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Pimobendan for myxomatous mitral valve degeneration in dogs | VETgirl Veterinary CE Podcasts

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In this VETgirl online veterinary CE podcast, we review the use of pimobendan in dogs with myxomatous mitral valve degeneration (MMVD). Pimobendan (commonly known as Vetmedin in the United States) is a phosphodiesterase III inhibitor and calcium sensitizer. It is commonly used as a therapy for congestive heart failure and is often referred to as an “inodilator” due to its positive inotropic and peripheral vasodilatory mechanisms of action.

Pimobendan has been demonstrated to have significant positive benefits in both humans and dogs with congestive heart failure; however concern persists that it may have the ability to potentiate arrhythmia activity based on the results of initial clinical trials in humans (This is based on indirect evidence via mortality data, not arrhythmia quantification data). Data evaluating the effects of pimobendan on arrhythmia severity in canine heart disease has been conflicting. Existing evidence that does support this premise in dogs has not demonstrated with any clarity that progressive arrhythmias in those patients were due to the drug itself and not simply the natural progression of the underlying heart disease.

So, Lake-Bakaar et al out of UC Davis wanted to evaluate whether pimobendan caused arrhythmias in canine heart disease patients in their study called “Effect of pimobendan on the incidence of arrhythmias in small breed dogs with myxomatous mitral valve degeneration.” They performed a prospective, double blinded randomized placebo-controlled crossover study (Woo hoo! This is rarely done in veterinary medicine, so huge kudos to them). They looked at 8 small breed dogs (which were less than 15 kgs) with controlled congestive heart failure due to MMVD (using furosemide and enalapril therapy).

This study lasted 5 weeks in total, with 2 weeks each on pimobendan and placebo and a one week washout period prior to crossover midway through the study. The patients had 24 hour Holter monitors on to evaluate average heart rate and arrhythmia severity. In total, 7/8 of the dogs completed the study. One dog was euthanized due to severe acute azotemia (after 14 days of placebo, a 7 day washout, and 2 days on  pimobendan). Pet owners also completed a quality of life survey and recorded sleeping respiratory rates (SRR) at home during specific time points.

So what’d they find in this study? They found a significant reduction in median heart rate between pimobendan and baseline but not pimobendan and placebo. There was also no significant difference in the quality of life survey results between pimobendan and placebo (Um, I guess this proves the placebo effect). There was a significant reduction in the median sleeping respiratory rate with pimobendan versus baseline and the placebo. Also, there was no significant differences in ventricular arrhythmias (e.g., VPCs) or supraventricular arrhythmias (e.g., APCs) per 24 hour among baseline, placebo, or pimobendan groups. No effect of time on arrhythmia severity was identified in this study also.

No specific proarrhythmic effect of pimobendan was identified in this study. The study’s crossover design allowed for control of time as an effect on arrhythmia progression. This study also showed reductions in indirect markers for resting sympathetic tone (which can reflect the degree of congestive heart failure control) such as respiratory rate and heart rate in favor of pimobendan versus baseline and/or placebo. It did not demonstrate any difference in quality of life, however, when assessed by the pet owner.

So, the take home messiage? There is no evidence of a proarrhythmic effect of pimobendan on dogs with congestive heart failure secondary to myxomatous mitral valve degeneration as identified in this small prospective study.

VETgirl’s take on this study? This was a nicely performed, albeit small, prospective study that should give some degree of confidence that pimobendan is not blatantly worsening arrhythmia severity in this population. It should be considered a pilot study, however, due to the very small sample size and short duration (dogs only received pimobendan for 2 weeks). Before any definitive conclusions can be made about pimobendan and arrhythmias, larger studies over longer durations of treatment are necessary. That said, kudos for the study design.

References:
1. Lake-Bakaar G, Singh MK, Kass PH et al. Effect of pimobendan on the incidence of arrhythmias in small breed dogs with myxomatous mitral valve degeneration. J Vet Cardiol 2015;17:120-128.

Abbreviations:

CHF: congestive heart failure

MMVD: myxomatous mitral valve degeneration

SRR: sleeping respiratory rate

VPC: ventricular premature contraction

APC: atrial premature contraction

 

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