Michele Borgarelli

Survival Characteristics and Prognostic Variables of Dogs with Mitral Regurgitation Attributable to Myxomatous Valve Disease

BACKGROUND There are few studies evaluating the natural history and prognostic variables in chronic mitral valve disease (CMVI) in a heterogeneous population of dogs. OBJECTIVES To estimate survival and prognostic value of clinical and echocardiographic variables in dogs with CMVI of varying severity. Five hundred and fifty-eight dogs belonging to 36 breeds were studied. METHODS Dogs were included after clinical examination and echocardiography. Long-term outcome was assessed by telephone interview with the owner. RESULTS The mean follow-up time was 22.7 +/- 13.6 months, and the median survival time was 19.5 +/- 13.2 months. In univariate analysis, age>8 years, syncope, HR>140 bpm, dyspnea, arrhythmias, class of heart failure (International Small Animal Cardiac Health Council), furosemide therapy, end-systolic volume-index (ESV-I)>30 mL/m(2), left atrial to aortic root ratio (LA/Ao)>1.7, E wave transmitral peak velocity (Emax)>1.2 m/s, and bilateral mitral valve leaflet engagement were associated with survival time when all causes of death were included. For the cardiac-related deaths, all the previous variables except dyspnea and EDV-I>100 mL/m(2) were significantly associated with survival time. Significant variables in multivariate analysis (all causes of death) were syncope, LA/Ao>1.7 m/s, and Emax>1.2 m/s. For cardiac-related death, the only significant variable was LA/Ao>1.7. CONCLUSIONS AND CLINICAL IMPORTANCE Mild CMVI is a relatively benign condition in dogs. However, some clinical variables can identify dogs at a higher risk of death; these variables might be useful to identify individuals that need more frequent monitoring or therapeutic intervention.

Effect of Pimobendan or Benazepril Hydrochloride on Survival Times in Dogs with Congestive Heart Failure Caused by Naturally Occurring Myxomatous Mitral Valve Disease: The QUEST Study

BACKGROUND Myxomatous mitral valve disease (MMVD) continues to be an important cause of morbidity and mortality in geriatric dogs despite conventional therapy. HYPOTHESIS Pimobendan in addition to conventional therapy will extend time to sudden cardiac death, euthanasia for cardiac reasons, or treatment failure when compared with conventional therapy plus benazepril in dogs with congestive heart failure (CHF) attributable to MMVD. ANIMALS Two hundred and sixty client-owned dogs in CHF caused by MMVD were recruited from 28 centers in Europe, Canada, and Australia. METHODS A prospective single-blinded study with dogs randomized to PO receive pimobendan (0.4-0.6 mg/kg/d) or benazepril hydrochloride (0.25-1.0 mg/kg/d). The primary endpoint was a composite of cardiac death, euthanized for heart failure, or treatment failure. RESULTS Eight dogs were excluded from analysis. One hundred and twenty-four dogs were randomized to pimobendan and 128 to benazepril. One hundred and ninety dogs reached the primary endpoint; the median time was 188 days (267 days for pimobendan, 140 days for benazepril hazard ratio = 0.688, 95% confidence limits [CL]=0.516-0.916, P= .0099). The benefit of pimobendan persisted after adjusting for all baseline variables. A longer time to reach the endpoint was also associated with being a Cavalier King Charles Spaniel, requiring a lower furosemide dose, and having a higher creatinine concentration. Increases in several indicators of cardiac enlargement (left atrial to aortic root ratio, vertebral heart scale, and percentage increase in left ventricular internal diameter in systole) were associated with a shorter time to endpoint, as was a worse tolerance for exercise. CONCLUSIONS AND CLINICAL IMPORTANCE Pimobendan plus conventional therapy prolongs time to sudden death, euthanasia for cardiac reasons, or treatment failure in dogs with CHF caused by MMVD compared with benazepril plus conventional therapy.

Comparison of primary mitral valve disease in German Shepherd dogs and in small breeds.

The case records of 58 German Shepherds (GS group) affected by mitral valve prolapse (MVP) and/or mitral valve regurgitation (MR), and 49 dogs weighing < 15 kg (D group), affected by chronic valvular disease (CVD) were reviewed. The dogs of the GS group were presented more often without a detectable heart murmur (p < 0.01), and less frequently with a high intensity heart murmur (p < 0.01). Atrial fibrillation (AF) was more common in the GS group (p < 0.001). MVP associated with mitral valve thickening was more common in the D group (p < 0.001). Fractional shortening (FS) was lower (p < 0.0001) and end-systolic volume index (ESV-I) was increased (p < 0.0001) in the GS group, whereas end-diastolic volume index (EDV-I) did not differ between the 2 groups. Prevalence and severity of pulmonary hypertension were similar in the 2 groups. Dogs with mitral valve disease weighing more than 20 kg had a 5.8 higher chance of developing decreased FS, increased ESV-I, AF and ventricular arrhythmias. In the GS group, the decreased FS and increased ESV-I were not associated with the presence of AF or ventricular arrhythmias (p > 0.05). It appears that GS may be affected both by mitral valve prolapse and mitral insufficiency. It also appears that a comparatively large proportion of GS shows no major mitral valve thickening or MVP, but still presents with significant mitral regurgitation, possibly suggesting a different cause for the important incompetence observed in most cases.

Prognostic Indicators for Dogs with Dilated Cardiomyopathy

The purpose of this study was to investigate the prognostic value of various clinical, ECG, echocardiographic, and Doppler echocardiographic variables in dogs with dilated cardiomyopathy. The relationship to survival of 11 variables was evaluated in 63 dogs. Studied variables were age at time of diagnosis, class of heart failure (HF), dyspnea, ascites, atrial fibrillation (AF), ejection fraction (EF), E-point septal separation, end-diastolic volume index, end-systolic volume index (ESV-I), and restrictive or nonrestrictive transmitral flow (TMF) pattern. Median survival time was 671 days (lower 95% confidence limit, 350 days). Survival curves showed that severity of HF, ascites, ESV-I greater than 140 mL/m2, EF less than 25%, and restrictive TMF pattern had a significant negative relation to survival time. Thirty-nine dogs with both sinus rhythm and AF presented adequate TMF recordings; in these dogs, after stratification by TMF pattern, the restrictive TMF pattern was the most important negative prognostic indicator. We conclude that in dogs with dilated cardiomyopathy the restrictive TMF pattern appears to represent a useful prognostic indicator. Class of HF, ascites, ESV-I, and EF are also useful indexes if an adequate TMF pattern is not recorded.

Use of signal analysis of heart sounds and murmurs to assess severity of mitral valve regurgitation attributable to myxomatous mitral valve disease in dogs.

OBJECTIVE To investigate use of signal analysis of heart sounds and murmurs in assessing severity of mitral valve regurgitation (mitral regurgitation [MR]) in dogs with myxomatous mitral valve disease (MMVD). ANIMALS 77 client-owned dogs. PROCEDURES Cardiac sounds were recorded from dogs evaluated by use of auscultatory and echocardiographic classification systems. Signal analysis techniques were developed to extract 7 sound variables (first frequency peak, murmur energy ratio, murmur duration > 200 Hz, sample entropy and first minimum of the auto mutual information function of the murmurs, and energy ratios of the first heart sound [S1] and second heart sound [S2]). RESULTS Significant associations were detected between severity of MR and all sound variables, except the energy ratio of S1. An increase in severity of MR resulted in greater contribution of higher frequencies, increased signal irregularity, and decreased energy ratio of S2. The optimal combination of variables for distinguishing dogs with high-intensity murmurs from other dogs was energy ratio of S2 and murmur duration > 200 Hz (sensitivity, 79%; specificity, 71%) by use of the auscultatory classification. By use of the echocardiographic classification, corresponding variables were auto mutual information, first frequency peak, and energy ratio of S2 (sensitivity, 88%; specificity, 82%). CONCLUSIONS AND CLINICAL RELEVANCE Most of the investigated sound variables were significantly associated with severity of MR, which indicated a powerful diagnostic potential for monitoring MMVD. Signal analysis techniques could be valuable for clinicians when performing risk assessment or determining whether special care and more extensive examinations are required.

Congenital heart disease in boxer dogs: results of 6 years of breed screening.

The aim of this study was to analyse the results of 6years (1999-2004) of mandatory breed screening for congenital heart disease in Boxer dogs using physical examination and echocardiography. Records of 1283 Boxers were reviewed and 165 dogs (12.86%) were found to be affected by heart disease, with aortic and pulmonic stenosis being the most frequent cardiac lesions. Comparison of these results with those of a previous survey showed a lower overall prevalence of both outflow obstructions, particularly of the more severe forms. A male predisposition for both aortic and pulmonic stenosis was evident from the study. Consistent with reports from other countries, soft left basilar heart murmurs were detected in both healthy dogs and dogs affected with congenital heart disease.

Evaluation of plasma activity of matrix metalloproteinase-2 and -9 in dogs with myxomatous mitral valve disease

OBJECTIVE To investigate whether plasma activity of matrix metalloproteinase (MMP)-2 and -9 was associated with severity of myxomatous mitral valve disease (MMVD) in dogs and to assess potential associations between MMP activity and dog characteristics, echocardiographic variables, systolic arterial blood pressure (SAP), heart rate, cardiac troponin I (cTnI) concentration, and C-reactive protein concentration. ANIMALS 75 client-owned dogs. PROCEDURES Severity of MMVD was assessed by use of echocardiography. Plasma activity of latent (pro-MMP) and active MMP-2 and -9 was analyzed via zymography. Plasma concentration of cTnI was analyzed with a high-sensitivity cTnI assay, and C-reactive protein concentration was analyzed with a canine-specific ELISA. RESULTS Pro-MMP-9, active MMP-9, and pro-MMP-2 were detected, but active MMP-2 was not. No significant differences were found in MMP concentrations among the 4 MMVD severity groups. Activity of pro-MMP-9 decreased with decreases in SAP and was higher in male dogs than in female dogs. Activity of MMP-9 decreased with increases in left ventricular end-systolic dimension and with decreases in SAP and cTnI concentration. Left ventricular end-systolic dimension was the variable most strongly associated with MMP-9 activity. No associations were found between the activity of pro-MMP-2 and investigated variables. CONCLUSIONS AND CLINICAL RELEVANCE Plasma MMP-9 activity decreased with increases in the end-systolic left ventricular internal dimension and decreases in SAP. Hence, evaluation of MMP-9 activity has the potential to provide unique information about the myocardial remodeling process in dogs with MMVD.

Use of contrast echocardiography for quantitative and qualitative evaluation of myocardial perfusion and pulmonary transit time in healthy dogs

OBJECTIVE To evaluate reproducibility of ejection fraction (EF), myocardial perfusion (MP), and pulmonary transit time (PTT) measured in a group of dogs by use of contrast echocardiography and to examine safety of this method by evaluating cardiac troponin I concentrations. ANIMALS 6 healthy dogs. PROCEDURES 2 bolus injections and a constant rate infusion of contrast agent were administered IV. Echocardiographic EF was determined by use of the area-length method and was calculated without and with contrast agent. The PTT and normalized PTT (PTT/mean R-R interval) were measured for each bolus. Constant rate infusion was used for global MP evaluation, and regional MP was calculated by use of a real-time method in 4 regions of interest of the left ventricle. Cardiac troponin I concentration was analyzed before and after contrast agent administration. Intraoberserver and interobserver variability was calculated. RESULTS EF was easier to determine with the ultrasonographic contrast agent. For the first and second bolus, mean ± SD PTT was 1.8 ± 0.2 seconds and 2.1 ± 0.3 seconds and normalized PTT was 3.4 ± 0.3 seconds and 3.5 ± 0.3 seconds, respectively. A coefficient of variation < 15% was obtained for global MP but not for the regional MPs. No differences were detected between precontrast and postcontrast cardiac troponin I concentrations. CONCLUSIONS AND CLINICAL RELEVANCE Contrast echocardiography appeared to be a repeat-able and safe technique for use in the evaluation of global MP and PTT in healthy dogs, and it improved delineation of the endocardial border in dogs.

Anatomic, histologic, and two-dimensional- echocardiographic evaluation of mitral valve anatomy in dogs

OBJECTIVE To compare echocardiographic variables of dogs with postmortem anatomic measurements and histologic characteristics of the mitral valve (MV). ANIMALS 21 cardiologically normal dogs. PROCEDURES The MV was measured echocardiographically by use of the right parasternal 5-chamber long-axis view. Dogs were euthanized, and anatomic measurements of the MV annulus (MVa) were performed at the level of the left circumflex coronary artery. Mitral valve leaflets (MVLs) and chordae tendineae were measured. Structure of the MVLs was histologically evaluated in 3 segments (proximal, middle, and distal). RESULTS Echocardiographic measurements of MVL length did not differ significantly from anatomic measurements. A positive correlation was detected between body weight and MVa area. There was a negative correlation between MVa area and the percentage by which the MVL area exceeded the MVa area. Anterior MVLs had a significantly higher number of chordae tendineae than did posterior MVLs. Histologically, layering of MVLs was less preserved in the distal segment, whereas the muscular component and adipose tissue were significantly more diffuse in the proximal and middle segments. CONCLUSIONS AND CLINICAL RELEVANCE The MV in cardiologically normal dogs had wide anatomic variability. Anatomic measurements of MVL length were correlated with echocardiographic measurements.

Echo-assisted percutaneous renal biopsy in dogs. A retrospective study of 229 cases.

Renal biopsies were carried out on 229 dogs using an echo-assisted, semi-automatic method. Complications arising after the biopsy were also evaluated. The biopsies were examined for the accuracy of diagnosis and the presence of histologically demonstrable primary renal pathologies. A retrospective study of the observed lesions and parenchymal echogenicity showed a correlation between these factors involving the tubulo-interstitial compartment. Histopathological renal lesions and their correlation with laboratory methods are the only parameters that allow a correct diagnostic, prognostic, and therapeutic work-up in cases of clinical kidney disease in canines.