J Vet Intern Med 2008;]]:1–12

C o m par is on of 3 Ult r as ou n d M e t h o d s f o r Q u a n t i f y i n g L e f t V e n t r i c u l a r Sy s t o l i c F u n c t i o n : C or r e l a t i o n w i t h Di s e a s e S e v e r i t y a n d P r o g n o s t i c V a l u e in Do g s w i t h M i t r a l V a l v e Di s e a s e F. Serres, V. Chetboul, R. Tissier, L. Poujol, V. Gouni, C. Carlos Sampedrano, and J.-L. Pouchelon 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 o11% (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 o .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. Key words: Canine; Echocardiography; Heart; Simpson; Teichholz.

itral 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 MRassociated 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

M

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: V ¼ 0:85A2 =L;

From the Unite´ de Cardiologie d’Alfort (Serres, Chetboul, Gouni, Carlos Sampedrano, Pouchelon), Unite´ Mixte de Recherche INSERM U841 (Chetboul, Gouni, Tissier, Carlos Sampedrano, Pouchelon), Unite´ de Me´decine (Poujol), and Unite´ de PharmacieToxicologie (Tissier), Ecole Nationale Ve´te´rinaire d’Alfort, Maisons-Alfort cedex, France. Corresponding author: Vale´rie Chetboul, DVM, PhD, DiplECVIM-CA (cardiology), Unite´ de Cardiologie d’Alfort, Ecole Nationale Ve´te´rinaire d’Alfort, 7 avenue du Ge´ne´ral de Gaulle, 94704 Maisons-Alfort cedex, France; e-mail: [email protected].

Submitted October 14, 2007; Revised January 9, 2008; Accepted January 23, 2008. Copyright r 2008 by the American College of Veterinary Internal Medicine 10.1111/j.1939-1676.2008.0097.x

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

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to the invasive method than GM. However, the withinand 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).

Materials and Methods Experimental Design Two separate studies were performed. Study 1 (Validation Protocol). The within- and between-day variability of GM and PM variables (ESVI, EDVI, and EF) were determined by performing 36 echocardiographic examinations on 6 healthy, awake dogs (age: 3.1
1.8 years [0.8 – 5.0 years]; weight: 22.7
11.2 kg [11 – 40 kg]) on 4 different days over a 2-week period: 1 Cane Corso (neutered female), 1 Beagle (neutered female), 1 Cocker Spaniel (neutered female), 1 Labrador (neutered female), 1 Brittany Spaniel (neutered male), and 1 Boxer (neutered male). The within- and between-day variability of the LV index of sphericity22 (LVSI) was also assessed. On a given day, 3 dogs were examined at 3 nonconsecutive times. Each variable was measured 3 times on 3 consecutive cardiac cycles using the same frame for GM, and using the same loop for the PM. The mean values were used to determine the within- and between-day variability. This protocol involved 1 single trained observer (VC). Study 2 (Prospective Study). The study population consisted of client-owned dogs that prospectively underwent a complete echocardiographic and Doppler examination at the Cardiology Unit (National Veterinary School of Alfort, France) during 2006 and 2007. These ultrasound examinations were performed by the observer involved in Study 1 (VC) and by 3 other observers (FS, VG, and CCS). The latter 3 observers had been trained by the 1st observer in the use of GM and PM for at least 1 year before performing the echocardiographic examinations. For each dog, the owner’s consent was obtained before enrollment in the study. In order to limit influence of the breed effect on systolic function, only small breed dogs (15 kg) were included in the study. Dogs receiving pimobendan were not included in the study because of the positive inotropic effect of this drug. Dogs from Study 2 were assigned to either Group 1 or 2. Group 1 consisted of healthy control dogs characterized by both normal physical and echo-Doppler examinations, whereas Group 2 included dogs with MVD. Diagnosis of MVD was based on the following criteria: (1) left systolic apical heart murmur of late appearance (age 41 year old), (2) no history of infectious disease, and (3) echocardiographic and Doppler signs of MVD, including irregularly thickened mitral valve leaflets (observed on the right parasternal 4-chamber view) and a color-flow jet

of systolic mitral insufficiency in the left atrium (observed on the left parasternal 4-chamber view). Dogs with MVD (Group 2) were included in the study only if the color-flow jet of systolic mitral insufficiency was adequate for color and continuous Doppler mode examination, allowing quantification of MR using the proximal isovelocity surface area (PISA) method as previously described and validated by our group.23,24 For each dog from Group 2, the degree of heart failure was also classified according to ISACHC recommendations,25 leading to 3 subgroups (subgroups 2-1, 2-2, and 2-3 corresponding to ISACHC classes 1, 2, and 3, respectively).

Echocardiography and Standard Doppler Examination Conventional echocardiographic and Doppler examinations were performed in awake standing dogs using continuous ECG monitoring with an ultrasound unitc equipped with 7.5–10, 5–7.5, and 2–5-MHz phased-array transducers as previously described and validated.26 Left Atrial and Ventricular Dimensions. Measurements of the aortic and left atrial diameters were obtained by a two-dimensional (2D) method using the right parasternal transaortic short axis view as previously described.27 The left atrium/aorta ratio (LA/Ao) was then calculated. LV measurements were first obtained from the right parasternal location using 2D-guided M-mode echocardiography according to recommendations of the American Society of Echocardiography (Fig 1A).28 LV systolic and diastolic diameters were then used for the respective calculation of ESV and EDV using the Teichholz formula as previously described.12 Ventricular volumes measured by this GM (GM-ESV and GM-EDV) were then indexed to body surface area (GM-ESVI and GMEDVI), which was derived from body weight using the described equation.29 Additionally, GM-derived ventricular volumes were used to calculate the LV ejection fraction (GM-EF) according to the following formula:12 EF ¼ 100  ðEDVESVÞ=EDV: LV volumes and indexed volumes were also measured by the 2 PM using the left apical 4-chamber view (Fig 1B and 1C). Briefly, long-axis images optimizing LV length and area were recorded and digitally stored. Frame-by-frame analysis was performed off-line, with selection of end-diastolic frames (corresponding to onset of qRs, ie, at the time of mitral valve closure) and end-systolic frames (corresponding to end of T wave, ie, last frame before mitral valve opening).19 The endocardial border on each selected image was traced and closed around the mitral annulus, thus delimiting the end-diastolic and end-systolic LV areas. Maximal diastolic and systolic LV lengths were also measured from the mitral annulus to the endocardial border of the LV apex. The LV volumes were then automatically calculated by a specific softwared and the subsequent EF (SDM-EF) by Simpson’s rules. As for GM, the 2 SDM-derived enddiastolic and end-systolic LV volumes were also indexed to body surface area (SDM-ESVI and SDM-EDVI, respectively).29 The same end-diastolic and end-systolic LV lengths and LV areas obtained from the left apical 4-chamber view were used to calculate LV volumes and EF using the LAM formula as described above, and LV volumes were then indexed to the body surface area (LAMESVI, LAM-EDVI, and LAM-EF, respectively).29 Lastly, LVSI defined as the ratio of LV end-diastolic length to the M-mode LV end-diastolic diameter was calculated according to the ESVC taskforce recommendations using the left apical 4-chamber view.22 Assessment of MR Severity. MR was quantitatively assessed on each dog from Group 2 by the PISA method as previously described and validated.23 The studied PISA variable was the regurgitation fraction (RF). Color-flow Doppler examination of the tricuspid valve was performed in all cases by use of the left apical 4-chamber view. When tricuspid regurgitation (TR) was

Assessment of Systolic Function in Dogs

3

A

LV

B LV

LV

LA

LA

Diastole

Systole

C

LV

LV

LA

Diastole

LA

Systole

Fig 1. Echographic measurement of left ventricular (LV) volumes. (A) Geometric method performed using 2D-guided M-mode echocardiography from the right parasternal short axis transventricular view according to recommendations of the American Society of Echocardiography.28 (B) Simpson’s derived method (SDM) performed on left parasternal apical 4-chamber view optimizing LV length and area. Using frame-by-frame analysis, end-diastolic frame (corresponding to onset of qRS, ie, at the time of mitral valve closure, left image) and end-systolic frame (corresponding to end of T wave, ie, last frame before mitral valve opening, right image) were selected. Left ventricular area was measured by tracing the endocardial border on each selected image and maximal LV length was measured from the mitral annulus to the endocardial border of the LV apex. (C) Length area method performed on the same view and using the same end-diastolic (left image) and end-systolic frame (right image) as SDM. LA, left atrium; LV, left ventricle.

identified, peak systolic TR velocity was quantitatively assessed by continuous-wave Doppler mode. Bernouilli’s equation was then applied to calculate the systolic right ventricle-to-right atrium pressure gradient across the tricuspid valve. Lastly, as previously described,5,6 the systolic pulmonary arterial pressure (SPAP) was determined by adding the estimated right atrial pressure (5 mmHg in dogs with a nonenlarged right atrium, 10 mmHg in dogs with an enlarged right atrium but no right-sided heart failure, and 15 mmHg in dogs with right-sided heart failure) to the systolic right ventricleto-right atrium pressure gradient.

Follow-Up Follow-up of all symptomatic dogs (subgroups 2-2 and 2-3) was assessed 5 months after initial presentation. Dogs were classified as survivors (S) if they were still alive or nonsurvivors (NS) if they died or were euthanized for unresponsive heart failure. Additionally, dogs were classified as having ‘‘stable disease’’ (StD) if they either remained in the same ISACHC class or improved their clinical status. Dogs that either died or for which progression of heart failure class was observed during the 5-month period (from

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ISACHC class 2 to 3 or from ISACHC class 3a to 3b) were classified as having ‘‘progressing disease’’ (PD). Dogs lost at follow-up or that died from noncardiac diseases were censored for the statistical analysis.

Statistical Analysis Data are expressed as mean
standard deviation (SD). Statistical analyses were performed by computer software.e The following linear model was used to determine the within-day and between-day variability of each GM and PM variable, and also that of LVSI (Study 1): Yijk ¼ m þ dayi þ dogj þ ðday  dogÞij þ eijk ; where Yijk is the kth value measured for dog j on day i, m is the general mean, dayi is the differential effect of day i, dogj is the differential effect of dog j, (day  dog)ij is the interaction term between day and dog, and eijk is the model error. The SD of repeatability was estimated as the residual SD of the model and the SD of reproducibility as the SD of the differential effect of day. The corresponding coefficients of variation (CV) were determined by dividing each SD by the mean. For Study 2, the descriptive statistical analysis was used for age, heart rate, body weight, sex, and clinical signs. The 3 different ultrasound techniques used to measure ESVI (GM, SDM, and LAM) were compared using Bland-Altman analysis.30 Correlations between markers of MR severity (LA/Ao, RF, and SPAP) and GM or PM variables were examined by applying the Pearson correlation analysis. Differences in continuous variables among groups (groups 1, 2-1, 2-2, and 2-3) were evaluated by a one way analysis of variance (ANOVA), followed if necessary by a Student’s t-test with Bonferroni’s correction. For all comparisons, Po.05 was considered significant.

Results Study 1: Within- and Between-Day Intraobserver Variability of GM and PM Variables The within- and between-day CV values (n 5 10) and the corresponding SD values are presented in Table 1. No significant interaction was observed between day and dog except for 1 GM variable (GM-EF).

Study 2: Prospective Study of GM and PM Variables on a Large Canine Population Ninety-five dogs affected by MVD with MR quantified by the PISA method were prospectively recruited from October 2006 to July 2007. Among those dogs, 13 (14%) were not included in the study because of a body weight 415 kg and 5 (5%) because of a concurrent treatment that might have exerted an influence on systolic function (pimobendan). Therefore, 77 dogs with MVD (Group 2) were included in the study. Additionally, 24 healthy small breed dogs were recruited during the same period (Group 1). Epidemiologic and Clinical Characteristics of the Healthy Control Group (Group 1, n 5 24) and Dogs with MVD (Group 2, n 5 77). The epidemiologic characteristics of dogs from Groups 1 and 2 are presented in Table 2. As expected, Group 2 was mostly composed of males (n 5 60, 78%), aged adult dogs (10.9
3.8 years, range: 3.0–17.0 years). English Toy Spaniels, Poodles, Yorkshire Terriers, and cross-breed dogs were overrepresented in both groups. As shown in Table 3, 49% (38/77) of the dogs with MVD were asymptomatic and therefore belonged to ISACHC class 1 (subgroup 2-1). The remaining 39 dogs were symptomatic and assigned to either ISACHC classes 2 (n 5 24/77, 31%) or 3 (n 5 15/77, 20%), ie, subgroups 2-2 and 2-3, respectively. Exercise intolerance and chronic cough were by far the most common clinical signs reported (respectively 31/39 and 24/39, ie, 79 and 62%, respectively) in those animals. Clinical signs indicative of right-sided congestive heart failure were also reported (ascites in 15% of the symptomatic dogs, n 5 6). None of the dogs from Group 1 received any treatment at the time of diagnosis, whereas 18/38 dogs from subgroup 2-1 (47%), 17/24 dogs from subgroup 2-2 (71%), and 14/15 dogs from subgroup 2-3 (93%) received at least 1 treatment for heart disease at the time of diagno-

Table 1. Within- and between-day variability, expressed as standard deviations (SD) and coefficients of variation (CV), of left ventricular index of sphericity, left ventricular volumes, and ejection fraction assessed by 3 different echocardiographic techniques: the Teichholz formula method (geometric method, GM), the Simpson’s derived, and the length area methods (planimetric methods, PM). Within-Day Independent Variable

Method of Measurement

2

ESVI (mL/m )

Teichholz formula method (GM) Simpson’s derived method (PM) Length area method (PM) EDVI (mL/m2) Teichholz formula method (GM) Simpson’s derived method (PM) Length area method (PM) Ejection fraction (%) Teichholz formula method (GM) Simpson’s derived method (PM) Length area method (PM) Left ventricular index of sphericity

Between-Day

SD

CV (%)

SD

CV (%)

1.92 0.88 2.44 3.13 1.63 4.31 2.36 1.23 3.03 0.045

5.2 3.2 8.1 3.3 2.3 5.6 3.9 2.0 5.0 3.3

3.57 1.21 3.18 6.01 1.80 3.7 4.04 1.21 5.50 0.084

9.7 4.4 10.6 6.4 2.5 4.8 6.7 2.0 9.0 6.2

Significant day-dog interaction (P 5 .035).

ESVI, end-systolic indexed left ventricular volume; EDVI, end-diastolic indexed left ventricular volume.

Assessment of Systolic Function in Dogs

Table 2. Demographic characteristics of healthy control dogs (Group 1, n 5 24) and dogs with mitral valve disease (Group 2, n 5 77). Dogs

Characteristics

Whole Group 1 Group 2 Dogs Population Healthy Control with MVD (n 5 101) (n 5 24) (n 5 77)

Sex Male

60% (61/101) Female 40% (40/101) Age (years) 9.4
4.5 (mean
SD, [range]) [2.0–17.0] Body weight (kg) 8.2
3.0 (mean
SD, [range]) [1.4–15.0] Breed Cavalier and King 28% Charles Spaniel (28/101) Poodle 16% (16/101) Cross breed 15% (15/101) Yorkshire Terrier 11% (11/101) Other breeds 30% (31/101)

4% (1/24) 96% (23/24) 4.7
2.8 [2.0–10.0] 8.1
2.8 [2.0–14.0]

78% (60/77) 22% (17/77) 10.9
3.8 [3.0–17.0] 8.2
3.1 [1.4–15.0]

29% (7/24) 8% (2/24) 13% (3/24) 8% (2/24) 42% (10/24)

27% (21/77) 18% (14/77) 16% (12/77) 12% (9/77) 27% (21/77)

, P o .05 versus Group 1.

sis. Treatment included angiotensin-converting enzyme inhibitors such as benazepril, enalapril, imidapril, and ramipril (47/77 dogs [61%]), furosemide (22/77 dogs [29%]), spironolactone (19/77 dogs [25%]), theophylline (6/77 dogs [8%]), amiodarone (2/77 dogs [3%]), and diltiazem (1/77 dog [1%]). Echocardiographic and Doppler Assessment of MR Severity in Dogs with MVD (Group 2, n 5 77). As an inclusion criterion, MR severity was evaluated by PISA method with calculation of RF (38.5
17.8%, reference range: 6.6–79.6%) on all the dogs from Group 2 (Table 3). TR adequate for indirect assessment of SPAP was possible in 13/24 dogs from Group 1 (54%) and 72/77 dogs from Group 2 (94%). Within Group 2, a significant correlation (P o .05) was found between RF and the LA/Ao ratio (r 5 0.67), between RF and SPAP (r 5 0.57), and between SPAP and the LA/Ao ratio (r 5 0.52) (Fig 2A–2C). A significant increase in LA/Ao ratio, RF, and SPAP was found from subgroup 2-1 to subgroup 2-3 (P o .05, Table 3). Additionally, LA/Ao and SPAP were significantly higher in all MVD groups (ie, Group 2, and subgroups 2-1, 2-2, and 2-3) than in Group 1 (Table 3). Assessment of LV Shape, Volumes, and Systolic Function in the Healthy Control Group (Group 1, n 5 24) and Dogs with MVD (Group 2, n 5 77). A significant decrease in LVSI was found in symptomatic dogs with MVD (subgroups 2-2 and 2-3) compared with asymptomatic dogs (both Group 1 and subgroup 2-1),

5

indicating that progression of MVD was associated with increased sphericity of the LV (P o .05, Table 3). Concomitantly to this increased LV sphericity and whatever the method used (GM or PM), a significant increase in EDVI was observed in subgroup 2-3 and in subgroup 2-2 compared with both Groups 1 and subgroup 2-1 (P o .05, Table 3). Additionally, SDM-ESVI and LAMESVI were significantly higher in subgroup 2-3 compared with both Group 1 and subgroup 2-1 (P o .05) (Fig 3). Finally, a significant increase in FS and EF calculated by the 3 echocardiographic methods was found from Group 1 to subgroup 2-3 (P o .05). These variables were also significantly positively correlated (P o .05) with RF in dogs from Group 2 (r 5 0.37, 0.35, 0.39, and 0.49 for FS, GM-EF, SDM-EF, and LAM-EF, respectively). Comparison between GM and PM for Assessment of LV Volumes in the Whole Study Population (n 5 101) Including 24 Healthy Dogs and 77 Dogs with MVD. When GM and PM were compared, a significant correlation (P o .05) was found between all methods for measurement of ESVI, with the correlation between LAM-ESVI and SDM-ESVI (r 5 0.92) being higher than between LAM-ESVI and GM-ESVI (r 5 0.71), and SDM-ESVI and GM-ESVI (r 5 0.67). For EDVI and EF, correlations were also significant among all groups (P o 0.05) with the correlation between LAM and SDM (r 5 0.96 and 0.71) being higher than between LAM and GM (r 5 0.84 and 0.53), and also between SDM and GM (r 5 0.86 and 0.56). For measurement of ESVI, GM gave significantly higher values than LAM and SDM in all groups (P o .05), whereas both PM gave nonsignificantly different results. In addition, Bland-Altman analysis revealed that the difference between PM and GM increased as the mean ESVI value increased (Fig 4A–4C). This finding was associated with high limits of agreements when PM and GM were compared because the 95% confidence interval (CI) of the difference between the values assessed by these techniques was 9.6
11.2 (for GM and SDM) and 8.5
10.6 (for GM and LAM) (Fig 4A and 4B). Conversely, the comparison between LAM and SDM showed tight limits of agreements (95% CI5  1.1
3.0, Fig 4C). Correlation of LV Volumes to MR Severity (Group 2, n 5 77). Correlation analysis failed to identify a significant correlation between ESVI (assessed by GM, SDM, and LAM) and RF (r 5 0.11, 0.2, and 0.15, respectively). Conversely, EDVI was significantly correlated to RF (r 5 0.46, 0.43, and 0.44, for GM, SDM, and LAM respectively, P o .05). Similarly, SPAP was not correlated to GM-, SDM-, and LAM-ESVI (r 5 0.19, 0.15, and 0.11, respectively). However, a significant positive correlation (P o .05) was found between SPAP and EDVI (r 5 0.34, 0.34, and 0.35, for GM, SDM, and LAM, respectively). Finally, LA/Ao was significantly correlated (P o .05) to both ESVI (r 5 0.37, 0.35, and 0.34, for GM, SDM, and LAM, respectively) and EDVI (r 5 0.74, 0.64, and 0.62, for GM, SDM, and LAM, respectively).

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Table 3. Standard echo-Doppler variables assessed in healthy control dogs (Group 1, n 5 24) and dogs with mitral valve disease (Group 2, divided in subgroups 2-1, 2-2, and 2-3 for corresponding ISACHC classes 1, 2, and 3, respectively; n 5 77). Dogs Echo-Doppler Quantitative Variables

Healthy Control (Group 1) (n 5 24)

Left atrium to aorta ratio Mean
SD 0.86
0.17 [range] [0.56–1.06] Regurgitant fraction (%) Mean
SD NM [range] SPAP (mmHg) Mean
SD 14
6.5 [range] [8–30] (Assessed in n dogs) (n 5 13) Fractional shortening Mean
SD 38.8
4.8 [range] [30–49] Geometric method (GM) GM-EDVI (mL/m2) Mean
SD 80.4
18.6 [range] [49.8–122.4] GM-ESVI (mL/m2) Mean
SD 23.4
7.3 [range] [13.2–38.0] GM-EF (%) Mean
SD 70.9
6.0 [range] [57.8–82.1] Planimetric methods Simpson’s derived method (SDM) SDM-EDVI (mL/m2) Mean
SD 47.6
8.4 [range] [32.9–69.1] SDM-ESVI (mL/m2) Mean
SD 15.9
3.9 [range] [9.5–25.4] SDM-EF (%) Mean
SD 66.5
6.4 [range] [54.4–75.7] Length area method (LAM) LAM-EDVI (mL/m2) Mean
SD 49.5
10.3 [range] [30.2–67.5] LAM-ESVI (mL/m2) Mean
SD 16.9
4.3 [range] [10.2–28.3] LAM-EF (%) Mean
SD 65.5
6.7 [range] [53.4–78.2] LVSI mean
SD 1.43
0.12 [range] [1.19–1.66]

Whole MVD Population (Group 2) (n 5 77)

MVD ISACHC 1 (Subgroup 2-1) (n 5 38)

MVD ISACHC 2 (Subgroup 2-2) (n 5 24)

MVD ISACHC 3 (Subgroup 2-3) (n 5 15)

1.58
0.70 [0.59–3.49]

1.04
0.27 [0.59–1.82]

1.89
0.54,z [1.21–3.11]

2.45
0.49,z,# [1.90–3.49]

38.5
17.8 [6.6–79.6]

27.8
14.7 [6.6–70.3]

46.1
13.9z [28.3–79.6]

53.2
13.8z [31.6–73.2]

52.1
27.8 [12–153] (n 5 72)

39.1
17.0 [12–75] (n 5 33)

56.0
31.1,z [18–153] (n 5 24)

74.5
27.4,z [33–126] (n 5 15)

45.9
8.7 [31–69]

42.0
7.0 [31–56]

47.8
6.9,z [32–60]

52.7
10.1,z [34–69]

130.8
52.5 [51.7–292.3]

100.8
31.1 [51.7–174.6]

146.7
42.0,z [93.1–228.3]

181.1
62.8,z,# [91.8–292.3]

28.8
14.7 [4.3–75.8]

26.6
11.1 [9.0–47.9]

29.8
13.0 [11.0–60.8]

32.8
23.3 [4.3–75.8]

77.4
8.7 [60.1–95.1]

73.6
7.8 [60.1–88.2]

79.5
7.3,z [60.2–88.7]

83.7
8.7,z [64.1–95.1]

75.2
27.5 [36.7–157.0]

63.6
17.9 [36.7–115.9]

77.4
25.0,z [37.8–128.4]

101.1
33.8,z,# [59.1–157.0]

19.2
7.2 [8.0–51.3]

17.9
5.2 [8.0–28.8]

18.9
7.2 [8.1–40.2]

23.0
10.1,z [10.5–51.3]

73.6
6.4 [60.9–86.2]

71.2
6.1 [60.9–83.1]

75.3
6.3,z [64.6–86.2]

77.2
5.2,z [67.3–84.7]

77.4
27.9 [35.4–164.4]

65.2
19.0 [35.4–105.4]

81.5
25.0,z [36.3–110.4]

101.5
34.5,z,# [46.5–164.4]

20.3
7.6 [8.3–57.8]

19.2
5.6 [8.9–36.0]

19.4
6.8 [10.2–39.9]

24.5
11.6,z [8.3–57.8]

72.6
7.4 [54.6–85.1] 1.31
0.17 [1.02–1.87]

69.6
7.4 [54.6–81.3] 1.38
0.17 [1.20–1.87]

75.3
6.5,z [60.0–85.1] 1.24
0.14,z [1.03–1.50]

75.9
6.3,z [63.5–83.7] 1.25
0.17,z [1.02–1.57]

: P o .05 versus Group 1. z

: P o .05 versus Subgroup 2-1. : P o .05 versus Subgroup 2-2. SPAP, systolic pulmonary arterial pressure; n, number of dogs for which variables were available; EDVI, end-diastolic volume indexed to body surface area; ESVI, end-systolic volume indexed to body surface area; EF, ejection fraction of the left ventricle; LVSI, left ventricular index of sphericity; SPAP, systolic pulmonary arterial pressure; NM, not measured. #

Assessment of Systolic Function in Dogs

A 3.5

A Geometric method ESVI (mL/m )

LA/Ao

2.5 2.0 1.5 1.0 0.5 0

10

20

30

40 50 RF (%)

60

70

80

B Length area method ESVI (mL/m )

140 120 100 80 60 40 20

r= 0.57; p