Effect of sampling time on urinary electrolytes following oral furosemide administration in dogs with myxomatous mitral valve disease

Introduction/ObjectivesUrine chemistry has received growing attention to estimate the diuretic response in dogs with cardiac disease.The aim of the study was to evaluate the impact of time elapsed between the oral furosemide administration and sample collection on urine chemistry in dogs with myxomatous mitral valve disease (MMVD) receiving diuretic therapy in American College of Veterinary Internal Medicine (ACVIM) stage C.Materials and methodsSeventy-three dogs with MMVD ACVIM stage C and 106 healthy dogs were prospectively included. Dogs with MMVD were divided, based on the time of sampling, in morning group (MMVD-MG) of one to 6 h and an evening group (MMVD-EG) over 6 h from oral furosemide administration. Analogously, healthy dogs sampled between 9 a.m. and 1 p.m. and between 2 and 7 p.m. were divided in a morning group (H-MG) and an evening group (H-EG), respectively. Urine chemistry, including fractional excretion of electrolytes, was evaluated and compared among groups.ResultsHigher excretion of sodium and chloride and higher urine sodium to urine potassium ratio (uNa⁺:uK⁺) were detected in MMVD-MG than MMVD-EG (P = 0.021, P = 0.038, and P = 0.016, respectively). Natriuresis, chloriuresis, and uNa⁺:uK+ were higher in MMVD-MG than H-MG, while no differences were found in the comparison between H-MG and H-EG and between MMVD-EG and H-EG.ConclusionsUrinary electrolyte excretion is significantly increased within 6 h from furosemide administration in MMVD ACVIM stage C dogs. Time of sampling from furosemide administration significantly affects urine chemistry in MMVD dogs and should be considered in clinical practice and the research field.     

Survival characteristics and prognostic variables of dogs with mitral regurgitation attributable to myxomatous valve disease

BACKGROUND: There are few studies evaluating the natural history and prognostic variables in chronic mitral valve disease (CMVI) in a heterogeneous population of dogs. OBJECTIVES: To estimate survival and prognostic value of clinical and echocardiographic variables in dogs with CMVI of varying severity. Five hundred and fifty-eight dogs belonging to 36 breeds were studied. METHODS: Dogs were included after clinical examination and echocardiography. Long-term outcome was assessed by telephone interview with the owner. RESULTS: The mean follow-up time was 22.7 +/- 13.6 months, and the median survival time was 19.5 +/- 13.2 months. In univariate analysis, age>8 years, syncope, HR>140 bpm, dyspnea, arrhythmias, class of heart failure (International Small Animal Cardiac Health Council), furosemide therapy, end-systolic volume-index (ESV-I)>30 mL/m(2), left atrial to aortic root ratio (LA/Ao)>1.7, E wave transmitral peak velocity (Emax)>1.2 m/s, and bilateral mitral valve leaflet engagement were associated with survival time when all causes of death were included. For the cardiac-related deaths, all the previous variables except dyspnea and EDV-I>100 mL/m(2) were significantly associated with survival time. Significant variables in multivariate analysis (all causes of death) were syncope, LA/Ao>1.7 m/s, and Emax>1.2 m/s. For cardiac-related death, the only significant variable was LA/Ao>1.7. CONCLUSIONS AND CLINICAL IMPORTANCE: Mild CMVI is a relatively benign condition in dogs. However, some clinical variables can identify dogs at a higher risk of death; these variables might be useful to identify individuals that need more frequent monitoring or therapeutic intervention.     

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 furosemide on left atrial pressure in dogs with mitral valve regurgitation

Background: The effects of furosemide on left atrial pressure (LAP) in dogs with mitral regurgitation (MR) have not been documented in a quantitative manner and between different routes of administration. Objective: To document LAP and echocardiographic parameters in MR dogs administered furosemide IV or PO, in order to document changes in LAP after furosemide treatment. Animals: Five healthy Beagle dogs (3 males and 2 females; aged 2 years) were used. Methods: Experimental, cross‐over, and interventional study. LAP was measured before the administration of furosemide, and 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours after administration. Furosemide 1, 2, or 4 mg/kg IV, PO or placebo was administered. Results: LAP was significantly decreased with all administrations of furosemide but not after placebo (P < .05, respectively). The max reduction was observed 1 hour (1 mg/kg IV, 15.04 ± 7.02 mmHg), 3 hours (2, 4 mg/kg IV, 13.28 ± 8.01, 9.23 ± 4.92 mmHg), 4 hours (1 mg/kg PO, 14.68 ± 11.51 mmHg), and 5 hours (2, 4 mg/kg PO, 13.19 ± 10.52, 10.70 ± 7.69 mmHg). E wave and E/Ea were significantly decreased corresponding to the reduction of LAP after administration of 2 and 4 mg/kg (P < .05, respectively). Conclusions and Clinical Importance: LAP was decreased in proportion to the dosage of furosemide, which did not significantly differ between IV and PO of the same dosages. E wave and E/Ea might be useful for the treatment evaluation of furosemide.     

Effects of oral administration of furosemide and torsemide in healthy dogs

OBJECTIVE: To investigate the diuretic effects, tolerability, and adverse effects of furosemide and torsemide after short- and long-term administration in healthy dogs. ANIMALS: 8 mixed-breed dogs. PROCEDURES: In a crossover study, furosemide (2 mg/kg), torsemide (0.2 mg/kg), or placebo (bifidobacterium [1 mg/kg]) was administered orally to each dog every 12 hours for 14 days. Blood and urine samples were collected before the study (baseline data) and at intervals on the 1st (short-term administration) and 14th day (long-term administration) of treatment for assessment of urine volume and specific gravity and selected clinicopathologic variables including BUN, creatinine, and aldosterone concentrations, and creatinine clearance. RESULTS: Compared with the baseline value, short-term administration of furosemide or torsemide immediately increased urine volume significantly; after long-term administration of either drug, urine specific gravity decreased significantly. Compared with the effect of placebo, the 24-hour urine volume was significantly increased after short-term administra-tion of furosemide or torsemide. In addition, it was significantly increased after long-term administration of torsemide, compared with that of short-term administration. Long-term administration of furosemide or torsemide increased the BUN and plasma creatinine con-centrations, compared with the baseline value. Compared with the baseline value, plasma aldosterone concentration was significantly increased after long-term administration of either drug and was significantly higher after torsemide treatment than after furosemide treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, diuretic resistance developed after 14 days of furosemide, but not torsemide, administration; however, both loop diuretics were associated with increased BUN and plasma creatinine concentrations, compared with values before treatment.     

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.     

Comparison of different radiographic scores with associated echocardiographic measurements and prediction of heart enlargement in dogs with and without myxomatous mitral valve disease

IntroductionStaging of myxomatous mitral valve disease (MMVD) requires an echocardiographic examination along with thoracic radiographs. The aims of this study were to calculate mean values for radiographic scores vertebral heart size (VHS), left atrial width (LA_Width), radiographic left atrial dimension (RLAD), and vertebral left atrial size (VLAS) in conventional and grayscale inverted images in healthy dogs and dogs with different stages of MMVD, and to find cutoff values for a stage assignment.AnimalsOne hundred fifty dogs in different stages of MMVD and 50 unaffected dogs were evaluated.MethodsRadiographic scores, echocardiographic left atrium-to-aorta ratio and normalized left ventricular internal dimension at end-diastole, and results of a clinical examination were obtained. Analyses were performed to evaluate the correlation between radiographic scores and echocardiographic values, to determine cutoff values for a radiographic stage assignment, and to compare measurements in conventional and inverted radiographs.ResultsAfter excluding breed-specific higher VHS, the means of VHS, LA_Width, RLAD, and VLAS were similar in the control group and stage B1. All radiographic scores increased in stages B2 and C. The cutoff values identifying heart enlargement, and therefore differentiating stages B1 and B2, were 11.0 for VHS, 1.8 for LA_Width, 2.0 for RLAD, and 2.3 for VLAS. Besides RLAD, scores were similar in conventional and inverted radiographs.ConclusionCutoff values for the different radiographic scores for stage assignment were calculated. Radiographic cardiac scores using either conventional or inverted grayscale could be a tool to differentiate between different stages of MMVD when echocardiography is unavailable.     

Use of the loop diuretic torsemide in three dogs with advanced heart failure

Diuretics are a mainstay of therapy in dogs with heart failure. In dogs with advanced heart failure, moderate to high doses of loop diuretics such as furosemide are used with diminishing effects as profound activation of neuroendocrine systems promote signs of congestive heart failure. The loop diuretic torsemide has several characteristics that make it suitable for treatment of advanced heart failure including longer half-life, increased potency of diuretic action, and anti-aldosterone effects. This case report details the administration of torsemide in 3 dogs with advanced heart failure and apparent furosemide resistance.     

Prediction of first onset of congestive heart failure in dogs with degenerative mitral valve disease: The PREDICT cohort study

ObjectiveTo identify risk factors for first-onset congestive heart failure (CHF) in dogs with degenerative mitral valve disease (DMVD).AnimalsEighty-two dogs with and without CHF secondary to DMVD were retrospectively assigned to a derivation cohort. Sixty-five dogs with asymptomatic DMVD were recruited into a prospective validation cohort.MethodsVariables associated with risk of CHF in dogs were identified in a derivation cohort and used to construct a predictive model, which was then prospectively tested through longitudinal examination of a validation cohort.ResultsLogistic regression analysis of the derivation cohort yielded a predictive model that included the left atrial to aortic root dimension ratio (LA:Ao) and plasma concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP). When this model was prospectively applied to the validation cohort, it correctly predicted first-onset of CHF in 69.2% of cases. Analysis of the validation cohort revealed that plasma NT-proBNP concentration and indexed left ventricular end-diastolic diameter (LVIDd:Ao) were independent risk factors for development of first-onset CHF in dogs with DMVD (NT-proBNP ≥1500 pmol/L, odds ratio (OR), 5.76, 95% confidence interval (CI), 1.37–24.28, P = 0.017; LVIDd:Ao ≥3, OR, 6.11, 95% CI, 1.09–34.05, P = 0.039).ConclusionsMeasures of left heart size and plasma NT-proBNP concentration independently estimate risk of first-onset of CHF in dogs with DMVD. These parameters can contribute to the management of dogs with DMVD.     

Serum concentrations of cardiac troponin I and cardiac troponin T in dogs with class IV congestive heart failure due to mitral valve disease

Objective: The objective of this study was to evaluate the incidence of circulating detectable serum levels of cardiac troponin I (CTnI) and circulating detectable serum levels of cardiac troponin T (CTnT) in dogs with class IV congestive heart failure (CHF) due to mitral valve disease (MVD) at admission. An additional study aim was to determine if detectable troponin levels correlated with the magnitude of several clinical parameters. Design: Prospective clinical investigation. Setting: Small animal emergency and critical care referral hospital. Interventions: Blood was collected before emergency treatment from 15 dogs presenting in class IV CHF due to MVD. Measurements: Serum concentrations of CTnI, CTnT at presentation. Main results: Six dogs (40%) had a detectable CTnI (median 0.24, range 0.12–0.31 ng/mL), and the remainder were less than 0.1 ng/mL and deemed non‐detectable. The one dog (7%) that had a detectable CTnT (0.02 ng/mL) also had a detectable CTnI (0.23 ng/mL). There was no statistical difference in survival to discharge between dogs with non‐detectable troponin levels and those with detectable troponin levels; however, dogs with detectable troponin levels had shorter overall survival times. Dogs with a detectable level of CTnI had a median survival of 67.5 days (range 1–390 days), and dogs with a non‐detectable level of CTnI had a median survival time of 390 days (range 20–912 days) (P=0.02). Conclusion: This study suggests that CTnI can be detected at admission in the blood of 40% of dogs with class IV CHF due to MVD. Dogs with non‐detectable levels of cardiac troponins had a significantly longer overall survival time. The encouraging results of this small pilot study warrant further investigation.     

Partial external mitral annuloplasty in dogs with myxomatous mitral valve degeneration and congestive heart failure: Outcome in 9 cases

Objective

To report the outcome of partial external mitral annuloplasty in dogs with congestive heart failure (CHF) due to mitral regurgitation caused by myxomatous mitral valve degeneration (MMVD).

Animals, materials and methods

Nine client-owned dogs with CHF due to mitral regurgitation caused by MMVD. Surgery consisted of a double row of pledget-butressed continuous suture lines placed into the left ventricle parallel and just ventral to the atrioventricular groove between the subsinuosal branch of the left circumflex coronary artery and the paraconal branch of the left coronary artery.

Results

Two dogs died during surgery because of severe hemorrhage. Two dogs died 12 and 36 h after surgery because of acute myocardial infarction. Three dogs were euthanized 2 and 4 weeks after surgery because of progression of CHF, 1 was euthanized 30 days after surgery for non-cardiac disease, and 1 survived for 48 months. In the 5 dogs that survived to discharge there was no significant change in the left atrium to aortic ratio with surgery (3.6 ± 0.56 before surgery; 3.1 ± 0.4 after surgery; p = 0.182), and no significant change in mitral regurgitant fraction in 4 dogs in which this measurement was made (78.7 ± 2.0% before surgery; 68.7 ± 7.5% after surgery; p = 0.09).

Conclusions

Partial external mitral annuloplasty in dogs with CHF due to MMVD was associated with high perioperative mortality and most dogs that survived to discharge failed to show clinically relevant palliation from this procedure. Consequently, partial external mitral annuloplasty is not a viable option for dogs with mitral regurgitation due to MMVD that has progressed to the stage of CHF.     

Association between atrial fibrillation and right-sided manifestations of congestive heart failure in dogs with degenerative mitral valve disease or dilated cardiomyopathy

IntroductionTo determine whether dogs with atrial fibrillation (AF) are more likely to develop right-sided manifestations of congestive heart failure (R-CHF) than dogs without AF.AnimalsTwo hundred twenty dogs diagnosed with congestive heart failure (CHF) secondary to degenerative mitral valve disease (DMVD, n = 155) or dilated cardiomyopathy (DCM, n = 65) at a referral institution.MethodsMedical records were reviewed to extract relevant clinical and echocardiographic data.ResultsFifty dogs had AF at the time of CHF diagnosis, including 17/155 (11.0%) dogs with DMVD and 33/65 (50.8%) dogs with DCM. Sixty dogs had R-CHF evidenced by cavitary effusions. Among DMVD dogs, R-CHF occurred in 13/17 (76.5%) dogs with AF compared with 10/138 (7.2%) dogs without AF; among DCM dogs, R-CHF occurred in 24/33 (72.7%) dogs with AF compared with 13/32 (40.6%) dogs without AF. Dogs with AF were more likely to manifest R-CHF signs than dogs without AF (p < 0.0001 for DMVD; p = 0.0125 for DCM). The presence of AF, diagnosis of DCM, and moderate to severe tricuspid regurgitation were associated with R-CHF in multivariate analysis. AF was the strongest predictor of R-CHF (odds ratio, 14.44; 95% confidence interval, 5.75–36.26).ConclusionsDogs with AF are more likely to manifest R-CHF than dogs without AF. Cavitary effusions are an expected finding in approximately three-quarters of dogs with AF and CHF secondary to either DCM or DMVD.