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.     

Plasma and platelet serotonin concentrations in healthy dogs and dogs with myxomatous mitral valve disease

ObjectivesSerotonin has been implicated in canine myxomatous mitral valve disease (MMVD); however, the sources of serotonin have not been fully elucidated. This study compared the concentration of serotonin in plasma and platelets of normal healthy small breed dogs with predisposition to MMVD and dogs with naturally occurring MMVD.Animals43 small-breed client-owned dogs with an approximate weight of <10 kg and age of 6 years or above were divided into 2 groups: a healthy control group (n = 20) and a group with echocardiographic evidence of MMVD (n = 23).Methods5 ml samples of blood were collected. Plasma and platelets were separated by centrifugation and assayed for serotonin measured by enzyme linked immunosorbent assay (ELISA).ResultsMedian plasma serotonin concentration was not significantly different (p = 0.3630) between normal healthy dogs (3.7 ng/ml) and dogs with MMVD (4.3 ng/ml). Males had higher plasma serotonin concentration than females (4.7 and 2.9 ng/ml respectively, p = 0.0043). Platelet serotonin concentration was not different between healthy dogs and dogs with MMVD (128.6 ng/10⁹ platelets and 176.6 ng/10⁹ platelets respectively, p = 0.4575). Age, echocardiographic indices and platelet count showed no correlation with plasma or platelet serotonin concentration.ConclusionsCirculating plasma serotonin is unlikely a major source of serotonin signaling in canine MMVD. Platelets could be a source of serotonin in canine MMVD through platelet adhesion to the mitral valve; however, the amount of serotonin stored in platelets of healthy dogs and dogs with MMVD is not different.     

Efficacy of enalapril for prevention of congestive heart failure in dogs with myxomatous valve disease and asymptomatic mitral regurgitation

We evaluated the long-term effect of early angiotensin-converting enzyme (ACE) inhibition (enalapril maleate) as monotherapy to postpone or prevent congestive heart failure (CHF) in asymptomatic dogs with mitral regurgitation (MR) attributable to myxomatous valvular disease (MVD) in a prospective, randomized, double-blinded, placebo-controlled multicenter trial involving 14 centers in Scandinavia. Two hundred twenty-nine Cavalier King Charles (CKC) Spaniels with MR attributable to MVD but no signs of CHF were randomly allocated to treatment with enalapril 0.25-0.5 mg daily (n = 116) or to placebo groups (n = 113). Each dog was evaluated by physical examination, electrocardiography, and thoracic radiography at entry and every 12 months (+/-30 days). The number of dogs developing heart failure was similar in the treatment and placebo groups (n = 50 [43%] and n = 48 [42%], respectively; P = .99). The estimated means, adjusted for censored observations, for the period from initiation of therapy to heart failure were 1,150 +/- 50 days for dogs in the treatment group and 1,130 +/- 50 days for dogs in the placebo group (P = .85). When absence or presence of cardiomegaly at the entrance of the trial was considered, there were still no differences between the treatment and placebo groups (P = .98 and .51, respectively). Multivariate analysis showed that enalapril had no significant effect on the time from initiation of therapy to heart failure (P = .86). Long-term treatment with enalapril in asymptomatic dogs with MVD and MR did not delay the onset of heart failure regardless of whether or not cardiomegaly was present at initiation of the study.     

Comparison of N-terminal pro-atrial natriuretic peptide and three cardiac biomarkers for discriminatory ability of clinical stage in dogs with myxomatous mitral valve disease

Plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) concentration increases with progression of myxomatous mitral valve disease (MMVD) in dogs. This multicentre, prospective study compared plasma NT-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP), ANP, and cardiac troponin I (cTnI) concentrations in dogs with MMVD for their characteristics and discriminatory ability to detect cardiac dilatation and congestive heart failure (CHF). Thirty-six healthy dogs and 69 dogs with MMVD were included. Clinical variables were obtained via physical examination, thoracic radiography, and echocardiography. The discriminatory ability of each cardiac biomarker (CB) to determine the presence or absence of cardiac dilatation (event 1) and CHF (event 2) was evaluated using the receiver operating characteristic curves. Plasma NT-proANP, NT-proBNP, and ANP concentrations showed a significant association with the left atrium/aorta ratio (P<0.01). The area under the curve of plasma NT-proANP and NT-proBNP concentrations were 0.72 and 0.75, respectively in event1 and 0.72 and 0.76, respectively in event2. Plasma NT-proANP and NT-proBNP concentrations showed sensitivity 80.0 and 80.0%; specificity 67.6 and 64.7% in event1 (cutoff value; 8,497.81 pg/ml and 1,453.00 pmol/l, respectively) and sensitivity 85.7 and 81.0%; specificity 60.4 and 64.6% in event2 (cutoff value; 8,684.33 pg/ml and 1,772.00 pmol/l, respectively). In dogs with MMVD, plasma NT-proANP, NT-proBNP, and ANP concentrations increase with left atrial enlargement. Particularly, plasma NT-proANP and NT-proBNP concentrations appeared to be equally useful in the discriminatory ability to detect cardiac dilatation and CHF.     

Body size, but neither age nor asymptomatic mitral regurgitation, influences plasma concentrations of dimethylarginines in dogs

Asymmetric dimethylarginine (ADMA) is a marker of various cardiovascular diseases in man. The aim of the present study was to test if Cavalier King Charles Spaniels (CKCS) with varying degrees of mitral regurgitation (MR) had increased plasma concentration of ADMA and furthermore, characterize the plasma level of ADMA and symmetric dimethylarginine (SDMA) in normal dogs. Seventy-six dogs were included (44 CKCS and 32 dogs of other breeds). The CKCS had various degrees of MR, whereas the remaining dogs had either no or minimal MR. Apart from cardiac murmurs, no dogs showed signs of cardiac or systematic disease. The degree of MR had no significant influence on ADMA (P = 0.33). Body weight was directly associated with ADMA (P = 0.0004) and creatinine was directly associated with SDMA (P<0.0001). Furthermore, the plasma concentration of ADMA was three to four times higher than found in healthy humans.     

Feasibility,safety, and tolerance of subcutaneous synthetic canine B-type natriuretic peptide (syncBNP) in healthy dogs and dogs with stage B1 mitral valve disease

Introduction

An important aspect of heart failure is the progressive ineffectiveness of the salutary natriuretic peptide system and its secondary messenger, 3′,5′-cyclic guanosine monophosphate (cGMP). In humans with acute heart failure, administration of exogenous natriuretic peptide is associated with improvement in clinical signs and reduction of cardiac filling pressures. This study aimed to determine the feasibility, tolerance, and safety of subcutaneous (SC) synthetic canine B-type natriuretic peptide (syncBNP) administration in dogs.

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.     

Anatomic regurgitant orifice area obtained using 3D-echocardiography as an indicator of severity of mitral regurgitation in dogs with myxomatous mitral valve disease

Objectives

To determine feasibility and repeatability of measuring the anatomic regurgitant orifice area (AROA) using real-time three-dimensional transthoracic echocardiography (RT3DE) in dogs with myxomatous mitral valve disease (MMVD), and to investigate differences in the AROA of dogs with different disease severity and in different American College of Veterinary Internal Medicine (ACVIM) stages.

Plasma N-terminal pro-B-type natriuretic peptide concentration helps to predict survival in dogs with symptomatic degenerative mitral valve disease regardless of and in combination with the initial clinical status at admission

Objectives

Although mitral valve disease (MVD) is the most common canine heart disease, readily available prognostic markers of the disease are still lacking. The aim of this study was to evaluate the comparative ability of N-terminal pro-B-type natriuretic peptide plasma concentration (NT-proBNP) and various echocardiographic variables to predict outcome in dogs with MVD.

Animals, materials and methods

Seventy-four dogs with ISACHC classes 2 and 3 MVD (Groups A and B, respectively) were prospectively recruited. NT-proBNP and several echo-Doppler variables at inclusion were compared as predictors of outcome at 6 months in 54/74 dogs.

Results

NT-proBNP was significantly higher in Group B than in Group A (P < 0.0001), and was the only tested variable significantly different between survivor and non-survivor dogs in both groups (P < 0.05). In the whole canine population, a threshold of 1500 pmol/L could discriminate survivor from non-survivor dogs with a sensitivity and specificity of 80% and 73%, respectively. When combining ISACHC class with NT-proBNP levels, a cut-off of 1265 pmol/L was predictive of survival in Group A, whereas the cut-off was 2700 pmol/L for Group B.

Conclusions

NT-proBNP is correlated with MVD severity and could be used in combination with clinical status to predict cardiac outcome.