Tolerance of torasemide in cats with congestive heart failure: a retrospective study on 21 cases (2016-2019).

BACKGROUND: In dogs with congestive heart failure (CHF), the efficacy of torasemide, a loop diuretic, has been demonstrated. However, unlike in dogs and humans little has been described about the use of torasemide in the cat with spontaneous CHF. The objectives of this retrospective study were therefore to describe the therapeutic use of oral torasemide in cats with spontaneous CHF, document its potential adverse effects while reporting the clinical course of this feline population following torasemide administration in addition to standard medical therapy. RESULTS: Medical records of 21 client-owned cats with CHF (median age = 10.6 years [interquartile range (IQR) = 6.5-11.2]) receiving torasemide were reviewed. Data collected included torasemide dosages, other concurrent medications, physical examination features, echocardiographic data, and potential adverse effects during follow-up. A survival analysis was performed to estimate the time from diagnosis to cardiac death. Dyspnea related to CHF was identified in all cats (pleural effusion [8/21], pulmonary edema [5/21] or both [8/21]), associated with ascites in 4/21 cats. The CHF cause was determined by echocardiography in all cats: hypertrophic (n = 10), restrictive (n = 6), arrhythmogenic right ventricular (n = 3), dilated (n = 1) cardiomyopathies, and aortic valve abnormality (n = 1). At initiation, median torasemide dosage was 0.21 mg/kg [IQR = 0.17-0.23] q24h. Clinical signs declined in most cats (20/21) during the first 2 weeks with no remarkable adverse events. Median survival time after torasemide prescription was 182 days [IQR = 46-330]. A contemporary control group including 54 cats with CHF, receiving furosemide as sole loop diuretic treatment was compared with the study group. Median (IQR) survival time of cats in the control group was not significatively different (p = 0.962) from that of the torasemide group, i.e., 148 days (9-364), although the torasemide group included significantly more cats with recurrent episodes of CHF (52%) that the control group (19%). CONCLUSIONS: This case series demonstrates that torasemide can be used in cats with spontaneous CHF. This therapeutic interest needs to be confirmed by prospective clinical trials.

TWO-DIMENSIONAL ECHOCARDIOGRAPHIC MEASUREMENTS IN THE BALL PYTHON (PYTHON REGIUS).

Reptiles can suffer from infectious and noninfectious cardiac pathologies, requiring the need for standardized diagnostic approaches and reference intervals. Despite the popularity of ball pythons (Python regius) as pets, echocardiographic measurements are unknown in this species. Twenty healthy adult ball pythons were evaluated to identify imaging planes, establish reference intervals for cardiac assessment by two-dimensional echocardiography, and study the effects of sex, body length, and body mass on heart rate, fractional shortening, and vascular, atrial, and ventricular dimensions. Echocardiography was performed under manual restraint. Most cardiac measurements were positively correlated with body length and mass, with the strongest correlation between ventricular end-systolic measurements and body length. The only significant difference found between sexes was for right and left atrial lengths. This study provides guidelines and reference intervals for two-dimensional echocardiographic measurements in adult healthy ball pythons.

HYPERTENSIVE HEART DISEASE AND ENCEPHALOPATHY IN A CENTRAL BEARDED DRAGON (POGONA VITTICEPS) WITH SEVERE ATHEROSCLEROSIS AND FIRST-DEGREE ATRIOVENTRICULAR BLOCK.

A 0.5 kg, 5-yr-old male bearded dragon (Pogona vitticeps) presented with a 2-mo history of lethargy, anorexia, and impaired locomotion. Upon physical examination, bradyarrhythmia (heart rate: 20 beats/min) and balance disorders were noted. Electrocardiography revealed a first-degree atrioventricular block (P-R interval: 360 ms). On echocardiography, all cardiac chambers were slightly above normal ranges. Complete blood count, blood biochemistry, and T4 were unremarkable except for mildly elevated aspartate aminotransferase. Adenovirus testing was negative by polymerase chain reaction. Following euthanasia, necropsy revealed marked thickening of the arterial trunks and histopathology confirmed multifocal atherosclerosis of efferent heart vessels, arteriosclerosis of cerebral arterioles, and multifocal spongiosis of brain tissue, more pronounced in the optic chiasma. Owing to its severity, atherosclerosis may have contributed to chronic arterial hypertension with damages to the heart, brain vessels, and brain tissue-optic chiasma.

RESTRICTIVE CARDIOMYOPATHY AND SECONDARY CONGESTIVE HEART FAILURE IN A MCDOWELL'S CARPET PYTHON (MORELIA SPILOTA MCDOWELLI).

Echocardiography is an established and noninvasive diagnostic tool used in herpetologic cardiology. Various cardiac lesions have been previously described in reptiles with the exception of restrictive cardiomyopathy. In this case report, restrictive cardiomyopathy and congestive heart failure associated with left atrial and sinus venosus dilation were diagnosed in a 2-yr-old captive lethargic McDowell's carpet python ( Morelia spilota mcdowelli), based on echocardiographic, Doppler, and histopathologic examinations. This cardiomyopathy was also associated with thrombosis within the sinus venosus.

PROPOSED SIMPLE METHOD FOR ELECTROCARDIOGRAM RECORDING IN FREE-RANGING ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

Electrocardiography represents a relevant diagnostic tool for detecting cardiac disease in animals. Elephants can present various congenital and acquired cardiovascular diseases. However, few electrophysiologic studies have been reported in captive elephants, mainly due to challenging technical difficulties in obtaining good-quality electrocardiogram (ECG) tracings, and no data are currently available for free-ranging Asian elephants (Elephas maximus). The purpose of this pilot prospective study was to evaluate the feasibility of using a simple method for recording ECG tracings in wild, apparently healthy, unsedated Asian elephants (n = 7) in the standing position. Successful six-lead recordings (I, II, III, aVR, aVL, and aVF) were obtained, with the aVL lead providing the best-quality tracings in most animals. Variables measured in the aVL lead included heart rate, amplitudes and duration of the P waves, QRS complexes, T and U waves, and duration of the PR, QT, and QU intervals. A negative deflection following positive P waves, representative of an atrial repolarization wave (Ta wave), was observed for five out of the seven elephants.

Surgical Treatment of Cor Triatriatum Sinister in a Cat Under Cardiopulmonary Bypass.

OBJECTIVE: To report the surgical repair of cor triatriatum sinister (CTS) incorporating heart-beating cardiopulmonary bypass (CPB) in a cat. STUDY DESIGN: Clinical case report. ANIMAL: Fourteen-month-old, 5.9-kg male castrated Maine Coon cat. MATERIALS AND METHODS: The cat had a 3 month history of inappetance, weight loss, and recurrent pulmonary edema. CTS with severe systolic pulmonary arterial (SPA) hypertension (124 mm Hg) was diagnosed by 2D echocardiography, color flow and continuous wave Doppler modes, and left atrial and pulmonary angiography. Surgery was performed through a left intercostal thoracotomy. CPB was initiated and the heart was kept beating. The left atrial appendage was opened and the intra-atrial membrane was excised. RESULTS: After 48 hours, the cat was doing well. Reduced SPA pressure (52 mm Hg) with decreased right heart enlargement was observed on ultrasound examination and the cat was discharged 6 days after surgery with oral antibiotics for 10 days, aspirin, and furosemide. Four months after surgery, the cat presented with increased activity and weight gain and was completely asymptomatic. Transthoracic echocardiography showed a marked improvement of all echo-Doppler variables with disappearance of SPA hypertension (24 mm Hg). Four years after surgery, the cat was still doing well with no recurrence of clinical signs despite the lack of medical treatment. CONCLUSION: CTS in the cat may be successfully treated by surgery facilitated by use of CPB leading to early and long-term substantial improvement in clinical status and cardiac function. CTS can safely be repaired under CPB in cats.

PREVALENCE OF VALVULAR REGURGITATIONS IN CLINICALLY HEALTHY CAPTIVE LEOPARDS AND CHEETAHS: A PROSPECTIVE STUDY FROM THE WILDLIFE CARDIOLOGY (WLC) GROUP (2008-2013).

The purpose of this prospective study was to evaluate transthoracic echocardiograms from clinically healthy large felids for the presence of valvular regurgitations (VR). Physiologic VR commonly occur in normal dogs and cats, but the percentage of large felids with VR has not been previously reported. During a 5-yr study period (2008-2013), 28 healthy animals were evaluated under general anesthesia: 16 cheetahs (Acinonyx jubatus soemmeringuii) with a mean age of 1.5±0.8 yr (range 0.7-3.5 yr), 5 Amur leopards (Panthera pardus orientalis), 1 snow leopard (Uncia uncia), and 6 clouded leopards (Neofelis nebulosa). For this study, all the leopards were gathered in one so-called "leopards group" with a mean age of 2.8±3.4 yr (range 0.3-10.7 yr). All valves observed in each view were examined for evidence of regurgitant jets and turbulent blood flow using the color-flow Doppler mode. Valves were also examined for structural changes. Mitral valve and aortic cusp abnormalities were considered to be of congenital origin. Mitral valve lesions led to mitral insufficiency in all the felids. Aortic cusp abnormalities led to aortic regurgitation in 94% of the cheetahs and 67% of the leopards. Leopards showed a predominance of early systolic mitral regurgitations, whereas all the mitral regurgitation jets in cheetahs were holosystolic. Tricuspid regurgitation was found in 81% of the cheetahs and in 50% of the leopards, whereas pulmonic regurgitation was detected in 44% of the cheetahs and 33% of the leopards. Interestingly, none of these tricuspid and pulmonic regurgitations were associated with two-dimensional structural valve abnormalities, thus suggesting their physiologic origin, as described in humans, cats, and dogs. In conclusion, subclinical valvular diseases are common in apparently healthy leopards and cheetahs. Longitudinal follow-up of affected animals is therefore required to assess their clinical outcome.

Long-term safety of dietary salt: A 5-year ProspEctive rAndomized bliNded and controlled stUdy in healThy aged cats (PEANUT study).

BACKGROUND: High-salt diets promote urine dilution and decrease urolithiasis risk. OBJECTIVE: Prospectively evaluate the safety of chronic high dietary salt intake (randomized controlled trial). ANIMALS: Twenty research colony neutered, healthy aged cats (11.5 years [10.0-11.6], median [interquartile range]). METHODS: Healthy cats were randomized to control or high-salt dry diets (sodium: 1.02 ± 0.16 [mean, SD] and 3.26 ± 0.30 g/Mcal metabolizable energy [ME], respectively; chloride: 2.26 ± 0.33 and 5.71 ± 0.28 g/Mcal ME, respectively), fed for up to 60 months. Assessments included CBC, plasma biochemistry, urinalysis, glomerular filtration rate (GFR), blood pressure, renal and cardiac (conventional Doppler and 2-dimensional color tissue Doppler) imaging, annually. Cats that died or were euthanized underwent necropsy. Diet effects over time were evaluated with linear mixed models. RESULTS: Follow-up duration (median [Interquartile range]) was similar between the control (38.7 months [28.6-48.2]) and high-salt group (51.4 months [45.7-59.0]). Diet had no significant effect on changes in GFR, blood pressure, plasma creatinine concentration, end-diastolic left ventricular (LV) wall thicknesses, LV internal diameters, LV systolic function, left atrial size, or systolic and diastolic Doppler variables. One control cat developed hypertension. One high-salt group cat developed persistent azotemia. Serial plasma biochemistry and urine specific gravity suggested early chronic kidney disease in 4 nonazotemic cats (2 per group), consistent with necropsy findings. CONCLUSIONS AND CLINICAL IMPORTANCE: In healthy aged cats, a commercial veterinary diet containing 3.26 ± 0.30 g/Mcal ME sodium was safe with regard to renal and cardiac function for up to 5 years.

Volumetric quantification identifies some left atrial dilations undetected by left atrium:aorta ratio measurements: A prospective echocardiographic study in 155 Cavalier King Charles Spaniels with and without degenerative mitral valve disease.

INTRODUCTION: Degenerative mitral valve disease (DMVD) is the most common canine heart disease with a high predisposition in Cavalier King Charles Spaniels (CKCSs). Mitral regurgitation related to DMVD can lead to left atrial (LA) dilation, which is associated with survival time. Left-atrial-to-aortic (LA:Ao) ratio assessed by two-dimensional echocardiography is commonly used to evaluate LA size. The objectives of this prospective observational study were therefore 1) to compare different echocardiographic methods (i.e., monoplane and biplane Simpson's methods of discs (SMOD) and area-length methods (ALM)) in evaluating LA volume (LAvol) in CKCSs, 2) to assess LA volumes according to DMVD severity and, 3) compare the ability of LAvol and LA:Ao ratio to identify LA enlargement in CKCSs with subclinical DMVD (i.e., American College of Veterinary Internal Medicine (ACVIM) stage B). MATERIALS AND METHODS: 155 CKCSs, either healthy or affected by DMVD, were recruited. Variability and concordance between volumetric methods were evaluated. Values were analyzed according to 2019 ACVIM stages. RESULTS: All Lin's concordance correlation coefficients regarding intra- and inter-observer variability were considered as very good to excellent. Monoplane methods and ALM produced higher values of LAvol than biplane methods and SMOD, respectively. The upper limit of normal end-systolic LAvol/body weight (LASvol/BW) was defined as 0.90 mL/kg. Left atrial volumes significantly increased with ACVIM stages. Additionally, 37% of stage B1 CKCSs demonstrated LA enlargement using LASvol/BW assessment, with significantly lower LASvol/BW values in dogs with regurgitation fraction ≤30% than in others (p<0.01). CONCLUSION: In CKCSs, LAvol methods are not interchangeable. In ACVIM stage B CKCSs, LAvol quantification is more effective to detect LA enlargement than LA linear measurements.

Congenital ventricular outflow tract obstructions in Boxer dogs: Results of a 17-year cardiovascular breed screening program in France (3126 dogs).

INTRODUCTION: Ventricular outflow tract obstructions including aortic (AS) and pulmonic stenosis (PS) are the most common canine congenital heart diseases, with Boxer dogs being predominantly affected. This has led to the French Boxer club adopting a mandatory national control program against AS and PS. The objective of this retrospective study was to analyze the results of 17 years of this cardiovascular breed screening program (2005-2021). MATERIALS AND METHODS: The records of untreated and non-anesthetized adult Boxer dogs screened between 2005 and 2021 were retrospectively reviewed. All dogs underwent physical examination and standard transthoracic echocardiography with concomitant ECG tracing. All examinations were reviewed by one single board-certified specialist in cardiology. RESULTS: Out of the 3126 dogs screened during the study period, 3001 dogs (female:male sex ratio = 2.2, median age [IQR] = 1.6 years [1.2-2.1]) were recruited for data analysis. A total of 218 operators were involved in the screening program. For most Boxer dogs (i.e., 93.8% for AS and 94.5% for PS), a single examination was required to obtain a definitive cardiac status, although most operators were non-specialist general practitioners. A left basilar systolic heart murmur was detected in all dogs with AS and PS, but also in 7.4% dogs free of heart diseases. A significantly higher proportion of the latter was detected when operators were board-certified specialists (P<0.001). Lastly, when comparing the start and the end of the breeding program, among dogs diagnosed with AS and PS (n = 364) in a French referral cardiology center, Boxer went from the 1st affected breed by AS to the 3rd, and from the 3rd affected breed by PS to the 6th. CONCLUSION: This 17-year screening program has experienced a strong involvement of veterinarians, breeders, and owners throughout France. This may have contributed to reduce AS and PS prevalence in Boxer dogs at the studied referral cardiology center.

Systolic third sound associated with systolic anterior motion of the mitral valve in cats with obstructive hypertrophic cardiomyopathy.

BACKGROUND: Third heart sounds in cats frequently are associated with hypertrophic cardiomyopathy (HCM) but their exact characterization and timing within the cardiac cycle remains unknown. OBJECTIVES: Characterize third heart sounds in cats by phonocardiography and test the ability of 3 observers with different levels of experience and training to recognize third systolic heart sounds in cats. ANIMALS: Fifty client-owned cats of different breeds presented for heart screening. METHODS: Cats were prospectively assessed using an electronic stethoscope (with digital recording) and then underwent full conventional echocardiographic examination. Audio recordings were blindly assessed in a random order by 3 observers: the cardiologist who collected clinical data, as well as a trained and an untrained junior veterinarian. Cohen's kappa coefficients were calculated to quantify agreement between the opinion of each observer and the echocardiography results (considered the gold standard). RESULTS: Twenty cats had a third systolic sound on phonocardiography and an obstructive HCM phenotype with systolic anterior motion of the mitral valve (SAM) on echocardiography. Agreement with echocardiography was very good for the experienced cardiologist, substantial for the trained junior veterinarian, and poor for the untrained junior veterinarian (kappa of 0.92, 0,64, and 0.08, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: We describe here a new auscultatory abnormality in cats with obstructive HCM. It could help a trained non-cardiologist veterinarian in suspecting obstructive HCM in cats based on auscultation only.

Prospective evaluation of a telmisartan suppression test as a diagnostic tool for primary hyperaldosteronism in cats.

BACKGROUND: In a previous study, telmisartan suppressed aldosterone secretion in healthy cats but not in cats with primary hyperaldosteronism (PHA). HYPOTHESES: Telmisartan suppresses aldosterone secretion in middle-aged healthy cat and cats with diseases that may result in secondary hyperaldosteronism, but not in those with PHA. ANIMALS: Thirty-eight cats: 5 with PHA; 16 with chronic kidney disease (CKD), subclassified as hypertensive (CKD-H) or non-hypertensive (CKD-NH); 9 with hyperthyroidism (HTH); 2 with idiopathic systemic arterial hypertension (ISH); and 6 healthy middle-aged cats. METHODS: Prospective, cross-sectional study. Serum aldosterone concentration, potassium concentration, and systolic blood pressure were measured before and 1 and 1.5 hours after PO administration of 2 mg/kg of telmisartan. The aldosterone variation rate (AVR) was calculated for each cat. RESULTS: No significant difference in the minimum AVR was observed among groups (median [quartile 1 (Q1); quartile 3 (Q3)]: 25 [0; 30]; 5 [-27; -75]; 10 [-6; -95]; 53 [19; 86]; 29 [5; 78]) for PHA, CKD, HTH, ISH, and healthy cats, respectively (P = .05). Basal serum aldosterone concentration (pmol/L) was significantly higher in PHA cats (median [Q1; Q3]: 2914 [2789; 4600]) than in CKD-H cats (median [Q1; Q3]: 239 [189; 577], corrected P value = .003) and CKD-NH cats (median [Q1; Q3]: 353 [136; 1371], corrected P value = .004). CONCLUSIONS AND CLINICAL IMPORTANCE: The oral telmisartan suppression test using a single dose of 2 mg/kg telmisartan did not discriminate cats with PHA from healthy middle-aged cats or cats with diseases that may result in secondary hyperaldosteronism.

Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS.

Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscular dystrophy (GRMD) dogs with left ventricular dysfunction (measured by echocardiography) and in isolated coronary arteries. eNOS and nNOS proteins in carotid arteries were measured by western blot and cyclic guanosine monophosphate (cGMP) content was analyzed by radioimmunoassay. Compared with controls, GRMD dogs had an impaired vasodilator response to acetylcholine. In isolated coronary artery, acetylcholine-elicited relaxation was nearly absent in placebo-treated GRMD dogs. This was explained by reduced nNOS and eNOS proteins and cGMP content in arterial tissues. Chronic bradykinin infusion (1 µg/min, 4 weeks) restored in vivo and in vitro vascular response to acetylcholine to the level of control dogs. This effect was NO-mediated through upregulation of eNOS and nNOS expression. In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin.

CardiOvascular examination in awake Orangutans (Pongo pygmaeus pygmaeus): Low-stress Echocardiography including Speckle Tracking imaging (the COOLEST method).

INTRODUCTION: Cardiovascular diseases have been identified as a major cause of mortality and morbidity in Borneo orangutans (Pongo pygmaeus pygmaeus). Transthoracic echocardiography is usually performed under anesthesia in great apes, which may be stressful and increase risks of peri-anesthetic complications in case of cardiac alteration. The aim of the present pilot study was hence to develop a quick and non-stressful echocardiographic method (i.e., the COOLEST method) in awake Borneo orangutans (CardiOvascular examination in awake Orangutans: Low-stress Echocardiography including Speckle Tracking imaging) and assess the variability of corresponding variables. MATERIALS AND METHODS: Four adult Borneo orangutans trained to present their chest to the trainers were involved. A total of 96 TTE examinations were performed on 4 different days by a trained observer examining each orangutan 6 times per day. Each examination included four two-dimensional views, with offline assessment of 28 variables (i.e., two-dimensional (n = 12), M-mode and anatomic M-mode (n = 6), Doppler (n = 7), and speckle tracking imaging (n = 3)), representing a total of 2,688 measurements. A general linear model was used to determine the within-day and between-day coefficients of variation. RESULTS: Mean±SD (minimum-maximum) images acquisition duration was 3.8±1.6 minutes (1.3-6.3). All within-day and between-day coefficients of variation but one (n = 55/56, 98%) were <15%, and most (51/56, 91%) were <10% including those of speckle tracking systolic strain variables (2.7% to 5.4%). DISCUSSION: Heart morphology as well as global and regional myocardial function can be assessed in awake orangutans with good to excellent repeatability and reproducibility. CONCLUSIONS: This non-stressful method may be used for longitudinal cardiac follow-up in awake orangutans.

Retrospective evaluation of hypertrophic cardiomyopathy in 68 dogs.

BACKGROUND: There is a lack of clinical data on hypertrophic cardiomyopathy (HCM) in dogs. HYPOTHESIS/OBJECTIVES: To investigate signalment, clinical signs, diagnostic findings, and survival in dogs with HCM. ANIMALS: Sixty-eight client-owned dogs. METHODS: Retrospective multicenter study. Medical records were searched between 2003 and 2015. The diagnosis of left ventricular (LV) hypertrophy was made by echocardiographic examination. RESULTS: Three hundred and forty-five dogs with LV hypertrophy were identified, of which 277 were excluded. The remaining 68 dogs were 0.3 to 14 years old and predominantly <10 kg (85%), and without a sex predilection. Twenty-four % were Shih Tzu and 24% terrier breeds. Most (80%) had a systolic heart murmur. Owner-determined exercise intolerance (37%) and syncope (18%) were most commonly reported signs. The majority (84%) of dogs had symmetrical LV hypertrophy, whereas asymmetrical septal and LV free wall hypertrophy was observed in 9% and 6% of dogs, respectively. Isolated basal interventricular septal hypertrophy was not observed. Commonly recorded were systolic anterior motion of the mitral valve (60%) and LV diastolic dysfunction (89% of dogs where diastolic function was evaluated). Six dogs died unexpectedly, and 3 developed congestive heart failure. Known survival times were between 1 day and 114 months after diagnosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypertrophic cardiomyopathy in dogs should be considered as a differential diagnosis if LV hypertrophy is identified. Small breed dogs are overrepresented, and it is uncommon for dogs with HCM to develop CHF although sudden death can occur.

Identification of 2 loci associated with development of myxomatous mitral valve disease in Cavalier King Charles Spaniels.

Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs. It is characterized by chronic progressive degenerative lesions of the mitral valve. The valve leaflets become thickened and prolapse into the left atrium resulting in mitral regurgitation (MR). MMVD is most prevalent in small to medium sized dog breeds, Cavalier King Charles Spaniels (CKCS) in particular. The onset of MMVD is highly age dependent, and at the age of 10 years, nearly all CKCS are affected. The incidence of a similar disease in humans-mitral valve prolapse-is 1-5%. By defining CKCSs with an early onset of MMVD as cases and old dogs with no or mild signs of MMVD as controls, we conducted a genome-wide association study (GWAS) to identify loci associated with development of MMVD. We have identified a 1.58 Mb region on CFA13 (P(genome) = 4.0 × 10(-5)) and a 1.68 Mb region on CFA14 (P(genome) = 7.9 × 10(-4)) associated with development of MMVD. This confirms the power of using the dog as a model to uncover potential candidate regions involved in the molecular mechanisms behind complex traits.

Chronic heart rate reduction with ivabradine improves systolic function of the reperfused heart through a dual mechanism involving a direct mechanical effect and a long-term increase in FKBP12/12.6 expression.

AIMS: To investigate the adaptations of left ventricular function and calcium handling to chronic heart rate reduction with ivabradine in the reperfused heart. METHODS AND RESULTS: Rabbits underwent 20 min coronary artery occlusion followed by 3 weeks of reperfusion. Throughout reperfusion, rabbits received ivabradine (10 mg/kg/day) or vehicle (control). Ivabradine reduced heart rate by about 20% and improved both ejection fraction (+35%) and systolic displacement (+26%) after 3 weeks of treatment. Interestingly, this was associated with a two-fold increase expression of FKBP12/12.6. There was no difference in the expressions of phospholamban, SERCA2a, calsequestrin, ryanodine, phospho-ryanodine, and Na(2+)/Ca(2+) exchanger in the two groups. Infarct scar and vascular density were similar in both groups. Administration of a single intravenous bolus of ivabradine (1 mg/kg) in control rabbits at 3 weeks of reperfusion also significantly improved acutely ejection fraction and systolic displacement. CONCLUSION: Chronic heart rate reduction protects the myocardium against ventricular dysfunction induced by myocardial ischaemia followed by 3 weeks of reperfusion. Beyond pure heart rate reduction, ivabradine improves global and regional systolic function of the reperfused heart through a dual mechanism involving a direct mechanical effect and a long-term adaptation in calcium handling, as supported by the increase in FKBP12/12.6 expression.

Red blood cell abnormalities occur in dogs with congenital ventricular outflow tract obstruction.

OBJECTIVE: To document RBC abnormalities in dogs with congenital ventricular outflow tract obstruction. ANIMALS: 62 dogs with pulmonic stenosis (PS) or aortic stenosis (AS) and 20 control dogs were recruited. PROCEDURES: The proportions of RBCs that were schistocytes, acanthocytes, and keratocytes were assessed. Complete blood cell counts were performed. Tested variables included hemoglobin concentration, hematocrit, and erythrocyte count. RESULTS: Median (interquartile range [IQR]) peak systolic Doppler-derived trans-stenotic pressure gradient (∆P) values were 161 mm Hg (108 to 215 mm Hg) and 134 mm Hg (125 to 165 mm Hg) for dogs with PS and AS, respectively. Hematologic abnormalities were detected in most dogs with AS or PS (54/62 [87%]) versus 8/20 [40%] in control dogs, with schistocytes found in 40 of 62 (65%; median, 0.1% RBCs; IQR, 0% to 0.3%), acanthocytes in 29 of 62 (47%; median, 0.3% RBCs; IQR, 0% to 0.9%), keratocytes in 39 of 62 (63%; median, 0% RBCs; IQR, 0% to 0.2%), and hemolytic anemia in 4 dogs with PS. No significant association was identified between these abnormalities and ∆P. However, 3 of 4 dogs with anemia had a ∆P > 200 mm Hg (range, 242 to 340 mm Hg). The dog with the highest ∆P value also had the most severe anemia and schistocytosis, and both resolved after balloon valvuloplasty. CLINICAL RELEVANCE: Poikilocytosis is common in dogs with congenital ventricular outflow tract obstruction, with anemia only observed in few dogs with high ∆P values.

Myocarditis and Subclinical-Like Infection Associated With SARS-CoV-2 in Two Cats Living in the Same Household in France: A Case Report With Literature Review.

This report provides the first clinical, radiographic, echocardiographic, and biological description of SARS-CoV-2-associated myocarditis with a 6-month follow-up in a 5-year-old obese male domestic shorthair cat (Cat-1) presented for refractory congestive heart failure, with high cardiac troponin-I level (5.24 ng/ml), and a large lingual ulcer. The animal was SARS-CoV-2 positive on serology. The other cat living in the same household (Cat-2) never showed any clinical sign but was also confirmed SARS-CoV-2 positive on serology. Both cats were SARS-CoV-2 PCR negative. Cat-1 had closer contact than Cat-2 with their owner, who had been in close contact with a coworker tested PCR positive for COVID-19 (Alpha (B.1.1.7) variant) 4 weeks before Cat-1's first episode of congestive heart failure. A focused point-of-care echocardiography at presentation revealed for Cat-1 numerous B-lines, pleural effusion, severe left atrial dilation and dysfunction, and hypertrophic cardiomyopathy phenotype associated with focal pulmonary consolidations. Both myocarditis and pneumonia were suspected, leading to the prescription of cardiac medications and antibiotics. One month later, Cat-1 recovered, with normalization of left atrial size and function, and radiographic and echocardiography disappearance of heart failure signs and pulmonary lesions. An extensive literature review of SARS-CoV-2-related cardiac injury in pets in comparison with human pathology is discussed.

Stabilizing Ryanodine Receptors Improves Left Ventricular Function in Juvenile Dogs With Duchenne Muscular Dystrophy.

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 Ca2+ in GRMD cardiomyocytes than in controls. ARM036 prevented those in vivo and in vitro dysfunctions in GRMD dogs. Myofilament Ca2+-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.