Evidence of altered fatty acid metabolism in dogs with naturally occurring valvular heart disease and congestive heart failure.

INTRODUCTION: Myxomatous mitral valve disease (MMVD) is the most common cardiac condition in adult dogs. The disease progresses over several years and affected dogs may develop congestive heart failure (HF). Research has shown that myocardial metabolism is altered in cardiac disease, leading to a reduction in ß-oxidation of fatty acids and an increased dependence upon glycolysis. OBJECTIVES: This study aimed to evaluate whether a shift in substrate use occurs in canine patients with MMVD; a naturally occurring model of human disease. METHODS: Client-owned dogs were longitudinally evaluated at a research clinic in London, UK and paired serum samples were selected from visits when patients were in ACVIM stage B1: asymptomatic disease without cardiomegaly, and stage C: HF. Samples were processed using ultra-performance liquid chromatography mass spectrometry and lipid profiles were compared using mixed effects models with false discovery rate adjustment. The effect of disease stage was evaluated with patient breed entered as a confounder. Features that significantly differed were screened for selection for annotation efforts using reference databases. RESULTS: Dogs in HF had altered concentrations of lipid species belonging to several classes previously associated with cardiovascular disease. Concentrations of certain acylcarnitines, phospholipids and sphingomyelins were increased after individuals had developed HF, whilst some ceramides and lysophosphatidylcholines decreased. CONCLUSIONS: The canine metabolome appears to change as MMVD progresses. Findings from this study suggest that in HF myocardial metabolism may be characterised by reduced ß-oxidation. This proposed explanation warrants further research.

The effect of myxomatous mitral valve disease severity on packed cell volume in dogs.

OBJECTIVES: The aim of this study was to examine whether associations between disease severity and packed cell volume exist in dogs with myxomatous mitral valve disease. MATERIALS AND METHODS: Data were selected from 289 dogs that had been examined at a research clinic (2004-2017) on multiple occasions (n=1465). American College of Veterinary Internal Medicine stage and echocardiographic measurements were entered in separate multivariable linear mixed effects models with packed cell volume as the dependent variable. Age, breed, sex, weight and blood urea nitrogen concentrations were additionally tested in these analyses to control for patient characteristics. RESULTS: Packed cell volume (% whole blood) in stages B1 and B2 (B1: 42.62 ±0.27, P=0.001; B2: 41.77± 0.42, P < 0.001) was lower than stage A (44.57 ±0.53). In stage C, packed cell volume was greater than both preclinical stages (C: 43.84 ±0.46). When the administration of loop diuretics was included in statistical models, packed cell volume was inversely related to normalised left ventricular internal diameters (ß: -2.37; 95% confidence intervals: -3.49, -1.25; P < 0.001). CLINICAL SIGNIFICANCE: Dogs with myxomatous mitral valve disease may develop reductions in packed cell volume as their disease progresses. Although this finding was statistically significant at a population level, it should be noted that the differences described are relatively small. This, along with other causes of variation in packed cell volume, means that changes would be challenging to appreciate within individual patients. Plasma volume depletion following diuretic administration may explain why findings differed in stage C.

Prognostic factors in dogs with presumed degenerative mitral valve disease attending primary-care veterinary practices in the United Kingdom.

BACKGROUND: Prognostic risk factors were identified for dogs with degenerative mitral valve disease (DMVD) monitored by veterinary cardiologists. The value of these measurements has not been determined in the wider primary care setting. OBJECTIVES: To evaluate whether plasma cardiac biomarkers and data obtained from routine history-taking and physical examination are predictive of survival in dogs with DMVD attending primary care practice. ANIMALS: Eight-hundred and ninety-three dogs with a presumptive diagnosis of DMVD recruited from 79 primary care veterinary practices in the United Kingdom. METHODS: Prospective cohort study. Primary care veterinary practitioners recorded clinical data. Plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) were measured at presentation. Cox regression models evaluated associations between risk factor variables and hazard of death (all-cause mortality and cardiac-related death). Flexible parametric models generated predicted survival probabilities for dogs with different combinations of prognostic risk factor variable values. RESULTS: Dogs with higher NT-proBNP and cTnI concentrations, higher heart rates, older dogs, females, and those reported to be exercise intolerant, dyspneic, and diagnosed with selected comorbidities had an increased hazard of death due to any cause. Dogs with higher concentrations of plasma biomarkers, higher heart rates, and heart murmur intensities, those with exercise intolerance and those receiving potent diuretics had a higher hazard of cardiac-related death. CONCLUSIONS AND CLINICAL IMPORTANCE: Cardiac biomarkers and key clinical findings identified in this study can help primary care veterinary practitioners identify dogs with DMVD that are at highest risk of death.

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study.

BACKGROUND: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. OBJECTIVES: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. ANIMALS: Three hundred and fifty-four dogs with MMVD and cardiomegaly. MATERIALS AND METHODS: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. RESULTS: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

Serum cardiac troponin I concentrations in dogs with generalised seizures.

OBJECTIVES: To determine if serum cardiac troponin I concentrations - measured with both a first-generation assay and a high-sensitivity assay - were greater in dogs with generalised seizures than in controls and to identify clinical variables associated with cardiac troponin I concentration. MATERIALS AND METHODS: Prospective study of 30 dogs with recent generalised seizures and 30 healthy controls. Serum cardiac troponin I concentration was measured using two commercially available assays, and the correlation of clinical factors with concentration was examined. RESULTS: Serum concentrations of cardiac troponin I were higher in dogs that had recent seizures compared to controls when measured by both assays. The predictors most clearly associated with cardiac troponin I concentration were number of seizures and age. Both predictors were positively associated with increasing concentrations of troponin I. CLINICAL SIGNIFICANCE: Serum cardiac troponin I concentration was significantly elevated in dogs that had recent generalised seizures when compared to controls, and concentrations were higher in dogs that experienced more seizures. This association may indicate that generalised seizures are associated with damage to the myocardium.

Treatment of dogs with compensated myxomatous mitral valve disease with spironolactone-a pilot study.

OBJECTIVES: Spironolactone improves outcome in dogs with advanced myxomatous mitral valve disease (MMVD). Its efficacy in preclinical MMVD is unknown. The hypothesis was the administration of spironolactone to dogs with compensated MMVD demonstrating risk factors for poorer prognosis will decrease the rate of disease progression. The aim was to provide pilot data to evaluate preliminary effects and sample size calculation for a definitive clinical trial. ANIMALS: Twenty-five client-owned dogs with MMVD with at least one of the following; left atrial to aortic ratio (LA:Ao) ≥ 1.5, normalized left ventricular internal diameter in diastole ≥ 1.6), N-terminal pro-B-type natriuretic peptide (NT-proBNP) > 550 pmol/L, cardiac troponin I > 0.025 ng/mL. METHODS: Prospective, single-center, equally randomized, placebo-controlled, double-blinded, parallel grouped pilot study. No dogs were receiving medications for cardiac disease before the enrollment. RESULTS: Twelve dogs received placebo; 13 received spironolactone. One dog in the spironolactone group died suddenly, 1 developed congestive heart failure, and 2 received suboptimal spironolactone doses. At enrollment, NT-proBNP was significantly higher in the spironolactone group (p=0.005). Left atrial to aortic ratio (p=0.002) and left ventricular internal diameter in diastole (p=0.005) increased over time in the placebo group, but not the spironolactone group; the change did not differ significantly between groups. The change in biomarker concentrations did not differ significantly between groups; there was a tendency toward an increase in NT-proBNP over time in the placebo group. Enrollment of 76 dogs would be necessary to demonstrate a difference in the change in LA:Ao over 6 months between the groups. CONCLUSIONS: Preliminary results support undertaking a larger clinical trial of treatment of dogs with preclinical MMVD with spironolactone.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.

BACKGROUND: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. HYPOTHESIS/OBJECTIVES: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. ANIMALS: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. METHODS: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. RESULTS: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

Differentiation of Cardiac from Noncardiac Pleural Effusions in Cats using Second-Generation Quantitative and Point-of-Care NT-proBNP Measurements.

BACKGROUND: Pleural effusion is a common cause of dyspnea in cats. N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement, using a first-generation quantitative ELISA, in plasma and pleural fluid differentiates cardiac from noncardiac causes of pleural effusion. HYPOTHESIS/OBJECTIVES: To determine whether NT-proBNP measurements using second-generation quantitative ELISA and point-of-care (POC) tests in plasma and pleural fluid distinguish cardiac from noncardiac pleural effusions and how results compare to the first-generation ELISA. ANIMALS: Thirty-eight cats (US cohort) and 40 cats (UK cohort) presenting with cardiogenic or noncardiogenic pleural effusion. METHODS: Prospective cohort study. Twenty-one and 17 cats in the US cohort, and 22 and 18 cats in the UK cohort were classified as having cardiac or noncardiac pleural effusion, respectively. NT-proBNP concentrations in paired plasma and pleural fluid samples were measured using second-generation ELISA and POC assays. RESULTS: The second-generation ELISA differentiated cardiac from noncardiac pleural effusion with good diagnostic accuracy (plasma: sensitivity, 95.2%, specificity, 82.4%; pleural fluid: sensitivity, 100%, specificity, 76.5%). NT-proBNP concentrations were greater in pleural fluid (719 pmol/L (134-1500)) than plasma (678 pmol/L (61-1500), P = 0.003), resulting in different cut-off values depending on the sample type. The POC test had good sensitivity (95.2%) and specificity (87.5%) when using plasma samples. In pleural fluid samples, the POC test had good sensitivity (100%) but low specificity (64.7%). Diagnostic accuracy was similar between first- and second-generation ELISA assays. CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of NT-proBNP using a quantitative ELISA in plasma and pleural fluid or POC test in plasma, but not pleural fluid, distinguishes cardiac from noncardiac causes of pleural effusion in cats.

Degenerative mitral valve disease: Survival of dogs attending primary-care practice in England.

This study aimed to evaluate survival of dogs with degenerative mitral valve disease (DMVD). A retrospective cohort study of dogs with DMVD attending primary-care practices in England was undertaken. Cases of DMVD were identified within the electronic patient records (EPRs) of practices sharing data with VetCompass. Kaplan-Meier curves were used to explore survival and Cox regression models identified factors associated with hazard of death. The EPRs from 111,967 dogs, attending 93 veterinary practices between January 2010 and December 2011 identified 405 cases diagnosed with DMVD giving a prevalence of diagnosed DMVD of 0.36% (95% CI: 0.29-0.45%). A further 3557 dogs were classified as possible cases (heart murmurs consistent with DMVD). Overall, a total of 3962 dogs were classified as heart murmur cases (possible and diagnosed DMVD), giving a prevalence of 3.54% (95% CI: 3.26-3.84%). One hundred and sixteen (28.6%) of the diagnosed DMVD cases were incident, newly diagnosed with DMVD. The mean age at diagnosis was 9.52 years (95% CI: 8.98-10.14 years). Fifty-eight (50.0%) of the incident cases died during the study period. The median survival time (MST) for all-cause mortality was 25.4 months (95% CI: 20.4-34.4 months) after disease detection for DMVD cases. For possible cases, 121 (29.7%) from a random sample of 407 possible DMVD cases were incident cases (newly detected heart murmur consistent with DMVD during the study period). The mean age at which a heart murmur was first recorded in possible cases was 9.73 years (95% CI: 9.02-10.44 years). Forty-nine (40.5%) possible cases died during the study period. The MST for all-cause mortality was 33.8 months (95% CI: 23.7-43.1 months) after a heart murmur was initially detected. In the multivariable survival analysis for possible and diagnosed cases, Cavalier King Charles Spaniels (CKCSs) and other purebreds had higher hazards of death than crossbreds. Dogs weighing ≥20.0kg and older dogs had an increased hazard of death compared with those <20.0kg and younger dogs, respectively. The study highlights poorer survival for all-cause mortality in CKCSs and larger dogs. The reported survival characteristics could aid veterinary surgeons' advice on the prognosis for dogs with DMVD and help the assessment of the impact of the condition at a population level.

Prevalence of and risk factors for degenerative mitral valve disease in dogs attending primary-care veterinary practices in England.

BACKGROUND: To date, epidemiological studies on degenerative mitral valve disease (DMVD) in dogs have largely reported referral caseloads or been limited to predisposed breeds. Analysis of primary-care data to identify factors associated with DMVD would help clinicians identify high-risk individuals and improve understanding. OBJECTIVES: To estimate the prevalence of and identify risk factors for DMVD in dogs attending primary-care veterinary practices in England. ANIMALS: Cases were identified within the electronic patient records of 111,967 dogs attending 93 practices. Four hundred and 5 dogs were diagnosed with DMVD (diagnosed cases) and a further 3,557 dogs had a heart murmur (HM) consistent with DMVD (possible cases). METHODS: Retrospective cross-sectional study design. Prevalence was adjusted for the sampling approach. Mixed effects logistic regression models identified factors associated with DMVD. RESULTS: Prevalence estimates of diagnosed DMVD and HMs consistent with DMVD (both diagnosed and possible cases) were 0.36% (95% confidence interval [CI]: 0.29-0.45) and 3.54% (95% CI: 3.26-3.84) respectively. In the multivariable analysis, males had higher odds of diagnosed DMVD than did females (odds ratio [OR] 1.40, 95% CI: 1.12-1.74). Insured dogs had increased odds of DMVD compared with noninsured dogs (OR 3.56, 95% CI: 2.79-4.55) and dogs ≥20 kg had approximately half the odds of DMVD diagnosis compared with dogs <20 kg (OR 0.51, 95% CI: 0.36-0.74). Strong associations between a DMVD diagnosis and individual breeds and age were identified. CONCLUSIONS AND CLINICAL IMPORTANCE: Degenerative mitral valve disease was a common disorder in practice-attending dogs. Knowledge of identified risk factors for DMVD could improve clinical diagnosis and direct future research.

Clinical severity score system in dogs with degenerative mitral valve disease.

BACKGROUND: Several risk factors already have been determined for dogs with degenerative mitral valve disease (DMVD). Risk factors often have been considered in isolation and have not always taken into account additional information provided by the history and physical examination (PE). HYPOTHESIS/OBJECTIVES: Data obtained from history and PE of dogs with DMVD provide prognostic information and can be used for risk stratification. ANIMALS: Client-owned dogs (n = 244) with DMVD recruited from first opinion practice. METHODS: Prospective longitudinal follow-up of dogs with DMVD. History and PE data were obtained at 6-month intervals and analyzed with time-dependent Cox models to derive relative risk of cardiac death. Independent hazard ratios were used to derive a clinical severity score (CSS), the prognostic value of which was evaluated by analyzing the median survival times for different risk groups and ROC analysis. Analysis of the progression of CSS over time also was undertaken. RESULTS: History of cough, exercise intolerance, decreased appetite, breathlessness (difficulty breathing) and syncope with PE findings of heart murmur intensity louder than III/VI and absence of respiratory sinus arrhythmia were independently associated with outcome and allowed development of the CSS. Clinical severity score distinguished groups of dogs with significantly different outcomes. CONCLUSIONS AND CLINICAL IMPORTANCE: Routinely obtained clinical findings allow risk stratification of dogs with DMVD. Results of ancillary diagnostic tests may be complementary to history and PE findings and always should be interpreted in conjunction with these findings.

Longitudinal electrocardiographic evaluation of dogs with degenerative mitral valve disease.

BACKGROUND: Increased heart rate (HR) and decreased heart rate variability (HRV) are evident in some dogs with degenerative mitral valve disease (DMVD). OBJECTIVES: Evaluation of the factors influencing HR and HRV (assessed by the vasovagal tonus index; VVTI) and their change over time in dogs with DMVD. ANIMALS: Client-owned dogs (n = 257) with DMVD recruited from first opinion practice. METHODS: Prospective longitudinal follow-up at six-monthly intervals of dogs with DMVD. Dogs followed up for at least 18 months (n = 102) were grouped according to their outcome as dogs dying/euthanized because of cardiac disease (n = 28; Group 1), noncardiac disease (n = 40; Group 2) and dogs alive (n = 34; Group 3). HR and VVTI were measured on 1-minute ECG recordings. Repeated measures linear models were constructed to investigate the factors that influence HR and VVTI and their changes over time. RESULTS: Heart rate and VVTI were affected by disease severity and were different in Cavaliers compared to other breeds. Group 1 and Group 2 dogs underwent an increase in HR and decrease in VVTI, evident at least 18 months before death. Group 1 had a further decrease in VVTI followed by an increase in HR approximately 1 year and 6 months before death, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with DMVD have an increase in HR and decrease in HRV over a year before death, with greater changes in those dogs dying/euthanized because of cardiac disease. Both HR and VVTI can potentially be regarded as biomarkers for all-cause mortality.

Fatal arrhythmogenic right ventricular cardiomyopathy in 2 related subadult chimpanzees (Pan troglodytes).

Cardiovascular disease is increasingly recognized as an important cause of morbidity and mortality in captive chimpanzees (Pan troglodytes). This report records 2 cases of sudden cardiac death in closely related subadult captive chimpanzees with marked replacement fibrosis and adipocyte infiltration of the myocardium, which resemble specific atypical forms of the familial human disease arrhythmogenic right ventricular cardiomyopathy. Changes were consistent with left-dominant and biventricular subtypes, which are both phenotypic variants found within human families with familial arrhythmogenic right ventricular cardiomyopathy. Previously reported fibrosing cardiomyopathies in chimpanzees were characterized by nonspecific interstitial fibrosis, in contrast to the replacement fibrofatty infiltration with predilection for the outer myocardium seen in these 2 cases. To the authors' knowledge, this case report is the first to describe cardiomyopathy resembling arrhythmogenic right ventricular cardiomyopathy in nonhuman primates and the first to describe left-dominant arrhythmogenic cardiomyopathy-type lesions in an animal.

Differentiating between feline pleural effusions of cardiac and non-cardiac origin using pleural fluid NT-proBNP concentrations.

OBJECTIVE: To assess whether pleural fluid and urine amino terminal proB-type natriuretic peptide (NT-proBNP) can distinguish cardiac from non-cardiac causes of pleural effusion. METHODS: Blood, urine and pleural fluid were prospectively collected from cats presenting with pleural effusion categorised as cardiac or non-cardiac in origin. NT-ProBNP concentrations were measured using a feline-specific enzyme-linked immunosorbent assay. Groups were statistically compared and receiver operating characteristic curves constructed to determine cut-offs to distinguish cardiac from non-cardiac pleural effusion in plasma, pleural fluid and urine. RESULTS: Forty cats with pleural effusion (22 cardiac and 18 non-cardiac) were studied. NT-proBNP concentrations in plasma and pleural fluid were strongly correlated. Plasma (P<0·001) and pleural fluid (P<0·001) NT-proBNP concentrations and urinary NT-proBNT/creatinine ratios (P=0·035) were significantly higher in the cardiac group. After receiver operating characteristic curve analysis a plasma NT-proBNP cut-off of 214·3 pmol/mL was suggested [sensitivity=86·4% (95% CI: 66·7 to 95·3%), specificity=88·9% (95% CI: 67·2 to 96·9%)] and a pleural fluid NT-proBNP cut-off of 322·3 pmol/mL was suggested [sensitivity=100% (95% CI: 85·1 to 100%), specificity=94·4% (95% CI: 74·2 to 99·0%)]. No cut-off with adequate sensitivity and specificity for urinary NT-proBNP/creatinine ratios was suggested. CLINICAL SIGNIFICANCE: Measurement of NT-proBNP in pleural fluid distinguishes cardiac from non-cardiac causes of pleural effusion in cats.

Prognostic indicators in cats with hypertrophic cardiomyopathy.

BACKGROUND: Left atrial (LA) enlargement, congestive heart failure (CHF), and aortic thromboembolism (ATE) are associated with decreased survival in cats with hypertrophic cardiomyopathy (HCM), but the prognostic value of echocardiographic variables has not been well characterized. HYPOTHESIS/OBJECTIVES: We hypothesized that LA echocardiographic variables and assessment of left ventricular (LV) diastolic and systolic function would have prognostic value in cats with HCM. ANIMALS: Two hundred eighty-two cats diagnosed with HCM. METHODS: Clinical and echocardiographic records of affected cats seen at the Royal Veterinary College from 2004 to 2009 were retrospectively analyzed. Only cats with echocardiographic confirmation of LV diastolic wall thickness ≥ 6 mm were included. Outcomes were obtained from clinical records or referring veterinarians and owners. RESULTS: Deaths occurred in 164 cats, of which 107 were believed to have been cardiac deaths. Univariable predictors of an increased risk of cardiac death included older age, absence of a murmur, presence of a gallop sound or arrhythmia, presentation with either CHF or ATE, extreme LV hypertrophy (≥ 9.0 mm), LV fractional shortening (FS%) ≤ 30%, regional wall hypokinesis, increased left atrial size, decreased left atrial function, spontaneous echo-contrast/thrombus or both, absence of left ventricular outflow tract obstruction, and a restrictive diastolic filling pattern. Cox's proportional hazard analysis identified LA dysfunction, low LV systolic function, and extreme LV hypertrophy as independent predictors of decreased cardiac survival time. CONCLUSIONS AND CLINICAL IMPORTANCE: Echocardiographic measurement of LA function, extreme LV hypertrophy, and LV systolic function provides important prognostic information in cats with HCM.

Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study.

BACKGROUND: Myxomatous mitral valve disease (MMVD) is an important cause of morbidity and mortality in dogs. OBJECTIVES: To compare, throughout the period of follow-up of dogs that had not yet reached the primary endpoint, the longitudinal effects of pimobendan versus benazepril hydrochloride treatment on quality-of-life (QoL) variables, concomitant congestive heart failure (CHF) treatment, and other outcome variables in dogs suffering from CHF secondary to MMVD. ANIMALS: A total of 260 dogs in CHF because of MMVD. METHODS: A prospective single-blinded study with dogs randomized to receive pimobendan (0.4-0.6 mg/kg/day) or benazepril hydrochloride (0.25-1.0 mg/kg/day). Differences in outcome variables and time to intensification of CHF treatment were compared. RESULTS: A total of 124 dogs were randomized to pimobendan and 128 to benazepril. No difference was found between groups in QoL variables during the trial. Time from inclusion to 1st intensification of CHF treatment was longer in the pimobendan group (pimobendan 98 days, IQR 30-276 days versus benazepril 59 days, IQR 11-121 days; P = .0005). Postinclusion, dogs in the pimobendan group had smaller heart size based on VHS score (P = .013) and left ventricular diastolic (P = .035) and systolic (P = .0044) dimensions, higher body temperature (P = .030), serum sodium (P = .0027), and total protein (P = .0003) concentrations, and packed cell volume (P = .030). Incidence of arrhythmias was similar in treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan versus benazepril resulted in similar QoL during the study, but conferred increased time before intensification of CHF treatment. Pimobendan treatment resulted in smaller heart size, higher body temperature, and less retention of free water.

Relationships between heart rate and age, bodyweight and breed in 10,849 dogs.

OBJECTIVES: To evaluate relationships between heart rate and clinical variables in healthy dogs and dogs examined at a referral hospital. METHODS: Clinical data were extracted from the electronic patient records of a first opinion group (5000 healthy dogs) and a referral hospital (5849 dogs). Univariable and multi-variable general linear models were used to assess associations between heart rate and clinical characteristics. Separate multi-variable models were constructed for first opinion and referral populations. RESULTS: In healthy dogs, heart rate was negatively associated with bodyweight (P<0.001) but was higher in Chihuahuas. The mean difference in heart rate between a 5 and 55 kg dog was 10.5 beats per minute. In dogs presenting to a referral hospital, heart rate was negatively associated with bodyweight (P<0.001) and the following breeds; border collie, golden retriever, Labrador retriever, springer spaniel and West Highland white terrier and positively associated with age, admitting service (emergency and critical care, emergency first opinion and cardiology) and the following breeds; Cavalier King Charles spaniel, Staffordshire bull terrier and Yorkshire terrier. CLINICAL SIGNIFICANCE: Bodyweight, age, breed and disease status all influence heart rate in dogs, although these factors account for a relatively small proportion of the overall variability in heart rate.

Efficacy of pimobendan in the prevention of congestive heart failure or sudden death in Doberman Pinschers with preclinical dilated cardiomyopathy (the PROTECT Study).

BACKGROUND: The benefit of pimobendan in delaying the progression of preclinical dilated cardiomyopathy (DCM) in Dobermans is not reported. HYPOTHESIS: That chronic oral administration of pimobendan to Dobermans with preclinical DCM will delay the onset of CHF or sudden death and improve survival. ANIMALS: Seventy-six client-owned Dobermans recruited at 10 centers in the UK and North America. METHODS: The trial was a randomized, blinded, placebo-controlled, parallel group multicenter study. Dogs were allocated in a 1:1 ratio to receive pimobendan (Vetmedin capsules) or visually identical placebo. The composite primary endpoint was prospectively defined as either onset of CHF or sudden death. Time to death from all causes was a secondary endpoint. RESULTS: The proportion of dogs reaching the primary endpoint was not significantly different between groups (P = .1). The median time to the primary endpoint (onset of CHF or sudden death) was significantly longer in the pimobendan (718 days, IQR 441-1152 days) versus the placebo group (441 days, IQR 151-641 days) (log-rank P = 0.0088). The median survival time was significantly longer in the pimobendan (623 days, IQR 491-1531 days) versus the placebo group (466 days, IQR 236-710 days) (log-rank P = .034). CONCLUSION AND CLINICAL IMPORTANCE: The administration of pimobendan to Dobermans with preclinical DCM prolongs the time to the onset of clinical signs and extends survival. Treatment of dogs in the preclinical phase of this common cardiovascular disorder with pimobendan can lead to improved outcome.

The combined prognostic potential of serum high-sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide concentrations in dogs with degenerative mitral valve disease.

BACKGROUND: Identification of factors associated with decreased survival in dogs with degenerative mitral valve disease (DMVD) will allow more accurate prognosis. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is negatively associated with survival in dogs with DMVD. In human patients, multimarker strategies provide superior risk stratification compared with single markers. HYPOTHESIS: High-sensitivity cardiac troponin I (hscTnI) and other clinical variables will be associated with survival time in dogs with DMVD. Measuring hscTnI and NT-proBNP in combination will be prognostically superior to measurement of either marker alone. The rate of change of these markers will vary according to cause of death. ANIMALS: Client-owned dogs (n = 202) with DMVD of varying severity and age-matched healthy control dogs (n = 30) recruited from first opinion private practice. METHODS: Prospective cohort study relating clinical variables at enrollment in dogs with DMVD to survival time (all-cause, cardiac, and noncardiac mortality). Multivariable Cox regression analysis was used to identify factors associated with survival. Measurements were obtained approximately every 6 months. Repeated measures models were constructed to assess changes over time. RESULTS: hscTnI, LVEDDN, heart rate, and age were independently associated with decreased survival time (all-cause mortality). Survival times were shortest in dogs in which both serum hscTnI and NT-proBNP were increased. hscTnI and NT-proBNP increased more rapidly in dogs that died of cardiac disease. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum hscTnI has prognostic value in dogs with DMVD. Measurement of NT-proBNP and hscTnI is prognostically superior to measuring either alone. Serial measurement strategies provide additional prognostic information.