Comparison of artificial intelligence to the veterinary radiologist's diagnosis of canine cardiogenic pulmonary edema.

Application of artificial intelligence (AI) to improve clinical diagnosis is a burgeoning field in human and veterinary medicine. The objective of this prospective, diagnostic accuracy study was to determine the accuracy, sensitivity, and specificity of an AI-based software for diagnosing canine cardiogenic pulmonary edema from thoracic radiographs, using an American College of Veterinary Radiology-certified veterinary radiologist's interpretation as the reference standard. Five hundred consecutive canine thoracic radiographs made after-hours by a veterinary Emergency Department were retrieved. A total of 481 of 500 cases were technically analyzable. Based on the radiologist's assessment, 46 (10.4%) of these 481 dogs were diagnosed with cardiogenic pulmonary edema (CPE+). Of these cases, the AI software designated 42 of 46 as CPE+ and four of 46 as cardiogenic pulmonary edema negative (CPE-). Accuracy, sensitivity, and specificity of the AI-based software compared to radiologist diagnosis were 92.3%, 91.3%, and 92.4%, respectively (positive predictive value, 56%; negative predictive value, 99%). Findings supported using AI software screening for thoracic radiographs of dogs with suspected cardiogenic pulmonary edema to assist with short-term decision-making when a radiologist is unavailable.

Classification of feline hypertrophic cardiomyopathy-associated gene variants according to the American College of Medical Genetics and Genomics guidelines.

Introduction: The correct labeling of a genetic variant as pathogenic is important as breeding decisions based on incorrect DNA tests can lead to the unwarranted exclusion of animals, potentially compromising the long-term health of a population. In human medicine, the American college of Medical Genetics (ACMG) guidelines provide a framework for variant classification. This study aims to apply these guidelines to six genetic variants associated with hypertrophic cardiomyopathy (HCM) in certain cat breeds and to propose a modified criterion for variant classification. Methods: Genetic samples were sourced from five cat breeds: Maine Coon, Sphynx, Ragdoll, Devon Rex, and British Short- and Longhair. Allele frequencies were determined, and in the subset with phenotypes available, odds ratios to determine the association with HCM were calculated. In silico evaluation followed with joint evidence and data from other publications assisting in the classification of each variant. Results: Two variants, MYBPC3:c.91G > C [A31P] and MYBPC3:c.2453C > T [R818W], were designated as pathogenic. One variant, MYH7:c.5647G > A [E1883K], was found likely pathogenic, while the remaining three were labeled as variants of unknown significance. Discussion: Routine genetic testing is advised solely for the MYBPC3:c.91G > C [A31P] in the Maine Coon and MYBPC3:c.2453C > T [R818W] in the Ragdoll breed. The human ACMG guidelines serve as a suitable foundational tool to ascertain which variants to include; however, refining them for application in veterinary medicine might be beneficial.

Immunofluorescent Localization of Plakoglobin Is Altered in Endomyocardial Biopsy Samples from Dogs with Clinically Relevant Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC).

Diagnosing the early stages of canine Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is complicated by day-to-day arrhythmia variability, and absence of reliable, transthoracic echocardiographic features. Definitive diagnosis requires histopathologic identification of transmural fibrofatty replacement of the right ventricle. Reduction of immunofluorescent signal for plakoglobin (PG) at the intercalated disc (ID) is reported in ARVC-affected humans and boxers. Our objective was to determine whether reduced immunofluorescent signal for PG in endomyocardial biopsy samples (EMBs) correspond with a histopathologic diagnosis of ARVC. Here, 49 dogs were evaluated: 43 with advanced cardiac disease and 6 non-clinical boxers with mild to moderate ventricular arrhythmia (VA) burden. EMBs were obtained from all dogs; samples were prepared with antibodies recognizing cadherin (PC) and PG and evaluated with confocal microscopy. Investigators were blinded to breed and clinical status. ARVC was histopathologically diagnosed in 8 out of 49 dogs. Of these, three out of eight had clinical signs consistent with ARVC (two boxers, one English bulldog) and reduced PG signal at ID; five out of eight were non-clinical boxers with moderate VA and no reduction in PG. A total of 41 out of 49 dogs were histopathologically diagnosed with non-ARVC cardiac disease; 1 out of 41 showed reduction of PG at ID, while 40 out of 41 had no PG reduction. These results suggest that EMB PG signal is reduced in dogs with advanced ARVC, but not in the occult phase of the disease. Additionally, presence of PG at ID supports a diagnosis of non-ARVC cardiac disease in dogs with clinical signs. These results may offer an additional test that helps differentiate advanced ARVC from other myocardial diseases.

ACVIM consensus statement guidelines for the classification, diagnosis, and management of cardiomyopathies in cats.

Cardiomyopathies are a heterogeneous group of myocardial disorders of mostly unknown etiology, and they occur commonly in cats. In some cats, they are well-tolerated and are associated with normal life expectancy, but in other cats they can result in congestive heart failure, arterial thromboembolism or sudden death. Cardiomyopathy classification in cats can be challenging, and in this consensus statement we outline a classification system based on cardiac structure and function (phenotype). We also introduce a staging system for cardiomyopathy that includes subdivision of cats with subclinical cardiomyopathy into those at low risk of life-threatening complications and those at higher risk. Based on the available literature, we offer recommendations for the approach to diagnosis and staging of cardiomyopathies, as well as for management at each stage.

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

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

Assessment of serum N-terminal pro-B-type natriuretic peptide concentration for differentiation of congestive heart failure from primary respiratory tract disease as the cause of respiratory signs in dogs.

OBJECTIVE: To determine whether serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration is useful in discriminating between cardiac and noncardiac (ie, primary respiratory tract disease) causes of respiratory signs (ie, coughing, stertor, stridor, excessive panting, increased respiratory effort, tachypnea, or overt respiratory distress) in dogs. DESIGN: Multicenter cross-sectional study. ANIMALS: P 115 dogs with respiratory signs. PROCEDURES: Dogs with respiratory signs were solicited for study. Physical examination, thoracic radiography, and echocardiography were used to determine whether respiratory signs were the result of cardiac (ie, congestive heart failure) or noncardiac (ie, primary respiratory tract disease) causes. Serum samples for NT-proBNP assay were obtained at time of admission for each dog. Receiver-operating characteristic curves were constructed to determine the ability of serum NT-proBNP concentration to discriminate between cardiac and noncardiac causes of respiratory signs. RESULTS: Serum NT-proBNP concentration was significantly higher in dogs with cardiac versus noncardiac causes of respiratory signs. In dogs with primary respiratory tract disease, serum NT-proBNP concentration was significantly higher in those with concurrent pulmonary hypertension than in those without. A serum NT-proBNP cutoff concentration > 1,158 pmol/L discriminated between dogs with congestive heart failure and dogs with primary respiratory tract disease with a sensitivity of 85.5% and a specificity of 81.3%. CONCLUSIONS AND CLINICAL RELEVANCE: Measuring serum NT-proBNP concentration in dogs with respiratory signs helps to differentiate between congestive heart failure and primary respiratory tract disease as an underlying cause.

Evaluation of serum 25-hydroxyvitamin D concentrations in a heterogeneous canine ICU population.

OBJECTIVE: To identify the prevalence of low serum 25-hydroxyvitamin D (25-OH-D) concentrations in critically ill dogs and determine whether vitamin D concentration measured at admission correlates with illness severity and patient outcome. DESIGN: Prospective observational study from December 2013 to July 2014. SETTING: Private referral teaching hospital ICU. ANIMALS: One hundred eleven critically ill dogs admitted to the ICU, and 28 apparently healthy control dogs. INTERVENTIONS: Measurement of 25-OH-D concentration and assessment of physiological parameters required to calculate illness severity scores. MEASUREMENTS AND MAIN RESULTS: Blood was sampled to measure serum 25-OH-D concentration, point-of-care laboratory data (packed cell volume, total plasma protein, venous blood gas, electrolytes, plasma lactate, and blood glucose concentration), platelet count, and serum albumin within 12 hours of admission. Primary disease etiologies were determined. Mentation score, Acute Patient Physiologic and Laboratory Evaluation (APPLE) fast score, length of ICU hospitalization, and survival to discharge were recorded. Low serum 25-OH-D concentrations were detected in 25% (28/111) of the ICU cohort; 25-OH-D concentrations (median; IQR) (89.2; 26.3 ng/mL [222; 140.0 nmol/L]) were significantly lower in hospitalized dogs compared with the healthy cohort (127.5; 44.5 ng/mL [318; 111.0 nmol/L]) (P < 0.0001). Serum 25-OH-D concentrations had a weak positive correlation with albumin (r = 0.34, P = 0.0003), but not with any other blood analyte evaluated. Serum concentration of 25-OH-D was also weakly correlated with APPLEfast score (r = 0.31, P = 0.001). 25-OH-D concentrations (median; IQR) were significantly higher in ICU dogs that survived to discharge (95.5; 55 ng/mL [238; 137 nmol/L]) compared with nonsurvivors (60.0; 54 ng/mL [149; 135 nmol/L]; P < 0.001). CONCLUSIONS: Low serum 25-OH-D was recorded in one-quarter of critically ill dogs, and was significantly lower in nonsurvivors in comparison to survivors. There was weak correlation between serum 25-OH-D and illness severity. Further studies are required to clarify relationships between vitamin D status and outcome.

Effect of Targeted Pulsed Electromagnetic Field Therapy on Canine Postoperative Hemilaminectomy: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

Intervertebral disc disease is one of the leading causes of paralysis in dogs. Pulsed electromagnetic field (PEMF) therapy has been advocated for improving wound healing and pain reduction; however, robust clinical trials are lacking. The present prospective, double-blind, placebo-controlled trial evaluated targeted PEMF therapy administered to 53 client-owned dogs who underwent hemilaminectomy for naturally occurring disk extrusion intervertebral disc disease. The dogs were randomized to receive either targeted PEMF (n = 27) or placebo treatment (n = 28). Wound healing, evaluated by visual analog score and wound evaluation scale, was significantly improved at 6 wk postoperatively in the treatment compared with the control group (P = .010 and .023, respectively). Pain medications were administered less frequently in dogs receiving PEMF treatment during the 7 day postoperative period compared with the control treatment group (P = .010) with codeine administered 1.8 times more frequently in the control group. No untoward effects were recorded in either treatment group. More frequent evaluation of outcome measures with larger patient numbers, as well as histologic samples, may be useful in future studies. Dogs receiving PEMF therapy following postoperative hemilaminectomy demonstrated improved wound scores at 6 wk and reduced mean number of owner-administered pain medications compared with the control group therapy.

Comparison of closed root planing with versus without concurrent doxycycline hyclate or clindamycin hydrochloride gel application for the treatment of periodontal disease in dogs.

OBJECTIVE To compare improvements in values for periodontal disease indices in dogs following treatment with closed root planing (CRP) alone, CRP with concurrent 8.5% doxycycline hyclate gel application, and CRP with concurrent 2% clindamycin hydrochloride reverse-polymer hydrogel application. DESIGN Randomized, blinded, controlled clinical trial. ANIMALS 34 client-owned dogs with periodontal pockets measuring 3.5 to 5.5 mm deep. PROCEDURES Dogs were randomly assigned to receive 1 of 3 treatments: CRP alone (n = 10) or CRP plus 8.5% doxycycline hyclate (12) or 2% clindamycin hydrochloride (12) gel applied within the periodontal pockets. Indices of periodontal disease severity were recorded before and 12 weeks after treatment, and outcomes were compared among treatment groups. RESULTS Except for gingivitis index, no significant differences were identified among the 3 treatment groups in the amount of improvement observed in values for periodontal disease indices following treatment. A minor but clinically unimportant improvement in mean gingivitis index values was identified for dogs treated with CRP plus doxycycline gel, which differed significantly from improvements in the other 2 groups. Teeth that were initially more severely affected (pocket depths, 5.0 to 5.5 mm) had the greatest amount of improvement, whereas teeth with only mildly high initial pocket depths (3.5 to 4.0 mm) had less improvement. CONCLUSIONS AND CLINICAL RELEVANCE Overall, addition of doxycycline or clindamycin gel application to CRP for the treatment of periodontal disease in dogs yielded no clinically relevant benefit over CRP during the 12-week follow-up period.

Utility of admission lactate concentration, lactate variables, and shock index in outcome assessment in dogs diagnosed with shock.

OBJECTIVE: To determine whether admission venous plasma lactate concentration, calculated lactate variables, or shock index (SI) could discriminate hospital survivors from nonsurvivors in dogs admitted with shock. DESIGN: Prospective investigation performed over a 19-month period. SETTING: Large urban private teaching hospital. ANIMALS: Twenty-three dogs consecutively admitted to the ICU from January 2008 to July 2009 with initial peripheral venous plasma lactate concentration >2 mmol/L (18.0 mg/dL) and clinical and hemodynamic parameters consistent with shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Heart rate, systolic blood pressure, and venous plasma lactate concentrations were serially recorded at predefined time points and used to calculate SI (SI = heart rate/systolic blood pressure) and lactate variables, including lactime (time lactate > 2.0 mmol/L), lactate clearance ([lactateinitial - lactatedelayed ]/lactateinitial × 100), and LACAREA (area under the lactate concentration versus time curve). Primary outcome was survival to discharge. Overall survival rate was 61%. Admission venous plasma lactate concentration did not differ between groups (P = 0.2). Lactime was shorter in survivors versus nonsurvivors (P = 0.02). Lactate clearance at 1, 10, 16, 24, and 36 hours, and final lactate clearance were greater in survivors versus nonsurvivors (P < 0.05). LACAREA at time intervals 0-1, 1-4, 4-10, 10-16, 16-24, 24-30, and 30-36 hours was larger in nonsurvivors versus survivors (P < 0.05). Total LACAREA did not differ between groups (P = 0.09). Admission SI and time to normalize SI (SI < 0.9) were not different between survivors and nonsurvivors (P > 0.05). CONCLUSIONS: While admission venous plasma lactate concentration could not discriminate between hospital survivors and nonsurvivors, lactate variables showed clinical utility to predict outcome in dogs with shock. Further studies are needed to determine SI reference ranges and optimal SI cut-off values to improve its prognostic ability in sick dogs.

ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs.

This report, issued by the ACVIM Specialty of Cardiology consensus panel, revises guidelines for the diagnosis and treatment of myxomatous mitral valve disease (MMVD, also known as endocardiosis and degenerative or chronic valvular heart disease) in dogs, originally published in 2009. Updates were made to diagnostic, as well as medical, surgical, and dietary treatment recommendations. The strength of these recommendations was based on both the quantity and quality of available evidence supporting diagnostic and therapeutic decisions. Management of MMVD before the onset of clinical signs of heart failure has changed substantially compared with the 2009 guidelines, and new strategies to diagnose and treat advanced heart failure and pulmonary hypertension are reviewed.

Plasma and tissue angiotensin-converting enzyme 2 activity and plasma equilibrium concentrations of angiotensin peptides in dogs with heart disease.

BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a homologue of angiotensin-converting enzyme (ACE) and produces angiotensin peptides (APs), such as angiotensin 1-9 and 1-7 that are vasodilatory and natriuretic, and act to counterbalance angiotensin II. HYPOTHESIS: Evidence of ACE2 can be found in tissues and plasma of dogs. Equilibrium concentrations of renin angiotensin aldosterone system (RAAS) APs differ in dogs with heart disease compared to healthy dogs and recombinant human ACE2 (rhACE2) alters relative concentrations of APs. ANIMALS: Forty-nine dogs with and 34 dogs without heart disease. METHODS: Immunohistochemistry and assays for tissue and plasma ACE2 activity and equilibrium concentrations of plasma RAAS APs were performed. RESULTS: Immunolabeling for ACE2 was present in kidney and myocardial tissue. Median plasma ACE2 activity was significantly increased in dogs with congestive heart failure (CHF; 6.9 mU/mg; interquartile range [IQR], 5.1-12.1) as compared to control (2.2 mU/mg; IQR, 1.8-3.0; P = .0003). Plasma equilibrium analysis of RAAS APs identified significant increases in the median concentrations of beneficial APs, such as angiotensin 1-7, in dogs with CHF (486.7 pg/mL; IQR, 214.2-1168) as compared to those with preclinical disease (41.0 pg/mL; IQR, 27.4-45.1; P < .0001) or control (11.4 pg/mL; IQR, 7.1-25.3; P = .01). Incubation of plasma samples from dogs with CHF with rhACE2 increased beneficial APs, such as angiotensin 1-9 (preincubation, 10.3 pg/mL; IQR, 4.4-37.2; postincubation, 2431 pg/mL; IQR, 1355-3037; P = .02), while simultaneously decreasing maladaptive APs, such as angiotensin II (preincubation, 53.4 pg/mL; IQR, 28.6-226.4; postincubation, 2.4 pg/mL; IQR, 0.50-5.8; P = .02). CONCLUSIONS AND CLINICAL IMPORTANCE: Recognition of the ACE2 system expands the conventional view of the RAAS in the dog and represents an important potential therapeutic target.

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.

Comparison of the pharmacokinetic properties of bisoprolol and carvedilol in healthy dogs.

OBJECTIVE: To compare the pharmacokinetic properties and bioavailability following oral and IV administration of bisoprolol, a second-generation beta1-adrenoceptor-selective blocking agent, with those of carvedilol, a third-generation beta1/beta2 and alpha1-adrenoceptor blocking agent, in dogs. ANIMALS: 12 healthy adult Beagles. PROCEDURES: A prospective, parallel group study was performed. The dogs were allocated to 1 of 2 groups (6 dogs/group) and were administered orally a 1 mg/kg dose of either bisoprolol or carvedilol. Following a 1-week washout period, each cohort received a 1 mg/kg dose of the same drug IV. Blood samples were collected before and after drug administration, and serum concentrations, pharmacokinetic variables, and bioavailability for each agent were assessed. RESULTS: After oral administration of bisoprolol, the geometric mean value of the area under the concentration-time curve extrapolated to infinity (AUCinf) was 2,195 microg/L (coefficient of variation [CV], 15%). After IV administration of bisoprolol, the dose-normalized geometric mean AUCinf was 2,402 microg/L (CV, 19%). Oral bioavailability of bisoprolol was 91.4%. After oral administration of carvedilol, the geometric mean AUCinf was 70 microg/L (CV, 81%). After IV administration of carvedilol, the geometric mean AUCinf was 491 microg/L (CV, 23%). Oral bioavailability of carvedilol was 14.3%. Total body clearance was low (0.42 L/h/kg) for bisoprolol and high (2.0 L/h/kg) for carvedilol. CONCLUSIONS AND CLINICAL RELEVANCE: After oral administration, carvedilol underwent extensive first-pass metabolism and had limited bioavailability; bisoprolol had less first-pass effect and higher bioavailability. Collectively, these differences suggested that, in dogs, bisoprolol has less interindividual pharmacokinetic variability, compared with carvedilol.

Assessment of acute injuries, exposure to environmental toxins, and five-year health surveillance of New York Police Department working dogs following the September 11, 2001, World Trade Center terrorist attack.

OBJECTIVE: To determine deployment logistics of New York Police Department (NYPD) working dogs that assisted in relief efforts at the World Trade Center (WTC) site following the September 11, 2001, terrorist attack; establish types and rates of related acute injuries and illnesses; identify environmental toxin exposures; and determine long-term (ie, 5-year) health effects of deployment. DESIGN: Prospective cohort study. ANIMALS: 27 working dogs. PROCEDURES: Deployment logistics for the period from September 11, 2001, through May 30, 2002, were determined, and acute health disorders were identified by means of physical examination; a questionnaire; interviews with dog handlers; and toxicologic (blood and hair samples), clinicopathologic, microbiologic (nasal swab specimens submitted for Bacillus anthracis culture), and radiographic methods. Long-term health surveillance ended September 21, 2006. RESULTS: Dogs worked a total of 1,428 days (15,148 hours) at the site. Seventeen of the 27 (62.9%) dogs had health disorders during the first week. Specific conditions included fatigue (incidence rate [events/1,000 active deployment hours], 13.1), conjunctival irritation (13.1), respiratory tract problems (12.4), decreased appetite (10.8), dehydration (10), and cuts (9.3). Only minor hematologic and serum biochemical abnormalities were identified. Bacterial culture of nasal swab specimens did not yield B anthracis. Only mild and infrequent health conditions were identified during the 5-year follow-up period. None of the dogs were identified as having chronic respiratory tract disease. Six dogs died of various causes. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that acute injuries and illnesses were common among NYPD working dogs deployed to the WTC disaster site, but that longterm health complications were minimal.

Clinical utility of serum N-terminal pro-B-type natriuretic peptide concentration for identifying cardiac disease in dogs and assessing disease severity.

OBJECTIVE: To determine whether serum N-terminal pro-B-type natriuretic (NT-proBNP) concentration could be used to identify cardiac disease in dogs and to assess disease severity in affected dogs. DESIGN: Cross-sectional study. ANIMALS: 119 dogs with mitral valve disease, 18 dogs with dilated cardiomyopathy, and 40 healthy control dogs. PROCEDURES: Serum NT-proBNP concentration was measured with an ELISA validated for use in dogs. Results of physical examination, thoracic radiography, echocardiography, and serum biochemical analyses were recorded for dogs with cardiac disease. RESULTS: Serum NT-proBNP concentration was significantly higher in dogs with cardiac disease than in control dogs, and a serum NT-proBNP concentration > 445 pmol/L could be used to discriminate dogs with cardiac disease from control dogs with a sensitivity of 83.2% and specificity of 90.0%. In dogs with cardiac disease, serum NT-proBNP concentration was correlated with heart rate, respiratory rate, echocardiographic heart size, and renal function. For dogs with cardiac disease, serum NT-proBNP concentration could be used to discriminate dogs with and without radiographic evidence of cardiomegaly and dogs with and without congestive heart failure. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that serum NT-proBNP concentration may be a useful adjunct clinical test for diagnosing cardiac disease in dogs and assessing the severity of disease in dogs with cardiac disease.

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.

Molecular composition of the intercalated disc in a spontaneous canine animal model of arrhythmogenic right ventricular dysplasia/cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by ventricular arrhythmias, sudden death, and fatty or fibrofatty replacement of right ventricular myocytes. Recent studies have noted an association between human ARVD/C and molecular remodeling of intercalated disc structures. However, progress has been constrained by limitations inherent to human studies. OBJECTIVE: We studied the molecular composition of the intercalated disc structure in a naturally occurring animal model of ARVD/C (Boxer dogs). METHODS: We studied hearts from 12 Boxers with confirmed ARVD/C and 2 controls. Ventricular sections from 4 animals were examined by immunofluorescent microscopy. Frozen tissue samples were used for Western blot analysis. Proteins investigated were N-cadherin, plakophilin 2, desmoplakin, plakoglobin, desmin, and connexin 43 (Cx43). RESULTS: In control dogs, all proteins tested by immunofluorescence analysis yielded intense localized signals at sites of end-to-end cell apposition. In contrast, myocardial tissues from ARVD/C-afflicted Boxers showed preservation of N-cadherin staining but loss of detectable signal for Cx43 at the intercalated disc location. Western blots indicated that the Cx43 protein was still present in the samples. Gene sequencing analysis showed no mutations in desmoplakin, plakoglobin, Cx43, or plakophilin 2. CONCLUSION: Mutation(s) responsible for ARVD/C in Boxers lead, directly or indirectly, to severe modifications of mechanical and electrical cell-cell interactions. Furthermore, significant reduction in gap junction formation may promote a substrate for malignant ventricular arrhythmias. This model may help to advance our understanding of the molecular basis, pathophysiology, and potential therapeutic approach to patients with ARVD/C.

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.

An in vitro comparison of the effects of voluven (6% hydroxyethyl starch 130/0.4) and hespan (6% hydroxyethyl starch 670/0.75) on measures of blood coagulation in canine blood.

OBJECTIVE: To assess primary and secondary hemostasis following in vitro dilution of canine whole blood (WB) with hydroxyethyl starch (HES) 130/0.4 and HES 670/0.75. DESIGN: In vitro experimental study. SETTING: Private practice, teaching hospital. ANIMALS: Twenty-five healthy dogs. INTERVENTIONS: Each dog underwent venipuncture and 18 mL of venous blood was sampled once. MEASUREMENTS AND MAIN RESULTS: Collected blood was separated in 4 aliquots. Aliquot A served as baseline sample. The remaining tubes of WB were diluted with 0.9% saline, HES 670/0.75 and HES 130/0.4 at a ratio of 1:5.5. Dilutional effects were evaluated using prothrombin time (PT), activated partial thromboplastin time (aPTT), packed cell volume (PCV), thromboelastography (TEG), and platelet closure time (Ct), which was measured using a platelet function analyzer (PFA). Clot strength (ie, G value) was calculated from measured TEG values. Significant increases in PT (P < 0.05) and aPTT (P < 0.05) were documented following WB dilution with saline. Dilution of WB with HES 670/0.75 and HES 130/0.4 resulted in significant hypocoagulable changes in K, MA and G (P < 0.05) compared to baseline and saline. When comparing saline to HES 670/0.75, both R and K values were significantly increased (P < 0.05). K value was significantly increased (P < 0.05) when comparing baseline to HES 130/0.4 and HES 670/0.75. Ct (P < 0.05) was significantly prolonged after WB dilution with HES solutions but not after saline. CONCLUSIONS: Dilution of WB with HES 670/0.75 and HES 130/0.4 resulted in changes in primary and secondary hemostasis. Although there were small differences between saline and HES 670/0.75, no differences between HES solutions were evident in this small study. This may suggest there would be minimal increases in bleeding risk when either solution is administered to dogs at low doses. Clinical relevance of our findings requires further investigation.