Hybrid balloon valvuloplasty for management of severe mitral stenosis in four symptomatic, adult dogs.

Four adult dogs weighing <10 kg presented for the evaluation of severe mitral valve stenosis with clinical signs. Owing to the size of the dogs, a hybrid surgical and interventional approach was utilized for balloon valvuloplasty. A left lateral thoracotomy was performed to allow direct entry through the left atrial wall. Transesophageal echocardiography was utilized for the entirety of the procedure in all dogs, and fluoroscopy was additionally used in two dogs. One dog had mild to moderate intra-operative bleeding from the left atrial wall during the procedure, but no other intra-operative complications were observed. No dogs developed a clinically relevant amount of worsened mitral regurgitation. Based on mitral leaflet mobility and transmitral flow profiles, there was perceived improvement in all four dogs. One dog died 6 h after extubation due to respiratory arrest. The remaining dogs survived to discharge and had resolution of clinical signs at home and discontinuation of heart failure medications. One dog died of an unknown cause at five months and another developed atrial fibrillation, and the owners elected to euthanize at ten months after the procedure. One dog continues to do well six months after the procedure as of the time of this writing. Hybrid balloon valvuloplasty can be a viable management option for small breed dogs with severe mitral stenosis exhibiting clinical signs, and both transesophageal echocardiography and fluoroscopy can be used intra-operatively to assist in successful procedural outcomes.

Transient high-grade second-degree atrioventricular block secondary to transvenous atrial septal defect occlusion in a dog.

A 1.2-year-old male-intact Standard Poodle underwent transvenous placement of an Amplazter™ atrial septal occluder for correction of a large secundum atrial septal defect. Thirty-six hours post-operatively, the dog developed high-grade Mobitz type II second-degree atrioventricular block, which resolved with time and corticosteroid administration by 12 days after the procedure. This case report outlines the observation, treatment, and resolution of high-grade Mobitz type II second-degree atrioventricular block, a known complication of atrial septal occluder placement in humans, not previously reported in veterinary literature.

Repeat balloon valvuloplasty for dogs with recurrent or persistent pulmonary stenosis.

INTRODUCTION/OBJECTIVES: Pulmonary stenosis (PS) is a common congenital defect in the dog. Severe valvar PS can be treated with balloon valvuloplasty (BV) to reduce obstruction severity and improve clinical signs. Repeat BV is often unnecessary, as restenosis is uncommon. Repeated pulmonary BV in people is generally successful and safe, but outcomes in dogs with recurrent or persistent stenosis have not been reported. The objectives of this study were to retrospectively evaluate outcomes of repeat BV in dogs. ANIMALS, MATERIALS, AND METHODS: Medical records and stored echocardiographic images were reviewed from dogs that received repeat BV for pulmonary valvar restenosis or persistent stenosis. Echocardiographic variables included maximum systolic ejection velocity (PVmax), velocity-derived maximal pressure gradient (PGmax) and velocity time integral (VTI) across the pulmonary valve, and ratios of pulmonic to aortic maximum velocity (PVmax/AVmax) and VTI (VTIPV/VTIAV). RESULTS: Twenty-three dogs were included; one underwent three BV procedures. The median time between BV procedures was 18.3 months (interquartile range, 6.3-43.6). One dog died during repeat BV, but no others experienced adverse effects. Reductions in PVmax, PGmax, and VTIPV after initial and repeat BV were 1.85 m/s, 76.2 mmHg, and 44.7 cm and 1.33 m/s, 55.6 mmHg, and 30.2 cm, respectively (all p < 0.01). Differences between pre-BV and post-BV PVmax, PGmax, VTIPV, PVmax/AVmax, and VTIPV/VTIAV were not different comparing initial to repeat BV (all p > 0.10). CONCLUSIONS: Repeat BV for recurrent or persistent PS is well tolerated and effective in a majority of dogs.

Idiopathic pulmonary arterial hypertension in a pot-bellied pig (Sus scrofa domesticus) with right-sided congestive heart failure.

Idiopathic pulmonary arterial hypertension is a rare disease reported in humans and dogs diagnosed as persistent elevation of pulmonary arterial blood pressure without predisposing or associated diseases. A four-month-old pot-bellied pig (Sus scrofa domesticus) was presented for decreased appetite, lethargy, respiratory distress, and occasional syncope. On physical examination, the pig was tachypneic with labored breathing, with a distended abdomen and a bilateral grade 4-5/6 parasternal systolic heart murmur. Systolic pulmonary arterial pressure was estimated at 95 mmHg by Doppler echocardiography, consistent with severe pulmonary hypertension. At autopsy, there was dilation of the main pulmonary artery and right ventricle. The lungs were diffusely rubbery, and there was tricavitary effusion. Microscopically, there was severe widespread pulmonary arterial concentric medial hypertrophy with rare plexiform lesions. The clinical history and gross and microscopic findings supported a diagnosis of idiopathic pulmonary arterial hypertension with subsequent right-sided congestive heart failure. Primary (idiopathic) pulmonary arterial hypertension should be considered as a differential diagnosis in young pigs with right-sided congestive heart failure.

Treatment of caudal cavoatrial junction obstruction in a dog with a balloon-expandable biliary stent.

A 2-year-old intact female mixed breed dog was presented for ascites. Echocardiography demonstrated severe obstruction at the level of the caudal right atrium. Initially, a variant of cor triatriatum dexter was diagnosed, and balloon catheter dilation was performed. However, ascites recurred within a week. Further imaging revealed an obstruction at the entrance of the caudal vena cava into the right atrium rather than a dividing membrane in the right atrium. The diagnosis was revised to suprahepatic obstruction of the caudal vena cava because of remnant Eustachian valve tissue. Deployment of a balloon-expandable biliary stent was performed relieving the obstruction. Fifteen months after stent deployment, the patient is doing well without reaccumulation of ascitic fluid.

Doppler-derived echocardiographic evidence of pulmonary hypertension in cats with left-sided congestive heart failure.

INTRODUCTION: Pulmonary hypertension (PH) caused by left-sided congestive heart failure (L-CHF) is common in dogs and contributes to clinical signs and outcome. The aim of this study was to evaluate the prevalence of Doppler echocardiography-derived PH in a population of cats with L-CHF. ANIMALS: The study involved 131 cats with L-CHF and 56 control cats. METHODS: The study design is retrospective, observational study. Tricuspid regurgitation velocity, right atrial dimension, right ventricular (RV) dimension and function, RV wall thickness, pulmonary artery (PA) dimension, Doppler-derived systolic time intervals of PA flow, and presence of septal flattening were evaluated. Pulmonary hypertension was considered if tricuspid regurgitation velocity was >2.7 m/s. RESULTS: Tricuspid regurgitation was present in 57/131 (44%) of cats with L-CHF and 24/56 (43%) in control cats based on color flow Doppler. Doppler-derived of PH was identified in 22/131 cats with L-CHF (17%). In 15/22 cats, PH was associated with cardiomyopathy, in 5/22 cases with congenital heart disease, and in 2/22 cases with other causes. Cats with Doppler-derived PH more often had chronic L-CHF, as opposed to acute L-CHF (p<0.05). All cats with Doppler-derived PH had subjectively-assessed right-sided heart enlargement, with larger right atrial and RV diameters (p<0.001), increased RV wall thickness (p<0.05), and higher prevalence of septal flattening (<0.001) and PA enlargement (p<0.05). CONCLUSIONS: Pulmonary hypertension identified by Doppler echocardiography is not a common finding in cats with L-CHF. Right-sided heart enlargement, more frequently observed, may raise the suspicion of PH in cats with L-CHF.

Echocardiographic Estimates of Right Ventricular Systolic Function in Dogs with Myxomatous Mitral Valve Disease.

BACKGROUND: Right ventricular (RV) dysfunction independently predicts outcomes in human myxomatous mitral valve disease (MMVD). There is limited information regarding RV systolic function in dogs with MMVD. HYPOTHESIS: Right ventricular systolic function differs among stages of disease, decreasing in decompensated MMVD. ANIMALS: Thirty-sixclient-owned dogs with MMVD not receiving oral cardiovascular medications. METHODS: Prospective clinical study. Dogs were categorized according to disease severity as ACVIM Stage B1, B2, or C. Seven echocardiographic indices of RV systolic function were measured. Groups were compared by 1-way ANOVA and Tukey's HSD test. Frequencies of cases with cardiac remodeling falling outside previously established reference intervals were compared using Fisher's exact test. Intra- and interobserver measurement variability was calculated for each RV function index. RESULTS: The indices TAPSE (P = 0.029), RV StL (P = 0.012), and RV StRL (P = 0.041) were significantly different between groups. A greater proportion of B2 dogs (7 of 12) had TAPSE values above reference intervals compared with B1 (2 of 12) or C (2 of 12) dogs (P = 0.027). Measurement variability of TAPSE, RV S', and RV StG was clinically acceptable. CONCLUSIONS AND CLINICAL IMPORTANCE: Right ventricular systolic function differs between stages of MMVD, increasing in stage B2, and declining in stage C. The prognostic importance of RV function indices, particularly TAPSE, might be worth evaluating in dogs with MMVD.

Effect of Body Position, Exercise, and Sedation on Estimation of Pulmonary Artery Pressure in Dogs with Degenerative Atrioventricular Valve Disease.

BACKGROUND: Severity of pulmonary hypertension (PH) in dogs is related to clinical signs and prognosis. HYPOTHESIS/OBJECTIVES: We hypothesized that Doppler echocardiographic (DE) indices of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) are influenced by independent factors that create clinically important variability of DE-based estimates of PH in dogs. ANIMALS: Thirty-eight client owned dogs with naturally acquired degenerative atrioventricular valve disease and tricuspid regurgitation (TR). METHODS: Dogs were prospectively enrolled, and target variables were acquired during 4 echocardiographic study periods (lateral recumbency, standing, lateral recumbency after a 6-minute walk test [6MWT], and lateral recumbency after sedation with butorphanol 0.25 mg/kg IM). Statistical methods included repeated measures ANOVA, mixed model analysis, and Chi-squared test of association. RESULTS: There was a significant increase in peak TR flow velocity (TRFV; P < 0.01) after sedation in 78% of dogs, with TRFV increasing by >0.4 m/s in 42% of dogs, independent of stroke volume. A significant effect of study period on DE-estimated PVR was not found (P = 0.15). There were negligible effects of sonographer, body position, and 6MWT on echocardiographic variables of PH. Clinically relevant cyclic variation of TRFV was found. There was an association between estimation of right atrial pressure based on subjective assessment and estimation based on cranial vena cava collapsibility (P = 0.03). CONCLUSIONS AND CLINICAL IMPORTANCE: The increase in TRFV observed with sedation could change assessment of PH severity and impact prognostication and interpretation of treatment response. Further studies with invasive validation are needed.

Interventional Closure of a Patent Ductus Arteriosus Using an Amplatz Canine Duct Occluder in an Alpaca Cria.

A 6-month old female alpaca cria presented to The Ohio State University for evaluation of a cardiac murmur. Echocardiography revealed a left-to-right shunting patent ductus arteriosus, a restrictive left-to-right shunting perimembranous ventricular septal defect, and secondary moderate left atrial and ventricular dilation. Aortic root angiography demonstrated a type IIA patent ductus arteriosus (PDA). Interventional closure of the PDA was successfully performed, without complication, using an Amplatz canine duct occluder. This case report describes the materials and methods used for interventional closure of a PDA in an alpaca cria.

Right ventricular involvement in feline hypertrophic cardiomyopathy.

OBJECTIVES: To evaluate right ventricular (RV) wall thickness and chamber dimensions in cats with hypertrophic cardiomyopathy (HCM). ANIMALS: One hundred fifty-one healthy control cats and 200 cats with HCM. METHODS: Retrospective, observational, clinical cohort study. Two-dimensional echocardiograms from all cats were analyzed. Right atrial diameter, RV free wall thickness, and RV chamber diameter were quantified using multiple imaging views. Conventional (mean ± 2 standard deviations) and allometrically scaled (Y = a × Mb) reference values were determined in normal cats and compared to values found in cats with HCM. Linear and logistic regression, multivariate regression, and mixed model analysis were performed to identify associations between RV wall thickness and severity of left ventricular (LV) hypertrophy, clinical severity of HCM, and presence of pleural effusion. RESULTS: Mean RV wall thickness was increased in HCM (p<0.001). Considering increased RV wall thickness in at least one segment, 94 (47%) and 112 (56%) cats with HCM had RV hypertrophy using upper reference limits based on mean + 2 standard deviations or allometric scaling, respectively. There was an association between severity of LV and RV hypertrophy (p<0.05). Left-sided congestive heart failure (n = 58) was associated with increased RV wall thickness in all segments compared to cats with preclinical HCM (p<0.001). Body weight had negligible effects on RV wall thickness (R2 0.08-0.17, p<0.001), whereas age and breed had no effect (p>0.05) in control cats. CONCLUSIONS: Increased RV wall thickness is common in cats with HCM and relates to severity of LV hypertrophy and clinical status.

Detection of hypoxia markers in the cerebellum after a traumatic frontal cortex injury: a human postmortem gene expression analysis.

PURPOSE: The response to traumatic brain injury (TBI) is complex and induces various biological pathways in all brain regions that contribute to bad outcomes. The cerebellar hypoxia after a frontal cortex injury may potentiate the pathophysiological impacts of TBI. Therefore, a gene expression analysis was conducted to determine the influence of hypoxia on TBIs. MATERIAL AND METHODS: Total RNA, including microRNAs, was isolated from the cerebellum of individuals who had died from severe frontal cortex injuries or due to natural causes of death (reference group). RESULTS: From a total of 19,596 genes, an average of 59.56% messenger RNAs (mRNAs) appeared expressed with 42 of them showing significant >2-fold differences of upregulated (n = 18) and downregulated (n = 24) genes. The validity of 14 candidate genes (with low p values and high fold differences or based on cited literature) was confirmed using qRT-PCR (Spearman correlation r(2) = 0.93). Only four genes appeared to be either upregulated (FOSB and IL6) or downregulated (HSD11B1 and HSPA12B). From a total of 667 microRNAs, altogether, 248 microRNAs appeared expressed with 13 of them showing significant differences in the mean gene expression. The combination of two mRNAs (HSPA12B/FOSB or IL6/HSD11B1) or two microRNAs (either miR-138/miR-744 or miR-195/miR-324-5p) completely discriminated both groups, a finding unaltered by potential confounders such as age at biosampling, survival time, and the postmortem interval. CONCLUSIONS: Cerebellar hypoxia markers are important to understand the pathophysiology of TBIs and could be used for therapeutic strategies or forensic purposes, e.g., to assess the severity of a brain injury.

Acute effects of ivabradine on dynamic obstruction of the left ventricular outflow tract in cats with preclinical hypertrophic cardiomyopathy.

BACKGROUND: Ivabradine is a negative chronotropic drug with minimal effects on central hemodynamics. Its effect on dynamic obstruction of the left ventricular outflow tract (LVOT) in cats with hypertrophic cardiomyopathy (HCM) remains unknown. HYPOTHESIS/OBJECTIVES: Ivabradine reduces dynamic obstruction of the LVOT in cats with HCM. ANIMALS: Twenty-eight client-owned cats with preclinical HCM and dynamic LVOT obstruction. METHODS: Randomized, double-blind, active-control single dose study. Cats received a single dose of either ivabradine (0.3 mg/kg PO) or atenolol (2 mg/kg PO). Heart rate, echocardiographic variables, and systolic blood pressure (SBP) were recorded before and 3 hours after drug administration. Statistical comparisons were made using ANCOVA. RESULTS: Peak velocity in the LVOT was significantly decreased compared to baseline for both drugs; however, the effect was more prominent with atenolol (mean reduction 2.53 m/s; 95% CI 2.07-3.13 m/s) compared to ivabradine (mean reduction 0.32 m/s; 95% CI -0.04 to 0.71 m/s; P < .0001). Echocardiographic indices of systolic function were largely unchanged by ivabradine, but significantly reduced by atenolol. CONCLUSIONS AND CLINICAL IMPORTANCE: A single dose of ivabradine decreases dynamic LVOT obstruction in cats with HCM, but the clinical effect is negligible and inferior compared to that achieved by atenolol.

Tachycardia-induced cardiomyopathy in a cat.

A 10-year-old male castrated Domestic Shorthair cat was evaluated for an asymptomatic tachyarrhythmia noted two weeks prior. Electrocardiography revealed a normal sinus rhythm with atrial premature complexes and paroxysms of supraventricular tachycardia with a heart rate between 300 and 400 min-1. Echocardiography was unremarkable, and concentrations of circulating cardiac troponin I, T4, and blood taurine were within reference ranges. The cat was treated with sotalol (2.1 mg/kg q12h, PO) but the arrhythmia was insufficiently controlled as determined during several re-examinations within a two-year time period. Twenty four months after initial presentation atrial fibrillation with fast ventricular response rate (200 to 300 min-1) was diagnosed, along with severe eccentric chamber remodeling and systolic dysfunction. The cat developed congestive heart failure and cardiogenic shock and was euthanized nearly 27 months after the first exam. Gross and histopathologic findings ruled out commonly seen types of primary myocardial disease in cats. The persistent nature of the tachyarrhythmia, the progressive structural and functional cardiac changes, and comparative gross and histopathologic post-mortem findings are consistent with the diagnosis of tachycardia-induced cardiomyopathy.

Comparison of forelimb and hindlimb systolic blood pressures and proteinuria in healthy Shetland Sheepdogs.

BACKGROUND: The prevalence of systemic hypertension (SHT) in Shetland Sheepdogs has not been reported. HYPOTHESIS/OBJECTIVES: SHT is common in Shetland Sheepdogs and positively correlated with proteinuria. Measurements of forelimb and hindlimb systolic arterial pressure (SAP) are comparable. ANIMALS: Seventy-two clinically healthy, client-owned Shetland Sheepdogs. METHODS: Forelimb and hindlimb SAP were recorded by Doppler ultrasonography. Proteinuria was quantified by urine dipstick, microalbuminuria, and protein:creatinine ratio (UPC). The relationship of UPC, anxiety, age, weight, and heart rate with forelimb SAP was evaluated. RESULTS: The mean forelimb and hindlimb SAP were 132 ± 20 and 118 ± 20 mmHg, respectively. The SAP exceeded 160 mmHg in 9 dogs, suggesting 13% prevalence of SHT. Four dogs had a UPC above 0.5; 2 of these had forelimb SAP exceeding 160 mmHg. Correlation of forelimb and hindlimb SAP was poor (r(2)  = 0.09; P = .011). Bland-Altman plots revealed substantial bias (-14 mmHg) between limb measurements with clinically unacceptable 95% limits of agreement (-60 to 33 mmHg). There was no correlation between forelimb SAP and UPC (P = .06) or anxiety level (P = .49). Age (P < .0001) and heart rate (P = .038) were significant predictors of forelimb SAP; weight (P = .73) was not. CONCLUSIONS: Prevalence of SHT was 13% and not correlated with proteinuria. Forelimb and hindlimb SAP were poorly correlated; therefore, trends in an individual animal should be monitored using the same measurement site. Additionally, values for Doppler SAP were determined in Shetland Sheepdogs.

Myocardial expression of hyperpolarization-activated, cyclic nucleotide-gated proteins in healthy cats and cats with hypertrophic cardiomyopathy.

In this article the myocardial expression of different hyperpolarization-activated, cyclic nucleotide-gated (HCN) isoforms in myocardial tissue from healthy control cats and cats with hypertrophic cardiomyopathy (HCM) was evaluated. Myocardial tissue samples of the left ventricle of control cats (n = 12) and cats with HCM (n = 4) were collected. Expression of feline HCN was determined by immunoblot analysis using antibodies against HCN2 and HCN4. Optical densities of HCN bands were compared among groups by use of the Mann-Whitney Rank Sum test. HCN4 was reliably detected in myocardial tissue whereas HCN2 was not. HCN4 expression was significantly increased in left ventricular (LV) myocardial samples of cats with HCM (P = 0.036) compared to control cats. Results indicate that myocardial HCN4 expression can be evaluated in cats by immunoblot analysis and that HCN4 expression is upregulated in LV myocardial tissue of cats with HCM. The pathophysiological importance of HCN overexpression with regard to myocyte function and altered automaticity deserves further study.

Cardiac troponin I in calves with congenital heart disease.

BACKGROUND: The association between plasma cardiac troponin I (cTnI) and the magnitude of cardiac enlargement in calves with congenital heart disease (CHD) are not well defined. OBJECTIVE: To investigate the relationship between plasma cTnI concentrations and cardiac size in healthy calves and calves with CHD. ANIMALS: A total of 19 healthy calves (control) and 12 Holstein calves with CHD (patent ductus arteriosus, ventricular septal defect, tetralogy of Fallot or double outlet right ventricle). METHODS: Case control study. All animals underwent a comprehensive transthoracic echocardiographic study to document cardiac health or presence of CHD. The vertebral heart score (VHS) was determined in each animal using right lateral survey radiographic images. Blood samples were collected via jugular venipuncture and plasma cTnI concentration and creatine kinase (CK) activity were determined by a 3rd generation immunoassay and an automatic biochemical analyzer, respectively. Groups were compared using Mann-Whitney U-test and receiver-operating characteristics (ROC) curve analysis. RESULTS: Calves with CHD had significantly larger VHS values and higher plasma cTnI concentrations (P < .001) compared to control. Creatine kinase activity was not different between the control and CHD groups of calves. Diagnostic cutoffs of VHS and plasma cTnI for discrimination of groups were 8.9 vertebrae and 0.035 ng/mL, respectively. The cTnI concentration in plasma was significantly correlated with VHS (r (2) =0.512, P < .001). CONCLUSION AND CLINICAL RELEVANCE: Our results suggest that determination of plasma cTnI concentrations in calves with clinical signs compatible with CHD might prove useful as a guide to quantify cardiac remodeling associated with increased cardiac size.

Multicenter evaluation of plasma N-terminal probrain natriuretic peptide (NT-pro BNP) as a biochemical screening test for asymptomatic (occult) cardiomyopathy in cats.

BACKGROUND: B-type natriuretic peptide concentrations reliably distinguish between cardiac and respiratory causes of dyspnea, but its utility to detect asymptomatic cats with occult cardiomyopathy (OCM) is unresolved. HYPOTHESIS/OBJECTIVES: Determine whether plasma N terminal probrain natriuretic peptide (NT-proBNP) concentration can discriminate asymptomatic cats with OCM from normal cats, and whether NT-proBNP concentration correlates with clinical, biochemical, and echocardiographic parameters. ANIMALS: One hundred and fourteen normal, healthy cats; 113 OCM cats. METHODS: Prospective, multicenter, case-controlled study. NT-proBNP was prospectively measured and cardiac status was determined from history, physical examination, and M-mode/2D/Doppler echocardiography. Optimal cut-off values were derived using receiver operating characteristic (ROC) curve analysis. RESULTS: NT-proBNP was higher (median, interquartile range [25th and 75th percentiles]) in (1) OCM (186 pmol/L; 79, 478 pmol/L) versus normal (24 pmol/L; 24, 32 pmol/L) (P < .001); and (2) hypertrophic obstructive cardiomyopathy (396 pmol/L; 205, 685 pmol/L) versus hypertrophic cardiomyopathy (112 pmol/L; 48, 318 pmol/L) (P < .001). In OCM, NT-proBNP correlated (1) positively with LVPWd (ρ = 0.23; P = .01), LA/Ao ratio (ρ = 0.31; P < .001), LVs (ρ = 0.33; P < .001), and troponin-I (ρ = 0.64; P < .001), and (2) negatively with %FS (ρ = -0.27; P = .004). Area under ROC curve was 0.92; >46 pmol/L cut-off distinguished normal from OCM (91.2% specificity, 85.8% sensitivity); >99 pmol/L cut-off was 100% specific, 70.8% sensitive. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma NT-proBNP concentration reliably discriminated normal from OCM cats, and was associated with several echocardiographic markers of disease severity. Further studies are needed to assess test performance in unselected, general feline populations, and evaluate relationships between NT-proBNP concentrations and disease progression.

Comparison of the effects of ivabradine and atenolol on heart rate and echocardiographic variables of left heart function in healthy cats.

BACKGROUND: Ivabradine is a novel negative chronotropic drug used for treatment of ischemic heart disease in people. Little is known about its effects and safety in cats. HYPOTHESIS/OBJECTIVES: Ivabradine is not inferior to atenolol with regard to clinical tolerance, heart rate (HR) reduction, and effects on cardiac function in healthy, lightly sedated cats. ANIMALS: Ten healthy laboratory cats. METHODS: Physical examination, systolic blood pressure measurement, and transthoracic echocardiography were performed in all cats at baseline and after oral administration (4 weeks each) of ivabradine (0.3 mg/kg q12h) and atenolol (6.25 mg/cat q12h; 1.0-1.7 mg/kg) in a prospective, double-blind, randomized, active-control, fully crossed study. A priori noninferiority margins for the effects of ivabradine compared with atenolol were set at 50% (f = 0.5) based on predicted clinical relevance, observer measurement variability, and in agreement with FDA guidelines. Variables were compared by use of 2-way repeated measures ANOVA. RESULTS: Ivabradine was clinically well tolerated with no adverse events observed. HR (ivabradine, P < .001; atenolol, P < .001; ivabradine versus atenolol, P = .721) and rate-pressure product (RPP) (ivabradine, P < .001; atenolol, P = .001; ivabradine versus atenolol, P = .847) were not different between treatments. At the dosages used, ivabradine demonstrated more favorable effects than atenolol on echocardiographic indices of left ventricular (LV) systolic and diastolic function and left atrial performance. CONCLUSIONS AND CLINICAL IMPORTANCE: Ivabradine is not inferior to atenolol with regard to effects on HR, RPP, LV function, left atrial performance, and clinical tolerance. Clinical studies in cats with hypertrophic cardiomyopathy are needed to validate these findings.

Pharmacokinetics of oral ivabradine in healthy cats.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method for the measurement of the novel heart rate-lowering drug ivabradine and its major metabolite, S-18982, was cross-validated in the plasma of eight healthy cats. Plasma concentrations were then determined after single and repeated oral administration of ivabradine. Individual plasma concentrations versus time from each cat were used in compartmental analysis using the commercially available software WinNonlin. Both ivabradine and S-18982 reached their maximum concentrations of 103.33 and 3.86 ng/mL within 1 h. Following repeated administration, areas under the plasma concentration-time curves for ivabradine and S-18982 did not significantly increase. Two-compartmental and one-compartmental models with first-order input and elimination provided the best fit to the data for ivabradine and S-18982, respectively. Both models were combined to produce a single 4-compartment model characterizing ivabradine and S-18982 pharmacokinetics. The results of this study indicate that repeated oral doses of ivabradine produced plasma drug concentrations suitable for 12-h dosing intervals in healthy cats. Furthermore, the analytical assay and combined ivabradine/S-18982 model provide tools for further evaluation of ivabradine pharmacokinetics and pharmacodynamics in future studies in cats.

Detection of congestive heart failure in dogs by Doppler echocardiography.

BACKGROUND: Echocardiographic prediction of congestive heart failure (CHF) in dogs has not been prospectively evaluated. HYPOTHESIS: CHF can be predicted by Doppler echocardiographic (DE) variables of left ventricular (LV) filling in dogs with degenerative mitral valve disease (MVD) and dilated cardiomyopathy (DCM). ANIMALS: Sixty-three client-owned dogs. METHODS: Prospective clinical cohort study. Physical examination, thoracic radiography, analysis of natriuretic peptides, and transthoracic echocardiography were performed. Diagnosis of CHF was based upon clinical and radiographic findings. Presence or absence of CHF was predicted using receiver-operating characteristic (ROC) curve, multivariate logistic and stepwise regression, and best subsets analyses. RESULTS: Presence of CHF secondary to MVD or DCM could best be predicted by E:isovolumic relaxation time (IVRT) (area under the ROC curve [AUC]=0.97, P<.001), respiration rate (AUC=0.94, P<.001), Diastolic Functional Class (AUC=0.93, P<.001), and a combination of Diastolic Functional Class, IVRT, and respiration rate (R2=0.80, P<.001) or Diastolic Functional Class (AUC=1.00, P<.001), respiration rate (AUC=1.00, P<.001), and E:IVRT (AUC=0.99, P<.001), and a combination of Diastolic Functional Class and E:IVRT (R2=0.94, P<.001), respectively, whereas other variables including N-terminal pro-brain natriuretic peptide, E:Ea, and E:Vp were less useful. CONCLUSION AND CLINICAL IMPORTANCE: Various DE variables can be used to predict CHF in dogs with MVD and DCM. Determination of the clinical benefit of such variables in initiating, modulating, and assessing success of treatments for CHF needs further study.