Alison Ramser, PhD
Postdoctoral Fellow, Department of Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA; E-mail: atramser@uark.edu
Dilated cardiomyopathy (DCM) is a significant cause of morbidity and mortality in canines.1 This condition is characterized by dilation and compromised contraction of the left or both heart ventricles. DCM has been the subject of much research in recent years. In 2019, the Food and Drug Administration (FDA) raised concerns about a potential link between pulse ingredientrich diets (grain-free diets) and DCM related to taurine deficiency. As a result, current research has focused on discerning a link between grain-free diets and the incidence of DCM.2 Recent research has suggested a possible affiliation of DCM with a deficiency in other amino acids and their precursors as well (Figure 1).
Figure 1. Graphical Summary: Decreased protein and amino acid intake leads to canine dilated cardiomyopathy, which is characterized by decreased systolic function, increased chamber dilation, and impaired contraction of left or both heart ventricles. Much research remains to be done to determine further definitive causation of this disease. Created with BioRender.com
Incidence
Dilated cardiomyopathy is the second most common heart disease in canines.3,4 Concerns have arisen that the incidence of this condition is increasing. Previously, canine DCM was primarily considered to be an inherited disease among specific breeds, however, there have been recent reports suggesting a possible link between certain types of diets and this disease.5,6,7,8,9 This condition is more prevalent in large and giant breeds (e.g., Irish Wolfhounds, German Shepherd Dogs, Doberman Pinschers, Golden Retrievers, etc.).4,10,11 Veterinary cardiologists have reported subjectively more frequent diagnoses of DCM in atypical breeds.10,12,13 Recent studies have sought to investigate an increased incidence of DCM due to variety of factors. There may be a potential link between this condition and environmental/regional, breed-specific, and/ or diet factors.14 Currently, research is primarily focused on dietmediated DCM, as concerns were raised by the FDA over incidence of this condition and grain-free pet food sales.4,15 An incidence rate of 0.4% was reported among all patients assessed at a specific veterinary teaching hospital in the United States from 1995-2010.16 Interestingly, a European study reports an incidence rate of 1.1%.17 Concerns over the incidence of this condition are rising, however, research shows a static overall trend in the incidence of DCM over time.14 The etiology of this condition still requires much research to identify.
Clinical Signs and Diagnosis
The clinical phase of DCM can be identified by decreased systolic function typically followed by chamber dilation, often progressing to congestive heart failure, arrhythmias, and in some cases, sudden death.14 This condition is characterized by dilation and compromised contraction of the left or both heart ventricles.18 A 2022 study also characterized the metabolomic profile of canines with DCM and found that oxidative stress was a major pathway implicated in DCM compared to healthy controls.19 Often times, DCM can go unnoticed for the majority of the condition, as symptoms are often not readily present until further development. This leads to difficulty diagnosing the condition. Once the condition is symptomatic, active exclusion of other potential causes of these symptoms must take place before a definitive clinical diagnosis can be made.18 Often, the clinical phase of DCM is a result of long-term progression. In fact, sudden cardiac death can sometimes be the first manifestation of the disease.3,18,20 Pre-screening and diagnosis are paramount in the treatment of DCM.21 Diagnosis of the disease is based on left ventricular dilation, depressed systolic function, altered geometry of the left ventricle (increased sphericity), left or bi-atrial enlargement, increased mitral valve M-mode E point to septal separation (EPSS), and arrhythmias recorded on the simultaneous electrocardiogram (ECG) through echocardiographic (echo) examination.18,22 Diagnosis of this condition is primarily based on these findings as well as active exclusion of other cardiovascular conditions.23 Veterinary cardiologists may employ a variety of diagnostic tests to evaluate the development of DCM. A definitive diagnosis can be made using echocardiographic findings to confirm symptoms such as reduced systolic function, enlarged left atrium, and/or dilated ventricular chambers.24,25,26 Physical examination, imaging modalities, electrocardiogram evaluation, twenty-four-hour Holter monitoring, and cardiac biomarkers may be used to diagnosis this condition.21,27 Physical examination of the canine may reveal irregular heart rhythm, weak pulse, systolic murmur with maximum intensity in the left sixth intercostal space.14,24 Imaging modalities such as thoracic radiography and echocardiography are crucial when diagnosing DCM as they can reveal increased enddiastolic and end-systolic diameter of the left ventricle, as well as fractional shortening.28,29 Arrhythmia of the ventricles can be detected using electrocardiographic evaluation, as well as atrial and ventricular enlargement.14,30 Twenty-four-hour Holter monitoring, however, is the benchmark evaluation method for detection of arrhythmias.31 Measurement of cardiac biomarkers such as cardiac troponin–I concentration (indicative of myocardial damage) offers a more complete analysis of the condition than other diagnostic tools alone.14,32 In the case of DCM, increasing concentration of cardiac troponin–I is associated with increasing myocardial damage.32
Diet Composition
In July 2019, the Food and Drug Administration (FDA) released a public statement reporting a total of 560 canines with diagnosed with possible diet-mediated cardiomyopathy.4,15 More than 90% of the diets consumed by the subjects at the time of diagnosis were grain-free and 93% of the diets contained peas and/or lentils.15 Several investigations into the incidence of this condition in relationship to grain-free diet consumption have been conducted in recent years as a result.33,34,35,36 In a study of 86 golden retrievers, researchers hypothesized that dogs eating non-traditional diets (e.g., grain-free diets containing peas and/or lentils) are at higher-risk for contracting diet-mediated DCM than dogs eating traditional diets (e.g. grain-inclusive diets).37 Results of this study suggested increased incidence of DCM in canines eating nontraditional diets, however, study design and statistical analysis are questionable as comparisons made between groups of differing sample sizes were done using the mean when the coefficient of variation should have been used. Additionally, the inclusion criteria for the non-traditional diet was very strict and required all five of the outlined criteria to be met, while inclusion criteria for the traditional diet was very broad and only required meeting two or more of the outlined criteria.37 Most recently, a meta-analysis reported a static overall incidence of the condition over time, while there was a five-fold increase in grain-free pet food sales (Figure 2). This study concluded there was no correlation between incidence of the condition and consumption of grain-free diets.14 Further research on dietary-mediation of the condition suggests that diets low in protein, taurine, and specific sulfur-containing amino acids may have a significant role in the development of DCM, as these nutrients are crucial for cardiac muscle development and function.3 Diets high in insoluble fiber have been shown to have antinutritive effects relating to decreased crude protein digestibility in the gut.38,39 A decrease in crude protein digestibility can affect the bioavailability of taurine, carnitine, and other amino acids.40 In a separate, non-controlled study, canines diagnosed with DCM who consumed diets supplemented with taurine and L-carnitine showed reduced clinical signs and longer lifespan.41 Therefore, diet-mediated DCM could be influenced by the metabolism of protein, taurine, and specific amino acid precursors. Future dietary mediations could also target oxidative stress and overall inflammation as both have been shown to be associated with DCM in canines.19
Figure 2. Annual Average Incidence Rate of DCM and Grain-free Pet Food Sales from 2000-201914
Nutrient Deficiencies
Cardiac muscle function is largely affected by taurine and it’s precursors (methionine and cysteine), and carnitine and it’s precursors (methionine and lysine).3,42 Copper, potassium, thiamine, selenium, and vitamin E deficiencies are also linked to myocardial damage, however, further research is required to determine a connection.3 Although non-essential, taurine is an important sulfur-containing amino acid that largely affects the functions of the cardiovascular, skeletal, and central nervous systems. Methionine and cysteine are sulfur containing amino acids that form the non-essential amino acid, taurine.43 The bioavailability of these precursors can affect the endogenous synthesis of taurine in the liver.43 Another important nutrient to consider is carnitine. Deficiencies in taurine and carnitine have been shown to be correlated with decreased myocardial function.44,45 Carnitine is endogenously synthesized in the liver as well and the bioavailability of its precursors, methionine and lysine, can affect the synthesis of the amino acid.46 In a human survival study, administration of carnitine in patients with DCM showed statistically significant survival rates when compared to a control group.47 Similarly, in a study conducted on a family of dogs with DCM, supplementation with carnitine showed greatly improved myocardial function. Withdrawal of carnitine supplementation lead to development of clinical symptoms of DCM.45
Recent reports from the FDA suggest a potential dietary-mediation in the incidence of DCM. As a result, much research has been done to investigate possible causation of this condition due to grain-free pet food. The most recent meta-analysis shows no correlation between incidence of the condition and grain-free pet food sales. Protein, taurine, and specific sulfur-containing amino acids are crucial for cardiac muscle development and function. Diets low in these nutrients may have a significant role in the development of DCM, however, much research remains to be done before definitive conclusions can be made on the etiology of the condition.
The authors declare that they have no conflicts of interest.
1. Walker AL, DeFrancesco TC, Bonagura JD, et al. Association of diet with clinical outcomes in dogs with dilated cardiomyopathy and congestive heart failure. J Vet Cardiol. 2022; 40: 99-109. doi: 10.1016/j.jvc.2021.02.001
2. Smith CE, Parnell LD, Lai C-Q, Rush JE, Freeman LM. Investigation of diets associated with dilated cardiomyopathy in dogs using foodomics analysis. Scientific Reports. 2021; 11: 15881. doi: 10.1038/s41598-021-94464-2
3. McCauley SR, Clark SD, Quest BW, Streeter RM, Oxford EM. Review of canine dilated cardiomyopathy in the wake of diet-associat ed concerns. J Anim Sci. 2020; 98: skaa155. doi: 10.1093/jas/skaa155
4. Dutton E, López-Alvarez J. An update on canine cardiomyopathies -is it all in the genes? J Small Anim Pract. 2018. doi: 10.1111/jsap.12841
5. Bakke AM, Wood J, Salt C, et al. Correction: Responses in randomised groups of healthy, adult Labrador retrievers fed grain-free diets with high legume inclusion for 30 days display commonalities with dogs with suspected dilated cardiomyopathy. BMC Vet Res. 2022; 18: 185.
doi: 10.1186/s12917-022-03291-8
6. Kaplan JL, Stern JA, Fascetti AJ, et al. Taurine deficiency and dilated cardiomyopathy in golden retrievers fed commercial diets. PLoS One. 2018; 13: e0209112. doi: 10.1371/journal.pone.0209112
7. Burns KM. Grain-Free Diets and Dilated Cardiomyopathy. https://todaysveterinarynurse.com/nutrition/grain-free-diets-and-dilated-cardiomyopathy/. Accessed January 25, 2023.
8. Lichtenberger J. Grain-free diets and dilated cardiomyopathy, an emerging problem? Paper presented at: the 2019 OVMA (Ontario Veterinary Medical Association) Conference; January 31, 2019 to February 2, 2019; Toronto, Canada. 118-120.
9. Gaar-Humphreys KR, Spanjersberg TC, Santarelli G, et al. Genetic basis of dilated cardiomyopathy in dogs and its potential as a bidirectional model. Animals (Basel). 2022; 12: 1679. doi: 10.3390/ani12131679
10. Freeman LM, Stern JA, Fries R, Adin DB, Rush JE. Diet-associated dilated cardiomyopathy in dogs: what do we know? J Am Vet Med Assoc. 2018; 253: 1390-1394. doi: 10.2460/javma.253.11.1390
11. Vollmar A. The prevalence of cardiomyopathy in the Irish wolfhound: A clinical study of 500 dogs. J Am Anim Hosp Assoc. 2000; 36: 125-132.
doi: 10.5326/15473317-36-2-125
12. Saito T, Suzuki R, Yuchi Y, Yasumura Y, Teshima T, Matsumoto H, Koyama H. A case of a small-breed dog with diet-related dilated cardiomyopathy showing marked improvements in cardiac morphology and function after dietary modification. Vet Sci. 2022; 9: 593.
doi: 10.3390/vetsci9110593
13. Adin D, Freeman L, Stepien R, et al. Effect of type of diet on blood and plasma taurine concentrations, cardiac biomarkers, and echocardiograms in 4 dog breeds. J Vet Inter Med. 2021; 35: 771-779. doi: 10.1111/jvim.16075
14. Quest BW, Clark SD, Garimella S, Konie A, Leach SB, Oxford EM. Incidence of canine dilated cardiomyopathy, breed and age distributions, and grain-free diet sales in the United States from 2000-2019: A retrospective survey. Front Anim Sci. 2020; 3. doi: 10.1101/2020.09.27.315770
15. U. S. Food and Drug Administration (FDA). Investigation into Potential Link between Certain Diets and Canine Dilated Cardiomyopathy. https://www.fda.gov/animal-veterinary/outbreaks-and-advisories/fda-investigation-potential-link-between-certain-diets-and-canine-dilated-cardiomyopathy. Accessed January 25, 2023.
16. Bellumori TP, Famula TR, Bannasch DL, Belanger JM, Oberbauer AM. Prevalence of inherited disorders among mixed-breed and purebred dogs: 27,254 cases (1995-2010). J Am Vet Med Assoc. 2013; 242: 1549-1555. doi: 10.2460/javma.242.11.1549
17. Fioretti M, Delli C. Epidemiological survey of dilatative cardiomyopathy in dogs. Veterinaria. 1988; 2: 1.
18. Dukes-McEwan J, Borgarelli M, Tidholm A, Vollmar AC, Häggström J. Proposed guidelines for the diagnosis of canine idiopathic dilated cardiomyopathy. J Vet Cardiol. 2003; 5: 7-19. doi: 10.1016/s1760-2734(06)70047-9
19. Smith CE, Parnell LD, Lai CQ, et al. Metabolomic profiling in dogs with dilated cardiomyopathy eating non-traditional or traditional diets and in healthy controls. Sci Rep. 2022; 12: 22585. doi: 10.1038/s41598-022-26322-8
20. Koch J, Pedersen HD, Jensen AL, Flagstad A. M-mode echocardiographic diagnosis of dilated cardiomyopathy in giant breed dogs. Zentralbl Veterinarmed A. 1996; 43: 297-304. doi: 10.1111/j.1439-0442.1996.tb00456.x
21. Wess G. Screening for dilated cardiomyopathy in dogs. J Vet Cardiol. 2022; 40: 51-68. doi: 10.1016/j.jvc.2021.09.004
22. Ward J, Ware W, Viall A. Association between atrial fibrillation and right-sided manifestations of congestive heart failure in dogs with degenerative mitral valve disease or dilated cardiomyopathy. J Vet Cardiol. 2019; 21: 18-27. doi: 10.1016/j.jvc.2018.10.006
23. Tidholm A, Jönsson L. Histologic characterization of canine dilated cardiomyopathy. Vet Pathol. 2005; 42: 1-8. doi: 10.1354/vp.42-1-1
24. Guglielmini C. Cardiovascular diseases in the ageing dog: Diagnostic and therapeutic problems. Vet Res Commun. 2003; 27: 555-560.
doi: 10.1023/b:verc.0000014216.73396.f6
25. Thomas DE, Wheeler R, Yousef ZR, Masani ND. The role of echocardiography in guiding management in dilated cardiomyopathy. Eur J Echocardiogr. 2009; 10: iii15-iii21. doi: 10.1093/ejechocard/jep158
26. Schober K, Hart T, Stern JA, et al. Detection of congestive heart failure in dogs by Doppler echocardiography. J Vet Intern Med. 2010; 24: 1358-1368. doi: 10.1111/j.1939-1676.2010.0592.x
27. Petrie J-P. Practical application of holter monitoring in dogs and cats. Clin Tech Small Anim Pract. 2005; 20(3): 173-181.
doi: 10.1053/j.ctsap.2005.05.006
28. Martin MWS, Stafford Johnson MJ, Celona B. Canine dilated cardiomyopathy: A retrospective study of signalment, presentation and clinical findings in 369 cases. J Small Anim Pract. 2009; 50: 23-29. doi: 10.1111/j.1748-5827.2008.00659.x
29. Bonagura JD, Visser LC. Echocardiographic assessment of dilated cardiomyopathy in dogs. J Vet Cardiol. 2022; 40: 15-50.
doi: 10.1016/j.jvc.2021.08.004
30. Morgan RV. Handbook of Small Animal Practice. 3rd ed. Philadelphia, USA: Saunders; 1997.
31. Singletary, G.E, Morris, N.A, Lynne O’Sullivan, M, Gordon, S.G, Oyama, M.A. Prospective evaluation of NT-proBNP assay to detect occult dilated cardiomyopathy and predict survival in doberman pinschers. J Vet Intern Med. 2012; 26: 1330-1336. doi: 10.1111/j.1939-1676.2012.1000.x
32. Langhorn R, Willesen JL. Cardiac troponins in dogs and cats. J Vet Intern Med. 2016; 30: 36-50. doi: 10.1111/jvim.13801
33. Adin D, DeFrancesco TC, Keene B, et al. Echocardiographic phenotype of canine dilated cardiomyopathy differs based on diet type. J Vet Cardiol. 2019; 21: 1-9. doi: 10.1016/j.jvc.2018.11.002
34. Banton S, Baynham A, Pezzali JG, von Massow M, Shoveller AK. Grains on the brain: A survey of dog owner purchasing habits related to grain-free dry dog foods. PLoS One. 2021; 16: e0250806. doi: 10.1371/journal.pone.0250806
35. Shalamoff A, Claremont C, Miller C, Neiman N. Kibble me this: The scientific and cultural debate over boutique, exotic, and grain-free canine nutrition. 2019. https://core.ac.uk/download/pdf/289019761.pdf. Accessed January 25, 2023.
36. Dunn S. Development and Management of Canine Adverse Food Reactions and its Connections to the Grain-Free Dog Food Movement. 2020. https://digitalcommons.liberty.edu/cgi/viewcontent.cgi?article=2020&context=honors. Accessed January 25, 2023.
37. Ontiveros ES, Whelchel BD, Yu J, 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: e0233206. doi: 10.1371/journal. pone.0233206
38. Wilfart A, Montagne L, Simmins PH, van Milgen J, Noblet J. Sites of nutrient digestion in growing pigs: Effect of dietary fiber. J Anim Sci. 2007; 85: 976-983. doi: 10.2527/jas.2006-431
39. Twomey LN, Pethick DW, Choct M, et al. The use of exogenous feed enzymes in reducing the anti-nutritive effects on dietary fibre in dog foods. Recent Advances in Animal Nutrition. 2001; 13: 179-186.
40. Ko KS, Fascetti AJ. Dietary beet pulp decreases taurine status in dogs fed low protein diet. J Anim Sci Technol. 2016; 58: 29.
doi: 10.1186/s40781-016-0112-6
41. Sanderson SL, Gross KL, Ogburn PN, 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: 1616-1623. doi: 10.2460/ajvr.2001.62.1616
42. Basili M, Pedro B, Hodgkiss-Geere H, Navarro-Cubas X, Graef N, Dukes-McEwan J. Low plasma taurine levels in English cocker spaniels diagnosed with dilated cardiomyopathy. Journal of Small Animal Practice. 2021; 62: 570-579. doi: 10.1111/jsap.13306
43. Huxtable RJ. Physiological actions of taurine. Physiol Rev. 1992; 72: 101-163. doi: 10.1152/physrev.1992.72.1.101
44. Sanderson SL. Taurine and carnitine in canine cardiomyopathy. Vet Clin North Am Small Anim Pract. 2006; 36: 1325-1343, vii-viii.
doi: 10.1016/j.cvsm.2006.08.010
45. Keene B, Panciera D, Atkins C, Regitz V, Schmidt M, Shug A. Myocardial L-carnitine deficiency in a family of dogs with dilated cardiomyopathy. J Am Vet Med Assoc. 1991; 198: 647-650.
46. Neumann S, Welling H, Thuere S, Kaup FJ. Plasma L-carnitine concentration in healthy dogs and dogs with hepatopathy. Vet Clin Pathol. 2007; 36: 137-140. doi: 10.1111/j.1939-165x.2007.tb00199.x
47. Rizos I. Three-year survival of patients with heart failure caused by dilated cardiomyopathy and L-carnitine administration. Am Heart J. 2000; 139: S120-S123. doi: 10.1067/mhj.2000.103917
10.17140/CTPOJ-7-125
10.17140/EPOJ-8-131
10.17140/UAOJ-7-147
© 2014-2024 I Openventio Publisher is licensed by Creative Commons Attribution, unless otherwise indicated.
