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.

Echocardiographic caudal vena cava measurements in healthy cats and in cats with congestive heart failure and non-cardiac causes of cavitary effusions.

BACKGROUND: Echocardiographic indices of the inferior vena cava have been associated with elevated right atrial pressures in humans. HYPOTHESIS/OBJECTIVES: Describe caudal vena caval (CVC) sonographic dimensions in healthy cats compared to cats with cardiogenic cavitary effusion (CCE), cardiogenic pulmonary edema (CPE), or non-cardiac causes of cavitary effusion (NCE). ANIMALS: 30 healthy control cats and 52 client-owned cats with CCE, CPE, or NCE examined at two university hospitals. METHODS: Sagittal 2-dimensional (2D) and M-mode CVC dimensions were acquired from the subxiphoid view. Caudal vena cava collapsibility index (CVC-CI) was calculated. Variables were compared between study groups using Kruskal-Wallis and Dunn's Bonferroni testing. Receiver operating characteristic curves were used to assess sensitivity and specificity for diagnostic categories. RESULTS: Healthy cats had sagittal 2D and M-mode (median, interquartile range) CVC maximal dimensions of 2.4 mm (1.3-4.0) and 3.4 mm (1.5-4.9) and CVC-CI of 52% (45.2-61.8) and 55% (47.8-61.3), respectively. The CVC maximal dimensions in healthy controls were smaller than in cats with cavitary effusions or pulmonary edema (all P<0.05). CVC-CI was different between CCE and NCE (P<0.0001) with cutoffs of CVC-CI ≤38% (2D) or ≤29% (M-mode) being 90.5% and 85.7% sensitive, and 94.4% and 100% specific for diagnosis of CCE, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Caudal vena cava measurements are larger in cats with cavitary effusions and cats with CPE than healthy cats. In cats with cavitary effusion, decreased CVC-CI, ≤38% (2D) or ≤29% (M-mode), was helpful in distinguishing between cardiogenic and noncardiogenic etiology.

Echocardiographic assessment of dilated cardiomyopathy in dogs.

Dilated cardiomyopathy (DCM) is a frequent cause of cardiac disability, congestive heart failure (CHF), and arrhythmic death in dogs. The etiology of DCM is usually idiopathic/genetic, but some causes of a DCM phenotype are reversible. The disease is classified into preclinical (occult) and clinical (overt) stages; the latter stems from heart failure with reduced ejection fraction. DCM is further characterized by clinical, electrocardiographic, circulating biomarker, and imaging abnormalities. The diagnosis of clinical DCM with CHF is straightforward; however, identification of the preclinical stage can be challenging. Echocardiography is central to the diagnosis of both stages and characterized by left ventricular (LV) systolic dysfunction with progressive chamber dilation and variable enlargements of the left atrium and right-sided chambers. Left ventricular dilation is defined by increased LV end-diastolic volumes, areas, and internal dimensions normalized to body size or indexed to the aorta. Systolic dysfunction is characterized by decreased LV ejection fraction, increased end-systolic volume, and reduced shortening across minor and longitudinal LV axes. Dyssynchrony can confound the interpretation of linear indices of systolic function. A comprehensive echocardiogram in DCM includes two-dimensional and M-mode studies, spectral and tissue Doppler imaging, and potentially three-dimensional echocardiography and myocardial strain imaging. Echocardiographic findings should be interpreted within the context of identifiable risks and comorbidities, physical diagnosis, complementary diagnostic testing, and limitations of current reference intervals. Ambiguous examinations should be repeated. Specific echocardiographic criteria for the diagnosis of DCM are proposed to encourage discussion and additional outcome and breed-specific echocardiographic studies of canine DCM.

Association of diet with clinical outcomes in dogs with dilated cardiomyopathy and congestive heart failure.

INTRODUCTION: Dilated cardiomyopathy (DCM) in dogs has been associated with feeding of grain-free (GF), legume-rich diets. Some dogs with presumed diet-associated DCM have shown improved myocardial function and clinical outcomes following a change in diet and standard medical therapy. HYPOTHESIS: Prior GF (pGF) diet influences reverse cardiac remodeling and clinical outcomes in dogs with DCM and congestive heart failure (CHF). ANIMALS AND METHODS: A retrospective study was performed with 67 dogs with DCM and CHF for which diet history was known. Dogs were grouped by diet into pGF and grain-inclusive (GI) groups. Dogs in the pGF group were included if diet change was a component of therapy. Survival was analyzed using Kaplan-Meier curves and the Cox proportional-hazards model. RESULTS: The median survival time was 344 days for pGF dogs vs. 253 days for GI dogs (P = 0.074). Statistically significant differences in median survival were identified when the analysis was limited to dogs surviving longer than one week (P = 0.033). Prior GF dogs had a significantly worse outcome the longer a GF diet was fed prior to diagnosis (P = 0.004) or if they were diagnosed at a younger age (P = 0.017). Prior GF dogs showed significantly greater improvement in normalized left ventricular internal diastolic diameter (P = 0.038) and E-point septal separation (P = 0.031) measurements and significant decreases in their furosemide (P = 0.009) and pimobendan (P < 0.005) dosages over time compared to GI dogs. CONCLUSIONS: Prior GF dogs that survived at least one week after diagnosis of DCM, treatment of CHF, and diet change had better clinical outcomes and showed reverse ventricular remodeling compared to GI dogs.

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.

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.

Methods and reliability of tissue Doppler imaging for assessment of left ventricular radial wall motion in horses.

BACKGROUND: Noninvasive assessment of left ventricular (LV) function is incompletely studied in horses. OBJECTIVES: The goals of this study were to investigate the feasibility, techniques, and reliability of tissue Doppler imaging (TDI) for characterization of LV radial wall motion in healthy horses. ANIMALS: Three Standardbreds, 3 Thoroughbreds; age 8-14 years; body weight 517-606 kg. METHODS: Repeated echocardiographic examinations were performed by 2 observers in unsedated horses using TDI. Test reliability was determined by estimating measurement variability, within-day interobserver variability, and between-day interobserver and intraobserver variability of all echocardiographic variables. Variability was expressed as coefficient of variation (CV) and the absolute value below which the difference between 2 measurements will lie with 95% probability. RESULTS: Assessment of LV radial wall motion by TDI was feasible in all horses. Measurement variabilities were very low (CV < 5%) to low (CV 5-15%) for most variables. Within-day interobserver variability as well as between-day interobserver and intraobserver variabilities were low to moderate (CV 16-25%) for most variables. All pulsed-wave TDI variables of systolic LV function showed very low to low variability, whereas some of the variables of LV diastolic and LA function showed moderate to high (CV > 25%) variability. Pulsed-wave TDI variables appeared more reliable than color TDI variables. CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of TDI indices of LV function is feasible and reliable in adult Standardbred and Thoroughbred horses. The clinical relevance of LV function assessment by TDI remains to be determined.

Left ventricular radial and circumferential wall motion analysis in horses using strain, strain rate, and displacement by 2D speckle tracking.

BACKGROUND: Noninvasive assessment of left-ventricular (LV) function is clinically relevant, but is incompletely studied in horses. OBJECTIVES: To document the feasibility, describe the techniques, and determine the reliability of 2D speckle tracking (2DST) for characterization of LV radial and circumferential wall motion in horses. ANIMALS: Three Standardbreds, 3 Thoroughbreds; age 8-14 years; body weight 517-606 kg. METHODS: Observational study. Repeated 2-dimensional echocardiographic examinations were performed in unsedated horses by 2 observers and subsequently analyzed by 2DST. Test reliability was determined for segmental and for averaged 2DST indices (including strain, strain rate, displacement, and rotation) by estimating measurement variability, within-day interobserver variability, between-day interobserver variability, and between-day intraobserver variability. Variability was expressed as coefficient of variation (percent) and the absolute value below which the difference between 2 measurements will lie with 95% probability. RESULTS: 2DST analyses were feasible in 16 of 18 echocardiographic studies. The automated tracking was accurate during systole but inaccurate during diastole. Reliability was higher for radial compared to circumferential measurements. For radial strain, radial systolic strain rate, and radial systolic displacement, the test-retest variabilities ranged between 2.4 and 33.1% for segmental and between 4.1 and 16.1% for averaged measurements. CONCLUSIONS AND CLINICAL IMPORTANCE: Systolic radial motion of the LV at the chordal level could be reliably characterized in horses by 2DST. Circumferential measurements were less reliable. Diastolic measurements were invalid because of inaccurate tracking. The clinical value of LV wall motion analysis by 2DST in horses requires further investigation.

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.

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.

Cardiovascular images: vascular hamartoma of the mitral valve in a horse.

An 8-month-old Hanoverian gelding was presented with a history of cardiac murmurs that were not apparent as a foal nor reported at the time of castration. Major echocardiographic findings included mitral valvular thickening, functional stenosis, and mitral regurgitation of sufficient severity to cause diastolic and systolic cardiac murmurs, left-sided volume overload, and pulmonary hypertension. Due to the hemodynamic severity of the lesion and poor prognosis for future performance and longevity, euthanasia was elected. On gross postmortem examination, there was focal fibrous epicarditis affecting the heart base, and the left atrium was moderately dilated. The mitral valve surface was irregular and contained several nodules along the atrial face of the cusp. Histologically, this lesion was diagnosed as a vascular hamartoma, which is rarely reported in veterinary species and has not been described in heart valves. This benign proliferative lesion, and concurrent valvular dysfunction, was associated with an unusual manifestation of clinically evident disease and should be differentiated from common incidental valvular lesions such as hematocysts.

Two-dimensional, long-axis echocardiographic ratios for assessment of left atrial and ventricular size in dogs.

INTRODUCTION: Left ventricular (LV) and left atrial (LA) enlargement affect management and outcome of dogs with cardiac disease. Short-axis, two-dimensional echocardiographic (2DE) images, indexed to the aorta (Ao), are frequently used to identify cardiomegaly. Long-axis images offer complementary views of the left heart. ANIMALS: Eighty healthy dogs and 25 dogs with MMVD. METHODS: Healthy dogs were prospectively recruited to determine reference intervals (Clinical Laboratory Standards Institute methodology) for long-axis ratios. Measurement variability and repeatability were quantified by intraclass correlation coefficient and coefficient of variation. Mean long-axis ratios from dogs with MMVD were compared with healthy dogs (unpaired t-test). In addition, the proportion of MMVD dogs exceeding the 97.5 percentile by LV/Ao and a conventional, allometric method were compared (McNemar's test). RESULTS: Two-dimensional echocardiographic long-axis reference intervals were as follows: left ventricular to aortic dimension (LV/Ao) 1.8-2.5; left atrial to aortic dimension (LA/Ao) 1.8-2.4, and left atrial to left ventricular dimension (LA/LV) 0.9-1.1. Intraobserver and interobserver measurement agreement was good-to-excellent (intraclass correlation coefficients ≥0.84), and day-to-day variability was low (coefficient of variations <4%). Left ventricular to aortic dimension, LA/Ao, and LA/LV were significantly greater in canine MMVD compared with healthy dogs (p<0.001). The percentages of MMVD dogs demonstrating LV dilatation by LV/Ao and conventional method were 68% and 36%, respectively (p=0.043, 95% confidence interval for difference 7.9%, 56.1%). CONCLUSIONS: Simple 2DE long-axis ratios of LV/Ao, LA/Ao, and LA/LV are repeatable and demonstrate clinical utility for identifying LV and LA enlargement in dogs with MMVD.

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.

Intranuclear paracrystals observed in striated muscle specific LIM protein-deficient mouse cardiomyocytes.

A paracrystalline structure was observed within left ventricular cardiomyocyte nuclei of MLP(-/-) mice. The paracrystal possessed cross lines, approximately 8.0 micro m long and 0.3 micro m wide, with a slender spindle shape and a periodicity of 13 nm. Paracrystals were best observed along the longitudinal orientation of myofibrils and were detected in less than 10% of the nuclei observed. One dimension of the protein unit forming the paracrystal was 8.5 nm long. The electron density of the paracrystal appeared to be slightly higher than that of heterochromatin, suggesting that RNA-associated proteins are constituents of the paracrystal. This is the first report of intranuclear paracrystals in cardiomyocytes, which appear to be unique to MLP(-/-) mice.

Double chambered right ventricle in 9 cats.

BACKGROUND: Double-chambered right ventricle (DCRV) is a frequently recognized cardiac congenital abnormality in humans. It has been described in dogs and in 1 cat. However systemic description of clinical and echocardiographic features of the disease in cats is currently lacking from the veterinary literature. ANIMALS: Nine cats with DCRV are described. RESULTS: The cats ranged from 4 months to 10 years of age. Eight cats at presentation were asymptomatic and 1 cat had chylothorax. In all cases echocardiography revealed abnormal fibromuscular bundles obstructing the mid-right ventricle, dividing the chamber into 2 compartments. The proximal right ventricular compartment was markedly hypertrophied, and right atrial dilation was usually present. The mean pressure gradient measured across the stenotic area was 130 +/- 50 mm Hg. Concurrent abnormalities included a ventricular septal defect (n = 2); aortic malalignment, aortic insufficiency (n = 1); and congenital peritoneal-pericardial diaphragmatic hernia (n = 1). Two cats had systolic anterior motion of the mitral valve, one of which had concurrent left ventricular hypertrophy. Five cats have remained asymptomatic for a median period of 3.6 years (range, 3.3-5 years) and 3 cats have developed clinical signs associated with congestive heart failure (at 2, 3.3, and 9 years). One cat showed progressive lethargy and exercise intolerance and underwent partial ventriculectomy at the age of 2 years. This cat died during the operation with electromechanical dissociation. CONCLUSIONS: DCRV is a congenital cardiac abnormality that may be more common than previously recognized.

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.

Echocardiographic assessment of the left ventricular outflow tract in the Boxer.

BACKGROUND: Soft, variable ejection murmurs are common in Boxers and are associated with increased left ventricular outflow tract (LVOT) ejection velocities. Whether these murmurs are physiologic or indicate mild aortic stenosis is controversial. Ejection velocity is impacted by LVOT area and ventricular stroke volume (SV), suggesting that these variables are pertinent to murmur development. HYPOTHESIS: Boxers with ejection murmurs have a smaller LVOT and equivalent SV indices, compared with values in dogs without murmurs. ANIMALS: Three age- and weight-matched groups of dogs--15 Boxers with soft ejection murmurs (group I); 15 Boxers without murmurs (group II); and 15 nonBoxer dogs without murmurs (group III)--were studied. METHODS: All dogs underwent 2-dimensional and Doppler echocardiographic examinations. The LVOT size at multiple levels; LVOT ejection velocity, stroke distance, and SV index; and right ventricular SV index were determined and compared by analysis of variance. RESULTS: Indexed LVOT areas in Boxer groups were not different, but were significantly smaller than those of non-Boxer dogs. Ejection velocities and stroke distances were significantly different across all groups, with group I having the highest and group III having the lowest values. Doppler SV indices (ml/m2) for group-I versus group-II Boxers were 70 +/- 16(SD) versus 62 +/- 12 for the LVOT (P = .27) and 58 +/- 12 versus 48 +/- 9 for the right ventricle (P = .14). CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest that a relatively smaller LVOT in Boxers predisposes them to increased ejection velocity and development of murmurs. The contribution of SV to the genesis of these often labile murmurs requires additional study.

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.

Cardiovascular-renal axis disorders in the domestic dog and cat: a veterinary consensus statement.

OBJECTIVES: There is a growing understanding of the complexity of interplay between renal and cardiovascular systems in both health and disease. The medical profession has adopted the term "cardiorenal syndrome" (CRS) to describe the pathophysiological relationship between the kidney and heart in disease. CRS has yet to be formally defined and described by the veterinary profession and its existence and importance in dogs and cats warrant investigation. The CRS Consensus Group, comprising nine veterinary cardiologists and seven nephrologists from Europe and North America, sought to achieve consensus around the definition, pathophysiology, diagnosis and management of dogs and cats with "cardiovascular-renal disorders" (CvRD). To this end, the Delphi formal methodology for defining/building consensus and defining guidelines was utilised. METHODS: Following a literature review, 13 candidate statements regarding CvRD in dogs and cats were tested for consensus, using a modified Delphi method. As a new area of interest, well-designed studies, specific to CRS/CvRD, are lacking, particularly in dogs and cats. Hence, while scientific justification of all the recommendations was sought and used when available, recommendations were largely reliant on theory, expert opinion, small clinical studies and extrapolation from data derived from other species. RESULTS: Of the 13 statements, 11 achieved consensus and 2 did not. The modified Delphi approach worked well to achieve consensus in an objective manner and to develop initial guidelines for CvRD. DISCUSSION: The resultant manuscript describes consensus statements for the definition, classification, diagnosis and management strategies for veterinary patients with CvRD, with an emphasis on the pathological interplay between the two organ systems. By formulating consensus statements regarding CvRD in veterinary medicine, the authors hope to stimulate interest in and advancement of the understanding and management of CvRD in dogs and cats. The use of a formalised method for consensus and guideline development should be considered for other topics in veterinary medicine.