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.     

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.     

Atrial natriuretic peptide concentration in dogs with congestive heart failure, chronic renal failure, and hyperadrenocorticism.

The function of atrial natriuretic peptide (ANP) is claimed to be control of salt and water homeostasis, and thus, the hormone may be involved in the pathogenesis of certain diseases with impaired volume regulation. We, therefore, studied plasma ANP concentration in dogs with chronic renal failure, congestive heart failure, and hyperadrenocorticism. Dogs with chronic renal failure had twofold higher plasma ANP concentration (16.2 +/- 5.8 fmol/ml), compared with healthy dogs (8.3 +/- 3.5 fmol/ml). An even more distinct increase (sixfold) of plasma ANP concentration was found in dogs with congestive heart failure (52.9 +/- 29.7 fmol/ml). In contrast, dogs with hyperadrenocorticism did not have high ANP plasma concentration (5.5 +/- 2.0 fmol/ml). High-performance liquid chromatographic analysis of plasma from dogs with congestive heart failure indicated that, in addition to the normal circulating form of ANP (99-126), the unprocessed precursor ANP (1-126) is detectable in the circulation. These qualitative and quantitative alterations of plasma ANP concentration in dogs further suggest involvement of this peptide in the development and/or maintenance of diseases associated with impaired volume regulation.     

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.

Plasma atrial and brain natriuretic peptide levels in dogs with congestive heart failure.

Plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured in 6 dogs with experimental mitral regurgitation (MR) and 19 canine patients with asymptomatic and symptomatic congestive heart failure (CHF). In dogs with experimental MR, ANP and BNP concentrations were significantly correlated with pulmonary capillary wedge pressure (PCWP) (ANP; r=0.852, P=0.0004, BNP; r=0.832, P=0.0008). ANP level was shown to have a predominant effect on PCWP in comparison with BNP using multiple regression analysis. In canine patients with asymptomatic and symptomatic CHF, ANP and BNP concentrations were significantly different among the heart failure classes according to the New York Heart Association functional classification (ANP; P=0.0165, BNP; P=0.0005). In addition, ANP and BNP levels in dogs with decompensated heart failure (n=10) significantly increased in comparison with those in dogs with compensated heart failure (n=9). There was however no correlation between ANP and BNP levels in each heart failure class. In conclusion, plasma ANP and BNP levels may become predictors of PCWP and the severity of heart failure in dogs with MR, although further investigations on ANP and BNP levels in more clinical cases are required.     

Right ventricular outflow tract fractional shortening: an echocardiographic index of right ventricular systolic function in dogs with pulmonary hypertension

Objectives

To create reference intervals for right ventricular outflow tract fractional shortening (RVOT-FS) in healthy dogs and examine diagnostic performance of this index in dogs with pulmonary hypertension (PH). In addition, we examine the impact of myxomatous mitral valve disease (MMVD) without PH on RVOT-FS.

Evaluation of circulating amino terminal-pro-B-type natriuretic peptide concentration in dogs with respiratory distress attributable to congestive heart failure or primary pulmonary disease

OBJECTIVE: To evaluate assessment of circulating amino terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration as a means to discriminate between congestive heart failure and primary pulmonary disease in dogs. DESIGN: Prospective case series. ANIMALS: 46 dogs with signs of respiratory distress or coughing. PROCEDURES: All dogs underwent physical and thoracic radiographic examinations. Dogs with evidence of heart disease (eg, murmur, arrhythmia, or large cardiac silhouette detected by radiography) also underwent echocardiography. Dogs with no evidence of heart disease or failure were included if they underwent bronchoalveolar lavage (with cytologic examination and bacterial culture of the lavage fluid). Blood samples for NT-proBNP assay were obtained within 12 hours of the diagnosis of heart failure or prior to bronchoalveolar lavage in dogs with primary pulmonary disease. Circulating concentrations of NT-proBNP were compared between groups and correlated with radiographic and echocardiographic measures of cardiac size. RESULTS: Congestive heart failure and primary pulmonary disease were diagnosed in 25 and 21 dogs, respectively. Dogs with congestive heart failure had significantly higher median serum or plasma NT-proBNP concentration (2,554 pmol/L; interquartile [25% to 75%] range, 1,651.5 to 3,475.5 pmol/L) than dogs with primary pulmonary disease (357 pmol/L; interquartile range, 192.5 to 565.5 pmol/L). Radiographic vertebral heart score and echocardiographic left atrial-to-aortic diameter ratio were not correlated with NT-proBNP concentration. Left ventricular end-diastolic diameter (measured echocardiographically) and NT-proBNP concentration were weakly correlated. CONCLUSIONS AND CLINICAL RELEVANCE: Serum or plasma NT-proBNP concentration assessment may be useful for discrimination of congestive heart failure from primary pulmonary disease in dogs with respiratory distress or cough.     

Prediction of clinically important acquired cardiac disease without an echocardiogram in large breed dogs using a combination of clinical,radiographic and electrocardiographic variables

IntroductionLarge breed (LB) dogs develop dilated cardiomyopathy (DCM) and myxomatous mitral valve disease (MMVD). Echocardiography is required for a definitive diagnosis but is not always available. Our objective was to assess the clinical utility of thoracic radiographs alone and in combination with physical examination and electrocardiography findings for the prediction of clinically important DCM or MMVD in LB dogs.AnimalsFour hundred fifty-five client-owned dogs ≥20 kg with concurrent thoracic radiographs and echocardiogram.Materials and methodsMedical records were reviewed and stored thoracic radiographs and echocardiographic images were measured to classify dogs as normal heart size (NHS), preclinical DCM, clinical DCM, preclinical MMVD (with cardiomegaly), clinical MMVD, or equivocal. Dogs with preclinical MMVD, without cardiomegaly, were classified as NHS. Vertebral heart size (VHS) and vertebral left atrial size (VLAS) were measured. Receiver operating characteristic curves and prediction models were derived.ResultsPrevalence of MMVD (39.3%) was higher than the prevalence of DCM (24.8%), though most MMVD dogs (67.0%) lacked cardiomegaly and were classified as NHS for analysis. The area under the curve for VHS to discriminate between NHS and clinical DCM/MMVD or preclinical DCM/MMVD was 0.861 and 0.712, respectively, while for VLAS, it was 0.891 and 0.722, respectively. Predictive models incorporating physical examination and electrocardiography findings in addition to VHS/VLAS increased area under the curve to 0.978 (NHS vs. clinical DCM/MMVD) and 0.829 (NHS vs. preclinical DCM/MMVD).ConclusionsThoracic radiographs were useful for predicting clinically important DCM or MMVD in LB dogs, with improved discriminatory ability when physical examination abnormalities and arrhythmias were accounted for.     

Two-dimensional,long-axis echocardiographic ratios for assessment of left atrial and ventricular size in dogs

Introduction

Left ventricular (LV) and left atrial (LA) enlargement affect management and outcome of dogs with cardiac disease. Short-axis, two-dimensional echocardiographic (2DE) images, indexed to the aorta (Ao), are frequently used to identify cardiomegaly. Long-axis images offer complementary views of the left heart.

Changes in platelet function in Dachshunds with early stages of myxomatous mitral valve disease

The aim of this study was to evaluate platelet function in Dachshunds during early stages of myxomatous mitral valve disease.Clinical examination and echocardiography were performed in 34 wirehaired standard sized Dachshunds. Platelet function was evaluated using the PFA-100 (reported as closure time). In addition, whole blood platelet aggregation response and hemostatic markers were evaluated.Significant longer PFA-100 closure time (CT) was found in 12 Dachshunds with mild mitral regurgitation (MR) compared to 22 Dachshunds with minimal MR. Only five Dachshunds responded to adenosine diphosphate in the whole blood aggregation analyses. There were no differences between the two dog groups in plasma fibrinogen, plasma von Willebrand factor (vWf) or vWf multimer distribution; however, there was a significant correlation between CT and plasma vWf concentration and CT and plasma fibrinogen concentration.The higher CT found in Dachshunds with mild MR suggests a form of platelet dysfunction in Dachshunds with MR.     

Holter monitoring in 36 dogs with myxomatous mitral valve disease

Objective Describe the presence of arrhythmias in dogs with myxomatous mitral valve disease (MMVD) and the potential association with class of heart failure and left atrial enlargement. Compare the standard electrocardiogram (ECG) with Holter monitoring for assessing heart rate (HR). Experimental procedure The study group of 36 dogs weighing less than 20 kg was divided into MMVD and no clinical signs (preclinical) or MMVD and clinical signs (clinical). A standard echocardiogram, ECG and 24-h Holter recording were obtained in all dogs. Results Minimum and mean Holter HRs were higher in the clinical group than in the preclinical group. Clinical dogs had more ventricular arrhythmias than preclinical dogs. An enlarged left atrium was associated with the presence of more supraventricular arrhythmias. Conclusions Arrhythmias are a common finding in dogs with MMVD and Holter monitoring is a reliable tool for both HR monitoring and diagnosis.     

Decreased systolic function and inadequate hypertrophy in large and small breed dogs with chronic mitral valve insufficiency

BACKGROUND: Systolic dysfunction associated with chronic mitral valve insufficiency (CMVI) has been demonstrated in experimental animal models and large breed (LB) dogs but has been reported as an uncommon finding in small breed (SB) dogs with naturally occurring disease. It has been suggested the myocardial failure could be, in part, because of an insufficient increase in left ventricular mass. HYPOTHESIS: To test if SB and LB dogs with CMVI and moderate heart failure have systolic dysfunction and if they have adequate eccentric hypertrophy. ANIMALS: Data from 38 SB and 18 LB dogs affected with CMVI were compared retrospectively with results from 2 groups of normal dogs (17 SB and 32 LB). METHODS: Systolic function was investigated echocardiographically by using percentage fractional shortening (FS), the ratio between observed and expected end-systolic diameter (ESD/ESDe), and end-systolic volume index (ESVI). Left ventricular hypertrophy was estimated by using the ratio between the thickness of the left ventricular free wall and the radius in diastole (h/R). RESULTS: Both affected SB and LB dogs had a significantly increased FS and ESVI (FS% SB 45.6 + 8.04 versus 40.06 + 8.9, P < .05; FS% LB 33.64 + 8.61 versus 27.3 + 7.3 P < .05; ESVI SB 30.0 +/- 2.3 mL/m2 versus 21.18 +/- 13.9 mL/m2, P < .05; ESVI LB 83.22 +/- 43.84 mL/m2 versus 36.43 +/- 13.30 mL/m2 versus P < .001). The h/R in affected animals was decreased (0.53 +/- 0.11 versus 0.41 +/- 0.12, P < .05 SB; 0.47 +/- 0.11 versus 0.38 +/- 0.09, P < .05, LB). CONCLUSIONS AND CLINICAL IMPORTANCE: Data from this study indicate that dogs with moderate heart failure caused by CMVI have systolic dysfunction. Inadequate hypertrophy of the left ventricle may be, in part, responsible for this finding.     

Hemostatic biomarkers in dogs with chronic congestive heart failure

BACKGROUND: Chronic congestive heart failure (CHF) in humans is associated with abnormal hemostasis, and abnormalities in hemostatic biomarkers carry a poor prognosis. Alterations in hemostatic pathways can be involved in the pathogenesis of CHF in dogs, and microthrombosis in the myocardium could contribute to increased mortality. HYPOTHESIS: That plasma concentration or activity of hemostatic biomarkers is altered in dogs with CHF and that these factors predict mortality. ANIMALS: Thirty-four dogs with CHF caused by either dilated cardiomyopathy (DCM, n=14) or degenerative valvular disease (CDVD, n=20) compared with 23 healthy age-matched control dogs were included in this study. Dogs with CHF were recruited from 2 referral cardiology clinics, and control dogs were owned by friends or colleagues of the investigators. METHODS: Clinical examination and echocardiography were performed in all dogs. Plasma fibrinogen and D-dimer concentrations, antithrombin and protein C activity, and thrombin-antithrombin complex (TAT) were measured in all dogs. RESULTS: Dogs with CHF had significantly higher fibrinogen (P = .04), D-dimer (P = .002), and TAT concentration (P < .0001), lower antithrombin (P < .0001) and protein C activity (P < .001) compared with control dogs. None of the hemostatic biomarkers were associated with risk of death. CONCLUSIONS AND CLINICAL IMPORTANCE: There is evidence of a procoagulant state in dogs with CHF. The lack of predictive value for survival might be due to the small number of dogs examined. Further studies are necessary to investigate the presence and importance of microthrombosis in dogs with CHF.