Characterization of left and right atrial function in healthy volunteers by cardiovascular magnetic resonance

Left atrial function

As a continuum of the left ventricle (LV), especially during diastole, LA size and function are very much influenced by ventricular compliance. LA size is a powerful predictor of adverse cardiovascular outcomes, but LA function has not been so extensively elaborated [20]. Technical advances have allowed the non-invasive characterization and quantitation of LA function with imaging techniques, including echocardiography, cardiac computed tomography [21], nuclear scintigraphy and CMR. Echocardiography is the simplest and most cost-effective method and has been validated for the study of LA function with two-dimensional linear and volumetric measurements [22], pulsed wave Doppler [23], acoustic quantification [24], tissue Doppler [25] and speckle tracking imaging [26]. Still, problems with acoustic window and reproducibility may affect their use. As for cardiac computed tomography and nuclear scintigraphy, the low temporal resolution and need for contrast and radiopharmaceutical agents limit their use.

CMR provides very accurate and reproducible volumetric measurements of both atria with the short axis method along the cardiac cycle, and it is the gold standard technique for the assessment of atrial volumes [16, 17]. The area-length method is more frequently used in clinical practice since it does not require additional acquisitions and the analysis is faster, but it relies on geometric assumptions and is less reproducible. More recently, CMR feature tracking analysis has been introduced that provides a faster assessment of LA function, with a loss of reproducibility as it also relies on the area length method [27, 28]. In our study we have obtained with the short axis method a reference range for all parameters of LA reservoir, conduit and booster pump functions, with differentiation into all subjects, males and females, and sub-division into age groups and absolute and BSA normalized values. For the whole group we obtained a value for total LA emptying—or ejection—fraction of 59?±?5.8 %, 35?±?6 % for passive emptying fraction and 36?±?6.8 % for active emptying fraction. Interestingly, the confidence intervals are wide and this could be due to the variable shape of the atria in normal subjects, resulting in a wide range of normal values in both men and women. Also, there are some values, both for LA and RA, where a negative confidence interval value is observed. This is only a result of the statistical modeling but should not be considered clinically as it is not physiologically possible. Very few data obtained with CMR are available to compare our results. Raman [29] found in a small group of 15 controls studied with either SSFP or gradient echo sequences a TEF of 32?±?5 %, hardly comparable to our results due to methodological differences. Hudsmith [30], using the biplane area-length method in 108 healthy subjects, obtained a TEF of 54?±?12 %. Le Ven [31], using a short axis volumetric method in 434 healthy adults, found LA ejection fraction of 59?±?8 % for males and 61?±?7 % for females. We have not found reports on other parameters measured with CMR for comparison. These have been measured with different echocardiographic techniques but they are not comparable [22, 24].

We observed that atrial volumes were associated to BSA, which were then normalized to this parameter. On multivariate analysis gender affected only one reservoir function parameter, EI, and one booster pump function marker, PAE, while it had a significant independent influence on most conduit function parameters including PEV, CV, PEF, PEI and PPE. There are very few CMR studies with which to compare our results. Le Ven [31] observed that gender was independently associated with LA ejection fraction (equivalent to TEF in our study) while Hudsmith [30] reported no differences in LA ejection fraction between males and females. Data are then controversial and in none of those studies were specific parameters of conduit or booster pump function measured. More data are available from echocardiography. Nikitin [32], with 2D echocardiography in 123 healthy volunteers, showed no differences with gender in LA function parameters, including EI, PEF and AEF. Accordingly, Morris [33] in 329 healthy adults studied with speckle tracking echocardiography showed no differences in peak atrial strain rate during atrial contraction and peak atrial strain during atrial relaxation, which would be concordant with our findings. Interestingly, though there is no clear knowledge or explanation for gender differences in atrial function, an animal study [34] has shown sexually dimorphic responses to extracellular calcium, isoproterenol and phenylephrine which would suggest a possible role of sex hormones in these differences.

We found differences between younger and older individuals for all absolute and normalized parameters, except on absolute and normalized TEV, with significantly lower reservoir and conduit function parameters and higher booster pump function parameters in the older age groups. There is a general agreement, using different imaging techniques, over the significant effect of age on global and regional LA function [22, 24, 35]. The decline in passive emptying probably represents an age related change in left ventricular properties leading to diastolic dysfunction, with an increase in active emptying which compensates for the decrease in early diastolic filling. Nevertheless, Hudsmith [30] found no influence of age on LA ejection fraction and Le Ven [31] did not assess this. The majority of studies have been carried out with varied echocardiographic techniques and results support our findings notwithstanding the methodological differences. Nikitin [32] found no effect of age on reservoir function, while there was a progressive decrease in conduit function and an increase in booster pump function with age. Triposkiadis [22] with pulsed wave Doppler echocardiography observed a clear effect of age on LA function with findings very similar to our study. Okamatsu [36], with two-dimensional speckle tracking echocardiography in 140 volunteers also observed that aging significantly decreases LA conduit function and increases booster function.

The differences observed with age might have clinical importance. For instance, in 1802 participants in the Dallas Heart Study [37] it was shown the incremental prognostic value of LA ejection fraction (LAEF), measured with the area-length method, beyond traditional risk factors, LV ejection fraction, and LV mass: decreasing LAEF [hazard ratio per 1 standard deviation, 8.0 %) was independently associated with mortality. In this study a significant association of LAEF with age was seen. If we examine that single parameter of LA function in our study, the lower limit of normality for LATEF for the whole group, as shown in Table 2, was 51 % in the younger age group and 44 % in the older age group which represents a decrease of 13 %, or 1.2 standard deviations. Consequently, even just for this single parameter the differences seen with age are sufficiently large and they would affect the clinical interpretation of the results. In another investigation carried out with echocardiographic techniques, LA EF was shown to be a powerful independent predictor of new-onset atrial fibrillation and atrial flutter in 574 elderly participants [20]. Patients at highest risk were those with both LAEF 49 % and LAVi 38 ml/m2, and LAEF was superior and incremental to LAV. In our CMR study, though we are aware that there is not an equivalence between parameters measured with echocardiography and CMR, a LATEF of 49 % would be abnormal in young people but it could be normal in the older.