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Archives of cardiovascular diseases
Volume 108, n° 12
pages 643-649 (décembre 2015)
Doi : 10.1016/j.acvd.2015.07.001
Received : 20 February 2015 ;  accepted : 31 July 2015
Echocardiographic measurement of left atrial volume: Does the method matter?
Importance du choix de la méthode de mesure du volume de l’oreillette gauche sur l’appréciation du degré de dilatation
 

Claire Cimadevilla a, c, , Berjeb Nadia a, Julien Dreyfus a, c, Fanny Perez a, Caroline Cueff a, Michaela Malanca a, Eric Brochet a, Bernard Iung a, b, c, Alec Vahanian a, b, c, David Messika-Zeitoun a, b, c
a AP–HP, Cardiovascular Division, Bichat Hospital, 46, rue Henri-Huchard, 75018 Paris, France 
b Inserm U698, Bichat Hospital, Paris, France 
c University Paris 7, Bichat Hospital, Paris, France 

Corresponding author.
Summary
Background

Four two-dimensional echocardiographic methods (cube, ellipsoid, Simpson's and area-length) can be used to assess left atrial volume (LAV).

Aims

To compare absolute LAV measurements and evaluate agreement regarding the semiquantitative assessment of degree of left atrial (LA) enlargement, between methods.

Methods

We prospectively measured LAV in 51 healthy volunteers using the four methods, and defined thresholds for moderate (mean+2 standard deviations [SDs]) and severe (mean+4 SDs) LA enlargement for each method. In 372 patients referred for echocardiography, we compared absolute LAV measurements and agreement between methods.

Results

LAV was significantly different between methods in the healthy volunteer group (11±4, 17±3, 26±6 and 28±7mL/m2, respectively; P <0.0001), resulting in different thresholds for moderate and severe LA enlargement. LAV was also significantly different in the 372 patients (30±20, 47±27, 61±34 and 65±36mL/m2, respectively; P <0.0001). Agreement regarding degree of LA enlargement (none, moderate, severe), using the area-length method as reference, was modest with the cube method (kappa=0.41), correct with the ellipsoid method (kappa=0.60) and excellent with Simpson's method (kappa=0.83).

Conclusion

The choice of the method had a major effect on assessment of degree of LA enlargement. Our results suggest that the cube and ellipsoid methods, which significantly underestimated LAV and provided modest agreement, should be disregarded. In contrast, Simpson's method and the area-length method were slightly different, but showed close agreement, and should be preferred, using dedicated thresholds (50 and 56mL/m2 respectively).

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Résumé
Contexte

Il existe quatre méthodes de mesure de l’oreillette gauche (OG) en échocardiographie transthoracique (cube, ellipse, Simpson's, aire/longueur).

Objectif

Évaluer l’impact du choix de la méthode de mesure du volume de l’OG en échocardiographie sur l’estimation de son degré de dilatation.

Méthodes

Nous avons calculé prospectivement le volume de l’OG avec chaque méthode chez 51 sujets sains, ainsi que les valeurs seuil permettant de définir une OG dilatée (moyenne+2DS), et très dilatée (moyenne+4DS). Nous avons comparé dans une cohorte de 372 patients les valeurs absolues de volume de l’OG et la concordance des quatre méthodes de mesure.

Résultats

Le volume OG était différent selon la méthode utilisée (11±4, 17±3, 26±6 et 28±7mL/m2, respectivement ; p <0,0001), avec en conséquence des valeurs seuil différentes pour définir une dilatation modérée ou sévère. Le volume OG était également différent pour les patients (30±20, 47±27, 61±34 et 65±36mL/m2, respectivement ; p <0,0001). La concordance pour définir le degré de dilatation OG (nulle, modérée, sévère) entre la méthode aire/longueur et la méthode du cube était modeste (kappa=0,41), correcte avec la méthode de l’ellipse (kappa=0,60) et excellente avec la méthode du Simpson (kappa=0,83).

Conclusion

Le choix de la méthode influence fortement l’appréciation du degré de dilatation de l’OG. Les méthodes aire/longueur et Simpson, contrairement à celle du cube et de l’ellipse, donnaient des volumes peu différents et une excellente concordance. Elles devraient être privilégiées dans l’évaluation de la dilatation OG en utilisant des seuils dédiés (50 et 56mL/m2 respectivement).

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Keywords : Left atrial volume, Echocardiography, Thresholds

Mots clés : Volume, Oreillette gauche, Échocardiographie, Valeurs seuil

Abbreviations : A/L, BSA, LA, LAV, LAVI


Background

Left atrial (LA) size is an important prognostic marker in various cardiovascular diseases, such as valvular heart disease, hypertension, dilated cardiomyopathy, hypertrophic cardiomyopathy and stroke [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11]. Transthoracic echocardiography is the most widely used method available to assess LA size, and the superiority of LA volume (LAV) over LA diameter is now well established [4, 7, 12, 13, 14]. Thus, LAV should be measured consistently during each echocardiogram. However, LAV can be calculated using different methods. The most accurate method remains a matter of debate, and the effect of the method on the assessment of the degree of LA enlargement has never been evaluated.

Thus, in this prospective study, we aimed: to compare LAV measurements between four methods (the cube method, the ellipsoid method, the biplane Simpson's method and the biplane area-length [A/L] method) to define specific thresholds for moderate and severe LA enlargement for each method, in a healthy volunteer group; and to evaluate the agreement between methods regarding the semiquantitative evaluation of the degree of LA enlargement, in a subset of patients referred for clinically indicated transthoracic echocardiography.

Methods
Population

We prospectively enrolled two different groups of participants: healthy volunteers with no history of cardiovascular disease (nurses, physicians and medical students enrolled in an ongoing prospective study [GENERAC, clinicalTrial.gov number NCT00647088]); and consecutive patients who underwent transthoracic echocardiography between January and December 2010 conducted by the last author (D.M.-Z.) using an IE33 ultrasound system (Philips, Amsterdam, Netherlands). Exclusion criteria were a poor echocardiographic window or incomplete data for the measurement of LAV by the four methods. All participants gave informed consent.

Clinical data

For each volunteer or patient, weight, high, body surface area (BSA), medical history and indication for echocardiography were collected. BSA was calculated as 2×√([weight (kg)×height (m)]/3600) and body mass index as (weight [kg]/height2 [cm]).

Echocardiography

All participants underwent comprehensive echocardiography prospectively, conducted by the same experienced physician (the last author, D.M.-Z.). All measurements were performed in end-systole just before mitral valve opening. LA anteroposterior diameter (D) was measured in parasternal long-axis view. Other measurements for LAV calculations were performed in the apical three- and four-chamber views using the zoom. The mediolateral diameter (D1), the area (A1) and the vertical length between the annulus and the posterior LA wall (L1) were measured in the four-chamber view. The area (A2) and the vertical length between the annulus and the posterior LA wall (L2) were measured in the apical three-chamber view (Figure 1).



Figure 1


Figure 1. 

Methodology of left atrial volume calculation: four different methods, using diameters and areas measured in (A) parasternal long-axis view (B) four-chamber view and (C) three-chamber view. A1 and A2: left atrial areas; D: anteroposterior diameter; D1: mediolateral diameter; L1 and L2: vertical lengths.

Zoom

LAV was calculated using the four methods. The formula for the cube method is: LAV=[π/6]×D3. The formula for the ellipsoid method is LAV=π (D×D1×L1)/6. In the biplane Simpson's method of disks, the left atrium (LA) is divided into a pile of disks perpendicular to the longitudinal length direction, in both the four-chamber and three-chamber views. The radius of each disk is measured from the longitudinal axis to the LA contour in the two perpendicular planes. The volume of each disk is calculated automatically, and LAV is calculated by the summation of the disk's volume: LAV=π/4Σ(i=1 to 20) ai×bi×L/N, where ai and bi are 20 discs obtained in the two orthogonal incidences (the four- and three-chamber views). The formula for the biplane A/L method is LAV=(8/3) π (A1×A2)/([L1+L2]/2)

Importantly the same tracing was used to perform all measurements (mediolateral diameter; vertical lengths L1 and L2; and LA areas A1 and A2) and to calculate LAV using the method of disks, to ensure that differences between methods were only due to the method and not to the tracing. Results were indexed to the BSA (LAV index [LAVI]).

Statistical analysis

Continuous variables are expressed as mean±standard deviation (SD), median [95% confidence interval] or number (percentage) of patients. Comparisons of LAVI measured by the different methods were made using one-way analysis of variance or a paired t test, as appropriate. For each method, moderate LA enlargement was defined as mean LAVI measured in the healthy population+2 SDs; severe LA enlargement was defined as mean LAVI+4 SDs. The agreement between methods regarding the semiquantitative assessment of the degree of LA enlargement in the patient group was evaluated using the kappa value. The A/L method – previously reported as providing the most accurate assessment of LAV compared with computed tomography – was used as reference. When the degree of LA enlargement was similarly graded between two methods, they were considered concordant. In contrast, if the degree of LA enlargement was different, methods were considered discordant (with over- or underestimation compared with the A/L method). A P value<0.05 was considered statistically significant. Statistics were performed using JMP software (SAS, Cary, NC, USA).

Results
Population

Fifty-one healthy volunteers and 372 patients were prospectively enrolled. Clinical and echocardiographic characteristics are presented in Table 1. Mean age in the healthy volunteer group was 33±12 years and 22 (43%) were men. Left ventricular ejection fraction and systolic pulmonary artery pressure were normal by design. Mean age in the patient group was 63±17 years, 204 (55%) were men, left ventricular ejection fraction was normal in 336 (90%) patients and 54 (15%) had an elevated systolic pulmonary artery pressure (>40mmHg). Two-hundred and eighty-three (76%) patients were referred for evaluation of valvular heart disease and the remaining patients (n =89; 24%) were referred for other reasons (ischaemic, dilated or hypertrophic cardiomyopathy and atrial fibrillation).

Left atrial volume in healthy volunteers

In the 51 healthy volunteers, mean LAVI was significantly different using the four different methods: 11±4mL/m2 using the cube method, 17±3mL/m2 using the ellipsoid method, 26±6mL/m2 using the biplane Simpson's method and 28±7mL/m2 using the biplane A/L method (P <0.0001) (Table 1). Mean LAVI measured using the biplane Simpson's method and the biplane A/L method was also significantly different (P <0.0001). Threshold values for defining moderate and severe LAVI enlargement for each method are presented in Table 2. For example, using the biplane A/L method, LAVI was moderately enlarged above 42mL/m2 and severely enlarged above 56mL/m2.

Left atrial size in the patient group

Mean LAVI in the patient group was also significantly different between the four methods: 30±20mL/m2 using the cube method, 47±27mL/m2 using the ellipsoid method, 61±34mL/m2 using the biplane Simpson's method and 65±36mL/m2 using the biplane A/L method (P <0.0001) (Table 1). Mean LAVI was also slightly but significantly different between the biplane Simpson's method and the biplane A/L method (P <0.0001).

Agreement between methods regarding degree of left atrial enlargement

Degree of LA enlargement (none, moderate or severe) according to each method, and using thresholds determined in the healthy volunteer group using the same method, are presented in Table 3. For example, using the biplane A/L method, 98 (26%) patients had a normal LA size (≤42mL/m2), 88 (24%) patients had a moderately enlarged LA (42mL/m2<LAVI56 mLm2) and 186 (50%) patients had a severely enlarged LA (LAVI>56mL/m2).

Using the cube method, LA was normal in 121 (33%) patients (≤19mL/m2), moderately enlarged in 80 (21%) patients (19mL/m2<LAVI27mL/m2) and severely enlarged in 171 (46%) patients (LAVI>27mL/m2). Compared with the A/L method, the degree of LA enlargement was underestimated in 86 (23%) patients, including 14 (4%) patients who had a normal LA size using the cube method, but a severely enlarged LA using the biplane A/L method. On the other hand, the degree of LA enlargement was overestimated in 52 (14%) patients, with 10 (3%) patients having a severely enlarged LA using the cube method, but a normal LA size using the A/L method. Overall, the agreement between two methods regarding the degree of LA enlargement was modest, with 138 (37%) patients classified differently (kappa=0.41) (Table 3).

Using the ellipsoid method, LA was normal in 139 (37%) patients (≤23mL/m2), moderately enlarged in 87 (24%) patients (23mL/m2<LAVI29 mL/m2) and severely enlarged in 146 (39%) patients (LAVI>29mL/m2). Compared with the A/L method, the degree of LA enlargement was underestimated in 87 (24%) patients and overestimated in only 9 (2%) patients. Thus, 276 (74%) patients were similarly classified, and agreement with the A/L method was only correct (kappa=0.60) (Table 3).

Using the biplane Simpson's method, LA was normal in 86 (23%) patients (≤38mL/m2), moderately enlarged in 82 (22%) patients (38mL/m2<LAVI50mL/m2) and severely enlarged in 204 (55%) patients (LAVI>50mL/m2). Compared with the A/L method, the degree of LA enlargement was underestimated in four (1%) patients and overestimated in 34 (9%) patients. Agreement between the biplane Simpson's method and the biplane A/L method was excellent, with a kappa value of 0.83 and 334 (90%) patients similarly classified (Table 3).

Effect of current recommendations

According to current recommendations by the American and European Societies of Echocardiography [15], LA is moderately enlarged above 34mL/m2 and severely enlarged above 40mL/m2. Using these thresholds, 12 (24%) in the healthy volunteer group were considered as having an enlarged LA when it was measured using the biplane Simpson's method, and six (12%) when it was measured using the biplane A/L method. In the patient group, 281 (76%) patients using the biplane Simpson's method and 294 (79%) patients using the biplane A/L method would have been classified as having moderate or severe LA enlargement. Agreement between the Societies and the thresholds proposed above were only modest (0.54 and 0.38, respectively).

Discussion

The main findings of the present study can be summarized as follows. First, we showed that echocardiographic methods used for measurement of LAV are not equivalent, resulting in different thresholds for the definition of LA enlargement (moderate or severe). Thus, there is no ‘universal’ threshold definition for LA enlargement, and a threshold is only valid for one given method. Second, even when using appropriate thresholds for each method, classification of the degree of LA enlargement is also dependent on the method used. A modest agreement was observed between the biplane A/L method and the cube method or the ellipsoid method. In contrast, we showed close agreement between the biplane Simpson's method and the biplane A/L method.

Left atrial diameter versus volume

LA diameter is usually measured in the parasternal long-axis view (anteroposterior diameter). Although this diameter has been (and unfortunately still is) used in clinical practice and research, it inaccurately represents the true LA size. The LA enlarges asymmetrically, with the anteroposterior dimension possibly constrained between the sternum and the spine. Thus LA size measured using a single diameter has limited accuracy, with underestimation of LA size and a wide range of error; assessment of LA size should therefore rely on volume measurement [7].

Absolute left atrial volume: comparison of methods

Using echocardiography, LAV calculation can be derived from measurements of diameters (cube method, ellipsoid method) or from measurements of areas (biplane Simpson's and A/L methods). In the present study, we show that each method provides significantly different measurements in both healthy volunteers and patients. Regarding the limitation of a single diameter measurement mentioned above, the limits of the cube method, which assumes the LA to be spherical, are obvious. The ellipsoid method is based on three diameters, assuming that the LA can be represented as a prolate ellipse, and has been shown, as in our study, to underestimate LAV [16]. Nevertheless, the ellipsoid method is still used frequently in clinical practice, even if methods based on area have been recommended [17]. We have previously shown that only the biplane A/L method, with a vertical length, provided accurate LAV measurements compared with computed tomography [7]. Using this methodology, we showed a 5–10% LAV underestimation using the Simpson's method compared with the A/L method. Thus, methods should not be considered as equivalent, and this finding may have important clinical implications for the definition of normalcy of LAV, which cannot be universal, but should depend on the method used.

Normalcy of left atrial volume and thresholds definition

These results raise uncertainties regarding the definition of normal LA size and thresholds for LA enlargement. Current recommendations provide a unique threshold value without clearly mentioning with which method it has been validated and which method should be used. The present study clearly demonstrates that as each method provides different LAV measurements, a specific threshold for each method would be more appropriate. It is worth noting that, whatever the method considered, the thresholds proposed in our study are different from those presented in the current recommendations (34mL/m2 for moderate LA enlargement and 40mL/m2 for severe enlargement), and using these thresholds, 12–24% of healthy volunteers would have been wrongly classified as having an enlarged LA. In contrast, our results, with the biplane A/L method as reference method, are in agreement with previous studies and current European Society of Cardiology recommendations on valvular heart disease [18], both in mitral stenosis (indication for anticoagulation) and in asymptomatic organic mitral regurgitation (LA remodelling and indication for surgery). Potential explanations are the prospective nature of the study, with dedicated attention to avoid foreshortening during imaging acquisition, careful contouring of the LA and, usually, use of a vertical longitudinal length. We cannot exclude the possible effect of the use of the three-chamber view instead of the commonly used two-chamber view, but this factor is minimal, in our opinion.

Degree of left atrial enlargement: agreement between methods

If absolute measurements and thresholds were different according to each method, the agreement between methods regarding the assessment of the degree of LA enlargement remained a pending question. Previous studies have evaluated the agreement between LAV and diameter, showing overall poor agreement, with a 50–60% rate of underestimation of LA enlargement using diameters [14, 19]. For the first time, using specific thresholds for each method defined in healthy volunteers, we evaluated the agreement between echocardiographic methods of LAV measurement (cube, ellipsoid, biplane Simpson's and biplane A/L methods). The agreement with the A/L method was modest for the cube method and only correct with the ellipsoid method. In contrast, close agreement between the biplane Simpson's and biplane A/L methods was observed.

Our results, showing that not only absolute results were different between methods, but also the assessment of the degree of LA enlargement, may have important implications. The cube method and the ellipsoid method significantly underestimated the absolute LAV value compared with the previously validated A/L method, and should be disregarded. In contrast, the biplane Simpson's method or the biplane A/L method may be used interchangeably, with the express condition that dedicated thresholds are used. Indeed, although both measurements were close, they were significantly different (5–10% difference), and despite being considered interchangeable in current recommendations, specific thresholds for each method should be proposed.

Study limitations

The present study deserves several comments. First, it was not a feasibility study, and patients with poor echogenic windows were excluded. Our aim was not to evaluate the more reproducible or feasible method, but to compare absolute measurements and degree of LA enlargement between methods. Importantly, we had previously assessed intra- and interobserver variability, which was approximately 8% for the biplane A/L method. In addition, the same LA contours were used for LAV calculation by the four methods, and differences reported in the present study were therefore only due to differences in methodology and not to the tracings. Second, we have no gold standard and used the biplane A/L method as reference, as we had previously validated this method against computed tomography. Use of three-dimensional echocardiography, computed tomography or magnetic resonance imaging would have been of interest, but was not performed in the present study [20, 21]. Importantly, the choice of the reference method can be questioned (we could not confirm in this study that the biplane A/L method provided the most accurate result against a gold-standard method), and thus terms such as under- or overestimation may be debatable. However, comparisons of absolute measurements and agreement regarding the assessment of the degree of LA enlargement are hypothesis free and therefore did not impeded the analysis performed in the present study. Third, the interpretation of the results may be limited by the size difference between the control group and the patient population (51 healthy volunteers versus 372 patients). However, confidence intervals for LAVI were narrow and could be used as a reference for normal values of LAVI. Finally, all measurements were adjusted to BSA. Caution has been advised regarding such adjustment in obese patients. There was no obese patient in the healthy volunteer group, and as paired comparisons were performed in the patient group, absolute LAV values would have provided exactly the same results.

Conclusions

In this prospective study, we have shown that echocardiographic methods used for LAV measurement are not equivalent. Use of an appropriate method and dedicated thresholds are pivotal for both an accurate measurement of LAV and an accurate assessment of the degree of LA enlargement. The cube and ellipsoid methods, which significantly underestimated LAV and provided modest agreement, should be disregarded. In contrast, the biplane Simpson's and A/L methods, which were slightly different, but showed close agreement, should be preferred, but using dedicated thresholds. Our results may have important clinical implications for daily routine echocardiographic practice.

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

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