Canine Heart Health and Genetic Testing

Canine heart disease can be a significant concern for breeders, and multiple tools are available for assessing heart health in breeding stock and puppies. Both phenotypic and genetic tests are important and must be interpreted together. Phenotype refers to a dog’s observable traits, whereas genotype refers to a dog’s genetic constitution. Phenotypic tests are typically performed by a veterinarian or board-certified cardiologist. DNA tests can be used to determine a dog’s genotype for specific genetic variants, but phenotype tests are required to obtain a diagnosis of heart disease.

The heart is a complex organ that can manifest disease in multiple ways. Some heart diseases are present at birth (congenital), whereas others develop as the dog ages. These conditions can lead to symptoms such as coughing, lethargy, exercise intolerance, fainting, and even sudden death if left untreated. Some common heart diseases seen in dogs include:

1. Degenerative Mitral Valve Disease (DMVD)
   • This middle to old age disease is the most common of all canine heart diseases. One of the heart valves, the mitral valve, becomes thickened and damaged as the dog ages. The valve can leak blood and cause heart enlargement that can progress to congestive heart failure (CHF). Although small breed dogs are more prone to developing this disease, any dog can be affected. At the time of writing this article, no genetic tests are available to help predict the occurrence of this disease.
2. Dilated Cardiomyopathy (DCM)
   • With DCM, the second most common form of heart disease in dogs, the heart chambers become enlarged (dilated) and the walls become thin. DCM can have multiple causes, including inherited and nutritional. Multiple genetic variants have been identified that are associated with DCM that are typically breed-specific tests. Although some of these variants are inherited in a simple Mendelian fashion, others are complex and represent risk factors. Age of onset can vary from breed to breed. For example, Portuguese Water Dogs can develop an inherited, juvenile form that typically manifests before 6 months of age, called Juvenile Dilated Cardiomyopathy.¹

Phenotypic tests are crucial for evaluating the current function of the heart. Some common tests include:

1. Auscultation: Auscultation involves listening to the heart sounds using a stethoscope. Abnormalities such as murmurs, irregular rhythms, or gallops can indicate underlying cardiac issues.
2. Echocardiography: Echocardiography, or cardiac ultrasound, provides detailed images of the heart’s structure and function. It helps assess chamber sizes, valve function, and overall cardiac performance.
3. Electrocardiography (ECG or EKG): ECG records the electrical activity of the heart, helping identify arrhythmias and conduction abnormalities.
4. Chest radiographs: Radiographs offer valuable insights into the size and shape of the heart, as well as detecting signs of congestive heart failure, such as pulmonary edema or pleural effusion.
5. Holter Monitoring: Holter monitoring involves continuous ECG recording over 24-48 hours, allowing for the detection of intermittent arrhythmias.
   • The American Boxer Club, Inc., for example, recommends routine Holter monitoring annually for breeding to help decrease the incidence of Boxer Cardiomyopathy.

Genetic testing related to canine cardiac health is most important for informing breeding practices when selecting breeding pairs. The AKC DNA Program is about to launch genetic testing in the coming months, and several genetic variants for heart health are included in this panel.

Parent Club Recommended DNA Cardiac Health Tests:

·       Dilated Cardiomyopathy (Schnauzer Type) ²

o   This specific genetic variant investigates a deletion in the RBM20 gene.

• Juvenile Dilated Cardiomyopathy in Portuguese Water Dogs (Available only through PennGen) ¹
  • This genetic variant investigates a locus on canine chromosome 8.

Other AKC DNA + Health Heart Tests:

• Cardiomyopathy and Juvenile Mortality³
  • This genetic variant is associated with severe heart disease that can cause death from heart failure by 8 weeks of age.
• Dilated Cardiomyopathy (Doberman Pinscher Type Risk Factor, Variant 1)^4,5
  • This specific genetic variant investigates a deletion in the PDK4 gene and is associated with disease in Doberman Pinschers, and its association with DCM in other breeds is not clear. This genetic variant is inherited in an autosomal dominant manner with incomplete penetrance. In other words, not every dog with this genetic variant goes on to develop the disease DCM.
• Dilated Cardiomyopathy (Doberman Pinscher Type Risk Factor, Variant 2)⁶
  • This specific genetic variant investigates a single nucleotide polymorphism (SNP) in the TTN gene and is associated with disease in Doberman Pinschers.

Canine genetic testing for heart disease represents a valuable tool in the arsenal against decreasing the risk of producing cardiac conditions in dogs. By leveraging the power of genetics, veterinarians and dog owners can work together to identify at-risk individuals, implement preventive measures, and provide personalized care to improve the overall cardiac health and well-being of our beloved canine companions. Each known genetic variant for DCM will be discussed in more detail in the coming months. As research continues to advance, genetic testing holds the promise of further enhancing our understanding and management of canine heart disease.

Citations:

1. Werner P, Raducha MG, Prociuk U, Sleeper MM, Van Winkle TJ, Henthorn PS. A novel locus for dilated cardiomyopathy maps to canine chromosome 8. Genomics. 2008 Jun;91(6):517-21.

1. Harmon MW, Leach SB, Lamb KE. Dilated Cardiomyopathy in Standard Schnauzers: Retrospective Study of 15 Cases. J Am Anim Hosp Assoc. 2017 Jan/Feb;53(1):38-44.

3. Gurtner C, Hug P, Kleiter M, Köhler K, Dietschi E, Jagannathan V, Leeb T. YARS2 Missense Variant in Belgian Shepherd Dogs with Cardiomyopathy and Juvenile Mortality. Genes (Basel). 2020 Mar 14;11(3):313. PubMed: 32183361
4. Meurs KM, Lahmers S, Keene BW, White SN, Oyama MA, Mauceli E, Lindblad-Toh K. A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher. Hum Genet. 2012 Aug; 131(8):1319-25.
5. Owczarek-Lipska M, Mausberg TB, Stephenson H, Dukes-McEwan J, Wess G, Leeb T. A 16-bp deletion in the canine PDK4 gene is not associated with dilated cardiomyopathy in a European cohort of Doberman Pinschers. Anim Genet. 2013 Apr;44(2):239.
6. Meurs KM, Friedenberg SG, Kolb J, Saripalli C, Tonino P, Woodruff K, Olby NJ, Keene BW, Adin DB, Yost OL, DeFrancesco TC, Lahmers S, Tou S, Shelton GD, Granzier HG. A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death. Hum Genet. 2019 May;138(5):515-524.