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.     

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.

     

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.     

Effect of atorvastatin on oxidative stress and inflammation markers in myxomatous mitral valve disease in dogs: A comparison of subclinical and clinical stages

Myxomatous mitral valve disease (MMVD) is the most common acquired cardiac disorder found in dogs. The disease process can lead to heart failure (HF) and has been found to be associated with oxidative stress and inflammation. Statins exert antioxidant and anti‐inflammatory effects in human HF patients. However, the beneficial effects of statins in MMVD dogs are still unclear. Thirty MMVD dogs were enrolled in the study and were divided into two groups: MMVD without HF dogs (n = 15) and MMVD with HF dogs (n = 15). Atorvastatin (8 mg kg^?1 day^?1) was administered orally to all dogs for 4 weeks. All dogs underwent physical examination and cardiac examination at the beginning and end of the experiment, including baseline values for hematology, blood chemistry profile, lipid profile, N‐terminal pro B‐type natriuretic peptide, oxidative stress marker (8‐isoprostane), and inflammatory marker (tumor necrosis factor alpha). The results showed that atorvastatin reduced plasma cholesterol levels in both groups. In addition, plasma concentrations of 8‐isoprostane, tumor necrosis factor alpha, and N‐terminal pro B‐type natriuretic peptide were significantly lower after atorvastatin administration, but only in MMVD dogs in the HF group. Atorvastatin found to be associated with possible antioxidant and inflammatory effects in dogs with HF secondary to MMVD. The potential benefits of statins in dogs with HF merits further investigation in larger, placebo‐controlled studies.     

Clinical efficacy of pimobendan versus benazepril for the treatment of acquired atrioventricular valvular disease in dogs

Seventy-six dogs with clinical acquired atrioventricular valvular disease were evaluated to determine the efficacy of pimobendan (n=41) versus benazepril hydrochloride (n=35) in a randomized, positive-controlled, multicenter study. The study was divided into 56-day and long-term evaluation periods. In a subgroup of dogs with concurrent furosemide treatment (pimobendan [n=31], benazepril [n=25]), the Heart Insufficiency Score improved in favor of pimobendan (P=0.0011), equating to a superior overall efficacy rating (P<0.0001) at day 56. Long-term median survival (i.e., death or treatment failure) for dogs receiving pimobendan was 415 days versus 128 days for dogs not on pimobendan (P=0.0022).     

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.     

Suspected sequential left atrial ruptures in a dog with myxomatous mitral valve disease

An 11-year-old mixed breed dog was presented with exercise intolerance and syncope. At admission, transthoracic echocardiography revealed myxomatous mitral valve disease (MMVD) associated with severe left atrial (LA) enlargement and moderate anechoic pericardial effusion with a hyperechoic density suggestive of a thrombus. Rupture of the LA free wall secondary to MMVD was suspected, and medical therapy with furosemide and pimobendan was initiated. After one month, recheck echocardiography showed mild anechoic pericardial effusion and an acquired atrial septal defect with a left-to-right intracardiac shunting flow. In light of the dog's history, the latter finding was suspected to be secondary to a further rupture of the LA wall due to MMVD, this time affecting the interatrial septum. The images described here allow us to suspect that sequential LA wall ruptures developed over time in the same subject affected by MMVD, a clinical presentation not previously described in veterinary medicine.     

Brain-natriuretic peptide and cyclic guanosine monophosphate as biomarkers of myxomatous mitral valve disease in dogs

Elevations in the plasma concentrations of natriuretic peptides correlate with increased severity of myxomatous mitral valve disease (MMVD) in dogs. This study correlates the severity of MMVD with the plasma concentrations of the biomarkers N-terminal fragment of the pro-brain-natriuretic peptide (NT-proBNP) and its second messenger, cyclic guanosine monophosphate (cGMP). Furthermore, the l-arginine:asymmetric dimethylarginine (ADMA) ratio was measured as an index of nitric oxide availability. The study included 75 dogs sub-divided into five groups based on severity of MMVD as assessed by clinical examination and echocardiography.Plasma NT-proBNP and cGMP concentrations increased with increasing valve dysfunction and were significantly elevated in dogs with heart failure. The cGMP:NT-proBNP ratio decreased significantly in dogs with heart failure, suggesting the development of natriuretic peptide resistance. Although the l-arginine:ADMA ratio decreased with increasingly severe MMVD, this was largely due to the older age of the dogs with heart failure.     

Lowered N-terminal pro-B-type natriuretic peptide levels in response to treatment predict survival in dogs with symptomatic mitral valve disease

ObjectivesIn humans with congestive heart failure (CHF), better outcome is correlated with lower natriuretic peptide (NP) levels after starting treatment and greater percentage reduction of NP levels. Therefore, the aim of this study was to determine the relationship between absolute and relative changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and pro-atrial natriuretic peptide 31–67 (proANP 31–67) and overall cardiac survival in patients with symptomatic myxomatous mitral valve disease (MMVD). Furthermore, we sought to compare clinical and echocardiographic status of 12-month survivors and non-survivors.Animals, materials and methods26 dogs with CHF due to MMVD. Initial NP levels, as well as absolute and percentage changes of follow-up NP levels (between 7 and 30 days after treatment start) and heart failure (HF) class were tested as potential predictors of overall cardiac survivorship. Additionally, various echocardiographic parameters, creatinine concentrations and furosemide doses were compared between 12-month survivors and non-survivors.ResultsDogs with follow-up NT-proBNP level <965 pmol/l had a significantly longer overall cardiac survival than patients with NT-proBNP level >965 pmol/l (P = 0.03). Dogs in a higher HF class had a significantly (P = 0.03) higher probability of shorter survival independent of their NP levels. When dogs were grouped by 12-month survival, only follow-up NT-proBNP levels were significantly different between groups.ConclusionsHF class at presentation and NT-proBNP levels after initiating treatment are predictive of mortality in patients with symptomatic MMVD. ProANP 31–67 levels, percentage reduction in NPs levels, creatinine or urea concentration, echocardiographic parameters and furosemide dose did not predict outcome.     

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.     

Effects of pimobendan for mitral valve regurgitation in dogs

Pimobendan has a dual mechanism of action: it increases myocardial contractility by increasing calcium sensitization to troponin C and it promotes vasodilation by inhibiting PDEIII. This study examined the effects of pimobendan on cardiac function, hemodynamics, and neurohormonal factors in dogs with mild mitral regurgitation (MR). The dogs were given 0.25 mg/kg of pimobendan orally every 12 hr for 4 weeks. With pimobendan, the heart rate and stroke volume did not change, but the systolic blood pressure gradually decreased and the degree of mitral valve regurgitation tended to decrease. Renal blood flow was significantly increased and the glomerular filtration rate was slightly increased at 2 and 4 weeks. Furthermore, over the 4-week period, the plasma norepinephrine concentration decreased significantly, the systolic index increased slightly, the left atrial diameter and the left ventricular diameters decreased significantly, and the heart size improved. Given these results, pimobendan appears to be useful for treating MR in dogs. However, further long-term studies of pimobendan involving a larger number of dogs with mild and moderate MR are needed to establish the safety of pimobendan and document improvements in quality of life.     

Heart rate variability parameters of myxomatous mitral valve disease in dogs with and without heart failure obtained using 24-hour Holter electrocardiography

Time-domain heart rate variability (HRV) parameters and the correlation between echocardiography and Holter examinations in dogs with myxomatous mitral valve disease (MMVD) were determined. Holter examination was also performed at different time frames: an entire 24-hour period, a four-hour period during sleep, and a four-hour period while awake. Ten healthy (control group) and 28 MMVD dogs, 15 with and 13 without heart failure, were evaluated. The SDANN (sd of the mean normal RR intervals for all five-minute segments during 24-hour Holter) and pNN(50) (percentage of differences between adjacent normal RR intervals that are >50 ms computed over 24-hour Holter) variables were significantly lower in the dogs with MMVD heart failure. The differences in HRV between the groups were only detected during the 24-hour evaluation period (P<0.05). There were high correlations (canonical analysis) between Holter and echocardiography examinations when considering pNN(50), SDANN, and LA/AO (left atrial to aortic root ratio) (r=0.92; P<0.05), indicating that both are important in evaluating MMVD dogs. SDANN and pNN(50) are measures of parasympathetic control of the heart, and thus, it is possible to infer that the MMVD dogs exhibit parasympathetic withdrawal during the development of heart failure.     

Assessment of global and regional left ventricular volume and shape by real-time 3-dimensional echocardiography in dogs with myxomatous mitral valve disease

Background: Left ventricular (LV) remodeling occurs in response to chronic volume overload. Real‐time 3‐dimensional (RT3D) echocardiography offers new modalities for LV assessment. Objective: To investigate LV changes in shape and volume in response to different severities of naturally acquired myxomatous mitral valve disease (MMVD) in dogs by RT3D echocardiography. Animals: Sixty‐five client‐owned dogs. Methods: Prospectively recruited dogs were classified by standard echocardiography into healthy, mild, moderate, and severe MMVD groups. Endocardial border tracking of LV RT3D dataset was performed, from which global and regional (automatically acquired basal, mid, and apical segments based on LV long‐axis length) end‐diastolic (EDV) and end‐systolic volumes (ESV), LV long‐axis length, and sphericity index were obtained. Results: Global and regional EDV and ESV (indexed to body weight) were most prominently increased in dogs with severe MMVD. All 3 regional LV segments contributed to increased global EDV and ESV with increasing MMVD severity, but mid‐EDV contributed the most to the global EDV increase. Furthermore, LV long‐axis length and LV sphericity index increased with increasing MMVD severity. Basal and apical EDV segments displayed the strongest association with sphericity index (P < .0001). Conclusions and Clinical Importance: The most prominent LV volume expansion was found in dogs with severe MMVD. Increased EDV, primarily in the mid‐segment, leads to rounding of LV apical and basal segments in response to increasing MMVD severity. Assessment of LV volume and shape potentially could allow early detection of dogs at risk for rapid progression into congestive heart failure.     

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.     

Comparison of electrocardiographic parameters in dogs with different stages of myxomatous mitral valve disease

This study evaluated changes in electrocardiographic (ECG) parameters according to the stage of myxomatous mitral valve disease (MMVD) in dogs, as well as the utility of ECG parameters as prognostic indicators for congestive heart failure (CHF). Medical records of dogs with MMVD were retrospectively searched. Dogs with MMVD (N = 101) were classified into stages B [B1 (n = 52) and B2 (n = 23)] and C (n = 26) according to the American College of Veterinary Internal Medicine guidelines. Baseline variables were collected; these included signalment, radiographic, echocardiographic, and ECG parameters. Corrected QT intervals (QTc) were calculated using the logarithmic (QTc1) and Fridericia (QTc2) formulas. The P wave duration, QTc1, and QTc2 were significantly longer in stage C than in stage B. The P wave duration cutoff of 43.5 ms had a diagnostic accuracy of 65% for differentiating CHF, with a sensitivity of 63% and a specificity of 90%. A cutoff value of 307.8 ms for QTc1 yielded a sensitivity of 62%, a specificity of 76%, and a diagnostic accuracy of 78%, and a cutoff value of 239.2 ms for QTc2 yielded a sensitivity of 62%, a specificity of 83%, and a diagnostic accuracy of 77% for diagnosing CHF. Therefore, prolonged P wave and QTc in dogs with MMVD may facilitate the prediction of CHF. Electrocardiography could provide clinicians with a readily available and cost-effective screening tool for predicting CHF, if the usefulness of ECG parameters can be verified.     

Predictive value of natriuretic peptides in dogs with mitral valve disease

Natriuretic peptides are useful in diagnosing heart failure in dogs. However, their usefulness in detecting early stages of myxomatous mitral valve disease (MMVD) has been debated. This study evaluated N-terminal (NT) fragment pro-atrial natriuretic peptide (NT-proANP) and NT-pro-brain natriuretic peptide (NT-proBNP) in 39 Cavalier King Charles Spaniels (CKCS) with pre-clinical mitral valve regurgitation (MR), sixteen dogs with clinical signs of heart failure (HF) and thirteen healthy control dogs. Twenty seven CKCS and ten control dogs were re-examined 4 years after the initial examination and the status of the dogs 5 years after the initial examination was determined by telephone calls to the owner. All dogs were evaluated by clinical examination and echocardiography. CKCS with severe MR had higher NT-proANP and NT-proBNP compared to controls and CKCS with less severe MR. Dogs with clinical signs of HF had markedly elevated NT-proANP and NT-proBNP. Plasma concentrations of the natriuretic peptides measured at re-examination could predict progression in regurgitant jet size.     

Tissue Doppler and Strain Imaging in Dogs with Myxomatous Mitral Valve Disease in Different Stages of Congestive Heart Failure

Background: Tissue Doppler imaging (TDI) including strain and strain rate (SR) assess systolic and diastolic myocardial function.
Hypothesis: TDI, strain, and SR variables of the left ventricle (LV) and the interventricular septum (IVS) differ significantly between dogs with myxomatous mitral valve disease (MMVD) with and without congestive heart failure (CHF).
Animals: Sixty-one dogs with MMVD with and without CHF. Ten healthy control dogs.
Methods: Prospective observational study.
Results: Radial motion : None of the systolic variables were altered and 3 of the diastolic velocities were significantly increased in dogs with CHF compared with dogs without CHF and control dogs. Longitudinal motion : 2 systolic velocities and 3 diastolic velocities were significantly increased in dogs with CHF compared with dogs without CHF and control dogs. Difference in systolic velocity time-to-peak between LV and IVS was significantly increased in dogs with MMVD with and without CHF compared with control dogs. In total, 11 (23%) of 48 TDI and strain variables differed significantly between groups. Left atrial to aortic ratio was positively correlated to early diastolic velocities, percentage increase in left ventricular internal diameter in systole was positively correlated to systolic and diastolic velocities, and mitral E wave to peak early diastolic velocity in the LV basal segment (E/Em) was positively correlated to radial strain and SR.
Conclusions and Clinical Importance: Few TDI and strain variables were changed in dogs with MMVD with and without CHF. Intraventricular dyssynchrony may be an early sign of MMVD or may be an age-related finding.     

Efficacy of Spironolactone on Survival in Dogs with Naturally Occurring Mitral Regurgitation Caused by Myxomatous Mitral Valve Disease

Background: Spironolactone, an aldosterone antagonist, has been demonstrated to decrease mortality in human patients when added to other cardiac therapies. Hypothesis: Spironolactone in addition to conventional therapy increases survival compared with conventional therapy in dogs with naturally occurring myxomatous mitral valve disease (MMVD). Animals: Between February 2003 and March 2005, 221 dogs were recruited in Europe. Nine dogs were excluded from analysis, leaving 212 dogs with moderate to severe mitral regurgitation (MR) caused by MMVD (International Small Animal Cardiac Health Council classification classes II [n = 190] and III [n = 21]). Methods: Double‐blinded, field study conducted with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin converting enzyme inhibitor, plus furosemide and digoxin if needed). Primary endpoint was a composite of cardiac‐related death, euthanasia, or severe worsening of MR. Results: Primary endpoint reached by 11/102 dogs (10.8%) in the spironolactone group (6 deaths, 5 worsening) versus 28/110 (25.5%) in control group (14 deaths, 8 euthanasia, 6 worsening). Risk of reaching the composite endpoint significantly decreased by 55% (hazard ratio [HR] = 0.45; 95% confidence limits [CL], 0.22–0.90; log rank test, P= .017). Risk of cardiac‐ related death or euthanasia significantly reduced by 69% (HR = 0.31; 95% CL, 0.13–0.76; P= .0071). Number of dogs not completing the study for cardiac and other miscellaneous reasons similar in spironolactone (67/102) and control groups (66/110). Conclusion and Clinical Importance: Spironolactone added to conventional cardiac therapy decreases the risk of reaching the primary endpoint (ie, cardiac‐related death, euthanasia, or severe worsening) in dogs with moderate to severe MR caused by MMVD.     

Holter monitoring in 36 dogs with myxomatous mitral valve disease

Objective Describe the presence of arrhythmias in dogs with myxomatous mitral valve disease (MMVD) and the potential association with class of heart failure and left atrial enlargement. Compare the standard electrocardiogram (ECG) with Holter monitoring for assessing heart rate (HR). Experimental procedure The study group of 36 dogs weighing less than 20 kg was divided into MMVD and no clinical signs (preclinical) or MMVD and clinical signs (clinical). A standard echocardiogram, ECG and 24-h Holter recording were obtained in all dogs. Results Minimum and mean Holter HRs were higher in the clinical group than in the preclinical group. Clinical dogs had more ventricular arrhythmias than preclinical dogs. An enlarged left atrium was associated with the presence of more supraventricular arrhythmias. Conclusions Arrhythmias are a common finding in dogs with MMVD and Holter monitoring is a reliable tool for both HR monitoring and diagnosis.