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1. This was a multicentre, double-blind, parallel study in 216 patients with mild to moderate (supine diastolic blood pressure = 95-115 mm Hg) essential hypertension. 2. After a 4-week placebo washout, patients were randomized to placebo or lisinopril 1.25, 5.20 or 80 mg once daily for 6 consecutive weeks. Supine and erect blood pressure was measured 24 h postdose at the end of weeks -2, 0, 2, 4, and 6. 3. There was a linear dose-response relationship for both supine and erect blood pressure. Diastolic blood pressure reductions in the lisinopril 20 and 80 mg day-1 groups were significantly greater than in the placebo or lisinopril 1.25 and 5 mg day-1 groups. 4. Lisinopril, at doses up to 80 mg day-1, was well tolerated. [ABSTRACT FROM AUTHOR]

Enalapril is the result of a targeted research programme to develop a non-mercapto converting enzyme inhibitor with a long duration of action and an improved safety profile for use in the therapy of hypertension and congestive heart failure. Over 3500 patients world-wide have received enalapril or enalaprilat. Long-term experience at present includes over 2500 patients. While enalapril and captopril produce similar efficacy, enalapril is better tolerated and appears not to be associated with occurrence of captopril-type side-effects, particularly the skin rash, taste loss, leukopenia and proteinuria. Enalapril and other converting enzyme inhibitors may be associated with renal insufficiency when given to patients with bilateral renovascular hypertension. [ABSTRACT FROM AUTHOR]

Objective: In dogs with diet-associated dilated cardiomyopathy (DCM), we have identified electron microscopic changes suggestive of abnormal lysosomal accumulation of phospholipids and consistent with the appearance of drug-induced phospholipidosis in people and other animals. The objective of this study was to compare concentrations of urine di-docosahexaenoyl (22:6)-bis(monoacylglycerol)phosphate (BMP), a biomarker of drug-induced phospholipidosis, in dogs with DCM eating high-pulse (HP) diets, dogs with DCM eating low-pulse (LP) diets, and healthy controls (control-HP and control-LP)., Methods: In this cross-sectional study, voided urine was collected from client-owned dogs with DCM from September 2018 through March 2020. Urine di-22:6-BMP was measured by LC-MS-MS and normalized to urine creatinine. Normalized di-22:6-BMP concentrations were compared among groups using mixed-effects-model analysis., Results: 53 dogs were included: DCM-HP (n = 25), DCM-LP (n = 4), control-HP (n = 10), and control-LP (n = 14). Mixed-effects models adjusted for age and sex showed that HP diet was significantly associated with higher normalized urine di-22:6-BMP concentrations. A 1-way ANOVA identified a significant difference among the 4 groups, with Tukey post hoc analysis showing that the DCM-HP group had significantly higher normalized urine di-22:6-BMP concentrations compared to the control-LP group. Normalized di-22:6-BMP concentrations were significantly positively correlated with diet pulse scores (r = 0.52)., Conclusions: High-pulse diets were significantly associated with higher normalized urine di-22:6-BMP concentrations., Clinical Relevance: These results support the possible presence of primary or secondary phospholipidosis in dogs with diet-associated DCM and provide a plausible mechanism for further investigation.

Sildenafil is a drug used to successfully manage a variety of cardiopulmonary disorders in people and dogs, but there is limited information on its use in cats. The objective was to review the medical records of cats that received sildenafil as part of their clinical management. Medical records and pharmacy databases were searched for cats that received sildenafil for ≥24 h between 2009 and 2021, and data were collected from medical records. Fifty-five cats received sildenafil for ≥24 h and were included in the study: 43 with primary cardiac disease (acquired, n = 28; congenital, n = 15) and 12 with primary respiratory disease. Side effects possibly attributed to sildenafil were identified in two cats (systemic hypotension, n = 1; polydipsia, n = 1), and sildenafil was discontinued in the cat with hypotension. Sildenafil was discontinued in an additional three cats due to a lack of improvement in clinical signs. No cat was documented to develop worsening pulmonary edema within 72 h of starting sildenafil. Median duration of sildenafil administration was 87 days (range, 2-2362 days). Sildenafil administration in cats appeared to be generally well-tolerated. Studies are needed to determine whether sildenafil administration to cats with cardiopulmonary disease improves the quality of life or survival times.

Background: Hypercoagulability has been documented in cats with cardiac disease. However, hemostatic parameters, including viscoelastic coagulation monitoring (VCM) have not been reported in cats with arterial thromboembolism (ATE)., Hypothesis/objectives: Compare VCM parameters in cats with acute cardiogenic ATE and in control cats., Animals: Sixteen cats with ATE and 30 control cats., Methods: Multicenter university-based prospective study. Cardiogenic ATE was diagnosed based on physical examination and by ultrasonographically-diagnosed left atrial enlargement. Viscoelastic coagulation monitor analysis, CBC, serum biochemistry profile and coagulation profile were performed at admission in cats with ATE. Analysis from healthy control cats was performed using blood collected by direct venipuncture. Our objective was comparison of VCM parameters clot time (CT), clot formation time (CFT), alpha angle (Angle), maximum clot formation (MCF), amplitude at 10 and 20 minutes (A10 and A20, respectively) and clot lysis index at 30 and 45 minutes (LI30 and LI45, respectively) between ATE and control cats., Results: Cats with ATE had a decreased angle compared to control cats, with a median (range) of 43° (30-48°) compared to 47° (14-59°; P = .01). The parameters A10, A20 and MCF were decreased in ATE cats compared to control cats with a median (range) of 19 units (8-32) compared to 22 units (6-38), 24.5 units (11-40) compared to 29 units (10-47) and 29.5 units (13-44) compared to 33.5 units (14-53), respectively (P = .01, .01 and .01, respectively). The parameters CT, CFT, LI30 and LI45 were similar between groups (P = .22, .09, .62 and .34, respectively)., Conclusions and Clinical Importance: Cats with cardiogenic ATE cats have VCM parameters consistent with hypocoagulability compared with healthy cats., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Apparently healthy dogs of various breeds eating nontraditional, high-pulse diets can have larger left ventricular diameter, lower systolic function, and more ventricular premature complexes (VPCs) compared with dogs eating traditional, low-pulse diets. It is unknown whether Irish Wolfhounds eating high-pulse diets have similar cardiac abnormalities., Hypothesis/objectives: To compare electrocardiographic and echocardiographic findings between Irish Wolfhounds eating high- or low-pulse diets., Animals: Ninety-seven Irish Wolfhounds., Methods: Retrospective study of Irish Wolfhounds that had echocardiography performed at dog shows between October 2018 and May 2021. Demographic information, echocardiographic measurements, cardiac rhythm (1-minute lead II rhythm strip), and main diet were recorded retrospectively. Diets were classified as high-pulse or low-pulse based on the presence and location of pulses (peas, lentils, chickpeas, or dry beans) on the ingredient list., Results: Thirty-five of 97 Irish Wolfhounds (36%) were eating high-pulse diets and 62 of 97 (64%) were eating low-pulse diets. There were no significant differences between diet groups in echocardiographic measurements. A significantly higher percentage of dogs in the high-pulse diet group (6/35 [17%]) had VPCs compared with those in the low-pulse diet group (1/62 [2%]; effect size = 0.15 [95% confidence interval: 0.004-0.31]; P = .005)., Conclusions and Clinical Importance: In this retrospective study of apparently healthy Irish Wolfhounds, high-pulse diets were associated with a higher prevalence of VPCs which could represent early cardiac abnormalities., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To determine the effects of cardiac cachexia on the metabolomic profile in dogs with myxomatous mitral valve disease (MMVD)., Animals: 3 groups of dogs with MMVD enrolled between November 30, 2018, and April 7, 2022: (1) Dogs with congestive heart failure (CHF) and cachexia (CHF-cachexia group; n = 10); (2) dogs with CHF that had no cachexia (CHF-no cachexia group; n = 10); and (3) dogs with asymptomatic disease (American College of Veterinary Internal Medicine [ACVIM] Stage B2) with no cachexia (B2 group; n = 10)., Methods: Metabolomic profiles were analyzed from serum samples using ultra-high-performance liquid chromatography-tandem mass spectroscopy. Dogs in the 3 groups were compared, with statistical significance defined as P < .05 with a low false discovery rate (q < .10) and nominal statistical significance defined as P < .05 but q > .10., Results: Numerous metabolites were significantly (n = 201) or nominally significantly (n = 345) different between groups. For example, when comparing the CHF-cachexia vs CHF-no cachexia groups, lipids were the predominant metabolite differences, including many medium- and long-chain dicarboxylates and dicarboxylate acylcarnitines. For comparisons of the CHF-cachexia vs B2 groups and the CHF-no cachexia vs B2 groups, amino acids, nucleotides, and cofactors/vitamins were the predominant metabolite differences., Clinical Relevance: Some significant metabolite differences were identified between dogs with and without cardiac cachexia.

Objective: To compare signalment, clinical signs, diet, echocardiographic findings, and outcome for pit bull-type breeds diagnosed between 2015 and 2022 with dilated cardiomyopathy (DCM) or with DCM diagnosed by a cardiologist but that did not meet all study echocardiographic criteria (DCM-C)., Animals: 91 dogs with DCM and 11 dogs with DCM-C., Procedures: Data were collected on clinical findings, echocardiographic measurements, and diet at the time of diagnosis (for 76/91 dogs); echocardiographic changes; and survival., Results: For dogs with diet information available for time of diagnosis, 64/76 (84%) dogs were eating nontraditional commercial diets, while 12/76 (16%) were eating traditional commercial diets. There were few differences between diet groups at baseline, with congestive heart failure and arrhythmias common in both groups. Thirty-four dogs with known baseline diet and diet change status had follow-up echocardiograms between 60 and 1,076 days later (traditional diet, n = 7; nontraditional diet that changed diets, 27; and nontraditional diet group without diet change, 0). Dogs in the nontraditional diet group that changed diets had a significantly greater decrease in normalized left ventricular diameter (diastolic, P = .02; systolic, P = .048) and the left atrium-to-aorta ratio (P = .002) and a significantly greater increase in fractional shortening (P = .02) compared to dogs eating traditional diets. Dogs eating nontraditional diets with diet change (n = 45; P < .001) and dogs eating traditional diets (12; P < .001) had a significantly longer survival time compared to dogs eating nontraditional diets without diet change (4). Dogs with DCM-C also had significant echocardiographic improvements after diet change., Clinical Relevance: Congestive heart failure and arrhythmias were common in pit bull-type breeds with DCM. Those eating nontraditional diets that changed diets had significant improvements in echocardiographic measurements after diet change.

Objectives: There are ongoing investigations into diet-associated dilated cardiomyopathy in dogs, but there has been minimal investigation into possible diet-associated dilated cardiomyopathy in cats. The objective of this study was to compare cardiac size and function, cardiac biomarkers and taurine concentrations in healthy cats eating high- vs low-pulse diets. We hypothesized that cats eating high-pulse diets would have larger hearts, lower systolic function and higher biomarker concentrations than cats eating low-pulse diets and that there would be no difference in taurine concentrations between the diet groups., Methods: Echocardiographic measurements, cardiac biomarkers, and plasma and whole-blood taurine concentrations were compared between cats eating high- and low-pulse commercial dry diets in a cross-sectional study., Results: There were no differences between the high- (n = 21) and low-pulse (n = 31) diet groups with regard to age, sex and breed, but more cats in the high-pulse group were overweight or obese (67% vs 39%; P  = 0.05). Diet duration was not different in the groups, but the range was wide (6-120 months). No differences were found between the diet groups for key cardiac measurements, biomarker concentrations, or plasma or whole-blood taurine concentrations. However, there were significant negative correlations between diet duration and measures of left ventricular wall thickness in the high-pulse, but not the low-pulse, diet group., Conclusions and Relevance: This study did not detect significant associations between high-pulse diets and cardiac size, function and biomarkers, but the secondary observation of significant negative correlations between time on high-pulse diets and left ventricular wall thickness warrants further evaluation.

Dilated cardiomyopathy (DCM), caused by genetic and environmental factors, usually progresses to heart failure, a major cause of death in elderly people. A diet-associated form of DCM was recently identified in pet dogs eating non-traditional (NT) diets. To identify potential dietary causes, we analyzed metabolomic signatures and gene set/pathway enrichment in (1) all dogs based on disease, diet, and their interactions and (2) dogs with DCM based on diet. Metabolomic analysis was performed in 38 dogs with DCM eating NT diets (DCM-NT), 8 dogs with DCM eating traditional diets, 12 healthy controls eating NT diets, and 17 healthy controls eating traditional diets. Overall, 153 and 63 metabolites differed significantly between dogs with DCM versus healthy controls and dogs eating NT versus traditional diets, respectively, with 12 metabolites overlapping both analyses. Protein-protein interaction networks and gene set enrichment analysis identified 105 significant pathways and gene sets including aging-related pathways (e.g., nuclear factor-kappa B, oxidative damage, inflammation). Seventeen metabolites differed significantly in dogs with DCM eating NT versus traditional diets (e.g., fatty acids, amino acids, legume biomarkers), suggesting different mechanisms for primary versus diet-associated DCM. Our multifaceted metabolomic assessment of DCM in dogs highlighted diet's role in some forms of DCM., (© 2022. The Author(s).)

Objective: To compare metabolomic profiles of dogs eating grain-free (GF) versus grain-inclusive (GI) diets (1) for healthy dogs at baseline and (2) for dogs with subclinical cardiac abnormalities at 12 months after a diet change., Sample: Serum samples from 23 dogs eating GF diets and 79 dogs eating GI diets, of which 17 (8 eating a GF diet and 9 eating a GI diet) were reevaluated 12 months after a diet change., Procedures: Metabolomic profiles were developed by means of ultrahigh-performance liquid chromatography-tandem mass spectroscopy of serum samples. Baseline results for the GF group were compared with those for the GI group. Dogs from both groups with subclinical cardiac abnormalities were transitioned to a GI, pulse-free, intervention diet, and samples collected 12 months later were compared between diet groups. Statistical significance for biochemical group differences was defined as P < .05 with a false discovery rate (q) < .10., Results: Baseline differences in lipid metabolism and amino acid metabolism were found between the GF and GI diet groups. There were 46 metabolites that were higher and 82 metabolites that were lower in the GF group (n = 23), compared with the GI group (79). Comparison of the GF (n = 8) and GI (9) groups 12 months after the diet change showed only 6 metabolites that were higher and 11 metabolites that were lower in the GF group, compared with the GI group., Clinical Relevance: Metabolomic pathway differences between dogs eating GF versus GI diets highlight the important effect of diet in metabolomics analyses. The clinical importance of these differences and how they might relate to cardiac disease in dogs remains undetermined.

Dilated cardiomyopathy (DCM) is a disease of the heart muscle that affects both humans and dogs. Certain canine diets have been associated with DCM, but the diet-disease link is unexplained, and novel methods are needed to elucidate mechanisms. We conducted metabolomic profiling of 9 diets associated with canine DCM, containing ≥ 3 pulses, potatoes, or sweet potatoes as main ingredients, and in the top 16 dog diet brands most frequently associated with canine DCM cases reported to the FDA (3P/FDA diets), and 9 non-3P/FDA diets. We identified 88 named biochemical compounds that were higher in 3P/FDA diets and 23 named compounds that were lower in 3P/FDA diets. Amino acids, amino acid-derived compounds, and xenobiotics/plant compounds were the largest categories of biochemicals that were higher in 3P/FDA diets. Random forest analyses identified the top 30 compounds that distinguished the two diet groups with 100% predictive accuracy. Four diet ingredients distinguished the two diet groups (peas, lentils, chicken/turkey, and rice). Of these ingredients, peas showed the greatest association with higher concentrations of compounds in 3P/FDA diets. Moreover, the current foodomics analyses highlight relationships between diet and DCM in dogs that can identify possible etiologies for understanding diet-disease relationships in dogs and humans., (© 2021. The Author(s).)

Objectives: The aim of the study was to evaluate cardiac size and early growth through echocardiographic, body weight (BW), body condition score (BCS), morphometric and biomarker changes in cats followed from 6 to 24 months of age., Methods: Twenty-four female European shorthair colony cats were evaluated at birth for BW and at 6, 12, 18 and 24 months of age for BW, BCS, head length (HL) and head width (HW), N-terminal pro B-type natriuretic peptide (NT-proBNP), insulin-like growth factor-1 (IGF-1) and echocardiographic measurements., Results: BCS, HW, left ventricular free wall in diastole, left atrium diameter and aortic diameter increased significantly between 6 and 12 months, while BW, HL and interventricular septum in diastole increased significantly between 6, 12 and 18 months, and BW decreased significantly between 18 and 24 months. NT-proBNP decreased significantly between 6 and 12 months. IGF-1 increased significantly between 6 and 12 months but decreased significantly between 12 and 18 months., Conclusions and Relevance: This study prospectively evaluated changes in echocardiographic measurements, BW, BCS, HL, HW, IGF-1 and NT-proBNP in cats during the first 2 years of life. Results show a comparable change over time for different variables. These findings contribute to the understanding of a possible relationship between cardiac measures and body size from young age through to adulthood.

Background: The benefits of pimobendan in the treatment of congestive heart failure (CHF) in cats with hypertrophic cardiomyopathy (HCM) have not been evaluated prospectively., Hypothesis/objectives: To investigate the effects of pimobendan in cats with HCM and recent CHF and to identify possible endpoints for a pivotal study. We hypothesized that pimobendan would be well-tolerated and associated with improved outcome., Animals: Eighty-three cats with HCM and recently controlled CHF: 30 with and 53 without left ventricular outflow tract obstruction., Methods: Prospective randomized placebo-controlled double-blind multicenter nonpivotal field study. Cats received either pimobendan (0.30 mg/kg q12h, n = 43), placebo (n = 39), or no medication (n = 1) together with furosemide (<10 mg/kg/d) with or without clopidogrel. The primary endpoint was a successful outcome (ie, completing the 180-day study period without a dose escalation of furosemide)., Results: The proportion of cats in the full analysis set population with a successful outcome was not different between treatment groups (P = .75). For nonobstructive cats, the success rate was 32% in pimobendan-treated cats versus 18.2% in the placebo group (odds ratio [OR], 2.12; 95% confidence interval [CI], 0.54-8.34). For obstructive cats, the success rate was 28.6% and 60% in the pimobendan and placebo groups, respectively (OR, 0.27; 95% CI, 0.06-1.26). No difference was found between treatments for the secondary endpoints of time to furosemide dose escalation or death (P = .89). Results were similar in the per-protocol sets. Adverse events in both treatment groups were similar., Conclusions and Clinical Importance: In this study of cats with HCM and recent CHF, no benefit of pimobendan on 180-day outcome was identified., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Background: Associations of diet with dilated cardiomyopathy are under investigation., Objectives: That cardiac assessment would show abnormalities in healthy dogs eating grain-free (GF) diets or diets with Food and Drug Administration (FDA)-listed ingredients of concern (peas, lentils, or potatoes) as top 10 ingredients (FDA-PLP), but not in dogs eating grain-inclusive (GI) diets or diets without FDA-listed ingredients of concern (PLP) in the top 10 ingredients (NoFDA-PLP)., Animals: One hundred eighty-eight healthy Doberman Pinschers, Golden Retrievers, Miniature Schnauzers, and Whippets., Methods: This study was an observational cross-sectional study. Echocardiograms, cardiac biomarkers, and blood and plasma taurine concentrations were compared between dogs eating GF (n = 26) and GI (n = 162) diets, and between FDA-PLP (n = 39) and NoFDA-PLP (n = 149) diets, controlling for age and breed. Demographic characteristics, murmurs, genetic status, and ventricular premature complexes (VPCs) during examination were compared between dogs eating different diet types., Results: No differences in echocardiographic variables, N-terminal pro-B-type natriuretic peptide or whole blood taurine were noted between dogs eating different diet types. Dogs eating GF diets had higher median high-sensitivity cardiac troponin I (hs-cTnI) (GF 0.076 ng/mL [Interquartile range (IQR), 0.028-0.156] vs. GI 0.048 [IQR, 0.0026-0.080]; P < .001) and higher median plasma taurine (GF 125 nmol/mL [IQR, 101-148] vs GI 104 [IQR, 86-123]; P = .02) than dogs eating GI diets. Dogs eating FDA-PLP diets had higher median hs-cTnI (0.059 ng/mL [IQR, 0.028-0.122]) than dogs eating NoFDA-PLP diets (0.048 [IQR, 0.025-0.085]; P = .006). A greater proportion of dogs eating FDA-PLP diets (10%) had VPCs than dogs eating NoFDA-PLP diets (2%; P = .04)., Conclusions and Clinical Importance: Higher hs-cTnI in healthy dogs eating GF and FDA-PLP diets might indicate low-level cardiomyocyte injury., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: The United States Food and Drug Administration is investigating possible diet-associated dilated cardiomyopathy (DCM) in dogs and cats., Objectives: To retrospectively review DCM cases for signalment, diet information, echocardiographic changes, and survival., Animals: Client-owned dogs (n = 71)., Methods: Medical records of dogs diagnosed with DCM between January 1, 2014 and September 30, 2018 were reviewed. Dogs were grouped into "traditional" or "nontraditional" diet categories and whether or not diet was changed after diagnosis., Results: For dogs eating nontraditional diets, those that had their diets changed had a larger percentage decrease in normalized systolic left ventricular internal dimension (P = .03) and left atrial:aorta ratio (P < .001) compared to those that did not have their diets changed. Survival time was significantly longer for dogs with DCM eating nontraditional diets that had their diets changed (median survival, 337 days; range, 9-1307 days) compared to dogs eating nontraditional diets that did not have their diets changed (median survival, 215 days; range, 1-852 days; P = .002)., Conclusions and Clinical Importance: Dogs with DCM eating nontraditional diets can experience improvement in cardiac function after diet change but additional research is needed to examine possible associations between diet and DCM., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

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)D 3 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)D 3 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)D 3 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)D 3 alone, only survival time and FS remained significant after including age., Conclusions and Clinical Importance: We report 25(OH)D 3 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., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Long-term use of doxorubicin (DOX) is limited by cumulative dose-dependent cardiotoxicity., Objectives: Identify plasma extracellular vesicle (EV)-associated microRNAs (miRNAs) as a biomarker for cardiotoxicity in dogs by correlating changes with cardiac troponin I (cTnI) concentrations and, echocardiographic and histologic findings., Animals: Prospective study of 9 client-owned dogs diagnosed with sarcoma and receiving DOX single-agent chemotherapy (total of 5 DOX treatments). Dogs with clinically relevant metastatic disease, preexisting heart disease, or breeds predisposed to cardiomyopathy were excluded., Methods: Serum concentration of cTnI was monitored before each treatment and 1 month after the treatment completion. Echocardiography was performed before treatments 1, 3, 5, and 1 month after completion. The EV-miRNA was isolated and sequenced before treatments 1 and 3, and 1 month after completion., Results: Linear mixed model analysis for repeated measurements was used to evaluate the effect of DOX. The miR-107 (P = .03) and miR-146a (P = .02) were significantly downregulated whereas miR-502 (P = .02) was upregulated. Changes in miR-502 were significant before administration of the third chemotherapeutic dose. When stratifying miRNA expression for change in left ventricular ejection fraction, upregulation of miR-181d was noted (P = .01). Serum concentration of cTnI changed significantly but only 1 month after treatment completion, and concentrations correlated with left ventricular ejection fraction and left ventricular internal dimension in diastole., Conclusion and Clinical Significance: Downregulation of miR-502 was detected before significant changes in cTnI concentrations or echocardiographic parameters. Further validation using a larger sample size will be required., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Cardiac disease in dogs impacts the quality of life (QoL) of their owners, but owners' QoL has not been comprehensively assessed in this population., Objectives: To develop, validate, and provide preliminary data from a health-related QoL (hrQoL) questionnaire for owners of dogs with cardiac disease., Subjects: A total of 141 owners of dogs with cardiac disease were studied., Methods: An owner hrQoL (O-hrQoL) questionnaire containing 20 items related to areas of a person's life that could be impacted by caring for a dog with cardiac disease was developed and administered to owners of dogs with cardiac disease. The highest possible total score was 100, with higher scores indicating a worse hrQoL. Readability, internal consistency, face and construct validity, and item-total correlations were assessed., Results: Median O-hrQoL score was 35 (range, 0-87). The questionnaire had good internal consistency (Cronbach's α = 0.933), construct validity (Spearman's r = 0.38-0.53; Kendall's τ = 0.30-0.43; P < .001), and item-total correlation (Spearman's r = 0.44-0.79; Kendall's τ = 0.34-0.66; all P < .001). Fifty percent of owners indicated a negative effect of dogs' cardiac disease on their own QoL, but all owners responded that caring for their dogs either had strengthened (n = 76; 53.9%) or had no effect on their relationship with their dog (n = 65; 46.1%)., Conclusions and Clinical Importance: The O-hrQoL questionnaire had good validity, and results suggest that owners' QoL is significantly impacted by caring for dogs with cardiac disease. Additional research on effective approaches to minimizing the negative effects of a dog's cardiac disease on the owner is warranted., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Cardiac cachexia is common in people and dogs with congestive heart failure (CHF). However, the prevalence and effects of cardiac cachexia in cats are unknown., Objectives: To determine the prevalence of cachexia and its associations with clinical laboratory and survival data in cats with CHF., Animals: One hundred twenty-five cats with CHF., Methods: Medical records of cats evaluated during a 40-month period were retrospectively reviewed to identify cats with cardiac cachexia using 7 different definitions. Clinical, laboratory, and survival data were compared between cats with and without cachexia., Results: Prevalence of cachexia ranged from 0 to 66.7% for the 7 definitions, with a prevalence of 41.6% using muscle condition score (MCS). Cats with cachexia (determined by MCS) were older (P < .001), more likely to have pleural effusion (P = .003), had significantly higher blood urea nitrogen (P < .001) and neutrophil concentrations (P = .01), and significantly lower body condition score (P < .001), body weights (P < .001), hematocrit (P = .007), and hemoglobin concentrations (P = .009). Survival time for cats with cachexia (determined by MCS) was significantly shorter than for cats without cachexia (P = .03). Cats that were underweight (P = .002) and cats with dilated cardiomyopathy (DCM) also had shorter survival times (P = .04)., Conclusions and Clinical Importance: The association between cachexia and reduced survival time emphasizes the importance of identifying and addressing this common problem in cats with CHF., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

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., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Cardiac cachexia, loss of muscle mass associated with congestive heart failure (CHF), is associated with increased morbidity and shorter survival times in people, but an association between cardiac cachexia and survival has not been reported in dogs., Objectives: To determine the prevalence of cachexia and its associations with clinical, laboratory, and survival data in dogs with CHF., Animals: Two hundred sixty-nine dogs with CHF., Methods: Retrospective cohort study. Cachexia was defined by 1 of 2 definitions: (1) mild, moderate, or severe muscle loss or (2) weight loss of ≥5% in 12 months or less. Variables were compared between dogs with and without cachexia., Results: One hundred thirty of 269 dogs (48.3%) had cardiac cachexia based on muscle loss, whereas 67 of 159 dogs (42.1%) with pre-evaluation body weights had cachexia based on weight loss. Dogs with cachexia (based on muscle loss) were significantly older (P = .05), more likely to have a cardiac arrhythmia (P = .02), had higher chloride concentrations (P = .04), and had a lower body condition score (P < .001), hematocrit (P = .006), hemoglobin (P = .006), and albumin (P = .004) concentrations. On multivariable analysis, cachexia (P = .05), clinically important tachyarrhythmias (P < .001), azotemia (P < .001), and being under- or overweight (both P = .003) were associated with shorter survival times., Conclusions and Clinical Importance: Cardiac cachexia in common in dogs with CHF and is associated with significantly shorter survival. This emphasizes the importance of preventing, diagnosing, and treating muscle loss in dogs with CHF., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Focused cardiac ultrasound (FCU) helps detect occult heart disease in human patients., Hypothesis: Focused cardiac ultrasound by a nonspecialist practitioner (NSP) will increase the detection of occult heart disease in asymptomatic cats compared with physical examination and ECG., Animals: Three hundred forty-three client-owned cats: 54 excluded and 289 analyzed., Methods: Multicenter prospective cohort study. Twenty-two NSPs were trained to perform FCU. Cats without clinical signs of heart disease were recruited, and NSPs performed the following in sequential order: physical examination, ECG, FCU, and point-of-care N-terminal pro-B-type natriuretic peptide assay (POC-BNP). After each step, NSPs indicated yes, no, or equivocal as to whether they believed heart disease was present. The level of agreement between the NSP diagnosis and a blinded cardiologist's diagnosis after echocardiogram was evaluated using Cohen's kappa test., Results: Cardiologist diagnoses included 148 normal cats, 102 with heart disease, and 39 equivocal ones. Agreement between NSP and cardiologist was slight after physical examination (kappa 0.253 [95% CI, 0.172-0.340]), did not increase after ECG (0.256 [0.161-0.345]; P = .96), increased after FCU (0.468 [0.376-0.558]; P = .002), and the level of agreement was similar after POC-BNP (0.498 [0.419-0.580]; P = .67). In cats with mild, moderate, and marked occult heart disease, the proportion of cats having a NSP diagnosis of heart disease after FCU was 45.6%, 93.1%, and 100%, respectively., Conclusions and Clinical Importance: Focused cardiac ultrasound performed by NSPs increased the detection of occult heart disease, especially in cats with moderate to marked disease. Focused cardiac ultrasound appears to be a feasible and useful tool to assist NSPs in the detection of heart disease in cats., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

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., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Pathophysiologic mechanisms for the development and progression of degenerative mitral valve disease (DMVD) remain elusive. Increased concentrations of circulating trimethylamine N-oxide (TMAO) and its precursors choline and l-carnitine are associated with the presence and severity of heart disease in people., Objectives: To determine if differences exist in plasma concentrations of TMAO, choline, or l-carnitine among dogs with DMVD and congestive heart failure (CHF), dogs with asymptomatic DMVD, and healthy control dogs., Animals: Thirty client-owned dogs: 10 dogs with CHF secondary to DMVD, 10 dogs with asymptomatic DMVD, and 10 healthy control dogs., Methods: A pilot cross-sectional study in which echocardiography was performed and fasting plasma concentrations of TMAO, choline, and l-carnitine (total and fractions) were measured., Results: TMAO (P = .03), total l-carnitine (P = .03), carnitine esters (P = .05), and carnitine esters to free carnitine ratio (E/F ratio; P = .05) were significantly higher in dogs with CHF compared to those with asymptomatic DMVD. TMAO (P = .02), choline (P = .01), total l-carnitine (P = .01), carnitine esters (P = .02), free carnitine (P = .02), and E/F ratio (P = .009) were significantly higher in dogs with CHF compared to healthy controls., Conclusions and Clinical Importance: Dogs with CHF secondary to DMVD had higher concentrations of TMAO compared to both asymptomatic DMVD dogs and healthy controls. Larger prospective studies are warranted to determine if TMAO plays a role in the development or progression of DMVD or CHF., (© 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

This study describes the use of vasopressors in critically ill cats. Records of 41 cats hospitalized in the ICU were evaluated. Signalment, blood pressure, underlying conditions, evidence of sepsis, type of treatment (surgical versus non-surgical), vasopressor type and duration, adverse events attributed to vasopressors, and survival were recorded. Twenty-one cats (51%) had an underlying disease considered amenable to surgical treatment while 20 (49%) cats did not. Evidence of sepsis was present in 24 (59%) cats. Thirty-four cats developed a Doppler blood pressure (DBP) > 80 mmHg during therapy, and 29 cats became normotensive (DBP > 90 mmHg). Seven cats did not increase their DBP to > 80 mmHg. All cats received dopamine and/or norepinephrine and 6 cats also received other vasopressors. Sixteen cats survived (39%). Surgical intervention was associated with a higher survival ( P = 0.004). Critically ill hypotensive cats may benefit from administration of vasopressors.

OBJECTIVE To evaluate use of an ultrasonographically and radiographically determined value, the vertebral epaxial muscle score (VEMS), for assessing muscle mass in cats. ANIMALS 30 healthy neutered cats of various body weights and between 1 and 6 years of age. PROCEDURES Mean epaxial muscle height was calculated from 3 transverse ultrasonographic images obtained at the level of T13. Length of T4 was measured on thoracic radiographs, and the VEMS (ratio of epaxial muscle height to T4 length) was calculated and compared with body weight. Ratios of epaxial muscle height to various anatomic measurements also were compared with body weight as potential alternatives to use of T4 length. RESULTS 1 cat was excluded because of a heart murmur. For the remaining 29 cats, mean ± SD body weight was 5.05 ± 1.40 kg. Mean epaxial muscle height was 1.27 ± 0.13 cm, which was significantly correlated (r = 0.65) with body weight. The VEMS and value for epaxial muscle height/(0.1 × forelimb circumference) were not significantly correlated (r = -0.18 and -0.06, respectively) with body weight, which is important for measures used for animals of various sizes. CONCLUSIONS AND CLINICAL RELEVANCE The VEMS and value for epaxial muscle height/(0.1 × forelimb circumference) can both be used to normalize muscle size among cats of various body weights. Studies are warranted to determine whether these values can be used to accurately assess muscle mass in cats with various adiposity and in those with muscle loss.

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., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Dogs with advanced heart failure are a clinical challenge for veterinarians but there are no studies reporting clinical features and outcome of this population., Hypothesis/objectives: To describe clinical findings and outcome of dogs with advanced heart failure caused by degenerative mitral valve disease (DMVD)., Animals: Fifty-four dogs with advanced heart failure because of DMVD., Methods: For study purposes, advanced heart failure was defined as recurrence of congestive heart failure signs despite receiving the initially prescribed dose of pimobendan, angiotensin-converting-enzyme inhibitor (ACEI), and furosemide >4 mg/kg/day. Data were collected for the time of diagnosis of Stage C heart failure and time of diagnosis of advanced heart failure. Date of death was recorded., Results: At the diagnosis of advanced heart failure, doses of pimobendan (n = 30), furosemide (n = 28), ACEI (n = 13), and spironolactone (n = 4) were increased, with ≥1 new medications added in most dogs. After initial diagnosis of advanced heart failure, 38 (70%) dogs had additional medications adjustments (median = 2 [range, 0-27]), with the final total medication number ranging from 2-10 (median = 5). Median survival time after diagnosis of advanced heart failure was 281 days (range, 3-885 days). Dogs receiving a furosemide dose >6.70 mg/kg/day had significantly longer median survival times (402 days [range, 3-885 days] versus 129 days [range 9-853 days]; P = .017)., Conclusions and Clinical Importance: Dogs with advanced heart failure can have relatively long survival times. Higher furosemide dose and non-hospitalization were associated with longer survival., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Muscle loss associated with disease (cachexia) or with aging (sarcopenia) is common in dogs, but clinically relevant methods for quantifying muscle loss are needed. We previously validated an ultrasound method of quantifying muscle size in dogs in a single breed. The goal of this study was to assess the variability and reproducibility of the Vertebral Epaxial Muscle Score (VEMS) in other dog breeds. Static ultrasound images were obtained from 38 healthy, neutered dogs of 5 different breeds between 1- and 5-years-old. The maximal transverse right epaxial muscle height and area at the level of the 13th thoracic vertebra (T13) were measured. Length of the 4th thoracic vertebra (T4) was measured from thoracic radiography. Ratios of the muscle height and area to vertebral length (height/T4 and area/T4, respectively) were calculated to account for differences in body size among breeds. Reproducibility testing was performed on 2 dogs of each breed (26% of the total) to determine intra- and inter-investigator reproducibility, as well as intra-class correlation. Mean height/T4 = 1.02 ± 0.18 and mean area/T4 = 3.32 ± 1.68. There was no significant difference for height/T4 ( P = 0.10) among breeds, but breeds were significantly different in area/T4 ( P < 0.001). Intra-class correlation ranged from 0.80 to 0.99. Testing showed better reproducibility for height/T4 compared to area/T4. The VEMS using height/T4 was valid and reproducible for healthy dogs of different sizes and body conformations. Studies assessing this technique in dogs with congestive heart failure and other diseases associated with muscle loss are warranted.

CASE DESCRIPTION 2 dogs with chylothorax were identified to have cardiac mass lesions obstructing the return of venous blood from the cranial vena cava. Chylous effusion was presumed to have been a result of an increase in cranial vena cava pressure affecting flow of chyle through the thoracic duct. CLINICAL FINDINGS Both dogs had tachypnea and pleural effusion requiring therapeutic thoracocentesis. Fluid analysis confirmed chylothorax. A heart-base mass was identified via echocardiography in each dog, and CT-angiographic findings confirmed obstruction to venous return in the cranial vena cava in both dogs and compression of the pulmonary artery in 1 dog. TREATMENT AND OUTCOME Each dog was anesthetized, and self-expanding endovascular stents were placed with fluoroscopic guidance. In both dogs, the site of stent placement was the cranial vena cava, and in 1 dog, an additional stent was positioned in the pulmonary artery. Chylous effusion resolved successfully in both dogs after surgery, with postoperative survival times exceeding 6 months. Complications included periprocedural arrhythmias in both dogs and eventual obstruction of the stent with tumor extension and fluid reaccumulation in 1 dog. CLINICAL RELEVANCE Endovascular stent placement may provide a useful palliative treatment for chylothorax secondary to vascular compression by a heart-base mass in dogs.

Hypertrophic cardiomyopathy (HCM) is a common disease in pet cats, affecting 10-15% of the pet cat population. The similarity to human HCM, the rapid progression of disease, and the defined and readily determined endpoints of feline HCM make it an excellent natural model that is genotypically and phenotypically similar to human HCM. The Maine Coon and Ragdoll cats are particularly valuable models of HCM because of myosin binding protein-C mutations and even higher disease incidence compared to the overall feline population. The cat overcomes many of the limitations of rodent HCM models, and can provide enhanced translation of information from in vitro and induced small animal models to human clinical trials. Physicians and veterinarians working together in a collaborative and interdisciplinary approach can accelerate the discovery of more effective treatments for this and other cardiovascular diseases affecting human and veterinary patients.

Background: Reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations after treatment have been associated with improved survival in people with congestive heart failure (CHF), but have not been reported in cats with CHF., Objectives: To evaluate changes in NT-proBNP concentrations in cats with CHF after treatment and determine whether serial NT-proBNP measurements provide prognostic information., Animals: Thirty-one client-owned cats., Methods: Prospective, observational study in cats with new onset CHF secondary to cardiomyopathy. Concentrations of NT-proBNP were measured within 4 hours of admission to the hospital, on the day of discharge, and at re-evaluation 7-10 days later., Results: Median NT-proBNP concentrations decreased significantly from admission (1,713 pmol/L [range, 160-3,784 pmol/L]) to discharge (902 pmol/L [range, 147-3,223 pmol/L]); P = .005) and from admission to re-evaluation (1,124 pmol/L [range, 111-2,727 pmol/L]; P = .024). Median survival time was 109 days (range, 1-709 days), with 5 cats still alive at the time of analysis. Cats with a larger percent decrease in NT-proBNP from admission to discharge had a longer survival time (P = .048). Cats with evidence of active CHF at the time of re-evaluation (P = .010) and cats whose owners had difficulty administering medications (P = .045) had shorter survival times., Conclusions and Clinical Importance: Cats with a larger percent decrease in NT-proBNP during hospitalization and no evidence of CHF at the time of re-evaluation had longer survival times. Additional studies are needed to determine whether NT-proBNP can help guide treatment in cats with CHF., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Pleural effusion is a common cause of dyspnea in cats. N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement, using a first-generation quantitative ELISA, in plasma and pleural fluid differentiates cardiac from noncardiac causes of pleural effusion., Hypothesis/objectives: To determine whether NT-proBNP measurements using second-generation quantitative ELISA and point-of-care (POC) tests in plasma and pleural fluid distinguish cardiac from noncardiac pleural effusions and how results compare to the first-generation ELISA., Animals: Thirty-eight cats (US cohort) and 40 cats (UK cohort) presenting with cardiogenic or noncardiogenic pleural effusion., Methods: Prospective cohort study. Twenty-one and 17 cats in the US cohort, and 22 and 18 cats in the UK cohort were classified as having cardiac or noncardiac pleural effusion, respectively. NT-proBNP concentrations in paired plasma and pleural fluid samples were measured using second-generation ELISA and POC assays., Results: The second-generation ELISA differentiated cardiac from noncardiac pleural effusion with good diagnostic accuracy (plasma: sensitivity, 95.2%, specificity, 82.4%; pleural fluid: sensitivity, 100%, specificity, 76.5%). NT-proBNP concentrations were greater in pleural fluid (719 pmol/L (134-1500)) than plasma (678 pmol/L (61-1500), P = 0.003), resulting in different cut-off values depending on the sample type. The POC test had good sensitivity (95.2%) and specificity (87.5%) when using plasma samples. In pleural fluid samples, the POC test had good sensitivity (100%) but low specificity (64.7%). Diagnostic accuracy was similar between first- and second-generation ELISA assays., Conclusions and Clinical Importance: Measurement of NT-proBNP using a quantitative ELISA in plasma and pleural fluid or POC test in plasma, but not pleural fluid, distinguishes cardiac from noncardiac causes of pleural effusion in cats., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Canine degenerative mitral valve disease (DMVD) is the most common form of heart disease in dogs. The objective of this study was to identify cellular and metabolic pathways that play a role in DMVD by performing metabolomics and transcriptomics analyses on serum and tissue (mitral valve and left ventricle) samples previously collected from dogs with DMVD or healthy hearts. Gas or liquid chromatography followed by mass spectrophotometry were used to identify metabolites in serum. Transcriptomics analysis of tissue samples was completed using RNA-seq, and selected targets were confirmed by RT-qPCR. Random Forest analysis was used to classify the metabolites that best predicted the presence of DMVD. Results identified 41 known and 13 unknown serum metabolites that were significantly different between healthy and DMVD dogs, representing alterations in fat and glucose energy metabolism, oxidative stress, and other pathways. The three metabolites with the greatest single effect in the Random Forest analysis were γ-glutamylmethionine, oxidized glutathione, and asymmetric dimethylarginine. Transcriptomics analysis identified 812 differentially expressed transcripts in left ventricle samples and 263 in mitral valve samples, representing changes in energy metabolism, antioxidant function, nitric oxide signaling, and extracellular matrix homeostasis pathways. Many of the identified alterations may benefit from nutritional or medical management. Our study provides evidence of the growing importance of integrative approaches in multi-omics research in veterinary and nutritional sciences.

MicroRNAs (miRNAs) are small non-coding RNAs that have shown promise as noninvasive biomarkers in cardiac disease. This study was undertaken to investigate the miRNA expression profile in dogs with myxomatous mitral valve disease (MMVD). 277 miRNAs were quantified using RT-qPCR from six normal dogs (American College of Veterinary Internal Medicine Stage A), six dogs with MMVD mild to moderate cardiac enlargement (ACVIM Stage B1/B2) and six dogs with MMVD and congestive heart failure (ACVIM Stage C/D). Eleven miRNAs were differentially expressed (False Discovery Rate < 0.05). Dogs in Stage B1/B2 or C/D had four upregulated miRNAs, including three cfa-let-7/cfa-miR-98 family members, while seven others were downregulated, compared to Stage A. Expression of six of the 11 miRNAs also were significantly different between dogs in Stage C/D and those in Stage B1/B2. The expression changes were greater as disease severity increased. These miRNAs may be candidates for novel biomarkers and may provide insights into genetic regulatory pathways in canine MMVD.

Background: Cats with hypertrophic cardiomyopathy (HCM) are larger and have higher insulin-like growth factor-1 (IGF-1) concentrations than cats without HCM., Hypothesis/objectives: The aim of this study was to assess echocardiographic findings in a colony of adult cats to determine the relationship between early growth and left ventricular hypertrophy (LVH)., Animals: Twenty-eight neutered adult cats (20 males, 8 females) from a colony ≥ 3 years of age for which growth curves were available., Methods: Case-control study. Physical examination and echocardiography were performed, and body weight, body condition score (BCS), and head length and width were measured. Circulating glucose, insulin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and IGF-1 concentrations were measured and growth data were collected. Stepwise multivariate analyses were performed., Results: Mean age was 5.2 ± 1.1 years. Current BCSs ranged from 4 to 9 (median, 6) and mean body weight was 4.88 ± 1.29 kg. Variation in body weight was apparent by 6 (mean = 3.26 ± 0.80 kg) and 12 months of age (mean = 4.02 ± 1.02 kg). Cardiac abnormalities included a cardiac murmur (n = 7; 24%), gallop (n = 3; 10%), and arrhythmia (n = 1; 4%). Fourteen of 28 cats (50%) had echocardiographic evidence of LVH. Head width (P = .017), body weight (P < .001), NT-proBNP (P = .023), and IGF-1 (P = .013-.022) were significantly associated with selected measures of LVH., Conclusions and Clinical Importance: Potential associations between body size, IGF-1, LVH, and HCM warrant future prospective studies., (Copyright © 2014 by the American College of Veterinary Internal Medicine.)

Background: Cardiac biomarkers provide objective data that augments clinical assessment of heart disease (HD)., Hypothesis/objectives: Determine the utility of plasma N-terminal pro-brain natriuretic peptide concentration [NT-proBNP] measured by a 2nd generation canine ELISA assay to discriminate cardiac from noncardiac respiratory distress and evaluate HD severity., Animals: Client-owned dogs (n = 291)., Methods: Multicenter, cross-sectional, prospective investigation. Medical history, physical examination, echocardiography, and thoracic radiography classified 113 asymptomatic dogs (group 1, n = 39 without HD; group 2, n = 74 with HD), and 178 with respiratory distress (group 3, n = 104 respiratory disease, either with or without concurrent HD; group 4, n = 74 with congestive heart failure [CHF]). HD severity was graded using International Small Animal Cardiac Health Council (ISACHC) and ACVIM Consensus (ACVIM-HD) schemes without knowledge of [NT-proBNP] results. Receiver-operating characteristic curve analysis assessed the capacity of [NT-proBNP] to discriminate between dogs with cardiac and noncardiac respiratory distress. Multivariate general linear models containing key clinical variables tested associations between [NT-proBNP] and HD severity., Results: Plasma [NT-proBNP] (median; IQR) was higher in CHF dogs (5,110; 2,769-8,466 pmol/L) compared to those with noncardiac respiratory distress (1,287; 672-2,704 pmol/L; P < .0001). A cut-off >2,447 pmol/L discriminated CHF from noncardiac respiratory distress (81.1% sensitivity; 73.1% specificity; area under curve, 0.84). A multivariate model comprising left atrial to aortic ratio, heart rate, left ventricular diameter, end-systole, and ACVIM-HD scheme most accurately associated average plasma [NT-proBNP] with HD severity., Conclusions and Clinical Importance: Plasma [NT-proBNP] was useful for discriminating CHF from noncardiac respiratory distress. Average plasma [NT-BNP] increased significantly as a function of HD severity using the ACVIM-HD classification scheme., (Copyright © 2014 by the American College of Veterinary Internal Medicine.)

n-3 fatty acids have some benefits in humans and dogs with cardiac disease, and plasma n-3 fatty acid concentrations have been shown to be decreased in dogs with congestive heart failure (CHF). However, there are no published studies reporting fatty acid concentrations in cats with cardiac disease. Therefore, the goal of this study was to compare serum fatty acid concentrations in normal cats and cats with hypertrophic cardiomyopathy (HCM), and determine if fatty acid concentrations correlate with left atrial size or the presence of CHF. Serum fatty acid concentrations were measured in normal cats and cats with HCM by gas chromatography. Twenty-three cats with HCM and 20 healthy controls were enrolled. Compared with healthy controls, cats with HCM had higher concentrations of palmitic acid (P = 0.01), docosahexanoic acid (DHA; P = 0.001) and total n-3 fatty acids (P = 0.03), and lower concentrations of linoleic acid (P = 0.03). Among cats with HCM, there were no differences in plasma fatty acid concentrations, and no association between left atrial dimension and fatty acid concentrations. Cats with HCM have some alterations in plasma fatty acids compared with healthy controls. Given the higher plasma concentrations of DHA, DHA supplementation is unlikely to have benefits in terms of correcting a deficiency; however, other effects of DHA or of supplementation of EPA warrant further investigation., (© ISFM and AAFP 2013.)

Background: Diet might influence progression of hypertrophic cardiomyopathy (HCM)., Objective: To investigate whether diet composition could alter clinical, biochemical, or echocardiographic variables in cats with HCM., Animals: Twenty-nine cats with HCM (International Small Animal Cardiac Health Council stage 1b) examined at a university teaching hospital., Methods: Randomized, placebo-controlled trial. After physical examination, echocardiogram, and blood collection, cats were randomized to 1 of 3 diets, which varied in carbohydrate and fat content and ingredients. Measurements were repeated after 6 months., Results: There were no significant differences among the 3 groups at baseline. After 6 months, there were no significant changes in the primary endpoints, left ventricular free wall (Group A, P = .760; Group B, P = .475; Group C, P = .066) or interventricular septal thickness in diastole (Group A, P = .528; Group B, P = .221; Group C, P = .097). Group A had significant increases in BUN (P = .008) and cholesterol (P = .021), while Group B had significant increases in BUN (P = .008), cholesterol (P = .007), and triglycerides (P = .005), and significant decreases in NT-proBNP (P = .013) and hs-troponin I (P = .043). Group C had significant decreases in body weight (P = .021), left atrial dimension (P = .035), interventricular septal thickness in systole (P = .038), and liver enzymes (P = .034-.038)., Conclusions and Clinical Importance: These data suggest that diet might influence some clinical, biochemical, and echocardiographic variables in cats with HCM., (Copyright © 2014 by the American College of Veterinary Internal Medicine.)

Background: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may improve heart failure class and survival in people with congestive heart failure (CHF) of various etiologies., Hypothesis/objectives: To evaluate the tolerability of atorvastatin in healthy dogs, and the short-term effects of atorvastatin on clinical markers of disease severity, lipid profiles, and markers of systemic inflammation and oxidative stress in dogs with CHF., Animals: Eleven normal dogs and 12 client-owned animals with CHF attributable to myxomatous mitral valve disease., Methods: Prospective nonblinded observational study. Normal dogs (n = 11) were first treated with atorvastatin and re-evaluated after 14 and 30 days for clinical tolerability and alterations in certain laboratory results. Subsequently, dogs with CHF (n = 12) were treated with atorvastatin at a dosage of 2 mg/kg q24 h for 8 weeks. Echocardiography, blood pressure (BP), quality of life questionnaire, and blood sampling were performed pre and post atorvastatin administration., Results: Atorvastatin was well tolerated and did not result in apparent adverse effects or biochemical abnormalities in healthy dogs and in dogs with CHF. Healthy dogs experienced a decrease in total cholesterol (TC) concentration (P = .03) after atorvastatin administration. Decreases in TC concentration (P = .02), non-HDL cholesterol concentration (P = .02), total white blood cell count (P = .03), neutrophils (P = .01), and systolic BP (P = .01) were noted in the CHF group after 8 weeks of atorvastatin., Conclusions and Clinical Importance: Atorvastatin was well tolerated at clinically relevant doses in healthy dogs and dogs with CHF. Further investigation into the effects of statin treatment in dogs with CHF is warranted., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

An interplay between growth, glucose regulation and hypertrophic cardiomyopathy (HCM) may exist, but has not been studied in detail. The purpose of this study was to characterize morphometric features, insulin-like growth factor-1 (IGF-1) and glucose metabolism in Maine Coon cats with HCM. Body weight, body condition score (BCS), head length and width, and abdominal circumference were measured in Maine Coon cats >2 years of age. Echocardiography and thoracic radiography (for measurement of humerus length, and fourth and twelfth vertebrae length) were also performed. Blood was collected for biochemistry profile, DNA testing, insulin and IGF-1. Sixteen of 63 cats had HCM [myosin binding protein C (MYBPC)+, n = 3 and MYBPC-, n = 13] and 47/63 were echocardiographically normal (MYBPC+, n = 17 and MYBPC-, n = 30). There were no significant differences in any measured parameter between MYBPC+ and MYBPC- cats. Cats with HCM were significantly older (P <0.001), heavier (P = 0.006), more obese (P = 0.008), and had longer humeri (P = 0.02) compared with the HCM- group. Cats with HCM also had higher serum glucose (P = 0.01), homeostasis model assessment (HOMA) and IGF-1 (P = 0.01) concentrations, were from smaller litters (P = 0.04), and were larger at 6 months (P = 0.02) and at 1 year of age (P = 0.03). Multivariate analysis revealed that age (P <0.001), BCS (P = 0.03) and HOMA (P = 0.047) remained significantly associated with HCM. These results support the hypothesis that early growth and nutrition, larger body size and obesity may be environmental modifiers of genetic predisposition to HCM. Further studies are warranted to evaluate the effects of early nutrition on the phenotypic expression of HCM.

Objective: To determine reference values for kaolin-activated thromboelastography in echocardiographically normal cats., Animals: 30 healthy cats without evidence of cardiomyopathy on echocardiographic examination., Procedures: All cats underwent echocardiographic examination, the findings of which were reviewed by a board-certified cardiologist. Cats that struggled (n = 10) received mild sedation with butorphanol and midazolam IM to permit phlebotomy without interruption in jugular venous blood flow. Blood samples were collected for analysis of thromboelastography variables, PCV, total solids concentration, platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen concentration, and antithrombin concentration., Results: All 4 thromboelastography variables had < 5% mean intra-assay variability. Mean values were as follows: reaction time, 4.3 minutes; clotting time, 1.6 minutes; α angle, 66.5°; and maximum amplitude, 56.4 mm. Compared with nonsedated cats, cats that required sedation had a significantly shorter clotting time and greater α angle, whereas reaction time and maximum amplitude were not significantly different., Conclusions and Clinical Relevance: Kaolin-activated thromboelastography was a reliable test with unremarkable intra-assay variability in echocardiographically normal cats. Sedation may affect certain thromboelastography variables, but the effect is unlikely to be clinically important. It remains unknown whether subclinical cardiomyopathy has a significant effect on thromboelastography variables in cats.

Objective: To develop, validate, and evaluate a questionnaire (Cats' Assessment Tool for Cardiac Health [CATCH] questionnaire) for assessing health-related quality of life in cats with cardiac disease., Design: Prospective study., Animals: 275 cats with cardiac disease., Procedures: The questionnaire was developed on the basis of clinical signs of cardiac disease in cats. A CATCH score was calculated by summing responses to questionnaire items; possible scores ranged from 0 to 80. For questionnaire validation, owners of 75 cats were asked to complete the questionnaire (10 owners completed the questionnaire twice). Disease severity was assessed with the International Small Animal Cardiac Health Council (ISACHC) classification for cardiac disease. Following validation, the final questionnaire was administered to owners of the remaining 200 cats., Results: Internal consistency of the questionnaire was good, and the CATCH score was significantly correlated with ISACHC classification. For owners that completed the questionnaire twice, scores were significantly correlated. During the second phase of the study, the CATCH score ranged from 0 to 74 (median, 7) and was significantly correlated with ISACHC classification., Conclusions and Clinical Relevance: Results suggested that the CATCH questionnaire is a valid and reliable method for assessing health-related quality of life in cats with cardiac disease. Further research is warranted to test the tool's sensitivity to changes in medical treatment and its potential role as a clinical and research tool.

Background: Congestive heart failure (CHF) is associated with endothelial dysfunction in people and in dogs with experimentally induced CHF, but this is not well characterized in dogs with naturally occurring CHF., Hypothesis/objectives: To evaluate endothelial function via assessment of reactive hyperemia (RH) in healthy dogs and dogs with CHF, and to assess for relationships with plasma biomarkers of vascular function and clinical markers of disease severity., Animals: Twenty client-owned animals with CHF due to myxomatous mitral valve disease (n = 15) or dilated cardiomyopathy (n = 5) and 17 healthy control dogs., Methods: Prospective case-controlled observational study. Dogs underwent blood sampling, echocardiography, and Doppler assessment of brachial artery velocity (VTI) at baseline and during reactive hyperemia (RH-VTI). RH-VTIs between control dogs and dogs with CHF were compared, and the relationships between RH-VTI, clinical parameters, and plasma biomarkers were assessed., Results: Dogs with CHF (96.5 ± 51.7%) had an attenuated % increase in VTI during RH compared to healthy controls (134.8 ± 58.7%; P = .04). Increasing ISACHC class (R(2) = 0.24; P = .004), plasma NT-proBNP (R(2) = 0.15; P = .03) and CRP (R(2) = 0.2; P = .02) were associated with reduced RH-VTI. Increased plasma CRP, NO(x) , and NT-proBNP concentrations were found in dogs with CHF (P < .02 for all). No differences were detected in other plasma markers., Conclusions and Clinical Importance: Dogs with CHF have an attenuated RH response, and increased plasma CRP and NO(x) concentrations. Doppler assessment of RH velocity could represent a novel noninvasive method of evaluating endothelial function in the dog., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)

Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) can distinguish congestive heart failure (CHF) from primary respiratory disease in cats with respiratory signs with approximately 90% diagnostic accuracy, but the additive benefit of NT-proBNP to improve the diagnosis obtained from conventional testing in individual cases remains unknown., Hypothesis: NT-proBNP will improve the diagnostic accuracy and confidence of general practice veterinarians in assessing cats with respiratory signs., Animals: Ten cats with respiratory signs., Methods: History, physical examination, thoracic radiographs, electrocardiogram (ECG), and biochemical analysis of 10 cats presented to the University of Pennsylvania or Tufts University with a history of respiratory signs were evaluated by 50 general practice veterinarians using an online survey tool. Participants were asked to provide (1) diagnosis of CHF or primary respiratory disease, and (2) level of confidence in their diagnosis (1, lowest to 10, highest) before and after disclosure of NT-proBNP results. Diagnoses (CHF, n = 5; primary respiratory, n = 5) were compared to the gold standard defined as consensus opinion of 3 board-certified cardiologists blinded to the NT-proBNP results., Results: Overall correctness of the practitioners was 69.2%, and significantly increased after practitioners were provided NT-proBNP results (87.0%, P = .0039). Median practitioner confidence before NT-proBNP disclosure was 6 (IQR, 5-8) and significantly increased after disclosure (8; IQR, 6-10; P = .0039)., Conclusions: These data indicate a relatively low accuracy and level of confidence in the diagnosis of feline respiratory signs. Use of NT-proBNP assay in conjunction with conventional evaluation by general practitioners significantly improved their diagnostic accuracy and confidence., (Copyright © 2012 by the American College of Veterinary Internal Medicine.)