Quantification of left ventricular volumes using monoplane and biplane

Anna Pilgram¹, Martin Beyerbach², Michael Fehr¹, Stephan O. Hungerbühler¹

1Small Animal Clinic

University of Veterinary Medicine Hannover, Foundation Bünteweg 9

D-30559 Hannover, Germany

2Department of Biometry, Epidemiology and Information Processing University of Veterinary Medicine Hannover, Foundation

Bünteweg 2

D-30559 Hannover, Germany

Corresponding author: Anna Pilgram, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, D-30559 Hannover, Germany, E-mail: anna.pilgram@tiho-hannover.de

Publikationen Abstract

Background:

In veterinary medicine there are no clear recommendations concerning the measurement of left ventricular volumes (LVV) assessed by monoplane and biplane Simpson’s method of discs (SMOD). Hitherto LVV measured by SMOD were indexed to body surface area (BSA). The aim of the present study was to find a suitable indexation method which was first investigated by normalizing LVV to body weight (BW), aortic root diameter (AoD) and BSA and second using an allometric equation to determine the adjusted power of BW. Moreover, to compare monoplane and biplane LVV variables of healthy dogs of varying breed.

Methods:

Thirty-eight healthy dogs were included in the study. End diastolic volume (EDV) and end systolic volume (ESV) were measured by monoplane SMOD, using the right-parasternal chamber view (SMOD-R4) and left-apical 2- (SMOD-L2) and 4-chamber view (SMOD-L4) as well as biplane SMOD (SMOD-BP). Coefficient of determination (r²) and linear regression analysis were applied to evaluate a residual dependence of LVV and BW after indexation using BW, AoD and BSA. LVV were normalized to BW (LVVI1) as well as to a calculated power of BW (LVVI2), using allometric scaling. Subsequently, the indexed LV parameters were compared within the examination planes applying least significant difference tests (LSD) and Bland-Altman analyses.

Results:

Using BW as index, the volumetric data showed a weak (r² < 0.08) remaining influence on BW in contrast to indexed data normalized to BSA and AoD (AoD: r² >

0.62, BSA: r² > 0.39). The scaling exponent (b) of LVVI2 (LVV/kgᵇ) showed to be very close to 1 (0.96 – 1.01). LSD tests revealed significant differences between SMOD-BP and SMOD-L4 (EDVI1, p = 0.01; ESVI1, p = 0.03). The comparison of SMOD-BP and SMOD-R4 as well as SMOD-L4 and SMOD-L2 showed no significant differences. The comparison of SMOD-L4 and SMOD-R4 revealed significances only for ESVI1 (p = 0.02).

Publikationen Conclusion:

We recommend indexation with BW for evaluating LVV in dogs because this indexation method showed the best alignment. Biplane and monoplane volumetric SMOD measurements are not equivalent; therefore SMOD-BP should be used in order to reflect the LV shape and volume.

Abbreviations:

1D: one-dimensional 2D: two-dimensional

2DE: two-dimensional echocardiography 3D: three-dimensional

AoD: Aortic root diameter

ASE: American Society of Echocardiography BSA: body surface area

BW: body weight

DCM: dilated cardiomyopathy

DMVD: degenerative mitral valve disease ED: enddiastole

EDV: enddiastolic volume EF: Ejection fraction ES: endsystole

ESV: endsystolic volume

LA/Ao: left atrial-to-aortic root ratio la2Ch: left-apical two-chamber la4Ch: left-apical four-chamber

Publikationen LV: left ventricular/ left ventricle

LVV: left ventricular volume MD: mean difference

rp4Ch: right-parasternal four-chamber SD: standard deviation

SMOD: Simpson’s method of discs

SMOD-R4, SMOD-BP, SMOD-L4, SMOD-L2: Simpson’s method of discs derived from the right-parasternal 4 chamber, the biplane, the monoplane, the left-apical 4-chamber and left-apical 2-4-chamber view

Publikationen Background

Two-dimensional echocardiography (2DE) plays a major role in veterinary clinical practice in order to evaluate ventricular internal dimensions of the heart. Common heart diseases in dogs like the degenerative mitral valve disease (DMVD) as well as dilated cardiomyopathy (DCM) were routinely classified by the assessment of left ventricular diameters or volumes based on two-dimensional (2D) images. These parameters are essential to evaluate the severity of disease hence to facilitate correct therapy. Left ventricular (LV) enddiastolic volume (EDV) gives good information about volume overload, whereas LV endsystolic volume (ESV) determines systolic function of the LV. Up to now the evaluation of the LV was mostly based on one-dimensional (1D) M-Mode measurements. However in former studies 1D methods revealed weaknesses in the estimate of LV abnormalities in comparison to multidimensional methods (TIDHOLM et al. 2010; WESS et al. 2010). Commonly used parameters like M-Mode based linear measurements of the LV internal diameter are prone to errors because of geometric assumptions. A frequently used 2D echocardiographic technique to measure left ventricular volumes (LVV) in humans is the biplane Simpson’s Method of Discs (SMOD), which is recommended by the American Society of Echocardiography (ASE) (LANG et al. 2005). For biplane SMOD (SMOD-BP), images of the LV are obtained from two orthogonal left apical views, the 4-chamber (la4Ch) and the 2-chamber (la2Ch) view. In case of a failure to display the la2Ch view, monoplane SMOD by the exclusive use of the la4Ch view is indicated and volume is calculated presuming a circular instead of an ellipsoid disk (LANG et al. 2005). Although biplane SMOD is considered to be superior to monoplane SMOD, in veterinary medicine the biplane method is not routinely used (SERRES et al. 2008; WESS et al. 2010; MEYER et al. 2013) since the la2Ch view is not part of the common echocardiographic examination. Furthermore, due to the fact that the right parasternal depiction of the 4-chamber view (rp4Ch) is often easier than the left-sided view, it is interesting whether the volumetric measurements using monoplane SMOD are comparable (WESS et al. 2010; MEYER et al 2013; SMETS et al. 2014). In one previous study with 34 healthy dogs and 39 dogs with DMVD and 12 dogs with DCM, biplane SMOD derived from a 3D data-set was comparable with 3D volumetric measurements in the assessment of EDV but monoplane

Publikationen

echocardiographic changes in Doberman pinchers with occult DCM (WESS et al.

2010). To the authors’ knowledge there are no studies comparing LV variables assessed by monoplane and biplane SMOD in dogs in a population of varying breeds. To measure LVV applying only the monoplane SMOD would make calculation and assessment easier and may confirm the routine usage of this method in clinical veterinary practice. Comparing cardiac volumes is complicated by different body weights. Therefore, hitherto volumetric data of SMOD were indexed to body surface area (BSA) (LANG et al. 2005; WESS et al. 2010; SUZUKI et al. 2013), which can be calculated with the aid of a simplified exponent : 𝑏𝑜𝑑𝑦 𝑤𝑒𝑖𝑔ℎ𝑡(𝑘𝑔) ^/ . Cornell et al. in their study on allometric scaling of M-mode parameters pointed out that volumetric data should be associated with body weight (BW), as a 3D parameter (CORNELL et al. 2004). This presumption agrees with another study which indexed SMOD derived parameters to BW (SMETS et al. 2014). Therefore, it is necessary first to establish a reliable indexation system before comparing the different methods of volumetric measurement.

The aims of the present study were to (1) determine a correct indexation method for LVV and (2) compare LV variables of healthy dogs in a large population of breeds measured by monoplane and biplane SMOD in order to compare if there are differences between the biplane and the conventional used monoplane methods.

Methods

The Animal Model

Thirty-eight healthy dogs which were privately owned and presented at the Small Animal Clinic, University of Veterinary Medicine Hannover, Germany were included in the study. Previously two presented dogs were excluded because of the inability to measure the la2Ch view. To consider the potential effect of weight on echocardiographic dimensions a body weight of 3.5 – 27 kg were included (BORGARELLI et al. 2004). All dogs underwent a general physical, electrocardiographic as well as complete echocardiographic examination and Doppler-derived echocardiographic measurements. Dogs were considered healthy based on normal findings of all performed examinations. Any congenital or acquired heart diseases as well as haemodynamically relevant extracardiac diseases were

Publikationen Echocardiography

The echocardiographic (M-Mode, 2D) examination was performed with an ultrasound unit (a) equipped with M5S- (2.0-4.5 MHz, large breeds) and 6S- (4.0-8.0 MHz, small breeds) phased-array transducers, both of them in harmonic mode, and simultaneous electrocardiographic monitoring. During the examination dogs were non-sedated and consecutively restrained in right and left lateral recumbent positions. Examinations were performed by one experienced person (S.O.H.). Image optimization was adapted consistently. It was focused on illustrating the ventricular maximum length and avoiding the illustration of papillary muscles. All images and loops were stored and transmitted to a workstation, equipped with commercially available software (b). The echocardiographic data were evaluated off-line by one person (A.P). For this purpose, LV internal dimensions of 3 digitally stored consecutive cardiac cycles were measured in enddiastole (ED) as well as endsystole (ES). Ejection fraction (EF) was calculated as follows: [(𝐸𝐷𝑉 − 𝐸𝑆𝑉) ÷ 𝐸𝐷𝑉] × 100.

Mean values were determined for further statistical analysis.

2DE Image acquisition and SMOD measurement

The recommendations for chamber quantification of the ASE (LANG et al 2005) were adopted. 2D echocardiography images were obtained from the la4Ch and la2Ch view as well as from rp4Ch view. ED was defined as the beginning of the QRS-complex at the point of mitral valve closure and ES as the frame with the smallest internal silhouette directly in front of the mitral valve opening. SMOD measurement was performed by manually tracing the endocardial border of selected frames in ED and ES. Papillary muscles and trabeculae were included in the internal volume as recommended previously (LANG et al. 2005). LV maximum lengths in ED and ES were measured by an automated but manual adjustable line starting from the middle of the mitral valve annulus to the LV apex. Calculation of LVV by SMOD was computed automatically by specific software and was based on the summation of multiple (usually 15) discs of the same height, whose diameters and cross sections were the result of the endocardial tracing (Figure 1). Consequently monoplane cross sections are circular whereas the biplane cross sections are ellipsoid due to one or two measured diameters. Monoplane SMOD was performed by LV imaging in right-parasternal 4-chamber view (SMOD-R4) as well as left-apical 4-chamber (SMOD-L4)

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and la2Ch view was used, utilizing the longer of the two measured lengths and considering both of the diameters for calculating the cross-sectional area to provide an ellipsoid disc. The measurement of the aortic root diameter (AoD), which was used for the indexation of LVV, was obtained by the 2D right parasternal short axis view. To determine the reproducibility of the different SMOD measurements in ED and ES ten echocardiograms were randomly selected to be measured twice by one person (intraobserver variability). Moreover a second investigator measured five of these echocardiograms for interobserver variability.

Statistical analysis

Statistical analyses were performed by commercially available computer software (c, d). A descriptive statistical analysis was used for age, body weight and sex. The BSA was calculated by using BW in grams and the following formula (BOON et al.

1983): (10.1 × 𝐵𝑊 ^. ) ÷ 10 . Linear regression analysis with coefficient of determination (r²) was applied to evaluate a residual dependence of LVV and BW after indexation using BW, AoD and BSA. LVV were normalized to BW (LVVI1) as well as to a calculated power of BW (LVVI2). This Index (LVVI2) was established by using a logarithmic form of allometric equation: 𝑙𝑜𝑔(𝑌) = 𝑙𝑜𝑔(𝑎) + 𝑏 × 𝑙𝑜𝑔(𝑀) and LVV indices and EF were expressed as mean ± standard deviation (SD). For group-comparisons one-way analyses of variance as well as least significant difference (LSD) tests for multiple pairwise mean comparisons were performed. Bland-Altman analysis was used to evaluate the limits of agreement (BLAND a. ALTMAN 1986). A comparisonwise error rate of 5 percent was used, so p-values of less than 0.05 were considered significant. The intra- and interobserver coefficients of variation (CV) for EDV and ESV were calculated as the SD of the mean difference between the measurements divided by the total mean and multiplied by 100.

Results

Thirty-eight dogs weighing between 3.5-27 kg were included in the study (median

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Tolling Retriever, 2 Pekingese, 2 small cross breeds (<15 kg), 5 large cross breeds (>15 kg) and 14 other breeds with n = 1. 18 dogs (47%) were female and 20 dogs (53%) were male.

Indexation

To determine a suitable index to minimize dependence of body weight on the volumetric data, EDV and ESV were first indexed with BSA, BW and AoD.

Regardless of the method of measurement, indexation with BSA and AoD revealed a clearly remaining influence of body weight (AO: r² > 0.62, BSA: r² > 0.39). However, by using BW as index (LVVI1) the volumetric data mainly showed a weak (r² < 0.08) remaining influence of body weight (Table 1), which was evident by illustrating linear regression analysis as well (Figure 2). For LVVI2 the scaling exponents for the LVV of each chamber-view are summarized in Table 2. All scaling exponents showed to be very close to 1. Results of the SMOD LVVI1 and LVVI2 are presented in Table 3.

LVV comparison of different examination planes

For further analyses the LVVI2 was used. For EDVI and ESVI obtained from the biplane SMOD measurements were significant different from the indices obtained from the la4Ch-view (EDVI, p = 0.01; ESVI, p = 0.03). The comparison of SMOD-BP and SMOD-R4 (EDVI, p = 0.11; ESVI, p = 0.14) as well as SMOD-L4 and SMOD-L2 (EDVI, p = 0.97; ESVI, p = 0.96) showed no significant differences. The comparison of SMOD-L4 and SMOD-R4 revealed significances for ESVI (p = 0.02), but not for

The comparison of left ventricular cavity lengths (Table 4) revealed significant higher values for the rp4Ch view than for la2Ch- (ED, p = 0.006; ES, p = 0.047) and la4Ch- view (ED, p = <0.0001; ES, p = <0.0001). The la2Ch view showed significant higher values in comparison to the la4Ch view (ED, p = 0.007; ES, p = 0.0004).

Publikationen EF

There were significant differences of the EF between SMOD-BP and SMOD-L4 (p = 0.048), SMOD-BP and SMOD-R4 (p = 0.047), SMOD-L4 and SMOD-L2 (p = 0.012) as well as SMOD-L4 and SMOD-R4 (p = 0.005). Means (± SD) were 53 % (±4.9) for SMOD-BP, 52 % (±5.4) for SMOD-L4, 54 % (±5.4) for SMOD-L2 and 54 % (±4.9) for SMOD-R4.

Reproducibility

Intra- and interobserver variability was low for all of the LV SMOD measurements.

The CV for each method is presented in Table 5.

Discussion

During the progression of DMVD the LV enlarges due to chronic volume overload (LORD et al. 2010; LJUNGVALL et al. 2011) and patients require reliable examinations to detect the cardiac remodeling which is meaningful concerning treatment decisions (ATKINS et al. 2009). 1D measurements of the LV internal diameter (M-Mode) proved to have several limitations especially in disease progression which is a reason to evaluate dilated ventricles by means of 2D echocardiography demonstrating fewer geometrical assumptions (SERRES et al.

2008; WESS et al. 2010). Biplane SMOD is recommended by the human ASE (LANG et al. 2005). Thus, especially in human medicine, it is a frequently used method. However, the plane of the la2Ch view is not easily depicted in dogs and is not part of the routine cardiac examination, therefore making monoplane SMOD a viable option also in view of it being time saving and more practicable. Moreover, biplane SMOD has limitations as well. The SMOD presupposes an orthogonality of the two required planes, which cannot always be ensured (KING et al. 1992;

RODEVAND et al. 1998). In human medicine, regional wall motion abnormalities caused by infarction are a further reason for using multiple planes for best possible examination of the whole heart (TAKEMOTO et al. 2003; ARAI et al. 2004; JENKINS et al. 2007). In dogs, this indication plays no major role because infarcts are rather atypical (DRIEHUYS et al. 1998). To the authors’ knowledge there are, as yet, only few studies comparing monoplane and biplane derived LV volumetric data in dogs (PENZL 2009).

Publikationen Indexation

In this study volumetric data of EDV and ESV were first indexed to BW, because of the fact that our results showed a remaining correlation to BW by using indexation to BSA as well as to AoD. After indexation of the LVV with AoD as a body-internal parameter, results showed a residual dependence to body weight. Consequently the published assumption that volumes are not linearly related to linear dimensions could be supported (CORNELL et al. 2004). Most former human and veterinary studies indexed SMOD derived parameters to BSA (LANG et al. 2005; WESS et al. 2010;

SUZUKI et al. 2013). A former study with 85 boxer dogs showed despite the indexation of LVV to BSA, remaining significant differences between the lighter female dogs in comparison to the heavier male dogs, which might indicate as well a still existing correlation with body weight after indexation to BSA. After indexing LVV to BW both sexes showed no significant difference anymore (SMETS et al. 2014).

This could have revealed an uncertainty of volume indexation method using BSA, which confirms with a published assumption that volumes correlate best with BW, whereas the cross-sectional areas correlate with BSA (CORNELL et al. 2004). This agrees with our results as well. Furthermore, our results of EDVI1 (indexed to BW) means (SMOD-BP: 2.41 ± 0.32 ml/kg) and ESVI1 means (SMOD-BP: 1.14 ± 0.18 ml/kg) of healthy dogs with different BW are nearly identical with the boxer breed specific results indexed to BW (EDVI: 2.4 ± 0.4 ml/kg; ESVI: 1.2 ± 0.2 ml/kg) (SMETS et al. 2014). Nevertheless, it must be considered that the values of the cardiac volumes indexed to BW are very small, which are theoretically capable of concealing a still existing influence. Furthermore it could be remarked that using BSA as an index still can be utilized for the purpose of breed-specific values because differences of weight play no major role. However another study established SMOD reference values using the la4Ch and rp4Ch view indexed to BSA for three different weight groups instead of a universal value (GERLACH 2009). In our study a wider range of dog breeds and sizes participated, even if there is no information about dogs weighting more than 30 kg. However, in the present study population values indexed to BSA or AoD showed large differences (AO: r² > 0.62, BSA: r² > 0.39);

consequently, a comparison of these indexation methods in this mixed population did not seem to be reasonable. Second indexation method was performed by indexing the LVV by a calculated power of BW with the aid of an allometric formulary (LVVI ).

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and the cardiac dimensions, conforms the assumption that the LVV are linearly related to body weight as well. Normalization of the LVV is performed by dividing it by BW raised by the previously calculated scaling exponent of 0.99 for EDV and ESV for SMOD-BP. The exponents of the allometric equation for the monoplane SMOD showed to be very close to 1 as well. The calculations of BSA is performed by using BW in grams and the following formula (BOON et al. 1983): (10.1 × 𝐵𝑊 ^. ) ÷ 10 . Simplified the formula is: 𝐵𝑆𝐴 = 10 × 𝐵𝑊 . Consequently the exponent should have been closer to 0.667 to confirm a linear relationship between LVV and BSA. The allometric equation enables a prediction of the expected EDV and ESV; however it requires tables for the different body weights. More beneficial are the indices for EDV and ESV, which could be calculated after measuring the LVV and supplying the body weight (Table 3). Simplified it can also be concluded that an indexation to BW should be sufficient.

Comparison of different examination planes

One of the aims of the present study was to compare the LVVI of SMOD-BP as a reference method with monoplane SMOD-L4 and SMOD-R4. The main ascertainment of the study is the disagreement between monoplane and biplane SMOD measurements in dogs. The cardiac volumetric measurements in ED and ES showed significant differences for the comparison of SMOD-BP and SMOD-L4. An explanation might be that the view of the la4Ch was frequently foreshortened. The SMOD formulary includes the longer of the two measured lengths which results in a significant higher calculated volume using the biplane method, because la4Ch view showed significant smaller heights than the la2Ch view. Surprisingly the calculated LVV of SMOD-L4 and SMOD-L2 didn’t show significant differences although the significant differences of lengths of these chamber views. An explanation could be that the monoplane formula assumes a round instead of an elliptical cross sectional area, which might lead to an overestimation of a calculated volume in case of a wider LV cross section. As a consequence it could be concluded that the exclusive measurement of only one chamber view for volume prediction is not appropriate to reflect the LV shape. This fact should be considered concerning the comparison of SMOD-L4 and SMOD-R4. In veterinary medicine most of the studies used a modified

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2015) as well as monoplane SMOD (SERRES et al. 2008). Both methods follow the assumption that the LV is symmetrical, because the la4Ch and rp4Ch view should match. However our results showed, like for the la4Ch and la2Ch view, a significant difference for the LV length measurements but not for the diastolic volumes. The

2015) as well as monoplane SMOD (SERRES et al. 2008). Both methods follow the assumption that the LV is symmetrical, because the la4Ch and rp4Ch view should match. However our results showed, like for the la4Ch and la2Ch view, a significant difference for the LV length measurements but not for the diastolic volumes. The

Im Dokument Linksventrikuläre Volumenerfassung mittels monoplaner und biplaner Scheibchensummationsmethode nach Simpson bei gesunden Hunden und Hunden mit degenerativer Mitralklappenendokardiose (Seite 35-66)