In the present study, we focused on the impact of LA function on outcome in patients with severe AS. To the best of our knowledge, this is the first study to extensively evaluate the prognostic value of LA functional assessment using classic volumetric parameters in current era severe AS patients. We found that LA function, evaluated by echocardiographic volumetric parameters, is a strong predictor of all-cause mortality, not only in patients who underwent AVR but also in patients who remained on conservative treatment. When compared to other classical prognostic factors in AS such as AVA, Vmax, MPG and LVEF, LA function was a better predictor of mortality during follow-up. Also, this effect of LA function on prognosis remains true even after adjustment for other factors that are known to affect prognosis in AS, such as age, LVEF, AVA, other concomitant valvular disease and comorbidities. Diminished LAEF (LAEF ≤ 53%) was associated with increased risk of all-cause death during follow-up, and was the best echocardiographic predictor in our study. Other LA functional parameters were still powerful predictors of adverse outcome, mainly LAAEF. Also, the impact of LA functional assessment remained significant across different AVA and LA volumes, in patients with preserved or depressed left ventricular systolic function and different degrees of left ventricular hypertrophy. Additionally, our results show that LA functional parameters remain good predictors of mortality after AVR, despite the important impact of the procedure on mortality of these patients. We also found that LA functional assessment is reproducible, easy and fast to obtain, as different phasic volumes were measured by the biplane method of disks, routinely used in the majority of echocardiography laboratories and the recommended method of measuring left atrial volume . Thus, based on the aforementioned findings, we suggest that LA functional evaluation should be performed in all patients evaluated for severe aortic stenosis and the results should be taken into consideration for the management of these patients.
The background of chronically increased left ventricular afterload in AS is associated with structural and functional changes in the LA. LA enlargement, the most common macroscopic LA structural change, has been considered the most direct noninvasive proof of increased LV filling pressure and diastolic dysfunction [6, 7]. Also, it has been recently associated with higher mortality, even after AVR [18, 30]. Besides LA dilatation, the ongoing pressure overload leads to disturbance in the LA three functional phases: reservoir, conduit and contractile phase , particularly in the contractile phase. In our study, we found a reduction in all phasic LA performances, when compared to control groups of patients without cardiac disease [8, 14, 31] and the results from NORRE study, in which 371 healthy subjects were enrolled in order to obtain normal ranges for echocardiographic measures of LA function . As reported in previous studies, the intrinsic left atrial myopathic disease can precede visible LA structural changes, being an early marker of increased LV filling pressures [8, 33]. This finding can explain the patients with normal LA volume and depressed LA function found in our cohort, which showed higher echocardiographic measures of diastolic dysfunction such as elevated septal e’ velocity and higher E/e’ ratios. As AS is a disease in which elevated intracavitary pressures play a very important role in its progression, the finding of LA functional change may represent an important milestone in which AVR may play an important role in its modification. As such, LA volume and function best capture the cardiac remodelling associated with AS, contrary to other echocardiographic variables.
While much is known about LA structural damage as a predictor of death in different diseases such as dilated cardiomyopathy , myocardial infarction , mitral regurgitation  and more recently in AS , there is limited information regarding LA function as a predictor of prognosis in patients with AS. There have been some reports showing that LA function assessed by speckle-tracking echocardiography can predict worse outcomes in AS patients. In a study conducted in our center, Marques-Alves et al. found that, in a population of patients with moderate and severe AS, LA global strain was the best discriminator of AS severity and a significant predictor of a composite of heart failure, death and AVR . The same study also found that atrial mechanics were better predictors of prognosis that LV global longitudinal strain, which was not a significant predictor of outcome. In another study by Todaro et al., which recruited 89 asymptomatic patients with severe AS and normal LVEF and 40 age- and gender-matched controls, in which LA and LV mechanics were measured by speckle-tracking echocardiography, LV global longitudinal strain, LA reservoir and LA stiffness were found to be strong predictors of adverse events during follow-up . However, on multivariate analysis only LV global longitudinal strain remained a significant predictor of events recurrence. Galli et al. also found that in a population of 128 patients with severe AS, global peak LA strain measured by speckle-tracking echocardiography was a significant independent predictor major adverse cardiac events . No study has evaluated the impact of volumetric assessment of LA function on outcome of severe AS patients, as in all LA function was assessed by speckle-tracking echocardiography. This technique has some advantages compared to volumetric methods, as it makes no geometric assumptions, does not need to make multiple plane acquisition and is, theoretically, less time consuming. Although the risk of LA foreshortening and the assumption of a geometric model of a non-symmetric chamber are real, we found LA volumetric assessment to be an easy, reproducible and fast method of LA evaluation. Besides, if the intention is to measure LA emptying fractions, the problem of foreshortening and eventual underestimation of LA volumes is less important, as it would not impact on the emptying fraction values. STE also has some limitations, as it is prone to suboptimal tracking of the endocardial border, is sensible to acoustic shadowing and reverberations, is not absolutely angle-independent and relies on good image quality. Moreover, each provider has his own software package and it is not available in every echocardiography laboratory.
Other published studies that addressed the impact of LA function on prognosis used as outcome a composite of heart failure, death and AVR , occurrence of symptoms and death  and major adverse cardiac events , outcomes that can be broad. In our study, the measured outcome was all-cause mortality, still, the best predictor of outcome found (LAEF representing LA reservoir function) showed very good predictive value. Also, our study had a long follow-up period compared to other studies, which is important not only to reduce immortality bias but also to better understand the clinical course of AS patients.
Our study had a retrospective design and, as such, has the inherent limitations of such studies. We did not record the specific indications for AVR, however, all decisions for AVR were taken in a heart team with extensive experience in valvular heart disease and who assures good practice according to guidelines. We included only patients with severe AS, so we can not extrapolate our findings to moderate or mild AS or even to other valvular diseases. Also, we excluded all patients with AF at the baseline exam and with previous history of the disease. This criterion excluded many patients from analysis. However, we registered the development of AF during follow-up, which gave us the possibility to evaluate its impact on patient prognosis. We did not record any analytical parameters such as natriuretic peptides or serum creatinine, thus, we did not know in what measure they could influence our results. Finally, we did not record the reason for conservative management, so we do not know the extent of patient AVR refusal or what led our heart team to make that decision.