The predictive value of clinical, radiographic, echocardiographic variables and cardiac biomarkers for assessing risk of the onset of heart failure or cardiac death in dogs with preclinical myxomatous mitral valve disease enrolled in the DELAY study.

OBJECTIVES: To identify the predictive value on time to onset of heart failure (HF) or cardiac death of clinical, radiographic, and echocardiographic variables, as well as cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I in dogs with preclinical myxomatous mitral valve disease (MMVD). ANIMALS: One hundred sixty-eight dogs with preclinical MMVD and left atrium to aortic root ratio ≥1.6 (LA:Ao) and normalized left ventricular end-diastolic diameter ≥1.7 were included. METHODS: Prospective, randomized, multicenter, single-blinded, placebo-controlled study. Clinical, radiographic, echocardiographic variables and plasma cardiac biomarkers concentrations were compared at different time points. Using receiving operating curves analysis, best cutoff for selected variables was identified and the risk to develop the study endpoint at six-month intervals was calculated. RESULTS: Left atrial to aortic root ratio >2.1 (hazard ratio [HR] 3.2, 95% confidence interval [95% CI] 1.9-5.6), normalized left ventricular end-diastolic diameter > 1.9 (HR: 6.3; 95% CI: 3.3-11.8), early transmitral peak velocity (E peak) > 1 m/sec (HR: 3.9; 95% CI: 2.3-6.7), and NT-proBNP > 1500 ρmol/L (HR: 5.7; 95% CI: 3.3-9.5) were associated with increased risk of HF or cardiac death. The best fit model to predict the risk to reach the endpoint was represented by the plasma NT-proBNP concentrations adjusted for LA:Ao and E peak. CONCLUSIONS: Logistic and survival models including echocardiographic variables and NT-proBNP can be used to identify dogs with preclinical MMVD at higher risk to develop HF or cardiac death.

DELay of Appearance of sYmptoms of Canine Degenerative Mitral Valve Disease Treated with Spironolactone and Benazepril: the DELAY Study.

INTRODUCTION: Efficacy of renin-angiotensin-aldosterone system (RAAS) blockade using angiotensin-converting enzyme inhibitors (ACEi) in dogs with preclinical myxomatous mitral valve disease (MMVD) is controversial. HYPOTHESIS: Administration of spironolactone (2-4 mg q 24 h) and benazepril (0.25-0.5 mg q 24 h) in dogs with preclinical MMVD, not receiving any other cardiac medications, delays the onset of heart failure (HF) and cardiac-related death. Moreover, it reduces the progression of the disease as indicated by echocardiographic parameters and level of cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). ANIMALS: 184 dogs with pre-clinical MMVD and left atrium-to-aortic root ratio (LA:Ao) ≥1.6 and normalized left ventricular end-diastolic diameter (LVEDDn) ≥1.7. METHODS: This is a prospective, randomized, multicenter, single-blinded, placebo-controlled study. Primary outcome variable was time-to-onset of first occurrence of HF or cardiac death. Secondary end points included effect of treatment on progression of the disease based on echocardiographic and radiographic parameters, as well as variations of NT-proBNP and cTnI concentrations. RESULTS: The median time to primary end point was 902 days (95% confidence interval (CI) 682-not available) for the treatment group and 1139 days (95% CI 732-NA) for the control group (p = 0.45). Vertebral heart score (p = 0.05), LA:Ao (p < 0.001), LVEDDn (p < 0.001), trans-mitral E peak velocity (p = 0.011), and NT-proBNP (p = 0.037) were lower at the end of study in the treatment group. CONCLUSIONS: This study failed in demonstrating that combined administration of spironolactone and benazepril delays onset of HF in dogs with preclinical MMVD. However, such treatment induces beneficial effects on cardiac remodeling and these results could be of clinical relevance.

Prevalence and prognostic importance of pulmonary hypertension in dogs with myxomatous mitral valve disease.

BACKGROUND: Pulmonary hypertension (PH) is common in dogs with myxomatous mitral valve disease (MMVD) but its effect on clinical outcome has not been investigated. HYPOTHESIS/OBJECTIVES: The presence of PH worsens the outcome in dogs with MMVD. To compare survival times of dogs with MMVD and PH to those without PH. ANIMALS: Two hundred and twelve client-owned dogs. METHODS: Case review study. Medical records of dogs diagnosed with ACVIM stage B2 and C MMVD between January 2010 and December 2011 were retrospectively reviewed. Long-term outcome was determined by telephone interview or from the medical record. End of the observation period was March 2013. PH was identified if tricuspid regurgitation peak velocity was >3 m/s. RESULTS: Two hundred and twelve were identified. Eighty-three dogs (39%) had PH. PH was more commonly identified in stage C compared to B2 (P < .0001). One hundred and five (49.5%) dogs died during the observation period. Median survival time for the entire study population was 567 days (95% CI 512-743). Stage C (P = .003), the presence of PH (P = .009), left atrial to aortic root ratio (LA/Ao) >1.7 (P = .0002), normalized left-ventricular end-diastolic diameter (LVEDn) >1.73 (P = .048), and tricuspid regurgitation pressure gradient (TRPG) >55 mmHg (P = .009) were associated with worse outcomes in the univariate analyses. The presence of TRPG >55 mmHg (HR 1.8 95% CI 1-2.9; P = .05) and LA/Ao > 1.7 (HR 2 95% CI 1.2-3.4; P = .01) remained significant predictors of worse outcome in the multivariate analysis. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with MMVD, moderate to severe PH worsens outcome.

The relevance of echocardiography heart measures for breeding against the risk of subaortic and pulmonic stenosis in Boxer dogs.

The aims of this study were to investigate the role and relative importance of auscultation and echocardiography traits as risk factors for the diagnosis of subaortic (SubAS) and pulmonic (PS) stenosis and to estimate the heritability (h(2)) of cardiac measurements taken through echocardiography for a random sample of Italian Boxer dogs. The data were cardiovascular examination results of 1,283 Italian Boxer dogs (686 females and 597 males) enrolled in the national screening program for heart defects arranged by the Italian Boxer Club. Examinations were performed during a 6-yr period by a group of 7 veterinary cardiologists following a standard protocol. Occurrence and severity of SubAS and PS were diagnosed, taking into account clinical and echocardiography findings such as the grade of cardiac murmur, direct ultrasound imaging of the anatomic obstructive lesions, and values of aortic or pulmonary blood flow velocities. A Bayesian logistic regression analysis was performed to identify clinical and echocardiography variables related to SubAS and PS diagnosis. Estimation of variance components for clinical and echocardiography traits was performed using a mixed linear animal model, Bayesian procedures, and the Gibbs sampler. Prevalence of SubAS (PS) was 8.4% (2.2) and 10.7% (6.4) for female and male dogs, respectively. Cardiac murmur, peak velocities, and annulus areas behaved as risk factors for SubAS and PS. The risk of a positive diagnosis for SubAS was 3 times greater for dogs with aortic annulus area <2.1 cm(2) relative to dogs with areas >2.37 cm(2), 84 times greater for dogs showing aortic peak velocities >2.19 m/s relative to dogs with peak velocities <1.97 m/s, and 41 times greater for dogs with moderate to severe murmur grades relative to dogs with absent murmur. Similar results were obtained for PS. The estimated h(2) for the occurrence of cardiac defects was 23.3% for SubAS and 8.6% for PS. Echocardiography and cardiac murmur grades exhibited moderate h(2) estimates and exploitable additive genetic variation. The estimated h(2) was 36, 24, and 20% for aortic annulus area, aortic peak velocity, and cardiac murmur score, respectively. For the area of the pulmonary annulus and peak pulmonary velocity, the estimated h(2) were smaller, ranging from 9.5 to 12.8%. These measures are candidate indicator traits that might be effectively used in dog breeding to reduce the prevalence and severity of cardiac defects.

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.