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.     

Efficacy of enalapril for prevention of congestive heart failure in dogs with myxomatous valve disease and asymptomatic mitral regurgitation

We evaluated the long-term effect of early angiotensin-converting enzyme (ACE) inhibition (enalapril maleate) as monotherapy to postpone or prevent congestive heart failure (CHF) in asymptomatic dogs with mitral regurgitation (MR) attributable to myxomatous valvular disease (MVD) in a prospective, randomized, double-blinded, placebo-controlled multicenter trial involving 14 centers in Scandinavia. Two hundred twenty-nine Cavalier King Charles (CKC) Spaniels with MR attributable to MVD but no signs of CHF were randomly allocated to treatment with enalapril 0.25-0.5 mg daily (n = 116) or to placebo groups (n = 113). Each dog was evaluated by physical examination, electrocardiography, and thoracic radiography at entry and every 12 months (+/-30 days). The number of dogs developing heart failure was similar in the treatment and placebo groups (n = 50 [43%] and n = 48 [42%], respectively; P = .99). The estimated means, adjusted for censored observations, for the period from initiation of therapy to heart failure were 1,150 +/- 50 days for dogs in the treatment group and 1,130 +/- 50 days for dogs in the placebo group (P = .85). When absence or presence of cardiomegaly at the entrance of the trial was considered, there were still no differences between the treatment and placebo groups (P = .98 and .51, respectively). Multivariate analysis showed that enalapril had no significant effect on the time from initiation of therapy to heart failure (P = .86). Long-term treatment with enalapril in asymptomatic dogs with MVD and MR did not delay the onset of heart failure regardless of whether or not cardiomegaly was present at initiation of the study.     

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.     

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).     

Cardiac Troponin I Is Associated with Severity of Myxomatous Mitral Valve Disease, Age, and C-Reactive Protein in Dogs

Background: Concentrations of cardiac troponin I (cTnI) and C-reactive protein (CRP) might be associated with cardiac remodeling in dogs with myxomatous mitral valve disease (MMVD). Age- and sex-dependent variations in cTnI concentration have been described.
Objective: To investigate whether plasma concentrations of cTnI and CRP are associated with severity of MMVD, and investigate potential associations of dog characteristics on cTnI and CRP concentrations.
Animals: Eighty-one client-owned dogs with MMVD of varying severity.
Methods: Dogs were prospectively recruited for the study. Dogs were classified according to severity of MMVD. Plasma cTnI was analyzed by a high sensitivity cTnI assay with a lower limit of detection of 0.001 ng/mL, and plasma CRP was analyzed by a canine-specific CRP ELISA.
Results: Higher cTnI concentrations were detected in dogs with moderate (0.014 [interquartile range 0.008–0.029] ng/mL, P = .0011) and severe (0.043 [0.031–0.087] ng/mL, P < .0001) MMVD, compared with healthy dogs (0.001 [0.001–0.004] ng/mL). Dogs with severe MMVD also had higher cTnI concentrations than dogs with mild (0.003 [0.001–0.024] ng/mL, P < .0001) and moderate ( P = .0019) MMVD. There were significant associations of age, CRP, heart rate, and left ventricular end-diastolic diameter, on cTnI concentration C-reactive protein did not differ among severity groups, but was significantly associated with cTnI, breed, and systolic blood pressure on CRP concentration.
Conclusions and Clinical Importance: Analysis of cTnI concentration has potential to increase knowledge of overall cardiac remodeling in dogs with MMVD. However, effect of age on cTnI needs consideration when assessing cTnI.     

Distinguishing cardiac and noncardiac dyspnea in 48 dogs using plasma atrial natriuretic factor, B-type natriuretic factor, endothelin, and cardiac troponin-I

BACKGROUND: It is challenging to differentiate congestive heart failure (CHF) from noncardiac cause of dyspnea. HYPOTHESIS: Circulating concentrations of atrial natriuretic peptide (NT-proANP), B-type natriuretic peptide (BNP), endothelin-I (ET-1), and cardiac troponin-I (cTnI) can be used to help distinguish between cardiac and noncardiac causes of dyspnea in dogs. ANIMALS: Forty-eight client-owned dogs admitted to a veterinary teaching hospital for respiratory distress. METHODS: Blood samples from patients were prospectively obtained. The etiology of dyspnea was determined by using physical examination, thoracic radiographs, and echocardiography. RESULTS: CHF was diagnosed in 22 dogs, and dyspnea of noncardiac origin (noHD group) was diagnosed in 26 dogs. Analyses revealed significant difference between groups for NT-proANP (geometric mean, 95% confidence [CI]; no HD: 0.26 nmol/mL, 95% CI 0.17-1.09; CHF: 1.38 nmol/mL, 95% CI 1.09-1.74 nmol/mL; P < .0001), BNP (noHD: 12.18 pg/mL, 95% CI 10.91-16.17 pg/mL; CHF: 34.97 pg/mL, 95% CI 23.51-52.02 pg/mL; P < .0001), and ET-1 (noHD: 0.32 fmol/mL, 95% CI 0.23-0.46 fmol/mL; CHF: 1.26 fmol/mL, 95% CI 0.83-1.91 fmol/mL; P < .0001). Plasma cTnI concentrations were not significantly different between groups (noHD: 0.29 ng/mL, 95% CI 0.12-0.72 ng/mL; CHF: 0.42 ng/mL, 95% CI 0.18-0.97, P = .53). Receiver operating curves indicated areas under the curve for NT-proANP, BNP, and ET-1 of 0.946, 0.886, and 0.849, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma NT-proANP, BNP, and ET-1, but not cTnI, appear useful for distinguishing between dogs with cardiac and noncardiac causes of dyspnea, with plasma NT-proANP having the highest sensitivity (95.5%) and specificity (84.6%).     

Comparative adverse cardiac effects of pimobendan and benazepril monotherapy in dogs with mild degenerative mitral valve disease: a prospective, controlled, blinded, and randomized study

BACKGROUND: Pimobendan (PIMO) is an inodilator that may have some beneficial effects in canine degenerative mitral valve disease (MVD). However, little information is available about its cardiac effects in dogs without systolic myocardial dysfunction. HYPOTHESIS: Compared to benazepril (BNZ), an angiotensin-converting enzyme inhibitor, PIMO may worsen valve regurgitation in early canine MVD. ANIMALS: Twelve Beagles with asymptomatic MVD were randomized into 2 groups (n = 6) receiving BNZ or PIMO at dosages of 0.25 mg/kg PO q24h and q12h respectively, for 512 days. METHODS: The study followed a blinded, randomized, prospective, and parallel group design. After day 512, the dogs were necropsied, and cardiac histopathology was performed in a blinded manner. RESULTS: A significant treatment effect was observed as soon as day 15 with increased systolic function in the PIMO group by comparison to baseline value as assessed by fractional shortening (P < .0001) and tissue Doppler variables (P = .001). Concurrently, the maximum area and peak velocity of the regurgitant jet signal increased (P < .001), whereas these variables remained stable in the BNZ group. Histologic grades of mitral valve lesions were more severe in the PIMO group than in the BNZ group. Moreover, acute focal hemorrhages, endothelial papillary hyperplasia, and infiltration of chordae tendinae with glycosaminoglycans were observed in the mitral valves of dogs from the PIMO group but not in those of the BNZ group. CONCLUSIONS AND CLINICAL IMPORTANCE: PIMO has adverse cardiac functional and morphologic effects in dogs with asymptomatic MVD. Additional investigation in dogs with symptomatic MVD is now warranted.     

Cardiac troponin-I concentration in dogs with cardiac disease

Cardiac troponin-I (cTnI) is a highly sensitive and specific marker of myocardial injury and can be detected in plasma by immunoassay techniques. The purpose of this study was to establish a reference range for plasma cTnI in a population of healthy dogs using a human immunoassay system and to determine whether plasma cTnI concentrations were high in dogs with acquired or congenital heart disease, specifically cardiomyopathy (CM), degenerative mitral valve disease (MVD), and subvalvular aortic stenosis (SAS). In total, 269 dogs were examined by physical examination, electrocardiography, echocardiography, and plasma cTnI assay. In 176 healthy dogs, median cTnI was 0.03 ng/mL (upper 95th percentile = 0.11 ng/mL). Compared with the healthy population, median plasma cTnI was increased in dogs with CM (0.14 ng/mL; range, 0.03-1.88 ng/mL; P < .001; n = 26), in dogs with MVD (0.11 ng/mL; range, 0.01-9.53 ng/mL; P < .001; n = 37), and in dogs with SAS (0.08 ng/mL; range, 0.01-0.94 ng/mL; P < .001; n = 30). In dogs with CM and MVD, plasma cTnI was correlated with left ventricular and left atrial size. In dogs with SAS, cTnI demonstrated a modest correlation with ventricular wall thickness. In dogs with CM, the median survival time of those with cTnI >0.20 ng/mL was significantly shorter than median survival time of those with cTnI <0.20 ng/mL (112 days versus 357 days; P = .006). Plasma cTnI is high in dogs with cardiac disease, correlates with heart size and survival, and can be used as a blood-based biomarker of cardiac disease.     

Hemostatic biomarkers in dogs with chronic congestive heart failure

BACKGROUND: Chronic congestive heart failure (CHF) in humans is associated with abnormal hemostasis, and abnormalities in hemostatic biomarkers carry a poor prognosis. Alterations in hemostatic pathways can be involved in the pathogenesis of CHF in dogs, and microthrombosis in the myocardium could contribute to increased mortality. HYPOTHESIS: That plasma concentration or activity of hemostatic biomarkers is altered in dogs with CHF and that these factors predict mortality. ANIMALS: Thirty-four dogs with CHF caused by either dilated cardiomyopathy (DCM, n=14) or degenerative valvular disease (CDVD, n=20) compared with 23 healthy age-matched control dogs were included in this study. Dogs with CHF were recruited from 2 referral cardiology clinics, and control dogs were owned by friends or colleagues of the investigators. METHODS: Clinical examination and echocardiography were performed in all dogs. Plasma fibrinogen and D-dimer concentrations, antithrombin and protein C activity, and thrombin-antithrombin complex (TAT) were measured in all dogs. RESULTS: Dogs with CHF had significantly higher fibrinogen (P = .04), D-dimer (P = .002), and TAT concentration (P < .0001), lower antithrombin (P < .0001) and protein C activity (P < .001) compared with control dogs. None of the hemostatic biomarkers were associated with risk of death. CONCLUSIONS AND CLINICAL IMPORTANCE: There is evidence of a procoagulant state in dogs with CHF. The lack of predictive value for survival might be due to the small number of dogs examined. Further studies are necessary to investigate the presence and importance of microthrombosis in dogs with CHF.     

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.     

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.     

Doppler echocardiography-derived evidence of pulmonary arterial hypertension in dogs with degenerative mitral valve disease: 86 cases (2001-2005)

OBJECTIVE: To determine the prevalence of Doppler echocardiography-derived evidence of pulmonary arterial hypertension (DEE-PAH) in dogs with mitral valve disease (MVD) classified according to the International Small Animal Cardiac Health Council (ISACHC) heart failure classification scheme and various echocardiographic and Doppler indices of MVD severity. DESIGN: Retrospective case series. ANIMALS: 617 dogs examined from 2001 to 2005 with MVD in ISACHC classes I to III. PROCEDURES: Dogs were examined echocardiographically. Criteria used for systolic and diastolic DEE-PAH were detection of high tricuspid (> or = 2.5 m/s) and telediastolic pulmonic (> or = 2.0 m/s) valvular peak regurgitant jet velocities, respectively, by use of continuous-wave Doppler echocardiography. RESULTS: 86 (13.9%) dogs with MVD had a diagnosis of DEE-PAH. Severity and prevalence of DEE-PAH increased with ISACHC class (3.0%, 16.9%, 26.7%, and 72.2% prevalences for ISACHC classes Ia, Ib, II, and III, respectively). A significant correlation between systolic or diastolic pulmonary arterial pressure and left atrial-to-aortic diameter ratio (LA/Ao) was detected. Doppler echocardiography-derived evidence of pulmonary arterial hypertension was detected in 18 dogs with values of LA/Ao within reference range, all of which had moderate (n = 2 dogs) or severe (16) mitral valve regurgitation on color Doppler imaging. CONCLUSIONS AND CLINICAL RELEVANCE: The prevalence and degree of DEE-PAH were related to the severity of MVD. Changes associated with DEEPAH may be detected in early stages of the disease, but only in dogs with severe mitral valve regurgitation.     

Diagnostic and prognostic value of endothelin-1 plasma concentrations in dogs with heart and respiratory disorders

The endothelin-1 (ET-1) plasma concentration was measured in dogs with spontaneous cardiac or respiratory diseases. Plasma samples were obtained from 76 healthy control dogs and 73 dogs, of which 58 were suffering from heart disease and 15 were suffering from respiratory disease. Dogs were evaluated using echocardiography, thoracic radiography, biochemical evaluation and a radioimmunoassay for ET-1. ET-1 plasma concentrations were significantly higher in dogs with spontaneous cardiac or respiratory diseases (mean [se] 5.3 [0.3] and 5.3 [0.6] pg/ml, respectively) than in healthy dogs (1.9 [0.1] pg/ml) (P<0.0001). ET-1 plasma concentrations increased with the class of heart failure (International Small Animal Cardiac Health Council classification) (P<0.0001) and with the severity of pulmonary disorders. ET-1 plasma concentrations were positively correlated with the extent of systolic pulmonary hypertension measured by Doppler echocardiography (P<0.05; r=0.75) and with the clinical outcome of dogs with respiratory disease. Evaluation of the ET-1 plasma concentration allowed differentiation between heart and respiratory disorders in dogs exhibiting clinical signs at exercise, but not in patients exhibiting clinical signs at rest.     

Chordae tendineae rupture in dogs with degenerative mitral valve disease: prevalence, survival, and prognostic factors (114 cases, 2001-2006)

Background:Degenerative mitral valve disease (MVD) is the most common heart disease in small breed dogs, and chordae tendineae rupture (CTR) is a potential complication of this disease. The survival time and prognostic factors predictive of survival in dogs with CTR remain unknown.
Hypothesis:The prevalence and prognosis of CTR in dogs with MVD increases and decreases, respectively, with heart failure class.
Animals:This study used 706 dogs with MVD.
Methods:The diagnosis of CTR was based on a flail mitral leaflet with the tip pointing into the left atrium during systole, which was confirmed in several 2-dimension imaging planes using the left and right parasternal 4-chamber views.
Results:CTR was diagnosed in 114 of the 706 dogs with MVD (16.1%) and most of these (106/114, 93%) had severe mitral valve regurgitation as assessed by color Doppler mode. CTR prevalence increased with International Small Animal Cardiac Health Council (ISACHC) clinical class (i.e., 1.9, 20.8, 35.5, and 69.6% for ISACHC classes Ia, Ib, II, and III, respectively [ P < .05]). Long-term follow-up was available for 57 treated dogs (angiotensin-converting enzyme inhibitors and diuretics) and 58% of these (33/57) survived > 1 year after initial CTR diagnosis (median survival time, 425 days). Clinical class, the presence of ascites or acute dyspnea at the time of diagnosis, heart rate, plasma urea concentration, and left atrial size were predictors of survival.
Conclusions and Clinical Relevance: CTR is associated with a higher overall survival time than previously supposed. Its prognosis mostly depends on a combination of clinical and biochemical factors.     

Sympathetic activation in dogs with congestive heart failure caused by chronic mitral valve disease and dilated cardiomyopathy

Baseline plasma norepinephrine (NE) and epinephrine (EPI) concentrations were measured in dogs with naturally acquired heart failure (HF) caused by either degenerative mitral valve disease and mitral regurgitation (MR) or idiopathic dilated cardiomyopathy (DCM). Compared with controls (clinically normal), dogs with HF had increased plasma NE concentration, which was correlated positively with clinical severity of HF. Dogs with the most severe degree of HF (New York Heart Association functional class IV) had mean NE concentration significantly (P less than 0.05) greater than that of dogs with all other functional classes of HF. Overall, mean NE concentration in dogs with DCM was greater than that in dogs with MR. Plasma EPI concentration was not different between control dogs and dogs with HF or between dogs with DCM or MR. Correlations were not found between the echocardiographically derived end systolic volume index (used as an estimate of myocardial function) and plasma NE and EPI concentrations or serum sodium or potassium concentration. Dogs with DCM, as a group, had a small but significant (P less than 0.05) decrease in serum sodium concentration, compared with dogs with MR. This difference was maintained only for class-IV HF when dogs were separated according to functional HF class. In dogs with DCM, significant inverse correlation was found between plasma NE and serum sodium concentrations. When grouped together, all dogs with HF maintained this relationship; however, dogs with MR did not have correlation between plasma NE and serum sodium concentrations. Plasma EPI and serum sodium concentrations were not correlated for any group. It was concluded that in dogs, plasma NE, but not EPI, concentration is high in relation to the clinical severity of naturally acquired HF.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of ramipril on left ventricular mass, myocardial fibrosis, diastolic function, and plasma neurohormones in Maine Coon cats with familial hypertrophic cardiomyopathy without heart failure

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common heart disease of cats, resulting in left ventricular (LV) hypertrophy, myocardial fibrosis, and diastolic dysfunction. HYPOTHESIS: Ramipril will reduce LV mass, improve diastolic function, and reduce myocardial fibrosis in cats with HCM without congestive heart failure (CHF). ANIMALS: This prospective, blinded, placebo-controlled study included 26 Maine Coon and Maine Coon cross-bred cats with familial HCM but without CHF. METHODS: Cats were matched for LV mass index (LVMI) and were randomized to receive ramipril (0.5 mg/kg) or placebo q24h for 1 year, with investigators blinded. Plasma brain natriuretic peptide (BNP) concentration, plasma aldosterone concentration, Doppler tissue imaging (DTI), and systolic blood pressure were measured at baseline and every 3 months for 1 year. Cardiac magnetic resonance imaging (cMRI) was performed to quantify LV mass and myocardial fibrosis by delayed enhancement (DE) cMRI at baseline and 6 and 12 months. Plasma angiotensin-converting enzyme (ACE) activity was measured on 16 cats 1 hour after PO administration. RESULTS: Plasma ACE activity was adequately suppressed (97%) in cats treated with ramipril. LV mass, LVMI, DTI, DE, blood pressure, plasma BNP, and plasma aldosterone were not different in cats treated with ramipril compared with placebo (P = .85, P = .94, P = .91, P = .89, P = .28, P = .18, and P = .25, respectively). CONCLUSION: Treatment of Maine Coon cats with HCM without CHF with ramipril did not change LV mass, improve diastolic function, alter DE, or alter plasma BNP or aldosterone concentrations in a relevant manner.     

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.     

Serum Cardiac Troponin I Concentration in Dogs with Precapillary and Postcapillary Pulmonary Hypertension

Background: Pulmonary hypertension (PH) is a disease condition leading to right-sided cardiac hypertrophy and, eventually, right-sided heart failure. Cardiac troponin I (cTnI) is a circulating biomarker of cardiac damage.
Hypothesis: Myocardial damage can occur in dogs with precapillary and postcapillary PH.
Animals: One hundred and thirty-three dogs were examined: 26 healthy controls, 42 dogs with mitral valve disease (MVD) without PH, 48 dogs with pulmonary hypertension associated with mitral valve disease (PH-MVD), and 17 dogs with precapillary PH.
Methods: Prospective, observational study. Serum cTnI concentration was measured with a commercially available immunoassay and results were compared between groups.
Results: Median cTnI was 0.10 ng/mL (range 0.10–0.17 ng/mL) in healthy dogs. Compared with the healthy population, median serum cTnI concentration was increased in dogs with precapillary PH (0.25 ng/mL; range 0.10–1.9 ng/mL; P < .001) and in dogs with PH-MVD (0.21 ng/mL; range 0.10–2.10 ng/mL; P < .001). Median serum cTnI concentration of dogs with MVD (0.12 ng/mL; range 0.10–1.00 ng/mL) was not significantly different compared with control group and dogs with PH-MVD. In dogs with MVD and PH-MVD, only the subgroup with decompensated PH-MVD had significantly higher cTnI concentration compared with dogs with compensated MVD and PH-MVD. Serum cTnI concentration showed significant modest positive correlations with the calculated pulmonary artery systolic pressure in dogs with PH and some echocardiographic indices in dogs with MVD and PH-MVD.
Conclusions and Clinical Importance: Serum cTnI is high in dogs with either precapillary and postcapillary PH. Myocardial damage in dogs with postcapillary PH is likely the consequence of increased severity of MVD.     

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.     

Auscultation and echocardiographic findings in Bull Terriers with and without polycystic kidney disease

OBJECTIVE: To investigate a possible association between Bull Terrier polycystic kidney disease (BTPKD) and cardiac disease, to determine the prevalence of mitral valve disease (MVD) and left ventricular outflow tract obstruction (LVOTO) in the Australian Bull Terrier population, and to compare auscultation and echocardiography in detection of cardiac disease in Bull Terriers. DESIGN: Ninety-nine Bull Terriers, ranging in age from 8 weeks to 13 years and 11 months were auscultated and examined using renal ultrasonography; 86 were also examined using echocardiography. The prevalence and severity of heart defects in dogs with BTPKD was compared with that in dogs without BTPKD. RESULTS: Nineteen of these 99 dogs were diagnosed with BTPKD. Forty-two percent of Bull Terriers with BTPKD and 28% of those without BTPKD had murmurs characteristic of mitral regurgitation or LVOTO. How recently an animal was descended from an ancestor with BTPKD was associated with presence (P = 0.008) and loudness of a murmur (P = 0.009). Overall, echocardiography detected MVD in 39% of Bull Terriers, with increased prevalence in older animals (P = 0.003). Mitral stenosis was found in eight cases. Fifty-three percent of dogs in this study had evidence of LVOTO, with obstruction consisting of a complex of lesions including dynamic or fixed subvalvular LVOTO, significantly narrowed left ventricular outflow tract or valvular aortic stenosis. Dogs with BTPKD, or those descended from dogs with BTPKD, were more likely to have MVD (P = 0.006), and while LVOTO was not more common in these dogs, if they did have LVOTO, they were more likely to have severe obstruction than dogs with no ancestors with BTPKD (analysed in three ways P = 0.028 to 0.001). In this study, 46% of Bull Terriers without a murmur or arrhythmia had cardiac disease detected on echocardiographic examination. CONCLUSION: Cardiac disease, especially MVD and LVOTO, was common in Bull Terriers in this study, and those with BTPKD had an increased risk of cardiac abnormalities. Auscultation did not detect a significant number of Bull Terriers with cardiac disease.