heart disease

Heart disease is a common problem in cats and dogs. Although cardiac physiology is the same between these species, some diseases are more common in dogs than cats.

Heart disease has been a focus of Morris Animal Foundation funding for almost 75 years, but there’s still a lot researchers don’t know. This article will review some of the Foundation’s latest studies and recent findings — and look at where cardiology research is heading.

THICK HEARTS AND BIG CLOTS —ATE AND HCM IN CATS

For nearly 40 years, Morris Animal Foundation has funded studies into hypertrophic cardiomyopathy (HCM) and aortic thromboembolism (ATE) in cats.

Aortic thromboembolism

One of the most influential was the FAT CAT study. Researchers considered whether clopidogrel or aspirin was superior in preventing a recurrence of ATE in cats that had survived a previous episode. Clopidogrel was found to be clearly superior in preventing recurrence, and cats receiving clopidogrel that did have another episode had a longer-than-average time to recurrence. Thanks to this study, clopidogrel is now a routine frontline therapy for cats with ATE.1

Although clopidogrel can be an important drug for preventing ATE in cats, not all cats metabolize the drug in the same way. This variation can result in improper drug dosing, which can lead to treatment failure. Foundation-funded researchers at the University of California, Davis, studied the genetics behind differences in clopidogrel metabolism, and are currently developing genetic test procedures to help veterinarians determine the best dose of the drug. The team hopes this will be a first step toward personalized medicine for cats suffering from HCM.2

Hypertrophic cardiomyopathy

HCM in asymptomatic cats can be difficult to detect using just a physical examination or even an X-ray. Echocardiography is the gold standard for diagnosing HCM, but it can be costly and time-consuming for owners as a screening test and can require referral to a cardiology specialist. A Foundation-funded team at Tufts University recognized the need for a quick test that could be done by a general veterinary practitioner during a routine office visit. The team developed a screening protocol that was effective in detecting moderate to marked HCM in asymptomatic cats and was easy for non-specialist veterinarians to learn and master.3

The Foundation was also a funding partner in one of the largest studies ever conducted on HCM in cats. An international team of collaborators from 21 countries contributed data on more than 1,700 cats, both with and without HCM. The findings of this massive undertaking were published in two papers. The team found that roughly 30% of the cats in the study developed complications secondary to their disease. Only 10% of cats with preclinical HCM lived what was defined as a “long life” (nine to 15 years of age). The researchers also found no significant difference in outcomes between cats with obstructive or nonobstructive HCM.4,5

GENETICS TAKES CENTER STAGE FOR DOGS WITH HEART DISEASE

The search for the genetic underpinnings of heart disease in dogs has been a subject of multiple studies funded by the Foundation over the last 20 years. Technological advances coupled with decreasing costs make it easier to analyze genetic data associated with complex conditions such as heart disease. Certain breeds are predisposed to different types of disease, suggesting an underlying genetic component. Identifying genetic abnormalities that may be responsible for disease is a first step toward new diagnostic tests and possibly even prevention.

Subvalvular aortic stenosis

Thanks in part to Foundation funding, genetic testing is now available for subvalvular aortic stenosis (SAS) in Newfoundland dogs. A group of talented researchers based at North Carolina State University was able to identify the genetic mutation responsible for the disease in this breed, leading to the development of a genetic test that is now commercially available. The results of this study were particularly significant because they represent the first genetic mutation identified for a congenital heart defect in dogs.6

NEW HORIZONS IN COMPANIONANIMALHEART DISEASE

The future is looking brighter for animal patients suffering from heart disease. The Foundation is funding several cutting-edge studies using the latest technological tools, new drugs, and innovative strategies to tackle heart disease.

  • One study at the University of California, Davis, is looking at rapamycin’s ability to reverse remodeling in dogs with severe SAS. Rapamycin inhibits one of the key regulators of cell growth and nutrient response, and there is evidence it prevents remodeling secondary to laboratory-induced cardiac pressure overload. Rapamycin has been safely used experimentally in dogs as a chemotherapeutic agent, and in studies of aging. Given the extremely poor prognosis for dogs with severe SAS, this study, if successful, could have a significant impact on canine patients diagnosed with this terrible disease, and their veterinarians.
  • A team at the University of Florida is testing whether it’s possible to use the gene-editing tool CRISPR/Cas9 to treat dilated cardiomyopathy (DCM) in Doberman pinschers. After taking stem cells from Dobermans and differentiating them into cardiomyocytes, researchers will attempt to use CRISPR/Cas9 to correct defects in genes important for heart function in dogs. Specifically, the team will edit a known mutation and two proteins associated with DCM, and measure its impact on heart cell function. If successful, the team hopes it can translate the treatment into a clinical trial. The genetics of HCM in cats is the subject of another newly-funded study. Estimates suggest one in seven cats will develop this disease. Although breed-specific tests to assess risk do exist, there are still large knowledge gaps in our understanding of the genetics underlying HCM. A team of geneticists at University of California, Davis, are using whole-genome sequencing techniques to develop the largest feline genetic data set ever studied.

The researchers are comparing cats with HCM, and geriatric cats without the disease. The team hopes to use this information to develop novel testing, and to identify new drug therapy targets to improve the care of cats with this devastating heart disease. In addition, the data set will be freely available as a first-of-its-kind, open-access genetic resource for other researchers, in an attempt to facilitate and accelerate research.

It will be exciting to see what these talented researchers discover about heart disease in dogs and cats

Myxomatous mitral valve disease

The same team turned their attention to my xomatous mitral valve disease (MMVD). Using funds granted through the first Mark L.Morris Jr. Investigator Award, the researchers spent five years studying the complex genetics of MMVD. Their aim was ambitious — to search for the gene(s) responsible for this common disease.

The group just completed its project and began to publish results. They didn’t find a single genetic variant that explained MMVD development in the population they studied. Likewise, they didn’t find a single breed-specific genetic variant for the development of MMVDin miniature poodles, dachshunds, Yorkshire terriers or Cavalier King Charles spaniels. However, the team did discover a specific signaling pathway that could be involved in the pathogenesis of MMVD across different breeds. More work is needed on teasing out the specifics, but the team hopes veterinarians will soon be able to screen dogs for MMVD via disruptions in this pathway.7

Another important finding from the project centered on differences between Yorkshire terriers and miniature Schnauzers diagnosed with MMVD. As part of their genetic research, the team reviewed medical records associated with dogs in the study. They noted that miniature Schnauzers were significantly younger at the time of MMVD diagnosis than Yorkshire terriers, and their clinical signs differed.8

The study generated several publications and has been a springboard for research groups to tackle complex genetic diseases. The authors’ findings also emphasized that even a common disease such as MMVD can be more complex than previously thought, and that gaining a deeper understanding of the problem can help veterinarians provide more personalized and effective care for their patients.9 

Cardiac disease remains one of the most common problems seen by veterinarians, affecting untold numbers of cats and dogs each year. Morris Animal Foundation, thanks to donor support, continues to fund innovative research in heart disease to help veterinarians provide the best care for their patients.

References:

  1. Hogan D, Fox P, Jacob K, 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). JVet Cardiol. 2015;17:S30.
  2. Ueda Y, Li RH, Nguyen N, et al. A genetic polymorphism inP2RY1impacts response to clopidogrel in cats with hypertrophic cardiomyopathy.Sci Rep. 2021;11:12522.
  3. Loughran K, Rush J, Rozanski E, et al. The use of focused cardiac ultrasound to screen for occult heart disease in asymptomatic cats.J Vet Intern Med. 2019;33(5):1892-1901.
  4. Fox P, Keene B, Lamb K, 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(3):9
  5. Fox P, Keene B, Lamb K, et al. Long-term incidence and risk of noncardiovascular and all-cause mortality in apparently healthy cats and cats with preclinical hypertrophic cardiomyopathy.J VetIntern Med. 2019;33(6):2572-2586.
  6. Stern J, White S, Lemkuhl L, et al. A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs.Hum Genet. 2014;133(9): 1139–1148.
  7. Williams B, Friedenberg S, Keene B, et al. Use of whole genome analysis to identify shared genomic variants across breeds in canine mitral valve disease.Hum Genet. 2021;140(11):1563-1568.
  8. DeProspero D, O’Donnell K, DeFrancesco T, et al. Myxomatous mitral valve disease in MiniatureSchnauzers and Yorkshire Terriers: 134 cases (2007-2016).J Am Vet Med Assoc. 2021;259(12):1428-1432.
  9. Adin D, Atkins C, Friedenberg S, et al. Prevalence of an angiotensin-converting enzyme genevariant in dogs.Canine Med Genet. 2021;8(1):6

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