Prophylactic impacts of Lagenaria siceraria against cardiomyopathy induced by doxorubicin in a rat model.

Background: Doxorubicin (DOX) is a chemotherapeutic drug applied clinically for the remedy of cancer, but its possibly life-threatening cardiotoxicity effects remain a concern. Aim: After that, this study evaluates the cardioprotective impacts of Lagenaria siceraria (LSS) oil on DOX induced cardiomyopathy in rats. Methods: Wistar male rats (n = 28, weighting 190-210 g) were arbitrarily allocated into four equal groups. Group 1 control group (CTR) received normal saline orally (1 ml/kg); group 2 (DOX) received DOX (10 mg/kg); group 3 (DOLS) received DOX + 3 g of Lagenaria siceraria seeds oil/kg; group 4 (LSSO) received LSSO (3 g/kg) daily for 18 days. The serum samples were collected to determine the creatine kinase-MB (CK-MB) isoenzyme, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and Troponin I activity. At the same time, the catalase, malondialdehyde (MDA), and reduced glutathione (GSH) were assessed in heart tissues. Additionally, histopathological investigations for the heart tissue were performed. Results: Results revealed no significant change in CK-MB levels between the DOLS group compared to the CTR group (p > 0.05). DOX group confirmed a substantial increase in AST, LDH, and Troponin1 serum levels compared to DOLS and LLSO groups (p < 0.05). The study demonstrated the antioxidant activity of LSS oil against DOX-induced toxicity. The DOX group significantly reduced GSH and catalase levels, with an increase in MDA levels compared to DOLS and LLSO groups. Histopathological analysis showed protective properties of LSS oil against myocardial damage caused by DOX. Conclusion: This study highlights the favorable impacts of LSS oil in mitigating DOX-triggered cardiotoxicity in a rat model.

Histologic characterization of spontaneous catecholamine-induced cardiomyopathy in laboratory New Zealand White rabbits.

Catecholamine-induced cardiomyopathy (CCM) is an entity associated with increased levels of catecholamines causing subendocardial and papillary muscle cardiomyocyte degeneration and necrosis. In 2020, 49 autopsies from early rabbit deaths in a colony used for medical device biocompatibility studies were submitted for microscopic examination. Of the 49 rabbits, 26 had histologic changes consistent with CCM. No common stressor for CCM was determined in affected rabbits. Animals were generally male, were 12-16-wk-old, and were found dead or had bloating, lethargy, and/or diarrhea. Those observed with clinical signs were euthanized and autopsied per the organization's standard operating procedures. Heart lesions consisted of various degrees of apical subendocardial myocardial degeneration and necrosis. Common non-cardiac lesions included pulmonary congestion and edema, hepatic congestion and centrilobular hepatocellular degeneration, and/or variable intestinal submucosal edema.

Myocardial injury in dogs: a retrospective analysis on etiological, echocardiographic, electrocardiographic, therapeutic, and outcome findings in 102 cases.

INTRODUCTION: In dogs, myocardial injury (MI) is a poorly characterized clinical entity; therefore, this study aimed to provide a detailed description of dogs affected by this condition. ANIMALS, MATERIALS, AND METHODS: Dogs diagnosed with MI according to the concentration of cardiac troponin I (cTnI) were retrospectively searched. Signalment, diagnostic, therapeutic, and outcome data were retrieved. Dogs were divided into six echocardiographic (dilated cardiomyopathy phenotype; hypertrophic cardiomyopathy phenotype; hypertrophic cardiomyopathy phenotype with systolic dysfunction; abnormal echogenicity only; endocarditis; and no echocardiographic abnormalities suggestive of MI), four electrocardiographic (abnormalities of impulse formation; abnormalities of impulse conduction; abnormalities of ventricular repolarization; and no electrocardiographic abnormalities suggestive of MI), and nine etiological (infective; inflammatory; neoplastic; metabolic; toxic; nutritional; immune-mediated; traumatic/mechanical; and unknown) categories. Statistical analysis was performed to compare cTnI values among different categories and analyze survival. RESULTS: One hundred two dogs were included. The median cTnI value was 3.71 ng/mL (0.2-180 ng/mL). Echocardiographic and electrocardiographic abnormalities were documented in 86 of 102 and 89 of 102 dogs, respectively. Among echocardiographic and electrocardiographic categories, the dilated cardiomyopathy phenotype (n = 52) and abnormalities of impulse formation (n = 67) were overrepresented, respectively. Among dogs in which a suspected etiological trigger was identified (68/102), the infective category was overrepresented (n = 20). Among dogs belonging to different echocardiographic, electrocardiographic, and etiological categories, cTnI did not differ significantly. The median survival time was 603 days; only eight of 102 dogs died due to MI. CONCLUSIONS: Dogs with MI often have an identifiable suspected trigger, show various echocardiographic and electrocardiographic abnormalities, and frequently survive to MI-related complications.

Arterial thromboembolism in a cat with transient myocardial thickening.

Feline arterial thromboembolism has been reported to be secondary to various feline cardiomyopathies; however, it has not been described in cats with transient myocardial thickening. A previously healthy, one-year-old, castrated male cat presented with acute paraparesis and congestive heart failure. Echocardiography revealed asymmetric left ventricular free wall thickening and left atrial enlargement. Antithrombotic treatment and cardiac medication resulted in reperfusion and mobility on day seven in one limb and on day 10 in the other. Different complications were managed successfully, including worsening acute kidney injury, inflammation, pleural effusion, and anemia. After three weeks, the cat was discharged and prescribed oral antithrombotic drugs (clopidogrel and rivaroxaban) and cardiac medication. Within five months, echocardiographic findings normalized, and medical treatment was gradually discontinued. To date, the cat remains healthy at 1735 days after the initial diagnosis and 1494 days after the last antithrombotic medication. To the best of our knowledge, this is the first case report on feline arterial thromboembolism combined with transient myocardial thickening, with favorable long-term survival.

Cardiomyopathy associated 5 (CMYA5) implicated as a genetic risk factor for radial hemimelia in Siamese cats.

OBJECTIVES: The present study aimed to determine the inheritance pattern and genetic cause of congenital radial hemimelia (RH) in cats. METHODS: Clinical and genetic analyses were conducted on a Siamese cat family (n = 18), including two siblings with RH. Radiographs were obtained for the affected kittens and echocardiograms of an affected kitten and sire. Whole genome sequencing was completed on the two cases and the parents. Genomic data were compared with the 99 Lives Cat Genome data set of 420 additional domestic cats with whole genome and whole exome sequencing data. Variants were considered as homozygous in the two cases of the siblings with RH and heterozygous in the parents. Candidate variants were genotyped by Sanger sequencing in the extended pedigree. RESULTS: Radiographs of the female kitten revealed bilateral absence of the radii and bowing of the humeri, while the male kitten showed a dysplastic right radius. Echocardiography suggested the female kitten had restrictive cardiomyopathy with a positive left atrial-to-aortic root ratio (LA:Ao = 1.83 cm), whereas hypertrophic cardiomyopathy was more likely in the sire, showing diastolic dysfunction using tissue Doppler imaging (59.06 cm/s). Twenty-two DNA variants were unique and homozygous in the affected kittens and heterozygous in the parents. Seven variants clustered in one chromosomal region, including two frameshift variants in cardiomyopathy associated 5 (CMYA5) and five variants in junction mediating and regulatory protein, P53 cofactor (JMY ), including a missense and an in-frame deletion. CONCLUSIONS AND RELEVANCE: The present study suggested an autosomal recessive mode of inheritance with variable expression for RH in the Siamese cat family. Candidate variants for the phenotype were identified, implicating their roles in bone development. These genes should be considered as potentially causal for other cats with RH. Siamese cat breeders should consider genetically testing their cats for these variants to prevent further dissemination of the suspected variants within the breed.

Sepsis-induced cardiomyopathy in animals: From experimental studies to echocardiography-based clinical research.

The term "sepsis-induced cardiomyopathy" (SIC) is used to describe transient cardiac dysfunction in septic patients. However, there is no universally accepted definition of SIC; a reduction in left ventricular ejection fraction (LVEF) is often used. In addition to systolic dysfunction, diastolic dysfunction is now recognized as an essential component of SIC. It can be emphasized that previous animal experiments played an essential role in revealing SIC and hemodynamic instability in sepsis and septic shock. The diagnostic and prognostic capabilities of echocardiography for the assessment of SIC have been extensively studied since its introduction into intensive care clinical practice. Recent studies in dogs, calves, and horses have shown that left and right ventricular systolic dysfunction, left ventricular diastolic dysfunction, and circulatory dysfunction can occur in sepsis, severe sepsis, and septic shock in animals. Echocardiographic variables have also shown that indices of left and right ventricular dysfunction and circulatory failure are valuable indicators of mortality in septic animals.

Cardiomyopathie induite par la septicémie chez l'animal : des études expérimentales à la recherche clinique basée sur l'échocardiographie. Le terme « cardiomyopathie induite par la septicémie ¼ (SIC) est utilisé pour décrire un dysfonctionnement cardiaque transitoire chez les patients septiques. Cependant, il n'y a pas de définition universellement acceptée du SIC; une réduction de la fraction d'éjection ventriculaire gauche (FEVG) est souvent utilisée. En plus de la dysfonction systolique, la dysfonction diastolique est maintenant reconnue comme une composante essentielle du SIC. On peut souligner que les expérimentations animales antérieures ont joué un rôle essentiel dans la révélation du SIC et de l'instabilité hémodynamique dans la septicémie et le choc septique. Les capacités diagnostiques et pronostiques de l'échocardiographie pour l'évaluation du SIC ont été largement étudiées depuis son introduction dans la pratique clinique des soins intensifs. Des études récentes sur des chiens, des veaux et des chevaux ont révélé qu'un dysfonctionnement systolique ventriculaire gauche et droit, un dysfonctionnement diastolique ventriculaire gauche et un dysfonctionnement circulatoire peuvent survenir dans la septicémie, la septicémie sévère et le choc septique chez les animaux. Les variables échocardiographiques ont également démontré que les indices de dysfonctionnement ventriculaire gauche et droit et d'insuffisance circulatoire sont des indicateurs précieux de la mortalité chez les animaux septiques.(Traduit par Dr Serge Messier).

Investigation of the cardiac effects of exercise testing on apparently healthy Boxer dogs.

BACKGROUND: Holter electrocardiographic monitoring is a cornerstone of diagnostic testing for arrhythmogenic cardiomyopathy (ACM) in Boxer dogs, but physical activity during monitoring is not controlled. In humans, exercise testing (ExT) can identify latent tachyarrhythmias associated with cardiomyopathy, and exercise increases serum cardiac troponin-I concentrations ([hs-cTnI]). These effects have not yet been investigated in Boxer dogs. HYPOTHESIS/OBJECTIVES: Subjecting Boxer dogs to brief, moderate-intensity ExT can identify changes in Holter recordings and [hs-cTnI] compared to baseline results. ANIMALS: Thirty overtly healthy, client-owned Boxer dogs. METHODS: Prospective interventional study. Dogs underwent baseline diagnostic testing including 24-hour Holter monitoring and [hs-cTnI], followed by brief ExT (accompanied, brisk stair-climbing and -descending for <5 minutes). RESULTS: Eleven dogs (37%) had >100 premature ventricular complexes (PVCs)/24 hours at baseline (3), ExT (3), or both (5). After ExT, these dogs had more PVCs/24 hours and greater increases in [hs-cTnI] compared to those with ≤100 PVCs/24 hours. Dogs with the striatin mutation had more PVCs/24 hours and a greater increase in [hs-cTnI] after ExT than did dogs without the striatin mutation. CONCLUSIONS AND CLINICAL IMPORTANCE: Exercise testing may improve the binary classification of Boxer dogs with or without ACM by increasing the number of PVCs and [hs-cTnI] in affected dogs to a greater degree than in unaffected dogs. This effect also is associated with presence or absence of the striatin mutation. Exercise should be a controlled variable when screening Boxer dogs for ACM.

The Role of Personalized Medicine in Companion Animal Cardiology.

Cardiomyopathies remain one of the most common inherited cardiac diseases in both human and veterinary patients. To date, well over 100 mutated genes are known to cause cardiomyopathies in humans with only a handful known in cats and dogs. This review highlights the need and use of personalized one-health approaches to cardiovascular case management and advancement in pharmacogenetic-based therapy in veterinary medicine. Personalized medicine holds promise in understanding the molecular basis of disease and ultimately will unlock the next generation of targeted novel pharmaceuticals and aid in the reversal of detrimental effects at a molecular level.

Phaeochromocytoma associated with cardiomyopathy and leukocytoclastic vasculitis in a dog.

Phaeochromocytomas are rare tumours of the adrenal medulla that can be associated with various presentations. Many of the better characterized clinical signs, including weakness, tachycardia and tachypnoea, are attributable to excessive and unregulated catecholamine secretion from functional tumours. In addition to catecholamine-induced cardiomyopathy and vasospasm, the invasive nature of phaeochromocytomas can lead to occlusion of the caudal vena cava contributing to systemic cardiovascular compromise. In humans, leukocytoclastic vasculitis is a rarely reported manifestation of catecholamine excess associated with phaeochromocytomas. We now describe a dog that had an invasive unilateral phaeochromocytoma with histological evidence of myocardial damage, consistent with catecholamine-induced cardiomyopathy, and leukocytoclastic vasculitis of small vessels in a range of tissues. We conclude that catecholamine excess may have played a role in the pathogenesis of vasculitis in this case. To the best of our knowledge, this is the first documented association between phaeochromocytoma and leukocytoclastic vasculitis in a non-human species.

Epidemiological, clinical, radiographic, echocardiographic findings and outcome in client-owned guinea pigs (Cavia porcellus) with cardiac disease: 80 cases (2010-2021).

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.

Acquired Systolic Dysfunction and Subsequent Congestive Heart Failure Following Treatment of Hypoadrenocorticism in Two Dogs.

Acquired cardiomyopathies have been described in human patients with hypoadrenocorticism. Several mechanisms have been described to explain the cardiac effects of primary adrenal insufficiency, but, clinically, these manifestations may be underappreciated in dogs. In humans, there is an infrequently described, reversible dilated cardiomyopathy in patients with hypoadrenocorticism. Two dogs were presented to a single referral center for evaluation of weakness or collapse and were subsequently diagnosed with hypoadrenocorticism after a full diagnostic workup. Following the diagnosis of hypoadrenocorticism and administration of glucocorticoids and desoxycorticosterone pivalate, both dogs developed left-sided congestive heart failure and had systolic dysfunction diagnosed by echocardiogram. Both dogs were euthanized; one because of recurrent congestive heart failure and another because of a concern for poor long-term prognosis and decreased quality of life. The purpose of this case report is to document multiple cases of hypoadrenocorticism-associated systolic dysfunction and subsequent cardiogenic pulmonary edema in dogs.

Left-dominant arrhythmogenic cardiomyopathy in a Fila Brasileiro dog.

Background: In human medicine, arrhythmogenic left ventricular cardiomyopathy was described as a primary disease of the heart characterized by fibroadipose replacement of the myocardium.. Case Description: We report the case of a dog, with history of syncope and irregular cardiac rhythm. Electrocardiogram, echocardiography, and a 24-hour Holter monitoring showed, respectively, the presence of premature ventricular complexes with right bundle branch block morphology, an increase of the left ventricle end-diastolic diameter with preserved fractional shortening and ejection fraction, and a sinus arrhythmia as baseline rhythm with supraventricular tachycardia episodes and ventricular complexes with left bundle branch block morphology. After the death of the canine, a postmortem examination showed cardiomegaly. Fibroadipose replacement of the septum and both ventricles, with left ventricle myocardial fibrosis, suggestive of previous necrosis, was observed. Conclusion: These findings are suggestive of left-dominant arrhythmogenic cardiomyopathy which, to the best of our knowledge, has not been described in veterinary medicine.

The effect of obesity and subsequent weight reduction on cardiac structure and function in dogs.

BACKGROUND: In people, the cardiovascular effects of obesity include systemic hypertension, cardiac remodelling and both systolic and diastolic dysfunction, whilst weight reduction can reverse myocardial remodelling and reduce risk of subsequent cardiovascular disease. To date, variable results are reported in studies of the effect of obesity and controlled weight reduction on cardiovascular morphology and function in dogs. This prospective study aimed to assess cardiac function, heart rate variability, cardiac biomarkers and body composition before and after weight reduction in pet dogs with obesity. Twenty-four client-owned dogs referred for weight management due to obesity were recruited. To assess the cardiac effects of obesity, body composition analysis (by dual energy X-ray absorptiometry, DEXA) and cardiovascular assessment (echocardiography, Doppler blood pressure, electrocardiography, cardiac biomarkers) were performed prior to weight management. Twelve dogs completed the study and reached target weight, receiving a further cardiovascular assessment and DEXA. A Wilcoxon-signed rank test was used to compare each variable pre- and post- weight reduction. RESULTS: Median (interquartile range) duration of weight loss was 224 days (124-245 days), percentage weight loss was 23% (18-31%) of starting weight. Median change in body fat mass was -50% (-44% to -55%; P = 0.004), whilst median change in lean mass was -7% (+ 1% to -18%, P = 0.083). Before weight reduction, diastolic dysfunction (evidence of impaired relaxation in all dogs), increased left ventricular wall thickness and mildly elevated systolic blood pressure (14/24 ≥ 160 mmHg, median 165 mmHg (140-183)) were common features in dogs with obesity. However, systolic left ventricular wall dimensions were the only variables that changed after weight reduction, with a decrease in both the systolic interventricular septum (P = 0.029) and systolic left ventricular free wall (P = 0.017). There was no evidence of decreased heart rate variability in dogs with obesity (P = 0.367), and no change in cardiac biomarker concentrations with weight reduction (N-terminal proBNP, P = 0.262; cardiac troponin I P = 0.657). CONCLUSIONS: Canine obesity results in diastolic dysfunction and left ventricular hypertrophy, the latter of which improves with significant weight and fat mass reduction. Further studies are required to clarify the clinical consequences of these findings.

Advanced imaging findings in a cat with left ventricular apical aneurysm.

An eight-year-old, male neutered, domestic shorthair cat presented with severe anemia. Two-dimensional echocardiography identified severe left ventricular apical dilation with wall thinning and akinesia. The basal portion of the left ventricle showed equivocal hypertrophy and subjective hyperkinesis. Speckle tracking echocardiography showed marked abnormalities in all deformation planes (longitudinal, circumferential, radial strain) and twist. Three-dimensional Bull's eye plot reconstruction was also performed. Post-mortem evaluation showed a pale and paper-thin left ventricular apex and histopathology confirmed full-thickness cardiomyocytes loss with fibrous replacement. Left ventricular acquired apical aneurysms are the result of chronic damage of the myocardium and are associated with many disease conditions in people, including coronary artery disease and cardiomyopathy. The exact pathophysiological mechanism could not be determined with certainty in the cat of the present report, but advanced echocardiographic evaluation added some fine details into the characterization of this infrequently reported abnormality.

Should we be screening cats for cardiomyopathy? If so, how?

Occult feline hypertrophic cardiomyopathy (HCM) can result in unexpected sudden death or congestive heart failure (CHF) following routine interventions such as anesthesia, fluid administration, or, potentially, administration of corticosteroids. Consequently, clinicians would like to be able to screen at-risk cats to detect occult HCM and either avoid the risky intervention or attempt to reduce the risk of death or CHF. Currently, the feline N-terminal-proBrain natriuretic peptide test is the only potential screening test for detecting occult HCM. However, some cardiologists have pointed out the poor sensitivity of the test precludes its use as a screening test. This interpretation appears somewhat flawed. Using the current rapid test will allow clinicians to correctly identify half of the cats with moderate-to-severe occult HCM. A small number of cats without HCM will also test positive, necessitating an ultimately needless echocardiographic evaluation to demonstrate their disease-free status. However, the low prevalence of HCM in the general cat population and the apparently much lower rate of adverse events than would be predicted brings into question whether clinicians should bother screening. Therefore, until a more sensitive and accurate screening test becomes available, clinicians will have to decide for themselves whether identifying half of the at-risk cats of sudden death and CHF with this test is better than identifying none of them.

Characterization of early phases of cardiomyopathy syndrome pathogenesis in Atlantic salmon (Salmo salar L.) through various diagnostic methods.

Since the first description of cardiomyopathy syndrome (CMS) in Atlantic salmon, in 1985, the disease caused by piscine myocarditisvirus (PMCV) has become a common problem in Atlantic salmon farming, not only in Norway, but also in other salmon farming countries like Scotland and Ireland. In the last years, CMS has been ranked as the most important salmon viral disease in Norway regarding both mortality and economic losses. Detailed knowledge of infection and pathogenesis is still lacking, a decade after the causal agent was first described, and there is a need for a wider range of methods/tools for diagnostic and research purposes. In this study, we compared the detection of PMCV- and CMS-related tissue lesions using previously used and well-known methods like histopathology and real-time RT-PCR to immunohistochemistry (IHC), a less used method, and a new method, RNAscope in situ hybridization. Tissue samples of three different cardiac compartments, mid-kidney and skin/muscle tissue were compared with non-lethal parallel samplings of blood and mucus. The development of pathological cardiac lesions observed in this experiment was in accordance with previous descriptions of CMS. Our results indicate a viremic phase 10- to 20-day post-challenge (dpc) preceding the cardiac lesions. In this early phase, virus could also be detected in relatively high amount in mid-kidney by real-time RT-PCR. Plasma and/or mid-kidney samples may, therefore, be candidates to screen for early-phase PMCV infection. The RNAscope in situ hybridization method showed higher sensitivity and robustness compared with the immunohistochemistry and may be a valuable support to histopathology in CMS diagnostics, especially in cases of untypical lesions or mixed infections.

Effect of cilobradine in cats with a first episode of congestive heart failure due to primary cardiomyopathy.

INTRODUCTION: Heart rate (HR) is often elevated in cats with cardiomyopathies (CMPs). Pharmacologic modulation of HR may reduce cardiac morbidity and mortality. OBJECTIVES: To investigate the effects of cilobradine vs. placebo, regarding time to cardiac mortality or morbidity in cats with first episode of congestive heart failure (CHF) due to primary CMP. ANIMALS: Three hundred and sixty-seven client-owned cats with primary CMP that had presented with a first episode of CHF at 50 centers in Europe. Per-protocol population comprised 193 cats (n = 89 cilobradine, n = 104 placebo). An interim analysis for futility was planned. METHODS: Prospective, randomized, placebo-controlled, double-blinded, multicenter clinical trial. Primary outcome variable was the time to a composite of cardiac mortality or cardiac morbidity. RESULTS: Median time to primary outcome was 84 days (95% confidence interval [CI]: 63-219 days) in the cilobradine group (CG) and 203 days in the placebo group (95% CI: 145-377 days) with observed hazard ratio of 1.44, indicating a higher hazard for the CG (P = 0.057). Mean HR was 28 beats per minute (bpm) lower at Day 7 (P < 0.0001) and remained 29 bpm lower at Day 360 (P = 0.026) in the CG than that in the placebo group. Although the number of adverse events did not differ, there were more serious adverse events in the CG. CONCLUSIONS: Heart rate reduction by cilobradine in cats with a first episode of CHF due to primary CMP did not reduce cardiac mortality and morbidity.

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

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

A review of the underlying genetics and emerging therapies for canine cardiomyopathies.

Cardiomyopathies such as dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are common in large breed dogs and carry an overall poor prognosis. Research shows that these diseases have strong breed predilections, and selective breeding has historically been recommended to reduce the disease prevalence in affected breeds. Treatment of these diseases is typically palliative and aimed at slowing disease progression and managing clinical signs of heart failure as they develop. The discovery of specific genetic mutations underlying cardiomyopathies, such as the striatin mutation in Boxer arrhythmogenic right ventricular cardiomyopathy and the pyruvate dehydrogenase kinase 4 and titin mutations in Doberman Pinschers, has strengthened our ability to screen and selectively breed individuals in an attempt to produce unaffected offspring. The discovery of these disease-linked mutations has also opened avenues for the development of gene therapies, including gene transfer and genome-editing approaches. This review article discusses the known genetics of cardiomyopathies in dogs, reviews existing gene therapy strategies and the status of their development in canines, and discusses ongoing challenges in the clinical translation of these technologies for treating heart disease. While challenges remain in using these emerging technologies, the exponential growth of the gene therapy field holds great promise for future clinical applications.