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Introduction /Objectives: The objectives were to conduct a survey of cardiologists on their recent experiences with cats that have dilated cardiomyopathy (DCM), and to retrospectively review individual cases of feline DCM. Animals, Materials and Methods Part One: A survey was distributed to cardiologists with questions regarding caseload and clinical management of cats with DCM diagnosed over the past two years. Part Two: Cardiologists completing the survey were invited to submit data from cats recently diagnosed with DCM. Data on signalment, clinical signs, diet, echocardiographic measurements, and outcome were recorded. Results Part One: From 52 completed surveys, many cardiologists responded that measuring and supplementing taurine and recommending a diet change in cats with DCM are common practices. Few (15%) cardiologists reported an increase in number of feline DCM cases over the past two years, although some had cases that improved even if taurine deficiency was not present. Part Two: Twenty of 37 (54%) cats ate low pea/lentil (low PL) diets and 14/37 (38%) ate high pea/lentil (high PL) diets at the time of diagnosis; three had incomplete diet information. Two of 13 cats (15%) in which taurine was measured had levels below the reference range. After adjusting for other variables, cats eating high PL diets that changed diets post-diagnosis had a significantly longer survival time compared to cats eating high PL diets that did not change diets post-diagnosis (P=0.025). Conclusions Additional research is warranted to determine whether there could be a possible association between diet and DCM in cats.

OBJECTIVE To evaluate whether mesenchymal stem cells (MSCs) can be safely administered IV to dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD) to improve cardiac function and prolong survival time. ANIMALS 10 client-owned dogs with CHF secondary to MMVD. PROCEDURES Dogs with an initial episode of CHF secondary to MMVD were enrolled in a double-blind, placebo-controlled clinical trial. Five dogs in the MSC group received allogeneic Wharton jelly–derived MSCs (2 X 106 cells/kg, IV), and 5 dogs in the placebo group received a 1% solution of autologous serum (IV) for 3 injections 3 weeks apart. Cell-release criteria included trilineage differentiation, expression of CD44 and CD90 and not CD34 and major histocompatability complex class II, normal karyotype, and absence of contamination by pathogenic microorganisms. Patients were followed for 6 months or until death or euthanasia. Echocardiographic data, ECG findings, serum cardiac biomarker concentrations, CBC, and serum biochemical analysis results were obtained prior to and 4 hours after the first injection and every 3 months after the final injection. RESULTS Lymphocyte and eosinophil counts decreased significantly 4 hours after injection, and monocytes decreased significantly only in dogs that received an MSC injection. No significant differences were seen in the echocardiographic variables, ECG results, serum cardiac biomarker concentrations, survival time, and time to first diuretic drug dosage escalation between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE This study showed that MSCs can be easily collected from canine Wharton jelly as an allogeneic source of MSCs and can be safely delivered IV to dogs with CHF secondary to MMVD.

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

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.

Objectives Growth differentiation factor (GDF) 11 has been shown to reduce cardiac hypertrophy in mice. Low levels of GDF-11 are associated with cardiac hypertrophy in humans. The authors hypothesized that plasma GDF-11 level is decreased in cats with hypertrophic cardiomyopathy (HCM). Given the close homology between GDF-11 and myostatin/GDF-8, GDF-8 levels were also assessed. Animals Thirty-seven client-owned cats were enrolled, including cats with normal cardiac structure (n = 16), cats with HCM or hypertrophic obstructive cardiomyopathy (HOCM; n = 14), and cats with HCM and congestive heart failure (CHF; n = 7). Methods Plasma samples were analyzed for GDF-8 and GDF-11 using liquid chromatography tandem-mass spectrometry. Levels of GDF-8 and GDF-11 were compared between cats with normal cardiac structure, HCM or HOCM, and CHF. Results No differences in GDF-11 concentrations were found between cats with normal cardiac structure and cats with HCM/HOCM, with or without history of CHF. Decreased GDF-8 concentrations were detected in cats with CHF compared to cats with HCM/HOCM without history of CHF (p=0.031) and cats with normal cardiac structure (p=0.027). Growth differentiation factor 8 was higher in cats with HOCM compared to those with CHF (p=0.002). No statistical difference was noted in GDF-8 level as a function of age, weight, or body condition score. Conclusions Plasma GDF-11 was not different between cats with HCM/HOCM and cats with normal cardiac structure regardless of age. Plasma GDF-8 was decreased in cats with CHF compared to cats with normal cardiac structure and cats with asymptomatic HCM/HOCM, suggesting a possible role in CHF development.

Non-syndromic mitral valve prolapse (MVP), or Barlow’s Disease, is a valvular heart disease with a prevalence of 2-3% in the human adult population. Consequences of MVP include mitral regurgitation that without surgical treatment can progress to congestive heart failure, arrhythmias and sudden death. Since MVP is a degenerative disease that worsens with age, surgical risk is of concern with an older population, necessitating the development of alternative strategies for early detection and effective medical intervention. Similar to humans, canine MVP is age-related with a lifetime prevalence close to 90%, providing a large population for study. Canine MVP represents a relevant spontaneous large animal model to dissect the mechanistic underpinnings of disease pathogenesis and evaluate novel treatment. We hypothesize that extracellular vesicles (EVs) and their associated non-coding RNA (ncRNA) may play a role in this disease by enabling propagation of the fibroblast-to-myofibroblast phenotypic switch in mitral valvular interstitial cells (VICs). VICs were isolated from 12 normal and 14 diseased canine mitral valves and cultured in defined chemical media for 48 hours. EVs were isolated from conditioned media using size exclusion chromatography. Total RNA was isolated from EVs with the Qiagen miReasy Plasma/Serum kit, and from VIC cells with the mirVana miRNA Isolation Kit. Sequencing libraries were created using QIAseq miRNA Library Kit, and RNAseq was performed with Illumina HiSeq 2500 sequencer with single read 100 base format. Reads were mapped to canine ncRNA databases (miRbase, RFam). VICs from diseased valves had higher expression of αSMA than cells from normal valves (p = 0.002) based on RT-qPCR. Sequence analysis showed decreased content of tRNA (p = 0.023) and miRNA precursor (p = 0.036) in EVs from diseased VICs, in addition to decreased expression of let-7f. Cells from diseased valves had lower Y-RNA content (p = 0.007). miR-8859a and miR-451 were preferentially packaged into EVs from both normal and diseased VICs. Preferential packaging of miR-155 was seen in normal VIC EVs and miR-191 in diseased VIC EVs. Functional roles of these miRs will need to be confirmed to determine their therapeutic potential for treatment of MVP.

A 13-year-old male castrated pomeranian cross was referred for evaluation of episodes of collapse and a suspected cardiac mass. The presence of a mass at the base of the heart within the pericardial space was confirmed by echocardiography. Additional diagnostics included computed tomography, ultrasound-guided fine-needle aspirate, and thoracic radiographs. The mass was surgically debulked and diagnosed as myxosarcoma via histopathology. This case report describes the diagnostic imaging, laboratory findings, and short-term positive clinical outcome of a dog with a myxosarcoma in a previously undescribed location.

Objective To describe the clinical use of rivaroxaban in the treatment of 4 dogs with vascular thrombosis, 2 with pulmonary thromboembolism and 2 with systemic thrombosis. Case Series Summary This report describes the use of a direct factor Xa anticoagulant newly approved in human patients for the treatment or prevention of arterial or venous thrombosis. The use of this medication in a clinical setting for canine patients with thromboembolism has not been described before. Two patients were treated with rivaroxaban for pulmonary thromboembolism. Decreases in thrombus size were seen in both patients, but one patient suffered acute respiratory distress and was euthanized while the other continued to do well at the time of this writing. The other 2 patients were treated for systemic thrombosis. Decreases in thrombus size were also noted. One patient later suffered hematochezia of unknown cause, and the other continued to do well at the time of this writing. New or Unique Information Provided This is the first published report of the use of a new oral direct factor Xa anticoagulant in dogs in a clinical setting for the treatment of both pulmonary and systemic thrombosis. In this case series, we share our limited experience in the use of this new medication, our strategy in determining appropriate dosages, and our monitoring protocol.

Myxomatous mitral valve disease (MMVD) is functionally and histologically identical to mitral valve prolapse (MVP) in humans. Currently, there are no medical treatments that can delay the progression of this valvular disease or associated cardiac remodelling. Therefore, there is a need to understand the molecular pathology associated with MMVD and MVP better, and thus identify potential therapeutic targets. Circulating exosomes contain small RNA, including miRNA, which reflect cell physiology and pathology. This study explored the association between circulating exosomal miRNA (ex-miRNA) content and MMVD, heart failure due to MMVD (MMVD-CHF) and ageing, which is strongly associated with MMVD. Ex-miRNA was isolated from old normal/healthy dogs (n = 6), young normal dogs (n = 7), dogs with MMVD (n = 7) and dogs with MMVD-CHF (n = 7). Separately, total plasma miRNA was isolated from normal dogs (n = 8), dogs with MMVD (n = 8) and dogs with MMVD-CHF (n = 11). Using reverse transcription quantitative polymerase chain reaction, exosomal miR-181c (p = 0.003) and miR-495 (p = 0.0001) significantly increased in dogs with MMVD-CHF compared to the other three groups. Exosomal miR-9 (p = 0.002) increased in dogs with MMVD and MMVD-CHF compared to age-matched (old) normal dogs. Exosomal miR-599 (p = 0.002) decreased in dogs with MMVD compared to old normal dogs. In total plasma, 58 miRNA were deemed significantly different (p

Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies suggest a high rate of stem cell activity with differentiation of progenitors to cardiomyocytes. Other studies suggest that new cardiomyocytes are born at a very low rate, and that they may be derived from the division of pre-existing cardiomyocytes. Here we show, by combining two different pulse-chase approaches--genetic fate-mapping with stable isotope labelling, and multi-isotope imaging mass spectrometry--that the genesis of cardiomyocytes occurs at a low rate by the division of pre-existing cardiomyocytes during normal ageing, a process that increases adjacent to areas of myocardial injury. We found that cell cycle activity during normal ageing and after injury led to polyploidy and multinucleation, but also to new diploid, mononucleate cardiomyocytes. These data reveal pre-existing cardiomyocytes as the dominant source of cardiomyocyte replacement in normal mammalian myocardial homeostasis as well as after myocardial injury.

Canine myxomatous mitral valve disease (MMVD) resembles the early stages of myxomatous pathology seen in human non-syndromic mitral valve prolapse, a common valvular heart disease in the adult human population. Canine MMVD is seen in older subjects, suggesting age-related epigenetic dysregulation leading to derangements in valvular cell populations and matrix synthesis or degradation. We hypothesized that valvular interstitial cells (VICs) undergo disease-relevant changes in miRNA expression. In primary VIC lines from diseased and control valves, miRNA expression was profiled using RT-qPCR and next generation sequencing. VICs from diseased valves showed phenotypic changes consistent with myofibroblastic differentiation (vimentinlow+, α-SMAhigh+), increases in senescence markers (p21, SA-β-gαl), and decreased cell viability and proliferation potential. RT-qPCR and miRNA sequencing analyses both showed significant (p

Objectives Cardiac cachexia, a loss of lean body mass caused by heart disease, often accompanies congestive heart failure (CHF). Blocking myostatin, which is a protein that inhibits muscle growth, appears to greatly enhance muscle size and strength in rodent models and human clinical trials. The objective of this study was to evaluate a dog-specific myostatin antagonist (CAP-031) in a pilot study to test its safety and efficacy in dogs with CHF and cardiac cachexia. Animals Dogs with CHF and cardiac cachexia. Methods Eligible dogs received four weekly subcutaneous injections of CAP-031. Endpoints were body weight, body condition score (BCS, on a 1–9 scale), muscle condition score (MCS, on a five-point scale, where 0 = no muscle loss and 4 = severe muscle loss), appetite, and a quality of life (QOL) score. Results Seven dogs with CHF and moderate-to-severe cachexia were enrolled in the study. For the six dogs that completed the study, the median age was 8.8 years (range 6.4–10.6). At baseline, the median body weight was 27.0 kg (range 17.3–62.0), the median BCS was 4 (2–5), and median MCS was 3 (3–4). There were no significant changes in body weight, BCS, appetite, or QOL score. The change in MCS (from a median of 3 at baseline to a median of 2.5 at week 4) was not statistically significant ( p = 0.06). Conclusions The myostatin antagonist appeared to be well tolerated in most dogs. Earlier identification of cachexia is important, and randomized, controlled trials of myostatin antagonists or other drugs to treat cardiac cachexia are needed.

To evaluate the responsiveness and optimal timing of a validated health-related quality of life questionnaire, and to assess the relationship between quality of life, severity of disease, and N-terminal pro B-type natriuretic peptide (NT-proBNP) in cats with acute congestive heart failure (CHF).Thirty client-owned cats with acute CHF.Echocardiography, International Small Animal Cardiac Health Council (ISACHC) stage, and NT-proBNP were assessed in cats within 36 h of admission. The Cats' Assessment Tool for Cardiac Health (CATCH) Questionnaire (range of 0-80, with 80 being the worst possible score) was completed by cat owners and ISACHC stage was assessed at the time of hospital discharge, 3 days after discharge, and 7-14 days after discharge. NT-proBNP concentration was reassessed 7-14 days after discharge.The ISACHC stage at time of admission improved significantly by reevaluation 7-14 days after discharge (P0.001). The decrease in median NT-proBNP concentration from time of admission (655 pmol/L; range, 188 to1500 pmol/L) to reevaluation (583 pmol/L; range, 41 to1500 pmol/L) was not significant (P = 0.59). Median CATCH score was 26 (range, 0-70) at baseline, 19 (range, 0 to 61) at discharge, and 19 (range, 2-49) 7-14 days after discharge (P = 0.89). CATCH scores did not correlate with NT-proBNP concentrations or ISACHC stage.These results suggest that the CATCH questionnaire requires further refinement for uses requiring a responsive instrument in cats with acute CHF.

Objective—To compare morphometric measurements and serum insulin-like growth factor (IGF-1) concentration in cats with and without hypertrophic cardiomyopathy (HCM), and assess the hypothesis that cats with HCM have larger body size and skeletal features and higher serum IGF-1 concentrations than healthy cats. Animals—25 cats with HCM and 22 healthy control cats. Procedures—Physical examination and echocardiography were performed to classify cats into the HCM and control groups. Data collected from each cat included diet history, body weight, body condition score, lengths of the humerus and 4th and 12th thoracic vertebrae, heart size, head length and width, and abdominal circumferences. Comparisons of these variables were made between groups. Results—Body condition score in HCM-affected and control cats did not differ significantly. However, median head width; lengths of the head, 4th and 12th thoracic vertebrae, and humerus; and body weight in the HCM-affected group were significantly greater than values in the control group. Median serum concentration of IGF-1 was not significantly different between groups. Conclusions and Clinical Relevance—These data suggested that among the study cats, those with HCM were skeletally larger, but not more obese, than healthy cats. Whether this was attributable to differences in early growth or other causes requires additional investigation.