2006 ACVIM Abstracts Increased adrenergic stimulation contributes to ventricular dilation, systolic dysfunction, and neurohormonal derangements in patients with dilated cardiomyopathy (DCM). Beta-adrenergic blocking agents, such as carvedilol, reduce remodeling and improve survival in humans with DCM, however, little is known regarding the safety and efficacy of such treatment in dogs with DCM. We sought to determine the effects of carvedilol on echocardiographic and neurohormonal parameters in dogs with DCM over a 4-month treatment period. Twenty-three dogs with symptomatic DCM were entered into a prospective, placebo-controlled, double-blinded randomized study. Patients were evaluated by cardiac ultrasound, ECG, thoracic radiographs, and epinephrine, norepinephrine, aldosterone, renin activity, and atrial and Btype natriuretic peptide assay. Dogs were randomized to carvedilol or placebo in a 2 : 1 fashion and medications titrated to 0.3 mg/kg q12hrs over a 4-week period, followed by 3 months of chronic therapy. Primary study endpoints involved echocardiographic left ventricular volume and function. Secondary endpoints involved neurohormonal activation. Sixteen dogs were randomized to carvedilol and 7 dogs to placebo. Baseline characteristics between groups were similar. One dog in each group died during the titration phase. After three months of chronic therapy, 13 dogs receiving carvedilol and 5 dogs receiving placebo were still alive. Carvedilol dogs experienced a statistically significant increase in left ventricular end-diastolic volume (LVVd change +8.6%; P 5 0.009) and LV end-systolic volume (LVVs change +14.6%; P 5 0.011) over the 4-month study period. LV volume of placebo dogs also increased, but these changes were not statistically significant (LVVd change +15.1%, P 5 0.16; LVVs change +13.2%, P 5 0.58). There was no difference in the mean change of LVVd and LVVs between carvedilol and placebo groups (LVVd P 5 0.30; LVVs P 5 0.50), suggesting that both groups experienced similar amounts of progressive LV enlargement. There was no difference in the absolute value or percent change in plasma ANP, BNP, renin activity, norepinephrine, epinephrine, or aldosterone between groups. In addition, there was no difference in the absolute value or percent change in radiographic heart size, systolic time intervals, blood pressure, heart rate, BUN, creatinine, sodium, or owner perceived quality-of-life between groups. Carvedilol administration did not improve echocardiographic or neurohormonal parameters of heart function over 3 months of chronic oral treatment. The lack of effect may be related to severity of disease, carvedilol dose, and brevity of follow-up time. Statistical power of the present study was adversely affected by a high mortality rate and small sample size.

ABSTRACT #75 ACUTE CARDIOVASCULAR EFFECTS OF PIMOBENDAN IN DOGS WITH STABLE CONGESTIVE HEART FAILURE DUE TO CHRONIC DEGENERATIVE ATRIOVENTRICULAR VALVE DISEASE. RM Roland1, SG Gordon,1 A Bahr2, MW Miller,1 AB Saunders.1 1 Department of Small Animal Clinical Science and Michael E. DeBakey Institute, and 2Department of Large Animal Clinical Science and Surgery, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX. Chronic degenerative atrioventricular valve disease (CVD) is the leading cause of canine congestive heart failure (CHF) and in advanced stages is associated with systolic dysfunction. Pimobendan (VetmedinH) is an orally active, rapidly absorbed inodilator demonstrating peak cardiovascular effects within 1–2 hours of administration in normal dogs. The hypothesis of this prospective study was that pimobendan (pimo) therapy on a background of conventional heart failure therapy (angiotensin converting enzyme inhibitors, diuretics, antiarrhythmics and additional afterload reducers as required) in dogs with stable CHF (furosemide dependant but not requiring contemporary dosage changes) due to CVD would result in acute (within 24 hours) favorable cardiovascular effects. Seven small breed dogs (,18 kg) with CVD and stable CHF were enrolled in the study. Dogs were hospitalized for 3 days. On days 1 and 3, all dogs were evaluated with a physical examination, thoracic radiographs, complete blood work, ECG, indirect systemic blood pressure (SBP), echocardiogram and radionuclide ventriculography (RNV). Throughout the study all dogs were maintained on their current medications and doses. On the evening of day 2 and morning of day 3 pimo was administered at a dose of 0.25–0.3 mg/ kg by mouth. Measured parameters were compared with a paired Student’s t test and a p value ,0.05 was considered significant. Lack of significant differences in PCV, BUN or creatinine suggested overall volume status was unchanged between day 1 and day 3. Significant reductions in left ventricular internal dimension in diastole (LVIDd) and two dimensional left atrial to aortic root ratio and a trend towards a decrease in vertebral heart score (p 5 0.07) suggested reduced overall cardiac size. Significant reductions of LVID in systole and LV short axis area in systole documented increased systolic function. No significant difference in SBP coupled with a significant increase in aortic TVI suggested balanced afterload reduction and enhanced forward

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cardiac output. Finally, significant reduction in the ratio of early mitral inflow to annular mitral E wave (E:Ea) suggested a reduction in left atrial pressure. Changes in RNV parameters including regurgitation fraction (RF), ejection fraction, peak emptying rate, peak filling rate and time to peak filling were insignificant overall but 5/7 showed significant reductions in RF. Finally, 5/7 and 2/7 dogs had prolapse and flail of their mitral valves respectively on day 1 of the study and these abnormalities were not changed after the administration of pimo. These data suggest when added to background of conventional heart failure therapy pimo produces favorable cardiovascular effects following two oral doses in stable CHF due to CVD with no adverse short term effects.

ABSTRACT #76 ASSOCIATION OF PIMOBENDAN WITH VENTRICULAR ARRHYTHMIAS IN DOGS WITH CONGESTIVE HEART FAILURE. SL Rosenthal, MJ Ferguson, BK Lefbom, WD Tyrrell. Chesapeake Veterinary Cardiology Associates, Towson, Maryland. Cardiac arrhythmias are a common finding in dogs with congestive heart failure. These arrhythmias can be associated with syncope and even sudden death. Certain positive inotropic agents have been implicated in human congestive heart failure (CHF) patients to increase the incidence of tachyarrhythmias and sudden death. Pimobendan, a positive inotrope with vasodilating properties, has recently been advocated in the treatment of CHF in the dog. It is classified as a phosphodiesterase III (PDE III)inhibitor that reduces the breakdown of cAMP leading to potentiation of the adrenergic signal transduction, increased contractility, and vasodilation. Sensitization of the myofilaments to calcium is another proposed mechanism for the positive inotropic effects of pimobendan. Agents that inhibit PDE III (eg. milrinone and amrinone) have been implicated in the worsening of ventricular arrhythmias and an increased incidence of sudden death in humans. The objective of this study was to evaluate the potential proarrhythmic effects of pimobendan when added to conventional treatment for CHF canine patients. 8 dogs (4 Doberman pinchers, 1 each of Dalmatian, Greyhound, Labrador Retriever and Shiloh Shepherd) with CHF that were stable on therapy for CHF were used in the study population. Each dog had been treated with digoxin, furosemide, and enalapril prior to the addition of pimobendan. A serum biochemical profile, serum digoxin level and 24 hour ambulatory electrocardiogram (Holter) recording were performed as a baseline. 3/8 dogs (37.5%) of the dogs had a predominant rhythm of atrial fibrillation at the initiation of the study. The Holter recording was repeated approximately three weeks (range 14–24 days) after the initiation of therapy with pimobendan (mean dose 0.23 mg/kg twice daily, range 0.19– 0.31 mg/kg). The frequency of ventricular premature contractions (VPC’s) increased by a mean of 1096 per 24 hours (range 2850 to +5775) or a mean increase of 102.1% per 24 hours (range 257%–+ 713%). 75% of the dogs had an increase in the number of VPC’s, 62.5% of the dogs had an increased number of ventricular couplets, 50% of the dogs had an increased number of ventricular triplets, 25% of the dogs had and increased number of ventricular runs, and 25% had an increase in periods of ventricular tachycardia. The mean heart rate decreased in 62.5% of the dogs with a decrease in the mean from 119.9 beats per minute to 109.6 beats per minute. The trend seen in these patients point toward an increased frequency of ventricular arrhythmias in dogs with congestive heart failure when pimobendan is added to traditional therapy for CHF. Causes of the increased ventricular ectopy can be attributed to the introduction of the pimobendan, a pharmacologic interaction with the other medications, or related to normal daily variation in Holter monitor recordings. Sudden death or syncope was not noted in any of the animals enrolled in this study, however, continued followup will be prudent to statistically rule this out.

ABSTRACT #77 DUAL-CHAMBER CARDIAC PACING IN 25 DOGS. HW Green III, DF Hogan, AE Vibert, RA Sanders. Purdue University School of Veterinary Medicine, West Lafayette, IN. Symptomatic bradyarrhythmias resulting from atrioventricular (AV) blockade or sick sinus syndrome (SSS) are the primary indications for artificial cardiac pacing in dogs. Fixed-rate ventricular demand (VVI) pacing systems are still most commonly used dogs although dual chambered adaptive-rate pacing systems have been previously described and the potential benefits to cardiovascular performance demonstrated in humans and dogs. This retrospective study examines the outcome of dual-chamber (2-lead) pacemaker implantation in 25 dogs.