Introduction
The 3 phasic functions of the RA are integral for RV filling and are as follows: reservoir function (filling associated with an inflow of blood from the vena cava during ventricular systole), conduit function (passive flow of blood from the RA into the RV during ventricular diastole), and booster pump function (active blood flow from the RA into the RV during atrial systole).1 Therefore, RA and RV function is closely related throughout the cardiac cycle.
Speckle-tracking echocardiography is a novel quantitative method that can be used to evaluate the myocardial function of the LA, left ventricle, and RV without the problems of angle dependence and geometric assumptions.2–5 Two-dimensional STE relies on the formation of speckles in echocardiographic images by reflection, scattering, and interference between the tissue and ultrasound beam. These speckles appear homogeneously distributed within the myocardium and can be tracked from frame to frame throughout the cardiac cycle.
Recently, several studies6–8 of people have shown that STE can be used to evaluate RA function. In people with PH, RALS is impaired and correlated with hemodynamic variables (ie, RA pressure and cardiac index), and impaired RALS can help predict clinical deterioration and prognosis.9–12
Results of 1 study13 of healthy dogs indicate that STE is feasible and yields repeatable and reproducible results for evaluating LA phasic function. One study14 of dogs with PH reveals that the area of the RA as determined with echocardiography is a useful predictor of right-sided heart failure. To date, however, no reports regarding RA function evaluated with STE in dogs have been published. Therefore, the primary objective of the study reported here was to evaluate the feasibility, repeatability, and reproducibility of determining RALS indices with STE and to report RALS indices for healthy dogs. The secondary objective was to determine correlations between sex, age, body weight, heart rate, and blood pressure and RALS indices in healthy dogs.
Materials and Methods
Animals
Dogs referred to the Veterinary Teaching Hospital of Hokkaido University between November 2014 and March 2018 were eligible for enrollment. Exclusion criteria were the presence of a heart murmur or pathological arrhythmia, a history of heart or respiratory disease, and administration of drugs known to affect the cardiovascular system. Ten Beagles that were part of a research colony and 110 client-owned dogs were enrolled; clients consented to enrollment. Fifty-seven dogs were female and 63 were male (female-to-male ratio, 0.9:1). Mean ± SD age was 6.5 ± 3.8 years (range, 0.5 to 15 years) and body weight was 9.2 ± 9.6 kg (range, 1.5 to 61.3 kg). Dogs were of 25 different breeds and types, and the most common were Chihuahua (n = 19 [15.8%]), Dachshund (15 [12.5%]), Beagle (10, [8.3%]), mixed breed (10 [8.3%]), and Poodle (9 [7.5%]). All dogs were determined to have normal heart anatomy and myocardial function on the basis of physical examination, including cardiovascular examination and indirect arterial blood pressure measurement (with a monitor that used the oscillometric method), and standard echocardiographic examination (B-mode, M-mode, pulsed- and continuous-wave Doppler, and color flow Doppler imaging). A small, thin central TR jet with color flow Doppler imaging and a faint TR signal with continuous-wave Doppler imaging indicated mild TR. Dogs with mild TR were not excluded from this study because mild TR is considered physiologic in many healthy dogs.15 The most common reasons for echocardiography of the dogs in this study were preanesthetic assessment for MRI (n = 66) and general health assessment (54).
Echocardiographic examination
Two-dimensional echocardiography was performed by 1 investigator (TM) with an ultrasound unita equipped with a 3- to 6-MHz sector probe.b All dogs were examined without sedation and with gentle restraint in left and right lateral recumbency. The frame rate was optimized to > 200 frames/s by narrowing the sector width and reducing image depth to focus on the RA. Peak TR velocity was recorded from the echocardiographic view that yielded the maximum velocity. A lead II ECG trace was simultaneously recorded during echocardiography.
A modified left apical 4-chamber view optimized for visualization of the right side of the heart and maximization of RV diameter at the heart base was achieved by rotating the transducer.14,16 The RV was not foreshortened, and visualization of the left ventricular outflow tract was avoided. Care was also taken to obtain the best images of the endocardial border of the RA. The area of the RA was estimated by planimetry at the end of ventricular systole, such that the endocardial border of the RA was manually traced from the lateral aspect of the tricuspid valve annulus to its septal aspect, excluding the cranial vena cava, caudal vena cava, and RA appendage (Figure 1).14,16 Values for RA area were normalized by dividing RA area by the dog's body surface area.14
Right atrial longitudinal strain was determined with STE by using conventional grayscale imaging from the same modified left apical 4-chamber view for estimation of the RA area.16 Three consecutive cardiac cycles were stored on a hard drive for later analysis with motion-tracking software.c Right atrial longitudinal strain was measured at 3 time points/cardiac cycle as follows: maximum RALS during ventricular systole (RALSmax), minimum RALS during ventricular diastole (RALSmin), and RALS before atrial systole (RALSa). The endocardial border of the RA was delineated into 6 segments (basal, middle, and apical lateral walls and apical, middle, and basal septum), and the tracing was adjusted to incorporate the entire RA myocardium. The beginning of the QRS complex (end diastole) was set as the reference from which the software generated an RALS curve for each of the 6 segments; then, the software generated a curve of the average of all 6 segments (Figure 1). A cine loop was previewed to confirm whether the segment mirrored the RA endocardial border throughout the cardiac cycle, and the tracing for the segment was manually adjusted if necessary. Right atrial longitudinal strain was expressed as a positive percentage. Right atrial longitudinal strain during ventricular systole was an indicator of reservoir function, εE was an indicator of conduit function, and εA was an indicator of booster pump function. These 3 phasic functions were calculated as follows:
Statistical analysis
Normal distribution of the data was determined with the Shapiro-Wilk test. Analyses were performed with statistical software.d Reference intervals were defined as central 95% intervals bounded by the 2.5th and 97.5th percentiles, and the upper and lower limits of the RI with 90% CIs were determined by means of a nonparametric approach.
To assess intraobserver within-day and interobserver agreement for measurements of RALS indices (εS, εE, and εA), 5 client-owned dogs were randomly selected. For within-day measurements, STE was performed twice in 1 day by 1 investigator (TM). Approximately 30 minutes elapsed between echocardiographic examinations. For interobserver agreement, echocardiography was performed by 2 investigators (TM and TO). Each investigator was blinded to their previous measurements. Approximately 30 minutes elapsed between echocardiographic examinations. The following linear model was used for variables in within-day and interobserver variability analyses17:
where Yijk is the kth value measured for dog j by investigator i, μ is the general mean, invi is the differential effect of investigator i (a fixed effect), dogj is the differential effect of dogj, (inv × dog)ij is the interaction term between the investigator and dog, and εijk is the model error. The SD of within-day repeatability was estimated as the residual SD of the model, and the SD of interobserver agreement was the SD of the differential effect of the investigator. The corresponding CVs were determined by dividing each SD by the mean. Agreement was considered high (ie, clinically acceptable) when the CV was < 20%.17,18 The percentage difference between measurements for the variability analysis was calculated as follows19–21:
Correlations between RALS indices and age, body weight, heart rate, normalized RA area, and TR velocity were determined by use of the Pearson correlation coefficient test. Differences regarding RALS indices between dogs with mild TR and those without TR and between males and females were evaluated with an unpaired t test. Multiple linear regression analysis with forward stepwise selection and Akaike information criteria was used to assess the relationship between RALS indices and sex, age, body weight, heart rate, and blood pressure. Values of P < 0.05 were considered significant.
Results
Repeatability and reproducibility of RALS indices
Intraobserver within-day agreement for all RALS indices was acceptable (range of CVs, 2.1% to 19.1%; Table 1). Interobserver agreement for all RALS indices was also acceptable (range of CVs, 4.7% to 17.1%).
Mean, median, and lower and upper limits and intraobserver within-day and interobserver CV and their percentage differences for RALS indices (εS, εE, and εA) obtained by STE for 120 healthy dogs (110 client-owned dogs and 10 healthy Beagles).
RALS index | Mean (SD) | Median | Lower limit (90% CI) | Upper limit (90% CI) | Intraobserver within-day* CV (%) (D [%]) | Interobserver* CV (%) (D [%]) |
---|---|---|---|---|---|---|
εS (%) | 32.5 (7.9) | 31.2 | 19.7 (16.1–20.5) | 54.9 (46.7–61.6) | 2.1 (2.7) | 4.7 (5.6) |
εE (%) | 14.7 (6.2) | 13.5 | 6.4 (5.6–7.5) | 30.8 (20.6–35.9) | 19.1 (24.4) | 17.1 (23.8) |
εA (%) | 17.2 (4.3) | 16.9 | 8.6 (7.4–9.5) | 26.5 (24.6–27.7) | 14.0 (17.3) | 11.0 (13.6) |
Results were obtained from 5 client-owned healthy dogs.
D = Difference, calculated by the following formula: ([maximum value – minimum value]/maximum value) × 100%.
RALS indices and dog characteristics
Mean, SD, median, lower and upper limits, and 90% CIs for the RALS indices derived from all 120 dogs were summarized (Table 1). All RALS indices did not significantly differ between male and female dogs. Mild physiologic TR was observed in 26 (21.7%) dogs. Indices of RALS also did not significantly differ between dogs without TR and with mild TR.
Correlation between RALS indices and dog characteristics
Age was negatively correlated with εS and εE but was not correlated with εA (Table 2; Figure 2). Normalized RA area was positively correlated with εS and εE but was not correlated with εA. Body weight, heart rate, mean blood pressure, and TR velocity were not correlated with RALS indices. With the multiple regression analysis, age was the only independent predictor of εS (standard β = −0.38; P < 0.001) and εE (−0.45; P < 0.001).
Correlation coefficients (r) for RALS indices and characteristics, normalized RA area (nRAA), and TR velocity for the dogs in Table 1.
RALS index | Body weight | Heart rate | Age | Blood pressure | nRAA* | TR velocity |
εS | 0.08 | −0.05 | −0.38† | −0.16 | 0.22† | 0.24 |
εE | 0.17 | −0.13 | −0.52† | −0.09 | 0.27† | 0.28 |
εA | -0.13 | −0.08 | 0.09 | −0.17 | −0.02 | 0.03 |
Calculated by RA area divided by a dog's body surface area.
P < 0.05.
Discussion
To the best of our knowledge, this was the first study that included a description of the feasibility, repeatability, and reproducibility of measurements of and reference intervals for RALS indices obtained with STE in healthy dogs. Previous studies2,14 of the RA of dogs have focused on RA area rather than RALS indices. Results of the present study yielded measurements of εS, εE, and εA derived by use of STE for a large group of nearly equal numbers of male and female dogs of various ages, body weights, and breeds without heart disease, which may be considered as reference intervals for such a group. With such diversity, the estimated reference intervals for the RALS indices of these healthy dogs may be helpful in determining RA function in clinical practice.
Intra- and interobserver repeatability and reproducibility, respectively, for the measurement of RALS indices were good, with CVs and percentage differences < 20% in a small number of dogs without heart disease, except for the percentage difference for εE. Yet this result was consistent with values reported in previous studies7,8 of healthy people.
Similar to a study7 of people, RALS indices for the dogs in the present study were higher than those reported13 for LA longitudinal strain indices obtained for healthy dogs by means of STE with the same ultrasound machine and software as was used in the present study (εS, median, 31.2% [present study] vs 25.4% [previous study]; εE, 13.5% vs 11.1%; εA, 16.9% vs 14.2%). These differences may be related to greater deformation of the RA and RV, especially at the tricuspid annulus, compared with that of the LA and left ventricle.7,22 Although the intervals of RALS indices, especially those for εS, were wide in the present study, the wide range of values for εS was similar to that obtained from a study23 of people (mean ± SD, 32.5 ± 7.9% vs 35.0 ± 7.0%).
In the present study, εS and εE were negatively correlated and significantly related with age, with the former similar to previous reports6,8 of people. In a previous study13 of healthy dogs, LA longitudinal strain during ventricular early diastole and ventricular systole were negatively correlated with age. This negative correlation may be caused by impaired early ventricular diastolic filling associated with increasing age.24 Therefore, the impact of increased age on εS and εE should be considered for dogs seen in clinical practice.
In contrast, εA was not correlated with age. This result conflicts with that of a study8 of healthy people in which a positive correlation was found between εA and age. In healthy dogs, LA longitudinal strain during atrial systole is also positively correlated with age.13 This positive correlation may be because of the compensatory mechanism for impaired early ventricular diastolic function. The disagreement may be caused in part by differences between dogs and people and between the RA and LA. In the present study, εA was an age-independent index in healthy dogs.
Also in the present study, RALS indices and TR velocity were not correlated, and indices for dogs with TR did not significantly differ from those for dogs without TR. However, TR was only mild in all dogs with TR. Yet volume overload associated with moderate or severe TR could enhance RA function on the basis of the Frank-Starling mechanism. Indeed in people, εS is a load-dependent index.25 Additionally, LA longitudinal strain was enhanced by volume overload in an experimental model of healthy dogs.26 A similar study of RALS with volume overload in dogs and a study that includes dogs with different degrees of TR are needed to confirm the lack of an effect of TR on RALS indices in the present study.
Right atrial longitudinal strain indices derived with STE are useful for the prediction of hemodynamic deterioration in and prognosis for people with PH.9–12,27 Patients with severe PH have significantly lower εS values, compared with those of healthy people, and the results of receiver operating characteristic analysis indicate that εS is useful to distinguish between patients with PH and healthy people.23 Moreover, εS well reflects pulmonary hemodynamics (ie, pulmonary arterial pressure and pulmonary vascular resistance),9–12 and the addition of εS to the RV longitudinal strain indices determined with STE improves the ability to predict poor outcomes for patients with PH.9,28,29,30,31 Recently, several studies2,32,33,34,35,36,37 of dogs have included echocardiographic indices for the assessment of RV function. As with people, comprehensive assessment of the right sideof the heart with STE may have clinical implications for better management of dogs with PH.
The present study had several limitations. First, only a small number of dogs without heart disease were evaluated to determine repeatability and reproducibility. Additionally, dogs without heart disease may have had extracardiac diseases that affected the echocardiographic parameters and therefore RALS indices. Second, dogs may have had subclinical heart disease, and follow-up examinations were not performed to determine whether they did. Third, no reference standard of RA function, such as MRI or 3-D echocardiography, was included. Fourth, RALS indices were determined with software specific for LV longitudinal strain because RALS-specific software had yet to be developed at the time of the study.
The present study revealed the feasibility, repeatability, and reproducibility for the measurement of and revealed estimated reference intervals for RALS indices derived from STE in healthy dogs. Both εS and εE were affected by age; therefore, age should be considered when interpreting these RALS indices. Indices obtained in the present study may serve as reference intervals to which indices obtained for dogs with heart disease, specifically right-sided heart disease, could be compared.
Acknowledgments
Funded in part by a Grant-in-Aid for Scientific Research from the Japanese Society for the Promotion of Science (Nos. 16K18800 and 19K06422).
The authors declare that there were no conflicts of interest.
Abbreviations
CV | Coefficient of variation |
εA | Right atrial longitudinal strain during atrial systole |
εE | Right atrial longitudinal strain during ventricular early diastole |
εS | Right atrial longitudinal strain during ventricular systole |
LA | Left atrium |
PH | Pulmonary hypertension |
RA | Right atrium |
RALS | Right atrial longitudinal strain |
RV | Right ventricle |
STE | Speckle-tracking echocardiography |
TR | Tricuspid regurgitation |
Footnotes
Artida, Canon Medical Systems Corp, Utsunomiya, Tochigi, Japan.
PST-50BT, Canon Medical Systems Corp, Utsunomiya, Tochigi, Japan.
2D Wall Motion Tracking, Canon Medical Systems Corp, Utsunomiya, Tochigi, Japan.
JMP, version 13.0, SAS Institute Inc, Cary, NC.
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