A New Approach to Classify Degenerative Mitral Valve Disease Patients Considering Discriminant Analysis of Echocardiographic Parameters
M.S. Oliveira; R.A.L. Muzzi; R.B. Araújo; L.A.L. Muzzi; D.F. Ferreira; E.F. Silva; G.A.O. Cavalcanti
Support by FAPEMIG.
Classifying a patient considering the degree of a disease is of great importance as a prognosis and it will lead the veterinarian in the choice of the best conduct to be adopted. For this reason, this classification must be done as good as possible. Bonagura et al. (1992) proposed, for veterinary cardiac patients, a method for assessment which is based on information from the patient's clinical status, that is easy to implement and can be widely used. However, it is a subjective method because it considers only qualitative information which is obtained during the clinical examination (situation of stress for the animal what may affect some parameters) and history (provided by the owner with no possibility for the veterinarian to be sure). Besides the subjectivity inherent to this way to collect data, the clinical course of a disease may be different for some patients with the same diagnosis. That is the reason why, in some cases, patients are clinically compensated (not necessarily due to the effect of drugs), besides having significant impairment of cardiac function. Thus, a method for cardiac patient classification which considers quantitative data of the cardiac function, based on echocardiographic examination, could result in more accurate prognostic information. The aim of this research was to establish a new method to classify dogs in healthy or heart diseased (chronic degenerative mitral valve disease--CDMVD) in mild, moderate and severe, considering echocardiographic parameters.
Materials and Methods
We used 40 dogs of various small breeds, ranging from 6 to 15 years old (mean 10.28 ± 2.76) and average weight of 6.46 ± 3.52 kg. The animals were divided into four groups of ten in each one. Control group was composed of healthy animals and aged over six years. Dogs with mitral valve prolapse in the echocardiographic examination were excluded from control group. In the other groups there were dogs with CDMVD diagnosed echocardiographically, aged over six years, presenting systolic murmur of mitral regurgitation and classified according to the degree of congestive heart failure (CHF) as suggested by Bonagura et al. (1992). Thus, the experimental groups were: Control group: healthy dogs; Group 1: dogs with CDMVD without clinical signs of CHF (class Ia and Ib: presence of heart murmur, without signs of CHF); Group 2: patients with CDMVD with mild to moderate CHF (class II: animals with signs of CHF when subjected to mild exercise or rest, exercise intolerance, cough, tachypnea, dyspnea and mild ascites); Group 3: patients with CDMVD and advanced CHF (class IIIa: animals have intense dyspnea, profound exercise intolerance, hypoperfusion at rest, cough and moderate ascites). The details of history, as the presence of cough, tiredness, exercise intolerance, syncope, tachypnea, dyspnea and progression of symptoms were considered in the classification of animals within the CHF. To perform echocardiography, the animals received a dose of 0.030mg/kg of acepromazine, intravenously. Dogs were positioned in lateral recumbency using right and left parasternal positions, and evaluated by two-dimensional, M, pulsed, continuous and color Doppler modes. Three measures of each variable were performed and their averages were analyzed. In two-dimensional mode were studied the cardiac chambers, especially the left atrium, the appearance of the mitral valve, the presence of pericardial effusion, the transverse diameter of mitral annulus and aortic root (Thomas et al., 1993). We also made the measures of the diameter of the left atrium (LA) and the aortic root (Ao) (Hansson et al., 2002) and the relationship between these parameters (LA/Ao). In M mode were obtained, at the end of systole and diastole, the internal dimension of the left ventricle, the thickness of the interventricular septum and posterior wall of the left ventricle, according to Lombard (1984). Then the values of the ejection fraction (EF) and the percent left ventricular fractional shortening (FS) were calculated. In the Doppler mode were evaluated the peak flow velocity of mitral valve (E and A waves), aortic flow (left ventricular outflow tract--LVOT), tricuspid and pulmonary flows, as well as the time-velocity integral (TVI) of mitral flow (TVIMV) and the aortic flow (TVIL-VOT). The values of mitral regurgitant flow (VMAX) and the TVI for the mitral regurgitation (TVIMR) were obtained (Boon, 1998). Mitral regurgitant stroke volume was calculated as the difference between mitral and aortic forward stroke volume integrated by pulsed Doppler; regurgitant fraction was calculated as mitral regurgitant stroke volume divided by mitral forward stroke volume. Stroke volume across the aortic valve was calculated by multiplying the cross-sectional area at the level of the aortic annulus by the time velocity integral of flow across that valve. Area was calculated from the peak diameter at the insertion of the aortic leaflets in the parasternal long-axis view, assuming a circular configuration (Lewis et al., 1984). Outflow velocities were obtained by pulsed Doppler echocardiography from the apex for optimal alignment with flow. The time velocity integral was calculated by tracing the modal velocity. The product of area and time-velocity integral provided the stroke volume. Mitral stroke volume was calculated as the product of peak mitral valve cross-sectional area at the level of the leaflets tips from the apical four-chamber view multiplied by the time-velocity integral of modal velocity at the level of the leaflet tips by pulsed Doppler echocardiography in the apical four-chamber view. All these analysis was obtained according to the volumetric method, with the achievement of mitral valve regurgitation fraction (RFMR) and the volume of left ventricular inflow, as performed by Enriquez-Sarano et al. (1994). Values for mitral annulus, aortic root, LA/Ao, FS, EF, TVILVOT, peak E, TVIMV, VMAX, TVIMR and RFMR obtained with the echocardiogram, were submitted to discriminant analysis (Ferreira, 2008) using the computer program SAS.
We established linear discriminant functions for each group, with the values obtained by echocardiography, as follows:
Control Group = -368.46 + 4.56 x (mitral annulus) + 73.99 x (aortic root) + 66.08 x (LA/Ao) -19.89 x (FS) + 18.44 x (EF) + 19.90 x (TVIL-VOT) + 0.22 x (peak E) + 255.72 x (TVIMV) + 25.78 (VMAX) -0.79 x (TVIMR) -0.69 x (RFMR)
Group 1 = -382.59 -25.31 x (mitral annulus) + 114.53 x (aortic root) + 62.82 x (LA/Ao) -19.49 x (FS) + 17.98 x (EF) + 265.57 x (TVILVOT) -6.79 x (peak E) + 110.34 x (TVIMV) + 29.49 (VMAX) -1.01 x (TVIMR) + 0.38 x (RFMR)
Group 2 = -450.05 -19.97 x (mitral annulus) + 113.35 x (aortic root) + 77.55 x (LA/Ao) -20.30 x (FS) + 18.69 x (EF) + 267.88 x (TVILVOT) -8.83 x (peak E) + 118.49 x (TVIMV) + 39.42 (VMAX) -1.22 x (TVIMR) + 0.23 x (RFMR)
Group 3 = -575.63 + 5.97 x (mitral annulus) + 86.25 x (aortic root) + 110.20 x (LA/Ao) -21.34 x (FS) + 19.73 x (EF) + 244.61 x (TVILVOT) -5.62 x (peak E) + 262.19 x (TVIMV) + 49.04 (VMAX) -1.71 x (TVIMR) -0.12 x (RFMR)
The method proposed in this report, resulted in linear functions with only 2.5% of error, being highly significant. Considering this discriminant analysis, only one of 40 dogs was inappropriately classified. This animal, classified in group 1, should be in group 2, according to the echocardiographic parameters.
Discussion and Conclusions
The linear discriminant function considers measurements obtained with the echocardiographic examination to allocate dogs in healthy (control group) or in patients with mild (group 1), moderate (group 2) and severe (group 3) CDMVD. As the linear functions reported here were highly significant equations, the method can be extrapolated for future classifications into healthy dogs and those with CDMVD. To perform this, the veterinarian may only procedure echocardiographic examination, taking the same measurements and replacing the values found in the four linear functions given above. The equation resulting in the greater value will indicate in which group the animal must be classified. The parameters should be considered in the following units of measure: mitral annulus (cm), aortic root (cm), LA/Ao, FS (%), EF (%), TVILVOT (m), peak E (m/s), TVIMV (m), VMAX (m/s), TVIMR (cm) and RFMR (%). The difference found in the classification of a dog in this study may be explained by the subjectivity of the first method which takes into account clinical aspects of CHF. For this animal no changes were detected in history and physical examination, to qualify it as class II of CHF, although it had echocardiographic parameters more similar to other dogs in group 2. However the main limitation of this new classification proposed here is that it requires the implementation of echocardiographic examination, not always available for veterinarians. Thus, this study showed that the discriminant analysis of echocardiographic parameters is an effective tool for classification dogs with CDMVD, providing quantitative data which allows a reliable classification.
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