Bilateral lysis of aortic saddle thrombus with early tissue plasminogen activator (BLASTT): a prospective, randomized, placebo-controlled study in feline acute aortic thromboembolism.

OBJECTIVES: The aim of this study was to investigate the impact of tissue plasminogen activator (TPA) on the treatment of feline aortic thromboembolism (FATE). METHODS: Cats diagnosed with FATE involving ⩾2 limbs were enrolled in a prospective, multicenter, double-blinded, randomized, placebo-controlled study within 6 h of an event. Diagnosis was made by clinical findings and one confirmatory criterion. Cats received placebo or TPA (1 mg/kg/h with the first 10% by bolus). All cats received pain control and thromboprophylaxis. The primary outcome was a change from baseline in a published limb score at 48 h. Secondary outcomes included 48 h survival, survival to discharge and complication proportions. Statistical analyses included pattern-mixture models, logistic regression and Fisher's exact, Student's t- and Mann-Whitney-Wilcoxon tests. RESULTS: Based on a power analysis, 40 cats were enrolled; however, only 20 survived to 48 h (TPA, n = 12; placebo, n = 8 [P = 0.34]). There was a statistically significant improvement in limb scores compared with baseline for both groups (P <0.001). Limb score at 48 h was 1 point lower (better) in the TPA group (P = 0.19). Thrombolysis had no statistically significant effect on 48 h survival (P = 0.22). Lower affected limb lactate was associated with better 48 h survival (odds ratio 1.53, 95% confidence interval 1.08-2.17; P = 0.02). The survival to discharge rates were 45% (TPA) and 30% (placebo; P = 0.51). Complications in the TPA and placebo groups included acute kidney injury (22% and 19%, respectively; P = 1.00) and/or reperfusion injuries (33% and 19%, respectively; P = 0.45). CONCLUSIONS AND RELEVANCE: Survival and complication rates of acute FATE were not different with or without thrombolysis. High in-hospital mortality decreased the statistical power to detect a statistically significant difference between treatments with regard to our primary outcome.

Effects of pimobendan on left atrial transport function in cats.

BACKGROUND: Arterial thromboembolism is a sequela of hypertrophic cardiomyopathy (HCM) in cats related to left atrial (LA) enlargement and dysfunction. HYPOTHESIS: Pimobendan improves LA transport function in cats. ANIMALS: Twenty-two client-owned cats with HCM and 11 healthy cats. METHODS: Prospective, double-blind, randomized, placebo-controlled clinical cohort study. Cats were randomized to receive either pimobendan (0.25 mg/kg PO q12h) or placebo for 4 to 7 days. Nineteen echocardiographic variables of LA size and function were evaluated. Statistical comparisons included t tests, analysis of variance, and multivariable analyses. RESULTS: Peak velocity of left auricular appendage flow (LAapp peak; mean ± SD, 0.85 ± 0.20 vs 0.71 ± 0.22 m/s; P = .01), maximum LA volume (P = .03), LA total emptying volume (P = .03), peak velocity of late diastolic transmitral flow (A peak velocity; 0.77 ± 0.12 vs 0.62 ± 0.17 m/s; P = .05), and A velocity time integral (A VTI; 3.05 ± 0.69 vs 3.37 ± 0.49; P = .05) were increased after pimobendan. Mean change after pimobendan was larger in cats with HCM compared to healthy cats for LA fractional shortening (2.1% vs -2.1%; P = .05), A VTI (0.58 vs 0.01 cm; P = .01), LAapp peak (0.20 vs 0.02 m/s; P = .02), LA kinetic energy (3.51 vs -0.10 kdynes-cm; P = .05), and LA ejection force (1.93 vs -0.07 kdynes; P = .01) in the multivariable model. The stronger effect of pimobendan in cats with HCM was independent of LA size. CONCLUSIONS AND CLINICAL IMPORTANCE: We identified positive, albeit minor, effects of pimobendan on LA function in cats with HCM. Whether or not treatment with pimobendan decreases the risk of cardiogenic embolism deserves further study.

Detection of congestive heart failure by Doppler echocardiography in cats with hypertrophic cardiomyopathy.

BACKGROUND: Left-sided congestive heart failure (CHF) is characterized by increased filling pressures and related Doppler echocardiographic (DE) filling patterns. HYPOTHESIS: Doppler echocardiographic variables of left ventricular filling derived from transmitral flow, pulmonary vein flow, and tissue Doppler can be used to detect CHF in cats with hypertrophic cardiomyopathy (HCM). ANIMALS: Forty-seven client-owned cats. METHODS: Prospective clinical cohort study. Cats underwent physical examination, thoracic radiography, analysis of N-terminal pro-brain natriuretic peptide (NT-proBNP), and transthoracic echocardiography and were divided into 3 age-matched groups: Group 1 (apparently healthy control), Group 2 (preclinical HCM), and Group 3 (HCM and CHF). Measured and calculated variables included respiratory rate, DE estimates, serum NT-proBNP concentration, and radiographic CHF score. Groups were compared using ANOVA, and receiver operating characteristic (ROC) curve and multivariate analyses were used to identify diagnostic cutoffs for the detection of CHF. RESULTS: Fifteen cats were in Group 1, 17 in Group 2, and 15 in Group 3. The ROC analysis indicated that the ratio of peak velocity of early diastolic transmitral flow to peak velocity of late diastolic transmitral flow (area under the curve [AUC], 1.0; diagnostic cutoff, 1.77; P = .001), ratio of left atrial size to aortic annular dimension (AUC, 0.91; diagnostic cutoff, 1.96; P = .003), left atrial diameter (AUC, 0.89; cutoff, 18.5 mm; P = .004), diastolic functional class (AUC, 0.89; cutoff, class 2; P = .005), respiratory (AUC, 0.79; cutoff, 36 breaths per minute [brpm]; P = .02), and the ratio of the peak velocity of fused early and late transmitral flow velocities to the peak velocity of the fused early and late diastolic tissue Doppler waveforms (AUC, 0.74; cutoff, 15.1; P = .05) performed best for detecting CHF. CONCLUSIONS AND CLINICAL IMPORTANCE: Various DE variables can be used to detect CHF in cats with HCM. Determination of the clinical benefit of such variables in initiating treatments and assessing treatment success needs further study.

ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs.

This report, issued by the ACVIM Specialty of Cardiology consensus panel, revises guidelines for the diagnosis and treatment of myxomatous mitral valve disease (MMVD, also known as endocardiosis and degenerative or chronic valvular heart disease) in dogs, originally published in 2009. Updates were made to diagnostic, as well as medical, surgical, and dietary treatment recommendations. The strength of these recommendations was based on both the quantity and quality of available evidence supporting diagnostic and therapeutic decisions. Management of MMVD before the onset of clinical signs of heart failure has changed substantially compared with the 2009 guidelines, and new strategies to diagnose and treat advanced heart failure and pulmonary hypertension are reviewed.

Overview of Equine Cardiac Disease.

Equine heart diseases can be categorized with morphologic, etiologic, and physiologic diagnoses and classified anatomically as diseases of the pericardium, myocardium, valves (endocardium), and great vessels. An appreciation of normal and pathologic physiology is a key to understanding diagnosis and therapy of heart disease. Pathophysiologic diagnoses include arrhythmias, congestive heart failure, and pulmonary hypertension. Heart rhythm disturbances can occur in isolation or with structural disease. Heart failure stems from arterial filling owing to insufficient cardiac output. Pulmonary hypertension is associated with strenuous exercise, left heart failure, bronchopulmonary diseases, and pulmonary arteriopathies. The etiopathogenesis of these disorders are incompletely understood.

Thrombolysis with tissue plasminogen activator (TPA) in feline acute aortic thromboembolism: a retrospective study of 16 cases.

OBJECTIVES: Thrombolytic therapy is a treatment of choice for people with acute ischemic events, but is uncommonly administered for feline aortic thromboembolism (FATE). This study reports selected clinical data and outcomes of acute FATE treated with tissue plasminogen activator (TPA). A reference group treated with current standard of care (SOC) was analyzed for comparison. METHODS: This was a retrospective study of FATE in two academic hospitals. TPA-treated cats with two or more limbs (n = 16) affected were compared with a SOC-treated group with two or more limbs affected (n = 38). A limb score based on motor function and pulse quality was calculated for each group. RESULTS: Limb score and proportion of congestive heart failure at admission was similar in both groups. Time from FATE to admission was shorter in the TPA group, with a median of 3 h (range 0-6 h) vs 6 h (range 0-48 h; P = 0.0004). The most common regimen received for TPA was 1 mg/kg over 1 h. Other treatments were similar to those of the SOC group and included analgesia, thromboprophylaxis and furosemide. Documented complications for TPA-treated cats included reperfusion injury (5/10) and acute kidney injury (AKI; 3/10). Discharge proportion rate was 44% (TPA) vs 29% (SOC; P = 0.351). There were no differences in short-term survival rate (56.2% vs 39.5%; P = 0.369), clinical improvement (56.2% vs 31%; P = 0.122), rates of reperfusion injury (50% vs 50%; P = 1.00) or AKI (30% vs 27%; P = 1.00) between the TPA-treated and SOC groups, respectively. CONCLUSIONS AND RELEVANCE: Survival and complication rates of TPA-treated cats and SOC-treated cats for acute FATE were similar.

Ischemic necrosis of the digits and hyperlipidemia associated with atherosclerosis in a Miniature American Shepherd.

CASE DESCRIPTION A 2.5-year-old 12-kg (26.4-lb) castrated male Miniature American Shepherd was referred because of a 3-week history of a localized crusted skin lesion on the digital pad of digit 3 of the right hind limb. CLINICAL FINDINGS Skin lesions were noted on the digital pads of the right hind limb. Serum biochemical analyses indicated severe hypercholesterolemia and hypertriglyceridemia. Ultrasonography of the terminal portion of the aorta and other major arterial vessels revealed substantial arteriosclerotic change. TREATMENT AND OUTCOME Medical treatments included administration of atorvastatin calcium, a low-fat diet, and omega-3 fatty acids to reduce serum lipids concentration; clopidogrel to prevent thrombosis; pentoxifylline to improve microcirculatory blood flow; clomipramine hydrochloride and trazodone hydrochloride to help with the behavioral problems; and gabapentin to help with pain management and behavioral problems. Surgical management included amputation of the initial digit involved, then eventually the entire initial limb involved. The response to treatment was poor, and euthanasia was elected. Postmortem findings revealed severe, widespread, and chronic intimal atherosclerosis; mild, widespread, and degenerative changes in the cerebral cortex; and edema and vascular congestion in the meninges. CLINICAL RELEVANCE To the authors' knowledge, this was the first report of skin necrosis secondary to atherosclerosis in a dog. Although the incidence of atherosclerosis has been considered very low in dogs, it should be investigated in dogs with severe hyperlipidemia. Primary hyperlipidemia has not been previously described in Miniature American Shepherd dogs but was the suspected underlying metabolic disorder.

Cutting balloon and high-pressure balloon dilation for palliative treatment of congenital double-chambered right ventricle and primary infundibular stenosis in a Golden retriever dog.

Combined cutting balloon and high-pressure balloon dilation was performed in a dog with a double-chambered right ventricle and severe infundibular stenosis of the right ventricular outflow tract. The peak systolic pressure gradient across the stenosis decreased by 65% after dilation (from 187 mmHg before to 66 mmHg after) affirming the intervention as successful. However, early re-stenosis occurred within 3 months leading to exercise intolerance, exercise-induced syncope, and right-sided congestive heart failure. Cutting balloon followed by high-pressure balloon dilation provided temporary but not long-term relief of right ventricular obstruction in this dog.

Quantification of myocardial stiffness using magnetic resonance elastography in right ventricular hypertrophy: initial feasibility in dogs.

INTRODUCTION: Myocardial stiffness is an important determinant of cardiac function and is currently invasively and indirectly assessed by catheter angiography. This study aims to demonstrate the feasibility of quantifying right ventricular (RV) stiffness noninvasively using cardiac magnetic resonance elastography (CMRE) in dogs with severe congenital pulmonary valve stenosis (PVS) causing RV hypertrophy, and compare it to remote myocardium in the left ventricle (LV). Additionally, correlations between stiffness and selected pathophysiologic indicators from transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging were explored. METHODS: In-vivo CMRE was performed on nine dogs presenting severe congenital PVS using a 1.5T MRI scanner. T1-MOLLI, T2-prepared-bSSFP, gated-cine GRE-MRE and LGE (PSIR) sequences were used to acquire a basal short-axis slice. RV and LV-free-wall (FW) stiffness measurements were compared against each other and also correlated to ventricular mass, RV and LV FW thickness, T1 and T2 relaxation times, and extracellular volume fraction (ECV). Peak transpulmonary pressure gradient and myocardial strain were also acquired on eight dogs by TTE and correlated to RV-FW systolic stiffness. Potential correlations were evaluated by Spearman's rho (rs). RESULTS: RV-FW stiffness was found to be significantly higher than the LV-FW stiffness both during end-systole (ES) (p=0.002) and end-diastole (ED) (p=0.029). Significant correlations were observed between RV-FW ES and LV-FW ED stiffness versus ECV (rs=0.75; p-value=0.05). Non-significant moderate correlations were found between LV-FW ES (rs=0.54) and RV-FW ED (rs=0.61) stiffness versus ECV. Furthermore, non-significant correlations were found between RV or LV-FW stiffness and the remaining variables (rs<0.54; p-value>0.05). CONCLUSION: This study demonstrates the feasibility of determining RV stiffness. The positive correlations between stiffness and ECV might indicate some interdependence between stiffness and myocardial extracellular matrix alterations. However, further studies are warranted to validate our initial observations.

Iatrogenic embolization and transcatheter retrieval of a ventricular septal defect occluder in a dog.

A 7-month-old Irish Setter underwent transcatheter therapy of a muscular ventricular septal defect (VSD) and pulmonary valve stenosis. Standard devices for muscular VSD closure could not span the interventricular septum due to right ventricular hypertrophy, and an Amplatzer post-infarction muscular VSD occluder with a wider waist was successfully implanted. Following VSD closure, inflation of the balloon dilation catheter during balloon pulmonary valvuloplasty resulted in iatrogenic embolization of the VSD occluder to the left ventricular outflow tract. Retrieval and reimplantation of the device was achieved using a snare catheter. This report describes a potential complication and management during intracardiac device implantation in a dog. Additionally, the case illustrates that the Amplatzer post-infarction muscular VSD occluder holds potential value in animals with a hypertrophied interventricular septum that cannot be spanned using a conventional device.

Congenital isolated cleft mitral valve leaflet and apical muscular ventricular septal defect in a Holstein calf.

A 5-week-old Holstein heifer calf presented for emergency treatment of signs referable to gastrointestinal disease and hypovolemic shock. Fluid resuscitation uncovered clinical signs of primary cardiac disease and echocardiography revealed multiple congenital cardiac defects. Malformations included a cleft anterior mitral valve leaflet resembling an isolated cleft mitral valve and an apically-located muscular ventricular septal defect. The echocardiographic and postmortem findings associated with these defects are presented and discussed in this report.

Echocardiographic assessment of right ventricular systolic function in conscious healthy dogs following a single dose of pimobendan versus atenolol.

OBJECTIVE: To quantify drug-induced changes in right ventricular (RV) systolic function after administration of pimobendan and atenolol. ANIMALS: 80 healthy privately-owned dogs. METHODS: Using a prospective, blinded, fully-crossed study design with randomized drug administration, RV systolic function was determined twice at two time periods; before and 3 h after administration of pimobendan (0.25 mg/kg PO) or atenolol (1 mg/kg PO). Indices of RV systolic function included tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), pulsed-wave tissue Doppler-derived systolic myocardial velocity of the lateral tricuspid annulus (S'), and speckle-tracking-derived global longitudinal RV free wall strain and strain rate. The effect of treatment on percent change from baseline RV function was analyzed with a linear mixed model including the covariates heart rate, body weight, age, gender, drug sequence, and time period. RESULTS: All indices showed a significant (p < 0.0001) increase and decrease from baseline following pimobendan and atenolol, respectively. Significant differences from baseline were attributed to drug treatment (p < 0.0001); whereas, effects of other covariates were not significant. The greatest percent changes, but also highest variability, were observed for S' and strain rate (p < 0.0001). Post-atenolol, a significantly greater proportion of dogs exceeded the repeatability coefficient of variation for FAC and S' compared to TAPSE (p ≤ 0.007). CONCLUSIONS: Echocardiographic indices in healthy dogs tracked expected changes in RV systolic function following pimobendan and atenolol and warrant study in dogs with cardiovascular disease.

Echocardiographic assessment of right ventricular systolic function in conscious healthy dogs: repeatability and reference intervals.

OBJECTIVES: To determine the feasibility, repeatability, intra- and interobserver variability, and reference intervals for 5 echocardiographic indices of right ventricular (RV) systolic function: tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), pulsed wave tissue Doppler imaging-derived systolic myocardial velocity of the lateral tricuspid annulus (S'), and speckle-tracking echocardiography-derived global longitudinal RV free wall strain and strain rate. To explore statistical relationships between RV systolic function and age, gender, heart rate, and bodyweight. ANIMALS: 80 healthy adult dogs. METHODS: Dogs underwent 2 echocardiographic examinations. Repeatability and intra-observer and inter-observer measurement variability were quantified by average coefficient of variation (CV). Relationships between RV function and age, heart rate and bodyweight were estimated by regression analysis. RESULTS: All indices were acquired with clinically acceptable repeatability and intra- and inter-observer variability (CVs < 10%). No differences were identified between male and female dogs. Allometric scaling by bodyweight demonstrated significant, clinically relevant correlations between RV function and bodyweight (all p ≤ 0.001) as follows: TAPSE - strong positive correlation (r(2) = 0.75); S' - moderate positive correlation (r(2) = 0.31); strain rate - moderate negative correlation (r(2) = 0.44); FAC and strain - weak negative correlations (r(2) = 0.22 and 0.14, respectively). Strain rate and FAC were positively correlated with heart rate (r(2) = 0.35 and 0.31, respectively). Allometric scaling generated bodyweight-based reference intervals for these RV systolic function indices. CONCLUSIONS: Echocardiographic indices of RV systolic function are feasible to obtain, repeatable, and affected by bodyweight. Studies of these indices in dogs with cardiovascular disease are needed.

Sequential segmental classification of feline congenital heart disease.

Feline congenital heart disease is less commonly encountered in veterinary medicine than acquired feline heart diseases such as cardiomyopathy. Understanding the wide spectrum of congenital cardiovascular disease demands a familiarity with a variety of lesions, occurring both in isolation and in combination, along with an appreciation of complex nomenclature and variable classification schemes. This review begins with an overview of congenital heart disease in the cat, including proposed etiologies and prevalence, examination approaches, and principles of therapy. Specific congenital defects are presented and organized by a sequential segmental classification with respect to their morphologic lesions. Highlights of diagnosis, treatment options, and prognosis are offered. It is hoped that this review will provide a framework for approaching congenital heart disease in the cat, and more broadly in other animal species based on the sequential segmental approach, which represents an adaptation of the common methodology used in children and adults with congenital heart disease.

Effect of treatment with atenolol on 5-year survival in cats with preclinical (asymptomatic) hypertrophic cardiomyopathy.

OBJECTIVES: To investigate the effect of treatment with atenolol on 5-year survival in cats with preclinical hypertrophic cardiomyopathy (HCM). ANIMALS: 63 Client-owned cats with preclinical HCM and 31 healthy control cats. METHODS: Prospective, observational, open-label, clinical cohort study. Cats with HCM were diagnosed by echocardiography, treated with atenolol (6.25-12.5 mg q12h, PO; n = 42) or untreated (n = 21), and were observed for 5 years after enrollment. The study end point was death from any cause. Cats of similar body weight, age, gender, and breed without evidence of heart disease were studied concurrently and served as controls. RESULTS: During the observational period, 27 cats with HCM died; 14 (22%) due to cardiac disease and 13 (21%) due to non-cardiac disease. Ten control cats (32%) died of non-cardiac disease. There was no significant difference (P = 0.307) in all-cause mortality between control and HCM. Cardiac mortality was higher in cats with HCM compared to control cats (P = 0.005). There was no significant difference in all-cause mortality (P = 0.729) and cardiac mortality (P = 0.897) between cats with HCM treated or untreated with atenolol. Age and left atrial size at diagnosis were the only predictors of 5-year outcome. CONCLUSIONS: Our study failed to demonstrate an effect of atenolol on 5-year survival in cats with preclinical HCM.

Clinical evaluation of the 3M Littmann Electronic Stethoscope Model 3200 in 150 cats.

Detection of murmurs and gallops may help to identify cats with heart disease. However, auscultatory findings may be subject to clinically relevant observer variation. The objective of this study was to evaluate an electronic stethoscope (ES) in cats. We hypothesized that the ES would perform at least as well as a conventional stethoscope (CS) in the detection of abnormal heart sounds. One hundred and fifty consecutive cats undergoing echocardiography were enrolled prospectively. Cats were ausculted with a CS (WA Tycos Harvey Elite) by two observers, and heart sounds were recorded digitally using an ES (3M Littmann Stethoscope Model 3200) for off-line analysis. Echocardiography was used as the clinical standard method for validation of auscultatory findings. Additionally, digital recordings (DRs) were assessed by eight independent observers with various levels of expertise, and compared using interclass correlation and Cohen's weighted kappa analyses. Using the CS, a heart murmur (n = 88 cats) or gallop sound (n = 17) was identified in 105 cats, whereas 45 cats lacked abnormal heart sounds. There was good total agreement (83-90%) between the two observers using the CS. In contrast, there was only moderate agreement (P <0.001) between results from the CS and the DRs for murmurs, and poor agreement for gallops. The CS was more sensitive compared with the DRs with regard to murmurs and gallops. Agreement among the eight observers was good-to-excellent for murmur detection (81%). In conclusion, DRs made with the ES are less sensitive but comparably specific to a CS at detecting abnormal heart sounds in cats.

Resolution of sustained narrow complex ventricular tachycardia and tachycardia-induced cardiomyopathy in a Quarter Horse following quinidine therapy.

Sustained narrow-QRS tachycardia of three months duration and left ventricular systolic dysfunction were identified in a fifteen-year-old Quarter Horse. No underlying cause for the tachyarrhythmia was found and no predisposing structural cardiac lesions were evident by echocardiography. Intravenous diltiazem and lidocaine were administered without achieving successful conversion of the arrhythmia. Oral quinidine therapy converted the tachyarrhythmia to sinus rhythm. Ventricular systolic dysfunction and chamber dilatation subsequently resolved. As with other species, echocardiographic features of dilated cardiomyopathy can be tachycardia-induced and may resolve following successful control of heart rate and rhythm.

Effects of treatment with ivabradine and atenolol on reproducibility of echocardiographic indices of left heart size and function in healthy cats.

OBJECTIVES: Data on reproducibility of echocardiographic indices in cats are commonly derived from studies in healthy, non-treated animals. However, medical treatment may alter reproducibility of such data possibly influencing interpretation of results of clinical trials assessing the effects of drugs on cardiovascular function. The objectives were therefore to investigate the effects of ivabradine and atenolol on reproducibility of echocardiographic indices of left heart function. ANIMALS: Eight healthy cats. METHODS: Repeated echocardiographic examinations were performed by two observers in mildly sedated cats at baseline and after four weeks of treatment (Group 1, ivabradine 0.3 mg/kg q12 h PO, n = 4; Group 2, atenolol 6.25 mg/cat q12 h PO, n = 4) in a prospective, double-blind, randomized study. Test reliability was determined by estimating measurement variability, within-day interobserver variability, and between-day intraobserver variability of all echocardiographic indices. Variability was expressed as coefficient of variation (CV) and the absolute value below which the difference between two measurements lay with 95% probability. Effects of treatments on variability were compared using linear mixed effects models ANOVA and Fisher's exact test. RESULTS: Overall, CVs ranged from 0.5 to 50.6% at baseline, 0.5-45.5% after ivabradine, and 0.5-23.3% after atenolol. Reproducibility of all variables determined did neither improve nor worsen consistently after either treatment although atenolol exhibited a tendency toward higher reliability with none of the CVs exceeding 24% as compared to ivabradine. CONCLUSIONS: Treatment of healthy cats with either atenolol or ivabradine had only minor effects on reproducibility of echocardiographic data. Whether these findings can be extrapolated to cats with hypertrophic cardiomyopathy deserves further study.