Canine myxomatous mitral valve heart disease: When to medicate?

Shutterstock.com

Myxomatous mitral valve disease (MMVD) is the leading cause of cardiovascular disease in dogs1,2 and our knowledge of this disease and how to treat it continues to evolve. Despite development of new drugs and treatment regimens, uncertainty remains about when to treat and what the best interventions are for some of these patients.

In 2009, a more objective classification system to categorize patients' heart disease was introduced and helped make treatment decisions easier.3 It is based on patient risk factors and clinical and diagnostic imaging signs:3

Stage A: Patients with no current structural heart disorder (e.g. no heart murmur) but that are high risk for developing heart disease (e.g. Cavalier King Charles Spaniels)

Stage B: Patients with structural cardiac changes (e.g. a heart murmur) but that are asymptomatic

• Stage B1: No radiographic or echocardiographic evidence of heart disease

• Stage B2: Radiographic or echocardiographic evidence of left-sided cardiomegaly

Stage C: Patients with current or past history of heart failure and evidence of structural heart disease

Stage D: Patients with end-stage heart failure that is refractory to standard therapy.

New data on intervention

Despite this information on categorizing heart disease severity, there had been little evidence to support the utility of medical intervention for patients with Stage B disease. However, in 2016, the results of a large prospective, randomized, placebo-controlled, blinded clinical trial to evaluate pimobendan treatment in dogs with Stage B2 disease were published.4 In the “Effect of pimobendan in dogs with preclinical myxomatous mitral valve disease and cardiomegaly” trial, or the EPIC trial for short, 360 client-owned dogs with Stage B2 MMVD were assigned to receive either 0.4 –  to 0.6 mg/kg/day (total dose divided into two administrations given about 12 hours apart) of pimobendan or placebo.4 The goal of the study was to determine if treatment with pimobendan would delay the onset of signs of left-sided congestive heart failure (CHF), euthanasia for a cardiac reason or death presumed to be cardiac in origin.4

To be included in the study, dogs had to:

• Be at least 6 years of age or older

• Have a body weight ≥ 4.1 kg and ≤ 15 kg

• Have at least a grade 3/6 heart murmur with the point of maximal intensity over the mitral valve

• Have radiographic evidence of cardiomegaly defined as a VHS > 10.5

• Have echocardiographic evidence of mitral valvular lesions and regurgitation as well as evidence of left atrial and left ventricular dilatation, defined as left atrial to aortic root ratio ≥ 1.6 and body weight normalized left ventricular internal diameter in diastole ≥ 1.7

Dogs receiving other cardiac medications (e.g. angiotensin-converting enzyme inhibitors, diuretics and many others) were excluded from enrollment. Dogs that received these medications during the study for less than five days (if sedation or anesthesia was required), or for less than three days (in the event of inadvertent administration) remained eligible to be included in the final analysis. Dogs were evaluated at one month and then every four months for the duration of the trial.

The study authors found that dogs with Stage B2 MMVD treated with pimobendan took 462 days (15 months) longer to develop CHF or die from MMVD than dogs receiving placebo. In other words, pimobendan prolonged their preclinical stage by 60%. Gastrointestinal side effects were minimal and noted with similar prevalence between the two groups.

What does this mean? 

Data from this Boehringer-Ingelheim-funded study supports the use of pimobendan in patients with Stage B2 MMVD.4 It is important to note that the dogs included in the study had to meet specific criteria, including both radiographic and echocardiographic evidence of heart enlargement.

Because not all patients will have access to echocardiography, and given the breed variability and potential low accuracy of using only VHS for assessment of heart enlargement, broader diagnostic requirements have been proposed to help practitioners determine when to initiate therapy in dogs with Stage B2 MMVD.5 These recommendations suggest that pimobendan be considered for dogs that meet the following criteria: 5

• Asymptomatic small breed dog

• Heart murmur characteristic of mitral regurgitation; at least 3/6 or greater

• VHS ≥ 11.5; or progression of heart size of ≥ 0.5 VHS units over a six-month period.

While early intervention in this subset of patients appears to prolong the time to onset of CHF, careful patient selection will be required to determine whether pimobendan treatment will be of benefit.

Link to studies:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5115200/

http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2009.0392.x/full

http://www.vetsmall.theclinics.com/article/S0195-5616(17)30036-0/fulltext

References

1. Buchanan JW. Prevalence of cardiovascular disorders In: Fox PR, editor; Sisson D, editor; Moise NS, editor. eds. Textbook of Canine and Feline Cardiology. Philadelphia: Saunders, W.B.; 1999:457–470.

2. Egenvall A, Bonnett BN, Hedhammar A, et al. Mortality in over 350,000 insured Swedish dogs from 1995-2000: II. Breed-specific age and survival patterns and relative risk for causes of death. Acta Vet Scand 2005;46:121–136.

3. Atkins C, Bonagura J, Ettinger S et al. Guidelines for the diagnosis and treatment of canine chronic valvular heart disease. J Vet Intern Med 2009;23(6):1142-1150.

4. Boswood A, Häggström J, Gordon SG et al. Effect of pimobendan in dogs with preclinical myxomatous mitral valve disease and cardiomegaly: The EPIC study-a randomized clinical trial. J Vet Intern Med 2016;30(6):1765-1179.  

5. Gordon SG, Saunders AB, Wesselowski SR. Asymptomatic canine degenerative valve disease: current and future therapies. Vet Clin North Am Small Anim Pract. 2017;47(5):955-975.