The US Food and Drug Administration (FDA) is currently investigating reports of dilated cardiomyopathy (DCM) in dog breeds not typically genetically prone to the disease. Over 90% of the affected dogs have been found to be eating certain pet foods containing peas, lentils, other legumes or potatoes as the main ingredients. These diets are typically labeled “grain-free”. The FDA are investigating this potential association, thought to be possibly linked with taurine deficiency. Alternative protein sources were not associated with the cases of DCM. The three brands most commonly encountered in atypical case reports of DCM by the FDA are Acana, Zignature and Taste of the Wild.

What is DCM?

DCM is a disease of the heart muscle and results in an enlarged heart. As the chambers enlarge the pumping action becomes less efficient, heart valves may leak and ultimately congestive heart failure results. Typically DCM in dogs is usually seen in large to giant breeds [1-4] with the exception of the Cocker Spaniel [5, 6].

The recent atypical cases reported to FDA are most commonly Golden Retrievers (GR), but also include more smaller breeds- Whippets, Shih Tzus and Miniature Schnauzers.

Nutritionally mediated DCM

Taurine

Taurine deficiency and its association with DCM is well described in both the cat and the dog [7] although the exact pathogenic pathway is not fully understood. Taurine is considered an essential nutritional amino acid in cats. Cats lack the enzyme activity to synthesize taurine from methionine and cysteine in the liver and CNS, deficiency is accepted as a direct cause of DCM in this species [8]. This is included under the umbrella description of nutritionally mediated DCM. Cats with nutritionally mediated DCM respond well to taurine supplementation, with myocardial function normalizing within 3-6 months [9].

More recently it has been recognized that taurine deficiency in dogs can also cause DCM, despite the fact that taurine is not considered nutritionally essential in this species. Studies have shown that when dogs with DCM and taurine deficiency are supplemented with taurine and L carnitine, several of the myocardial changes resolve, ventricular function improves and supportive cardiac medication can be withdrawn in the majority of these dogs [6, 10, 11]. These studies suggest a direct causal relationship between taurine deficiency and development of DCM. Some dogs with nutritionally mediated DCM do not appear to have a taurine deficiency; however, this is according to the existing reference ranges which we are understanding may be more variable between breeds than previously known [12].

Dietary factors and DCM

Other dietary factors have been linked to nutritionally mediated DCM, most notably grain-free, legume rich, protein restriction [13] or a combination of these [14]. This may be linked with taurine levels or have another pathophysiological mechanism resulting in DCM. The FDA noted that the number of atypical DCM cases being reported was inversely proportional to the size of the manufacturer- small boutique manufacturers are associated with proportionally more cases than large manufacturers. This suggests that these diets may not be formulated with the same level of nutritional expertise (understanding of bioavailability, digestibility, fermentability and interactions of food constituents) and quality control, which could introduce potential issues with some products [15]. Home cooked diets should be avoided also for this reason.

In a 2019 study, dogs fed a grain-free diet were found to have greater left ventricular size  and reduced sphericity index compared to dogs fed a grain based diet [16]. In a large 2020 study, GR fed grain-free diets have been found to have significantly lower taurine concentrations, more frequent systolic dysfunction and echocardiographic changes consistent with nutritionally mediated DCM [12]. Of all breeds represented in research and in the FDA report, GR are consistently reported to be the most commonly associated with nutritionally mediated DCM [17]. There is no literature to support genetic DCM in GR and thus the role of nutritional factors in GR appear more relevant than other breeds [12].

Food regulations

Cat food must have taurine supplemented in quantities established by the American Association of Feed Control Officials (AAFCO) and National Research Council (NRC). To date there are no stated requirements for dog food. The extent to which dogs may require taurine supplementation is still under investigation and may be breed dependent. Breed specific reference ranges are being formulated [12] which may help authorities publish taurine requirements for dog foods.

Conclusion

Greater understanding of nutritionally mediated DCM is needed and the role that dietary taurine levels, grain-free formulations, nutritional precision and the interaction of these, may play in the disease. Until this understanding is established, it is not advisable to recommend grain-free, legume rich diets, especially in breeds shown to be particularly susceptible to nutritionally mediated DCM such as the GR.

References:

1. Stern, J.A. and Y. Ueda, Inherited cardiomyopathies in veterinary medicine. Pflugers Arch, 2019. 471(5): p. 745-753.
2. Vollmar, C., et al., Dilated cardiomyopathy in 151 Irish Wolfhounds: Characteristic clinical findings, life expectancy and causes of death. Vet J, 2019. 245: p. 15-21.
3. Meurs, K.M., et al., A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death. Hum Genet, 2019. 138(5): p. 515-524.
4. Tidholm, A. and L. Jönsson, A retrospective study of canine dilated cardiomyopathy (189 cases). J Am Anim Hosp Assoc, 1997. 33(6): p. 544-50.
5. Broschk, C. and O. Distl, [Dilated cardiomyopathy (DCM) in dogs–pathological, clinical, diagnosis and genetic aspects]. Dtsch Tierarztl Wochenschr, 2005. 112(10): p. 380-5.
6. Kittleson, M.D., et al., Results of the multicenter spaniel trial (MUST): taurine- and carnitine-responsive dilated cardiomyopathy in American cocker spaniels with decreased plasma taurine concentration. J Vet Intern Med, 1997. 11(4): p. 204-11.
7. Hayes, K.C., Taurine nutrition. Nutr Res Rev, 1988. 1(1): p. 99-113.
8. Pion, P.D., et al., Taurine deficiency myocardial failure in the domestic cat. Prog Clin Biol Res, 1990. 351: p. 423-30.
9. Pion, P.D., et al., Response of cats with dilated cardiomyopathy to taurine supplementation. J Am Vet Med Assoc, 1992. 201(2): p. 275-84.
10. Fascetti, A.J., et al., Taurine deficiency in dogs with dilated cardiomyopathy: 12 cases (1997-2001). J Am Vet Med Assoc, 2003. 223(8): p. 1137-41.
11. Backus, R.C., et al., Taurine deficiency in Newfoundlands fed commercially available complete and balanced diets. J Am Vet Med Assoc, 2003. 223(8): p. 1130-6.
12. Ontiveros, E.S., et al., Development of plasma and whole blood taurine reference ranges and identification of dietary features associated with taurine deficiency and dilated cardiomyopathy in golden retrievers: A prospective, observational study. PLoS One, 2020. 15(5): p. e0233206.
13. Sanderson, S.L., et al., Effects of dietary fat and L-carnitine on plasma and whole blood taurine concentrations and cardiac function in healthy dogs fed protein-restricted diets. Am J Vet Res, 2001. 62(10): p. 1616-23.
14. Kaplan, J.L., et al., Taurine deficiency and dilated cardiomyopathy in golden retrievers fed commercial diets. PLOS ONE, 2018. 13(12): p. e0209112.
15. Mansilla, W.D., et al., Special topic: The association between pulse ingredients and canine dilated cardiomyopathy: addressing the knowledge gaps before establishing causation1. J Anim Sci, 2019. 97(3): p. 983-997.
16. Adin, D., et al., Echocardiographic phenotype of canine dilated cardiomyopathy differs based on diet type. J Vet Cardiol, 2019. 21: p. 1-9.
17. Kramer, G.A., et al., Plasma taurine concentrations in normal dogs and in dogs with heart disease. J Vet Intern Med, 1995. 9(4): p. 253-8.

Administration USF& D. FDA Investigating potential connection between diet and cases of canine heart disease [Internet]. [cited 23 Jul 2018]. Available: https://www.fda.gov/animalveterinary/newsevents/ cvmupdates/ucm613305.htm

Postdate: 20th August 2020