The left atrium (LA) plays an essential role in the cardiovascular system, as it functions as a blood reservoir, conduit, and booster pump. The importance of the reservoir function is emphasized by the fact that 42% of the left ventricular (LV) stroke volume is stored in the LA during LV systole.¹⁾ Furthermore, LA size is known to be an important risk factor for the development of atrial fibrillation²⁾ and a major predictor of cardiac death and clinical outcome in patients with dilated cardiomypathy.³⁾ In addition, LA size has a crucial role in mitral valve competency,⁴⁾ and also reflects the chronicity and duration of LA hypertension and LV diastolic dysfunction.⁵⁾

The atrial walls consist of intricately intermingled muscular bundles oriented circumferentially and longitudinally⁶⁾ with individual contractilities. Tissue velocity, strain, and strain rate have been shown to be less load-dependent regional quantitative parameters that reflect regional contraction and relaxation.^{7), 8)} Although numerous tissue Doppler imaging studies have been undertaken to assess LV contraction and relaxation, LA tissue velocities and strain have been relatively neglected. Some researchers have used sonomicrometry to measure strain, but these investigations have been performed using open chest animal models.⁹⁾ Real time 3-dimensional echocardiography provides more spatial information on the cardiac chambers and more accurate measures of true LA volume.^{10), 11)} However, few reports have been issued concerning the association between LA regional tissue velocity and strain, and LA volume change in humans.

In the current study, we have comprehensively determined non-invasive variables, such as LA regional tissue velocity, strain, strain rate, and volume in real clinical situations in the hope of adding to our understanding of normal LA contractile physiology and extending this information to patients with mitral stenosis (MS) or mitral regurgitation (MR). Specifically, we have evaluated the longitudinal, radial, and circumferential myocardial contractility of the LA wall using tissue Doppler imaging to measure regional tissue velocity, strain, and strain rate. LA time-volume curves were obtained by real time 3-dimensional echocardiography. We assessed the relationship between peak systolic tissue velocity and maximal LA volume and between time-to-peak strain and time-to-maximal LA volume. Furthermore, these parameters were compared between echocardiographically-normal hearts and hearts of patients with MS (pressure overload state) or MR (volume overload state). In this study, we sought to investigate the hypotheses that longitudinal and circumferential contractilities are more important than radial factors in determining LA volume change due to anatomic fiber orientation, and that volume and pressure overloads have different effects on LA contractility.

In the present study, we investigated the hypotheses that longitudinal and circumferential contractile parameters are more important than radial factors when determining LA volume change, and that pressure and volume overloads have different effects on LA contractility. The study showed that LA longitudinal and circumferential deformations were more related than radial deformation in determining LA volume and function in healthy controls, and that the LA volume change of patients with MS was related with more extensive segmental contractile parameters than in patients with MR. The posterior wall was unexpectedly shown to have an important role in determining LA volume change in this study.

Many studies have examined LA systolic function using a variety of parameters, such as LA emptying volume and LA emptying volume fraction,^{13), 14)} LA fractional shortening or fractional area change,¹⁵⁾ Doppler transmitral flow parameters (peak A wave velocity and its time-velocity integral, or E/A ratio,¹⁶⁾ LA work load,¹⁷⁾ LA appendage flow velocities,¹⁸⁾ atrial ejection fraction,¹⁹⁾ and LA kinetic energy²⁰⁾) and by tissue Doppler imaging of the mitral annulus during atrial systole.²¹⁾ However, some of these measurements require invasive procedures,^{17), 20)} whereas other measurements are highly sensitive to changes in cardiac loading conditions, LV systolic function, and autonomic state.^{19), 22)} The assessment of LA function is thus complex and the accuracies of these parameters in terms of measuring atrial contractility is limited. However, tissue Doppler imaging and 3-dimensional echocardiography are relevant to the non-invasive evaluations of regional tissue contractility and volume data. Furthermore, tissue Doppler imaging is relatively independent of preload and afterload changes,^{7), 8)} and enable quantitative assessment of LA contractile function.²³⁾ This is the first report to address LA physiology in relation to associations between LA volume change and regional tissue velocities and strains in humans.

In the healthy control group, the LA posterior walls had significantly lower tissue velocities than the anterior walls. This may have been due to a limited motion and contractility of the posterior wall due to the insertions of four pulmonary veins and their associated muscular structures.⁶⁾ Circumferential and radial tissue velocities were found to be significantly lower than longitudinal tissue velocities, which demonstrates the important role played by longitudinal muscular motion in LA volume changes. However, myocardial deformations did not follow the same patterns as motion changes. The LA septal longitudinal strain was lower than that of the anterior wall due to differences in muscular components. In healthy controls, maximal and minimal LA volumes were positively correlated with LA active emptying and filling velocities, but no significant correlation was found for LA active emptying fraction. LA contractility did not change in line with volume changes within the range of normal values. The maximal LA volumes were negatively correlated with the posterior wall longitudinal peak systolic strains and strain rate due to an expanding deformational reserve of the posterior wall in the case of a small LA volume. The time-to-maximal LA volume was positively correlated with the time-to-posterior wall longitudinal peak strain and longitudinal peak tissue tracking, and with the time-to-circumferential peak strain. These findings suggest that longitudinal deformation of the posterior wall and circumferential deformation, rather than radial deformation, are important determinants of LA volume despite low tissue velocities at these walls. The LA active emptying fraction was positively correlated with the posterior wall longitudinal peak systolic and late diastolic tissue velocities. The above findings show that posterior wall tissue velocity is an important factor of LA contractility.

LA volumes were larger in both the MS and MR patient groups than in the healthy controls, but no significant difference was found between the two patient groups. The LA active emptying fraction values of the patient groups were lower than the normal controls due to an exhausted atrial wall after LA enlargement, or due to LA booster pump failure as a result of LA afterload mismatch in MS patients as in patients with hypertrophic cardiomyopathy.²⁴⁾ These findings are consistent with previous reports.^{25), 26)} The mean LA filling velocity of the patients with MR was greater than that of patients with MS, despite similar maximal LA volumes and active emptying velocities. This finding is a natural result of systolic mitral regurgitant volume. Almost all regional tissue velocities were lower in the patients with MS and MR than in controls, despite regional differences. The septal longitudinal peak systolic and late diastolic tissue velocities were not significantly different in the patient groups and controls, which was probably due to a membranous thin septal wall as compared with other LA walls, and sensitivity to the left and right atrial volume and pressure changes.

Patients with MS had a negative correlation between LA volume and LA active emptying fraction, which was not observed in healthy controls. Furthermore, patients with MR had a negative correlation between the minimal LA volume and the LA active emptying fraction. Therefore, an increased volume due to compensatory adaptation to an increased afterload and preload resulted in decreased LA contractility in these patients. In patients with MS, the maximal LA volume was negatively correlated with the radial peak systolic tissue velocity and the longitudinal late diastolic tissue velocity of the posterior wall. However, the maximal LA volume was positively correlated with the radial peak systolic tissue velocity in patients with MR. The cause of this difference cannot be explained although it is possible that pressure and volume overload may induce different effects on the regional Frank-Starling mechanism of the LA in the radial direction.

In patients with MS, the time-to-maximal LA volume was positively correlated with the time-to-longitudinal peak strain of the anterior and posterior wall, whereas the MR patients had a positive correlation between the time-to-maximal LA volume and the times-to-longitudinal peak strain of the lateral and posterior walls, and the time-to-circumferential peak strain. The importance of the longitudinal deformation in terms of determining the time-to-maximal LA volume was preserved in both patient groups despite regional differences, but the importance of circumferential deformation for determining the time-to-maximal LA volume was preserved in the patients with MR only. Furthermore, the patients with MR showed a positive correlation between the time-to-maximal LA volume and the time-to-longitudinal peak tissue tracking of the posterior wall and septum, and the time-to-circumferential peak tissue tracking, rather than the time-to-radial peak tissue tracking of the LA, whereas patients with MS had additional positive correlations between the time-to-maximal LA volume and the time-to-longitudinal peak tissue tracking of the anterior and lateral walls. In the patients with MS, the LA active emptying fraction showed a positive correlation with the longitudinal late diastolic strain rates of the anterior and lateral walls, whereas in the patients with MR, the LA active emptying fraction had positive correlations with the longitudinal late diastolic strain rates of the posterior and lateral walls and with the radial late diastolic strain rates. The LA of the patients with MS revealed a greater pathologic physiology than those of MR patients.

This study had several limitations. First, tissue Doppler imaging is angle-dependent, whereas the recently developed 2-D speckle tracking imaging is independent of angle. However, the thickness of a region of interest cannot be reduced to include exclusively thin atrial walls in 2-D speckle tracking imaging. Accordingly, we selected tissue Doppler imaging to measure tissue velocities and strains of thin LA walls. Second, the mean age of the patients with MR was greater than the healthy controls and the patients with MS, and thus the results may have been influenced by patient age. However, aging increases LA tissue velocities and active emptying fractions due to augmented atrial contractility.²⁷⁾ In the present study, the patients with MR had lower LA regional tissue velocities and active emptying fractions than healthy controls. Therefore, age may have attenuated the results in MR patients. Third, this study did not present a comparison with a gold standard, such as cardiac MRI, due to cost.

In conclusion, this is the first report to address LA physiology in relation to associations between LA volume change and regional tissue velocities and strains in humans. LA longitudinal and circumferential deformations are more related than radial deformation in determining LA volume and function in healthy controls. The LA posterior wall was unexpectedly shown to have an important role in determining LA volume change in this study. The LA of patients with MS revealed a greater pathologic physiology than of the patients with MR. The results of this study have a clinical impact on understanding the regional influence in LA volume change and function and understanding the different time sequences of the development of atrial fibrillation in patients with MS and MR.

This study was supported by a grant of the Korean Society of Cardiology (Industrial-Educational Cooperation, 2005).