Response of cats with dilated cardiomyopathy to taurine supplementation.

Between October 1986 and September 1988, 37 cats with moderate to severe idiopathic myocardial failure (dilated cardiomyopathy) were evaluated. Clinical management of these cats was similar to that described in the literature, except that it also included administration of 500 or 1,000 mg of the sulfur amino acid, taurine per day. Early death (death within the first 30 days of treatment) occurred in 14 (38%) cats. One cat was lost to follow-up evaluation. Twenty-two cats (59%) had marked clinical and echocardiographic improvement and survived longer than 240 days. In all but 1 cat, the observed improvement in echocardiographic measurements persisted. Hypothermia and thromboembolism were positively associated with an increased risk of early death. Administration of digoxin did not significantly affect survival. All 22 cats that survived greater than 30 days remained clinically stable despite withdrawal of all medications except taurine. Administration of taurine was eventually discontinued in 20 of the 22 cats and adequate taurine intake was thereafter provided for in the food. The clinical response and 1-year survival rate of 58% (21 of 36 cats with a known outcome) in the taurine-treated group represents a marked improvement, compared with a 1-year survival rate of 13% (4 of 31 cats with a known outcome) in a retrospectively evaluated population of 33 cats with dilated cardiomyopathy.     

Efficacy of digoxin administration in dogs with idiopathic congestive cardiomyopathy

Digoxin administration (0.22 mg/m2 of body surface BID) to 10 large-breed dogs with congestive cardiomyopathy increased shortening fraction more than 5.5% in 4 of the dogs. This group of dogs lived longer than the group that did not have a positive inotropic response to digoxin. Heart rate decreased in both groups of dogs. Base-line jugular PVO2 were low in all dogs. Jugular PVO2 decreased significantly in the group that did not respond to digoxin, presumably because of decreased cardiac output. Jugular PVO2 consistently increased in dogs that had a positive inotropic response to digoxin. Base-line shortening fraction, heart rate, and PVO2 did not predict which dogs would respond to digoxin. Serum digoxin concentrations were consistently between 1.5 and 2.5 ng/ml. It was concluded that digoxin administration is not efficacious in all dogs with congestive cardiomyopathy and that the positive inotropic response is not predicted by base-line shortening fraction, heart rate, or jugular PVO2. Dogs that do respond to digoxin usually live longer than those that do not. Jugular PVO2 can be used to separate dogs that do respond from dogs that do not respond to digoxin as long as the base-line PVO2 is low. The negative chronotropic effects of digoxin may be detrimental to dogs that do not have a positive inotropic effect from digoxin.     

Prognostic indicators for dogs with dilated cardiomyopathy

The purpose of this study was to investigate the prognostic value of various clinical, ECG, echocardiographic, and Doppler echocardiographic variables in dogs with dilated cardiomyopathy. The relationship to survival of 11 variables was evaluated in 63 dogs. Studied variables were age at time of diagnosis, class of heart failure (HF), dyspnea, ascites, atrial fibrillation (AF), ejection fraction (EF), E-point septal separation, end-diastolic volume index, end-systolic volume index (ESV-I), and restrictive or nonrestrictive transmitral flow (TMF) pattern. Median survival time was 671 days (lower 95% confidence limit, 350 days). Survival curves showed that severity of HF, ascites, ESV-I greater than 140 mL/m2, EF less than 25%, and restrictive TMF pattern had a significant negative relation to survival time. Thirty-nine dogs with both sinus rhythm and AF presented adequate TMF recordings; in these dogs, after stratification by TMF pattern, the restrictive TMF pattern was the most important negative prognostic indicator. We conclude that in dogs with dilated cardiomyopathy the restrictive TMF pattern appears to represent a useful prognostic indicator. Class of HF, ascites, ESV-I, and EF are also useful indexes if an adequate TMF pattern is not recorded.     

Clinical findings in cats with dilated cardiomyopathy and relationship of findings to taurine deficiency.

Between October 1986 and September 1988, 37 cats with moderate to severe idiopathic myocardial failure (dilated cardiomyopathy) were evaluated prospectively. Low plasma taurine concentration and diet history including foods that can cause taurine deficiency were documented in most of the cats. Comparison with a retrospectively studied population of 33 cats with dilated cardiomyopathy diagnosed between 1980 and 1986 demonstrated that the clinical and historical findings in the 33 retrospectively studied cats were similar to those in the 37 cats studied prospectively. Clinical findings in the 2 groups were also similar to findings previously reported in the literature. Because clinical findings and diet history were similar in the prospective and retrospective groups, we believe that many cats in the latter group had diet-induced taurine deficiency. These findings support the conclusion that most cases of dilated cardiomyopathy in cats have a common etiopathogenesis related to diet and as such are preventable.     

Effect of pimobendan on the clinical outcome and survival of cats with non-taurine responsive dilated cardiomyopathy

This retrospective study was designed to assess the effect of pimobendan on the median survival time (MST) of cats with non-taurine responsive dilated cardiomyopathy (DCM). Thirty-two client-owned cats with a left ventricular internal dimension at end systole (LVIDs) >14 mm, a fractional shortening (FS) <28% and a lack of response to taurine therapy were included over a 9-year period (2001-2010). These cats were divided into pimobendan (n=16) and non-pimobendan (n=16) treatment groups. All cats received standard treatment with frusemide, taurine and benazepril or enalapril. Nine cats in the non-pimobendan group also received digoxin. The MST of the pimobendan group (49 days; range 1 to >502 days) was four times that of the non-pimobendan group (12 days; 1 to 244 days). The difference in survival between the two groups was statistically significant (P = 0.048). Hypothermia and FS <20% were associated with a poor prognosis. No adverse effects to pimobendan were noted.     

Hypercoagulability in cats with cardiomyopathy

BACKGROUND: Arterial thromboembolism (ATE) is a common complication of feline cardiomyopathy; however, the pathogenesis of ATE is unknown. HYPOTHESIS: Systemic activation of the coagulation cascade (hypercoagulability) and endothelial injury promote ATE in cardiomyopathic cats. ANIMALS: Healthy cats (n = 30) and 3 groups of cardiomyopathic cats: Group (1) left atrial enlargement only (LAE [n = 11]), ie, left atrial to aortic ratio >1.4; Group (2) LAE with spontaneous echocardiographic contrast, atrial thrombi or both (SEC-T [n = 16]); and Group (3) acute ATE with LAE (n = 16). METHODS: Hypercoagulability was defined by 2 or more laboratory abnormalities reflecting coagulation factor excess (high fibrinogen concentration or Factor VIII coagulant activity), inhibitor deficiency (low antithrombin activity), or thrombin generation (high thrombin-antithrombin complex [TAT] and d-dimer concentrations). High von Willebrand factor antigen concentration (vWF : Ag) was considered a marker of endothelial injury. Data were analyzed using nonparametric statistics. RESULTS: The 3 groups of cats with cardiac disease had higher median fibrinogen concentrations than did the healthy cats. Criteria of hypercoagulability were found exclusively in cats with SEC-T (50%) and ATE (56%). Hypercoagulability was not associated with left atrial size or congestive heart failure (CHF). ATE cats had significantly higher median vWF : Ag concentration than did the other groups. CONCLUSION AND CLINICAL IMPORTANCE: Systemic hypercoagulability is evident in many cardiomyopathic cats, often without concurrent CHF or overt ATE. Hypercoagulabilty may represent a risk factor for ATE. High vWF : Ag in ATE cats was attributed to downstream endothelial injury from the occlusive thrombus.     

Carvedilol in dogs with dilated cardiomyopathy

BACKGROUND: Dilated cardiomyopathy (DCM) is characterized by reduced systolic function, heightened sympathetic tone, and high morbidity and mortality. Little is known regarding the safety and efficacy of beta-blocker treatment in dogs with DCM. HYPOTHESIS: Carvedilol improves echocardiographic and neurohormonal variables in dogs with DCM over a 4-month treatment period. METHODS: Prospective, placebo-controlled, double-blinded randomized study. Dogs with DCM underwent echocardiography, ECG, thoracic radiographs, and neurohormonal profiling, followed by titration onto carvedilol (0.3 mg/kg q12h) or placebo over a 4-week period and subsequently received 3 months of therapy. Primary study endpoints included left ventricular volume and function. RESULTS: Sixteen dogs received carvedilol and 7 received placebo. At study end, 13 carvedilol dogs and 5 placebo dogs were alive. There was no difference in the mean percentage change in left ventricular volume at end-diastole (LVVd), left ventricular end-systolic volume (LVVs), and ejection fraction (EF) between treatment groups, suggesting that both groups experienced similar amounts of disease progression. Carvedilol treatment did not result in significant changes in neurohormonal activation, radiographic heart size, heart rate, or owner perceived quality-of-life. Baseline B-type natriuretic peptide (BNP) predicted dogs in the carvedilol-treated group that maintained or improved their EF over the study duration. CONCLUSIONS AND CLINICAL IMPORTANCE: Carvedilol administration did not improve echocardiographic or neurohormonal indicators of heart function. The lack of effect may be related to severity of disease, carvedilol dose, or brevity of follow-up time. Statistical power of the present study was adversely affected by a high fatality rate in study dogs and small sample size.     

Efficacy of tinidazole for treatment of cats experimentally infected with Tritrichomonas foetus

OBJECTIVE: To determine the efficacy of tinidazole for treatment of cats with experimentally induced Tritrichomonas foetus infection. ANIMALS: 8 specific-pathogen-free kittens. PROCEDURES: Tinidazole was tested for activity against a feline isolate of T foetus in vitro. Kittens were infected orogastrically with the same isolate and treated or not with tinidazole (30 mg/kg, PO, q 24 h for 14 days). Amoxicillin was administered 28 weeks after completion of tinidazole administration to induce diarrhea. Feces were repeatedly tested for T foetus by use of PCR assay and microbial culture for 33 weeks. RESULTS: Tinidazole killed T foetus at concentrations >or= 10 microg/mL in vitro. In experimentally induced infection, tinidazole administered at 30 mg/kg decreased T foetus below the limit of molecular detection in 2 of 4 cats. Recrudescent shedding of T foetus, as elicited by amoxicillin-induced diarrhea, was diminished in cats that received prior treatment with tinidazole. CONCLUSIONS AND CLINICAL RELEVANCE: Although tinidazole decreased the detection of T foetus and treated cats were resistant to later efforts to incite the infection, inability of tinidazole to eradicate infection in many cats poses a serious impediment to the drug's effectiveness in practice.     

Animal models of dilated cardiomyopathy for translational research

Animal models of cardiovascular disease have proved critically important for the discovery of pathophysiological mechanisms and for the advancement of diagnosis and therapy. They offer a number of advantages, principally the availability of adequate healthy controls and the absence of confounding factors such as marked differences in age, concomitant pathologies and pharmacological treatments. Dilated cardiomyopathy (DCM) is the third cause of heart failure (HF) and is characterized by progressive ventricular dilation and functional impairment in the absence of coronary lesions and/or hypertension. Over the past thirty years, investigators have developed numerous small and large animal models to study this very complex syndrome. Genetically modified mice are the most widely and intensively utilized research animals and allow high throughput studies on DCM. However, to translate discoveries from basic science into medical applications, research in large animal models becomes a necessary step. An accurate large animal model of DCM is pacing-induced HF. It is obtained by continuous cardiac pacing at a frequency three- to fourfold higher than the spontaneous heart rate and is mostly applied to dogs, but also to pigs, sheep and monkeys. To date, this model can still be considered a gold standard in HF research.     

Efficacy of iopanoic acid for treatment of spontaneous hyperthyroidism in cats

Iopanoic acid is an iodine containing oral cholecystographic agent that has been used to treat hyperthyroidism in humans and has recently been evaluated in an experimental model of feline hyperthyroidism. The aim of this study was to evaluate the efficacy of iopanoic acid in cats with spontaneous hyperthyroidism. Eleven cats were included in the study. Eight were treated initially with 50mg orally q 12h and three were treated with 100mg orally q 12h. Prior to treatment (baseline) and at 2, 4, and 12 weeks of treatment, owner questionnaires, physical exams, complete blood count, biochemistry analyses, and T(3) and T(4) concentrations were evaluated. The mean serum T(3) concentration decreased with treatment at all time periods compared to baseline. Mean T(4) concentrations were increased at weeks 4 and 12 compared to baseline. Five cats had a partial response during the initial 4 weeks of therapy, but the effects were transient and no significant improvements in clinical signs or physical exam findings were noted at any time period. Results suggest that iopanoic acid may be beneficial for acute management of thyrotoxicosis in some cats, but is not suitable for long-term management.     

Measurements of plasma endothelin immunoreactivity in healthy cats and cats with cardiomyopathy

Plasma concentrations of endothelin-1 (ET-1), the most potent endogenous pressor substance discovered to date, are abnormally high in humans with congestive heart failure (CHF), and they correlate with the degree of functional impairment. We sought first to validate a human sandwich ELISA kit that targets that portion of the amino acid sequence that is identical in cats. The assay demonstrated linearity (R2 = .9968) and parallelism (P = .5339), recovery of spiked human ET-1 in cat plasma averaged 98.7%, and intraassay precision had a coefficient of variation <10%. We subsequently determined ET-1 immunoreactivity in healthy cats and in cats with myocardial disease with and without CHF, systemic thromboembolism (STE), or both. Plasma ET-1 immunoreactivity was measured in 12 healthy cats and in 28 cats with primary myocardial disease, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive or unclassified cardiomyopathy (RCM and UCM), respectively. Plasma ET mean (95% CI) concentrations were 0.777 (0.6536-0.924) fmol/mL in the control cats, 1.427 (0.922-2.209) fmol/mL in 12 cats with cardiomyopathy (HCM = 11, RCM/UCM = 1) but without CHF or evidence of STE, and 2.360 (1.666-3.343) fmol/mL in 16 cats with cardiomyopathy (HCM = 8, RCM/UCM = 7, DCM = 1) and CHF (n = 15) or STE (n = 4). Plasma immunoreactivity of ET-1 was significantly higher in cats with myocardial disease without CHF/STE versus normal cats (P < .05) and in cats with myocardial disease with CHF/STE versus normal cats (P < .001).     

Evaluation of extended-release diltiazem once daily for cats with hypertrophic cardiomyopathy

Serum diltiazem concentrations were evaluated following either 30 mg or 60 mg of an extended-release diltiazem administered orally once daily to 13 cats. Sequential blood samples were obtained over 24 hours. Both dosages usually resulted in elevated serum concentrations of >200 ng/mL at 6, 12, 18, and 24 hours. The 30-mg dosage was sometimes associated with low serum concentrations of <50 ng/mL at 18 and 24 hours. The 60-mg dosage (9.3 to 14.8 mg/kg) was associated with lethargy, gastrointestinal disturbances, and weight loss in nine (36%) of 25 client-owned cats. Gastrointestinal disturbances were recognized within 1 week, and weight loss was detected after 2 to 6 months of treatment.     

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.     

Efficacy of protamine zinc insulin for treatment of diabetes mellitus in cats

OBJECTIVE: To evaluate effects of protamine zinc insulin (PZI) on control of glycemia in cats with newly diagnosed diabetes mellitus or poorly controlled diabetes. DESIGN: Clinical trial. ANIMALS: 67 diabetic cats. PROCEDURE: 34 cats with newly diagnosed diabetes and 33 cats with poorly controlled diabetes were treated with PZI twice daily for 45 days. Control of glycemia was assessed on days 7, 14, 30, and 45 by evaluation of clinical response, change in body weight, serum fructosamine concentration, blood glucose concentration measured 1, 3, 5, 7, and 9 hours after administration of PZI, lowest blood glucose concentration, and mean blood glucose concentration during the 9-hour period after administration. Adjustments in dosage of PZI were made as needed to attain control of glycemia. RESULTS: For all cats, a significant increase in mean dosage of PZI and significant decreases in 9-hour mean blood glucose concentration, lowest mean blood glucose concentration, and mean serum fructosamine concentration were detected. For cats with poorly controlled diabetes, 9-hour mean blood glucose concentration and mean serum fructosamine concentration were significantly decreased on day 45, compared with day 0. Ninety percent of owners reported improvement or resolution of clinical signs by day 45. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that PZI was effective for control of glycemia in cats with newly diagnosed or poorly controlled diabetes and may be used as an initial treatment or as an alternative treatment in cats that do not respond to treatment with other types of insulin.     

Pulsed tissue Doppler imaging in normal cats and cats with hypertrophic cardiomyopathy

Myocardial motion was quantified in normal cats (n = 25) and cats with hypertrophic cardiomyopathy (HCM) (n = 23) using the pulsed tissue Doppler imaging (TDI) technique. A physiologic nonuniformity was documented in the myocardial motion of normal cats, which was detected as higher early diastolic velocities, acceleration, and deceleration in the interventricular septum compared with the left ventricular free wall (LVFW). HCM cats exhibited lower early diastolic velocities, acceleration, and deceleration and also prolonged isovolumic relaxation time compared with normal cats. These differences were detected mainly along the longitudinal axis of the heart. A cutoff value of E' in the LVFW along the longitudinal axis >7.2 cm/s discriminated normal from HCM cats with a sensitivity of 92% and a specificity of 87%. The physiologic nonuniformity of myocardial motion during diastole was lost in affected cats. Systolic impairment (decreased late-systolic velocities in most segments along the longitudinal axis and decreased early systolic acceleration in both mitral annular sites) was evident in HCM cats irrespective of the presence of left ventricular outflow tract obstruction and congestive heart failure. Postsystolic thickening was recorded in the LVFW along the longitudinal axis only in affected cats (n = 6) and was another finding indicative of systolic impairment in the HCM of this species. This study identified both diastolic and systolic impairment in cats with HCM compared with normal cats. The study also documents the normal physiologic nonhomogeneity in myocardial motion in cats and the subsequent loss of this feature in the HCM diseased state.