Biologic variability of N-terminal pro-brain natriuretic peptide in healthy dogs and dogs with myxomatous mitral valve disease

Introduction

To determine the biologic variability of N-terminal pro-brain natriuretic peptide (NTproBNP) in healthy dogs and dogs with various stages of myxomatous mitral valve disease (MMVD).

Aldosterone breakthrough in dogs with naturally occurring myxomatous mitral valve disease

Introduction

Aldosterone breakthrough (ABT) is the condition in which angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers fail to effectively suppress the activity of the renin angiotensin aldosterone system. The objective of this study was to determine if ABT occurs in dogs with naturally occurring myxomatous mitral valve disease receiving an ACEI, using the urine aldosterone to creatinine ratio (UAldo:C) as a measure of renin angiotensin aldosterone system activation.

Efficacy and safet of pimobendan in canine heart failure caused by myxomatous mitral valve disease

OBJECTIVES: To evaluate the clinical efficacy and safety of pimobendan by comparing it with ramipril over a six-month period in dogs with mild to moderate heart failure (HF) caused by myxomatous mitral valve disease (MMVD). METHODS: This was a prospective randomised, single-blind, parallel-group trial. Client-owned dogs (n = 43) with mild to moderate HF caused by MMVD were randomly assigned to one of two groups, which received either pimobendan (P dogs) or ramipril (R dogs) for six months. The outcome measures studied were: adverse HF outcome, defined as failure to complete the trial as a direct consequence of HF; maximum furosemide dose (mg/kg/day) administered during the study period; and any requirement for additional visits to the clinic as a direct consequence of HF. RESULTS: Treatment with pimobendan was well tolerated compared with treatment with ramipril. P dogs were 25 per cent as likely as R dogs to have an adverse HF outcome (odds ratio 4.09, 95 per cent confidence interval 1.03 to 16.3, P = 0.046). CLINICAL SIGNIFICANCE: R dogs had a higher overall score and thus may have had more advanced disease than P dogs at baseline (P = 0.04). These results should be interpreted cautiously but such a high odds ratio warrants 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.     

The outcome of surgical mitral valve repair with loop-in-loop technique in dogs with different stage myxomatous mitral valve disease

ObjectivesSurgical mitral valve repair is a possible option for dogs with myxomatous mitral valve disease. However, information on surgical results and postoperative echocardiography is limited. This study aimed to verify the stage-specific surgical results of mitral valve repair and postoperative echocardiographic changes for two years following surgery.AnimalsAdult dogs (n = 55) treated with surgical mitral valve repair using the loop-in-loop technique were included in this study. Medical records were retrospectively reviewed.ResultsNinety percent of cases (50/55) survived to discharge, which survival was significantly decreased in myxomatous mitral valve disease advanced-stage dogs, Stage B2 (n = 14): 100%, Stage C (n = 27): 96.2%, and Stage D (n = 14): 71.4%. Significant reductions of overall heart size (vertebral heart score: preoperative 11.4 vs. post one month 10.2, P < 0.001), left atrium (left atrium to aortic root ratio: preoperative 2.3 vs. post one month 1.5, P < 0.001) and left ventricle (left ventricular end-diastolic diameter [normalized for bodyweight]: preoperative 2.2 vs. post one month 1.5, P < 0.001) were documented one month after surgery, showing successful management of mitral regurgitation. All medications for mitral valve disease were discontinued three months after surgery. The recurrence of mitral regurgitation was not evident during the two-year follow-up period.ConclusionsSurgical mitral valve repair with the loop-in-loop technique is associated with significant decreases in indices of cardiac size at one-month post-repair. Disease stage influences operative survival after surgical mitral valve repair.     

Retrospective evaluation of notched and fragmented QRS complex in dogs with naturally occurring myxomatous mitral valve disease

Myxomatous mitral valve disease (MMVD) is the most common cardiac disease in dogs. The association of QRS notching (nQRS) or fragmentation (fQRS) with disease severity is currently unknown. The study objective was to assess the prevalence of nQRS and fQRS in dogs with MMVD and its severity according to ACVIM classification and to compare the results with a group of healthy dogs. This retrospective cross-sectional study included 34 healthy control dogs and 155 dogs with spontaneous MMVD (42% of dogs in class B1, 23% in class B2 and 35% in class C). fQRS was defined as nQRS complexes in two contiguous leads in the frontal plane (leads I and aVL) and (II, III or aVF). A one-way ANOVA with Bonferroni post-hoc test was used to assess the differences in continuous data between control and MMVD groups. Of the MMVD group, 58% showed nQRS in at least one lead and 27% presented fQRS. There was no difference between the number of leads with a nQRS and disease severity (p = 0.75) nor did the number of leads with a nQRS correlate with left atrial size (r = 0.48; p = 0.5). The number of dogs with fQRS did not differ among classes of MMVD (p = 0.21). nQRS and fQRS were more prevalent in dogs with MMVD compared to control dogs (p < 0.01). This study did not identify any relationship between the number of leads with a nQRS and disease severity. However, dogs with MMVD had a higher prevalence of nQRS and fQRS compared to control group.     

Incremental predictive value of echocardiographic indices of right ventricular function in the assessment of long-term prognosis in dogs with myxomatous mitral valve disease

IntroductionFew studies have evaluated the utility of echocardiographic indices of right ventricular (RV) function in predicting prognosis in dogs with myxomatous mitral valve disease (MMVD).AnimalsSixty-seven client-owned dogs were diagnosed with MMVD.Materials and methodsclinical cohort study. Dogs diagnosed with American college of veterinary internal medicine (ACVIM) stage B2, C or D between April 2014 and March 2017 were enrolled. Long-term outcomes were assessed by telephone or from the medical record. The primary end-point was defined as cardiac-related death. Echocardiographic indices of RV function, including the RV Tei index, free wall and septal RV longitudinal strain, were obtained. Univariable and multivariable Cox proportional hazard analyses were used to identify variables predictive of cardiac-related death.ResultsTwenty-four dogs died during the follow-up period. The median follow-up time was 482 days, and the median survival time for dogs with cardiac-related death was 230 days. For cardiac-related death, peak early diastolic mitral inflow velocity, ACVIM stage C or D, tricuspid regurgitation velocity, RV Tei index and RV end-diastolic area were predictors in univariable Cox proportional hazard analysis. In multivariable Cox proportional analysis adjusted for the left atrial to aorta ratio, peak early diastolic mitral inflow velocity and ACVIM stage, an increase in the Tei index by 0.1 increased the hazard ratio of cardiac-related death by 33% (95% confidence interval, 16–70%; P = 0.002).ConclusionsIn dogs with MMVD, RV dysfunction assessed by the Tei index is an independent predictor of cardiac-related death.     

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.     

R-R interval variations influence the degree of mitral regurgitation in dogs with myxomatous mitral valve disease

Mitral regurgitation (MR) due to myxomatous mitral valve disease (MMVD) is a frequent finding in Cavalier King Charles Spaniels (CKCSs). Sinus arrhythmia and atrial premature complexes leading to R-R interval variations occur in dogs. The aim of the study was to evaluate whether the duration of the R-R interval immediately influences the degree of MR assessed by echocardiography in dogs. Clinical examination including echocardiography was performed in 103 privately-owned dogs: 16 control Beagles, 70 CKCSs with different degree of MR and 17 dogs of different breeds with clinical signs of congestive heart failure due to MMVD. The severity of MR was evaluated in apical four-chamber view using colour Doppler flow mapping (maximum % of the left atrium area) and colour Doppler M-mode (duration in ms). The influence of the ratio between present and preceding R-R interval on MR severity was evaluated in 10 consecutive R-R intervals using a linear mixed model for repeated measurements.MR severity was increased when a short R-R interval was followed by a long R-R interval in CKCSs with different degrees of MR (P < 0.005 when adjusted for multiple testing). The relationship was not significant in control dogs with minimal MR and in dogs with severe MR and clinical signs of heart failure. In conclusion, MR severity increases in long R-R intervals when these follow a short R-R interval in CKCSs with different degrees of MR due to asymptomatic MMVD. Thus, R-R interval variations may affect the echocardiographic grading of MR in CKCSs.     

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.     

Left atrial volume and function in dogs with naturally occurring myxomatous mitral valve disease

Objective

Myxomatous mitral valve disease (MMVD) induces progressive left atrial (LA) enlargement. The LA modulates left ventricular filling and performance through its reservoir, conduit, and contractile function. Assessment of LA size and function may provide valuable information on the level of cardiac compensation. Left atrial function in dogs with naturally occurring MMVD remains largely unexplored. The objective of this study was to evaluate LA volume and function in dogs with naturally occurring MMVD.

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.     

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.     

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)     

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.     

Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease

ObjectivesTo evaluate the predictive value of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers for progression of mitral regurgitation caused by myxomatous mitral valve disease.AnimalsSeventy-eight privately owned Cavalier King Charles spaniels with naturally occurring myxomatous mitral valve disease.MethodsProspective longitudinal study comprising 312 measurements over a 4.5 year period. Clinical values were recorded, NT-proANP concentrations were measured by radioimmunoassay, and NOx were analyzed colorimetrically. To predict congestive heart failure (CHF), Cox proportional hazards models with time-varying covariates were constructed.ResultsThe hazard ratio for NT-proANP (per 1000 pmol/l increase) to predict future CHF was 6.7 (95% confidence interval, 3.6–12.5; p < 0.001). The median time to CHF for dogs with NT-proANP levels >1000 pmol/l was 11 months (95% confidence interval, 5.6–12.6 months), compared to 54 months (46 – infinity) for dogs with concentrations ≤1000 pmol/l (p < 0.001). Due to intra- and inter-individual variability, most corresponding analyses for NOx were insignificant but dogs reaching CHF had a lower mean NOx concentration than dogs not reaching CHF (23 vs. 28 μmol/l, p = 0.016). Risk of CHF increased with increase in heart rate (>130 beats per minute) and grade of murmur (≥3/6).ConclusionsThe risk of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool to identify dogs that may develop CHF within months.