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The objective of this prospective observational study was to assess systolic arterial blood pressure (SABP) in small-breed dogs with degenerative mitral valve disease (MVD) from different International Small Animal Cardiac Health Council (ISACHC) heart failure classes. For this purpose, 103 client-owned dogs weighing <20kg (mean ± standard deviation, 8.5 ±3.0 kg; aged 9.8 ± 2.9 years) and presenting with MVD diagnosed by echo-Doppler examination were enrolled. Nineteen healthy dogs (9.9 ±2.3 years; 8.7 ± 4.2 kg) were concurrently recruited as controls. SABP was measured in unsedated dogs using the Doppler method according to the recommendations in the American College of Veterinary Medicine consensus statement. SABP was significantly increased in dogs in ISACHC class I (n = 53; median, interquartile range 140mmHg, 130-150 mmHg) and class 2 (n = 21; 140mmHg, 130-150 mmHg), compared to the control group (n = 19; 130 mmHg, 120-140 mmHg; P<0.01 and P< 0.05, respectively), but remained within the reference interval (<160 mmHg). Conversely, dogs in ISACHC class 3 showed a significantly lower SABP (n = 29, 120 mmHg, 110-130 mmHg) than those from all other ISACHC classes (P< 0.001) and the controis (P< 0.05). Additionally, SABP < 120 mmHg was recorded in 13/103 dogs (13%). The 13 dogs were all ISACHC class 3 (3a or 3b) and were under medical treatment for heart failure. In conclusion, MVD was often associated with SABP values that were within the reference interval, but at its upper end. However, a significant decrease in SABP was observed in dogs with ISACHC heart failure class 3. Whether such low SABP values resulted from an MVD-related decrease in cardiac output, an afterload reduction owing to cardiac treatment, or both, remains to be determined. [ABSTRACT FROM AUTHOR]

Background Azotemia occurs frequently in dogs with degenerative mitral valve disease ( DMVD). It could indicate changes in renal hemodynamics. Hypothesis/Objectives To assess the renal resistive index ( RI) in dogs with DMVD, and the statistical link between heart failure class, azotemia, echo-Doppler parameters, several plasma variables, and RI. Animals Fifty-five dogs with naturally occurring DVMD were used ( ISACHC class 1 [ n = 28], 2 [ n = 19], and 3 [ n = 8]). Methods Observational, blinded study, performed under standardized conditions. Physical examination, renal ultrasonography, and echo-Doppler examinations were performed in awake dogs. The RI of the renal, interlobar, and arcuate arteries were measured. Plasma creatinine, urea, and N-terminal pro-B-type natriuretic peptide concentrations ( NT-pro BNP) were determined. Statistical links between variables and RI were tested by means of a general linear model. Results Although the RI of renal and arcuate arteries were unaffected by ISACHC class, the left interlobar RI increased ( P < .001) from 0.62 ± 0.05 (mean ± SD) in class 1 to 0.76 ± 0.08 in class 3. It was also higher ( P < .001) in azotemic (0.74 ± 0.08) than in non-azotemic (0.62 ± 0.05) dogs. Similar findings were observed for right interlobar RI. Univariate analysis showed a positive statistical link between NT-pro BNP ( P = .002), urea ( P < .001), creatinine ( P = .002), urea-to-creatinine ratio ( P < .001), left atrium-to-aorta ratio ( P < .001), regurgitation fraction ( P < .001), systolic pulmonary arterial pressure ( P < .001), shortening fraction ( P = .035), and RI. Conclusion and Clinical Importance In dogs with DMVD, interlobar RI increases with heart failure severity and azotemia but a cause and effect relationship remains to be established. [ABSTRACT FROM AUTHOR]

Background: A mutation in the sarcomeric gene coding for the myosin-binding protein C gene has been identified in a colony of Maine Coon cats with hypertrophic cardiomyopathy (MyBPC3-A31P mutation). However, the close correlation between genotype and phenotype (left ventricular hypertrophy [LVH] and dysfunction) has never been assessed in a large population, particularly in heterozygous (Hetero) cats. Objectives: To investigate LV morphology and function with echocardiography and tissue Doppler imaging (TDI) in a population of Maine Coon cats tested for the MyBPC3-A31P mutation with focus on Hetero animals. Animals: Ninety-six Maine Coon cats. Methods: Prospective observational study. Cats were screened for the MyBPC3-A31P mutation and examined with both echocardiography and 2-dimensional color TDI. Results: Fifty-two out of 96 cats did not have the mutation (wild-type genotype, Homo WT), 38/96 and 6/96 were Hetero- and homozygous-mutated (Homo M) cats, respectively. Only 11% of Hetero cats (4/38) had LVH and 29% (10/34) of Hetero cats without LVH were >4 years old (4.1–11.5 years). LVH was also detected in 2 Homo WT cats (4%). A significantly decreased ( P < .05) longitudinal E/A (ratio between early and late diastolic myocardial velocities) in the basal segment of the interventricular septum was observed in Hetero cats without LVH (n = 34) compared with Homo WT cats without LVH (n = 50), thus confirming that the Hetero status is associated with regional diastolic dysfunction ( P < .05). Conclusions: The heterozygous status is not consistently associated with LVH and major myocardial dysfunction. Moreover, Homo WT cats can also develop LVH, suggesting that other genetic causes might be implicated. [ABSTRACT FROM AUTHOR]

Becker muscular dystrophy (BMD) is an X-linked disorder due to in-frame mutations in the DMD gene, leading to a less abundant and truncated dystrophin. BMD is less common and severe than Duchenne muscular dystrophy (DMD) as well as less investigated. To accelerate the search for innovative treatments, we developed a rat model of BMD by deleting the exons 45-47 of the Dmd gene. Here, we report a functional and histopathological evaluation of these rats during their first year of life, compared to DMD and control littermates. BMD rats exhibit moderate damage to locomotor and diaphragmatic muscles but suffer from a progressive cardiomyopathy. Single nuclei RNA-seq analysis of cardiac samples revealed shared transcriptomic abnormalities in BMD and DMD rats and highlighted an altered end-addressing of TMEM65 and Connexin-43 at the intercalated disc, along with electrocardiographic abnormalities. Our study documents the natural history of a translational preclinical model of BMD and reports a cellular mechanism for the cardiac dysfunction in BMD and DMD offering opportunities to further investigate the organization role of dystrophin in intercellular communication., (© 2024. The Author(s).)

Serum triglyceride concentrations increase in dogs with obesity, which is typically assessed by body condition score (BCS), however little is known about changes that take place in non-obese dogs in overweight condition. Further, the associations of triglyceride levels with other markers of energy homeostasis are poorly characterised in healthy animals. The present study aimed to evaluate associations between both BCS and triglyceride concentrations with other markers of lipid and glucose metabolism in healthy, non-obese dogs, as well as to assess whether these markers change significantly in non-obese dogs with overweight as compared to their lean counterparts. Serum concentrations of cholesterol, free fatty acids, triglycerides, insulin, glucose and fructosamine were measured in 532 healthy, client-owned dogs, assigned either to 'lean' (BCS: 3-5) or 'overweight' (BCS: 6-7) categories. Generalised linear mixed models were used to assess associations between BCS categories, triglyceride concentrations and other variables, correcting for the effect of breed. Compared with lean dogs, overweight dogs had a greater serum cholesterol concentration (95% CI, 5.3-6.2 mmol/L or 205-237 mg/dL versus 5.1-5.4 mmol/L or 198-210 mg/dL, p  = 0.0032), insulin concentration (95% CI, 17.5-22.1 μU/ml versus 16.7-18.0 μU/ml, p  = 0.0374) and were older (95% CI, 4.0-5.3 versus 3.4-3.7 years, p  = 0.0005). Triglyceride concentrations were positively associated with fructosamine ( r 2  = 0.31, p  = 0.0012), cholesterol ( r 2  = 0.25, p  < 0.0001), insulin ( r 2  = 0.14, p  = 0.0030) and glucose ( r 2  = 0.10, p  = 0.0014) concentrations, and negatively associated with free fatty acid concentrations ( r 2  = 0.11, p  < 0.0001). However, there was no association between triglyceride concentrations and age. In conclusion, both BCS and triglyceride concentrations were associated with other markers of glucose and lipid metabolism in non-obese healthy dogs, amongst which those with overweight showed metabolic changes as compared to their lean counterparts. Triglyceride concentrations were associated with an increase in insulin and fructosamine concentrations that might reflect an early-phase impairment in glucose tolerance which, surprisingly, was concurrent with lower basal free fatty acid concentrations., Competing Interests: AG is an employee of the University of Liverpool, but his post is financially supported by Royal Canin. AG has also received financial remuneration for providing educational material, speaking at conferences, and consultancy work from this company; all such remuneration has been for projects unrelated to the work reported in this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gomez-Fernandez-Blanco, Peeters, Farnir, Höglund, Gouni, Wiberg, Lundgren Willesen, Hanås, McEntee, Tiret, Häggström, Lohi, Chetboul, Fredholm, Seppälä, Lequarré, German and Merveille.)

Objective: To characterize epidemiological, clinical, radiographic, and echocardiographic features of cardiac diseases in guinea pigs examined at a referral exotics center., Animals: 80 guinea pigs., Procedures: Medical records of guinea pigs that had echocardiography performed between June 2010 and January 2021 were reviewed., Results: The percentage of guinea pig patients with cardiovascular disease was 2.8%. Clinical signs included dyspnea (46/80), lethargy (18/80), and anorexia (10/80). The most common physical examination finding was heart murmur (10/80). Radiographic abnormalities included subjective cardiomegaly (37/67), pleural effusion (21/67), and increased lung opacity (40/67). Median (range) vertebral heart score on right lateral (48/67) and ventrodorsal (39/67) projections was 9.0 vertebrae (6.6 to 13.2 vertebrae) and 10.8 vertebrae (7.9 to 13.2 vertebrae), respectively. The most common echocardiographic diagnosis was cardiomyopathy (30/80), categorized as restrictive (11/30), hypertrophic (10/30), or dilated (9/10). Other cardiac diseases included cor pulmonale (21/80), pericardial effusion (18/80), congenital heart disease (6/80), acquired valvular disease (3/80), and cardiovascular mass (2/80). Congestive heart failure was present in 36 of 80. Median survival time from diagnosis was 2.5 months (95% CI, 1.1 to 6.2 months). Animals that died from heart disease had a significantly shorter survival time than those that died from a noncardiac disease (P = .02)., Clinical Relevance: On radiographs, cardiomegaly, pleural effusion, and alveolar or interstitial lung pattern should be considered as indications for echocardiography in guinea pigs. Cardiomyopathy (restrictive, hypertrophic, or dilated), cor pulmonale, and pericardial effusion were the most common echocardiographic diagnoses. Further studies on diagnosis and treatment of cardiovascular diseases in guinea pigs are needed.

Thoracic radiography is commonly used to assess the size of the heart and diagnose cardiac disease in ferrets. Several standardized radiographic heart size indicators have been introduced in this species and values in healthy ferrets have been reported. To date, none of these indicators has been tested in ferrets with cardiac disease. The aim of this prospective and retrospective, analytical observational design study was to assess the accuracy of the modified vertebral heart score (mVHS) and the cardio-vertebral ratio (CVR) in the radiographic detection of cardiomegaly in ferrets. Thoracic radiographs of 24 ferrets with confirmed heart diseases, 22 ferrets with non-cardiac diseases and normal-sized hearts on echocardiogram, and 24 healthy ferrets were mixed and examined by three independent and blinded radiologists who measured mVHS and CVR in right lateral (RL) and ventrodorsal (VD) radiographs. For all readers, ferrets with cardiac disease had significantly higher mVHS and CVR than ferrets without cardiac disease on echocardiography. Optimal cut-points for predicting cardiac enlargement were 6.25 vertebrae and 7.25 vertebrae for RL-mVHS and VD-mVHS, and 1.58 and 1.80 for RL-CVR and VD-CVR, respectively. Using these cut-points, the accuracy was good for indicators measured in RL radiographs (92.9% for RL-mVHS; 91.4% for RL-CVR) and moderate for indicators measured in VD radiographs (88.6% for VD-mVHS; 85.7% for VD-CVR). Findings supported the use of mVHS and CVR for evaluating the size of the heart in diseased ferrets, with caution in values interpretation when pericardial fat prevents precise delineation of the cardiac silhouette contour especially on VD radiographs., (© 2022 American College of Veterinary Radiology.)

Background: Duchenne muscular dystrophy is associated with progressive deterioration in left ventricular (LV) function. The golden retriever muscular dystrophy (GRMD) dog model recapitulates the pathology and clinical manifestations of Duchenne muscular dystrophy. Importantly, they develop progressive LV dysfunction starting at early age., Objectives: The authors tested the cardioprotective effect of chronic administration of the ARM036, a small molecule that stabilizes the closed conformation of the cardiac sarcoplasmic reticulum ryanodine receptor/calcium release channel (RyR2) in young GRMD-dogs., Methods: Two-month-old GRMD-dogs were treated with ARM036 or placebo for 4 months. Healthy-dogs of the same genetic background served as controls. Cardiac function was evaluated by conventional and 2-dimensional speckle-tracking echocardiography. Cardiac cellular and molecular analyses were performed at 6 months old., Results: Conventional echocardiography showed normal LV dimensions and ejection fraction in 6-month-old GRMD dogs. Interestingly, 2-dimensional speckle-tracking echocardiography revealed decreased global longitudinal strain and the presence of hypokinetic segments in placebo-treated GRMD dogs. Single-channel measurements revealed higher RyR2 open probability at low resting Ca 2+ in GRMD cardiomyocytes than in controls. ARM036 prevented those in vivo and in vitro dysfunctions in GRMD dogs. Myofilament Ca 2+ -sensitivity was increased in permeabilized GRMD cardiomyocytes at short sarcomere length. ARM036 had no effect on this parameter. Cross-bridge cycling kinetics were altered in GRMD myocytes and recovered with ARM036 treatment, which coincided with the level of myosin binding protein-C-S glutathionylation., Conclusions: GRMD-dogs exhibit early LV dysfunction associated with altered myofilament contractile properties. These abnormalities were prevented pharmacologically by stabilizing RyR2 with ARM036., Competing Interests: Funding Support and Author Disclosures This study was supported by the Association Française contre les Myopathies (AFM) (OC N°11590, AL N°15083, SB N° 14389, 15208, 15632, 16396, and 17124) and by Institut de Recherches Servier (Suresnes, France). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The domestic dog represents an ideal model for identifying susceptibility genes, many of which are shared with humans. In this study, we investigated the genetic contribution to individual differences in 40 clinically important measurements by a genome-wide association study (GWAS) in a multinational cohort of 472 healthy dogs from eight breeds. Meta-analysis using the binary effects model after breed-specific GWAS, identified 13 genome-wide significant associations, three of them showed experimental-wide significant associations. We detected a signal at chromosome 13 for the serum concentration of alanine aminotransferase (ALT) in which we detected four breed-specific signals. A large proportion of the variance of ALT (18.1-47.7%) was explained by this locus. Similarly, a single SNP was also responsible for a large proportion of the variance (6.8-78.4%) for other measurements such as fructosamine, stress during physical exam, glucose, and morphometric measurements. The genetic contribution of single variant was much larger than in humans. These findings illustrate the importance of performing meta-analysis after breed-specific GWAS to reveal the genetic contribution to individual differences in clinically important measurements, which would lead to improvement of veterinary medicine.

Background: Restrictive cardiomyopathy (RCM) is a common primary cardiomyopathy of cats. However, little information is available regarding prognostic variables in large populations of cats with RCM., Objectives: To characterize the epidemiological, clinical, and echocardiographic features of cats with RCM and to document their survival times and risk factors for cardiac death (CD)., Animals: Ninety-two cats with RCM., Methods: Retrospective study. Diagnosis of RCM was based on echocardiographic and Doppler criteria. Median survival time to CD and adjusted hazard ratios (HR) were estimated by the Kaplan-Meier method and multivariate Cox models, respectively., Results: The feline population (median age [interquartile range], 8.6 years [4.1-12.4]; body weight, 4.0 kg [3.3-4.7]) included 83 cats (90%) with the myocardial RCM form and 9 (10%) with the endomyocardial fibrosis RCM form. Most RCM cats (64/92, 70%) were symptomatic at the time of diagnosis, with dyspnea related to congestive heart failure in 57 of 64 cats (89%). The median survival time of the 69 cats with the myocardial RCM form and available follow-up was 667 days (range, 2-3710 days) considering CD. Independent of age, biatrial enlargement, and arrhythmias, increase of the left atrium (LA)-to-aorta (Ao) ratio (hazard ration [HR], 2.5 per 0.5-unit increase; 95% confidence interval [CI], 1.5-4.2; P < .001) and presence of severe LA enlargement (end-diastolic LA : Ao ≥2; HR, 3.4; 95% CI, 1.3-8.7; P = .01) were significantly associated with shorter time to CD., Conclusions and Clinical Importance: Cardiac death is common in RCM cats, and LA enlargement seems independently associated with decreased survival time in these cats., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)