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.     

Decreased sympathetic tone after short-term treatment with enalapril in dogs with mild chronic mitral valve disease

Heart rate variability (HRV) and echocardiography were performed in 14 dogs with mitral regurgitation (MR) before and after 14 days of 0.5 mg/kg/day of enalapril treatment. All dogs were in heart failure stages B1 and B2. After enalapril treatment, left ventricular end diastolic diameter (LVEDd), left ventricular end diastolic diameter normalized for body weight (LVEDdN) and percent mitral regurgitant jet decreased (P < 0.05). The diastolic blood pressure decreased (P < 0.05). Increased time domain parameters of HRV were found. For frequency domain analysis, the total frequency (TF) increased significantly (P < 0.05). The normalized low frequency (LF norm) decreased while normalized high frequency (HF norm) increased causing significant reduction in LF/HF (P < 0.05). Before enalapril treatment, LF was correlated with end diastolic volume (EDV) (P < 0.01) and LVEDd (P < 0.05). In conclusion, MR dogs receiving enalapril treatment for 14 days had increased cardiac parasympathetic tone while sympathetic tone was suppressed. The decreased sympathetic activity corresponded to the reduction in cardiac preload and afterload.     

The outcome of surgical mitral valve repair with loop-in-loop technique in dogs with different stage myxomatous mitral valve disease

ObjectivesSurgical mitral valve repair is a possible option for dogs with myxomatous mitral valve disease. However, information on surgical results and postoperative echocardiography is limited. This study aimed to verify the stage-specific surgical results of mitral valve repair and postoperative echocardiographic changes for two years following surgery.AnimalsAdult dogs (n = 55) treated with surgical mitral valve repair using the loop-in-loop technique were included in this study. Medical records were retrospectively reviewed.ResultsNinety percent of cases (50/55) survived to discharge, which survival was significantly decreased in myxomatous mitral valve disease advanced-stage dogs, Stage B2 (n = 14): 100%, Stage C (n = 27): 96.2%, and Stage D (n = 14): 71.4%. Significant reductions of overall heart size (vertebral heart score: preoperative 11.4 vs. post one month 10.2, P < 0.001), left atrium (left atrium to aortic root ratio: preoperative 2.3 vs. post one month 1.5, P < 0.001) and left ventricle (left ventricular end-diastolic diameter [normalized for bodyweight]: preoperative 2.2 vs. post one month 1.5, P < 0.001) were documented one month after surgery, showing successful management of mitral regurgitation. All medications for mitral valve disease were discontinued three months after surgery. The recurrence of mitral regurgitation was not evident during the two-year follow-up period.ConclusionsSurgical mitral valve repair with the loop-in-loop technique is associated with significant decreases in indices of cardiac size at one-month post-repair. Disease stage influences operative survival after surgical mitral valve repair.     

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.     

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.

Partial external mitral annuloplasty in dogs with myxomatous mitral valve degeneration and congestive heart failure: Outcome in 9 cases

Objective

To report the outcome of partial external mitral annuloplasty in dogs with congestive heart failure (CHF) due to mitral regurgitation caused by myxomatous mitral valve degeneration (MMVD).

Animals, materials and methods

Nine client-owned dogs with CHF due to mitral regurgitation caused by MMVD. Surgery consisted of a double row of pledget-butressed continuous suture lines placed into the left ventricle parallel and just ventral to the atrioventricular groove between the subsinuosal branch of the left circumflex coronary artery and the paraconal branch of the left coronary artery.

Results

Two dogs died during surgery because of severe hemorrhage. Two dogs died 12 and 36 h after surgery because of acute myocardial infarction. Three dogs were euthanized 2 and 4 weeks after surgery because of progression of CHF, 1 was euthanized 30 days after surgery for non-cardiac disease, and 1 survived for 48 months. In the 5 dogs that survived to discharge there was no significant change in the left atrium to aortic ratio with surgery (3.6 ± 0.56 before surgery; 3.1 ± 0.4 after surgery; p = 0.182), and no significant change in mitral regurgitant fraction in 4 dogs in which this measurement was made (78.7 ± 2.0% before surgery; 68.7 ± 7.5% after surgery; p = 0.09).

Conclusions

Partial external mitral annuloplasty in dogs with CHF due to MMVD was associated with high perioperative mortality and most dogs that survived to discharge failed to show clinically relevant palliation from this procedure. Consequently, partial external mitral annuloplasty is not a viable option for dogs with mitral regurgitation due to MMVD that has progressed to the stage of CHF.     

Increased pulmonary transit times in asymptomatic dogs with mitral regurgitation

Pulmonary transit time (PTT) normalized to heart rate (nPTT) is a measure of the pulmonary blood volume (PBV) to stroke volume ratio (PBV/SV). It is an index of cardiac performance. To determine the effect of compensated mitral regurgitation (CMR) and decompensated mitral regurgitation (DMR) caused by valvular endocardiosis on the index nPTT, we measured nPTT by first-pass radionuclide angiocardiography and ECG in 13 normal dogs, 18 dogs with CMR, and 13 dogs with DMR. PTT was measured as time between onset of appearance of activity at the pulmonary trunk and the left atrium. In the normal dogs, the relationship between PTT and mean R-R interval (mRR) was PTT = 4.08 x mRR + 0.15 (R2 = 0.71). Normal nPTT was 4.4 +/- 0.6 (SD) (range. 3.6-5.3). in CMR, 6.3 +/- 1.6 (SD) (range, 4.0-9.7). and in DMR, 11.9 +/- 3.4 (SD) (range, 8.0-18.8). The differences among all groups were significant. Heart rates were 110 +/- 22 bpm in normal dogs, 111 +/- 20 in dogs with CMR, and 144 +/- 18 in dogs with DMR (P < .001 for difference between DMR group and normal and CMR groups). Increased nPTT in CMR indicates preclinical heart pump dysfunction. Heart rate-normalized pulmonary transit times may be a useful index of heart function in mitral regurgitation.     

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.     

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.

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.     

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.

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.     

Associations between N-terminal procollagen type III,fibrosis and echocardiographic indices in dogs that died due to myxomatous mitral valve disease

ObjectivesTo evaluate associations between N-terminal procollagen type III (PIIINP), a serum biomarker of collagen biosynthesis, and myocardial fibrosis in dogs with naturally-occurring myxomatous mitral valve disease (MMVD).AnimalsTwenty-two dogs with echocardiographically-confirmed MMVD were prospectively recruited from a hospital population. All died as a result of MMVD and their hearts were available for post mortem examination.MethodsEchocardiographic measurements and serum PIIINP concentrations were obtained from all dogs prior to death or euthanasia. Serum PIIINP concentrations (μg/mL) were measured using a validated commercially available radioimmunoassay. Myocardial tissue samples were collected post mortem and myocardial fibrosis was scored. The average fibrosis score for all cardiac sites in the heart was designated the global fibrosis score (GFS). The average fibrosis score for all papillary muscle sites was designated the papillary fibrosis score (PFS). Univariate and multivariate linear regression analyses were used separately to evaluate associations between GFS and PFS, respectively, and PIIINP and echocardiographic variables.ResultsLeft ventricular end-diastolic diameter normalized for body weight (LVEDDN) and PIIINP were weakly independently positively associated with both GFS and PFS. LVEDDN and PIIINP were weakly negatively correlated.ConclusionsBoth LVEDDN and serum PIIINP increase with increasing fibrosis score, although these relationships were not strong enough to be clinically useful. Although LVEDDN and PIIINP were positively correlated with fibrosis, PIIINP decreased with increasing LVEDDN, suggesting a complex interplay between fibrosis and remodeling in MMVD.     

C-reactive protein concentration in dogs with chronic valvular disease

The purpose of the study reported here was to determine whether dogs with chronic valvular disease have increased plasma C-reactive protein concentration, compared with that in clinically normal dogs. Blood was collected from 47 dogs with physical and echocardiographic evidence of chronic valvular disease and from 20 healthy controls. C-reactive protein concentration was determined with a commercial canine C-reactive protein enzyme immunoassay. Compared with controls, dogs with chronic valvular disease had higher plasma concentration of C-reactive protein (median 2.17 microg/mL [range, 0.86-33.8 microg/mL]) versus 1.43 microg/mL [range, 0.84-4.99 microg/mL]; P < .001). C-reactive protein concentration was not related to the presence of congestive heart failure or murmur grade. The results of this study suggest that increased concentration of C-reactive protein is found in dogs with chronic valvular disease.     

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.     

Decreased plasma concentration of nitric oxide metabolites in dogs with untreated mitral regurgitation

Endothelium-dependent (nitric oxide [NO]-mediated) vasodilation is impaired in humans with heart failure. This dysfunction is an important therapeutic target. The plasma concentration of the NO metabolites nitrate and nitrite (collectively referred to as NOx) is a measure of whole-body NO production, provided that the dietary intake of the ions is low. Fifty clinically healthy dogs older than I year (median 5.0 years; interquartile interval 2.6-8.2 years) were studied, including 9 controls of various breeds, 23 Cavalier King Charles Spaniels (CKCSs) with no or minimal mitral regurgitation (MR), 9 CKCSs with mild MR (regurgitant jet occupying 15-50% of the left atrial area), and 9 CKCS with moderate to severe MR (jet >50%) due to myxomatous valve disease. None of the dogs received medication. The dogs were given NOx-free water and a diet with a low concentration of NOx for 96 hours before blood sampling. Multiple linear regression analysis revealed that dog group, but not gender, age, serum creatinine concentration, and platelet count, was associated with NOx concentrations. Control dogs had the same NOx concentration (median 20.0 microM; interquartile interval 15.1-25.5 microM) as CKCSs without MR (median 18.7 microM; interquartile interval 15.5-25.9 microM). Compared to CKCSs without MR, the NOx concentration was lower in CKCSs with mild (median 12.9 microM; interquartile interval 11.0-13.5 microM; P = .04) and moderate to severe (median 11.2 microM; interquartile interval 6.9-17.1 microM; P = .02) MR. In conclusion, CKCSs with mild to severe, clinically silent MR have decreased plasma NOx concentrations, suggesting that endothelial dysfunction develops early in the course of developing MR in dogs.     

Prevalence of mitral valve regurgitation in 79 asymptomatic Norfolk terriers

Objectives

To determine the prevalence of mitral valve regurgitation (MR) in asymptomatic Swedish Norfolk terriers.

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.     

Effects of carvedilol treatment in dogs with chronic mitral valvular disease

BACKGROUND: Stimulation of the sympathetic nervous system occurs during the development of heart failure in dogs with chronic mitral valvular disease (CMVD). HYPOTHESIS: The use of beta-blockers to modulate the activation of the sympathetic nervous system would be useful in dogs with CMVD. ANIMALS: Group A included 13 dogs who received the conventional treatment (digoxin, benazepril, a reduced sodium diet, and codeine, and a diuretic when indicated), and group B included 12 dogs who received the protocol above plus carvedilol (0.3 mg/kg q12h). METHODS: Blinded, placebo, controlled study. RESULTS: The main echodopplercardiographic variables, heart rate, biochemical data, functional classification (FC) (New York Heart Association) and quality of life score (functional evaluation of cardiac health questionnaire) were assessed at baseline (TO) and after 3 months (T1). Only group B showed improvement in score of quality of life (13.8 +/- 8.8 versus 6.0 +/- 6.3; P < .001), in FC (2.4 - 0.9 versus 1.8 +/- 0.7; P = .032) and a reduction in systolic blood pressure (151.2 +/- 18.3 versus 124.5 +/- 23.4; P = .021). Two deaths from group A and 1 from B were related to CMVD. CONCLUSION: The studied dose of carvedilol in this group did not improve the sympathetic activation and echocardiographic variables over 3 months of chronic oral treatment. However, the results suggested a beneficial effect on the quality of life score, functional classification, and a reduction on systolic blood pressure.     

Decreased platelet function in Cavalier King Charles Spaniels with mitral valve regurgitation

With aggregometry, increased platelet activity has been reported in Cavalier King Charles Spaniels (CKCS) without mitral regurgitation (MR). In contrast, dogs with MR have been found to have decreased platelet activity. The purpose of this study was to test an easy bedside test of platelet function (the Platelet Function Analyzer [PFA-100]) to see if it could detect an increase in platelet activity in CKCS without MR and a decrease in platelet activity in CKCS with MR. This study included 101 clinically healthy dogs > 1 year of age: 15 control dogs of different breeds and 86 CKCS. None of the dogs received medication or had a history of bleeding. The PFA-100 evaluates platelet function in anticoagulated whole blood under high shear stress. Results are given as closure times (CT): the time it takes before a platelet plug occludes a hole in a membrane coated by agonists. The CT with collagen and adenosine-diphosphate as agonists was similar in control dogs (median 62 seconds; interquartile interval 55-66 seconds) and CKCS with no or minimal MR (55; 52-64 seconds). The CT was higher in CKCS with mild MR (regurgitant jet occupying 15-50% of the left atrial area) (75; 60-84 seconds; P = .0007) and in CKCS with moderate to severe MR (jet > 50%) (87: 66-102 seconds; P < .0001). CKCS with mild, moderate, and severe, clinically inapparent MR have decreased platelet function. The previous finding of increased platelet reactivity in nonthrombocytopenic CKCS without MR could not be reproduced with the PFA-100 device.