Results of the veterinary enalapril trial to prove reduction in onset of heart failure in dogs chronically treated with enalapril alone for compensated, naturally occurring mitral valve insufficiency

OBJECTIVE: To determine the efficacy of long-term enalapril administration in delaying the onset of congestive heart failure (CHF). DESIGN: Placebo-controlled, double-blind, multicenter, randomized trial. ANIMALS: 124 dogs with compensated mitral valve regurgitation (MR). PROCEDURES: Dogs randomly assigned to receive enalapril or placebo were monitored for the primary endpoint of onset of CHF for < or = 58 months. Secondary endpoints included time from study entry to the combined endpoint of CHF-all-cause death; number of dogs free of CHF at 500, 1,000, and 1,500 days; and mean number of CHF-free days. RESULTS: Kaplan-Meier estimates of the effect of enalapril on the primary endpoint did not reveal a significant treatment benefit. Chronic enalapril administration did have a significant benefit on the combined endpoint of CHF-all-cause death (benefit was 317 days [10.6 months]). Dogs receiving enalapril remained free of CHF for a significantly longer time than those receiving placebo and were significantly more likely to be free of CHF at day 500 and at study end. CONCLUSIONS AND CLINICAL RELEVANCE: Chronic enalapril treatment of dogs with naturally occurring, moderate to severe MR significantly delayed onset of CHF, compared with placebo, on the basis of number of CHF-free days, number of dogs free of CHF at days 500 and study end, and increased time to a combined secondary endpoint of CHF-all-cause death. Improvement in the primary endpoint, CHF-free survival, was not significant. Results suggest that enalapril modestly delays the onset of CHF in dogs with moderate to severe MR.     

Effect of benazepril on survival and cardiac events in dogs with asymptomatic mitral valve disease: a retrospective study of 141 cases

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) improve quality of life and extend the life span of dogs with naturally acquired ISACHC class II-III congestive heart failure (CHF). However, their effects on asymptomatic heart disease remain controversial. HYPOTHESIS: Benazepril (BNZ), an ACEI, could have beneficial effects at the asymptomatic stage of degenerative mitral valve disease (MVD). ANIMALS: Dogs with ISACHC class Ia MVD and moderate-to-severe mitral regurgitation (MR) assessed by the color Doppler mapping technique at entry (Day 0) were retrospectively included. METHODS: Dogs were assigned to the treated group (BNZ group) if they received BNZ (and no other cardiac medication) from Day 0 or to the untreated group (UT group) if they did not receive any cardioactive treatment until occurrence of CHF. RESULTS: A total of 141 dogs were included in the study, 66 in the BNZ group (dosage: 0.30 +/- 0.13 mg/kg) and 75 in the UT group. In the population (n = 93) including all breeds except Cavalier (CKC) and King Charles Spaniels (KC), median survival time to all causes of death in the BNZ group (n = 34, 3.3 years) was significantly longer than in the UT group (n = 59, 1.9 years) as was time to cardiac event (P < .05). Conversely, no effect of the BNZ treatment was observed in the CKC and KC population. CONCLUSIONS AND CLINICAL RELEVANCE: BNZ had beneficial effects in asymptomatic dogs other than CKC and KC affected by MVD with moderate-to-severe MR. Breed distribution should be taken into account for interpretation of clinical trials performed in dogs with cardiac disease.     

Controlled Clinical Evaluation of Enalapril in Dogs With Heart Failure: Results of the Cooperative Veterinary Enalapril Study Group The COVE Study Group

The clinical efficacy and safety of enalapril were evaluated in dogs with moderate or severe heart failure. This study was conducted at 19 centers and included 211 clientowned dogs with heart failure caused by mitral regurgitation (MR) due to acquired valvular disease or dilated cardiomyopathy (DCM). Dogs of various breeds, ages, and weights were included in the study. Replicates of 2 dogs each were formed, using separate allocation schedules for dogs with MR or DCM. One dog within each replicate received placebo tablets (vehicle tablets without enalapril) PO sid or bid, and the other dog received enalapril tablets at approximately 0.5 mg/kg sid or bid, based on individual need. In addition to the experimental drug, all dogs, except 1 in the placebo group, received furosemide; 73.3% of the dogs in the placebo group and 78.3% of those in the enala pril group received digoxin. Doses of enalapril or placebo were administered for approximately 28 days. In the placebo group, 68.6% of the dogs completed the study compared with 84.9% in the enalapril group; the difference between groups was significant ( P = .01). Significantly ( P = .01) more dogs in the placebo group compared with the enalapril group died or were removed from the study because of progression of heart failure. On day 28, all 14 clinical variables measured improved significantly ( P = .01) in the enalapril group compared with the placebo group. Five dogs (3 from the placebo group and 2 from the enalapril group) had to be removed from the study as a result of azotemia.     

Plasma atrial and brain natriuretic peptide levels in dogs with congestive heart failure.

Plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured in 6 dogs with experimental mitral regurgitation (MR) and 19 canine patients with asymptomatic and symptomatic congestive heart failure (CHF). In dogs with experimental MR, ANP and BNP concentrations were significantly correlated with pulmonary capillary wedge pressure (PCWP) (ANP; r=0.852, P=0.0004, BNP; r=0.832, P=0.0008). ANP level was shown to have a predominant effect on PCWP in comparison with BNP using multiple regression analysis. In canine patients with asymptomatic and symptomatic CHF, ANP and BNP concentrations were significantly different among the heart failure classes according to the New York Heart Association functional classification (ANP; P=0.0165, BNP; P=0.0005). In addition, ANP and BNP levels in dogs with decompensated heart failure (n=10) significantly increased in comparison with those in dogs with compensated heart failure (n=9). There was however no correlation between ANP and BNP levels in each heart failure class. In conclusion, plasma ANP and BNP levels may become predictors of PCWP and the severity of heart failure in dogs with MR, although further investigations on ANP and BNP levels in more clinical cases are required.     

Brain natriuretic peptide concentration in dogs with heart disease and congestive heart failure

Plasma brain natriuretic peptide concentration ([BNP]) is high in humans with cardiac disease and is further increased with congestive heart failure (CHF). The hypotheses of this study were that dogs with moderate to severe mitral regurgitation due to myxomatous mitral valve disease (MVD) would have increased plasma [BNP] compared to normal dogs, that plasma [BNP] would be higher in dogs with CHP, and that plasma [BNP] would predict premature death from cardiovascular disease. The study population consisted of 34 dogs: 9 normal dogs and 25 dogs with MVD. Patients were divided into 4 groups: group 1-10 dogs with moderate to severe MVD and no radiographic evidence of CHF; group II--6 dogs with severe MVD and mild CHF; group III--7 dogs with severe MVD and moderate CHF; and group IV--2 dogs with severe MVD and severe CHF. Diagnostic tests included thoracic radiographs, an echocardiogram, a serum chemistry profile, and the measurement of plasma [BNP] by a canine-specific radioimmunoassay. There was a significant positive correlation between the plasma [BNP] and heart disease/failure groups (P = .0036). Plasma [BNP] increased with progressively increasing severity of MVD and CHE Group I dogs had higher plasma [BNP] than did control dogs (P < .0001), and plasma [BNP] was higher in dogs with CHF (groups II-IV versus group I; P = .012). Plasma [BNP] was also weakly positively correlated with left atrial size (r = 0.43, P = .04). For every 10-pg/mL increase in plasma [BNP], the mortality rate over 4 months' time increased approximately 44%.     

Effects of Enalapril on Exercise Tolerance and Longevity in Dogs With Heart Failure Produced by Iatrogenic Mitral Regurgitation

This study was conducted to evaluate the effects of enalapril on exercise capacity and longevity in dogs with left-sided heart failure produced by iatrogenic mitral regurgitation. After surgical creation of mitral regurgitation, 18 dogs were allocated into replicates according to exercise capacities. One dog in each replicate received placebo, and the other received 0.5 mg/kg of enalapril sid for 9 days and bid thereafter. Exercise tolerance was studied after 10, 19, 52 to 53, and 80 to 81 days, respectively. Finally, the percentage of dogs in each group that survived 357 days was compared. The duration of exercise for dogs in the placebo and enalapril groups did not differ at baseline ( P> .1) or after 19 days (P > .1). Dogs that received enalapril had significantly reduced (P < .0011 exercise tolerance at day 10, and significantly increased (P = .002) exercise tolerance at days 52 to 53 and 80 to 81 when compared with controls. At 357 days, 22% of dogs receiving placebo were alive, compared with 67% of dogs receiving enalapril; however, these differences were not statistically significant (P = .124). This study shows that enalapril increases exercise tolerance in dogs with left-sided heart failure induced by iatrogenic mitral regurgitation. J Vet Intern Med 1996;10:85–87. Copyright © 1996 by the American College of Veterinary Internal Medicine .     

A double-blind,randomized, placebo-controlled study of pimobendan in dogs with dilated cardiomyopathy

A double-blind, randomized, placebo-controlled study was conducted to examine the effect on heart failure class and survival of pimobendan, an oral calcium-sensitizing inodilator, in dogs with dilated cardiomyopathy (DCM). Pimobendan (0.3-0.6 mg/kg body weight/d) or placebo was administered to English Cocker Spaniels (CSs; n = 10) and Doberman Pinschers (DPs: n = 10) that had DCM in addition to background therapy of furosemide, enalapril, and digoxin. Addition of pimobendan to standard triple therapy was associated with a significant improvement in heart failure class, regardless of breed (P < .02, Mann-Whitney rank sum test). Overall, 8 of 10 animals in the pimobendan-treated group, and 1 of 10 animals in the placebo group improved their heart failure status by at least I modified New York Heart Association functional class after initial stabilization (P = .005, Fisher's exact test). Pimobendan had no significant effect on survival in the CSs (P = 0.77, log-rank test), but DPs treated with pimobendan had significantly longer survival times compared with placebo (P < .02, log-rank test), with a median survival time of 329 days in the pimobendan group compared with 50 days in the placebo group, and a hazard ratio of 3.4 (95% confidence interval 1.4-39.8). Pimobendan resulted in significant improvement in heart failure class when added to standard therapy in this group of dogs with DCM, and may have contributed to improved survival in DPs.     

Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy

BACKGROUND: Despite traditional therapy of a diuretic, angiotensin converting enzyme inhibitor, digoxin, or a combination of these drugs, survival of dogs with dilated cardiomyopathy (DCM) is low. Pimobendan, an inodilator, has both inotropic and balanced peripheral vasodilatory properties. HYPOTHESIS: Pimobendan when added to conventional therapy will improve morbidity and reduce case fatality rate in Doberman Pinschers with congestive heart failure (CHF) caused by DCM. ANIMALS: Sixteen Doberman Pinschers in CHF caused by DCM. METHODS: A prospective randomized, double-blind, placebo-controlled study with treatment failure as the primary and quality of life (QoL) indices as secondary outcome variables. Therapy consisted of furosemide (per os [PO] as required) and benazepril hydrochloride (0.5 mg/kg PO q12h) and dogs were randomized in pairs and by sex to receive pimobendan (0.25 mg/kg PO q12h) or placebo (1 tablet PO q12h). RESULTS: Pimobendan-treated dogs had a significant improvement in time to treatment failure (pimobendan median, 130.5 days; placebo median, 14 days; P= .002; risk ratio = 0.35, P= .003, lower 5% confidence limit = 0.13, upper 95% confidence limit = 0.71). Number and rate of dogs reaching treatment failure in the placebo group precluded the analysis of QoL. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan should be used as a first-line therapeutic in Doberman Pinschers for the treatment of CHF caused by DCM.     

Survival and echocardiographic data in dogs with congestive heart failure caused by mitral valve disease and treated by multiple drugs: a retrospective study of 21 cases

This retrospective study reports the survival time [onset of congestive heart failure (CHF) to death from any cause] of 21 dogs with mitral regurgitation (MR) and CHF treated with a combination of furosemide, angiotensin-converting enzyme inhibitor (ACEI, benazepril, or enalapril), pimobendan, spironolactone, and amlodipine. Baseline echocardiographic data: end-systolic and end-diastolic volume indices (ESVI and EDVI), left atrium to aorta ratio (LA/Ao), and regurgitant fraction (RF) are reported. Median survival time (MST) was 430 d. Initial dosage of furosemide (P = 0.0081) and LA/Ao (P = 0.042) were negatively associated with survival. Baseline echocardiographic indices (mean ± standard deviation) were 40.24 ± 16.76 for ESVI, 161.48 ± 44.49 mL/m(2) for EDVI, 2.11 ± 0.75 for LA/Ao, and 64.71 ± 16.85% for RF. Combining furosemide, ACEI, pimobendan, spironolactone, and amlodipine may result in long survival times in dogs with MR and CHF. Severity of MR at onset of CHF is at least moderate.     

Effect of Pimobendan on Echocardiographic Values in Dogs with Asymptomatic Mitral Valve Disease

Background: Pimobendan (PIMO) is a novel inodilator that has shown promising results in the treatment of advanced mitral valve disease (MVD), but little is known about its hemodynamic effects, especially regarding the mitral regurgitant volume in naturally occurring MVD.
Hypothesis: The addition of pimobendan to treatment decreases the regurgitant fraction (RF) in dogs with asymptomatic MVD.
Animals: Twenty-four client-owned dogs affected by International Small Animal Cardiac Health Council class Ib MVD.
Methods: Prospective, blinded, and controlled clinical trial. Dogs were assigned to a PIMO treatment group (n = 19) (0.2–0.3 mg/kg q12h) or a control group (n = 5). Echocardiographic evaluations were performed over a 6-month period.
Results: The addition of PIMO to treatment did not decrease the RF of dogs affected by asymptomatic class 1b MVD over the study period ( P = .85). There was a significant increase in the ejection fraction of the PIMO treated dogs at 30 days (80.8 ± 1.42 versus 69.0 ± 2.76, corrected P = .0064), and a decrease in systolic left ventricular diameter (corrected P = .011) within the PIMO group compared with baseline. However, this improvement in systolic function was not sustained over the 6-month trial period.
Conclusion and Clinical Importance: This study did not identify beneficial long-term changes in the severity of mitral regurgitation after addition of PIMO to angiotensin converting enzyme inhibitor treatment of dogs with asymptomatic MVD.     

Plasma endothelin-1 immunoreactivity in normal dogs and dogs with acquired heart disease

We sought to measure plasma endothelin-1 (ET-1) concentrations in normal dogs and to compare them with those measured in dogs with acquired heart disease with or without pulmonary edema. A sandwich enzyme-linked immunosorbent assay kit was validated and used to measure ET-1 immunoreactivity in plasma samples obtained from 32 normal dogs and 46 dogs with either dilated cardiomyopathy (DCM, n = 27) or degenerative valvular disease (CDVD, n = 19) with (n = 30) or without (n = 16) overt congestive heart failure (CHF). Plasma ET-1 concentrations (geometric mean, 95% confidence interval of geometric mean) were 1.17 (1.04-1.32) fmol/mL in the 32 normal control dogs, 1.25 (0.981-1.60) fmol/mL in 16 dogs with DCM (n = 9) or CDVD (n = 7) without CHF, and 2.51 (2.10-3.01) fmol/mL in 30 dogs with DCM (n = 18) and CDVD (n = 12) with CHE Plasma immunoreactivity of ET-1 was significantly higher in dogs with CHF in comparison with normal dogs (P < .001) and dogs with heart disease without CHF (P < .001). No significant difference was found between normal dogs and dogs with heart disease but without CHF (P > .05). Significant correlations were between plasma ET-I concentrations and left atrial:aortic ratio (P < .0001, r2 = .39), left ventricular internal dimension at end-diastole indexed to aortic diameter (P < .0001, r2 = .30) or body surface area (BSA) (P = .0071, r2 = .10), and left ventricular internal dimension at end-systole indexed to aortic diameter (P = .0003, r- = .17) or BSA (P = .0008, r2 = .15).     

Association of Plasma N-Terminal Pro-B-Type Natriuretic Peptide Concentration with Mitral Regurgitation Severity and Outcome in Dogs with Asymptomatic Degenerative Mitral Valve Disease

Background: The clinical outcome of dogs affected by degenerative mitral valve disease (MVD) without overt clinical signs is still poorly defined, and criteria for identification of animals that are at a higher risk of early decompensation have not yet been determined.
Hypothesis: N-terminal pro-B-type natriuretic peptide plasma concentration (NT-proBNP) is correlated with mitral regurgitation (MR) severity and can predict disease progression in dogs with asymptomatic MVD.
Animals: Seventy-two dogs with asymptomatic MVD, with or without heart enlargement (International Small Animal Cardiac Health Council: ISACHC classes 1a and 1b), and a control group of 22 dogs were prospectively recruited.
Methods: Severity of MR was quantitatively assessed from the regurgitation fraction (RF) by the proximal isovelocity surface area method. Consequences of MR were evaluated from measurements of the left atrium/aorta ratio (LA/Ao), fractional shortening (FS), end-diastolic and end-systolic left ventricular volumes indexed to body surface area (EDVI and ESVI). The relevance of these echo-Doppler indices and NT-proBNP for prediction of outcome at 12 months was studied.
Results: A significant correlation was found between NT-proBNP and RF, LA/Ao, FS, and EDVI ( P < .05). NT-proBNP was higher in dogs with MVD (ISACHC classes 1a and 1b) compared with the control group ( P = .025 and < .001, respectively). The difference was not significant when only dogs from ISACHC class 1a with RF < 30% were considered. Lastly, NT-proBNP was higher in dogs that underwent MVD decompensation at 12 months ( P < .05).
Conclusions and Clinical Importance: NT-proBNP is correlated with MVD severity and prognosis in dogs with asymptomatic MVD.     

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.

     

Effect of thyroid hormone supplementation on survival of euthyroid dogs with congestive heart failure due to systolic myocardial dysfunction: a double-blind, placebo-controlled trial

Nineteen euthyroid dogs of 12 breeds with echocardiographic signs of dilated cardiomyopathy (DCM) and radiographic and clinical signs of congestive heart failure (CHF) were evaluated in a randomised, double-blind, and placebo-controlled study. The dogs received either thyroxine or placebo as an adjunct to digoxin, furosemide and propranolol. The group assignment of individual dogs and serum concentrations of thyroid hormones remained unknown to owners and investigators during the entire study period. Dogs were evaluated clinically and with electrocardiography (ECG), thoracic radiography, echocardiography and measurement of total thyroxine (tT4) and thyroid stimulating hormone (TSH) before beginning of the trial, and then one week, 2 months, 6 months and yearly after initial examination, and, when applicable, at the time of euthanasia. End-point of the study was euthanasia (n = 17) due to severe congestive heart failure or sudden death (n = 2). Survival times ranged from 17 to 1030 days (median 187 days) in the placebo group, and from 18 to 1000 days (median 73 days) in the treatment group. There was no statistically significant difference in survival times between the treatment group and the placebo group (p = 0.46). Post mortem and histopathologic examinations revealed the attenuated wavy fiber type of DCM in 11 dogs, and myocardial infarcts, arteriosclerosis and chronic valvular disease in one dog. In conclusion, there was a wide range in survival times of dogs treated with digoxin, furosemide and propranolol. Adding thyroid hormones to the treatment did not significantly influence survival.     

Size and Shape of Right Heart Chambers in Mitral Valve Regurgitation in Small-Breed Dogs

Background: The contribution of right heart (RH) chamber enlargement to general heart enlargement seen on thoracic radiographs in mitral regurgitation (MR) is not known.
Objectives: To determine the size and shape of the RH chambers in normal dogs and dogs with varying degrees of MR.
Animals: Fifty-four privately owned dogs: 13 normal, 41 with varying degrees of MR including 25 with congestive heart failure (CHF).
Methods: Archived first pass radionuclide angiocardiograms were used to produce static images of the RH and left heart (LH) chambers. Indexes of size and shape of the RH and LH chambers were related to severity of MR determined by heart rate-normalized pulmonary transit time (nPTT), vertebral heart scale (VHS), and clinical status. RH shape was measured by a circularity index of RH short axis/long axis.
Results: A 2nd degree polynomial fit best described the ratios; RH/LH dimension to nPTT ( R ²= 0.62) and to VHS ( R ²= 0.43), RH/LH area to nPTT ( R ²= 0.64) and to VHS ( R ²= 0.58), all P < .001. RH circularity was decreased in CHF, P < .001. In CHF, the RH chambers of 16 dogs were both flattened and enlarged, whereas 9 had convex septal borders.
Conclusions: RH chambers are not significantly dilated in dogs with mild to moderate MR without CHF. In CHF, RH chambers enlarge and also may be compressed by the LH chambers. Pulmonary hypertension probably is present in some dogs with CHF. Increased sternal contact is not a useful sign of right-sided heart dilatation in MR.     

Prospective clinical evaluation of an ELISA B-type natriuretic peptide assay in the diagnosis of congestive heart failure in dogs presenting with cough or dyspnea

BACKGROUND: B-type natriuretic peptide (BNP) is increased in dogs with congestive heart failure (CHF). HYPOTHESIS: The purpose of this study was to evaluate the clinical utility of a novel canine-specific enzyme-linked immunosorbent assay of BNP for the diagnosis of CHF in dogs presenting with either cough or dyspnea. ANIMALS: Three hundred and thirty dogs from 2 large university teaching hospitals. METHODS: We prospectively measured plasma BNP concentrations in 3 groups of dogs: (1) normal adult dogs (n = 75), (2) dogs with asymptomatic heart disease (n = 76), and (3) dogs with cough or dyspnea (n = 179). The final diagnosis of dogs with cough or dyspnea and the severity of CHF (International Small Animal Cardiac Health Council Heart Failure Classification [ISACHC]) were determined by medical record review by a study cardiologist who was blinded to the results of the BNP assay. RESULTS: Dogs with CHF had a higher median BNP concentration (24.6 pg/mL) than dogs with noncardiac causes of cough or dyspnea (2.6 pg/mL) (P < .0001). The area under the curve was 0.91 for the receiver operating curve analysis of the diagnostic accuracy of the BNP measurement to differentiate CHF from other causes of cough or dyspnea. The median BNP concentrations in dogs were 3.0 pg/mL with ISACHC I, 17.8 pg/mL with ISACHC II, and 30.5 pg/mL with ISACHC III. (P < .0001) CONCLUSION AND CLINICAL IMPORTANCE: Measurement of BNP is useful in establishing or in excluding the diagnosis of CHF in dogs with cough or dyspnea. B-type natriuretic peptide concentrations rose significantly as a function of severity of CHF.     

Association between exogenous atrial natriuretic peptide and hemodynamics in dogs with congestive heart failure produced by experimental mitral regurgitation

Association between exogenous atrial natriuretic peptide (ANP) and hemodynamic changes was ascertained in 3 dogs with overt congestive heart failure (CHF(+)) and 3 dogs without congestive heart failure (CHF(-)) caused by experimental mitral regurgitation (MR). The hemodynamic measurements were recorded in all dogs during and after 1 hr infusion of ANP at the rate of 0.1 (low dose), 0.5 (medium dose) and 1.0 (high dose) microg/kg/min, respectively. Heart rate, mean arterial pressure, pulmonary capillary wedge pressure (PCWP) and systemic vascular resistance decreased significantly during and after ANP infusion even with low dose in the CHF(+). Stroke volume, stroke volume index and cardiac output in the CHF(+) during and after ANP infusion showed an increasing trend as compared with the CHF(-). Double product, an indicator of myocardial oxygen consumption, significantly decreased during and after ANP administration at all doses in the CHF(+). These findings indicate that even at low dose, exogenous ANP improves cardiac performance and reduces myocardial oxygen consumption in the CHF(+), and suggest that ANP has beneficial effects in the treatment of dogs with overt congestive heart failure resulting from MR.     

Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: the QUEST study

Background: Myxomatous mitral valve disease (MMVD) continues to be an important cause of morbidity and mortality in geriatric dogs despite conventional therapy. Hypothesis: Pimobendan in addition to conventional therapy will extend time to sudden cardiac death, euthanasia for cardiac reasons, or treatment failure when compared with conventional therapy plus benazepril in dogs with congestive heart failure (CHF) attributable to MMVD. Animals: Two hundred and sixty client‐owned dogs in CHF caused by MMVD were recruited from 28 centers in Europe, Canada, and Australia. Methods: A prospective single‐blinded study with dogs randomized to PO receive pimobendan (0.4–0.6 mg/kg/d) or benazepril hydrochloride (0.25–1.0 mg/kg/d). The primary endpoint was a composite of cardiac death, euthanized for heart failure, or treatment failure. Results: Eight dogs were excluded from analysis. One hundred and twenty‐four dogs were randomized to pimobendan and 128 to benazepril. One hundred and ninety dogs reached the primary endpoint; the median time was 188 days (267 days for pimobendan, 140 days for benazepril hazard ratio = 0.688, 95% confidence limits [CL] = 0.516–0.916, P= .0099). The benefit of pimobendan persisted after adjusting for all baseline variables. A longer time to reach the endpoint was also associated with being a Cavalier King Charles Spaniel, requiring a lower furosemide dose, and having a higher creatinine concentration. Increases in several indicators of cardiac enlargement (left atrial to aortic root ratio, vertebral heart scale, and percentage increase in left ventricular internal diameter in systole) were associated with a shorter time to endpoint, as was a worse tolerance for exercise. Conclusions and Clinical Importance: Pimobendan plus conventional therapy prolongs time to sudden death, euthanasia for cardiac reasons, or treatment failure in dogs with CHF caused by MMVD compared with benazepril plus conventional therapy.     

Neurohormonal and circulatory effects of short-term treatment with enalapril and quinapril in dogs with asymptomatic mitral regurgitation

The aim of the study was to compare the effect of 2 angiotensin-converting enzyme (ACE) inhibitors on neurohormonal and circulatory variables in Cavalier King Charles Spaniels (CKCSs) with asymptomatic mitral regurgitation (MR). Ten CKCSs with mild to severe untreated MR were treated with 2 ACE inhibitors, quinapril and enalapril (each at 0.5 mg/kg PO q24h for 7 days), in a double-blind, crossover study with a washout period of 7 days between treatments. Blood samples were drawn and echocardiography was performed on days 0, 7, 14, and 21. Both treatments reduced ACE activity (P < .001) and increased renin activity (P < .001) and atrial natriuretic peptide concentration (P < .005). The ACE inhibitors had no effect on the concentrations of nitrate and nitrite (NOx) or asymmetric dimethylarginine (ADMA). On day 0, a lower NOx concentration (P = .02) was found in samples taken in the clinic as compared to samples taken in the homes of the dogs. Quinapril caused a significant reduction in more variables that reflect the severity of MR (eg, jet size and left ventricular end diastolic diameter) than did enalapril. However, in terms of specific variables, no significant difference was identified between the effects of the 2 treatments on MR. These results suggest that ACE inhibitors do not affect NOx and ADMA concentrations in asymptomatic dogs, but exercise, stress, or some combination may influence NOx concentrations in these dogs.     

Practices and outcome of artificial cardiac pacing in 154 dogs

Artificial pacing (AP) is a treatment for symptomatic bradyarrhythmias unresponsive to medical therapy. This retrospective study was designed to define the practices and outcome of AP in dogs at 7 referral institutions participating in the Companion Animal Pacemaker Registry and Repository (CANPACERS). The indications, implantation techniques, complications, long-term outcome, and owner satisfaction were examined. One hundred fifty-four dogs were identified as undergoing AP from January 1, 1991, to January 1, 1996. Third-degree atrioventricular (AV) block (n = 91; 59%) and sinus node dysfunction (n = 45; 29%) were the most common indications for AP Transvenous endocardial AP systems were implanted in 136 dogs (88%), and epicardial systems were implanted in 18 (12%). Complications associated with AP were reported in 84 dogs (55%). Major complications occurred in 51 dogs (33%), including dislodgement of the pacing lead (n = 15; 10%), generator failure (n = 10; 6%), cardiac arrest during implantation (n = 9; 6%), and infection (n = 7; 5%). Minor complications occurred in 47 dogs (31%), including seroma formation (n = 18; 12%), muscle twitch (n = 17; 11%), and inconsequential arrhythmias (n = 15; 10%). Fourteen dogs (9%) experienced both major and minor complications. Survival analysis revealed 1-, 2-, and 3-year survival rates of 70, 57, and 45%, respectively. Age and presence of preexisting congestive heart failure (CHF) had a negative effect on survival (P = .001). Sixty percent of dogs with preexisting CHF died within 1 year of implantation, whereas 25% of dogs without heart failure died during the same period. Owners rated their satisfaction with the procedure as high in 80% of the dogs.