Effects Of Pimobendan Research Articles

The effect of pimobendan and enalapril use on blood serum trace element levels in dogs with myxomatous mitral valve disease

Background and objectiveMyxamatous mitral valve disease (MMVD) is a common acquired heart disease in dogs that can lead to progressive and long-term congestive heart failure (CHF). Pimobendan and angiotensin converting enzyme inhibitors (ACEI) are commonly used in MMVD treatment. Trace elements are essential for maintaining cardiovascular functions. Synergistic or antagonistic interactions between some trace elements and substances are widely known. In our study, it was aimed to evaluate the effects of treatment duration, age, weight and gender on serum trace element levels in dogs with MMVD by using pimobendan and enalapril as monotherapy. Material-Methods13 dogs with MMVD were treated with pimobendan (0.25–0.3 mg/kg, q12h, PO Vetmedin®) and 21 dogs with MMVD were treated with enalapril (0.25–0.5 mg/kg, q12h, PO Enapril®) for at least 30 days. The serum trace element levels (Cu, Zn, Fe, Co, Mg, Mn, Se, Cr) of all patients were measured with Inductively coupled plasma-Optical emission spectroscopy device. Relevances were evaluated related to treatment duration, age, weight and gender in each treatment group. ResultsAdjusted R2 values of the model, which included treatment, treatment duration, treatment x duration interaction, age, weight and gender as predictors, were negative except for Se. Furthermore, the model explained only 10.4% of the variation in Se. The effect of age was significant in the model of Se (β = 0.462; P = 0.028). Treatment duration also tended to be significant in the prediction of Se concentration (β = -0.364; P = 0.086). ConclusionWe consider that treatment (enalapril vs. pimobendan), treatment duration, treatment x duration interaction, weight and gender were not good predictors of trace elements. In our study, age contributed significantly only to the Se level.

The Effect of Pimobendan and Enalapril Use on Blood Serum Trace Element Levels in Dogs with Myxomatous Mitral Valve Disease

The Effect of Pimobendan and Enalapril Use on Blood Serum Trace Element Levels in Dogs with Myxomatous Mitral Valve Disease

Acute Effects of Pimobendan on Cardiac Function in Dogs With Tachycardia Induced Dilated Cardiomyopathy: A Randomized, Placebo-Controlled, Crossover Study.

Background: Pimobendan provides a significant survival benefit in dogs with cardiac disease, including degenerative mitral valve disease and dilated cardiomyopathy (DCM). Its positive inotropic effect is well-known, however, it has complex effects and the mechanisms behind the survival benefit are not fully characterized. Secondary hemodynamic effects may decrease mitral regurgitation (MR) in DCM, and the benefits of pimobendan may extend to improved cardiac relaxation and improved atrial function.Hypothesis/Objectives: Our objective was to investigate the acute cardiac effects of pimobendan in dogs with a DCM phenotype. We hypothesized that pimobendan would increase left atrial (LA) contractility, reduce mitral regurgitation, improve diastolic function, and lower circulating NT-ProBNP levels.Animals: Seven purpose-bred Beagles were studied from a research colony with tachycardia induced DCM phenotype.Methods: The effects of pimobendan were studied under a placebo-controlled single-blinded cross-over design. In short, dogs underwent baseline and 3 h post-dose examinations 7 days apart with echocardiography and a blood draw. Dogs were randomized to receive oral placebo or 0.25 mg/kg pimobendan after their baseline exam. Investigators were blinded to treatments until all measurements were compiled.Results: When treated with pimobendan, the dogs had significant increases in systolic function and decreases in MR, compared to when treated with placebo.There were no detectable differences in left atrial measures, including LA size, LA emptying fraction, LA functional index or mitral A wave velocity. Heart rate decreased significantly with pimobendan compared to placebo. There was also a decrease in isovolumetric relaxation time normalized to heart rate. NT-proBNP levels had a high degree of variability.Conclusions: Improved mitral regurgitation severity and improved lusitropic function may contribute to the reported survival benefit for dogs with cardiac disease administered pimobendan. Pimobendan did not overtly improve LA function as assessed by echocardiography, and NT-proBNP was not significantly changed with a single dose of this medication. Further studies are needed to better characterize LA effects with other imaging modalities, to better quantify the total improvement of MR severity, and to assess chronic use of pimobendan on diastolic function in DCM.

Acute pharmacodynamic effects of pimobendan in client-owned cats with subclinical hypertrophic cardiomyopathy

BackgroundPrior studies have suggested that pimobendan is associated with several positive effects in cats, including improved survival in cats with congestive heart failure and improved left atrial function in research colony cats with hypertrophic cardiomyopathy (HCM) and normal cats. However, there is still a paucity of pharmacodynamic data refuting or supporting the use of pimobendan in a clinical cat population. This clinical trial aimed to evaluate the pharmacodynamic effects and tolerability of a single dose of pimobendan in cats with HCM. Echocardiograms and Doppler-derived systolic blood pressures were performed in 21 client-owned cats with subclinical HCM at baseline and 90-min after oral administration of 1.25 mg of pimobendan (Vetmedin). Seven additional cats were evaluated post-placebo administration to account for intra-day variability.ResultsHeart rate, systolic blood pressure, and murmur grade were not significantly different between baseline and post-pimobendan evaluations. Left auricular blood flow velocity, left atrial size, and left ventricular fractional shortening were not significantly different between baseline and post-pimobendan evaluations.Mean (± standard deviation) tissue Doppler peak systolic velocity of the mitral annulus was significantly higher following pimobendan (7.4 cm/s ± 1.5 vs 8.5 ± 1.6; p = 0.02). Median (min, max) left-ventricular outflow tract maximum velocity was significantly higher following pimobendan [1.9 m/sec (1.5, 3.4) vs 2.6 m/sec (2.0, 4.0); p = 0.01]. Mean right-ventricular outflow tract maximum velocity was also significantly higher following pimobendan (1.5 m/s ± 0.51 vs 2.0 ± 0.53; p = 0.004). Mean left atrial fractional shortening was significantly higher following pimobendan (28% ± 6 vs 32% ± 7; p = 0.02).No adverse events were observed following pimobendan administration.Right ventricular outflow tract velocity was significantly higher following placebo in control cats (1.02 ± 0.21 versus 1.31 ± 0.31; p = 0.01). No other significant differences were detected.ConclusionsIn client-owned cats with HCM, pimobendan acutely increased left atrial function and mildly increased left ventricular systolic function. Left ventricular outflow tract velocity was increased after pimobendan. Pimobendan was well tolerated in the acute setting in cats with HCM. The findings of this prospective, acute-dosing study confirm previous findings in research animals and retrospective analyses and suggest that chronic dosing studies are safe and warranted.

Effects of pimobendan on left atrial transport function in cats.

BackgroundArterial thromboembolism is a sequela of hypertrophic cardiomyopathy (HCM) in cats related to left atrial (LA) enlargement and dysfunction.HypothesisPimobendan improves LA transport function in cats.AnimalsTwenty‐two client‐owned cats with HCM and 11 healthy cats.MethodsProspective, double‐blind, randomized, placebo‐controlled clinical cohort study. Cats were randomized to receive either pimobendan (0.25 mg/kg PO q12h) or placebo for 4 to 7 days. Nineteen echocardiographic variables of LA size and function were evaluated. Statistical comparisons included t tests, analysis of variance, and multivariable analyses.ResultsPeak velocity of left auricular appendage flow (LAapp peak; mean ± SD, 0.85 ± 0.20 vs 0.71 ± 0.22 m/s; P = .01), maximum LA volume (P = .03), LA total emptying volume (P = .03), peak velocity of late diastolic transmitral flow (A peak velocity; 0.77 ± 0.12 vs 0.62 ± 0.17 m/s; P = .05), and A velocity time integral (A VTI; 3.05 ± 0.69 vs 3.37 ± 0.49; P = .05) were increased after pimobendan. Mean change after pimobendan was larger in cats with HCM compared to healthy cats for LA fractional shortening (2.1% vs −2.1%; P = .05), A VTI (0.58 vs 0.01 cm; P = .01), LAapp peak (0.20 vs 0.02 m/s; P = .02), LA kinetic energy (3.51 vs −0.10 kdynes‐cm; P = .05), and LA ejection force (1.93 vs −0.07 kdynes; P = .01) in the multivariable model. The stronger effect of pimobendan in cats with HCM was independent of LA size.Conclusions and Clinical ImportanceWe identified positive, albeit minor, effects of pimobendan on LA function in cats with HCM. Whether or not treatment with pimobendan decreases the risk of cardiogenic embolism deserves further study.

Effects of Pimobendan on Prolonging Time to Rehospitalization or Frequency of Rehospitalization in Patients with Heart Failure: A Retrospective Cohort Study Using a Medical Administrative Database (PREFER Study).

BackgroundAs approximately 24% of patients with chronic heart failure are rehospitalized within 1 year and heart failure is aggravated by repeated hospitalizations, greater importance was attached to the prevention of hospitalization.ObjectiveThe objective of this study was to investigate the influence of pimobendan on rehospitalization of patients with advanced heart failure using a Japanese medical administrative database.MethodsFrom January 2010 to February 2018, patients hospitalized two or more times for heart failure were selected for analysis. The primary endpoint was the incidence of hospitalizations for heart failure during the follow-up period, which was compared between pimobendan prescription and non-prescription groups after propensity score matching.ResultsThe total number of patients with heart failure included during the study period was 1 421 110 and we matched 276 patients in both groups. The incidence of rehospitalization throughout the period to completion of follow-up was 365.23/1000 people/yr (95% confidence interval [CI]: 327.78–402.69) in the pimobendan prescription group and 537.81/1000 people/yr (95% CI: 492.36–583.27) in the non-prescription group. The cumulative incidence at 365 days was significantly lower in the pimobendan prescription group (pimobendan prescription group: 35.4% (95% CI: 29.8–41.8), non-prescription group: 51.2% (95% CI: 45.1–57.7), (P < 0.001). The adjusted hazard ratio in the pimobendan prescription group was 0.556 (95% CI: 0.426–0.725, P < 0.001).ConclusionPimobendan was suggested to extend the time to rehospitalization for patients with advanced heart failure. It is necessary to verify the results of this study by performing a prospective study. In addition, the influence of pimobendan on general heart failure patients must be examined.

Effect of pimobendan on left atrial function: an echocardiographic pilot study in 11 healthy cats

Objectives– To evaluate the effect of a single dose of pimobendan on left atrial (LA) function in healthy cats. Animals– Eleven client owned healthy cats. Material and methods– Standardized and repeated echocardiographic examinations were performed on healthy and conscious cats before and after a single dose of orally administered pimobendan (1.25 mg/cat). Left atrial systolic functional parameters were assessed. Results– Some of the tested parameters of LA function showed significant improvement after pimobendan administration, whereas no significant effect on left ventricular function was observed. In particular, LA minimal diameters obtained from M-mode images in short (p=0.018) and long (p=0.009) axis reduced after pimobendan administration, whereas LA fractional shortening from short (p=0.027) and long (p=0.042) axis and LA appendage emptying velocity (p<0.001) significantly increased. A mild increase in heart rate (p=0.001), and a transient increase on the peak systolic wave pulmonary vein velocity (p=0.008) were also recorded as a possible effect. Conclusions– A single dose of pimobendan appears to impact LA function in healthy cats. However, because of the small number of cats included, and the absence of a placebo group, these results cannot be definitively separated from the effect of time. Additional studies are needed to understand if similar effects are observed in cats with cardiomyopathy and LA dilatation.

Effect of Pimobendan in The Treatment of Pulmonary Hypertension in a Cat with Giant Right Atrium

Effect of Pimobendan in The Treatment of Pulmonary Hypertension in a Cat with Giant Right Atrium

Effect of pimobendan on physical fitness, lactate and echocardiographic parameters in dogs with preclinical mitral valve disease without cardiomegaly.

Pimobendan has gained enormous importance in the treatment of mitral valve disease in dogs. The current consensus statement of the American College of Veterinary Internal Medicine (ACVIM) recommends a treatment for dogs with symptomatic disease and dogs with asymptomatic disease with radiographic and echocardiographic signs of cardiomegaly. To investigate whether these dogs also benefit from a therapy with pimobendan, 21 dogs with mitral valve disease ACVIM B1 underwent a standardized submaximal exercise test on a treadmill. In this double-blinded and randomized study, the animals were divided into two groups, one receiving pimobendan and the other a placebo. At the first visit and at every follow-up appointment (at days 90 and 180), heart rate during the complete exercise test and lactate before and after running were measured. In addition to this, a questionnaire was completed by the dogs’ owners and all dogs were given an echocardiographic examination to detect any changes and to observe if the disease had progressed. Due to the diagnosis of leishmaniosis, one dog in the pimobendan group was retrospectively removed from the study so that 20 dogs were included for statistical analysis. No differences were observed at any time between the pimobendan-group and the placebo-group regarding heart rate. At day 180, the increase in lactate after exercise was significantly lower than in the placebo-group. The increase in the pimobendan-group at day 180 was lower than at day 90. Most of the dog owners from the pimobendan-group declared that their dogs were more active at day 90 (6/10) and at day 180 (8/10), while most dog owners from the placebo-group observed no changes regarding activity at day 90 (8/10) and day 180 (6/10). It can be concluded that the results of this study indicate that some dogs with mitral valve disease ACVIM B1 might benefit from a therapy with pimobendan.

Effect of Pimobendan on NT-proBNP and c troponin I before and after a submaximal exercise test in dogs with preclinical mitral valve disease without cardiomegaly \u2013 a randomised, double-blinded trial

BackgroundExercise testing in conjunction with measurement of cardiac biomarkers NT-proBNP and cTnI is a useful tool for monitoring the effect of treatment on cardiac patients. Administering Pimobendan in dogs with degenerative mitral valve disease (DMVD) and cardiomegaly results in delaying the onset of clinical symptoms and prolonging life. Its effect in dogs with DMVD without cardiomegaly has not been well examined. The aim of the current study was to investigate the effect of administering Pimobendan in dogs with DMVD without cardiomegaly using exercise testing in conjunction with measuring cardiac biomarkers in addition to echocardiography.Twenty-one dogs with asymptomatic DMVD without echocardiographic signs of cardiomegaly participated in a randomised, double-blinded trial. Dogs were divided into a Pimobendan-group (n = 11) and a placebo-group (n = 10) in a double-blinded study design and underwent a standardised submaximal exercise test (SSET). One dog in the Pimobendan-group was retrospectively removed from the study after being diagnosed with Leishmaniosis. Cardiac biomarkers NT-proBNP and cTnI were measured before and after exercise. Follow-up appointments were performed at days 90 and 180.ResultsDogs in the Pimobendan-group had significantly lower post-exercise NT-proBNP-levels after being administered Pimobendan than at the beginning of the study. They also had lower pre- and post-exercise-NT-proBNP-levels than those dogs in the placebo-group. There was neither a significant difference regarding the measured cTnI levels nor an increase in cTnI between the groups at any time.ConclusionsPimobendan lowers NT-proBNP in dogs with presymptomatic mitral valve disease without cardiomegaly before and after submaximal exercise. This indicates a reduction in cardiac wall stress. If dogs with asymptomatic DMVD without cardiomegaly benefit from treatment with Pimobendan (for example, through a longer survival time) warrants further investigation.

Effect of pimobendan on cytokine levels in doxorubicin-induced cardiotoxicity

Effect of pimobendan on cytokine levels in doxorubicin-induced cardiotoxicity

Is treatment with pimobendan associated with an increased risk of arrhythmias in dogs with heart disease?

Pimobendan is a positive inotrope and balanced vasodilator via its actions as a calcium sensitiser and phosphodiesterase III inhibitor, respectively.1 There is strong evidence for its use in the treatment...

Cardiology update: the EPIC study and what it means for treatment of myxomatous mitral valve disease

The results of a study published in 2016 brought welcome news to the world of veterinary cardiology. Myxomatous mitral valve disease (MMVD) is the most common form of acquired heart disease diagnosed in dogs. Before this study released its results, treatment of MMVD was restricted to when dogs developed heart failure as a result of the disease. Despite effective treatment, median survival time is less than a year when dogs are diagnosed with heart failure. Therefore, The Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study – A Randomized Clinical Trial (2016), chose to look at treating MMVD with pimobendan in an attempt to prolong the period before heart failure developed. The EPIC study proved conclusively that administration of pimobendan could delay the onset of heart failure by, on average, 15 months, both safely and effectively.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study – A Randomized Clinical Trial

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study – A Randomized Clinical Trial

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study—A Randomized Clinical Trial

BackgroundPimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown.Hypothesis/ObjectivesAdministration of pimobendan (0.4–0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac‐related death, or euthanasia.Animals360 client‐owned dogs with MMVD with left atrial‐to‐aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5.MethodsProspective, randomized, placebo‐controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac‐related death, or euthanasia.ResultsMedian time to primary endpoint was 1228 days (95% CI: 856–NA) in the pimobendan group and 766 days (95% CI: 667–875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47–0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952–NA) in the pimobendan group and 902 days (95% CI: 747–1061) in the placebo group) (P = .012).Conclusions and Clinical ImportanceAdministration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

In this issue - September 2016: Portable negative pressure wound therapy for skin grafts in dogs · Wellness testing in small animals · Effects of pimobendan on myocardial perfusion and pulmonary transit time in dogs · Rispens CVI988 vaccine virus and Marek's disease virus in poultry · A field study of ovulation in oestrus mares · Post-weaning growth of beef

In this issue - September 2016: Portable negative pressure wound therapy for skin grafts in dogs · Wellness testing in small animals · Effects of pimobendan on myocardial perfusion and pulmonary transit time in dogs · Rispens CVI988 vaccine virus and Marek's disease virus in poultry · A field study of ovulation in oestrus mares · Post-weaning growth of beef

Effect of pimobendan on the incidence of arrhythmias in small breed dogs with myxomatous mitral valve degeneration

ObjectiveTo determine if pimobendan, a phosphodiesterase III inhibitor and calcium sensitizer with positive survival benefits, has an effect on incidence of arrhythmias compared to placebo in small breed dogs with congestive heart failure (CHF) due to myxomatous mitral valve degeneration (MMVD). AnimalsEight client-owned small breed dogs (<15 kg) with CHF due to MMVD. MethodsA prospective double-blind randomized placebo-controlled crossover study design was used. Data were recorded at baseline and 2 weeks post-administration of placebo or pimobendan. Average heart rate and incidence of arrhythmia were determined from 24 h Holter analysis. Owners completed a quality of life (QOL) questionnaire at each time point and recorded sleeping respiratory rates (SRR). Mixed effects analysis of variance, with dog as the random variable was used to compare values obtained between baseline, placebo, and pimobendan. ResultsCompared to baseline, QOL scores were significantly improved following administration of either placebo or pimobendan (p = 0.021 and p < 0.001, respectively). No significant differences in type or incidence of supraventricular or ventricular arrhythmia were identified. Average heart rate with pimobendan was significantly lower than baseline (p < 0.001). Compared to baseline, SRR was significantly lower with pimobendan (p = 0.004), and significantly different from placebo (p = 0.045). ConclusionsNo significant difference between pimobendan and placebo was found on incidence of supraventricular or ventricular arrhythmia. The decrease in average heart rate and SRR may be reflective of superior heart failure control achieved with pimobendan therapy.

Amrinone, Forerunner of Novel Cardiotonic Agents, Caused Paradigm Shift of Heart Failure Pharmacotherapy

Amrinone has been a great forerunner of noncatechol and nonglycoside novel cardiotonic agents and given an extraordinary strong impact in the development of novel cardiotonic agents. Unexpectedly, amrinone failed to rescue the patients with chronic heart failure, thereby produced a prominent paradigm shift from inotropic to cardioprotective therapy, and contributed to advances in the current pharmacotherapy of chronic heart failure. In this study, Alousi et al showed that amrinone is a potent, long-acting positive inotropic agent when given orally or intravenously to either anesthetized or unanesthetized dogs. Amrinone was orally active with a rapid onset of action and duration of >5 hours and showed a wide separation between the positive inotropic and chronotropic effect. Amrinone increased contractile force and the rate of force development without changes in duration of the contractile cycle or time-to-peak tension, and in action potential or excitability even when it was given in relatively high concentrations. The toxicological studies attested to a low toxicity of amrinone ≤10 mg/kg, with less serious side effects such as lowering in blood pressure and an increase in heart rate compared with cardiac glycosides and catecholamines. The therapeutic index of amrinone was wide in contrast to that of cardiac glycosides that have a therapeutic index of ≈2 to 3, with life-threatening arrhythmias. Of greater interest was that amrinone did not increase cardiac output of the normal (nonfailing), but increased that of the failing heart model. The mechanism of action of amrinone, however, was shown only by exclusion criteria. Amrinone did not seem to act via a catecholamine mechanism because its inotropic effect was not blocked by the β-receptor blocking agent propranolol or by depletion of cardiac norepinephrine with reserpine. It was reported that there were no significant changes in the level of cardiac cAMP or phosphodiesterase (PDE) that could be responsible …

HEART's Original [臨床研究] ピモベンダンが心機能および脳血流に及ぼす影響の検討～心プール・脳血流シンチグラフィを用いて～

HEART's Original [臨床研究] ピモベンダンが心機能および脳血流に及ぼす影響の検討～心プール・脳血流シンチグラフィを用いて～

The Effect of Pimobendan on Left Atrial Pressure in Dogs with Mitral Valve Regurgitation

The effects of pimobendan on left atrial pressure (LAP) in dogs with mitral valve disease (MR) have not been documented in a quantitative manner. The objective was to document and study the short-term effects of pimobendan on LAP and echocardiographic parameters in MR dogs. Eight healthy Beagle dogs weighing 10.0-14.7 kg (3 males and 5 females; aged 2 years) were used. Experimental, cross-over, and interventional study. Dogs with surgically induced MR received pimobendan at either 0.25 mg/kg or 0.50 mg/kg p.o. q12h for 7 days and then, after a 7-day wash-out period, the other dosage. LAP was measured for 30 minutes at baseline and again on days 1, 2, 4, and 7 of pimobendan administration. Mean LAP was significantly decreased after the administration of 0.25 mg/kg (15.81 ± 5.44 mmHg to 12.67 ± 5.71 mmHg, P < .001) and 0.50 mg/kg (15.76 ± 5.45 mmHg to 10.77 ± 5.23 mmHg, P < .001). Also, the 0.50 mg/kg group led to a significantly lower LAP (P < .01) compared with the 0.25 mg/kg group. Significant reduction was seen for the first time 4 days after the administration of 0.25 mg/kg and a day after the administration of 0.50 mg/kg. Pimobendan decreased LAP in a dose-dependent manner in dogs with acute MR caused by experimental chordal rupture. This study did not evaluate adverse effects of high-dose pimobendan, and additional studies in clinical patients are warranted.