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Background: End-systolic volume index (ESVI) is a marker of systolic function, which can be assessed by the geometric (GM, based on Teichholz formula) or 2 planimetric methods (PM, Simpson's derived and length area methods).
Hypothesis: Systolic dysfunction (SyD) may be observed in dogs with mitral valve disease (MVD) and is better assessed by PM than GM, which does not take into account the longitudinal left ventricular systolic shortening.
Animals: Six healthy dogs were used to determine the variability of the tested variables (Study 1). These variables were then prospectively assessed (Study 2) in 101 small breed dogs: 77 dogs with MVD and 24 healthy controls (CD).
Methods: ESVI was measured by GM and PM in awake dogs.
Results: All within- and between-day coefficients of variation were <11% (Study 1). For Study 2, a nonlinear overestimation of ESVI was observed by GM compared with PM. PM-derived ESVI was significantly increased in ISACHC class 3 dogs compared with ISACHC class 1 dogs and exerted a significant influence on cardiac events at 5 months in dogs with MVD from ISACHC classes 2 and 3 (P < .05).
Conclusions and Clinical Importance: ESVI can be calculated by GM and PM with good repeatability and reproducibility. However, GM overestimates ESVI in a nonlinear way. Therefore, PM-derived ESVI should be preferred for the detection of SyD that is present at the late stages of the disease.
Mitral valve disease (MVD) is the most common acquired heart disease in the dog.1–4 The natural history of this pathologic condition is usually slowly progressive with an asymptomatic period of variable and unpredictable duration. Various complications such as pulmonary arterial hypertension (PH),5 chordae tendinae rupture,6 and cardiac arrhythmiasa may influence prognosis and clinical progression of the disease. Another potential MVD complication also described in humans with mitral regurgitation (MR) is left ventricular (LV) systolic dysfunction (SyD).7–9 However, the detection of MR-associated LV SyD remains challenging in both humans and dogs. Assessment of SyD in humans with MR may rely on comparison between pre- and postoperative values of echographic variables when mitral valve replacement or repair is performed.7–9 However, such studies are currently difficult to undertake in the dog, because mitral valve surgery is a very rare treatment option for canine MVD.10,11
Several M-mode echocardiographic indices such as fractional shortening (FS) or ejection fraction (EF) are commonly used for the noninvasive evaluation of systolic function in the dog.12 However, these parameters are dependent on both wall stress and loading conditions, which may be altered in the case of MR.13–15
End-systolic volume index (ESVI) is another echocardiographic variable, which has been shown to be a load-independent predictor of postoperative SyD in humans.7,8 This index has also been demonstrated to be relatively independent of experimental increased preload in the dog.16 Three ultrasound methods may be used to evaluate ESVI: the Teichholz method, also called the geometric method (GM), using M-mode linear measurement of the LV systolic diameter,12,17 and 2 planimetric methods (PM), including the Simpson's derived method of disks (SDM) and the length-area method (LAM).18,19
Unlike SDM and LAM, the Teichholz method does not involve direct measurement of longitudinal LV dimension, and this may lead to either overestimation or underestimation of LV volume in dogs with globoid or elongated hearts, respectively. Using SDM, heart volume is measured as the summation of parallel cylinders, whose diameters are derived from endocardial border tracing performed on 1 or 2 orthogonal LV apical views. The LAM relies on the following simple formula:
where V is the LV volume, A is the LV area, and L is the LV length measured on a single plane apical view.
Unlike the Teichholz method, both SDM and LAM have been validated against invasive methods in the anesthetized dog with good correlations between stroke volumes and EF assessed by PM and those calculated either by thermodilution or cineangiography in both normal and ischemic states.20,21 Additionally, in 1 study, GM and PM were used and compared with the conductance catheter technique in healthy anesthetized dogs with various drug-induced changes in loading conditions.b In this report, PM were more closely correlated to the invasive method than GM. However, the within- and between-day variability of SDM- and LAM-derived variables (ESVI, end-diastolic volume index [EDVI], and EF) has never been assessed in the awake dog, nor that of GM variables. Moreover, these 3 echocardiographic techniques have never been compared with each other in dogs with naturally occurring heart diseases. In other words, whether or not LV volumes could be indistinctly assessed by PM or GM in cardiac dogs remains unknown. Lastly, the comparative correlation between MVD severity and these LV shape and volume indices as well as the prognostic value of the latter have never been assessed in the context of spontaneous canine MVD.
The aims of this study were therefore to (1) determine the comparative within- and between-day variability of ESVI, EDVI, and EF assessed by both GM and PM in healthy dogs (Study 1), (2) quantify and compare these LV variables in a large population of healthy and diseased dogs affected by MVD, and (3) analyze their correlation with several clinical and echo-Doppler markers of MVD severity as well as their comparative prognostic value (Study 2).
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Few studies have focused on systolic function in dogs with MVD.12,31 We report the intraobserver variability of markers for quantifying LV shape, volumes, and function calculated by different echocardiographic methods (GM and PM) and association in dogs with MVD with regard to heart failure severity, several echocardiographic and Doppler variables (LA/Ao, RF, and SPAP), and short-term prognosis.
The within- and between-day variability of LV volumes and EF assessed by 3 different echocardiographic techniques (ie, Teichholz formula method, SDM, LAM) were good and comparable in the awake standing dog. The within- and between-day CV values for all indices (ESVI, EDVI, and EF) were <11% (2–10.6%) without any interaction between dog and day for the 2 PM (SDM, LAM). Similar results were obtained for LVSI, which combines 1 M-mode variable (LV end-diastolic diameter) and 1 2D variable (LV end-diastolic length measured on the left apical 4-chamber view). These results are similar to those obtained in humans.32
Study 2 results demonstrate that MVD progression is associated with a change in LV shape. This shape alteration is characterized by an increased sphericity as shown by the significant decrease in LVSI with ISACHC heart failure class. Because the Teichholz formula does not take into account this progressive change in LV shape during the time course of the disease,33 the GM is inaccurate for assessing LV volumes and the subsequent EF in dogs with MVD. This inadequacy of GM compared with the 2 other “anatomic-based” methods tested here (SDM and LAM) was confirmed by the Bland-Altman results, which indicate that GM overestimates ESVI in a nonlinear way. This bias is of major importance because it means that GM leads to an overestimation of LV size that becomes more marked with disease progression. These results are consistent with a comparative echographic and catheter-based study performed on dogs with drugs-induced changes in loading conditions.b Moreover, there were tight limits of agreement between the 2 PM. From a practical point of view, this finding is of importance because LAM can be easily performed with any commercially available echocardiographic system, without requiring a specific software (which is not the case for SDM).
The results of Study 2 also confirm the presence of increased ESVI in dogs with symptomatic MVD, as already reported in large- and small-breed dogs.12 This confirms that a “global” SyD becomes apparent during the course of the disease. However, although our study included more diseased small-breed dogs than in the Borgarelli et al report12 (77 versus 18, respectively), an increased ESVI could not be identified in ISACHC class 2 dogs (subgroup 2-2). This lack of statistical significance was probably related to the particularly wide range of ESVI observed in both healthy and diseased dogs, with all methods performed. The use of indices indexed to body surface area should theoretically have limited the influence of a weight effect. However, in the present study a marked individual variability exists, leading to an important overlap between healthy and diseased dogs, therefore, limiting the possibility to determine a clear pathologic threshold. For example, the use of a GM-ESVI higher than 30 mL/m2, a threshold commonly described as indicative of SyD in humans (but never validated in the dog),7,12 would lead to the diagnosis of SyD in 37.5% (9/24) and 53% (8/15) of symptomatic dogs (ISACHC classes 2 and 3, respectively) from the present study. However, the same threshold would also “detect” SyD in 34% (13/38) of ISACHC class 1 dogs and 29% (7/24) of healthy control dogs. This wide range of ESVI observed in healthy dogs may be related to interbreed differences in systolic function, presence of occult primary myocardial disease, athletic ability, or differences in autonomic nervous system tone. The same factors of interindividual variation may also be found in diseased dogs, because of the potential interaction between hyperkinesia secondary to MR and SyD intrinsically related to MVD. Finally, one may hypothesize that right ventricular alteration related to PH may also be responsible for a change in LV volume. In symptomatic dogs, the estimated SPAP was frequently markedly increased, reaching a similar level in certain cases to systemic pressure. This increased SPAP could exert an influence on LV volume by both decreasing LV preload and “mechanically” limiting LV expansion with flattening of the interventricular septum. This probably explains why some dogs with severe MVD in our study showed decreased LV volumes when assessed by GM. These limitations may be overcome by new promising noninvasive imaging techniques such as tissue Doppler imaging derived techniques. Recently, the diagnostic interest of myocardial strain and strain rate imaging has been described in dogs with MVD,f alterations in these parameters being observed in dogs with severe MR compared with control dogs.
Indirect assessment of MR incompetence (assessed by RF) and its consequences on pulmonary vascular tone (assessed by SPAP) have already been described by our group to be significantly correlated to heart failure classes, left atrial size, and also to each other.5,23 The present study confirms these previous results, but fails to show a significant correlation between ESVI and both RF and SPAP. This lack of correlation between ESVI and these 2 markers of MR severity may be explained by the fact that in symptomatic dogs, RF and SPAP were markedly increased in almost all dogs, whereas ESVI showed greater variability.
Nevertheless, although PM-derived ESVI, RF, and SPAP appear to be relatively independent of each other, the present results also indicate that all these variables represent prognostic factors for survival or disease worsening of symptomatic MVD. To date, the prognostic interest of ESVI has only been retrospectively studied in dogs with asymptomatic MVD, and was found to exert no influence over probability of the disease worsening.g
The current studies have several limitations. First, the validation protocol was performed in healthy dogs of various sizes, and the results are not necessarily transposable to small breed diseased dogs. Additionally, this validation protocol did not include assessment of interobserver variability. Second, in our study, as is commonly the case in humans,18 PM relied on the left apical window, which may truncate the apex.b The right parasternal long axis 4-chamber view might have been a useful alternative.b Additionally, the dogs in Group 1 were significantly younger and with a different sex ratio than those in Group 2, and an influence of age or sex on systolic function may be hypothesized. However, ESVI has already been demonstrated to be independent of age when young and old dogs of the same breed were compared.34 More than 5 dog breeds were used in the present study, and this represents another limitation. A clear breed effect on systolic function has been demonstrated using the tissue Doppler imaging technique.27 Therefore, a comparison of PM and GM systolic variables to catheter-based measurements within a single breed of diseased dogs, together with the assessment of inter- and intraobserver variabilities, would have been the ideal protocol design.
In conclusion, according to our results, the use of GM based on the Teichholz formula should not be recommended for the assessment of LV volume in dogs with MVD, because this method does not take into account the increasing sphericity that occurs during the disease progression. The 2 PM may be used instead with acceptable repeatability, reproducibility, and good limits of agreement. However, a pathologic threshold for PM-ESVI allowing diagnosis of SyD in dogs with MVD could not be fixed from the present results, owing to an important overlap of values between healthy dogs and dogs with MVD from different ISACHC classes. Further studies should, therefore, be carried out to establish breed-specific reference ranges of PM variables. Until such studies are completed, the detection of SyD using PM-ESVI should rely on longitudinal follow-up on the same animal. The long-term prognostic value of PM systolic variables also needs to be assessed in further prospective studies.
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aO'Sullivan ML, O'Grady MR, Walker C, et al. Frequency of ventricular ectopy in dogs with chronic mitral valve disease and congestive heart failure treated with pimobendan or benazepril. Presented at the 25th Annual ACVIM Forum Seattle, WA, June 6–9, 2007. J Vet Intern Med 2007;21:587 (abstract)
bDe Morais HAS, Bonagura JD, Muir III WW, Nakade T. Left ventricular volumes obtained by echocardiography in intact dogs: Validation using the conductance catheter. Presented at the 15th Annual ACVIM Forum, Lake Buena Vista, FL, May 22–25, 1997. J Vet Intern Med 1997;11:140 (abstract)
cVivid 7, General Electric Medical System, Waukesha, WI
dEchopac Dimension, General Electric Medical System
eSystat version 10.0, SPSS Inc, Chicago, IL
fWess G, Javornik A, Keller K, et al. Differences in systolic function between small and large breed dogs with myxomatous mitral valve degeneration assessed by myocardial strain and strain rate measurements. Presented at the 25th Annual ACVIM Forum, Seattle, WA, June 6–9, 2007. J Vet Intern Med 2007;21:590 (abstract)
gCrosara S, Borgarelli M, La Rosa G, et al. Natural history and risk predictors of chronic degenerative mitral valve disease in asymptomatic dogs. Presented at the 17th Annual ECVIM Forum, Budapest, Hungary, September 13–15, 2007 (abstract)