic regression using the enter method was used to determine independent predictors for moderate and severe MR. A p-value < 0.05 was considered statistically significant.
Results
Of a total of ninety-seven patients, fifty of them had mild, twenty-three of them had moderate, and twenty-four of them had severe MR, with a mean age of 54 ± 16.1 years. 52.6% of the population were male; the rates of chronic diseases in the population were as follows: 38.1% had hypertension, 23.7% had diabetes mellitus, and 25.8% had coronary artery disease. As expected, coronary artery disease incidence was significantly higher in the severe MR group. As classified LAA types, 41.2% had chicken wings, 23.7% had windsock, 18.6% had cactus, and 9.3% had cauliflower type (Table 1).
Table 1.
Demographic and clinical data of the study population according to the grade of mitral regurgitation
| Mild MR n = 50 |
Moderate MR n = 23 |
Severe MR n = 24 |
P Value | |
|---|---|---|---|---|
| Age, year | 48.12 ± 15.4 | 63.26 ± 9.78 | 57.67 ± 17.64 | < 0.001 |
| Gender, male, n (%) | 26 (52.0) | 12 (52.2) | 13 (54.2) | 0.984 |
| Comorbidities, n (%) | ||||
| HT | 17 (34.0) | 11 (47.8) | 9 (37.5) | 0.527 |
| DM | 11 (22.0) | 8 (34.8) | 4 (16.7) | 0.329 |
| CAD | 3 (6.0) | 10 (43.5) | 12 (50.0) | < 0.001 |
| Transthoracic Echocardiographic Findings | ||||
| LVEF, % | 60.0 ± 3.0 | 52.0 ± 17.0 | 55.0 ± 20.0 | 0.009 |
| LVEDD, mm | 45.3 ± 4.1 | 51.0 ± 5.2 | 52.2 ± 6.3 | < 0.001 |
| LVESD, mm | 30.0 ± 5.5 | 32.0 ± 9.0 | 32.0 ± 4.4 | < 0.001 |
| IVS, mm | 9.9 ± 1.0 | 11.5 ± 1.8 | 10.2 ± 1.6 | 0.001 |
| PWT, mm | 9.7 ± 0.9 | 10.9 ± 1.4 | 9.8 ± 1.0 | 0.002 |
| LA short axis, mm | 35.0 ± 5.1 | 41.8 ± 6.0 | 42.2 ± 4.8 | < 0.001 |
| LA volume, mL | 32.3 ± 19.0 | 60.0 ± 26.2 | 57.3 ± 35.9 | < 0.001 |
| LASr, % | 30.6 ± 9.1 | 13.0 ± 13.4 | 16.0 ± 11.9 | < 0.001 |
| LAScd, % | 17.0 ± 8.7 | 7.1 ± 7.1 | 8.3 ± 5.8 | < 0.001 |
| LASct, % | 11.8 ± 8.7 | 6.8 ± 5.0 | 7.8 ± 7.4 | < 0.001 |
| Transesophageal Echocardiography | ||||
| LAA Type, n (%) | 0.264 | |||
| Cactus | 6 (12) | 8 (34.8) | 5 (20.8) | |
| Windsock | 12 (24.0) | 6 (26.1) | 7 (29.2) | |
| Chicken Wing | 27 (54.0) | 7 (30.4) | 8 (33.3) | |
| Cauliflower | 5 (10.0) | 2 (8.7) | 4 (16.7) | |
| Eccentric MR, n (%) | 5 (10.0) | 7 (30.4) | 8 (33.3) | < 0.001 |
| MAD, mm | 36.0 ± 3.0 | 35.0 ± 4.0 | 37.5 ± 6.5 | 0.229 |
| LA SEC, n (%) | 0 (0.0) | 6 (26.1) | 9 (37.5) | < 0.001 |
| LAA Long Dia | 81.3 ± 11.4 | 85.6 ± 16.9 | 93.3 ± 20.3 | 0.009 |
| LAA Short Dia | 27.4 ± 4.2 | 29.5 ± 4.8 | 30.6 ± 8.0 | 0.055 |
| LAA SEC, n (%) | 0 (0.0) | 6 (26.1) | 7 (29.2) | < 0.001 |
| LAA Area | 3.25 ± 0.97 | 3.92 ± 1.09 | 4.02 ± 1.59 | 0.013 |
| LAA Volume | 2.91 ± 1.40 | 4.05 ± 2.20 | 4.70 ± 3.28 | 0.004 |
| LAA-PW | 0.55 ± 0.32 | 0.38 ± 0.21 | 0.50 ± 0.20 | 0.029 |
| LAASr, % | 16.7 ± 6.7 | 10.0 ± 3.7 | 8.2 ± 3.5 | < 0.001 |
| LAAScd, % | 10.6 ± 4.9 | 6.4 ± 3.0 | 4.9 ± 3.0 | < 0.001 |
| LAASct, % | 6.1 ± 3.5 | 3.6 ± 2.8 | 3.3 ± 2.1 | < 0.001 |
CAD coronary artery disease, Dia diameter, DM diabetes mellitus, HT hypertension, IVS interventicular septum, LA left atrium, LAA left atrial appendage, LAAScd left atrial appendage conduit strain, LAASct left atrial appendage contraction strain, LAASr left atrial appendage reservoir strain, LVEDD left ventricular end diastolic diameter, LVEF left ventricular ejection fraction, LVESD leftventricular end systolic diameter, MAD mitral annular diameter, MR mitral regurgitation, PW pulse wave, PWT posterior wall thickness, SEC spontaneous echo contrast
Bold value indicates the significance of p < 0.05
LA diameter was statistically significantly higher in the moderate and severe MR groups than in the mild MR group (41.8 ± 6.0 mm vs. 42.2 ± 4.8 mm vs. 35.0 ± 5.1 mm, p < 0.001; respectively).
Transesophageal echocardiography
SEC incidence in LA and LAA were significantly higher in the severe MR group (p < 0.001). LAA volume was significantly different between severe MR and mild MR, while there were no significant differences seen between the other groups. Patients with severe MR had larger LAA volume than mild MR (p = 0.048). LAA’s long axis diameter was significantly longer in the severe MR group than in the mild or moderate MR group (p = 0.033). There was no statistically significant difference regarding LAA short axis diameter and heart rate between groups. LAA area was significantly different between the three groups (p = 0.013).
2D speckle tracking evaluation
LA longitudinal strain of the reservoir, conduit, and contractile phases were statistically significantly lower in moderate and severe MR group than mild MR group (Table 1).
LAA strain parameters, including LAASr, LAAScd, and LAASct, were lower in the severe and moderate MR groups when compared with mild MR. The mild MR group had better LAASr than moderate and severe MR (16.7 ± 6.7 vs. 10.0 ± 3.7 vs. 8.2 ± 3.5, p < 0.001; respectively). When the groups were compared couple, LAASr was lower in moderate and severe than mild MR group (p < 0.001, p < 0.001, respectively); however, there was no difference between moderate and severe MR. Similar with LAASr, LAAScd and LAASct were decreased in moderate and severe MR group than mild MR (10.6 ± 4.9 vs. 6.4 ± 3.0 vs. 4.9 ± 3.0, p < 0.001; 6.1 ± 3.5 vs. 3.6 ± 2.8 vs. 3.3 ± 2.1, p < 0.001; respectively). When the groups were compared couple, there was no statistically significant difference regarding LAAScd and LAASct between the moderate and severe MR groups (Table 2). In contrast, a significant difference was observed between these and the mild MR groups. Figure 3 illustrates the comparison of LAASr, LAAScd, and LAASct between mild, moderate, and severe mitral regurgitation status. As shown in Fig. 3, all LAA strain parameters (LAASr, LAAScd, LAASct) showed a stepwise decrease with increasing MR severity.
Table 2.
Comparison of left atrial appendage structural and functional parameters between MR groups
| Group 1–2 (mild-moderate) |
P value Group 1–3 (mild-severe) |
Group 2–3 (moderate-severe) |
||
|---|---|---|---|---|
| LAA Long Dia (mm) | 0.609 | 0.033 | 0.421 | |
| LAA Short Dia (mm) | 0.224 | 0.220 | 0.927 | |
| LAA Area (cm2) | 0.046 | 0.106 | 0.993 | |
| LAA Volume (mL) | 0.090 | 0.048 | 0.811 | |
| LAA-PW (msn) | 0.003 | 0.006 | 0.476 | |
| LAASr (%) | < 0.001 | < 0.001 | 0.294 | |
| LAAScd (%) | < 0.001 | < 0.001 | 0.295 | |
| LAASct (%) | 0.006 | < 0.001 | 0.973 | |
MR mitral regurgitation; group 1, mild MR; group 2, moderate MR; group 3, severe MR, LAA left atrial appendage, Dia diameter, PW pulse wave velocity, LAASr left atrial appendage reservoir strain, LAAScd left atrial appendage conduit strain, LAASct left atrial appendage contraction strain; bold value indicates the significance of p < 0.05
Fig. 3.
A comparison of left atrial appendage strains between mild, moderate and severe mitral regurgitation is illustrated in a box-plot graph. The global longitudinal strain of the left atrial appendage (LAA) in three phases. LAA cycle phases are defined as LAASr, reservoir phase; LAAScd, conduit phase; LAASct, contraction phase
There was no statistically significant difference regarding LAA strain, area and volume between degenerative and functional MR.
As compared to the LAA strain between SEC (+) and SEC (-) groups, the LAA reservoir and conduit phase strain is lower in the SEC positive group than the SEC negative group (11.13 ± 2.42 vs. 13.26 ± 7.03, p = 0.04; 6.58 ± 2.39 vs. 8.42 ± 4.98, p = 0.04; respectively) (Table 3).
Table 3.
Comparison of the relation between spontaneous echo contrast and left atrial appendage functions
| SEC (-) | SEC (+) | P value | |
|---|---|---|---|
| LAA volume (ml) | 3.46 ± 2.32 | 4.70 ± 2.09 | 0.08 |
| LAA area (cm2) | 3.47 ± 1.17 | 4.43 ± 1.38 | 0.03 |
| LAApw (cm/s) | 0.55 ± 0.21 | 0.40 ± 0.20 | 0.03 |
| LAASr (%) | 13.26 ± 7.03 | 11.13 ± 2.42 | 0.04 |
| LAAScd (%) | 8.42 ± 4.98 | 6.58 ± 2.39 | 0.04 |
| LAAct (%) | 4.83 ± 3.45 | 4.55 ± 2.54 | 0.73 |
SEC spontaneous echo contrast; pw, pulse wave velocity, LAASr left atrial appendage reservoir strain, LAAScd left atrial appendage conduit strain, LAASct left atrial appendage contraction strain; bold value indicates the significance of p < 0.05
Multivariate regression analysis showed that LASr and LAASr are independent predictive factors for moderate and severe MR (OR 0.839; 95% CI: 0.715, 0.986; p = 0.033, OR 0.897; 95% CI: 0.811, 0.992; p = 0.034, OR 0.783; 95% CI: 0.654, 0.938; p = 0.008; respectively (Table 4).
Table 4.
Univariate and multivariate logistic regression analysis showing the independent echocardiographic predictors of moderate to severe mitral regurgitation
| Univariate | Multivariate | |||
|---|---|---|---|---|
| Odds ratio 95% CI | p-value | Odds ratio 95% CI | p-value | |
| Age | 1.957 (1.025–1.090) | < 0.001 | 0.994 (0.934–1.059) | 0.861 |
| CAD | 13.787 (3.757–50.597) | < 0.001 | 4.529 (0.464–44.214) | 0.194 |
| LA | 1.305(1.168–1.459) | < 0.001 | 1.150 (0.940–1.408) | 0.174 |
| LASr | 0.820(0.762–0.884) | < 0.001 | 0.889 (0.798–0.991) | 0.033 |
| LAAPW | 0.022(0.002–0.244) | 0.002 | 0.435 (0.006–31.637) | 0.703 |
| LAASr | 0.735(0.645–0.836) | < 0.001 | 0.809 (0.662–0.989) | 0.039 |
| LAA Area | 1.705(1.172–2.479) | 0.005 | 0.375 (0.026–5.346) | 0.469 |
| LAA Volume | 1.462(1.133–1.887) | 0.004 | 1.549 (0.346–6.927) | 0.567 |
| LVEDD | 1.307(1.165-1,467) | < 0.001 | 1.078 (0.885–1.313) | 0.455 |
| LVEF | 0.703(0.589–0.840) | < 0.001 | 0.897 (0.755–1.065) | 0.214 |
| MAD | 1.064(0.942–1.201) | 0.316 | ||
CAD Coronary artery disease, LA left atrium, LAA left atrial appendage, LAASr left atrial appendage reservoir strain, LVEDD left ventricular end diastolic diameter, LVEF left ventricular ejection fraction, MAD mitral annular diameter, PW pulse wave
Bold value indicates the significance of p < 0.05
ROC curve was used to explore the association between impaired LAASr, LAAScd, LAASct and moderate-to-severe MR. The area under the curve was 0.843 (95% CI 0.755–0.909) for LAASr, 0.814 (95% CI 0.722–0.886) for LAAScd, 0.731 (95% CI 0.631–0.816) for LAASct. The ROC curve analysis results was shown at Fig. 4.
Fig. 4.
The ROC curve of the left atrial appendage strains to determine mitral regurgitation severity
Reproducibility
Interobserver variability was assessed by intraclass correlation coefficients (ICCs) and Bland-Altman analysis for LAA strain. Inter-observer ICC were 0.413 for LAASr, 0.268 for LAAScd and, 0.099 for LAASct. As shown in Fig. 5, these analyses confirm lower reproducibility of strain imaging in different, independent cardiac cycles recorded in the same patient but briefly after each other.
Fig. 5.
Inter-observer variability is shown for left atrial appendage strains
Discussion
This prospective study is the first to use echocardiographic measures to assess the effects of MR-induced volume overload on the LAA. The structural and physiological effects of volume overload on the LAA were evaluated using echocardiographic measures. Our research shows that strain analysis might be a practical and precious technique for assessing LAA mechanics in MR patients. Specifically, patients with advanced MR showed considerably lower LAA strain values than mild MR, indicating compromised mechanical performance. The following summary of the study’s primary findings: [1] Moderate and severe MR were associated with reduced LA and LAA functions, including reservoir, conduit, and contractile phase strain, [2] Patients with moderate-to-severe MR had considerably larger LAA diameters and areas, [3] Patients with SEC (+) had reduced LAA reservoir and conduit phase strain, lower LAA peak flow velocity and larger LAA area. More longitudinal research is necessary to confirm these results and elucidate the possible predictive value of LAA strain measurements.
MR is one of the valvular diseases that affects the functions of the LA and LAA [11]. The effects of MR on the LA include LA volume overload due to the regurgitant flow from the LV during systole [12]. Continuous volume overload causes LA remodeling over time in patients with chronic MR. LA remodeling is atrial tissue’s structural and functional response to sustained electrical, mechanical, and metabolic stressors [13]. Over time, elevated atrial pressure contributes to functional remodeling, leading to impaired atrial contraction. Advanced imaging methods such as speckle-tracking strain analysis or volumetric indications such as LA ejection fraction can be employed [14]. Compatibly with the literature moderate and severe MR had lower LA strain values than mild MR in our study. So many studies designed to evaluate LA functions in MR however, this is the first study in the literature to assess detailed LAA functions in MR.
Kamel et al. found that patients with mitral stenosis had a larger LA and a lower LAA EF on standard echocardiographic evaluation compared to the control group. They showed that persistently elevated atrial pressure first causes LA and LAA dilatation, which is followed by functional impairment, and they ascribed these findings to elevated LA pressure as a result of mitral stenosis [15]. Similarly, our investigation found significant LA dilatation in patients with advanced MR. Additionally, patients with severe MR showed notable dilatation in LAA area measurements, and speckle-tracking strain analysis confirmed this structural modification. LAA echocardiographic assessment is difficult due to its complex geometrical shape. Two-dimensional measurements of volume, size, and area have limited use because of these anatomical complexity and variety from person to person [16]. Strain analysis have gained importance as a new advances to evaluate regional or global functions of myocardium.
Although there are so many echocardiographic methods for the detailed evaluation of LA functions, there is limited data about LAA assessment. LAA peak emptying and filling flow velocity have been the only predictors for LAA functions for many years. Peak flow velocity lower than 20 cm/sec is strongly associated with thrombus or SEC development [17]. A previous study found that LAA longitudinal strain is significantly impaired in non-valvular AF patients with SEC or thrombus. The mentioned study suggests using LAA deformation parameters to detect thrombus or SEC in patients with sinus rhythm or AF besides conventional echocardiographic measurements [18]. There is no established echocardiographic method for the LAA strain, unlike the LA strain. Previous studies defined LAA strain as peak positive or negative longitudinal strain; however, clinical use is limited [9, 19]. E. Baris¸ Kaya et al. evaluated LAA strain with tissue-Doppler imaging and found a correlation between LAA strain recovery and peak flow velocity after AF cardioversion [20]. It is a well-known fact that LAA functions are impaired with AF. Chronic AF is related to pectinate muscle dysfunction and LAA dilatation. LAA functions are impaired at the end of this remodeling [21]. A study which is designed to evaluate LAA functions as a predictor of subclinical AF in patients with ischemic stroke, measure LAA strain similar to LA strain in triphasic curves; LAA reservoir strain, LAA contraction strain and, LAA conduction strain [22]. Although the lack of standard approach to measure LAA strain in literature, it would be beneficial to base LAA strain calculations on the LA strain due to the similarity of their similar hemodynamic properties. We expect future studies to shed light on this issue. In our study, we aimed to evaluate LAA deformation with a method similar to LA strain in patients without AF. LA strain is a well-established diagnostic tool with three phases: the reservoir phase is the isovolumetric relaxation, the conduit phase is the early diastole with the blood flow into LV, and the contractile phase is the late diastole-atrium contraction. We planned to measure LAA strain with three phases instead of global longitudinal strain, considering that the atrial appendage’s hemodynamics are similar to LA’s. LAA strain parameters could be associated with SEC (+) and AF, even in patients without clinically apparent AF.
MR and AF coexisting is a frequent clinical situation as is known. Hemodynamically important MR cause atrial cardiomyopathy via LA dilatation and increased LA pressure. Interstitial fibrosis, hypertrophy in atrial myocytes, and chronical inflammatory changes are the additional factors [23]. LA enlargement and atrial cardiomyopathy are the precursors for AF development. Previous studies showed that clinical and subclinical AF deteriorates LAA strain [8, 18, 22]. In our study, we excluded the AF patients to evaluate the independent effect of MR on LAA function however, this selection bias may restricts the clinical applicability of the findings. Future studies may include both MR and AF subgroups to better assess the additive or interactive effects of both conditions on LAA function.
LAA functions are deteriorated in mitral stenosis due to pressure overload and atrial remodeling. Previous studies showed LA and LAA strain decrease in mitral stenosis and improved after mitral balloon valvuloplasty or mitral valve replacement [15, 24]. In light of these findings, we evaluated the LAA structure and functions with speckle-tracking echocardiography in MR. Reservoir phase strain is defined as isovolumetric relaxation and the early predictor of diastolic dysfunction. Conduit phase strain is correlated with an early diastolic filling, and contractile phase strain is related to late diastolic functions. In the present study, reservoir, conduit, and contractile phase strain of LAA were impaired in moderate and severe MR groups. There was no statistically significant difference between moderate and severe MR. As expected, hemodynamically important MR is associated with not only LA functions but also, has important effects on LAA functions.
TOE is the valuable diagnostic tool to deciding mitral valve surgery in severe MR. While decision is primarily depend on LV diameter, LA enlargement, EF, and pulmonary artery pressure, these parameters often reflects the late stages of atrial-ventricular remodelling. LAA strain is the novel marker for the early prediction of LAA mechanical dysfunction. In this context, decreased LAA strain could complement existing echocardiographic parameters and may be beneficial for refining risk stratification and timing of intervention in selected patients. Further prospective studies are required to make clear LAA strain usefulness in clinical practice.
Conclusion
Clinically important MR was associated with reduced LAA functions detected by speckle-tracking echocardiography. LAA strain might be used to predict the unfavorable effects of MR on LA and LAA.
Limitations
This study has several limitations. The most important limitation of the study is the small number of participants. LAA is not yet standadized. The lack of established acquisition and analysis protocols may have contributed to measurement variability. Inter-observer reproducibility was low, particularly for LAAct, as reflected by poor interclass correlation coefficients despite a small mean bias on Bland-Altman analysis. Also, comparing the methods for LAA strain including GLS and three phases strain might be valuable. As a cross-sectional observational study, it can only demonstrate an association between MR severity and reduced LAA function, not establish a causal or temporal relationship. Also, excluding AF patients may restricts the clinical practicability of our results.
Acknowledgements
We thank the physicians and participants involved in this study.
Authors’ contributions
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Belma Yaman], [Funda Başyiğit], [Nazlı Turan], [Yunus Emre Özbebek], and [Tuğba Kayhan Altuner]. The first draft of the manuscript was written by [Belma Yaman], [Nazlı Turan] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript
Funding
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Data availability
The datasets used and/or analyzed during the current study are available within the article.
Declarations
Ethics approval and consent to participate
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Ankara Etlik City Hospital. Informed consent was obtained from all individual participants included in the study.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available within the article.