Indexing of Left Atrial Volume by Body Surface Area and Height in a Brazilian Population without Previous Heart Disease and with a Normal Heart on Echocardiography. Behavior in Obese and Overweight Patients

Background: Left atrial (LA) volume indexing for body surface area (BSA) may underestimate LA size in obese and overweight people. Since LA volume is a risk marker for some cardiovascular events, it is suggested that indexing for height would be an alternative more appropriate method. The aims of this study were to find normal and the best cutoff values for LA volume indexed for height in our population. Methods: Echocardiograms from 2018 to 2021 were reviewed and patients without known cardiac disease and completely normal echocardiograms that had the left atrial volume (LAvol) measured by biplane Simpson’s method were included. LAvol was indexed by BSA (ml/m2), by height (LAvol/m), by height raised to exponent 2.7 (ml/ m2.7) and by height squared (ml/h2). Results: A total of 545 patients, 50.5 ± 13.4 y., 335 females (61,5%) were analyzed. There were 145 normal weight (26.6%), 215 overweight (39.4%), 154 obese (28.3%) and 31 low weight (5.7%) patients. To establish normal values we included only the normal weight group and considered normal values from 2SD below to 2SD above the mean. Mean and normal values were: LAvol/h 26.0 ±4.5, 17 – 35 ml/m, LAvol/ht2 16 ± 2.8, 10.4 - 21.6 ml/ ht2 and LAvol/ht2.7 11.4 ± 2.2, 7.0 - 15.8 ml/m2.7. The normal LAvol/ht2.7 differed between male and female (11.4 ± 2.4 and 12.8 ± 2.6, p < 0.001). LA diameter, LAvol, LAvol/h, LAvol/h2 and LAvol/ht2.7 increased progressively from low-weight, normal weight, overweight and obese patients (p< 0.0001), but not LAvol/BSA. When indexing LAvol for height, for height2 and for height2.7 20.8%, 22.7% and 21.4% of the obese patients, respectively, were reclassified as enlarged LA, and 7.4%, 8.8% and 8.4% of the overweight patients as well. Using ROC curve analysis, LAvol/h2 had the highest AUC ant the best predictive value to identify LA enlargement and LAvol/BSA the worst one. Conclusions: Normal values for LAvol indexed for height by three different methods are described in normal individuals. We reinforce that LAvol indexation for BSA underestimates LA size in obese and overweight patients and in these groups, specially, indexing for height2 is probably the best method to evaluate LAvol.


Introduction
Increased left atrial (LA) volume is a risk marker for atrial fibrillation, stroke, and heart failure, and it has been correlated with increased cardiovascular mortality [1][2][3][4][5][6][7]. International guidelines and clinical practice recommend that LA volume be indexed to body surface (B.S.A.) [8,9]. However, in obese individuals there is a tendency to underestimate these values, often placing individuals with an enlarged left atrium as normal, after indexing by a high B.S.A.. This is an important problem, because obesity is associated with atrial fibrillation [10] and it appears to be mediated by left atrial dilatation [11]. The prevalence of obesity is increasing, it is likely that prevalence of obesity-related AF will increase as well. B.S.A. is an isometric measure, which assumes that LA size has a linear relationship to body size. However, organ size (i.e., heart size) and body size do not grow proportionally; in other words, their relationship is nonlinear [12]. Many parameters can be indexed for height, especially in obese individuals. Alternative forms of scaling, including allometric size variable such as height raised to an exponent, may help address this issue [12,13]. The normal values and how the left atrial volume indexed for height behaves in obese and overweight individuals under normal conditions of cardiovascular health is not well explained in the literature, especially in a Brazilian population. The current work aims to clarify these questions.

Methods
This is a pilot, observational, descriptive, retrospective study. Echocardiographic data, age, sex, weight, height and body surface were obtained from the data file of the echocardiography service of Hospital Ana Nery, from 2018-2021. Patients with normal echocardiograms, in sinus rhythm, with no history or evident cardiovascular disease (mild systemic arterial hypertension and non-insulin dependent diabetes without target organs involvement), were included independent of any other factor. In all patients, in addition to LA volume, LA and LV dimensions, wall thickness, left ventricular mass, LV ejection fraction, and aortic root diameter were also recorded. Left atrial volumes were obtained by the Simpson's biplane method of disks using apical four chamber and two chamber views at ventricular end-systole. The data of each patient were reviewed to verify there was no missing data and to be sure that the exam was normal, with special attention to LV diastolic dysfunction parameters, such as the E' waves of the medial and lateral mitral annulus. Exclusion criteria: any parameter of abnormality such as LA maximum diameter at the parasternal long axis > 40mm, indexed LA volume > 34ml/m², left ventricular wall relative thickness > 0.42, increased left ventricular indexed mass, ejection fraction less than 55%, any change suggesting LV diastolic dysfunction such as reduced medial (< 7cm/s) or lateral (<10cm/s) and mitral regurgitation more than minimal. A total of 645 charts reported as normal echocardiograms were reviewed, and 545 patients were included in the study. The protocol of the study was approved by the Research Ethics Committee of the Hospital Ana Nery (HAN/SESAB), Salvador-BA, which waived the need to obtain written informed consent.
The LA volume were than indexed for B.S.A., height, height² and height 2.7 in four groups of patients:

Data Analysis
Quantitative data are described as mean ± standard deviation and IC 95%. Categorical data are described as an absolute number and percentage. The means, standard deviations (SD) and 95% confidence intervals (CI) of the quantitative variables were obtained for the total of patients and for the subgroups. To comparisons, we considered normal indexed left atrial volume for height, height² and height 2.7 the interval from 2 SD below and 2 SD above the mean of the normal weight group (B.M.I. ≥ 20 kg/m² and < 25 kg/ m²). Student's t test was used to compare means between two independent groups, and the ANOVA test of variance for comparisons between the three groups according to B.M.I. (normal, overweight, and obese) with the Bonferroni test for post hoc analysis between pairs of groups. The chi-square test was used to compare categorical variables. Receiver operating characteristic (ROC) curve analysis was used to identify the indexation method that best predicted increased LA. Statistical analysis were performed with IBM SPSS statistics version 21. Statistical significance was considered as P < 0.05 two-tailed.

Results
A total of 545 patients, mean age 50.5 ± 13.4 y., 335 females (61,5%) and 210 males (38.5%) were analyzed. The anthropometric measurements are detailed in table I. There were 145 normal weight (26.6%), 215 overweight (39.4%), 154 obese (28.3%) and 31 low weight (5.7%) patients. Obesity was more commonly seem in females (75%) just as and height 2.7 . Sixteen of 215 (7.4%) of overweight patients and 32 of 154 (20.8%) obese patients were reclassified from normal to dilated left atrium when indexed by height, 19 of 215 (8.8%) and 35 of 154 (22.7%), respectively, when indexed by height 2 , and 18 of 215 (8.4%) and 33 of 154 (21.4%), respectively, when indexed by height 2.7 according to gender (figure 2). In the normal weight group, only one patient was reclassified as enlarged LA when indexed by height 2 or by height 2.7 and 3 patients were reclassified when indexed by height. No low-weight patients were reclassified as enlarged LA when indexed by height, using any one of the three methods. The results of ROC analyses for the best cutoff values to identify LA enlargement in obese or overweight patients are shown in Figure 3 and Table IV. LA was considered enlarged if at least two of the three indexation methods by height were above normal values. LA volume indexation by height² had the highest area under curve (AUC 1.0, 95% CI 0.999-1.0) followed by LAvol/ht 2.7 (AUC 0.989, 95% CI 0.98-0.997), LAvol/h (AUC 0.972, 95% CI 0.957-there was a trend towards more overweight in women (59%). The LA diameter and volume progressively increased from low-weight (Low-wt), normal, overweight (Over-wt) and obese groups (table II and figure 1). When indexed by BSA the LA volume did not differ between groups. Otherwise, when indexing by height, height 2 and height 2.7 , we observed a progressive and statistically significant increase in the volume of the left atrium ( figure 1)