Systemic calcinosis in a Quarter Horse gelding homozygous for a myosin heavy chain 1 mutation.

CASE DESCRIPTION: A 9-year-old Quarter Horse gelding was presented for lethargy, decreased appetite, polyuria and polydipsia (PU/PD), and severe muscle wasting suggestive of immune-mediated myositis. CLINICAL FINDINGS: The horse displayed lethargy, fever, tachyarrhythmia, inappetence, PU/PD, and severe epaxial and gluteal muscle wasting. Clinicopathologic findings were consistent with previously reported cases of systemic calcinosis in horses, including increased muscle enzyme activity, hyperphosphatemia, increased calcium-phosphorus product, hypoproteinemia, and an inflammatory leukogram. A diagnosis of systemic calcinosis was established by histopathologic evaluation of biopsy specimens from skeletal muscle, lung, and kidney. TREATMENT AND OUTCOME: Symptomatic treatment was complemented by IV treatment with sodium thiosulfate to reverse calcium-phosphate precipitation in soft tissue and PO aluminum hydroxide to decrease intestinal phosphorus absorption and serum phosphorus concentration. CLINICAL RELEVANCE: This is the first report in the veterinary literature of an antemortem diagnosis of systemic calcinosis in the horse that was successfully treated and had favorable long-term outcome.

Circulating renin-angiotensin-aldosterone system activity in cats with systemic hypertension or cardiomyopathy.

BACKGROUND: Activity of the circulating renin-angiotensin-aldosterone system (RAAS) has not been comprehensively characterized in cats with systemic hypertension (SH) or cardiomyopathy (CM), and the effects of furosemide or amlodipine treatment on the RAAS have not been fully evaluated in cats. HYPOTHESIS/OBJECTIVES: To document RAAS activity in cats with SH or CM compared to healthy cats and determine how RAAS profiles change with furosemide or amlodipine treatment. ANIMALS: Sixty-six client-owned cats: 15 with SH (7 amlodipine-treated, 8 untreated), 17 with advanced CM (7 furosemide-treated, 10 not furosemide-treated), and 34 healthy cats. METHODS: Equilibrium concentrations of RAAS peptides and aldosterone were quantified in serum samples by liquid chromatography-mass spectrometry. Variables were compared between groups using Kruskal-Wallis analysis with post hoc Holms-corrected Dunn's testing. RESULTS: Compared with healthy cats, cats with CM had higher concentrations of angiotensin I, aldosterone, and plasma renin activity (all P < .01), and these differences remained significant (P < .03) after considering subgroups of untreated or furosemide-treated cats. Compared with healthy cats, untreated cats with SH showed no differences in RAAS biomarkers, whereas amlodipine-treated cats had higher concentrations of angiotensins I, II, III, IV, and 1-7, aldosterone, and plasma renin activity (all P < .03). Multivariable analysis determined that furosemide and amlodipine treatments were independent predictors of increased RAAS biomarker concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with CM had increased RAAS activity, whereas cats with untreated SH did not. Furosemide and amlodipine both led to nonspecific activation of both classical and alternative RAAS pathways in cats.

Utility of point-of-care lung ultrasound for monitoring cardiogenic pulmonary edema in dogs.

BACKGROUND: Point-of-care lung ultrasound (LUS) is an effective tool to diagnose left-sided congestive heart failure (L-CHF) in dogs via detection of ultrasound artifacts (B-lines) caused by increased lung water. HYPOTHESIS/OBJECTIVES: To determine whether LUS can be used to monitor resolution of cardiogenic pulmonary edema in dogs, and to compare LUS to other indicators of L-CHF control. ANIMALS: Twenty-five client-owned dogs hospitalized for treatment of first-onset L-CHF. METHODS: Protocolized LUS, thoracic radiographs (TXR), and plasma N-terminal pro-B-type natriuretic peptide were performed at hospital admission, hospital discharge, and recheck examinations. Lung ultrasound findings were compared between timepoints and to other clinical measures of L-CHF. RESULTS: From time of hospital admission to discharge (mean 19.6 hours), median number of LUS sites strongly positive for B-lines (>3 B-lines per site) decreased from 5 (range, 1-8) to 1 (range, 0-5; P < .001), and median total B-line score decreased from 37 (range, 6-74) to 5 (range, 0-32; P = .002). Lung ultrasound indices remained improved at first recheck (P < .001). Number of strong positive sites correlated positively with respiratory rate (r = 0.52, P = .008) and TXR edema score (r = 0.51, P = .009) at hospital admission. Patterns of edema resolution differed between LUS and TXR, with cranial quadrants showing more significant reduction in B-lines compared to TXR edema score (80% vs 29% reduction, respectively; P = .003). CONCLUSIONS AND CLINICAL IMPORTANCE: Lung ultrasound could be a useful tool for monitoring resolution of pulmonary edema in dogs with L-CHF.

Vitamin D status in cats with cardiomyopathy.

BACKGROUND: Low vitamin D concentrations have been associated with advanced heart disease and poorer outcomes in people and dogs. Vitamin D status typically is assessed by serum 25(OH)D concentration. However, cats also produce notable amounts of a C-3 epimer of 25(OH)D (3-epi). HYPOTHESIS/OBJECTIVES: Determine if vitamin D status, estimated by 25(OH)D3 alone or combined with 3-epi (summation vitD), is lower in cats with cardiomyopathy (CM) compared to clinically normal (N) cats and if indicators of disease severity are associated with vitamin D status. ANIMALS: Privately owned cats, 44 with CM and 56 N. METHODS: Cross-sectional observational study using clinical and echocardiographic findings, diet history, and serum 25(OH)D3 and 3-epi measurements. RESULTS: Cat age was negatively related to vitamin D status. Summation vitD was lower in CM cats (median = 47.1 ng/mL) compared to N cats (median = 58.65 ng/mL) both before (P = .03) and after (P = .04) accounting for age. However, 25(OH)D3 became nonsignificant between CM and N cats after age was included. Summation vitD was related positively to survival time and fractional shortening (FS), but negatively to left atrial enlargement (LAE) severity, both before and after accounting for age. For 25(OH)D3 alone, only survival time and FS remained significant after including age. CONCLUSIONS AND CLINICAL IMPORTANCE: We report 25(OH)D3 and 3-epi concentrations in CM and N cats. Age had an important (negative) relationship to vitamin D status. After accounting for age, summation vitD was lower in CM cats. Vitamin D status was related positively to survival time and FS, but negatively to LAE severity.

Long-term incidence and risk of noncardiovascular and all-cause mortality in apparently healthy cats and cats with preclinical hypertrophic cardiomyopathy.

BACKGROUND: Epidemiologic knowledge regarding noncardiovascular and all-cause mortality in apparently healthy cats (AH) and cats with preclinical hypertrophic cardiomyopathy (pHCM) is limited, hindering development of evidence-based healthcare guidelines. OBJECTIVES: To characterize/compare incidence rates, risk, and survival associated with noncardiovascular and all-cause mortality in AH and pHCM cats. ANIMALS: A total of 1730 client-owned cats (722 AH, 1008 pHCM) from 21 countries. METHODS: Retrospective, multicenter, longitudinal, cohort study. Long-term health data were extracted by medical record review and owner/referring veterinarian interviews. RESULTS: Noncardiovascular death occurred in 534 (30.9%) of 1730 cats observed up to 15.2 years. Proportion of noncardiovascular death did not differ significantly between cats that at study enrollment were AH or had pHCM (P = .48). Cancer, chronic kidney disease, and conditions characterized by chronic weight-loss-vomiting-diarrhea-anorexia were the most frequently recorded noncardiovascular causes of death. Incidence rates/risk of noncardiac death increased with age in AH and pHCM. All-cause death proportions were greater in pHCM than AH (65% versus 40%, respectively; P < .001) because of higher cardiovascular mortality in pHCM cats. Comparing AH with pHCM, median survival (study entry to noncardiovascular death) did not differ (AH, 9.8 years; pHCM, 8.6 years; P = .10), but all-cause survival was significantly shorter in pHCM (P = .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: All-cause mortality was significantly greater in pHCM cats due to disease burden contributed by increased cardiovascular death superimposed upon noncardiovascular death.

Lung ultrasonography findings in dogs with various underlying causes of cough.

OBJECTIVE: To characterize lung ultrasonography (LUS) findings in dogs with a primary clinical complaint of cough. ANIMALS: 100 client-owned coughing dogs. PROCEDURES: A standardized LUS examination was performed for all dogs to quantify the number of B lines and identify subpleural abnormalities at 4 sites on each hemithorax. The final clinical diagnosis (reference standard) was determined by medical record review, and sensitivity and specificity of LUS for the diagnosis of selected causes of cough was determined. RESULTS: Common underlying causes of cough included dynamic airway collapse (n = 37), cardiogenic pulmonary edema (CPE; 12), and bronchitis (10). Compared with dogs with other causes of cough, dogs with bacterial pneumonia (n = 7) were more likely to have subpleural shred signs, whereas dogs with pulmonary neoplasia (4) were more likely to have subpleural nodule signs. Dogs with CPE had higher total B-line scores and higher numbers of LUS sites strongly positive for B lines (> 3 B lines/site) than other dogs. The LUS criteria of total B-line score ≥ 10 and presence of ≥ 2 sites strongly positive for B lines were each 92% sensitive and 94% specific for CPE diagnosis. Notably, 18% (16/88) of dogs with noncardiac causes of cough had been treated previously with diuretics because of prior CPE misdiagnosis. CONCLUSIONS AND CLINICAL RELEVANCE: LUS profiles in dogs with cough differed by the underlying cause. In dogs with a clinical history of cough, this imaging modality could be diagnostically useful, particularly to help exclude the possibility of underlying CPE.

Clinicopathologic, hemodynamic, and echocardiographic effects of short-term oral administration of anti-inflammatory doses of prednisolone to systemically normal cats.

OBJECTIVE: To evaluate the clinicopathologic, hemodynamic, and echocardiographic effects of short-term administration of anti-inflammatory dosages of prednisolone to systemically normal cats. ANIMALS: 10 cats with allergic dermatitis and 10 healthy control cats. PROCEDURES: Cats with allergic dermatitis were randomly allocated to 2 groups and received 2 dosages of prednisolone (1 and 2 mg/kg/d, PO, for 7 days) in a crossover design followed by 9-day tapering and 14-day washout periods. Each prednisolone-treated cat was matched to a healthy control cat on the basis of sex, neuter status, age (± 1 year), and body weight (± 10%). Control cats received no treatment during the 35-day observation period. Clinicopathologic, echocardiographic, and hemodynamic variables were measured at baseline (day 0) and predetermined times during and after prednisolone administration and compared within and between the 2 treatment groups. RESULTS: Prednisolone-treated cats had expected clinicopathologic alterations (mild increases in neutrophil and monocyte counts and serum concentrations of albumin, cholesterol, and triglycerides) but systolic arterial blood pressure; blood glucose, serum potassium, and cardiac biomarker concentrations; urinary sodium excretion; and echocardiographic variables did not differ significantly from baseline at any time. Statistically significant, albeit clinically irrelevant, increases in blood glucose and N-terminal pro-B-type natriuretic peptide concentrations were observed between baseline and the prednisolone pharmacokinetic steady state (7 days after initiation) only when the 2-mg/kg dosage was administered. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated short-term oral administration of anti-inflammatory dosages of prednisolone did not cause relevant hemodynamic, echocardiographic, or diabetogenic effects in systemically normal cats with allergic dermatitis.

Myocardial hypertrophy associated with long-term phenylpropanolamine use in a dog.

CASE DESCRIPTION A 9-year-old spayed female Dalmatian was examined because of progressive pelvic limb paraparesis. CLINICAL FINDINGS The dog had a history of chronic urinary incontinence and had been treated with phenylpropanolamine (PPA) for almost 8.5 years. Intervertebral disk disease at T12-13 was diagnosed, and a hemilaminectomy was performed. Three days after surgery, the dog developed a ventricular tachyarrhythmia. Severe left and mild right ventricular hypertrophy were detected by echocardiography. TREATMENT AND OUTCOME The arrhythmia was controlled with sotalol. Phenylpropanolamine administration was discontinued immediately before surgery and was not resumed. Heart rate and rhythm and blood pressure were within reference limits, and the ventricular hypertrophy had almost completely resolved 5 months later. Sotalol administration was discontinued. Shortly after the 5-month recheck evaluation, PPA administration was resumed, albeit at a lower dosage than that before surgery, for control of urinary incontinence. At the 10-month recheck evaluation, the dog was hypertensive and ventricular hypertrophy had recurred. Discontinuation of PPA administration was recommended but not heeded. The dog developed marked azotemia 1.5 years after surgery, which was managed by the referring veterinarian, and was subsequently lost to follow-up. CLINICAL RELEVANCE The fact that the ventricular hypertrophy almost completely resolved when PPA administration was discontinued and then recurred after it was resumed strongly suggested the drug was an important contributing factor to the cardiac disease of this patient. Patients receiving PPA on a long-term basis should be frequently monitored for cardiac disease, and use of other adrenergic receptor agonists should be avoided in such patients.

Evaluation of point-of-care thoracic ultrasound and NT-proBNP for the diagnosis of congestive heart failure in cats with respiratory distress.

BACKGROUND: The diagnosis of congestive heart failure (CHF) in cats is challenging. Point-of-care (POC) thoracic ultrasound and NT-proBNP testing are emerging tools that may aid in diagnosis. HYPOTHESIS/OBJECTIVES: To assess the diagnostic accuracy of POC lung ultrasound (LUS), focused cardiac ultrasound (FCU), and NT-proBNP in predicting a final diagnosis of CHF. ANIMALS: Fifty-one cats in respiratory distress. METHODS: Blood NT-proBNP, LUS, and FCU evaluating left atrial (LA) size and presence of pericardial effusion (PCEFF) were performed in all cats. Lung ultrasound findings including pleural effusion (PLEFF), number of B-lines, and sub-pleural abnormalities were noted. Medical records were evaluated for final diagnosis. RESULTS: Thirty-three of 51 (65%) cats were diagnosed with CHF. Lung ultrasound and blood NT-proBNP were significant predictors of CHF in a multivariate model. The LUS criterion that maximized accuracy for CHF diagnosis was presence of >1 site strongly positive for B-lines (>3 B-lines per site), resulting in sensitivity of 78.8%, specificity of 83.3%, and area under the curve (AUC) of 0.833. Subjective LA enlargement was 97.0% sensitive and 100% specific for CHF (AUC 0.985). Presence of PCEFF also was 100% specific, but only 60.6% sensitive, for CHF (AUC 0.803). A positive blood NT-proBNP test was 93.9% sensitive and 72.2% specific for the diagnosis of CHF (AUC 0.831). CONCLUSIONS AND CLINICAL IMPORTANCE: Point-of-care diagnostic techniques of LUS, FCU, and NT-proBNP are useful to diagnose CHF in cats with respiratory distress.

International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats: The REVEAL Study.

BACKGROUND: Hypertrophic cardiomyopathy is the most prevalent heart disorder in cats and principal cause of cardiovascular morbidity and mortality. Yet, the impact of preclinical disease is unresolved. HYPOTHESIS/OBJECTIVES: Observational study to characterize cardiovascular morbidity and survival in cats with preclinical nonobstructive (HCM) and obstructive (HOCM) hypertrophic cardiomyopathy and in apparently healthy cats (AH). ANIMALS: One thousand seven hundred and thirty client-owned cats (430 preclinical HCM; 578 preclinical HOCM; 722 AH). METHODS: Retrospective multicenter, longitudinal, cohort study. Cats from 21 countries were followed through medical record review and owner or referring veterinarian interviews. Data were analyzed to compare long-term outcomes, incidence, and risk for congestive heart failure (CHF), arterial thromboembolism (ATE), and cardiovascular death. RESULTS: During the study period, CHF, ATE, or both occurred in 30.5% and cardiovascular death in 27.9% of 1008 HCM/HOCM cats. Risk assessed at 1, 5, and 10 years after study entry was 7.0%/3.5%, 19.9%/9.7%, and 23.9%/11.3% for CHF/ATE, and 6.7%, 22.8%, and 28.3% for cardiovascular death, respectively. There were no statistically significant differences between HOCM compared with HCM for cardiovascular morbidity or mortality, time from diagnosis to development of morbidity, or cardiovascular survival. Cats that developed cardiovascular morbidity had short survival (mean ± standard deviation, 1.3 ± 1.7 years). Overall, prolonged longevity was recorded in a minority of preclinical HCM/HOCM cats with 10% reaching 9-15 years. CONCLUSIONS AND CLINICAL IMPORTANCE: Preclinical HCM/HOCM is a global health problem of cats that carries substantial risk for CHF, ATE, and cardiovascular death. This finding underscores the need to identify therapies and monitoring strategies that decrease morbidity and mortality.

Effects of short-term anti-inflammatory glucocorticoid treatment on clinicopathologic, echocardiographic, and hemodynamic variables in systemically healthy dogs.

OBJECTIVE To investigate mechanisms by which anti-inflammatory doses of orally administered intermediate-acting glucocorticoids (prednisone) could predispose dogs to progression of heart disease or congestive heart failure. ANIMALS 11 client-owned dogs with allergic dermatitis and 11 matched healthy control dogs. PROCEDURES Clinicopathologic, echocardiographic, and hemodynamic variables were measured. Dogs with allergic dermatitis then received prednisone (1 mg/kg, PO) once daily for 14 consecutive days beginning on day 0 (baseline), followed by a tapering and washout period; control dogs received no treatment. Measurements were repeated on days 7, 14, and 35. Linear mixed modeling was used to compare changes in variables across measurement points and between dog groups. RESULTS Prednisone administration caused no significant changes in serum sodium or potassium concentration, blood glucose concentration, or target echocardiographic variables. The change from baseline in systolic arterial blood pressure at day 7 was significantly greater in prednisone-treated dogs than in control dogs. Expected changes in hematologic and serum biochemical values with prednisone administration (neutrophilia, eosinopenia, isosthenuria, and high serum alkaline phosphatase and alanine aminotransferase activities) also occurred in the prednisone-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that anti-inflammatory doses of orally administered glucocorticoids have the potential to adversely impact cardiac function in dogs by causing an increase in blood pressure and thus increased cardiac afterload.

Replacing the enzyme alpha-L-iduronidase at birth ameliorates symptoms in the brain and periphery of dogs with mucopolysaccharidosis type I.

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by loss of activity of α-l-iduronidase and attendant accumulation of the glycosaminoglycans dermatan sulfate and heparan sulfate. Current treatments are suboptimal and do not address residual disease including corneal clouding, skeletal deformities, valvular heart disease, and cognitive impairment. We treated neonatal dogs with MPS I with intravenous recombinant α-l-iduronidase replacement therapy at the conventional 0.58 mg/kg or a higher 1.57 mg/kg weekly dose for 56 to 81 weeks. In contrast to previous results in animals and patients treated at a later age, the dogs failed to mount an antibody response to enzyme therapy, consistent with the induction of immune tolerance in neonates. The higher dose of enzyme led to complete normalization of lysosomal storage in the liver, spleen, lung, kidney, synovium, and myocardium, as well as in the hard-to-treat mitral valve. Cardiac biochemistry and function were restored, and there were improvements in skeletal disease as shown by clinical and radiographic assessments. Glycosaminoglycan levels in the brain were normalized after intravenous enzyme therapy, in the presence or absence of intrathecal administration of recombinant α-l-iduronidase. Histopathological evidence of glycosaminoglycan storage in the brain was ameliorated with the higher-dose intravenous therapy and was further improved by combining intravenous and intrathecal therapy. These findings argue that neonatal testing and early treatment of patients with MPS I may more effectively treat this disease.

Cardiac toxicity from phenylpropanolamine overdose in a dog.

A 5-year-old, 29-kg, female Labrador retriever developed tachypnea, tachycardia, and ataxia following ingestion of approximately 48 mg/kg of phenylpropanolamine. Initial diagnostic tests showed multiform ventricular tachycardia, left ventricular dilatation with a focal dyskinetic region in the dorsal interventricular septum, and elevations in creatinine kinase and cardiac troponin I. All abnormalities resolved within 6 months. The transient electrocardiographic, echocardiographic, and biochemical abnormalities were consistent with myocardial necrosis from infarction or direct catecholamine-induced myocardial toxicity.

Echocardiographic and radiographic changes associated with systemic hypertension in cats.

The purpose of this study was to assess the effects of systemic hypertension (SHT) on echocardiographic and radiographic cardiovascular variables in affected cats compared with healthy geriatric cats. Secondary objectives were to determine whether there were any relationships between these findings and age or systolic blood pressure (SBP). Fifteen healthy cats (>8 years of age with normal SBP) and 15 hypertensive cats (SBP > 180 mm Hg) were studied. Each cat was evaluated for standard echocardiographic parameters and 4 different aortic root dimensions. Seventeen variables were measured from right lateral and dorsoventral radiographic views. Left ventricle wall thickness was greater in the SHT group (5.1 +/- 0.9 mm) than in the healthy cats (4.2 +/- 0.5 mm). Left ventricular hypertrophy in the SHT cats often was not severe, and mean measures were considered normal. Some cats had asymmetrical septal hypertrophy (ASH) in the basilar portion of the septum as determined from the 2-dimensional view of the left ventricular outflow tract. ASH was greater in cats with SHT. Comparisons of the proximal ascending aorta indicated the presence of dilatation in the SHT cats, and comparison of the ascending aorta to the aortic annulus was helpful in differentiating between the 2 groups. The distal aortic root measurements and ratios evaluated by echocardiography were significantly different between the 2 groups of cats (P = .0001) and were significantly correlated with SBP (P = .0001) but not age (P > .3).