Abbreviations : BMI body mass index, BSA body surface area, RA right atrial, RV Right ventricle.
Discussion
This is the first study to provide normative age-related data for RALS in a Sub-Saharan African population. Additionally, we have also provided complementary data regarding RAVI according to age and gender in this population. RALS had tendency to decrease with age concurrent with a decline in RV diastolic function despite no alteration in RAVI, and BMI was an important independent predictor of RALS. Even though there was a tendency of RAVI to be higher in males, RAVI and RALS were not influenced significantly by gender.
Previous studies using 2DE by Y Wang et al. in 1984, and S. Kou et al. from the Normal Reference Ranges for Echocardiography (NORRE) study 2013, were focused on Caucasians populations, and were in line with the ASE and ESC 2015 chamber quantification guideline document, which states that RAVI should be <33 mL/m2 (or <35 mL/m2 in men and <31 mL/m2 in women)(23,24). In this study we found that, while the lower limits were similar to those of ASE and ESC guidelines, the upper margins were much lower (20.8 ± 6.3 mL/m2 in male and 18.7 ± 5.2 in females). Studies in African and Asian populations by Nel et al. and Asian by Karki et al. respectively have also observed the same pattern.(25,26) Soulat-Dufour with WASE study 2,008 healthy adult individuals around the world, has shown that generally, Asian subjects have lower BSA compared to subjects in non-Asian countries.(16) Ethnicity may cause variation in genetics and parameters of BSA and BMI and thus may directly influence echocardiographic measures. Thus, correlation between ethnicity and RA volumetric parameters is important.
In this study, there was a trend towards higher RAVI in males when compared to females but no influence of age on RAVI was noted. The aforementioned finding was akin to the recent study by Nel et al. and the WASE pertaining to RAVI in a normal population. Grünig et al. and D’Ascenzi et al. have shown that males have a larger RA area compared to females, explaining volume differences between the gender.(27,28) D’Oronzio et al ,Y. Wang et al. and Peluso et al. using 2DE and 3DE respectively, did not find any correlation between atrial volume and ageing for reasons that are not fully understood.(23,29,30)In the current study the mean RALS was 32.7 ± 10.5% , which was lower than the value reported by Padeletti et al. and D’Ascenzi et al.(22,28) In the aforementioned Italian comprising 84 and 74 subjects, RALS was documented using the 2D STE and the mean RALS was 49 ± 13% and 48±12.68 % respectively .(22,28) The above-mentioned studies were done in a group of subjects with overall lower BMI ( 22.4± 3.5 kg/m2) in contrast to the current study ( 24-34.9 kg/m2) and, is the likely explanation for higher RALS in their cohort. The following paragraph describes in detail the influence of obesity on RALS.
Obesity has been a health problem of growing significance all over the world; its prevalence is increasing in both developed and developing countries. According to WHO data, 39% of the global population above 18 years of age are overweight and of these ,13% are obese. In Africa there is a significant obesity trends, with increments in BMI documented in both gender.(36) Micklesfield et al. studied South Africa population from Soweto and demonstrated a significant gender difference with regard to BMI, with women being remarkably overweight and obese.(37)
In this study 67% of normal volunteers had BMIs above 25 kg/m2 , which occurred more commonly in women (49 %). BMI was the only independent predictor of RALS in this study. An inverse relationship was noted between BMI and RALS in the current study. Recent study by Chirinos et al. quantified left atrium (LA) strain and strain rate (SR) via STE among 1,531 middle-aged community-based participants enrolled in the Asklepios study. They demonstrated that longitudinal LA strain measured using STE decreased with elevated BMI.(33)
Obesity has been shown to have many effects on cardiovascular structure and function. Excess adiposity imposes an increased metabolic demand on the body and both cardiac output and total blood volume are elevated in obesity leading to a hyperdynamic circulation, which causes LV and RV structural changes in obesity and subsequently leads to increased ventricular mass and cavity dilatation. Obesity is the main lead in tissues fibrosis formation.(38) Sokmen et al., and Csige et al. showed that uncomplicated obesity was associated with RV and RA dilatation, and increased thickness of the RV free wall. Also, these structural indices were found to be positively correlated with BMI. Myocardial fat accumulation as a consequence of obesity, may cause atrial interstitial fibrosis and subsequently atrial dilatation and stiffness.(39,40) This may be a possible mechanism explaining the inverse relationship of BMI and RALS in this study, that obesity may result in RA fibrosis, stiffness with a consequent reduction in myocardial deformation and RALS.
Furthermore, this study demonstrates that RALS tended to decrease with age and males tended to have higher values compared to females, though this finding did not reach statistical significance.
Aging is associated with the development of myocardial fibrosis. Fibrotic tissue is stiffer and less compliant, resulting in subsequent cardiac dysfunction.(31,32) . We hypothesised that a combination of stiff RA and RV diastolic dysfunction associated with age related myocardial fibrosis will have a poor myocardial deformation and this may result in age related decrease in RALS. However, we did not perform biomarkers or CMR imaging to objectively assess for presence of fibrosis in this study.
The trend towards gender differences of RALS (though not statistically relevant) could be multifactorial in this study. In addition to a difference in biology, a higher BMI in females compared to males may explain the aforementioned finding. Male participants were also younger and had higher RAVI and likely more compliant RA compared to females which translated into higher RALS. Further, males had a lower heart rate compared to females ( 65.0 (59.0-76.5) beats/min vs 76.0 (67.0-82.5) beats/min, P=0.002) which allowed for a prolonged filling time of RA chamber and thus increased stretch of the right atrial wall with resultant higher RALS.
Padeletti et al. did not find differences in RALS gender and ageing. This lack of association between RALS , gender and aging may be related to the limited capacity of the software in identifying all the segments of the RA due to the higher tricuspid annulus deformation compared to the mitral valve .. Furthermore, this may be attributed to varying sample sizes and racial differences in the two studies . With the recent technologies Nemes et al., and Yang-Yang Qu et al. using three-dimensional speckle tracking echocardiography (3DSTE) and CMR respectively , have demonstrated obvious gender differences in RA strain. In contrast to our findings, they noted RA strain to be higher in females and showed an age related decline in both genders.(34,35) The differences in analysis software and technique used by the above-mentioned studies may explain the discordances in results. Further studies are warranted to confirm our findings in a larger African population and also to further assess RALS. We have also confirmed the utility of RALS as a marker of subclinical disease in this population as we did not see changes in RAVI with age but noted a trend towards lower RALS with increasing age., Thus, RALS may anticipate the RA impairment in diseases prior to changes in traditional parameters such as RA size and volumes. This may aid in earlier diagnosis of disease and prompt treatment strategies at a subclinical stage of the disease.