Effect of a specially formulated diet on progression of heart enlargement in dogs with subclinical degenerative mitral valve disease.

BACKGROUND: Previous studies in dogs with degenerative mitral valve disease (DMVD) have identified altered myocardial energy metabolism and oxidation, which might contribute to cardiac hypertrophy. Diets rich in medium chain fatty acids and antioxidants are a potential means of treatment. A previous clinical study found significantly smaller left atrial diameter (LAD) and left atrium-to-aorta diameter ratio (LA : Ao) in dogs with subclinical DMVD fed a specially formulated diet vs control diet for 6 months. HYPOTHESIS/OBJECTIVES: A specially formulated diet will slow or arrest left heart enlargement in dogs with subclinical DMVD over 365 days. ANIMALS: One hundred twenty-seven dogs with unmedicated subclinical DMVD; 101 dogs in the per protocol cohort. METHODS: Randomized double-blinded controlled multicenter clinical trial. RESULTS: The study's primary composite outcome measure was the sum of percentage change in LAD and left ventricular internal dimension at end-diastole (LVIDd) at day 365. In the per protocol cohort, the outcome measure increased by 8.0% (95% confidence interval [CI], 2.9%-13.1%) in dogs receiving the test diet vs 8.8% (95% CI, 5.1%-12.5%) in dogs receiving control diet (P = .79). Neither component of the primary outcome measure was significantly different between groups (LAD, P = .65; LVIDd, P = .92). No difference was found in mitral valve E wave velocity (P = .36) or the proportion of dogs withdrawn from the study because of worsening DMVD and heart enlargement (P = .41). CONCLUSIONS AND CLINICAL IMPORTANCE: Feeding a specially formulated diet for 365 days was not associated with a significantly different rate of change of left heart size in dogs with subclinical DMVD as compared to control.

Accuracy of history, physical examination, cardiac biomarkers, and biochemical variables in identifying dogs with stage B2 degenerative mitral valve disease.

BACKGROUND: Treatment is indicated in dogs with preclinical degenerative mitral valve disease (DMVD) and cardiomegaly (stage B2). This is best diagnosed using echocardiography; however, relying upon this limits access to accurate diagnosis. OBJECTIVES: To evaluate whether cardiac biomarker concentrations can be used alongside other clinical data to identify stage B2 dogs. ANIMALS: Client-owned dogs (n = 1887) with preclinical DMVD prospectively sampled in Germany, the United Kingdom, and the United States. METHODS: Dogs that met inclusion criteria and were not receiving pimobendan (n = 1245) were used for model development. Explanatory (multivariable logistic regression) and predictive models were developed using clinical observations, biochemistry, and cardiac biomarker concentrations, with echocardiographically confirmed stage B2 disease as the outcome. Receiver operating characteristic curves assessed the ability to identify stage B2 dogs. RESULTS: Age, appetite, serum alanine aminotransferase activity, body condition, serum creatinine concentration, murmur intensity, and plasma N-terminal propeptide of B-type natriuretic peptide (NT-proBNP) concentration were independently associated with the likelihood of being stage B2. The discriminatory ability of this explanatory model (area under curve [AUC], 0.84; 95% confidence interval [CI], 0.82-0.87) was superior to NT-proBNP (AUC, 0.77; 95% CI, 0.74-0.80) or the vertebral heart score alone (AUC, 0.76; 95% CI, 0.69-0.83). A predictive logistic regression model could identify the probability of being stage B2 (AUC test set, 0.86; 95% CI, 0.81-0.91). CONCLUSION AND CLINICAL IMPORTANCE: Our findings indicate accessible measurements could be used to screen dogs with preclinical DMVD. Encouraging at-risk dogs to seek further evaluation could result in a greater proportion of cases being appropriately managed.

Risk indictors in cats with preclinical hypertrophic cardiomyopathy: a prospective cohort study.

OBJECTIVES: This study aimed to identify indicators of the risk of progression of preclinical hypertrophic cardiomyopathy (HCM). METHODS: This was a prospective cohort study following a population of cats with preclinical HCM. Cats serially underwent physical examination, blood pressure measurement, blood sampling and echocardiography. Development of congestive heart failure (CHF), arterial thromboembolism (ATE) or sudden death (SD) were considered cardiac-related events. Associations between factors recorded at baseline, and on revisit examinations, and the development of a cardiac-related event were explored using receiver operator characteristic (ROC) analysis. RESULTS: Forty-seven cats were recruited to the study and were followed for a median period of 1135 days. Fifteen cats (31.9%) experienced at least one cardiac-related event; six CHF, five ATE and five SD. One cat experienced a cardiac-related event per 10.3 years of patient follow-up. Cats with increased left atrial (LA) size and higher concentrations of N-terminal pro B-type natriuretic peptide (NTproBNP) at baseline were more likely to experience an event. Cats with a greater rate of enlargement of LA size between examinations were also more likely to experience an event. CONCLUSIONS AND RELEVANCE: Factors easily measured, either once or serially, in cats with preclinical HCM can help to identify those at greater risk of going on to develop clinical signs.

Temporal changes in clinical and radiographic variables in dogs with preclinical myxomatous mitral valve disease: The EPIC study.

BACKGROUND: The Evaluation of pimobendan in dogs with cardiomegaly caused by preclinical myxomatous mitral valve disease (EPIC) study monitored dogs with myxomatous mitral valve disease (MMVD) as they developed congestive heart failure (CHF). OBJECTIVES: To describe the changes in clinical and radiographic variables occurring as dogs with MMVD and cardiomegaly develop CHF, compared to similar dogs that do not develop CHF. ANIMALS: One hundred and thirty-five, and 73 dogs that did or did not develop CHF, respectively. MATERIALS AND METHODS: The following variables were evaluated in 2 groups of dogs (dogs that did or did not develop CHF): Heart rate (HR), clinic respiratory rate (RR), home-measured resting respiratory rate (RRR), rectal temperature (RT), body weight (BW), and vertebral heart sum (VHS). Absolute value and rate of change of each variable were calculated for each day a dog was in study. Daily means were calculated and plotted against time. The onset of CHF or last visit before leaving the study were set as reference time points. RESULTS: The most extreme values and rate of change occurred in variables immediately before onset of CHF. Vertebral heart sum increased earliest. Heart rate, RR, and RRR also increased. Rectal temperature and BW decreased. Increases in RR and RRR were most extreme and occurred immediately before CHF. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with MMVD and cardiomegaly experience increases in HR, RR, RRR, and VHS, and decreases in BW and RT as they develop CHF. The variables with highest absolute change and rate of change were RR and RRR. These findings reinforce the value of RR and RRR as indicators of impending or incipient CHF.

Speckle tracking echocardiography in cats with preclinical hypertrophic cardiomyopathy.

BACKGROUND: Cats with hypertrophic cardiomyopathy (HCM) have decreased left ventricular (LV) longitudinal deformation detected by mitral annular plane systolic excursion (MAPSE) and speckle tracking echocardiography. People with preclinical HCM have decreased systolic LV longitudinal and radial strain (S) and strain rate (SR), with preserved circumferential S and SR. HYPOTHESIS/OBJECTIVES: Cats with preclinical HCM have decreased systolic LV deformation compared to normal cats. ANIMALS: Seventy-three client-owned cats with (n = 37) and without (n = 36) preclinical HCM. METHODS: Retrospective echocardiographic study. Left and right ventricular longitudinal S and SR, LV radial and circumferential S and SR were calculated by STE. Left ventricular mass was also calculated. Correlation between STE variables and LV hypertrophy was determined and receiver-operating characteristic (ROC) curves were plotted for prediction of HCM. RESULTS: Cats with HCM had smaller absolute longitudinal S (-14.8 ± 3.3% vs -19.7 ± 2.7%, P < .001), longitudinal SR (-2.36 ± 0.62 vs -2.95 ± 0.68 second-1 , P < .001), radial S (46.2 ± 21.3% vs 66.7 ± 17.6%, P < .001), and radial SR (5.60 ± 2.08 vs 6.67 ± 1.8 second-1 , P < .001) compared to healthy controls. No difference was observed for circumferential S and SR. Cats with HCM had greater LV mass (13.2 ± 3.7 g vs 8.6 ± 2.7 g, P < .001). The ROC with the greatest area under the curve (AUC) for the identification of HCM (0.974) was plotted from a logistic regression equation combining LV mass, MAPSE at the free wall, and LV internal diameter in diastole (LVIDd). CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with preclinical HCM have decreased long axis and radial deformation. Decreased longitudinal deformation and decreased LVIDd are factors that would support a diagnosis of HCM.

Factors associated with disease progression in dogs with presumed preclinical degenerative mitral valve disease attending primary care veterinary practices in the United Kingdom.

BACKGROUND: Factors associated with disease progression in dogs with preclinical (stage B) degenerative mitral valve disease (DMVD) have not been evaluated previously in primary care veterinary practice. OBJECTIVES: To evaluate whether plasma cardiac biomarkers, clinical signs, and physical examination findings are associated with clinical progression (reaching the composite endpoint of initiation of treatment with a potent diuretic or cardiac death) in dogs presumed to have stage B DMVD. ANIMALS: Six-hundred and eighty-four dogs diagnosed with DMVD recruited from 73 primary care practices in the United Kingdom. Dogs were not receiving potent diuretics at recruitment. METHODS: Prospective cohort study design. Primary care veterinarians recorded the presence or absence of clinical signs and physical examination findings. Baseline plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin I were measured. Cox regression models measured associations between risk factor variables and clinical progression. Flexible parametric models generated predicted probabilities of reaching the composite endpoint for dogs with different combinations of prognostic risk factor variables. RESULTS: Plasma NT-proBNP, heart rate, heart murmur intensity, presence of a cough, being a Cavalier King Charles Spaniel, and being prescribed pimobendan were associated with clinical progression to initiation of treatment with a potent diuretic or cardiac-related death. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with stage B DMVD identified as having a high risk of disease progression might benefit from more frequent monitoring or further diagnostic evaluation. The prognostic factors identified could facilitate risk stratification of dogs presenting with preclinical DMVD.

Ten-minute chat.

Adrian Boswood is professor of cardiology at the Royal Veterinary College. He recently led a study on mitral valve disease, the findings of which will benefit many older dogs.

COMPARISON OF HIGH-DEFINITION OSCILLOMETRIC AND DIRECT ARTERIAL BLOOD PRESSURE MEASUREMENT IN ANESTHETIZED CHEETAHS (ACINONYX JUBATUS).

Blood pressure measurement reveals important insights into the health of conscious and anesthetized individuals. This is of particular interest in cheetahs (Acinonyx jubatus), which in captivity are known to suffer from chronic diseases that may be associated with hypertension and which often require immobilization for transport or veterinary treatment. Invasive testing methods are considered the gold standard but are not practical in many settings. Consequently, it is important to evaluate the use of noninvasive methods in this species. Measurements for systolic, diastolic, and mean arterial pressure obtained using high-definition oscillometry (HDO) at the coccygeal artery were compared to simultaneous direct measurements obtained via catheterization of the femoral or dorsal pedal artery in eight anesthetized captive cheetahs during nine anesthetic events. Overall, HDO and direct measurements agreed most closely for mean arterial pressure, and the poorest agreement was observed for systolic pressure. There was a tendency for low diastolic pressures to be underestimated and for high diastolic pressures to be overestimated. Across all three parameters, HDO measurements from the tail overestimated directly measured pressures in the femoral artery and underestimated those in the dorsal pedal artery. HDO agreed most closely with directly measured dorsal pedal pressures. Mean arterial pressure showed the greatest precision (standard deviation of 10.2 mm Hg) and lowest bias (-1.2 mm Hg), with 75.9% of readings within 10 mm Hg of the direct dorsal pedal pressure. Agreement with systolic pressure was hindered by a high bias (-10.4 mm Hg), but if a correction factor of +10 mm Hg was applied to all systolic measurements, agreement was improved and 65.7% of readings were within 10 mm Hg of the direct pressure. When compared to criteria defined by the American College of Veterinary Internal Medicine for validation of blood pressure devices, results were favorable, but a limited sample size prevented formal validation.

The effects of storage conditions on measurements of canine N-terminal pro-B-type natriuretic peptide.

OBJECTIVES: The study aims were to assess the temporal stability following storage at room temperature, the effect of up to 4 freeze-thaw cycles and the effect of simulated freezer failure on measurements of canine N-terminal pro-B-type natriuretic peptide (NT-proBNP) in serum and protease-inhibited (PI) plasma. ANIMALS: Twenty-five blood samples were collected from 16 dogs with myxomatous mitral valve disease. METHODS: Aliquots of canine serum and PI plasma were stored at room temperature (17-26 °C) for 30 min, 6, 24, 48 and 72 h, respectively. Further aliquots were subjected to between 1 and 4 freeze-thaw cycles. A further aliquot was transferred to storage at 4 °C for 24 h while a paired aliquot remained at -80 °C. All samples were returned to storage at -80 °C until subsequent analysis. N-terminal pro-B-type natriuretic peptide was measured in serum and PI plasma samples using first- and second-generation versions of a commercially-available ELISA. Repeated measures models were used to assess change in NT-proBNP measurements. Wilcoxon signed ranks were used to compare paired measurements. RESULTS: N-terminal pro-B-type natriuretic peptide concentrations declined over time in all samples stored at room temperature. Of the four situations tested, the rate of decrease was lowest for PI plasma samples measured using the second-generation assay. N-terminal pro-B-type natriuretic peptide is stable in samples subjected to up to 4 freeze-thaw cycles and in previously-frozen samples stored at 4 °C for 24 h. CONCLUSIONS: Use of the second-generation assay, compared with the first-generation, resulted in significantly higher recovery of NT-proBNP measured in PI plasma stored at room temperature. Transport of serum at room temperature for NT-proBNP measurement is not recommended.

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

OBJECTIVES: To 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). ANIMALS: Twenty-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. METHODS: Echocardiographic 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. RESULTS: Left 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. CONCLUSIONS: Both 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.

Associations among serum N-terminal procollagen type III concentration, urinary aldosterone-to-creatinine ratio, and ventricular remodeling in dogs with myxomatous mitral valve disease.

OBJECTIVE: To assess relationships among serum N-terminal procollagen type III concentration, urinary aldosterone-to-creatinine concentration ratio (UAC), and clinical variables in dogs with myxomatous mitral valve disease (MMVD) and healthy dogs. ANIMALS: 162 dogs with MMVD and 24 healthy control dogs of comparable age and body weight. PROCEDURES: Blood and urine samples were collected from each dog. Dogs with MMVD underwent echocardiography and ECG. Ventricular diameter measurements were normalized for body weight. Serum N-terminal procollagen type III and urinary aldosterone concentrations were measured via radioimmunoassay. Each dog was examined on 1 to 3 occasions. Examinations were repeated at approximately 6-month intervals. RESULTS: Serum N-terminal procollagen type III concentration decreased with increasing severity of MMVD and was negatively associated with age and left ventricular end-diastolic and end-systolic diameters. The UAC increased with prior percentage change in left ventricular end-diastolic diameter per month, subsequent percentage change in left ventricular end-systolic diameter per month, and treatment with diuretics and was negatively associated with age. Both UAC and serum N-terminal procollagen type III concentration were higher in Cavalier King Charles Spaniels than in other breeds when other measured variables were controlled for. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with MMVD, echocardiographic indicators of left ventricular remodeling appeared to be associated with a decrease in serum concentration of a marker of collagen type III turnover and an increase in urinary aldosterone concentration.

Selected echocardiographic variables change more rapidly in dogs that die from myxomatous mitral valve disease.

OBJECTIVES: To determine if echocardiographic measurements change at a greater rate in dogs with myxomatous mitral valve disease (MMVD) that die of cardiac mortality. ANIMALS: Client-owned dogs (n = 242) with MMVD of varying severity were recruited from first opinion private practice. Only dogs which died during the study period (n = 102) were included in statistical analyses. METHODS: Prospective cohort study comparing the rate of change of echocardiographic variables between dogs that experienced cardiac mortality and those that experienced non-cardiac mortality. Measurements were repeated approximately every 6 months and repeated measures linear models were constructed to estimate the rate of change of each variable over time. RESULTS: Left ventricular (LV) end-diastolic diameter, normalized for body weight (LVEDDN) increased over time in both mortality groups. LV end-systolic diameter, normalized for body weight (LVESDN), LV end-diastolic diameter to LV free wall thickness in diastole (LVEDD/LVFWd) ratio, E wave velocity, E- to A-wave velocity ratio and left atrial to aortic root diameter ratio all increased over time in the cardiac mortality group, but did not change in the non-cardiac mortality group. MR velocity decreased over time in the cardiac mortality group but did not change in the non-cardiac mortality group. Tricuspid regurgitation jet velocity increased over time in both mortality groups. A wave velocity and fractional shortening did not change over time in either mortality group. CONCLUSIONS: Serial echocardiographic examination every 6-12 months is useful to identify dogs with progressive MMVD that are at increased risk of cardiac mortality.

Ultrasonographic measurement of flow-mediated vasodilation in dogs with chronic valvular disease.

OBJECTIVES: To measure flow-mediated vasodilation (FMD) in healthy dogs and in client-owned dogs with chronic valvular disease (CVD) and to investigate possible correlations between markers of CVD severity and FMD. ANIMALS: Twelve dogs with CVD and 11 healthy weight-matched dogs. METHODS: Brachial artery FMD following 5 min inflation of a cuff around the antebrachium was measured in 12 dogs with CVD and 11 healthy weight-matched dogs. Measurements were also obtained in the healthy dogs 5 min after cuff placement but without inflation ('sham cuff placement'). Dogs with CVD underwent echocardiography to confirm and characterize their disease. RESULTS: In healthy dogs (median age 4 [2-6] years), median FMD was 7.7% versus 3.4% with sham cuff placement (P = 0.003). In dogs with CVD (median age 8 [4-16] years) median FMD was 5.5% versus 7.7% in healthy dogs (P = 0.131). FMD showed an inverse correlation with left ventricular end-diastolic diameter normalized for body weight (r = -0.76, P = 0.0043). CONCLUSIONS: Brachial FMD in dogs with early CVD inversely correlates with severity of left ventricular remodelling.