Effect of severity of rheumatic mitral stenosis on left atrial strain and strain rate in patients with sinus rhythm.

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1 Effect of severity of rheumatic mitral stenosis on left atrial strain and strain rate in patients with sinus rhythm. Mohamed Ismail Ahmed, MD. Abstract Introduction and background: Atrial function is mainly determined from atrial volumes and volumederived indices that are load-dependent, time-consuming and difficult to reproduce because they are observer-dependent. Moreover these indices do not accurately evaluate atrial reservoir function. Various applications of tissue Doppler imaging including Tissue Velocity imaging, strain and strain rate imaging were used in the assessment of ventricular systolic and diastolic function. Recently they were validated to correlate with LA volumes. Aim: The aim of this study is to assess atrial function in patients with mild and moderate to severe MS compared to normal individuals by Strain and strain rate imaging. Subjects and methods: We studied 30 patients with mild mitral stenosis (group A), 30 patents with moderate to severe MS (group B): and 30 healthy individuals (group C): Standard twodimensional (2-D) and Doppler echocardiograms with superimposed TVI images were performed. Standard echocardiographic images were digitized during three consecutive cardiac cycles in cineloop format for off-line analysis. Strain and strain rate imaging for measurement of regional atrial function was done. The strain and strain rates were determined at the basal left atrial wall. Results: The mean age was 37.50±17.77 years in group A compared to 37.23±17.73 years in group B and 35.56±15.47 years in control group. There were 17 females in group A and 13 females in group B and 14 females in group C. There was no difference between the 3 groups regarding age and sex (P>0.05). There is reduction of the mean peak S sr in group A (1.536±.46 1/s) compared to (3.236±0.841/s) in group B and (4.950±0.5 1/s) in group C. This difference was statistically highly significant. (P< 0.01).There is also reduction of the mean peak E sr in group A (-1.774±1.21 1/s) compared to ( ±1.221/s) in group B and (-5.700±1.38 1/s) in group C. This difference was statistically highly significant. (P< 0.01).There is reduction of the mean peak A sr in group A (-1.180±.68 1/s) compared to (-3.616±0.85 1/s) in group B and (-5.700±1.38 1/s) in group C. This difference was statistically highly significant. (P< 0.01). The mean peak positive strain was markedly reduced in group A (12.573±3.488 %) compared to (17.833±5.45) in group B and (34.466±10.64%) in group C. This difference was statistically highly significant. The mean peak negative strain was markedly reduced in group A (-7.800±3.48 %) compared to ( ±4.81 %) in group B and ( ±3.78%) in group C. This difference was statistically highly significant. Conclusion: Strain and strain rate may provide a simple, and potentially clinically useful tool for quantifying atrial function in patients with mitral stenosis. Atrial pump function, conduit function and reservoir function are impaired in mild mitral stenosis and the degree of impairment increases with increasing the severity of mitral stenosis. Additional studies are required to evaluate the impact of these indices on risk for development of AF and hence prognosis in patients with mitral stenosis and value of therapeutic interventions. Key words: left atrial function atrial strain rate atrial strain Mitral stenosis Introduction Normal left atrial (LA) function consists of reservoir, conduit and pump function (1,2). Reservoir function occurs during left ventricular (LV) systole when the mitral valve is closed, the LA is relaxed, and the mitral annulus is temporarily displaced toward the apex (3). The left atrium acts as a conduit in diastole, when the mitral

2 leaflets open and allow blood to enter the left ventricle. At end-diastole, the left atrium contracts, and the pump function occurs (4). In mitral stenosis LA function may be disrupted because of increased LA afterload. Mitral stenosis resulting from rheumatic heart disease is associated with considerable fusion of the commissures and reduction of mitral valve apparatus and leaflet mobility (5, 6). Moreover, there is a marked increase in LA dimension and, consequently, an impairment of the LA pump function (5). Finally, when atrial fibrillation ensues, complete loss of LA pump function occurs as a result of cessation of LA systole (7). Left atrial appendage dysfunction may occur in patients with mitral stenosis in sinus rhythm and is associated with complications. (8) There is evidence that there is impairment of atrial contribution to ventricular filling even in mild mitral stenosis (9) Many methods were used previously to assess atrial function; invasive and non invasive. However; they are either difficult to be applied, time-consuming, inaccurate as they are load-dependent, and difficult to reproduce because they are observerdependent. Moreover some of these indices do not accurately evaluate atrial reservoir function. (10, 11). Recently the development of tissue Doppler imaging has enabled us to accurately evaluate myocardial properties in a load independent and reproducible method. Strain rate and strain imaging has the advantage of being not affected by translational movements i.e. reflects actually the myocardial deformation (12). Strain and strain rate imaging were used in the assessment of regional function of the LV, and RV. Normal values for strain and strain rate for atrial function were described For LA. Moreover; strain and strain rate values for the LA lateral wall, were correlated with the LA volumetric indicators during the contractile, reservoir and conduit LA phases (13). Assessment of atrial function in patient with mitral stenosis using strain and strain rate imaging was not done before. In this study the left atrial function in patients with mitral stenosis was measured by strain rate and strain imaging and compared with normal and healthy individuals. Relation between the severity of MS and indices atrial function is also determined. Patients and methods The study included 90 individuals; 30 patients with mild rheumatic mitral stenosis (mitral valve area (MVA) more than 1.5 cm²), 30 patients with moderate to severe rheumatic mitral stenosis (MVA less than 1.5 cm²) and 30 healthy individuals without mitral stenosis and with normal echo study were included as controls. All the patients were in sinus rhythm. Patients With coronary artery disease, hypertension, diabetes mellitus, mitral incompetence, associated aortic valve disease, patients with AF were excluded from the study.

3 Every patient was subjected to the following: Thorough history taking. Full clinical examination. 12 leads ECG. Full 2D, M-mode & Doppler transthoracic echocardiographic study in standard precordial views. LA regional longitudinal function & deformation properties were studied using strain and strain rate imaging and analysis techniques. All data were plotted into tables & statistically studied. Echocardiographic and Doppler studies: Echocardiographic and Doppler examination were performed using Vingmed Vivid 5 machine with 2.5 phased array imaging transducer with pulsed and continuous wave Doppler and color flow imaging capabilities. All patients were examined in supine and left lateral recumbent position. Examinations were performed by one experienced investigator; all the measurements of the ventricular parameters were recorded using the leading edge technique and following the recommendations of the American Society of Echocardiography, (14), where each dimension was measured at both end diastolic coinciding with ''R'' wave and end systole at the smallest systolic dimension, (15). The following measurements were obtained from the M-mode guided pictures in the parasternal short axis view: Left ventricular internal dimensions both at end diastole and systole (LVIDd and LVIDs) measured in cm. Thickness of interventricular septal (IVSd) and posterior wall at end diastole (PWTd) measured in cm. LV ejection fraction (EF) was calculated by modified Simpson s method (15). Left atrial (LA) diameter in parasternal long axis view was measured by M-mode. (16) Mitral valve echo score was also evaluated according to Wilkins score (17). MVA was calculated by planimetry and. Mean transmitral diastolic gradients was calculated by Doppler studies (18). Color flow Doppler was used to detect the presence of valvular regurgitation. Strain and strain rate calculation A Vingmed Vivid 5 GE machine Horton Norway echocardiographic machine was used in the examination of all patients. Apical 4 chamber view was used. The frame rate was increased to 150 to 200 per second. This was achieved by narrowing the angle of echo beam. Three cineloops were recorded and stored on the echopac using Tissue Doppler Mode. All cycles were gated with ECG. Offline analysis was done for the recorded cineloops to calculate longitudinal stain and strain rate between two points in the basal part of left atrial wall. The distance between these 2 points was equal to 9 mm. The segment of analysis lies in the basal part of lateral atrial wall midway between the epicardium and endocardium. This method of measurement of LA strain and strain rate correlates with LA volumetric indicators during the contractile, reservoir and conduit LA phases (14). Statistical analysis: All statistical procedures were performed by means of a personal computer using SPSS statistical package version 9. The mean peak atrial stain and strain rate in patients with mild and moderate to severe MS were compared with the

4 The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. sample of normal individuals. The relation between the severity of mitral stenosis and various indices for assessment of atrial function was also determined. Categorical variables were compared by Chi square test. Numerical results were expressed as mean ± SD. Independent T test was used to compare the clinical and echocardiographic variables between patients and control subjects. One way ANOVA was used to compare numerical data of the 3 groups. Correlation between variables was evaluated by Pearson s correlation. Differences were considered significant when P was less Figure (1): the pattern of LA strain rate for a normal individual. The figure shows three cycles; The S wave (S sr ) is 7 1/s.E wave (E sr) is -4 1/s.A wave (A sr) is -10 1/s. The atrial strain rate curve is characterized by 3 main waves, S, E and A, which coincide with the ventricular systolic, early diastolic and late diastolic periods respectively. The direction of the atrial strain rate is just the opposite to that of the ventricular strain rate curve. Negative strain rate makes the means that the segment is becoming shorter and a positive strain rate means that the segment is becoming longer. The S wave is a positive wave that reflects atrial reservoir function, the E wave is a negative wave representing rapid atrial filling, and the late diastolic negative strain rate peak reflects the regional atrial pump function (A wave).the strain rate is calculated from average of three cycles, in 1/s. Figure (2): the pattern of LA strain for a normal individual.

5 The figure shows two cycles, The peak negative strain (atrial systole) is -20 %.The peak positive strain (atrial reservoir) is 20 %. The atrial Strain curve Shows initial negative wave corresponding to atrial contraction, then positive wave representing atrial reservoir function. Results The study included 90 individuals. They were divided into 3 groups (A, B, C) those with moderate and severe rheumatic mitral stenosis; MVA less than 1.5cms (group A), and those with mild mitral stenosis; MVA more than 1.5 Cm² (group B), and a control group of normal individual without MS (group C). The age, gender, echocardiographic data and atrial size and function by strain and strain rate imaging were compared in the three groups. There was no statistically significant difference between the 3 groups regarding age, sex, left ventricular wall thickness, left ventricular end diastolic (LVEDD) and end systolic diameter (LVESD), left ventricular end-diastolic (LVEDV) and end-systolic volume (LVESV) and ejection fraction (EF). However, LA diameter was highest in group A (46.26 mm) compared to groups B (42.70 mm) and C (40.43 mm), post Hoc tests showed that the difference between the 3 groups was statistically significant. (p<0.05) (Table 1) C. Table 1; Age, gender and echocardiographic parameters of groups; A, B and Control Group C (N=30) MVA >1.5 cm² Group B (N=30) MVA<1.5 Cm² Group A (N=30) 35.56± ± ± Age, years 14(46.6%) 13 (43.3%) 17 (56.6%) Female, n 40.43±3.276* 42.70±2.972* 46.26±5.638* LA diameter (mm) 8.4± ± ±0.12 LVPWT (mm) 8.3± ± ±0.12 IVST (mm) 83±11 82±12 80±14 LVEDV (ml) 42±11 43±10 42±9 LVESV (ml)

6 64±7 62±5 63±8 EF (%) * p<0.05 The mitral valve area (MVA), mean transmitral pressure gradient (MPG) and echoscore were shown in table 2. The mean MVA was significantly lower in group A, mean MPG and echoscore were significantly higher in group A than in group B. Table 2; MVA, MPG and echoscore of groups; A and B. MVA<1.5 Cm² Group A (N=30) MVA >1.5 cm² Group B (N=30) T test P value MVA 1.047± ± MPG ± ± Echoscore 7.633± ± The S wave on strain rate curve (S sr) and peak positive wave on strain curve were used as an index of reservoir function The E wave on strain rate curve (E sr) was used as an index of atrial conduit function. The A wave on strain rate curve (A sr) and peak negative wave on strain curve was used as an index of atrial contractile function. The mean peak values were compared using one-way ANOVA. Table 3; the atrial function in the 3 groups, using strain rate and strain imaging. MVA<1.5 Cm² Group A (N=30) MVA >1.5 cm² Group B (N=30) MVA<1.5 Cm² Group C (N=30) F ANOVA p-value S sr(1/s) 1.536± ± ± A sr(1/s) ± ± ± E sr(1/s) ± ± ± Peak Strain (%)(negative) Peak Strain (%) (positive) ± ± ± ± ± ± All variables of strain rate (S sr, E sr and A sr) were lowest in group A and highest in group C. This difference was statistically highly significant. (P < 0.01). By doing Post Hoc tests to detect the least significance difference it was found that there is a statistically significant difference between the 3 groups. (Table 3). Similarly the

7 mean peak positive strain and negative strain were lowest in group A; and highest in group C. This difference was statistically highly significant. (P < 0.01). By doing Post Hoc tests to detect the least significance difference it was found that there is a statistically significant difference between the 3 groups. (Table 3). Thus, there is starting deterioration of atrial function in mild mitral stenosis, increasing with the increase of mitral stenosis severity. Correlations: The MVA narrowing and higher transmitral pressure gradient were correlated with impairment of strain and strain rate indices of atrial function (Atrial strain rate S, E and A as well as positive and negative strain). (FIG; 3,4,5 Tables 4,5). Similarly, increased age of the patients is correlated significantly with impairment of atrial function. (Table 6). Table (4): Correlation of MVA, to the Left atrial diameter and left atrial strain and strain rate parameters in mitral stenosis patients. Correlations MVA r P-value LA diameter Atrial S sr Atrial E sr Atrial A sr Atrial positive strain (R) Atrial negative strain (S) Highly Significant; P<0.01 Table (5): Correlation of MPG, to the Left atrial diameter and left atrial strain and strain rate parameters in mitral stenosis patients. Correlations r MPG P-value LA diameter Atrial S sr

8 The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. Atrial E sr Atrial A sr Atrial positive strain (R) Atrial negative strain (S) Highly Significant; P<0.01 Table (6): Correlation of Age, to the Left atrial diameter and left atrial strain and strain rate parameters in mitral stenosis patients. Correlations r P-value LA diameter Atrial S sr Atrial E sr Atrial A sr Atrial positive strain (R) Atrial negative strain (S) Highly Significant; P<0.01 Figure (3): Correlation between Mitral Valve Area and atrial S strain rate.

9 The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. Figure (4): Correlation between Mitral Valve Area and atrial A strain rate. Figure (5): Correlation between Mitral Valve Area and atrial E strain rate. Fig (6) The Figure shows the Strain rate of the left atrial free wall of a patient with mild MS (MVA=1.7 cm) on an average of three cycles. The S wave (S sr) is 3 1/s, E wave (E sr) is -2 1/s and A wave (A sr) is -4 1/s.

10 The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. Fig (7) the figure shows the strain of left atrial free wall of a patient with mild mitral stenosis, the peak negative strain is -12 and peak positive strain is 10. Fig (8)The figure shows the left atrial strain rate of a patient with tight MS (MVA =1 Cm²)There is reduction of the peak sr S wave to 1.4 1/s.There is reduction of E sr wave to /s.The A sr wave is markedly reduced to /s.

11 The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. Fig (9) Strain rate imaging of left atrial free wall of a patient with tight MS MVA =1 Cm². The strain curve of a patient with tight MS. The peak negative strain is - 5%.The peak positive strain is 10%. Discussion It is known that LA function is influenced by both atrial and ventricular factors. The atrial factors include LA contractility and relaxation, LA pressure and compliance and rhythm abnormalities. The ventricular factors include mitral annular displacement, LV compliance and relaxation. Mitral stenosis alters physiology and influences LA function. During atrial contraction, resistance is increased at the mitral valve, causing elevated LA pressure. In addition, there is increased atrial afterload (at the mitral

12 valve level) during atrial contraction, which may account for the decreased LA pump function. (5,6,) Mitral stenosis patients are prone to developing atrial arrhythmias, particularly atrial fibrillation and atrial flutter with worse outcome. Thirty to forty percent of patients with symptomatic MS develop atrial fibrillation (19). Thus; the proper assessment of atrial function is particularly important in patients with mitral stenosis as it gives an idea about the prognosis. However; the previously used methods for assessment of the atrial function are difficult or inaccurate. M-mode from parasternal long axis view provides a rapid and easy way that gives an idea about atrial size (16) however it is inaccurate as it measures left atrial dimension in one plane. Other sophisticated techniques have been used to assess LA function (20, 21) these methods require invasive determination of LA pressure to generate pressure-dimension loops. Several modalities such as nuclear scintigraphy and angiography have been used to assess LA performance by measuring changes in LA volume over time.(22,23). These techniques are limited by their expense, low temporal resolution, geometric assumptions, the need for contrast or radiopharmaceutical agents, and cumbersome acquisition. Hand drawn LA areas from two dimensional echocardiographic images are easier to acquire and have demonstrated abnormalities of LA function in patients with hypertension and dilated cardiomyopathy.(24,25) Manually traced two dimensional echocardiographic LA areas are limited by poor temporal resolution (typically 2-3 area values per cardiac cycle) and tracing of LA endocardial borders on a frame-frame basis is labor intensive and tedious. Doppler echocardiography has also been used to evaluate LA function. Several reports have suggested using pulmonary venous systolic flow as an indicator of LA reservoir function.(26,27) The peak velocity of mitral inflow during atrial contraction together with the atrial filling fraction have been used as non-invasive markers of LA booster pump function.(28, 29)These mitral inflow Doppler indices, however, provide no information on atrial size or reservoir and conduit function. Pulsed wave Doppler can be combined with mitral orifice area to compute LA ejection force (30); however, this parameter likewise only assesses LA active contractile function. Recently tissue Doppler imaging was used for the assessment of left atrial function. It has the value of assessment of the atrial reservoir, conduit and contractile function with low intra-and inter-observer variability (13). Other investigators showed that SR imaging combined with TVI enables noninvasive quantification of LA dysfunction due to hypertension and paroxysmal AF. They found that in hypertensive patients, paroxysmal AF decreases the efficiency, not the ability, of LA myocardia to reserve potential energy, which suggests that LA myocardial reservoir function decreases. This leads to decreased total active atrial contraction. (12) Atrial myocardial deformation properties predict maintenance of sinus rhythm after external cardioversion of recent-onset lone atrial fibrillation. Patients with higher atrial strain and strain rate appear to have a greater likelihood of staying in sinus rhythm. LA function assessment using atrial strain and strain rate were confirmed as independent predictors of sinus rhythm maintenance by multivariable analysis. (32)

13 Also, atrial strain rate echocardiography can predict success or failure of cardioversion for atrial fibrillation. (33) Thus assessment of left atrial function using strain and strain rate imaging is of clinical importance. In this study atrial and strain rate imaging were used to assess left atrial function in patients with mitral stenosis. The study included 30 patients with mild mitral stenosis; 30 patients with moderate to severe MS, and 30 normal individuals as control. The 3 groups were compared regarding the clinical and echocardiographic data (age, sex, LA size as assessed by m-mode, LV dimensions, EF). LA function was assessed by strain and strain rate imaging and compared in the 3 groups. The left atrial size by M-mode was highest in the group A, and lowest in group C. The difference between the 3 groups was statistically significant. Strain and strain rate imaging has the value of detecting minor differences in atrial function as well as assessment of reservoir, conduit and contractile function. This method of assessment of atrial function in mitral stenosis was not used before. Regarding atrial reservoir function; it was assessed by S wave on strain rate curve and the peak positive strain wave on atrial strain curve. Both values were markedly reduced in patients with moderate to severe MS, moderately decreased in patients with mild mitral stenosis compared to the normal group. The difference between the 3 groups was statistically highly significant. Thus mitral stenosis results in progressive deterioration of atrial reservoir function that may predispose to AF. Atrial reservoir indices were shown to be an independent predictor of maintenance of sinus rhythm after AF (32). Conduit phase was assessed on atrial strain rate curve by peak E wave. Similarly, it was lowest in group A and highest in group C. The difference between the 3 groups was statistically highly significant. Atrial pump function was assessed by A wave on SR curve and peak negative wave on strain curve. Both parameters were reduced in group A than in group B than in group C. Post Hoc tests showed this difference was statistically highly significant. (P < 0.01). Thus there is progressive impairment of left atrial function as a result of mitral stenosis that is related to the degree of severity of mitral stenosis. Starting even in mild mitral stenosis. The degree of impairment of LA function indices were correlated significantly with narrowing of MVA and increase of transmitral pressure gradient. This method of assessment of atrial function was not used before in mitral stenosis. However, other investigators (9) studied the atrial contribution to filling in mitral stenosis by combining noninvasive studies of patients with computer modeling. They found that there is impairment of atrial booster pump function contribution to ventricular filling which is more evident in severe mitral stenosis than in mild mitral stenosis. In addition, other investigators using echocardiography combined with hemodynamic studies, demonstrated that patients with mitral stenosis have increased LA size and

14 decreased LA pump function, as indicated by the decreased LA systolic emptying index and the decreased LA stroke work index. They also showed that the pressure area relation of the atrium rapidly returns to normal after relieving the increased LA afterload impedance by valvuloplasty. This finding suggests that the changes in LA contraction and LA chamber stiffness are not due to structural alterations of the LA because these changes would take time to resolve but are related to the degree of mitral stenosis. (34) In this study, age was significantly correlated with impairment of left atrial function, this may predispose to atrial arrhythmias in old age. Conclusion: This study showed that SR and S imaging is feasible and simple method for assessment of atrial function and it can evaluate impairment of the atrial booster pump function, reservoir function and conduit function. All of strain and strain rate indices were impaired in mild mitral stensosis compared to normal individuals. Also this indices are related to severity of mitral stenosis being more impaired in moderate to severe mitral stenosis. This impairment increases with age. Deterioration of atrial function may make the patients more prone for AF and thromboemolic complications. Recommendation: Further studies are needed to evaluate the prognostic impacts of strain rate and strain indices on maintenance of sinus rhythm in mitral stenosis patients and the development of complications. If these data are verified in future studies, then additional pharmacological therapy and maintenance of anticoagulants for a longer period may need to be considered in those with lower atrial train and strain rate measurements. References 1. Matsuzaki M, Tanitani M, Toma Y, et al. Mechanism of augmented left atrial pump function in myocardial infarction and essential hypertension evaluated by left atrial pressure dimension relation. Am J Cardiol. 1991; 67: Matsuda Y, Toma Y, Ogawa H, et al. Importance of left atrial function in patients with myocardial infarction. Circulation. 1983; 67: Keren G, Sonnenblick EH, LeJemtel TH. Mitral annulus motion. Relation to pulmonary venous and transmitral flows in normal subjects and in patients with dilated cardiomyopathy. Circulation. 1988;78: Grant C, Bunnell IL, Greene DG. The reservoir function of the left atrium during ventricular systole. An angiocardiographic study of atrial stroke volume and work. Am J Med. 1964; 37: Klein AL, Bailey AS, Cohen GI, et al. Effects of mitral stenosis on pulmonary venous flow as measured by doppler transesophageal echocardiography. Am J Cardiol. 1993; 72: Feldman T. Rheumatic heart disease. Curr Opin Cardiol. 1996; 11: Leistad E, Christensen G, Ilebekk A. Effects of atrial fibrillation on left and right atrial dimensions, pressures, and compliances. Am J Physiol. 1993; 264:H1093 H Golbazi Z, Cicek D, Canbay A et al. Left atrial appendage function in patients with mitral stenosis in sinus rhythm.. Eur J Echocardiogr Mar; 3(1): JS Meisner, G Keren, OE Pajaro, et al. Atrial contribution to ventricular filling in mitral stenosis. Circulation1991, Vol 84, Clarkson PBM, Wheeldon NM, Lim PO, et al. Left atrial size and function: assessment using echocardiographic automatic boundary detection. Br Heart J 1995; 74: Feinberg MS, Waggoner AD, Kater KM, et al. Echocardiographic automatic boundary detection to measure left atrial function after the maze procedure. J Am Soc Echocardiogr 1995; 8:

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