Transapical balloon dilation of cor triatriatum sinister in a cat.

A hybrid surgical approach was utilized to address cor triatriatum sinister in a 10-month-old castrated male domestic shorthair cat. Prior to surgery, open-mouth breathing occurred with exertion. The procedure was guided by transesophageal echocardiography and fluoroscopy. A minithoracotomy was performed, and the left atrial membrane was accessed via an introducer placed through the left ventricular apex. Sequential balloon dilations were performed, and the mean transmembrane gradient under anesthesia was reduced from 16 mmHg to 2.23 mmHg. Four months after surgery, the transmembrane mean gradient remained lower than prior to intervention. The cat tolerated surgery well and remains free of clinical signs nine months after surgery.

Hypereosinophilic syndrome with cardiac infiltration and congestive heart failure in a cat.

Hypereosinophilic syndrome is an uncommon disorder in the cat. It is a heterogeneous group of conditions defined by a persistent hypereosinophilia associated with organ damage directly attributable to tissue hypereosinophilia. A seven-year-old castrated domestic shorthair cat presented to the emergency service for dyspnea. Initial physical examination identified the presence of a grade III/VI systolic left parasternal murmur with no gallop or arrhythmia. A snap N-terminal-pro hormone brain natriuretic peptide was abnormal, and a point-of-care ultrasound revealed mild pleural effusion, scant pericardial effusion, and an enlarged left atrium. There was leukemia (72.35 K/uL, reference range 4.5-15.7 K/uL) predominated by eosinophilia (33.84 K/uL; reference range 0-1.9 K/uL). On echocardiogram, there was concentric hypertrophy of the left ventricular walls with irregular endocardial borders. The left atrium was enlarged with evidence of spontaneous echogenic contrast. The mitral valve was thickened with a vegetative lesion on the anterior leaflet. Despite treatment, the patient experienced cardiopulmonary arrest, and cardiopulmonary resuscitation was unsuccessful. Complete necropsy with histopathology revealed eosinophilic infiltrates in multiple organs and the presence of a severe, acute-on-chronic, fibrinous, and eosinophilic-granulomatous endomyocarditis with mural thrombosis and marked endocardial fibrosis. This case represents an unusual presentation of the hypereosinophilic syndrome in the cat with cardiac involvement and congestive heart failure as a primary clinical sign.

Primary cardiac hemangiosarcoma in a horse: echocardiographic and necropsy findings.

Cardiac hemangiosarcoma, especially primary, is infrequently reported in the horse and remains a diagnostic challenge because of vague clinical signs and difficulty to reach an antemortem diagnosis. A 17-year-old American Quarter Horse gelding was presented with a history of tongue swelling and secondary aspiration pneumonia. Initial assessment indicated dehydration, and thoracic ultrasound revealed an abnormal structure within the myocardium alongside the previously suspected aspiration pneumonia. A subsequent, complete echocardiogram identified a large, heterogeneous, ill-defined mass invading and replacing the normal myocardium of the right ventricular free wall. Because of lack of improvement the horse was euthanized, and postmortem examination confirmed primary cardiac hemangiosarcoma with no further masses identified in other organs. This case is an unusual presentation of primary cardiac hemangiosarcoma for which echocardiography played a significant role in identifying a cardiac mass.

Echocardiographic assessment of right ventricular systolic function in Boxers with arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVES: To determine whether there are differences in measures of longitudinal right ventricular (RV) systolic function among Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC) compared with healthy control Boxer dogs. To explore relationships between markers of RV systolic function and age, body weight, gender, arrhythmia frequency, and markers of left ventricular (LV) systolic function in Boxer dogs. ANIMALS: The study included 50 client-owned Boxer dogs. METHODS: This is a retrospective echocardiographic study. Tricuspid annular plane systolic excursion (TAPSE) and pulsed wave tissue Doppler imaging-derived systolic myocardial velocity of the lateral tricuspid annulus (S') were measured in healthy control Boxers (n = 18), Boxers with ARVC and normal LV systolic function (n = 19), and Boxers with ARVC and reduced LV systolic function (n = 13). RESULTS: Tricuspid annular plane systolic excursion (p=0.002) and S' (p=0.001) were significantly different between affected and control groups. Significant correlations were found between measures of left heart size and function and both TAPSE and S'. No correlations were found between RV function parameters and age, gender, or body weight in this fairly homogeneous, single-breed population. Receiver operating characteristic curve analysis revealed that both TAPSE and S' had an area under the curve of 0.77 in distinguishing healthy Boxers from those with ARVC. CONCLUSIONS: Tricuspid annular plane systolic excursion and S' are reduced in Boxers with ARVC. In contrast to prior studies evaluating these parameters in dogs of different breeds and body types, no correlation was found between markers of RV function and body weight in this population of Boxer dogs.

Extracardiac intrapericardial myxosarcoma causing right ventricular outflow tract obstruction in a dog.

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

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study.

BACKGROUND: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. OBJECTIVES: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. ANIMALS: Three hundred and fifty-four dogs with MMVD and cardiomegaly. MATERIALS AND METHODS: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. RESULTS: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.

BACKGROUND: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. HYPOTHESIS/OBJECTIVES: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. ANIMALS: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. METHODS: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. RESULTS: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

A novel, blocking, Fc-silent anti-CD40 monoclonal antibody prolongs nonhuman primate renal allograft survival in the absence of B cell depletion.

CD40-CD154 pathway blockade prolongs renal allograft survival in nonhuman primates (NHPs). However, antibodies targeting CD154 were associated with an increased incidence of thromboembolic complications. Antibodies targeting CD40 prolong renal allograft survival in NHPs without thromboembolic events but with accompanying B cell depletion, raising the question of the relative contribution of B cell depletion to the efficacy of anti-CD40 blockade. Here, we investigated whether fully silencing Fc effector functions of an anti-CD40 antibody can still promote graft survival. The parent anti-CD40 monoclonal antibody HCD122 prolonged allograft survival in MHC-mismatched cynomolgus monkey renal allograft transplantation (52, 22, and 24 days) with accompanying B cell depletion. Fc-silencing yielded CFZ533, an antibody incapable of B cell depletion but still able to potently inhibit CD40 pathway activation. CFZ533 prolonged allograft survival and function up to a defined protocol endpoint of 98-100 days (100, 100, 100, 98, and 76 days) in the absence of B cell depletion and preservation of good histological graft morphology. CFZ533 was well-tolerated, with no evidence of thromboembolic events or CD40 pathway activation and suppressed a gene signature associated with acute rejection. Thus, use of the Fc-silent anti-CD40 antibody CFZ533 appears to be an attractive approach for preventing solid organ transplant rejection.

Prospective analysis of outcomes and economic factors of same-day bilateral cataract surgery in the United States.

PURPOSE: To evaluate the visual and economic benefits of same-day bilateral cataract surgery versus separate-day bilateral cataract surgery in the United States. SETTING: Private practice, Amarillo, Texas, USA. DESIGN: Prospective controlled nonrandomized clinical trial. METHODS: A cohort of patients having same-day bilateral cataract surgery was age-matched with a cohort of control patients who had standard separate-day bilateral cataract surgery. The primary outcome was a comparison of the direct cost for the patient, physician, ambulatory surgery center (ASC), and third-party payer. RESULTS: The same-day cohort (42 patients, 84 eyes) had similar baseline characteristics and postoperative outcomes as the control cohort (42 patients, 84 eyes). The same-day cohort had less total distance traveled for care (P = .0039 and P < .0001 for in-town and out-of-town residents, respectively), less total time spent traveling for care (P = .0008 and P < .0001 for in-town and out-of-town residents, respectively), less total number of visits required for care (P < .0001), and less total time for vision recovery (P < .0001) than the control cohort. The physician and ASC reimbursements were lower in the same-day cohort (P = .0028 and P = .0016, respectively), whereas the total physician time spent caring for the patient in surgery was not different between the 2 groups (P = .7310). The total ASC expenses were higher in the same-day cohort (P < .0001). The total third-party payer cost was significantly less in the same-day cohort (P < .0001). CONCLUSION: Visual and economic benefits for the patient can be achieved with same-day bilateral cataract surgery in the U.S. at the present time. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Short-term effects of atorvastatin in normal dogs and dogs with congestive heart failure due to myxomatous mitral valve disease.

BACKGROUND: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may improve heart failure class and survival in people with congestive heart failure (CHF) of various etiologies. HYPOTHESIS/OBJECTIVES: To evaluate the tolerability of atorvastatin in healthy dogs, and the short-term effects of atorvastatin on clinical markers of disease severity, lipid profiles, and markers of systemic inflammation and oxidative stress in dogs with CHF. ANIMALS: Eleven normal dogs and 12 client-owned animals with CHF attributable to myxomatous mitral valve disease. METHODS: Prospective nonblinded observational study. Normal dogs (n = 11) were first treated with atorvastatin and re-evaluated after 14 and 30 days for clinical tolerability and alterations in certain laboratory results. Subsequently, dogs with CHF (n = 12) were treated with atorvastatin at a dosage of 2 mg/kg q24 h for 8 weeks. Echocardiography, blood pressure (BP), quality of life questionnaire, and blood sampling were performed pre and post atorvastatin administration. RESULTS: Atorvastatin was well tolerated and did not result in apparent adverse effects or biochemical abnormalities in healthy dogs and in dogs with CHF. Healthy dogs experienced a decrease in total cholesterol (TC) concentration (P = .03) after atorvastatin administration. Decreases in TC concentration (P = .02), non-HDL cholesterol concentration (P = .02), total white blood cell count (P = .03), neutrophils (P = .01), and systolic BP (P = .01) were noted in the CHF group after 8 weeks of atorvastatin. CONCLUSIONS AND CLINICAL IMPORTANCE: Atorvastatin was well tolerated at clinically relevant doses in healthy dogs and dogs with CHF. Further investigation into the effects of statin treatment in dogs with CHF is warranted.

Systemic inflammation and endothelial dysfunction in dogs with congestive heart failure.

BACKGROUND: Congestive heart failure (CHF) is associated with endothelial dysfunction in people and in dogs with experimentally induced CHF, but this is not well characterized in dogs with naturally occurring CHF. HYPOTHESIS/OBJECTIVES: To evaluate endothelial function via assessment of reactive hyperemia (RH) in healthy dogs and dogs with CHF, and to assess for relationships with plasma biomarkers of vascular function and clinical markers of disease severity. ANIMALS: Twenty client-owned animals with CHF due to myxomatous mitral valve disease (n = 15) or dilated cardiomyopathy (n = 5) and 17 healthy control dogs. METHODS: Prospective case-controlled observational study. Dogs underwent blood sampling, echocardiography, and Doppler assessment of brachial artery velocity (VTI) at baseline and during reactive hyperemia (RH-VTI). RH-VTIs between control dogs and dogs with CHF were compared, and the relationships between RH-VTI, clinical parameters, and plasma biomarkers were assessed. RESULTS: Dogs with CHF (96.5 ± 51.7%) had an attenuated % increase in VTI during RH compared to healthy controls (134.8 ± 58.7%; P = .04). Increasing ISACHC class (R(2) = 0.24; P = .004), plasma NT-proBNP (R(2) = 0.15; P = .03) and CRP (R(2) = 0.2; P = .02) were associated with reduced RH-VTI. Increased plasma CRP, NO(x) , and NT-proBNP concentrations were found in dogs with CHF (P < .02 for all). No differences were detected in other plasma markers. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with CHF have an attenuated RH response, and increased plasma CRP and NO(x) concentrations. Doppler assessment of RH velocity could represent a novel noninvasive method of evaluating endothelial function in the dog.

Effects of buthionine sulfoximine treatment on diaphragm contractility and SR Ca2+ pump function in rats.

The purpose of this study was to examine the effects of glutathione (GSH) depletion and cellular oxidation on rat diaphragm contractility and sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) function in vitro under basal conditions and following fatiguing stimulation. Buthionine sulfoximine (BSO) treatment (n = 10) for 10 days (20 mM in drinking water) reduced (P < 0.05) diaphragm GSH content (nmol/mg protein) and the ratio of GSH to glutathione disulfide (GSH/GSSG) by 91% and 71%, respectively, compared with controls (CTL) (n = 10). Western blotting showed that Hsp70 expression in diaphragm was not increased (P > 0.05) with BSO treatment. As hypothesized, basal peak twitch force (g/mm(2)) was increased (P < 0.05), and fatigability in response to repetitive stimulation (350-ms trains at 100 Hz once every 1 s for 5 min) was also increased (P < 0.05) in BSO compared with CTL. Both Ca(2+) uptake and maximal SERCA activity (mumol.g protein(-1).min(-1)) measured in diaphragm homogenates that were prepared at rest were increased (P < 0.05) with BSO treatment, an effect that could be partly explained by a twofold increase (P < 0.05) in SERCA2a expression with BSO. In response to the 5-min stimulation protocol, both Ca(2+) uptake and maximal SERCA activity were increased (P < 0.05) in CTL but not (P > 0.05) in BSO diaphragm. We conclude that 1) cellular redox state is more optimal for contractile function and fatigability is increased in rat diaphragm following BSO treatment, 2) SERCA2a expression is modulated by redox signaling, and 3) regulation of SERCA function in working diaphragm is altered following BSO treatment.

Oxidative stress and nitric oxide synthase in skeletal muscles of rats with post-infarction, compensated chronic heart failure.

AIM: Involvement of oxidative stress and nitric oxide synthase (NOS) isoforms in skeletal muscle cellular adaptations to chronic heart failure (CHF) is controversial, and possible muscle fibre-type heterogeneity in the oxidative stress and NOS responses to CHF have not been examined. Consequently, we hypothesized that the changes in determinants of elevated oxidative and nitrosylative stress associated with CHF would occur in skeletal muscle and would be similar in predominantly type I slow twitch muscle (soleus) and type II fast twitch muscle (plantaris) of rats. METHODS: The purpose of this study was to measure NOS isoforms (endothelial, inducible and neuronal NOS) and antioxidant enzymes (SOD-1, SOD-2, catalase) by protein immunoblot as well as markers of oxidative stress by biochemical assays in soleus and plantaris muscle sections of the rat hind limb. This was performed for control and post-infarction, compensated CHF rats. RESULTS: Twelve weeks after coronary artery ligation-induced moderate CHF, soleus exhibited decreased SOD-1, SOD-2 and eNOS, but increased iNOS and nNOS isoforms assessed by immunoblot. This was associated with elevated lipid and DNA oxidative damage assessed by biochemical assays. In contrast, plantaris muscle exhibited no changes in antioxidant enzymes or NOS isoforms, and had lower lipid and DNA oxidative damage. CONCLUSION: These observations suggest a heretofore unreported muscle fibre-type-specific response of oxidative stress and NOS isoforms to CHF is of importance in understanding the cellular mechanisms of skeletal muscle dysfunction in CHF.

Na+-K+-ATPase properties in rat heart and skeletal muscle 3 mo after coronary artery ligation.

This study was designed to determine whether chronic heart failure (CHF) results in changes in Na(+)-K(+)-ATPase properties in heart and skeletal muscles of different fiber-type composition. Adult rats were randomly assigned to a control (Con; n = 8) or CHF (n = 8) group. CHF was induced by ligation of the left main coronary artery. Examination of Na(+)-K(+)-ATPase activity (means +/- SE) 12 wk after the ligation measured, using the 3-O-methylfluorescein phosphatase assay (3-O-MFPase), indicated higher (P < 0.05) levels in soleus (Sol) (250 +/- 13 vs. 179 +/- 18 nmol.mg protein(-1).h(-1)) and lower (P < 0.05) levels in diaphragm (Dia) (200 +/- 12 vs. 272 +/- 27 nmol.mg protein(-1).h(-1)) and left ventricle (LV) (760 +/- 62 vs. 992 +/- 16 nmol.mg protein(-1).h(-1)) in CHF compared with Con, respectively. Na(+)-K(+)-ATPase protein content, measured by the [(3)H]ouabain binding technique, was higher (P < 0.05) in white gastrocnemius (WG) (166 +/- 12 vs. 135 +/- 7.6 pmol/g wet wt) and lower (P < 0.05) in Sol (193 +/- 20 vs. 260 +/- 8.6 pmol/g wet wt) and LV (159 +/- 10 vs. 221 +/- 10 pmol/g wet wt) in CHF compared with Con, respectively. Isoform content in CHF, measured by Western blot techniques, showed both increases (WG; P < 0.05) and decreases (Sol; P < 0.05) in alpha(1). For alpha(2), only increases [red gastrocnemius (RG), Sol, and Dia; P < 0.05] occurred. The beta(2)-isoform was decreased (LV, Sol, RG, and WG; P < 0.05) in CHF, whereas the beta(1) was both increased (WG and Dia; P < 0.05) and decreased (Sol and LV; P < 0.05). For beta(3), decreases (P < 0.05) in RG were observed in CHF, whereas no differences were found in Sol and WG between CHF and Con. It is concluded that CHF results in alterations in Na(+)-K(+)-ATPase that are muscle specific and property specific. Although decreases in Na(+)-K(+)-ATPase content would appear to explain the lower 3-O-MFPase in the LV, such does not appear to be the case in skeletal muscles where a dissociation between these properties was observed.

Skeletal muscle glycogen phosphorylase a kinetics: effects of adenine nucleotides and caffeine.

This study aimed to determine physiologically relevant kinetic and allosteric effects of P(i), AMP, ADP, and caffeine on isolated skeletal muscle glycogen phosphorylase a (Phos a). In the absence of effectors, Phos a had Vmax = 221 +/- 2 U/mg and Km = 5.6 +/- 0.3 mM P(i) at 30 degrees C. AMP and ADP each increased Phos a Vmax and decreased Km in a dose-dependent manner. AMP was more effective than ADP (e.g., 1 microM AMP vs. ADP: Vmax = 354 +/- 2 vs. 209 +/- 8 U/mg, and Km = 2.3 +/- 0.1 vs. 4.1 +/- 0.3 mM). Both nucleotides were relatively more effective at lower P(i) levels. Experiments simulating a range of contraction (exercise) conditions in which P(i), AMP, and ADP were used at appropriate physiological concentrations demonstrated that each agent singly and in combination influences Phos a activity. Caffeine (50-100 microM) inhibited Phos a (Km approximately 8-14 mM, approximately 40-50% reduction in activity at 2-10 mM P(i)). The present in vitro data support a possible contribution of substrate (P(i)) and allosteric effects to Phos a regulation in many physiological states, independent of covalent modulation of the percentage of total Phos in the Phos a form and suggest that caffeine inhibition of Phos a activity may contribute to the glycogen-sparing effect of caffeine.