The prevalence of cardiomyopathy in the Irish wolfhound: a clinical study of 500 dogs

The prevalence of cardiomyopathy in Irish wolfhounds was evaluated by retrospective review of the results of cardiovascular examinations carried out in 500 dogs presented for veterinary services at the author's practice. Abnormalities were found in 209 (41.8%) of the dogs examined. Dilated cardiomyopathy (DCM) was diagnosed in 121 (24.2%) of the dogs and was accompanied by atrial fibrillation in 106 dogs. Seventeen dogs were suffering from advanced congestive heart failure (CHF), and 55 dogs were suffering from mild to moderate CHF as a result of DCM. Congestive heart failure was most commonly characterized by mild to severe pleural effusion due to right-sided heart failure in addition to pulmonary edema. Rhythm disturbances without evidence of DCM were detected in 48 dogs. Forty dogs had echocardiographic abnormalities without signs of DCM. Soft to moderate mitral regurgitations were diagnosed in 13 (2.6%) of these 40 dogs examined. In 39 dogs that died as a result of DCM, the median survival time from the time of diagnosis was 5.1 months, and in 59 dogs with DCM that are still alive, the median survival time is 15.7 months.     

Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy

BACKGROUND: Despite traditional therapy of a diuretic, angiotensin converting enzyme inhibitor, digoxin, or a combination of these drugs, survival of dogs with dilated cardiomyopathy (DCM) is low. Pimobendan, an inodilator, has both inotropic and balanced peripheral vasodilatory properties. HYPOTHESIS: Pimobendan when added to conventional therapy will improve morbidity and reduce case fatality rate in Doberman Pinschers with congestive heart failure (CHF) caused by DCM. ANIMALS: Sixteen Doberman Pinschers in CHF caused by DCM. METHODS: A prospective randomized, double-blind, placebo-controlled study with treatment failure as the primary and quality of life (QoL) indices as secondary outcome variables. Therapy consisted of furosemide (per os [PO] as required) and benazepril hydrochloride (0.5 mg/kg PO q12h) and dogs were randomized in pairs and by sex to receive pimobendan (0.25 mg/kg PO q12h) or placebo (1 tablet PO q12h). RESULTS: Pimobendan-treated dogs had a significant improvement in time to treatment failure (pimobendan median, 130.5 days; placebo median, 14 days; P= .002; risk ratio = 0.35, P= .003, lower 5% confidence limit = 0.13, upper 95% confidence limit = 0.71). Number and rate of dogs reaching treatment failure in the placebo group precluded the analysis of QoL. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan should be used as a first-line therapeutic in Doberman Pinschers for the treatment of CHF caused by DCM.     

Pimobendan in heart failure therapy--a silver bullet?

Pimobendan is a novel agent with properties that are highly desirable in the clinical management of congestive heart failure (CHF) secondary to both dilated cardiomyopathy (DCM) and chronic degenerative valvular disease in dogs. Review of available data suggests that pimobendan is safe, well tolerated, and leads to enhanced quality of life in dogs with CHF secondary to DCM or chronic valvular disease when used in combination with furosemide or other conventional therapies (e.g., angiotensin-converting enzyme inhibitors, digoxin). Pimobendan leads to a reduction in mortality from CHF associated with DCM, and ongoing studies are evaluating its effects on mortality associated with chronic valvular disease.     

Association between atrial fibrillation and right-sided manifestations of congestive heart failure in dogs with degenerative mitral valve disease or dilated cardiomyopathy

IntroductionTo determine whether dogs with atrial fibrillation (AF) are more likely to develop right-sided manifestations of congestive heart failure (R-CHF) than dogs without AF.AnimalsTwo hundred twenty dogs diagnosed with congestive heart failure (CHF) secondary to degenerative mitral valve disease (DMVD, n = 155) or dilated cardiomyopathy (DCM, n = 65) at a referral institution.MethodsMedical records were reviewed to extract relevant clinical and echocardiographic data.ResultsFifty dogs had AF at the time of CHF diagnosis, including 17/155 (11.0%) dogs with DMVD and 33/65 (50.8%) dogs with DCM. Sixty dogs had R-CHF evidenced by cavitary effusions. Among DMVD dogs, R-CHF occurred in 13/17 (76.5%) dogs with AF compared with 10/138 (7.2%) dogs without AF; among DCM dogs, R-CHF occurred in 24/33 (72.7%) dogs with AF compared with 13/32 (40.6%) dogs without AF. Dogs with AF were more likely to manifest R-CHF signs than dogs without AF (p < 0.0001 for DMVD; p = 0.0125 for DCM). The presence of AF, diagnosis of DCM, and moderate to severe tricuspid regurgitation were associated with R-CHF in multivariate analysis. AF was the strongest predictor of R-CHF (odds ratio, 14.44; 95% confidence interval, 5.75–36.26).ConclusionsDogs with AF are more likely to manifest R-CHF than dogs without AF. Cavitary effusions are an expected finding in approximately three-quarters of dogs with AF and CHF secondary to either DCM or DMVD.     

Plasma endothelin-1 immunoreactivity in normal dogs and dogs with acquired heart disease

We sought to measure plasma endothelin-1 (ET-1) concentrations in normal dogs and to compare them with those measured in dogs with acquired heart disease with or without pulmonary edema. A sandwich enzyme-linked immunosorbent assay kit was validated and used to measure ET-1 immunoreactivity in plasma samples obtained from 32 normal dogs and 46 dogs with either dilated cardiomyopathy (DCM, n = 27) or degenerative valvular disease (CDVD, n = 19) with (n = 30) or without (n = 16) overt congestive heart failure (CHF). Plasma ET-1 concentrations (geometric mean, 95% confidence interval of geometric mean) were 1.17 (1.04-1.32) fmol/mL in the 32 normal control dogs, 1.25 (0.981-1.60) fmol/mL in 16 dogs with DCM (n = 9) or CDVD (n = 7) without CHF, and 2.51 (2.10-3.01) fmol/mL in 30 dogs with DCM (n = 18) and CDVD (n = 12) with CHE Plasma immunoreactivity of ET-1 was significantly higher in dogs with CHF in comparison with normal dogs (P < .001) and dogs with heart disease without CHF (P < .001). No significant difference was found between normal dogs and dogs with heart disease but without CHF (P > .05). Significant correlations were between plasma ET-I concentrations and left atrial:aortic ratio (P < .0001, r2 = .39), left ventricular internal dimension at end-diastole indexed to aortic diameter (P < .0001, r2 = .30) or body surface area (BSA) (P = .0071, r2 = .10), and left ventricular internal dimension at end-systole indexed to aortic diameter (P = .0003, r- = .17) or BSA (P = .0008, r2 = .15).     

Antioxidant status and biomarkers of oxidative stress in dogs with congestive heart failure

Alterations in antioxidant status and oxidative stress have been documented in dogs with dilated cardiomyopathy (DCM). The purpose of this study was to more broadly assess this relationship in dogs with congestive heart failure (CHF). Malondialdehyde (MDA), 8-F(2alpha)-isoprostane, protein carbonyls, reduced (GSH) and oxidized (GSSG) glutathione, vitamins A, C, and E, and oxygen radical absorbance capacity (ORAC) were measured from a single venous blood sample from dogs with CHF secondary to DCM or chronic valvular disease (CVD) and in healthy controls. Nineteen dogs with CHF (14 CVD and 5 DCM) and 12 healthy controls were enrolled in the study. Concentrations of 8-F(2alpha)-isoprostane (CHF: 44.6 pg/mL [range, 27.1-98.0 pg/mL], controls: 25.3 pg/ mL [range, 11.1-80.4 pg/mL]) but not MDA (CHF: 4.11 microM [range, 1.89-6.39 microM], controls: 3.88 microM [range, 2.14-4.72 microM]) or protein carbonyls (0.69 nmol/mg protein [range, 0.37-1.67 nmol/mg protein], controls: 0.80 nmol/mg protein [range, 0.40-1.14 nmol/mg protein]) were significantly higher in the dogs with CHF than in the controls. Vitamin E concentration (CHF: 2,215 microg/ dL [range, 916-3,499 microg/dL], controls: 2,820 microg/dL [range, 1,738-3,775 microg/dL]) and GSH:GSSG (CHF: 12.0 [range, 3.69-30.1], controls: 22.7 [range, 12.5-227]) were significantly lower, whereas ORAC (CHF: 824 micromol Trolox equivalent/L [range, 304-984], controls: 497 micromol Trolox equivalent/L [range, 258-759]) and vitamin C (CHF: 0.90 mg/dL [range, 0.55-2.02 mg/dL], controls: 0.72 mg/dL [range, 0.43-0.85 mg/dL]) concentrations were higher in dogs with CHF than in controls. Vitamin A concentrations were not different between dogs with CHF and controls. No differences in any of the parameters were detected between dogs with DCM versus those with CVD. Some antioxidant defenses are decreased in dogs with CHF, and some biomarkers of oxidative stress are increased in dogs with CHF. The effect of dietary interventions to correct this imbalance in antioxidant defenses warrants further study.     

Neuroendocrine evaluation of cardiac disease.

Current evidence favors the view that regardless of etiology, there is a predictable sequence of neuroendocrine activation that operates in most dogs and cats with progressive heart disease and that it is largely, but not entirely, independent of etiology. The natriuretic peptides and sympathetic nervous system seem to be early responders to developing cardiac and hemodynamic perturbations in both species. BNP plays a particularly prominent role in cats, possibly as a reflection of disease etiology. Shortly thereafter, plasma endothelin concentrations rise, reflecting the impact of the hemodynamic alterations on the vasculature. Endothelin and the natriuretic peptides directly suppress plasma renin release but have divergent effects on aldosterone. Activation of the tissue RAAS may operate early on to further the progression of heart failure, but evidence of plasma RAAS activation occurs comparatively late and near the time of development of overt CHF. Finally, in animals with severe CHF that are prone to hypotension,vasopressin levels may also rise, contributing to the retention of free water and congestion that is refractory to diuretics. Although oversimplified, this scenario seems to be consistent with data obtained in human, canine, and feline patients. These observations provide some impetus for evaluating ACE inhibitors in cats and beta-receptor-blocking drugs in dogs and cats. Perhaps we are also a little closer to identifying useful biochemical markers that can aid in the diagnosis of heart disease, guide therapy, and improve our understanding of the biologic processes occurring in our patients.     

Aldosterone receptor antagonists – how cardiovascular actions may explain their beneficial effects in heart failure

Ovaert, P., Elliott, J., Bernay, F., Guillot, E., Bardon, T. Aldosterone receptor antagonists – how cardiovascular actions may explain their beneficial effects in heart failure. J. vet. Pharmacol. Therap. 33 , 109–117. Historically, aldosterone receptor antagonists (ARA) have been classified as ‘potassium sparing diuretics’. However, the positive effect of spironolactone, the most extensively studied ARA, on morbidity and mortality observed in humans suffering cardiac insufficiency could not be explained by the renal effect of the drug alone, and a pivotal clinical study has led to extensive research. Many experimental studies have demonstrated that ARA have previously unexpected beneficial effects on the cardiovascular system including reduction in remodelling of the vascular smooth muscle cells and myocytes and improvement of endothelial cell dysfunction in heart failure. These effects improve vascular compliance and slow down the progression of left ventricular dysfunction and end‐organ damage. Furthermore, aldosterone receptor blockade also restores the baroreceptor reflex, improving heart rate variability in heart failure in humans. Some of these effects have been demonstrated in dog models of cardiac disease and so justified further investigation of the potential benefit of ARA in dogs with congestive heart failure (CHF). Positive effects of spironolactone on morbidity and mortality appear to have been seen in studies conducted in dogs suffering from naturally occurring CHF. In addition, eplerenone has been shown to have benefits in canine models of heart failure. The precise mechanisms by which ARA produce these beneficial effects in dogs remain to be determined but this group of drugs clearly provide therapeutic actions out‐with their diuretic effects.     

Evaluation of dietary patterns in dogs with cardiac disease

OBJECTIVE: To determine the dietary patterns and intake of nutrients of concern in dogs with cardiac disease. DESIGN: Prospective study. ANIMALS: 82 dogs with dilated cardiomyopathy (DCM) or chronic valvular disease. PROCEDURE: Owners of dogs were contacted and given a standardized telephone questionnaire regarding diet and a 24-hour food recall to determine daily intake of calories, protein, fat, sodium, potassium, and magnesium. RESULTS: Among the 82 dogs, 71% had no congestive heart failure (CHF), and 29% had CHF or a history of CHF. Sixty-one percent of dogs had concurrent diseases. Anorexia was or had been evident in 34% of dogs and was significantly more common in the CHF group and in dogs with DCM. Most dogs (92%) received some treats and table food, with a median percentage of daily calories from treats of 19% (range, 0% to 100%). Most owners (57%) that administered pills used human or pet foods for pill administration. Most dogs ate more than the Association of American Feed Control Officials (AAFCO) minimum values for fat and protein. Daily sodium intake varied from 14 to 384 mg/100 kcal, compared with the AAFCO minimum of 17 mg/100 kcal. A median of 25% of total daily sodium came from treats and table food (range, 0% to 100%). Dogs with CHF ate significantly more sodium, compared with dogs with no CHF. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary intake for dogs with cardiac disease is highly variable and often not optimal.     

Assessment of diastolic function by Doppler echocardiography in normal Doberman Pinschers and Doberman Pinschers with dilated cardiomyopathy

BACKGROUND: Assessment of diastolic function in patients with dilated cardiomyopathy (DCM) has the potential to add valuable information regarding hemodynamics, disease severity, and prognosis. The purpose of this study was to determine transmitral flow (TMF), isovolumic relaxation time (IVRT), pulmonary venous flow (PVF), flow propagation velocity (Vp), and mitral annular velocities by tissue Doppler in Doberman Pinschers with and without DCM. HYPOTHESIS: It was anticipated that normal and DCM Dobermans would differ with respect to these parameters, and that associations with time to congestive heart failure (CHF) or death would be found. ANIMALS: Thirty client-owned Doberman Pinschers (10 each of normal, occult DCM, and overt DCM) were studied. METHODS: Each dog underwent echocardiography with or without thoracic radiography (to confirm CHF) for classification as normal or DCM-affected, followed by collection of echocardiographic diastolic parameters. RESULTS: The group with occult DCM exhibited features of pseudonormal TMF, reduced systolic to diastolic PVF ratio, and reduced Vp. Shorter early TMF deceleration time (DTE) was associated with shorter time to CHF or sudden death. The group with overt DCM exhibited restrictive TMF, blunted systolic PVF, and reduced early and late diastolic mitral annular velocities. CONCLUSIONS AND CLINICAL IMPORTANCE: Doberman Pinschers showed evidence of moderate and severe diastolic dysfunction in occult and overt DCM, respectively. Short DTE may be a useful predictor of onset of CHF or sudden death.     

Effect of medical therapy on survival of patients with dilated cardiomyopathy.

Few studies have been conducted that focus on survival as the end point of medical therapy of CHF. No vigorous studies have been conducted in dogs. It is generally accepted that diuretic therapy is an essential component of the therapy of CHF in cardiomyopathic dogs. Significant symptomatic improvement is afforded by diuretics, and acute death may be prevented. In this context diuretics can be said to improve survival. However, diuretics do not alter the natural progression of cardiomyopathy and in this context do not favorably influence long-term survival. Digitalis glycosides have been shown in humans to improve various parameters of CHF in a subset of patients with either atrial fibrillation or third heart sounds. In dogs, these gallop heart rhythms due to third heart sounds are usually associated with myocardial failure due to dilated cardiomyopathy. In spite of symptomatic improvement, no study has demonstrated an unequivocal favorable effect of digoxin on survival of patients with dilated cardiomyopathy. Likewise, there is no convincing evidence of an adverse effect on survival. Newer, powerful inotropes, such as milrinone, often demonstrate impressive short-term improvements in left ventricular function, clinical signs, and exercise tolerance in patients with CHF. However, their long-term benefits are much less impressive, they are arrhythmogenic, and they have not been shown to prolong survival. In fact, long-term milrinone therapy in humans has had an unfavorable influence on mortality. Vasodilators offer the potential advantage of increasing left ventricular performance without an associated increase in myocardial oxygen demand and cardiac rhythm disturbances. The only vigorous survival study that unequivocally demonstrated improved survival of patients with advanced CHF due to myocardial failure, including dilated cardiomyopathy, was the Consensus Trial. Survival of patients receiving enalapril was significantly better than those receiving placebo. In fact, the trial was stopped prematurely by the ethical review committee when it became obvious that the results favored the enalapril group. Although the use of beta-adrenergic blocking drugs in cardiomyopathic patients with CHF is controversial and associated with a risk of short-term deterioration of left ventricular function, their use in human medicine is gaining acceptance. Although hemodynamic and clinical evidence of improvement has been demonstrated along with withdrawal-associated deterioration, the only study purporting a beneficial effect on survival used retrospective controls.(ABSTRACT TRUNCATED AT 400 WORDS)     

Observations on the development of congestive heart failure in Irish wolfhounds with dilated cardiomyopathy

Records of previous electrocardiographic (ECG) and echocardiographic examinations of 39 Irish wolfhounds with cardiac failure, obtained during a 10-year survey, were examined to establish whether previously detected abnormalities might be prognostic indicators for the development of congestive heart failure (CHF) due to dilated cardiomyopathy (DCM) in later life. Eighteen dogs (46 per cent) had had atrial fibrillation (AF) at their first examination. Other ECG abnormalities detected at previous examinations were ventricular and supraventricular premature contractions, first and second degree atrioventricular block, P mitrale and left anterior fascicular and right bundle branch blocks. All 39 dogs had developed AF by the time of onset of CHF. The mean age at which CHF was diagnosed was 77 months in males and 86 months in females. The mean age at which AF was first detected was 45 months in males and 59 months in females, and the mean time from the first detection of AF to CHF was 27 months in males and 24 months in females. Previous echocardiographic examinations in eight dogs, over a period of up to five years, revealed progressive left atrial and left ventricular dilatation. Fractional shortening was reduced to below the normal range at the onset of CHF compared with previous examinations in three cases but increased in five. It appears, therefore, that certain ECG abnormalities, especially AF, and/or progressive ventricular and atrial dilatation, may be indicators of 'occult' DCM in wolfhounds.     

Heart rate turbulence after ventricular premature beats in healthy Doberman pinschers and those with dilated cardiomyopathy

Objectives

To describe the measurement of heart rate turbulence (HRT) after ventricular premature beats and compare HRT in healthy Doberman pinschers and those with dilated cardiomyopathy (DCM), with and without congestive heart failure (CHF).

A prospective genetic evaluation of familial dilated cardiomyopathy in the Doberman pinscher

BACKGROUND: The Doberman Pinscher is one of the most common breeds of dogs to develop dilated cardiomyopathy (DCM), a primary heart muscle disorder characterized by myocardial dysfunction, cardiac arrhythmias, and congestive heart failure. In the Doberman Pinscher, the disease is typically adult onset, and a familial etiology has been suggested. HYPOTHESIS: DCM in the Doberman Pinscher, is a familial disease linked to a specific genetic marker. ANIMALS: The study comprised an extended family of Doberman Pinschers with a history of DCM. METHODS: Participating dogs were prospectively evaluated over an 8-year period. Phenotype of participating dogs was determined by annual echocardiography and ambulatory electrocardiography, and the pedigree was evaluated to determine a specific mode of inheritance. Three hundred seventy-two microsatellite markers were selected and genotyped to cover the 38 autosomal chromosomes. Phenotyping, genotyping, and pedigree information was entered into a database, and parametric, 2-point analysis was performed. Markers were considered to be linked to the development of DCM if the logarithm of odds LOD score was >/= 3.0. RESULTS: An autosomal dominant mode of inheritance was defined by the appearance of the disease in multiple generations, equal gender representation (P = .973) and male-to-male transmission. A maximum LOD score of 1.31 was obtained for I marker on chromosome 20, a score not high enough to be associated with DCM. CONCLUSION: DCM in the Doberman Pinscher is a familial disease inherited as an autosomal dominant trait. The causative gene(s) responsible for this condition remain unresolved. Association studies by means of array technology may provide new insights into gene identification.     

Vasopressin, cortisol, and catecholamine concentrations in dogs with dilated cardiomyopathy

OBJECTIVE: To evaluate plasma concentrations and urinary excretion of vasopressin and cortisol and urinary excretion of catecholamines in dogs with dilated cardiomyopathy (DCM). ANIMALS: 15 dogs with clinical signs of DCM, 15 dogs with preclinical DCM, and 15 control dogs. PROCEDURE: Physical examinations, thoracic radiography, ECG, and echocardiography were performed on all dogs. Blood and urine samples were collected. RESULTS: Plasma concentration of vasopressin and the urine cortisol-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM and dogs with preclinical DCM, compared with control dogs. Plasma vasopressin concentration was significantly higher in dogs with clinical signs of DCM, compared with dogs with preclinical DCM. Urine vasopressin-to-urine creatinine ratio was significantly increased in dogs with clinical signs of DCM, compared with dogs with preclinical DCM and control dogs. Urine epinephrine-to-urine creatinine ratio and urine norepinephrine-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM, compared with control dogs. Plasma concentration of cortisol and urine dopamine-to-urine creatinine ratio did not differ significantly among groups. CONCLUSIONS AND CLINICAL RELEVANCE: According to this study, the neuroendocrine pattern is changed in dogs with preclinical DCM. These changes are even more pronounced in dogs with clinical signs of DCM. Analysis of concentrations of vasopressin, cortisol, and catecholamines may aid in identification of the clinical stages of DCM. These findings may also provide a basis for additional studies of the possible beneficial effects of vasopressin antagonists and beta-adrenergic receptor antagonists in the treatment of dogs with congestive heart failure and DCM.     

Heart rate variability in the dog: is it too variable?

The purpose of the study was to evaluate resting heart rate variability (HRV) as a simple noninvasive screening test for early autonomic derangement, heralding the development of occult dilated cardiomyopathy (DCM). Time and frequency domain HRV parameters were evaluated in 32 healthy Doberman pinschers, as potential predictors of the development of occult DCM within the following year and correlated with plasma catecholamines, markers of sympathoexcitation. Ten Dobermans with occult DCM and 8 Dobermans with congestive heart failure (CHF) were positive controls. Seven of the 32 "healthy" dogs developed occult DCM over the course of the study. None of the HRV parameters were associated with the development of occcult DCM based on univariate logistic regression. In dogs who developed occult DCM, plasma norepinephrine (NE) was inversely correlated with % fractal power (r = -0.81, P = 0.05). In dogs with occult DCM (positive controls), plasma NE was inversely correlated with fractal power (r = -0.81, r = 0.03), total power (r = -0.08, P = 0.03), high frequency power (r = -0.75, P = 0.05) and the standard deviation of the RR (r = -0.83, P = 0.02). The great inherent variability of the test may have limited our ability to discriminate between physiologic and pathophysiologic data, rendering this methodology inadequate as a screening test for early occult DCM. However, the negative correlations of NE with various forms of spectral power in dogs with occult DCM suggests that early in the natural history of DCM, there is parasympathetic withdrawal. A reduction in the nonharmonic, fractal component may be the first recognizable abnormality in the power spectrum of dogs who will develop DCM.     

Histologic characterization of canine dilated cardiomyopathy

Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The clinical diagnosis is based on findings on echocardiographic and Doppler examinations, with the active exclusion of other acquired or congenital heart diseases. However, the echocardiographic criteria for the diagnosis of DCM are not wholly specific for the disease, and histologic examination may be necessary for final diagnosis. Review of reports on histologic findings in dogs with clinically diagnosed DCM reveals two histologically distinct forms of DCM: 1) cardiomyopathy of Boxers and Doberman Pinschers, corresponding to the "fatty infiltration-degenerative" type and 2) the form seen in many giant, large-, and medium-sized breeds, including some Boxers and Doberman Pinschers, classified as the "attenuated wavy fiber" type of DCM. The histologic changes of the attenuated wavy fiber type of DCM may precede clinical and echocardiographic signs of heart disease, thus indicating an early stage of DCM.     

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.     

Association of diet with clinical outcomes in dogs with dilated cardiomyopathy and congestive heart failure

IntroductionDilated cardiomyopathy (DCM) in dogs has been associated with feeding of grain-free (GF), legume-rich diets. Some dogs with presumed diet-associated DCM have shown improved myocardial function and clinical outcomes following a change in diet and standard medical therapy.HypothesisPrior GF (pGF) diet influences reverse cardiac remodeling and clinical outcomes in dogs with DCM and congestive heart failure (CHF).Animals and methodsA retrospective study was performed with 67 dogs with DCM and CHF for which diet history was known. Dogs were grouped by diet into pGF and grain-inclusive (GI) groups. Dogs in the pGF group were included if diet change was a component of therapy. Survival was analyzed using Kaplan–Meier curves and the Cox proportional-hazards model.ResultsThe median survival time was 344 days for pGF dogs vs. 253 days for GI dogs (P = 0.074). Statistically significant differences in median survival were identified when the analysis was limited to dogs surviving longer than one week (P = 0.033). Prior GF dogs had a significantly worse outcome the longer a GF diet was fed prior to diagnosis (P = 0.004) or if they were diagnosed at a younger age (P = 0.017). Prior GF dogs showed significantly greater improvement in normalized left ventricular internal diastolic diameter (P = 0.038) and E-point septal separation (P = 0.031) measurements and significant decreases in their furosemide (P = 0.009) and pimobendan (P < 0.005) dosages over time compared to GI dogs.ConclusionsPrior GF dogs that survived at least one week after diagnosis of DCM, treatment of CHF, and diet change had better clinical outcomes and showed reverse ventricular remodeling compared to GI dogs.     

Capturing the dynamics of systemic Renin‐Angiotensin‐Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs

Mochel, J. P., Peyrou, M, Fink, M, Strehlau, G, Mohamed, R, Giraudel, J. M., Ploeger, B, Danhof, M. Capturing the dynamics of systemic Renin‐Angiotensin‐Aldosterone System (RAAS) peptides heightens the understanding of the effect of benazepril in dogs. J. vet. Pharmacol. Therap.  36 , 174–180. In dogs, activation of the Renin‐Angiotensin‐Aldosterone System (RAAS) is an important feature of congestive heart failure (CHF). Long‐term increases in angiotensin II (AII) and aldosterone (ALD) lead to the progression of heart failure to its end stage. Angiotensin‐converting enzyme inhibitors (ACEIs) are the foremost therapeutic option in the management of CHF. Recent literature has challenged the efficacy of ACEIs, based on modest reduction in urinary aldosterone (UALD) excretion despite marked inhibition of ACE activity. This study was designed to heighten the understanding of the effect of benazepril, a potent ACEI, on the RAAS, using a low‐sodium diet as an experimental model of RAAS activation. Time course profiles of RAAS peptides and related areas under the curve (AUC_{24 hours}) were used for comparison between benazepril and placebo groups. Results indicated substantial changes in the dynamics of these biomarkers. At presumed benazeprilat steady state, significant differences in AUC_{24 hours} of plasma renin activity (+90%), angiotensin I (+43%), and AII (?53%) were found between benazepril and placebo‐treated dogs. ALD decreased by 73% in plasma but only by 5% in urine. In conclusion, despite modest reduction in UALD excretion, benazepril markedly influences RAAS dynamics in dogs.