Prevalence of an angiotensin-converting enzyme gene variant in dogs.

BACKGROUND: Genetic heterogeneity of the canine angiotensin converting enzyme (ACE) gene is functionally important because the degree of aldosterone breakthrough with ACE-inhibitor therapy is greater in variant positive dogs compared to variant negative dogs, but the prevalence of the variant is not known. The purpose of this study was to determine ACE gene variant-positive prevalence in a population of 497 dogs of different breeds. RESULTS: Overall variant-positive prevalence was 31%, with 20% of dogs heterozygous and 11% of dogs homozygous. The variant was overrepresented in Irish Wolfhounds (prevalence 95%; P < .001), Dachshunds (prevalence 90%; P < .001), Cavalier King Charles Spaniels (prevalence 85%; P < .001), Great Danes (prevalence 84%; P < .001), and Bull Mastiffs (prevalence 58%; P = .02). Irish Wolfhounds were more likely to be homozygous than heterozygous (P < .001). CONCLUSIONS: Nearly one-third of dogs in this study were positive for a functionally important ACE gene variant, with wide prevalence variability between breeds. The clinical importance of high ACE gene variant-positive prevalence in some breeds requires further study because the highest prevalences were found in breeds that are predisposed to heart disease and therefore may be treated with ACE-inhibitors.

Aorto-left atrial fistula secondary to infective aortic endocarditis and endarteritis in a cat with valvular aortic stenosis.

A cat previously diagnosed with valvular aortic stenosis developed acute respiratory distress. A new continuous heart murmur was noted on physical exam. Echocardiographic examination revealed vegetative lesions on the aortic valve and continuously shunting blood flow from the aorta into the left atrium. Despite initial treatment for left-sided congestive heart failure, the cat died suddenly. In addition to confirming aortic valve endocarditis and an acquired aorto-left atrial shunt, pathological examination identified vegetative lesions on the luminal surface of the ascending aorta. Although antemortem aerobic blood culture, 16s bacterial ribosomal DNA PCR, and Bartonella PCR failed to identify causative organisms, Escherichia coli was identified on postmortem tissue culture of the aortic lesion. This represented a unique case of primary valvular aortic stenosis with secondary infective aortic endocarditis, infective aortic endarteritis, and aorto-left atrial fistula in a cat. It highlighted potential adverse outcomes of aortic stenosis that are more commonly recognized in humans and dogs.

Echocardiographic assessment of right heart size and function in dogs with pulmonary valve stenosis.

INTRODUCTION/OBJECTIVES: We sought to determine the prevalence and clinical significance of right heart remodeling and right ventricular (RV) dysfunction in dogs with pulmonary valve stenosis (PS). We also sought to evaluate repeatability of several measurements of severity of PS, right heart size, and RV function in dogs with PS. ANIMALS, MATERIALS AND METHODS: Several indices of right atrial (RA) size and RV size and function were prospectively evaluated in 48 dogs with PS. Regression analysis was used to determine if indices of right heart size and function were independently associated with maximum transpulmonary pressure gradient (max PG) and adverse clinical findings (exercise intolerance, syncope, or right heart failure). Eight dogs underwent a second echocardiogram performed by the same operator to assess repeatability of the echocardiographic indices, which was quantified by coefficient of variation (CV) and repeatability coefficient. RESULTS: Increased RA size (81%), increased RV wall thickness (83%), and decreased tricuspid annular plane systolic excursion (TAPSE [81%]) were common. Right atrial size, end-diastolic RV area, and RV wall thickness were independently associated with max PG. Decreased TAPSE was independently associated with adverse clinical findings. All indices except RA area (18.6%) and RV systolic velocity (20.7%) had CVs <15%. Repeatability coefficients are available to help distinguish a true change versus measurement variability during serially obtained exams. CONCLUSIONS: Right heart remodeling and RV dysfunction are common in dogs with PS and are associated with echocardiographic and clinical severity. Results support the quantitative assessment of right heart size and function in dogs with PS.

Feasibility, safety, and tolerance of subcutaneous synthetic canine B-type natriuretic peptide (syncBNP) in healthy dogs and dogs with stage B1 mitral valve disease.

INTRODUCTION: An important aspect of heart failure is the progressive ineffectiveness of the salutary natriuretic peptide system and its secondary messenger, 3',5'-cyclic guanosine monophosphate (cGMP). In humans with acute heart failure, administration of exogenous natriuretic peptide is associated with improvement in clinical signs and reduction of cardiac filling pressures. This study aimed to determine the feasibility, tolerance, and safety of subcutaneous (SC) synthetic canine B-type natriuretic peptide (syncBNP) administration in dogs. ANIMALS: Six privately owned dogs. MATERIALS AND METHODS: Dogs were enrolled in a modified 3 + 3 phase I trial. Three dogs initially received doses of 2.5 and 5 µg/kg SC syncBNP followed by an additional three dogs dosed at 5 and 10 µg/kg. Hemodynamic monitoring was performed for 120 min after each injection. Blood and urine samples were collected at 45 and 120 min after injection of 5 µg/kg. Major adverse clinical events that would potentially halt testing were pre-defined. RESULTS: Four healthy dogs and two dogs with stage B1 mitral valve disease were recruited. Synthetic canine B-type natriuretic peptide was well tolerated at all doses. Synthetic canine B-type natriuretic peptide at 5 µg/kg significantly increased median plasma cGMP (baseline cGMP, 131.5 pmol/mL [range, 91.9-183.6 pmol/mL]; 45 min, 153.6 pmol/mL [140.3-214.3 pmol/mL]; 120 min, 192.7 pmol/mL [139.1-240.1 pmol/mL]; p=0.041). DISCUSSION AND CONCLUSIONS: We report for the first time administration of syncBNP in privately owned dogs. Administration of SC syncBNP was feasible, well tolerated, safe, and increased plasma cGMP concentration. Further studies using exogenous syncBNP for treatment of heart disease are warranted.

Echocardiographic Assessment of Right Ventricular Size and Function in Cats With Hypertrophic Cardiomyopathy.

BACKGROUND: Studies evaluating right ventricular (RV) structural and functional abnormalities in feline hypertrophic cardiomyopathy (HCM) are limited. HYPOTHESIS: Right ventricular structural and functional abnormalities are present in cats with HCM and are associated with clinical severity. ANIMALS: Eighty-one client-owned cats. METHODS: Retrospective 2-dimensional (2D) echocardiographic study. Right atrial diameter (RAD), RV free wall thickness (RVFWd), RV internal dimension (RVIDd), RV fractional area change (FAC), and tricuspid annular plane systolic excursion (TAPSE) were measured in control cats (n = 26), cats with subclinical HCM (subclinical HCM; n = 31), and cats with HCM and congestive heart failure (HCM + CHF; n = 24). RESULTS: Right heart size (RAD, RVFWd, and RVIDd) and RV function (FAC and TAPSE) significantly (all P < .05) increased and decreased, respectively, in the HCM + CHF group compared with controls. In the subclinical HCM group, only RVFWd was significantly (P < .05) higher than in controls. Compared with reference intervals derived from controls, 29% of cats with HCM had increased RVFWd. Increased left ventricular free wall thickness, increased RVIDd and decreased TAPSE independently correlated with increased left atrial size. Cats with HCM and pleural effusion were significantly more likely to have increased RVFWd and had increased RAD and decreased TAPSE compared with cats without pleural effusion. CONCLUSIONS AND CLINICAL IMPORTANCE: Right ventricular remodeling and dysfunction occur in some cats with HCM and may be associated with clinical severity. Our results support involvement of RV in the pathophysiology of HCM in some cats and support echocardiographic assessment of the RV in cats with HCM.

Platelet Activation and Clopidogrel Effects on ADP-Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3.

BACKGROUND: Clopidogrel is commonly prescribed to cats with perceived increased risk of thromboembolic events, but little information exists regarding its antiplatelet effects. OBJECTIVE: To determine effects of clopidogrel on platelet responsiveness in cats with or without the A31P mutation in the MYBPC3 gene. A secondary aim was to characterize variability in feline platelet responses to clopidogrel. ANIMALS: Fourteen healthy cats from a Maine Coon/outbred mixed Domestic cat colony: 8 cats homozygous for A31P mutation in the MYPBC3 gene and 6 wild-type cats without the A31P mutation. METHODS: Ex vivo study. All cats received clopidogrel (18.75 mg PO q24h) for 14 days. Before and after clopidogrel treatment, adenosine diphosphate (ADP)-induced P-selectin expression was evaluated. ADP- and thrombin-induced platelet aggregation was measured by optical aggregometry (OA). Platelet pVASP and ADP receptor response index (ARRI) were measured by Western blot analysis. RESULTS: Platelet activation from cats with the A31P mutation was significantly (P = .0095) increased [35.55% (18.58-48.55) to 58.90% (24.85-69.90)], in response to ADP. Clopidogrel treatment attenuated ADP-induced P-selectin expression and platelet aggregation. ADP- and PGE1 -treated platelets had a similar level of pVASP as PGE1 -treated platelets after clopidogrel treatment. Clopidogrel administration resulted in significantly lower ARRI [24.13% (12.46-35.50) to 11.30% (-7.383 to 23.27)] (P = .017). Two of 13 cats were nonresponders based on OA and flow cytometry. CONCLUSION AND CLINICAL IMPORTANCE: Clopidogrel is effective at attenuating platelet activation and aggregation in some cats. Cats with A31P mutation had increased platelet activation relative to the variable response seen in wild-type cats.

Effects of 0.5% Timolol Maleate Ophthalmic Solution on Heart Rate and Selected Echocardiographic Indices in Apparently Healthy Cats.

BACKGROUND: Echocardiographic assessment of diastolic function is challenging in cats, partially because of transmitral flow pattern fusion associated with high heart rates. With heart rate (HR) reduction, transmitral flow waveforms separate, allowing identification of diastolic dysfunction. Timolol, an ophthalmic, nonselective beta-blocker used in glaucoma is safe and transiently decreases HR in clinical trials. HYPOTHESIS: Administration of timolol ophthalmic solution decreases HR and facilitates echocardiographic assessment of diastolic function in cats without inducing clinically relevant adverse effects. ANIMALS: Twenty-five apparently healthy cats. METHODS: Electrocardiograms and echocardiograms including transmitral flow patterns were evaluated before and 20 minutes after ocular administration of 1 drop of timolol 0.5% solution. Twenty cats underwent treatment with timolol, and 5 different cats served as untreated controls to evaluate the effects of acclimation to the hospital environment on HR. RESULTS: Acclimation to the hospital had no effect on HR in control cats. After timolol administration, a significant median HR reduction of 25 bpm was observed (P < .0001). Timolol had no effect on E/A ratio in cats without E/A fusion (7/20, P = .44). Of the 13 cats with E and A waves that were fused before timolol application, separation of these waves was identified in 8 cats (62%) after timolol treatment. No bradyarrhythmias were noted after timolol administration, but 2 cats had first-degree atrioventricular block. Timolol resulted in resolution of dynamic outflow tract obstruction in 6 of 6 cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Ocular administration of timolol safely decreases HR in cats and could facilitate assessment of diastolic function.

Diagnostic Value of Right Pulmonary Artery Distensibility Index in Dogs with Pulmonary Hypertension: Comparison with Doppler Echocardiographic Estimates of Pulmonary Arterial Pressure.

BACKGROUND: Noninvasive diagnosis of pulmonary hypertension (PH) primarily relies upon Doppler echocardiography of tricuspid regurgitation (TR). However, TR might be absent or difficult to measure. HYPOTHESIS/OBJECTIVES: To determine the diagnostic value of right pulmonary artery distensibility (RPAD) index for prediction of Doppler-derived estimates of pulmonary artery (PA) pressure compared to other indices of PH in dogs. ANIMALS: Sixty-nine client-owned dogs with TR. METHODS: Prospective observational study. Dogs were allocated to groups according to TR pressure gradient (TRPG): TRPG <36 mmHg (control, n = 22), TRPG 36-50 (n = 16), TRPG 50-75 (n = 14) and TRPG >75 mmHg (n = 17). Right pulmonary artery distensibility index, acceleration time to peak PA flow (AT), AT: ejection time of PA flow (AT:ET) and main PA size: aorta size (MPA:Ao) were calculated in each dog. RESULTS: Right pulmonary artery distensibility index demonstrated the strongest correlation (r = -0.90; P < .0001) to TRPG followed by MPA:Ao (r = 0.78; P < .0001), AT (r = -0.69; P < .0001) and AT:ET (r = -0.68; P < .0001). RPAD index possessed the most accurate cutoff (<29.5%; Sensitivity [Sn] 0.84, Specificity [Sp] 0.95) to predict TRPG >50 mmHg compared to AT (<53.9 ms; Sn 0.74, Sp 0.87), AT:ET (<0.30; Sn 0.61, Sp 0.97) and MPA:Ao (>1.04; Sn 0.94, Sp 0.74). All intra- and interobserver measurement variabilities exhibited coefficients of variation ≤13%. CONCLUSIONS AND CLINICAL IMPORTANCE: Right pulmonary artery distensibility index is an accurate predictor of TRPG and should be particularly useful if TR is absent or difficult to measure.

Atrial Fibrillation in Eight New World Camelids.

BACKGROUND: There is limited information on the incidence of clinical signs, concurrent illness and treatment options for atrial fibrillation (AF) in New World Camelids (NWC). OBJECTIVE: Describe clinical signs and outcome of AF in NWC. ANIMALS: Eight New World Camelids admitted with AF. METHODS: A retrospective observational study of camelids diagnosed with AF based on characteristic findings on electrocardiogram (ECG). RESULTS: All animals had an irregularly irregular heart rhythm detected on physical examination and 4 cases had obtunded mentation on admission. Three camelids were diagnosed with AF secondary to oleander intoxication, 3 animals had underlying cardiovascular disease, 1 was diagnosed with lone AF and 1 had AF diagnosed on examination for a urethral obstruction. Five of eight animals survived to discharge and nonsurvivors consisted of animals which died or were euthanized as a result of cardiovascular disease (2/8) or extra-cardiac disease unrelated to the AF (1/8). CONCLUSIONS AND CLINICAL IMPORTANCE: Atrial fibrillation occurs in NWC in association with cardiovascular disease, extra-cardiac disease or as lone AF. Amiodarone and transthoracic cardioversion were attempted in one llama with lone AF, but were unsuccessful. Atrial fibrillation was recorded in 0.1% of admissions.

Sudden death associated with QT interval prolongation and KCNQ1 gene mutation in a family of English Springer Spaniels.

BACKGROUND: A 5-year-old, healthy English Springer Spaniel died suddenly 4 months after delivering a litter of 7 puppies. Within 4 months of the dam's death, 3 offspring also died suddenly. HYPOTHESIS: Abnormal cardiac repolarization, caused by an inherited long QT syndrome, is thought to be responsible for arrhythmias leading to sudden death in this family. ANIMALS: Four remaining dogs from the affected litter and 11 related dogs. METHODS: Physical examination and resting ECG were done on the littermates and 9 related dogs. Additional tests on some or all littermates included echocardiogram with Doppler, Holter monitoring, and routine serum biochemistry. Blood for DNA sequencing was obtained from all 15 dogs. RESULTS: Three of 4 littermates examined, but no other dogs, had prolonged QT intervals with unique T-wave morphology. DNA sequencing of the KCNQ1 gene identified a heterozygous single base pair mutation, unique to these 3 dogs, which changes a conserved amino acid from threonine to lysine and is predicted to change protein structure. CONCLUSIONS AND CLINICAL IMPORTANCE: This family represents the first documentation in dogs of spontaneous familial QT prolongation, which was associated with a KCNQ1 gene mutation and sudden death. Although the final rhythm could not be documented in these dogs, their phenotypic manifestations of QT interval prolongation and abnormal ECG restitution suggested increased risk for sudden arrhythmic death. The KCNQ1 gene mutation identified is speculated to impair the cardiac repolarizing current IKs, similar to KCNQ1 mutations causing long QT syndrome 1 in humans.

Efficient Bell state analyzer for time-bin qubits with fast-recovery WSi superconducting single photon detectors.

We experimentally demonstrate a high-efficiency Bell state measurement for time-bin qubits that employs two superconducting nanowire single-photon detectors with short dead-times, allowing projections onto two Bell states, |ψ⁻〉 and |ψ⁺〉. Compared to previous implementations for time-bin qubits, this yields an increase in the efficiency of Bell state analysis by a factor of thirty.

Natural history of arrhythmogenic right ventricular cardiomyopathy in the boxer dog: a prospective study.

BACKGROUND: Boxer arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease that may result in sudden death or heart failure. HYPOTHESIS/OBJECTIVES: To prospectively study the natural history of Boxer ARVC. ANIMALS: 72 dogs (49 ARVC, 23 controls). METHODS: Boxers >1 year of age were recruited for annual reevaluation. CONTROLS were defined as being ≥6 years of age and having <50 ventricular premature complex (VPCs)/24 h. ARVC was defined as ≥300 VPCs/24 h in the absence of other disease. Dogs were genotyped for the striatin deletion when possible. Descriptive statistics were determined for age; VPC number; annual change in VPC number; and left ventricular (LV) echocardiographic dimensions. Survival time was calculated. RESULTS: Controls: median age of 7 years (range, 6-10); number of VPCs 12 (range, 4-32). Median time in study of 6 years (range, 2-9). Seventeen of 23 were genotyped (5 positive, 12 negative). ARVC: median age of diagnosis of 6 (range, 1-11). Median time in study 5 years (range, 3-8). A total of 33% were syncopal and 43/49 were genotyped (36 positive, 7 negative). Yearly change in VPCs was 46 (range, -7,699 to 33,524). Annual percentage change in LV dimensions was 0, and change in fractional shortening (FS%) was 2%. Two dogs had FS% <20%. Although ARVC dogs died suddenly, there was no difference in survival time between groups. ARVC median age of survival was 11 years, and for controls was 10 years. CONCLUSIONS/CLINICAL IMPORTANCE: Arrhythmogenic right ventricular cardiomyopathy is a disease of middle age and frequently is associated with the striatin deletion. Syncope occurs in approximately 1/3 of affected dogs; systolic dysfunction is uncommon. The prognosis in many affected dogs is good.

Identification of PDE5A:E90K: a polymorphism in the canine phosphodiesterase 5A gene affecting basal cGMP concentrations of healthy dogs.

BACKGROUND: Cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE5A) is the target of phosphodiesterase inhibitors such as sildenafil. Polymorphisms in the PDE5A gene that may predict response to therapy with sildenafil and nitric oxide, be linked to disease progression, and aid in risk assessment have been identified in human beings. Identification of polymorphisms in PDE5A could affect the physiologic actions of PDE5A and the effects of phosphodiestrase type 5 inhibitor drugs. HYPOTHESIS/OBJECTIVE: Functional polymorphisms exist in the canine PDE5A gene. Specific objectives were to identify PDE5A polymorphisms and evaluate their functional relevance. ANIMALS: Seventy healthy dogs. METHODS: The exonic, splice-site, 3' and 5' untranslated regions of the canine PDE5A gene were sequenced in 15 dogs and aligned with the canine reference sequence. Identified polymorphisms were evaluated in 55 additional, healthy, unrelated dogs of 20 breeds. Plasma was collected from 51 of these dogs and cGMP was measured. An unpaired t-test and one-way ANOVA with Dunnett's test of multiple comparisons were used to evaluate the effect of genotype on cGMP. RESULTS: A common exonic polymorphism was identified that changed glutamic acid to lysine and resulted in significantly lower cGMP concentrations in the group with polymorphism versus the wild type group (P = .014). Additionally, 6 linked single nucleotide polymorphisms in the 3' untranslated region were identified that did not alter cGMP concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE: A polymorphism exists in the canine PDE5A gene that is associated with variable circulating cGMP concentrations in healthy dogs and warrants investigation in diseases such as pulmonary hypertension.

Association of dilated cardiomyopathy with the striatin mutation genotype in boxer dogs.

BACKGROUND: Myocardial disease in the Boxer dog is characterized by 1 of 2 clinical presentations, dilated cardiomyopathy (DCM) characterized by ventricular systolic dysfunction, dilatation and tachyarrhythmias, and arrhythmogenic right ventricular cardiomyopathy (ARVC) characterized by ventricular tachyarrhythmias, syncope, and sudden death. Boxer ARVC has been associated with a deletion in the striatin gene in some families. HYPOTHESIS/OBJECTIVES: We hypothesized that both presentations represent a single disease, and the development of DCM in the Boxer is associated with the striatin deletion. ANIMALS: Thirty-three adult Boxer dogs with DCM, 29 adult Boxer dogs with the striatin deletion and ARVC, and 16 Boxers without cardiac disease. METHODS: DNA samples were evaluated for the striatin deletion. Association of the deletion with the DCM phenotype was tested by a Fisher's exact test. T-tests were used to evaluate potential differences between the positive heterozygous and positive homozygous groups with DCM with regard to age, LVIDD, LVIDS, and FS%. RESULTS: Thirty of 33 dogs with DCM were positive for the striatin deletion. The striatin mutation and the homozygous genotype were strongly associated with the DCM phenotype (P < .001 and P = .005). There was no statistical difference between the heterozygous and homozygous groups with regard to age and echocardiographic measurements. CONCLUSIONS AND CLINICAL IMPORTANCE: This study demonstrates an association between DCM in the Boxer dog and the striatin mutation, particularly with the homozygous genotype. The observation that 3/33 dogs developed DCM and lacked the striatin mutation suggests that there is at least 1 other cause of DCM in the Boxer dog.

Effect of body position on electrocardiographic recordings in dogs.

OBJECTIVE: To determine whether body position (standing vs right lateral recumbency) altered the quality of the electrocardiogram (ECG) and value of ECG variables in dogs when the ECG was recorded using American Heart Association guidelines for frequency response. DESIGN: Crossover study using a convenience sample. METHODS: ECGs were recorded twice in 65 sled dogs in random order with each dog standing or placed in right lateral recumbency. Lead II and three semi-orthogonal leads (I, aVF, and V10 ) were recorded and muscle tremor artefact was assessed. RESULTS: Lead II ECGs obtained from dogs in right lateral recumbency had less muscle tremor artefact and consequently a shorter QRS duration than ECGs obtained with the dogs standing. The P, Q, R and S wave amplitudes differed in selected leads and the mean electrical axis was shifted 20° to the right when dogs were in right lateral recumbency. CONCLUSIONS: Right lateral recumbency improves the quality of ECG recording in dogs by decreasing muscle tremor artefact, alters the amplitude of P, R and S waves in specific leads and results in a rightward shift in the mean electrical axis, relative to standing.

Familial subvalvular aortic stenosis in golden retrievers: inheritance and echocardiographic findings.

OBJECTIVES: To describe the echocardiographic findings and pedigree analysis of golden retrievers with subvalvular aortic stenosis. METHODS: Seventy-three golden retrievers were evaluated by auscultation and echocardiography. A subcostal continuous-wave Doppler aortic velocity ê2·5 m/s and presence of a left basilar systolic ejection murmur were required for diagnosis of subvalvular aortic stenosis. Three echocardiographic characteristics were recorded: evidence of aortic insufficiency, subvalvular ridge or left ventricular hypertrophy. A disease status score was calculated by totalling the number of echocardiographic -characteristics per subject. RESULTS: Thirty-two of 73 dogs were affected and their aortic velocities were as follows: range 2·5 to 6·8 m/s, median 3·4 m/s and standard deviation 1·2 m/s. Echocardiographic characteristics of 32 affected dogs were distributed as follows: left ventricular hypertrophy 12 of 32, aortic insufficiency 20 of 32 and subvalvular ridge 20 of 32. Disease status score ranged from 0 to 3 with a median of 2. There was a statistically significant correlation between aortic velocity and disease status score (r=0·644, P<0·0001). Subvalvular aortic stenosis was observed in multiple generations of several families and appears familial. CLINICAL SIGNIFICANCE: Subvalvular aortic stenosis in the golden retriever is familial. Severity of stenosis correlates well with cumulative presence of echocardiographic characteristics (left ventricular hypertrophy, subvalvular ridge and aortic insufficiency).

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.

Estimation of left ventricular filling pressure by Doppler echocardiography in dogs with pacing-induced heart failure.

BACKGROUND: Congestive heart failure (CHF) is a common clinical syndrome characterized by elevated filling pressure. HYPOTHESIS: Doppler echocardiographic (DE) variables of left ventricular (LV) filling can predict a decline of LV end-diastolic pressure (LVEDP) induced by acute preload reduction in dogs with compensated CHF. ANIMALS: Five male hound dogs. METHODS: Dogs previously instrumented with a transvenous cardiac pacemaker and a LV pressure gauge were paced at 160-180 bpm to induce mild CHF characterized by LVEDP > 20 mmHg. LVEDP and 9 DE variables of LV filling derived from diastolic time intervals, transmitral and pulmonary venous flow, and tissue Doppler imaging were measured simultaneously at baseline and 30, 60, 120, and 240 minutes after furosemide (4 mg/kg, IV) or placebo (0.9% saline, IV). Repeated measures analysis of variance and correlation analysis were used to determine the association between the decline of LVEDP after furosemide and DE measures of LV filling pressure (LVFP). RESULTS: Furosemide but not placebo decreased LVEDP (P < .001). The ratio of early transmitral flow velocity to LV isovolumic relaxation time (E : IVRT) predicted LVEDP best (R(2)= .50; P < .001). Correlations were also found between LVEDP and IVRT, E, ratio between E and late diastolic transmitral flow velocity (E : A), and early diastolic velocity of the mitral annulus (Ea). The ratio of E to Ea (E : Ea) was not useful in the prediction of LVEDP in this model. CONCLUSION AND CLINICAL IMPORTANCE: E : IVRT can be used to predict LVFP in dogs with mild left-sided CHF induced by rapid pacing.

Saccade initiation and accuracy in gaze shifts are affected by visual stimulus significance.

The effect of visual stimulus significance on saccade latency and accuracy in gaze shifts was investigated. Stimulus significance refers to the temporal proximity of an imperative stimulus. It was hypothesized that stimulus significance serves as a cue that influences the observer's expectancy for a forthcoming event. Twenty-one undergraduate students participated in two experiments involving monitoring of visual events. Stimuli were a sequence of 1,000 single-digit integers presented one at a time at 9 degrees of visual angle to the left or right of a fixation point in random order. The subject was required to make a manual response after the presentation of a sequence of two odd integers. The probability of the subsequent integer being odd, a "target," after the presentation of an odd integer was 0.75. The integer after a target was always an even integer. When stimulus location was unpredictable (Experiment 1), latency of visually guided saccades to the target was shorter (p < .01) than to the nontarget stimuli. Under the condition of predictable stimulus location (Experiment 2), anticipatory saccades to the target occurred earlier (p < .01), more frequently (p < .01), and more accurately (p < .05). Our results suggest that both timing and accuracy of gaze shift are affected by the observer's expectation of future events.