Evaluation of right ventricular function using conventional and real-time three-dimensional echocardiography in healthy dogs and dogs with myxomatous mitral valve disease.

INTRODUCTION/OBJECTIVES: To compare conventional and three-dimensional (3D) echocardiographic indices of right ventricular (RV) systolic function in dogs with various stages of myxomatous mitral valve disease (MMVD), classified according to the 2009 guidelines of the American College of Veterinary Internal Medicine (ACVIM), with those from normal dogs. ANIMALS: Seventy-eight unsedated dogs (22 healthy controls, 23 ACVIM stage B1 MMVD, 20 ACVIM stage B2 MMVD, and 13 ACVIM stage C MMVD) were included in the study. MATERIALS AND METHODS: All dogs underwent conventional and 3D echocardiography. Three-dimensional RV end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) were recorded. Right ventricular EDV, ESV, and SV were indexed to bodyweight. Echocardiographic variables were compared across groups using a Kruskal-Wallis test with subsequent post hoc analysis using Dunn's method for multiple comparisons between groups. A P-value of <0.05 was considered significant. RESULTS: Right ventricular EDV was smaller in stage B1 (P=0.012), stage B2 (P=0.035), and stage C (P=0.004) dogs than in controls. Stage B2 (P=0.003) and stage C (P<0.001) dogs had smaller RV ESV than controls. Stage B1 dogs had smaller RV SV than controls (P=0.012). Right ventricular EF was greater in stage C dogs than in controls (P=0.003) and in stage B1 (P=0.017) dogs. CONCLUSIONS: Several 3D echocardiographic indices of RV systolic function differ between dogs with advanced MMVD when compared with normal dogs. Further investigation is required to determine if these differences have clinical implications.

Accuracy of echocardiographically estimated pulmonary artery pressure in dogs with myxomatous mitral valve disease.

INTRODUCTION: Echocardiographically identified pulmonary hypertension is an independent predictor of poor outcome in dogs affected by myxomatous valvular degeneration (MMVD). Systolic pulmonary arterial pressure is routinely estimated based on its relationship with the Doppler-determined velocity of tricuspid regurgitation as defined by the simplified Bernoulli equation (sPAP_D). Experimental studies suggest that the method is imperfect, but its accuracy in dogs with MMVD is not known. ANIMALS: Twenty dogs affected by MMVD that had cardiac remodeling and measurable tricuspid regurgitation. METHODS: A flow-directed thermodilution monitoring catheter was percutaneously placed in the right external jugular vein and advanced to the main pulmonary artery. Pulmonary arterial systolic pressure was recorded (systolic pulmonary arterial pressure obtained by right heart catheterization [sPAP_C]). A second operator contemporaneously acquired tricuspid regurgitant velocity spectra to calculate sPAP_D. Each operator was blinded to the result of the other techniques. RESULTS: Technical difficulties prevented the analysis of catheterization data in two dogs. Eighteen measurement pairs were therefore used for comparison of sPAP_C and sPAP_D through correlation and Bland-Altman analysis. A statistically significant bias between sPAP_C and sPAP_D (mean difference = 0.5 mmHg; confidence interval = -6.5 mmHg, +7.5 mmHg) was not detected. The interval of agreement between the techniques was wide (-27.3 mmHg, +28.2 mmHg). A significant linear association between the two techniques was not identified (r = 0.11, p=0.17). CONCLUSION: Echocardiographically estimated pulmonary artery pressure poorly agrees with sPAP_C measurement in dogs affected by MMVD and cardiac remodeling with or without previously diagnosed congestive heart failure. In these dogs, sPAP_D could under- or over-estimate sPAP_C by more than 20 mmHg, and therefore caution should be used when interpreting sPAP_D.

Mitral valve repair in dogs using an ePTFE chordal implantation device: a pilot study.

OBJECTIVE: Mitral valve (MV) regurgitation due to degenerative MV disease is the leading cause of cardiac death in dogs. We carried out preliminary experiments to determine the feasibility and short-term effects of beating-heart MV repair using an expanded polytetrafluorethylene (ePTFE) chordal implantation device (Harpoon TSD-5) in dogs. ANIMALS: This study involved six healthy purpose-bred Beagles (weight range 8.9-11.4 kg). MATERIAL AND METHODS: Following a mini-thoracotomy performed under general anesthesia, the TSD-5 was used to place 1 or 2 artificial ePTFE cords on the anterior MV leaflet or the posterior MV leaflet via a left-ventricular transapical approach. The procedure was guided and monitored by transesophageal echocardiography. Postoperative antithrombotic treatment consisted of clopidogrel or a combination of clopidogrel and apixaban. Dogs were serially evaluated by transthoracic echocardiography at day 1, 7, 14, 21, and 30. The hearts were then examined for evaluation of tissues reactions and to detect signs of endothelialization. RESULTS: One or two chords were successfully implanted in five dogs. Four dogs completed the 30 days follow-up. One dog died intra-operatively because of aortic perforation. One dog died early post-operatively from a hemorrhagic pleural effusion attributed to overly aggressive antithrombotic treatment. One dog developed a thrombus surrounding both the knot and the synthetic cord. Postmortem exam confirmed secure placement of ePTFE knots in the mitral leaflets in all dogs and the presence of endothelialization of the knots and chords. CONCLUSIONS: These preliminary results demonstrate the feasibility of artificial chordal placement using an ePTFE cordal implantation device in dogs.

Mitral valve morphology assessed by three-dimensional transthoracic echocardiography in healthy dogs and dogs with myxomatous mitral valve disease.

OBJECTIVE: To assess differences in morphology of the mitral valve (MV) between healthy dogs and dogs affected by myxomatous mitral valve disease (MMVD) using real-time transthoracic three-dimensional echocardiography (RT3DE). ANIMALS: Thirty-four were normal dogs and 79 dogs were affected by MMVD. METHODS: Real-time transthoracic three-dimensional echocardiography mitral datasets were digitally recorded and analyzed using dedicated software. The following variables were obtained and compared between healthy dogs and dogs with MMVD at different stages: antero-posterior annulus diameter, anterolateral-posteromedial annulus diameter, commissural diameter, annulus height, annulus circumference, annulus area, anterior leaflet length, anterior leaflet area, posterior leaflet length, posterior leaflet area, non-planar angle, annulus sphericity index, tenting height, tenting area, tenting volume, the ratio of annulus height and commissural diameter. RESULTS: Dogs with MMVD had a more circular MV annulus compared to healthy dogs as demonstrated by an increased annulus sphericity index (p=0.0179). Affected dogs had a less saddle-shaped MV manifest as a decreased annulus height to commissural width ratio (p=0.0004). Tenting height (p<0.0001), area (p<0.0001), and volume (p<0.0001) were less in affected dogs. CONCLUSIONS: Real-time transthoracic three-dimensional echocardiography analysis demonstrated that dogs affected by MMVD had a more circular and less saddle-shaped MV annulus, as well as reduced tenting height area and volume, compared to healthy dogs. Multiple variables differed between dogs at different stages of MMVD. Diagnostic and prognostic utility of these variables, and the significance of these changes in the pathogenesis and natural history of MMVD, require further attention.

Assessment of mitral valve morphology using three-dimensional echocardiography. Feasibility and reference values.

OBJECTIVES: To evaluate the feasibility of real time transthoracic three-dimensional echocardiography (RT3DE) for evaluation of normal canine mitral valves (MVs), and to provide reference values for this technique. ANIMALS: Forty-three cardiologically healthy, not sedated dogs. METHODS: Transthoracic RT3DE mitral datasets were acquired during two consecutive 6-month periods. The datasets were analyzed using commercially available software. An MV model was drawn using a semiautomated procedure and MV variables were obtained and calculated. The ratio between annulus height and commissural diameter was used as an index of the annulus' saddle-shaped non-planarity. After evaluation of associations between measured variables and body size, the datasets were used to generate reference intervals. Coefficients of variation (CVs), variance components, and repeatability coefficients were calculated for the evaluation of intra-observer, inter-observer, and day-to-day variability. RESULTS: Datasets could be analyzed in 34 of 43 (79%) dogs. 68 percent of datasets obtained during the first 6-month period could be analyzed and 90% obtained during the second period could be analyzed. An allometric relationship was identified for most MV variables. The MV annulus appeared elliptical and saddle-shaped. Inter- and intra-observer CVs were less than 20%. Coefficient of variation greater than 20% was calculated for the inter-day variation for some variables. Operator and observer were primarily responsible for the variation of most of the variables. CONCLUSIONS: Evaluation of canine mitral valves by transthoracic RT3DE is feasible. Canine MVs of healthy dogs analyzed using RT3DE are elliptical and saddle-shaped. Reference intervals for the measured MV variables are proposed.

Identification of DNA variants in the canine beta-1 adrenergic receptor gene.

Beta-adrenergic receptor antagonists are utilized for the management of several cardiac diseases in the dog. In humans the beneficial effects of beta-adrenergic receptor antagonists are variable and are associated with a genetic variability in the beta one adrenergic receptor gene (ADRB1). To determine if DNA variants were present in the canine ADRB1 gene, DNA from five breeds of dogs was evaluated. Two deletions were identified within the region of the gene that encodes the cytoplasmic tail of ADRB1. The functions of this region are not well understood although it is important in differentiating subtypes of adrenergic receptors and may be associated with control of receptor downregulation. The functional consequences of these identified variants deserve further study.

Familial subvalvular aortic stenosis in golden retrievers: inheritance and echocardiographic findings.

OBJECTIVES: To describe the echocardiographic findings and pedigree analysis of golden retrievers with subvalvular aortic stenosis. METHODS: Seventy-three golden retrievers were evaluated by auscultation and echocardiography. A subcostal continuous-wave Doppler aortic velocity ê2·5 m/s and presence of a left basilar systolic ejection murmur were required for diagnosis of subvalvular aortic stenosis. Three echocardiographic characteristics were recorded: evidence of aortic insufficiency, subvalvular ridge or left ventricular hypertrophy. A disease status score was calculated by totalling the number of echocardiographic -characteristics per subject. RESULTS: Thirty-two of 73 dogs were affected and their aortic velocities were as follows: range 2·5 to 6·8 m/s, median 3·4 m/s and standard deviation 1·2 m/s. Echocardiographic characteristics of 32 affected dogs were distributed as follows: left ventricular hypertrophy 12 of 32, aortic insufficiency 20 of 32 and subvalvular ridge 20 of 32. Disease status score ranged from 0 to 3 with a median of 2. There was a statistically significant correlation between aortic velocity and disease status score (r=0·644, P<0·0001). Subvalvular aortic stenosis was observed in multiple generations of several families and appears familial. CLINICAL SIGNIFICANCE: Subvalvular aortic stenosis in the golden retriever is familial. Severity of stenosis correlates well with cumulative presence of echocardiographic characteristics (left ventricular hypertrophy, subvalvular ridge and aortic insufficiency).

Identification of beta-1 adrenergic receptor polymorphisms in cats.

In human beings, genetic polymorphisms within the beta-1 adrenergic receptor (ADRB1) gene have been associated with variable pharmacologic responses to beta blocker therapy. Beta-blockers are commonly given to cats with heart disease, particularly hypertrophic cardiomyopathy, a common cause of feline heart disease. We hypothesized that polymorphisms are present in the feline ADRB1 gene, which could result in an altered pharmacologic response to beta-blocker therapy. We sequenced the feline ADRB1 gene in 42 cats of five breeds. We identified three polymorphisms within the ADRB1 gene. Two polymorphisms did not change the amino acid produced and are unlikely to be clinically significant. A third polymorphism identified was an AA/CC substitution at the 830-831 base pair sites. This alteration changed the amino acid produced from proline to glutamine at position 277 and computer modeling predicts an altered protein structure. Further study is warranted to determine if this polymorphism alters response to beta blocker therapy.