Echocardiographic evaluation of velocity ratio, velocity time integral ratio, and pulmonary valve area in dogs with pulmonary valve stenosis.

BackgroundVelocity ratio, velocity time integral (VTI) ratio, and pulmonary valve area indexed to body surface area (iPVA) are methods of assessment of pulmonary valve stenosis (PS) severity that are less dependent on blood flow. Studies evaluating these methods are limited.ObjectivesTo determine the effects of butorphanol, atenolol, and balloon valvuloplasty (BV) on velocity ratio, VTI ratio, iPVA, mean PG, and max PG.AnimalsTwenty-seven dogs with PS (max PG >50 mm Hg).MethodsProspective study. All dogs underwent an echocardiogram at baseline, 5-minutes after administration of butorphanol (0.2-0.25 mg/kg IV), and 2-to-4 weeks after atenolol (1-1.5 mg/kg q12h). Twenty-one of these were evaluated 24-hours after BV.ResultsThere were no significant differences (P > .05) amongst any of the methods of assessment of PS severity after butorphanol. After atenolol, mean (SD) of mean (57.0 [21.0] mm Hg) and max PG (93.1 [33.8] mm Hg) were significantly decreased (P ≤ .047) compared with baseline (65.2 [26.2] mm Hg and 108 [44.4] mm Hg, respectively). After atenolol, there were no significant (P ≥ .12) differences in velocity ratio (0.29 [0.09]), VTI ratio (0.18 [0.05]), or iPVA (0.43 [0.16] cm2 /m2 ) compared with baseline (0.30 [0.09], 0.19 [0.09], 0.44 [0.17] cm2 /m2 , respectively).Conclusions and clinical importanceAtenolol might reduce mean and max PG but does not alter less flow-dependent methods of assessment of PS severity (velocity ratio, VTI ratio, and iPVA) in dogs with PS. Results support an integrative approach to assessment of PS severity that includes less flow-dependent methods, particularly in states of altered flow or right ventricular function

Cardiac Effects of a Single Dose of Pimobendan in Cats With Hypertrophic Cardiomyopathy; A Randomized, Placebo-Controlled, Crossover Study

Background: Pimobendan has been shown to impart a significant survival benefit in cardiomyopathic cats who receive it as part of heart failure therapy. However, use of pimobendan remains controversial in cats with hypertrophic cardiomyopathy (HCM) due to lack of pharmacodynamic data for pimobendan in cats with HCM and due to theoretical concerns for exacerbating left ventricular outflow tract obstructions. Hypothesis/Objectives: Our objective was to investigate the cardiac effects of pimobendan in cats with HCM. We hypothesized that pimobendan would not exacerbate left ventricular outflow tract obstructions and that it would improve echocardiographic measures of diastolic function. Animals: Thirteen purpose-bred cats were studied from a research colony with naturally-occurring HCM due to a variant in myosin binding protein C. Methods: Cats underwent two examinations 24 h apart with complete standard echocardiography. On their first day of evaluation, they were randomized to receive oral placebo or 1.25 mg pimobendan 1 h prior to exam. On their second examination, they were crossed over and received the remaining treatment. Investigators were blinded to all treatments. Results: The pimobendan group had a significant increase in left atrial fractional shortening (pimobendan group 41.7% ± 5.9; placebo group 36.1% ± 6.0; p = 0.04). There was no significant difference in left ventricular outflow tract (LVOT) velocities between the groups (pimobendan group 2.8 m/s ± 0.8; placebo group 2.6 m/s ± 1.0). There were no significant differences between the number of cats with LVOT obstructions between groups (12 in pimobendan group; 11 in placebo group; p = 1.00). There were no detectable differences in any systolic measures, including left ventricular fractional shortening, mitral annular plane systolic excursion, and tricuspid annular plane systolic excursion. Doppler-based diastolic function assessment was precluded by persistent tachycardia. Conclusions: Improved left atrial function in the pimobendan group could explain some of the reported survival benefit for HCM cats in CHF. Pimobendan did not exacerbate LVOT obstructions and thus may not be contraindicated in HCM cats with LVOT obstructions. Future studies are needed to better characterize other physiologic effects, particularly regarding diastolic function assessment, and to better assess safety of pimobendan over a longer time-course.Center for Companion Animal Health at the University of California Davis, School of Veterinary Medicine [2016-15-F]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Aberrant migration and surgical removal of a heartworm (Dirofilaria immitis) from the femoral artery of a cat.

A cat was evaluated for an acute-onset of right pelvic limb paresis. Thoracic radiographs revealed normal cardiac size and tortuous pulmonary arteries. Abdominal ultrasound identified a heartworm (HW) extending from the caudal abdominal aorta into the right external iliac artery and right femoral artery. The cat was HW-antigen positive. Echocardiography revealed a HW within the right branch of the main pulmonary artery and evidence of pulmonary hypertension. An agitated-saline contrast echocardiogram revealed a small right to left intracardiac shunt at the level of the atria. Surgical removal of the HW was performed with no substantial postoperative complications. There was return of blood flow and improved motor function to the limb. The cat remains mildly paretic on the affected limb with no other clinical signs

Closure of a patent ductus arteriosus in a 2-week-old llama cria using an Amplatz canine duct occluder.

A two-week-old female llama cria was brought to the UC Davis Large Animal Hospital for evaluation of a cardiac murmur and suspected syncopal episodes. A grade IV/VI left basilar continuous murmur was present on cardiac auscultation. Echocardiography revealed a left-to-right shunting patent ductus arteriosus (PDA), mild left ventricular enlargement, scant pericardial effusion, and a suspected persistent left cranial vena cava. The PDA was successfully closed with an Amplatz canine duct occluder. Mild mitral regurgitation was present on echocardiography performed 7 d following PDA occlusion. No syncopal episodes were observed in hospital prior to or following PDA occlusion. At approximately 1 mo following PDA closure, a grade I/VI left apical systolic murmur was present and the cria's body condition was improved. Key clinical message: Patent ductus arteriosus closure is achievable in New World camelids using interventional cardiology which provides a minimally invasive treatment option for valuable or companion animals. Since interventional cardiac catheterization is commonly performed in small animal species, veterinary cardiologists are well-equipped to apply these skills to camelids

A genetic polymorphism in P2RY1 impacts response to clopidogrel in cats with hypertrophic cardiomyopathy.

Clopidogrel is converted to its active metabolite by cytochrome P450 isoenzymes and irreversibly inhibits platelet activation by antagonizing the adenosine-diphosphate (ADP) receptor. It is frequently used in cats with hypertrophic cardiomyopathy (HCM) to prevent thromboembolic complications. However, significant interpatient variability of the response to clopidogrel therapy has been suspected. In this study, we assessed the impact of single nucleotide polymorphisms (SNPs) within ADP receptor (P2RY1, P2RY12) and cytochrome P450 isoenzyme (CYP2C41) genes on platelet inhibition by clopidogrel administration in cats with HCM. Forty-nine cats completed the study, and blood samples were obtained before and after clopidogrel therapy to assess the degree of platelet inhibition based on flow cytometry and whole blood platelet aggregometry. Plasma concentrations of clopidogrel metabolites were measured after the last dose of clopidogrel. Whole blood platelet aggregometry revealed a significant reduction of platelet inhibition by clopidogrel in cats with the P2RY1:A236G and the P2RY12:V34I variants. The association with the P2RY1:A236G variant and clopidogrel resistance remained significant after adjustment for multiple comparisons. This study demonstrated that a genetic polymorphism in the P2RY1 gene altered response to clopidogrel therapy and suggests that clinicians may consider alternative or additional thromboprophylactic therapy in cats with the P2RY1:A236G variant

A genetic polymorphism in P2RY 1 impacts response to clopidogrel in cats with hypertrophic cardiomyopathy

Abstract Clopidogrel is converted to its active metabolite by cytochrome P450 isoenzymes and irreversibly inhibits platelet activation by antagonizing the adenosine-diphosphate (ADP) receptor. It is frequently used in cats with hypertrophic cardiomyopathy (HCM) to prevent thromboembolic complications. However, significant interpatient variability of the response to clopidogrel therapy has been suspected. In this study, we assessed the impact of single nucleotide polymorphisms (SNPs) within ADP receptor (P2RY1, P2RY12) and cytochrome P450 isoenzyme (CYP2C41) genes on platelet inhibition by clopidogrel administration in cats with HCM. Forty-nine cats completed the study, and blood samples were obtained before and after clopidogrel therapy to assess the degree of platelet inhibition based on flow cytometry and whole blood platelet aggregometry. Plasma concentrations of clopidogrel metabolites were measured after the last dose of clopidogrel. Whole blood platelet aggregometry revealed a significant reduction of platelet inhibition by clopidogrel in cats with the P2RY1:A236G and the P2RY12:V34I variants. The association with the P2RY1:A236G variant and clopidogrel resistance remained significant after adjustment for multiple comparisons. This study demonstrated that a genetic polymorphism in the P2RY1 gene altered response to clopidogrel therapy and suggests that clinicians may consider alternative or additional thromboprophylactic therapy in cats with the P2RY1:A236G variant

Aberrant migration and surgical removal of a heartworm (Dirofilaria immitis) from the femoral artery of a cat.

A cat was evaluated for an acute-onset of right pelvic limb paresis. Thoracic radiographs revealed normal cardiac size and tortuous pulmonary arteries. Abdominal ultrasound identified a heartworm (HW) extending from the caudal abdominal aorta into the right external iliac artery and right femoral artery. The cat was HW-antigen positive. Echocardiography revealed a HW within the right branch of the main pulmonary artery and evidence of pulmonary hypertension. An agitated-saline contrast echocardiogram revealed a small right to left intracardiac shunt at the level of the atria. Surgical removal of the HW was performed with no substantial postoperative complications. There was return of blood flow and improved motor function to the limb. The cat remains mildly paretic on the affected limb with no other clinical signs

Pharmacokinetics of a single dose of Aficamten (CK‐274) on cardiac contractility in a A31P MYBPC3 hypertrophic cardiomyopathy cat model

Hypertrophic cardiomyopathy (HCM) is the most prevalent cardiac disease in cats and lacks efficacious preclinical pharmacologic intervention, prompting investigation of novel therapies. Genetic mutations encoding sarcomeric proteins are implicated in the development of HCM and small molecule myosin inhibitors are an emerging class of therapeutics designed to target the interaction of actin and myosin to alleviate the detrimental effects of inappropriate contractile protein interactions. The purpose of this study was to characterize the pharmacodynamic effects of a single oral dose of the novel cardiac myosin inhibitor aficamten (CK-274) on cardiac function in purpose bred cats with naturally occurring A31P MYBPC3 mutation and a clinical diagnosis of HCM with left ventricular outflow tract obstruction (LVOTO). Five purpose bred cats were treated with aficamten (2 mg/kg) or vehicle and echocardiographic evaluations were performed at 0, 6, 24, and 48 h post-dosing. High dose aficamten (2 mg/kg) reduced left ventricular fractional shortening (LVFS%) by increasing the LV systolic internal dimension (LVIDs) and reduced isovolumic relaxation time (IVRT) compared with baseline without significant adverse effects. The marked reduction in systolic function and reduced IVRT coupled with an increased heart rate in treated cats, suggest a lower dose may be optimal. Further studies to determine optimal dosing of aficamten are indicated

Effects of Aficamten on cardiac contractility in a feline translational model of hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease in humans and cats and lacks efficacious pharmacologic interventions in the preclinical phase of disease. LV outflow tract obstruction (LVOTO) is commonly observed in HCM-affected patients and is a primary driver of heart failure symptoms and reduced quality of life. Novel small-molecule cardiac myosin inhibitors target actin-myosin interactions to alleviate overactive protein interactions. A prospective, randomized, controlled cross-over study was performed to evaluate pharmacodynamic effects of two doses (0.3 and 1 mg/kg) of a next-in-class cardiac myosin inhibitor, aficamten (CK-3773274, CK-274), on cardiac function in cats with the A31P MYBPC3 mutation and oHCM. Dose-dependent reductions in LV systolic function, LVOT pressure gradient, and isovolumetric relaxation times compared to baseline were observed. Promising beneficial effects of reduced systolic function warrant further studies of this next-in-class therapeutic to evaluate the benefit of long-term administration in this patient population