Use of pimobendan in cats: a practical evidence-based review

Abstract

Practical relevance:

Cardiomyopathies are a common condition and the leading cause of congestive heart failure (CHF) in cats; however, to date there have been limited therapeutic options available. Commonly used therapeutics include diuretics for CHF and antithrombotics 2 to reduce the risk of arterial thromboembolism (ATE), which do not directly affect myocardial function. This review summarizes the evidence for the use of pimobendan, a phosphodiesterase III inhibitor and calcium channel sensitizer, in feline cardiomyopathies. Potential benefits of pimobendan in cats include improved left ventricular systolic and diastolic function, reduced platelet aggregation, reduction in left atrial size, and improved left atrial and auricular systolic function.

Drug details:

Pimobendan is indicated for the treatment of CHF in conditions associated with systolic dysfunction (including dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and some cases with non-specific phenotypes) and has been used in the treatment of CHF secondary to hypertrophic cardiomyopathy. A dosage of pimobendan of 0.25 mg/kg PO q12h is generally well tolerated, and an approved oral solution is now available in the UK, EU, USA, Japan and Australia, which may facilitate administration in some cats; it should be noted, however, that pimobendan is not licensed for use in cats and marketing authorizations may vary between countries. Adverse events are uncommon with pimobendan but include gastrointestinal upset (anorexia, vomiting), transient changes in heart rate and possible worsening arrhythmias at higher doses. The use of pimobendan is contraindicated in cats with fixed obstructions of the left or right ventricular outflow tract (ie, congenital heart disease – pulmonic or aortic valvular stenosis).

Audience:

This article reviews the use of pimobendan in cats for primary care veterinarians and includes practical case examples that reflect the typical use and recommendations for usage of pimobendan by the authors.

Keywords

Cardiomyopathy vetmedin therapy congestive heart failure stage C stage D

Introduction

Cardiomyopathies are common in cats, with hypertrophic cardiomyopathy (HCM) being the most common phenotype (see ‘HCM in cats’ box).^16–19 Despite limited evidence, conventional treatments for cats with cardiomyopathy and CHF include diuretics, renin–angiotensin– aldosterone system inhibitors (ie, angiotensin-converting enzyme inhibitors, spironolactone) and antithrombotic therapy (ie, clopidogrel, factor Xa inhibitors) for thromboembolism prophy-laxis.^1,20–27 Pimobendan (Vetmedin; Boehringer Ingelheim) has also been increasingly used across the globe in recent years,^1,28 primarily in cats with clinical cardiomyopathies (ACVIM stages C–D),^29,30 with the LV systolic dysfunction of some cats with HCM, as described in the ‘HCM in cats’ box, providing a potential rationale for the use of this drug in these patients.^4–6 Pimobendan is a phosphodiesterase III inhibitor and calcium channel sensitizer that prolongs survival times in dogs with CHF secondary to myxomatous mitral valve disease and dilated cardiomyopathy (DCM), and delays the onset of CHF in dogs with ACVIM stage B2 myxomatous mitral valve disease and subclinical DCM.^31–33 However, while the inotropic, lusitropic and systemic vasodilatory effects of pimobendan have been documented in dogs, similar published data in cats are so far limited.^31,34–37

Studies reporting the use of pimobendan in cats with CHF secondary to a variety of cardiomyopathies show that this drug is well tolerated, although efficacy data are controversial and limited.^{30,27,38–40} One retrospective study, which included treatment of cats with documented mild LVOTO, reported that the median survival time in the cats with stage C HCM increased with pimobendan treatment compared with control cats (626 days vs 103 days, respectively).⁴¹ However, a 6-month prospective, multicenter, double-blind randomized placebo-controlled non-pivotal exploratory field study in cats with CHF secondary to HCM with or without LVOTO failed to demonstrate a difference between placebo and pimobendan in the proportion of cats completing the planned 6-month followup period. This study did confirm that pimobendan was well tolerated, with no difference in adverse events reported between placebo and pimobendan.⁴⁰

Pimobendan’s potential combination of increased inotropic and systemic vasodilatory effects has prompted concerns that it could cause, or worsen, dynamic LVOTO or mid-LV obstruction in cats with HCM by increasing the severity of obstruction while simultaneously lowering periperhal pressure. This could, in turn, lead to theoretical increases in myocardial oxygen demand, tachycardia, arrhythmias or peripheral hypotension. Research evaluating the safety and efficacy of pimobendan in cats with dynamic LVOTO is minimal and conflicting. One study reported worsened dynamic LVOTO in a cat with complex congenital heart disease including mitral valve dysplasia receiving pimobendan,⁴² while a more recent study reported that dynamic LVOTO did not worsen in cats with HCM receiving a single dose of pimobendan.³⁹ In two studies, cats with HCM and dynamic LVOTO were either excluded from the study at the onset³⁰ or excluded from statistical analysis (n = 3) due to worsening dynamic LVOTO despite a lack of clinical decline.⁴⁰ However, two relatively large retrospective studies included cats with HCM and LVOTO and reported no adverse outcomes.^29,30 The balance of this evidence suggests that, in some cases, pimobendan may cause a mild increase in LV outflow tract velocities, but it does not appear to cause clinical concern or reportable adverse events. However, to the authors’ knowledge, there are no studies to date that have evaluated the effects of pimobendan in cats with moderate to severe baseline LVOTO.²⁸

What is known about pimobendan in cats?

Studies describing the use of pimobendan in cats are summarized in Table 1. Most pharmacokinetic and pharmacodynamic data are derived from normal healthy animals and, as such, continue to be a potential limitation of their application in diseased animals. To improve clarity, the following sections are separated into healthy normal cats and cats with cardiomyopathy.

Table 1

Studies describing pimobendan use in cats

References	Design	Number of cats treated with pimobendan	Inclusion criteria	Concurrent medication	Study conclusion(s)	Reported adverse events (n, %)	Pimobendan dose	Survival time
MacGregor et al, 2011³⁰	Retrospective	170	HCM, NSCM, DCM, ARVC, myocardial infarction, primary mitral valve disease, heartworm disease, congenital disease (PDA, cor triatriatum sinister)	ACEi, diuretics, antithrombotic	Pimobendan was well tolerated when used with a variety of medications	Agitation, anorexia, vomiting, constipation (n = 5, 2.9%)	0.08–0.42 mg/kg PO q12h	1–870 days
Hanzlicek et al, 2012⁴³	Prospective	18	Healthy	None	Pharmacokinetics: pimobendan has a high volume of distribution and rapid oral absorption with peak plasma concentration in 20–40 mins in cats. Elimination half-life is 0.7–0.8 h	Vomiting, ptyalism (n = 2, 11.1%)	0.28 or 0.31 mg/kg PO (singledose and multidose [seven doses total])	Not applicable
Gordon	Retrospective	27	NSCM (n = 11),	Enalapril, benazepril,	Pimobendan was	Severe	0.25–0.30	32–339
et al, 2012⁴²	cohort study		DCM (n = 8), ARVC (n = 4), congenital heart disease (n = 3), HCM (n = 1)	furosemide, clopidogrel, diltiazem, atenolol, spironolactone, sotalol, digoxin	well tolerated in cats with CHF	hypotension in congenital mitral valve dysplasia case with LVOTO (n = 1, 3.7%)	mg/kg PO q12h	days
Hambrook and Bennett, 2012³⁸	Retrospective case control	16	DCM	Furosemide, taurine and benazepril, enalapril	Pimobendan improved survival of cats with non-taurine-responsive DCM	None	0.16–0.37 mg/kg PO q12h	1–>502 days
Reina-Doreste et al, 2014⁴¹	Retrospective case control	27	Stage C/D: CHF secondary to HCM or hypertrophic obstructive cardiomyopathy	Furosemide, enalapril, benazepril, atenolol, clopidogrel, aspirin, dalteparin	Pimobendan was well tolerated in cats with HCM and HCM-LVOTO and pimobendan increased median survival time	None	0.15–0.45 mg/kg/day PO (divided into 2–3 doses)	MST 626 days
Yata et al, 2016⁴⁴	Prospective, randomized, blinded, crossover	8	Healthy	None	Pharmacokinetics: rapidly absorbed and converted to active metabolite. Pharmacodynamics: improved some echocardiographic measures of LV systolic function in healthy cats	Vomiting, ventricular premature beat (n = 3, 37.5%)	0.625 and 1.25 mg PO (single dose)	Not applicable
Miyagawa et al, 2016⁴⁵	Blinded, randomized, prospective, parallel	12	Healthy (n = 6 pimobendan, n = 6 benzepril)	None	Pimobendan did not cause adverse effects in healthy cats	None (histopathology)	0.25 mg/kg PO q12h (multidose, 506 days)	Not applicable
Oldach et al, 2019³⁹	Prospective, randomized, placebo-controlled, crossover	13	HCM stage B: laboratory colony cats with myosin binding C variant	None	Pimobendan increased LA function and did not exacerbate LVOTO	Presyncopal episode (n = 1, 7.7%)	1.25 mg PO (single dose)	Not applicable
Ward et al, 2020²⁹	Retrospective	260	CHF (stage C or D): 57 with LVOTO, 203 non-obstructive	Furosemide, torsemide, enalapril, benazepril, clopidogrel, aspirin, dalteparin, apixaban, spironolactone, atenolol, diltiazem, sotalol, amlodipine, sildenafil	Pimobendan was well tolerated in cats with CM and CHF regardless of presence of LVOTO	Hyporexia/ anorexia, vomiting, lethargy, subclinical hypotension (n = 12, 4.6%)	0.12–1.74 mg/kg/day PO	0–2674 days
Baron Toaldo et al, 2020⁴⁶	Prospective pilot study	11	Healthy	None	Pimobendan improved LA function in healthy cats	None	1.25 mg PO (single dose)	Not applicable
Schober et al, 2021⁴⁰	Prospective, double-blind, randomized, non-pivotal, exploratory field study	83	Stage C HCM (recently controlled CHF): 30 with LVOTO, 53 without LVOTO	Furosemide, clopidogrel	No benefit of pimobendan identified overall	Increased LVOTO severity (n = 4, 4.8%). Similar percentage of adverse events between pimobendan and placebo	0.30 mg/kg PO q12h	Not designed to assess survival. This was a 6-month exploratory field study
Kochie et al, 2021⁴⁷	Prospective, double-blind, randomized, placebo-controlled clinical cohort	33	11 healthy, 22 HCM (stage B2/C-stable)	Clopidogrel, amitriptyline, apixaban, enalapril, levetiracetam	Pimobendan improved LA function in cats with HCM	LVOTO (n = 2, 6.1%)	0.25 mg/kg PO q12h (multidose [4–7 days])	Not applicable
Oldach et al, 2021⁴⁸	Prospective	21	21 HCM (stage B)	Enalapril, benazepril, clopidogrel, fluticasone, ciclosporin, fluoxetine	Acute improvement in LA function and mild improvement in LV systolic function	None	1.25 mg PO (single dose)	Not applicable
Kost et al, 2021⁴⁹	Prospective	11	Healthy	None	Pimobendan improved right ventricular and right atrial function	None	1.25 mg PO (single dose)	Not applicable
Fujii et al, 2021⁵⁰	Prospective, crossover	6	Healthy	None	Pimobendan did not affect minimum, mean or maximum HR on Holter analysis but did affect cardiac rhythm at higher dose	Escape, idioventricular, idiojunctional complexes (n = 4 at 0.5 mg/kg, 66.7%)	0.5, 0.25 or 0.125 mg/kg PO q12h (multidose [15 days])	Not applicable
Sugimoto et al, 2022⁵¹	Prospective, crossover	5	Healthy	None	Pimobendan improved LV systolic function and improvements were dependent on plasma concentration	None	0.5, 0.25 or 0.125 mg/kg PO q12h (multidose [14 days])	Not applicable
Romito et al, 2022⁵²	Case series	2	TMT caused by Toxoplasma gondii, CHF	Clindamycin, furosemide, clopidogrel, heparin	Both cats responded to the treatment protocol and medications were ultimately discontinued when TMT resolved	None	0.20–0.25 mg/kg PO q12h	Not applicable
Kennerly et al, 2023⁵³	Prospective, crossover	6	Healthy	None	Pimobendan did not alter a limited assessment of platelet function in healthy cats	None	0.625 mg then 1.25 mg PO q12h (multidose [7 days])	Not applicable
Sugimoto et al, 2023⁵⁴	Prospective, placebo controlled, randomized crossover	6	Healthy	None	Pimobendan increased LV systolic function and cardiac output in healthy cats	None	0.075 mg/kg, 0.15 mg/kg, 0.3 mg/kg IV (single dose)	Not applicable
Ishizaka et al, 2024⁵⁵	Prospective	5	Healthy	None	Pimobendan increased HR and LV systolic function	Paroxysmal ventricular tachycardia (n = 1)	0.15 mg/kg IV q12h (multidose [3 days])	Not applicable

ACEi = angiotensin-converting enzyme inhibitor; ARVC = arrhythmogenic right ventricular cardiomyopathy; CHF = congestive heart failure;

CM = cardiomyopathy; DCM = dilated cardiomyopathy; HCM = hypertrophic cardiomyopathy; HR = heart rate; LA = left atrial; LV = left ventricular; LVOTO = left ventricular outflow tract obstruction; MST = median survival time; NSCM = non-specific cardiomyopathy; PDA = patent ductus arteriosus; TMT = transient myocradial thickening

Healthy normal cats

Pharmacokinetic data evaluating pimobendan administration in healthy cats reveals a high volume of distribution and a rapid absorption after oral administration.^43,44 Maximal plasma concentration is achieved 40 mins and 20 mins after oral doses of 0.625 mg and 1.25 mg, respectively.⁴⁴ Cats appear to achieve higher plasma concentrations of pimobendan than dogs at similar mg/kg doses.^43,44,56 After administration, pimobendan is rapidly converted to the biologically active metabolite O-desmethyl-pimobendan (ODMP). Maximal plasma concentrations of ODMP are achieved after 1 h.⁴⁴ In contrast to dogs, cats convert less pimobendan to ODMP, which may be due to species differences in cytochrome P-450 isoenzyme activities.⁴⁴ The elimination half-life for pimobendan in cats is between 0.7 and 0.8 h.⁴⁴

The pharmacodynamic effects of pimoben-dan have been explored in various studies. Administration of single oral doses of 0.625 mg or 1.25 mg of pimobendan to healthy cats changed several echocardiographic parameters associated with systolic function; however, the magnitude of the changes was small and thus may not be clinically rele-vant.⁴⁴ A single oral dose study in healthy cats showed no significant effect on echocardiographic parameters of LV systolic function, but demonstrated improved LA function⁴⁶ in addition to positive effects on multiple echocardiographic parameters of right ventricular and right atrial function.⁴⁴ Another study of five healthy cats comparing doses of 0.125, 0.25 and 0.5 mg/kg of pimobendan q12h for 14 days found improved LV systolic function in the 0.25 and 0.5 mg/kg groups, with significant correlation between cardiac function and plasma concentrations of pimobendan and ODMP, highlighting the effectiveness of a higher dose of pimobendan; however, again, the magnitude of the changes were small and thus may not be clinically relevant.⁵¹ Short-term administration of pimobendan (0.25 and 0.5 mg/kg PO q12h) increased peak longitudinal strain rate in healthy cats, despite a lack of change in fractional shortening or peak systolic velocity of the lateral mitral annulus.⁵⁰ These data suggest that advanced echocardiographic measurements may be required to fully assess the effects of oral pimobendan on systolic function in cats. Intravenous pimo-bendan (0.15 and 0.3 mg/kg), on the other hand, increased LV fractional shortening, peak systolic velocity of the lateral mitral annulus and echocardiographically calculated cardiac output in healthy sedated cats.⁵⁴

The effect of pimobendan on heart rate and cardiac rhythm in healthy cats has also been investigated in numerous small studies (4–11 cats). The results are variable and challenging to interpret, however, as any documented changes are small in magnitude and of unknown clinical significance in a species where the presence and burden of arrythmias is not well characterized in either health or the presence of cardiomyopathy. A study analyzing heart rates obtained by echocardiogram after a single oral dose of pimobendan demonstrated a mild increase in heart rate,⁴⁶ while another study reported a decrease in heart rate.⁴⁴ The reported heart rate changes in both studies would not be considered clinically relevant.^44,46 Twenty-four hour Holter electrocardiogram monitoring in healthy cats before and after short-term oral administration of twice daily placebo or 0.125, 0.25 or 0.5 mg/kg of pimobendan did not change the total number of heart beats or number of ventricular premature complexes, or change the minimum, mean or maximum heart rate in a 24 h period, suggesting that oral pimobendan administration may not affect heart rate in normal cats; however, this study was also small.⁵⁰ A higher number of idioventricular/ idiojunctional beats and escape complexes were observed in cats administered 0.5 mg/kg q12h pimobendan.⁵⁰ While these arrhythmias did not appear to be malignant in these healthy cats, the results suggested that a degree of caution should be exercised when using higher doses of pimobendan in cats with heart disease pending more thorough exploration of these potential effects. Holter data following intravenous administration of pimobendan (0.15 mg/kg q12h for 3 days) in five healthy cats revealed a significant increase in the total number of heart beats in 24 h and in mean heart rate compared with placebo.⁵⁵ Two of the five cats in this study had increased numbers of arrhythmias posttreatment (including a paroxysm of ventricular tachycardia in one cat), while the other three cats showed a decreased number of arrhythmias post-treatment.⁵⁵ To date, limited conclusions can be drawn with regard to expected heart rate and rhythm parameters associated with pimobendan use in cats, particularly in cats with heart disease.

In addition to cardiovascular effects, phosphodiesterase inhibitors also have the potential to reduce platelet aggregation. Several phosphodiesterase III inhibitors used in humans have demonstrable antiplatelet activ-ity.^57–62 In healthy cats administered two clinically relevant doses of pimobendan (0.625 and 1.25 mg/cat q12h) for 7 days, pimoben-dan did not alter a limited assessment of platelet function.⁵³

Cats with HCM

Varying pharmacodynamic effects of pimo-bendan have been demonstrated in cats with HCM. In a study of purpose-bred research colony cats with HCM and normal LA size to mild LA enlargement (stage B1), no changes in LV systolic function or exacerbation of dynamic LVOTOs were observed after a single 1.25 mg oral dose of pimobendan, but increased LA fractional shortening was observed.³⁹ A single-dose study in client-owned cats with HCM and normal LA size to mild LA enlargement (stage B1) replicated the increase in LA fractional shortening 90 mins after a 1.25 mg oral dose of pimobendan, documented a mild increase in LV systolic function with increased peak systolic velocity of the mitral annulus, and increased left and right ventricular outflow tract velocities.⁴⁸ A study focusing on echocardiographic parameters associated with LA size and function in client-owned cats with stage B or C stable HCM after short-term administration of pimobendan (0.25 mg/kg q12h) demonstrated modest improvements in LA systolic function.⁴⁷

In summary, to date the pharmacodynamic effects of pimobendan in cats with cardiomyopathy characterized by normal to mild LA enlargement include improved LA function, a possible small increase in LV systolic function and a mild increase in outflow tract velocities.

Practical considerations for pimobendan use in cats

Dose

No pimobendan formulations have been approved for use in cats. Given the pharmacodynamic data available to date, 1.25 mg PO q12h has become the most clinically utilized dosage of pimobendan in cats, with minimal to no adverse effects attributed to this dosing scheme. For an average-sized cat this corresponds to a weight-based dose of approximately 0.25 mg/kg. Adjustments may be considered based on an individual cat’s weight and according to clinical response.

Pimobendan is available as approved tablets and capsules in various strengths.⁶³ The availability of approved oral solutions could facilitate easier and more accurate dosing, therefore increasing its potential use in cats for both acute and chronic treatment.

Until further investigation into cardiac rhythm and rate changes are investigated in cats with heart disease treated with higher doses of pimobendan, dose escalation above 0.25 mg/kg q12h should be pursued with caution and close monitoring. In a clinical setting, pimobendan is often given in conjunction with other medications including diuretics, antiplatelet drugs and dobutamine without apparent interactions; however, this has not specifically been investigated to date.^{29,30,38,41,42,64}

Indications, contraindications and adverse effects

Pimobendan has been evaluated as a therapy for managing CHF in cats; relevant conditions and recommendations are summarized in Tables 2 and 3. Ventricular systolic dysfunction can be a feature of many types of cardiomyopathy, including HCM, a cardiomyopathy that traditionally features diastolic dys-function.^10,11 Feline cardiomyopathies typically associated with ventricular systolic dysfunction include dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and some cases with nonspecific phenotypes. Systolic dysfunction also occurs secondarily to myocardial infarction or as an end-stage presentation of any cardiomyopathy. Systolic dysfunction is characterized on echocardiographic examination by focal areas of reduced wall motion or global reduction in ventricular systolic function.

Table 2

Recommendations for pimobendan use in cats with cardiomyopathy diagnosed by echocardiography

	Pimobendan indication
	Stage B2: subclinical with substantial LA dilation in most cases	Stage C: current or historical left-sided CHF	Stage D: left-sided CHF refractory to standard therapy
Cardiomyopathy
Dilated cardiomyopathy	Consider*	Recommended	Recommended
Hypertrophic cardiomyopathy – normal ventricular systolic function	Not indicated as unknown	Consider* (case scenario 1)	Recommended
Hypertrophic cardiomyopathy – reduced ventricular systolic function	Not indicated as unknown	Recommended (case scenario 3)	Recommended (case scenario 3)
Hypertrophic cardiomyopathy – obstructive (left ventricular outflow tract obstruction)	Not indicated as unknown (case scenario 5)	Relative contraindication if moderate to severe obstruction* (case scenario 6)	Consider as rescue therapy with owner approval*
Any other cardiomyopathy (ARVC, non-specific, restrictive) – with normal ventricular systolic function	Not indicated as unknown	Consider*	Consider as rescue therapy with owner approval*
Any other cardiomyopathy (ARVC, non-specific, restrictive) – with reduced ventricular systolic function	Consider*	Recommended with owner approval (case scenarios 3 and 4)	Recommended as rescue therapy with owner approval (case scenario 3)
Transient myocardial thickening
Transient myocardial thickening with normal ventricular systolic function	Not applicable	Consider*	Not applicable
Transient myocardial thickening with reduced ventricular systolic function	Not applicable	Recommended*	Not applicable
Congenital heart disease
Left-to-right shunts (patent ductus arteriosus, septal defects)	Not indicated as unknown	Consider*	Recommend as rescue therapy with owner approval*
Fixed outflow tract obstruction (eg, pulmonic stenosis)	Contraindicated	Contraindicated	Consider as rescue therapy with owner approval*

Note: Strong evidence-based therapeutic options are limited for cats with cardiomyopathy. Most cats with stage C cardiomyopathy can be stabilized with furosemide. The clinical use of most other chronic medications are controversial in cats with stages B2, C and D cardiomyopathy. The above reflects the authors’ current treatment strategies and recommendations

Consultation with a cardiologist would be beneficial

ARVC = arrhythmogenic right ventricular cardiomyopathy; CHF = congestive heart failure; LA = left atrial

Table 3

Recommendations for pimobendan use in cats with heart disease NOT confirmed and characterized by echocardiography

	Pimobendan indication
	Stage B2: subclinical with substantial LA dilation in most cases	Stage C: current or historical left-sided CHF	Stage D: left-sided CHF refractory to standard therapy
Presumed diagnosis of cardiomyopathy – with NO evidence of poor perfusion	Never indicated in subclinical disease without an echocardiographic diagnosis	Not indicated in cats easily stabilized on empirical CHF therapy (case scenario 2)	Recommended as rescue therapy with owner approval*
Presumed diagnosis of cardiomyopathy – with evidence of poor perfusion	Never indicated in subclinical disease without an echocardiographic diagnosis	Consider*	Recommended as rescue therapy with owner approval*

Note: For some diagnoses, peer-reviewed clinical data are limited or absent; some recommendations are therefore based on anecdotal reports and the authors’ experience

Consultation with a cardiologist could be beneficial

CHF = congestive heart failure; LA = left atrial

Pimobendan use has been reported in cats with conditions associated with systolic dys-function,^30,38,42 and has also been used in the treatment of CHF secondary to HCM with and without dynamic LVOTO, where global routine measures of ventricular systolic function are normal.^4,29,40 Dynamic LVOTO in cats with HCM can be intermittent and heart rate dependent, and in cats where pimobendan is associated with the new onset or exacerbation of dynamic LVOTO or mid-LV obstruction, the magnitude and therefore clinical significance of any worsening of the obstruction varies.^40,47 Clinical decompensation has generally not been identified when pimobendan is used in cats with dynamic LVOTO, but can occur in rare cases.^{30,40–42
,48} The development of systemic hypotension, weakness, collapse, sinus tachycardia or worsening arrhythmias, or the presence of a new or louder murmur suggesting exacerbation of an obstruction, should prompt re-evaluation of the patient, and pimobendan should be discontinued if considered likely to be the causative factor. Routine monitoring, including auscultation, electrocardiography, indirect systemic blood pressure and echocardiography to assess dynamic LVOTO, can detect complications early and guide treatment adjustments.

Transient myocardial thickening of the left ventricle can mimic HCM and can also result in CHF. Transient myocardial thickening is often associated with an antecedent event and elevated cardiac troponin I, and is characterized by eventual clinical improvement with resolution of CHF and reverse remodeling of the heart to normal within months.⁶⁵ Pimobendan has been used in the management of CHF secondary to transient myocardial thickening caused by Toxoplasma gondii.⁵²

Pimobendan has also been used to manage CHF due to a variety of congenital heart conditions, predominantly in diseases characterized by left-to-right shunting (patent ductus arteriosus, septal defects) or in the presence of marked atrial enlargement.^66–68 Pimobendan use is not recommended in cats with fixed obstructions of the left or right ventricular outflow tract (ie, aortic or pulmonic stenosis or fixed midventricular obstructions). In general, consultation with a cardiologist is recommended when considering pimobendan use in cases of congenital heart disease.

Reported adverse effects with pimobendan administration are uncommon and are predominantly characterized by gastrointestinal upset (ptyalism, anorexia, vomiting, diarrhea), transient changes in heart rate and possible worsening arrhythmias at higher doses.^{30,38,39,41,43,44}

Conclusions

Pimobendan appears to be well tolerated in cats, with minimal adverse effects at a dosage of 1.25 mg PO q12h. Although the current level of evidence for pimobendan use in cats with cardiomyopathy is low (eg, retrospective case series, studies in other species and expert opinion), the reported short-term pharmacodynamic effects (eg, improved LA function; mild, possibly clinically insignificant increase in LV systolic function; absence of clinical concerns related to mild LVOTO) support a favorable potential clinical utility in cats with ACVIM stages C and D cardiomyopathies in the absence of clinically significant LVOTO or other heart disease associated with a fixed obstruction. The development of evidence-based recommendations for pimobendan use in feline cardiomyopathy with and without LVOTO will require adequately powered, randomized controlled studies with pragmatic endpoints.

Key Points

✜ Cardiomyopathies are a common condition of cats for which evidence-based therapeutic options are limited.

✜ Most cats with stage C cardiomyopathy can be stabilized with furosemide. The addition of additional chronic medications are controversial in cats with stage C cardiomyopathy. In cats with stage C cardiomyopathy and no evidence of LVOTO, pimobendan can be considered; however, the risk vs benefit profile of polypharmacy strategies in cats should be considered when initiating new medications, and owners should be informed when recommendations are not evidence based.

✜ In cats with stage C cardiomyopathy and no confirmation of LA size or risk factors for ATE, the empirical use of chronic thromboprophylaxis is controversial. In stage B2 or C cardiomyopathies characterized by the presence of high-risk factors for ATE, empirical use of thromboprophylaxis can be considered.

✜ The safety of pimobendan in cats with severe LVOTO has not been established.

✜ A new approved pimobendan oral solution is available in some countries (UK, EU, USA, Japan and Australia) and could facilitate accurate and easier dosing of cats.

✜ While further research is needed to establish strong evidence-based recommendations for pimobendan use in cats, available data suggest that oral pimobendan in cats is generally well tolerated with minimal adverse effects.

Footnotes

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. All authors have received funding from Boehringer Ingelheim Animal Health within the past 5 years for some or all of the following activities: research, travel, speaking fees, consultancy fees and preparation of educational materials.

Funding

The authors of this commissioned Clinical Spotlight review received an honorarium; as for all JFMS articles, this Clinical Spotlight article went through peer review. All authors have received funding from Boehringer Ingelheim Animal Health within the past 5 years for some or all of the following activities: research, travel, speaking fees, consultancy fees and preparation of educational materials.

Ethical approval

This work did not involve the use of animals and therefore ethical approval was not specifically required for publication in JFMS.

Informed consent

This work did not involve the use of animals (including cadavers) and therefore informed consent was not required. For any animals or people identifiable within this publication, additional informed consent for publication was obtained.

ORCID iD

Sonya G Gordon

Ashley B Saunders

Sonya Wesselowski

Alice Watson

References

Luis Fuentes

Abbott

Chetboul

et al. ACVIM consensus statement guidelines for the classification, diagnosis, and management of cardiomyopathies in cats. J Vet Intern Med 2020; 34: 1062–1077.

Häggström

Luis Fuentes

Wess

Screening for hypertrophic cardiomyopathy in cats. J Vet Cardiol 2015; 17 Suppl 1: S134–S149.

Fox

Liu

S-K

Maron

BJ.

Echocardiographic assessment of spontaneously occurring feline hypertrophic cardiomyopathy. Circulation 1995; 92. DOI: 10.1161/01.cir.92.9.2645.

Wess

Sarkar

Hartmann

Assessment of left ventricular systolic function by strain imaging echocardiography in various stages of feline hypertrophic cardiomyopathy. J Vet Intern Med 2010; 24: 1375–1382.

Sampedrano

Chetboul

Gouni

et al. Systolic and diastolic myocardial dysfunction in cats with hypertrophic cardiomyopathy or systemic hypertension. J Vet Intern Med 2006; 20: 1106–1115.

Sugimoto

Fujii

Sunahara

et al. Assessment of left ventricular longitudinal function in cats with subclinical hypertrophic cardiomyopathy using tissue Doppler imaging and speckle tracking echocardiography. J Vet Med Sci 2015; 77: 1101–1108.

Schober

Todd

Echocardiographic assessment of left ventricular geometry and the mitral valve apparatus in cats with hypertrophic cardiomyopathy. J Vet Cardiol 2010; 12: 1–16.

Fox

Keene

Lamb

et al. International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats: the REVEAL study. J Vet Intern Med 2018; 32: 930–943.

Elliott

Gimeno

Tome

et al. Left ventricular outflow tract obstruction and sudden death risk in patients with hypertrophic cardiomyopathy. Eur Heart J 2006; 27: 1933–1941.

10.

Schober

Chetboul

Echocardiographic evaluation of left ventricular diastolic function in cats: hemodynamic determinants and pattern recognition. J Vet Cardiol 2015; 17 Suppl 1: S102–133.

11.

Bright

Herrtage

Schneider

JF.

Pulsed Doppler assessment of left ventricular diastolic function in normal and cardiomyopathic cats. J Am Anim Hosp Assoc 1999; 35: 285–291.

12.

Al-Saady

Obel

Camm

AJ.

Left atrial appendage: structure, function, and role in thromboembolism. Heart 1999; 82: 547–554.

13.

Schober

Maerz

Assessment of left atrial appendage flow velocity and its relation to spontaneous echocardiographic contrast in 89 cats with myocardial disease. J Vet Intern Med 2006; 20: 120–130.

14.

Payne

Borgeat

Connolly

et al. Prognostic indicators in cats with hypertrophic cardiomyopathy. J Vet Intern Med 2013; 27: 1427–1436.

15.

Keene

Atkins

Bonagura

et al. ACVIM consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. J Vet Intern Med 2019; 33: 1127–1140.

16.

Paige

Abbott

Elvinger

et al. Prevalence of cardiomyopathy in apparently healthy cats. J Am Vet Med Assoc 2009; 234: 1398–1403.

17.

Abbott

JA.

Feline hypertrophic cardiomyopathy: an update. Vet Clin North Am Small Anim Pract 2010; 40: 685–700.

18.

Côté

Manning

Emerson

et al. Assessment of the prevalence of heart murmurs in overtly healthy cats. J Am Vet Med Assoc 2004; 225: 384–388.

19.

Payne

Luis Fuentes

Boswood

et al. Population characteristics and survival in 127 referred cats with hypertrophic cardiomyopathy (1997 to 2005). J Small Anim Pract 2010; 51: 540–547.

20.

DeFrancesco

TC.

Management of cardiac emergencies in small animals. Vet Clin North Am Small Anim Pract 2013; 43: 817–842.

21.

Hogan

Brainard

BM.

Cardiogenic embolism in the cat. J Vet Cardiol 2015; 17 Suppl 1: S202–S214.

22.

Hogan

Fox

Jacob

et al. Secondary prevention of cardiogenic arterial thromboembolism in the cat: the double-blind, randomized, positive-controlled feline arterial thromboembolism; clopidogrel vs aspirin trial (FAT CAT). J Vet Cardiol 2015; 17 Suppl 1: S306–S317.

23.

Smith

Tobias

Jacob

et al. Arterial thromboembolism in cats: acute crisis in 127 cases (1992–2001) and long-term management with low-dose aspirin in 24 cases. J Vet Intern Med 2003; 17: 73–83.

24.

Dirven

Cornelissen

JM.

Arterial thromboembolism in cats [article in German]. Tijdschr Diergeneeskd 2009; 134: 974–980.

25.

Luis Fuentes

. Arterial thromboembolism: risks, realities and a rational first-line approach. J Feline Med Surg 2012; 14: 459–470.

26.

Stokol

Brooks

Rush

et al. Hypercoagulability in cats with cardiomyopathy. J Vet Intern Med 2008; 22: 546–552.

27.

Gordon

Côté

Pharmacotherapy of feline cardiomyopathy: chronic management of heart failure. J Vet Cardiol 2015; 17 Suppl 1: S159–S172.

28.

Jianwei

Zhihong

et al. Research progress in the classification and staging of feline cardiomyopathy and the treatment of feline cardiomyopathy with pimobendan. Mod J Anim Husb Vet Med 2024: 91–96.

29.

Ward

Kussin

Tropf

et al. Retrospective evaluation of the safety and tolerability of pimobendan in cats with obstructive vs nonobstructive cardiomyopathy. J Vet Intern Med 2020; 34: 2211–2222.

30.

MacGregor

Rush

Laste

et al. Use of pimobendan in 170 cats (2006–2010). J Vet Cardiol 2011; 13: 251–260.

31.

Boswood

Haggstrom

Gordon

et al. Effect of pimobendan in dogs with preclinical myxomatous mitral valve disease and car-diomegaly: the EPIC study – a randomized clinical trial. J Vet Intern Med 2016; 30: 1765–1779.

32.

Summerfield

Boswood

O’Grady

et al. Efficacy of pimobendan in the prevention of congestive heart failure or sudden death in Doberman Pinschers with preclinical dilated cardiomyopathy (the PROTECT Study). J Vet Intern Med 2012; 26: 1337–1349.

33.

Häggström

Boswood

O’Grady

et al. 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. J Vet Intern Med 2008; 22: 1124–1135.

34.

Haggstrom

Boswood

O’Grady

et al. Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study. J Vet Intern Med 2013; 27: 1441–1451.

35.

Fuentes

VL.

Use of pimobendan in the management of heart failure. Vet Clin North Am Small Anim Pract 2004; 34: 1145–1155.

36.

Boyle

Leech

A review of the pharmacology and clinical uses of pimobendan. J Vet Emerg Crit Care (San Antonio) 2012; 22: 398–408.

37.

Asanoi

Ishizaka

Kameyama

et al. Disparate inotropic and lusitropic responses to pimobendan in conscious dogs with tachycardia-induced heart failure. J Cardiovasc Pharmacol 1994; 23: 268–274.

38.

Hambrook

Bennett

PF.

Effect of pimobendan on the clinical outcome and survival of cats with non-taurine responsive dilated cardiomyopathy. J Feline Med Surg 2012; 14: 233–239.

39.

Oldach

Ueda

Ontiveros

et al. Cardiac effects of a single dose of pimobendan in cats with hypertrophic cardiomyopathy; a randomized, placebo-controlled, crossover study. Front Vet Sci 2019; 6. DOI: 10.3389/fvets.2019.00015.

40.

Schober

Rush

Luis Fuentes

et al. Effects of pimobendan in cats with hypertrophic cardiomyopathy and recent congestive heart failure: results of a prospective, double-blind, randomized, nonpivotal, exploratory field study. J Vet Intern Med 2021; 35: 789–800.

41.

Reina-Doreste

Stern

Keene

et al. Case-control study of the effects of pimoben-dan on survival time in cats with hypertrophic cardiomyopathy and congestive heart failure. J Am Vet Med Assoc 2014; 245: 534–539.

42.

Gordon

Saunders

Roland

et al. Effect of oral administration of pimobendan in cats with heart failure. J Am Vet Med Assoc 2012; 241: 89–94.

43.

Hanzlicek

Gehring

Kukanich

et al. Pharmacokinetics of oral pimobendan in healthy cats. J Vet Cardiol 2012; 14: 489–496.

44.

Yata

McLachlan

Foster

et al. Singledose pharmacokinetics and cardiovascular effects of oral pimobendan in healthy cats. J Vet Cardiol 2016; 18: 310–325.

45.

Miyagawa

Machida

Toda

et al. Comparison of the effects of long-term pimobendan and benazepril administration in normal cats. J Vet Med Sci 2016; 78: 1099–1106.

46.

Baron Toaldo

Pollesel

Diana

. Effect of pimobendan on left atrial function: an echocardiographic pilot study in 11 healthy cats. J Vet Cardiol 2020; 28: 37–47.

47.

Kochie

Schober

Rhinehart

et al. Effects of pimobendan on left atrial transport function in cats. J Vet Intern Med 2021; 35: 10–21.

48.

Oldach

Ueda

Ontiveros

et al. Acute pharmacodynamic effects of pimobendan in client-owned cats with subclinical hypertrophic cardiomyopathy. BMC Vet Res 2021; 17. DOI: 10.1186/s12917-021-02799-9.

49.

Kost

Glaus

Diana

et al. Effect of a single dose of pimobendan on right ventricular and right atrial function in 11 healthy cats. J Vet Cardiol 2021; 37: 52–61.

50.

Fujii

Sugimoto

Omichi

et al. A pilot study investigating the effect of pimobendan on the cardiac rhythm and selected echocardiographic parameters of healthy cats. J Vet Cardiol 2021; 35: 74–83.

51.

Sugimoto

Sugita

Orito

et al. Repeated-dose pharmacodynamics of pimobendan in healthy cats. Animals (Basel) 2022; 12. DOI: 10.3390/ani12080981.

52.

Romito

Fracassi

Cipone

Transient myocardial thickening associated with acute myocardial injury and congestive heart fail-ure in two Toxoplasma gondii-positive cats. JFMS Open Rep 2022; 8. DOI: 10.1177/20551169221131266.

53.

Kennerly

Coleman

Jasper

et al. Effects of orally administered pimobendan on platelet function in healthy adult cats. Am J Vet Res 2023; 84. DOI: 10.2460/ajvr.23.05.0103.

54.

Sugimoto

Mochizuki

Akashi

et al. Effects of intravenous pimobendan on cardiovascular parameters in healthy sedated cats. Top Companion Anim Med 2023; 53–54. DOI: 10.1016/j.tcam.2023.100769.

55.

Ishizaka

Katagiri

Ogawa

et al. A pilot study of the proarrhythmic effects of pimo-bendan injection in clinically healthy cats. Vet Res Commun 2024; 48: 3177–3186.

56.

Yata

McLachlan

Foster

et al. Pharmacokinetics and cardiovascular effects following a single oral administration of a nonaqueous pimobendan solution in healthy dogs. J Vet Pharmacol Ther 2016; 39: 45–53.

57.

Barradas

Jagroop

O’Donoghue

et al. Effect of milrinone in human platelet shape change, aggregation and thromboxane A2 synthesis: an in vitro study. Thromb Res 1993; 71: 227–236.

58.

Manns

Brenna

Colman

et al. Differential regulation of human platelet responses by cGMP inhibited and stimulated cAMP phosphodiesterases. Thromb Haemost 2002; 87: 873–879.

59.

Eldor

Vlodavsky

Fuks

et al. Different effects of aspirin, dipyridamole and UD-CG 115 on platelet activation in a model of vascular injury: studies with extracellular matrix covered with endothelial cells. Thromb Haemost 1986; 56: 333–339.

60.

Pattison

Astley

Eason

et al. A comparison of the effects of three positive inotropic agents (amrinone, milrinone and medorinone) on platelet aggregation in human whole blood. Thromb Res 1990; 57: 909–918.

61.

Muller

Weisenberger

et al. Dipyridamole alone or combined with low-dose acetylsalicylic acid inhibits platelet aggregation in human whole blood ex vivo. Br J Clin Pharmacol 1990; 30: 179–186.

62.

Anfossi

Massucco

Piretto

et al. Interplay between milrinone and adenosine in the inhibition of human platelet response. Gen Pharmacol 1996; 27: 1149–1154.

63.

Margiocco

Warren

Borgarelli

et al. Analysis of weight uniformity, content uniformity and 30-day stability in halves and quarters of routinely prescribed cardiovascular medications. J Vet Cardiol 2009; 11: 31–39.

64.

Murphy

Stepien

Tjostheim

et al. Management and short-term outcome of 74 cases of acute congestive heart failure in cats (2017–2022) [abstract]. J Vet Intern Med 2024; 38: 3537–3694.

65.

Novo Matos

Pereira

Glaus

et al. Transient myocardial thickening in cats associated with heart failure. J Vet Intern Med 2018; 32: 48–56.

66.

Scansen

Schneider

Bonagura

JD.

Sequential segmental classification of feline congenital heart disease. J Vet Cardiol 2015; 17 Suppl 1: S10–S52.

67.

Bascunan

Thieman Mankin

Saunders

et al. Patent ductus arteriosus in cats (Felis catus): 50 cases (2000–2015). J Vet Cardiol 2017; 19: 35–43.

68.

Markovic

Scansen

Potter

BM.

Role of computed tomography angiography in the differentiation of feline truncus arteriosus communis from pulmonary atresia with ventricular septal defect. J Vet Cardiol 2017; 19: 514–522.