Purina Nutrition Exchange: March 2022

Best Practices for Diagnosis and Intervention in Canine MMVD

Bruce Keene, DVM, MSc, DACVIM (Cardiology)

Q: Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs in many parts of the world. Which dogs are at greatest risk—and why?

There is a genetic component to the development of the pathological changes that lead to MMVD, with a variety of genes influencing its development.¹ Certain breeds—many of them smaller dogs under 15 to 20 kilograms in body weight—are at greater risk. These include Cavalier King Charles Spaniels, Dachshunds, Miniature Poodles and Chihuahuas.^2,3 While it is less common, large-breed dogs can also develop MMVD, and when they do, the disease seems to progress faster than in small-breed dogs.⁴ MMVD is also more common in male dogs than female, at a ratio of about 1.5 to 1.⁵

Dogs initially acquire the pathologic lesion in the valve that leads to the disease, then over time develop the leaky valve that causes the typical heart murmur. The age of the dog when it develops mitral valve regurgitation is critical because there typically is a 3- to 5-year span of time between initial detection of a heart murmur and the onset of clinical signs associated with heart failure. Not all dogs that develop MMVD progress to clinical signs of heart failure.⁶ Cavalier King Charles Spaniels are at special risk because they often develop MMVD at a much earlier age (i.e., 5 or 6) than other dogs. Their disease doesn’t necessarily progress faster, but it begins much earlier in life.

Q: Given that not every practitioner has access to echocardiography and other advanced diagnostics, what screening steps and follow-up do you recommend?

Heart murmurs in dogs can be detected during routine checkups via auscultation so, practically speaking, the best screening test for MMVD continues to be listening with a stethoscope. Dogs with soft intensity grade 1 and 2 murmurs do not need an extensive work-up, and there is no reason to alarm their owners. Practitioners can simply inform owners that they will be keeping an eye on the situation through yearly follow-ups.

If the murmur is louder than a grade 2/6, the ACVIM consensus panel guidelines on MMVD recommend baseline imaging.⁷ Echocardiography is the gold standard for measuring left atrial size and ventricular size and evaluating the mitral valve, but imaging can be as simple as chest radiographs. It is also important to ensure the dog’s blood pressure is normal, since the onset of systemic hypertension can worsen mitral regurgitation and accelerate the progression of mitral valve disease, and basic blood work is recommended to rule out anemia and kidney disease. If these tests are normal and the heart size as determined by the Vertebral Left Atrial Score is less than 2.8, with a breed-adjusted Vertebral Heart Score less than 10.5, no further evaluation is typically needed.

Q: What have recent studies revealed about interventions for dogs with MMVD?

The EPIC Study clearly demonstrated the benefits of pimobendan administration to dogs with preclinical MMVD.⁸ Timely administration of this medication can extend the asymptomatic period of the disease by about 15 months. For most owners, this time is significant, because a dog’s best quality of life is always going to be before he or she develops clinical signs of heart failure. Our goal is to prolong that period. In later stages of the disease, we’ve learned that switching dogs that have become refractory to diuretic therapy from furosemide to torsemide⁸ can provide many patients with months of more comfortable life.

Finally, we’re beginning to see success with surgical mitral valve repair. Currently this involves open-heart surgery, which makes it cost-prohibitive for most owners. My hope is that in the coming years we will have a minimally invasive option that will be more affordable and accessible.

Cardiac Nutrition Research Breakthrough in Management of Canine MMVD Patients

Qinghong Li, PhD

The journey to discover new ways for nutrition to help dogs with myxomatous mitral valve disease (MMVD) has been a long one at Purina. As the principal investigator for this research at Purina, I have traveled this journey since our team began studying MMVD more than 10 years ago.

Identifying a Nutrition Target for Dogs with MMVD

Before a solution to a problem can be found, it is essential to first analyze the problem itself. Purina scientists applied metabolomic and transcriptomic technologies to study the molecular pathways in dogs with preclinical MMVD compared to healthy dogs as a means of better understanding how the disease develops. From analyzing gene expression and metabolite profiles in affected dogs, researchers learned that dogs with early MMVD do not produce energy as efficiently as dogs with healthy hearts and this energy deficiency plays a causal role in the pathogenesis of the disease.¹

Long-chain fatty acids, which are oxidized and converted by mitochondria to adenosine triphosphate (ATP), are the heart’s primary energy source; however, using metabolomics and transcriptomic technologies, Purina scientists found that dogs with MMVD experienced altered energy metabolism in cardiac tissues, as well as an increase in markers of oxidative stress and inflammation.¹

Meanwhile, by studying the gut microbiota of dogs at all stages of MMVD, we have learned that dysbiosis is a factor in the disease’s development. Shifts in the gut microbiota begin in the early, preclinical stages of MMVD, with dysbiosis increasing with the severity of the disease.<sup2.3sup>

Dietary Intervention Makes a Difference in Dogs with Early MMVD

With nutrition targets identified, Purina researchers next focused their research on developing a cardiac protection blend, or CPB [see “Cardiac Protection Blend Addresses Energy Crisis in Dogs with MMVD”], that could be fed to dogs in hopes of slowing the progression of MMVD while the disease is still at an early stage. A six-month dietary study demonstrated the efficacy of a diet containing the CPB in helping reduce left atrial enlargement and stabilize mitral regurgitation, as well as slowing the progression of mitral valve disease in dogs at early stages.⁴

At the beginning of the study, 19 dogs with stage B1 or B2 MMVD as established by the ACVIM consensus guidelines for MMVD and 17 age-, sex-, body condition- and breed-matched healthy dogs were enrolled. In each health group, half of the dogs were randomly designated as control dogs while the other half were fed the CPB for six months. Key findings were: 

• No dogs in the CPB-fed group showed progression of MMVD, but more than one-third of the control dogs progressed from B1 to B2.

• The CPB-fed dogs had about a 3% average left atrial size reduction while the control-fed dogs showed an average 10% increase in left atrial size from baseline.

• 30% of dogs in the CPB-fed group showed improvement in mitral regurgitation.

• No change was noted in the healthy dogs.

Nutritional Intervention Supports Cardiac Function at a Cellular Level

Having observed clinical changes in dogs with early-stage MMVD through dietary intervention in the six-month study, investigators further supported these findings by examining metabolomic changes in the dogs that were supplemented with the CPB. Analysis of blood samples from these dogs identified metabolites suggesting that improvement in energy metabolism, decreased oxidative stress and decreased inflammation were benefits of the dietary intervention.⁵

Purina Scientists Continue to Research Benefits of Dietary Intervention for MMVD Patients

Purina continues to work with internal and external collaborators on clinical trials to investigate and analyze the effects of MMVD on dogs and how early intervention with the CPB can benefit these patients.

Cardiac Protection Blend Addresses Energy Crisis in Dogs with MMVD

Jason Gagné, DVM, DACVIM (Nutrition)

Nutritional intervention for dogs with MMVD is not a new concept. For years, veterinarians have recommended cardiac diets for dogs in clinical heart failure to help control the clinical signs of disease. Historically, however, no nutritional changes were recommended for dogs with myxomatous mitral valve disease until patients reached at least stage B2.

At this point, mild sodium restriction has been advised, followed by further sodium restriction as the disease progresses. High palatability and anti-inflammatory properties have been other common attributes of cardiac diets.

With the launch of Purina® Pro Plan® Veterinary Diets CC CardioCare™ for dogs, veterinarians can intervene earlier in the disease process—specifically, when dogs are at Stage B1, as evidenced by a heart murmur without evidence of cardiac remodeling. The nutrients in Purina’s Cardiac Protection Blend (CPB) were formulated to specifically address the metabolic changes that occur in early MMVD.

This CPB is composed of amino acids, omega-3 fatty acids, magnesium, vitamin E and medium-chain triglycerides (MCTs). This blend has been shown to:

• Improve mitral regurgitation (MR) in 30% of dogs with early-stage mitral valve disease

• Increase serum omega-3 and decrease omega-6 fatty acid concentrations to help nutritionally manage dogs with cardiac conditions

• Increase serum arginine and citrulline (which are precursors of nitric oxide) to promote vasodilation

• Improve energy use as signified by biomarkers of fatty acid oxidation

Purina Institute Offers CentreSquare™ Resources for Clinics

CentreSquare is a new online toolkit of resources developed by the Purina Institute to facilitate client-friendly nutrition conversations. Visit purinainstitute.com/centresquare to explore this new resource and access bite-sized nutrition content for your clients and staff . To learn more about Purina’s research on canine myxomatous mitral valve disease, click on “Therapeutic Nutrition” and “Cardiovascular Disorders”.

The specific cardiac benefits of this dietary approach for dogs with early-stage MMVD include supporting cardiac function, slowing the progression of mitral valve disease, helping to stabilize MR and reduce left atrial enlargement in dogs at early stages, and helping to stabilize cardiac parameters as measured by echocardiography.

CC CardioCare may also benefit dogs in congestive heart failure (Stages C and D) and dogs with other conditions that benefit from moderate sodium reduction.