Review of canine dilated cardiomyopathy in the wake of diet-associated concerns
Abstract
Dilated cardiomyopathy (DCM) has been in the literature and news because of the recent opinion-based journal articles and public releases by regulatory agencies. DCM is commonly associated with a genetic predisposition in certain dog breeds and can also occur secondary to other diseases and nutritional deficiencies. Recent communications in veterinary journals have discussed a potential relationship between grain-free and/or novel protein diets to DCM, citing a subjective increase in DCM in dog breeds that are not known to have a genetic predisposition for the disease. This literature review describes clinical presentations of DCM, common sequelae, treatment and preventative measures, histopathologic features, and a discussion of the varied etiological origins of the disease. In addition, current literature limitations are addressed, in order to ascertain multiple variables leading to the development of DCM. Future studies are needed to evaluate one variable at a time and to minimize confounding variables and speculation. Furthermore, to prevent sampling bias with the current FDA reports, the veterinary community should be asked to provide information for all cases of DCM in dogs. This should include cases during the same time period, regardless of the practitioner’s proposed etiology, due to no definitive association between diets with specific characteristics, such as, but not limited to, grain-free diets and those containing legumes, novel protein diets, and those produced by small manufacturers to DCM in dogs. In summary, in order to determine if certain ingredients, categories of diets, or manufacturing processes are related to an increased risk of DCM, further studies investigating these variables are necessary.
Introduction
Historically, dilated cardiomyopathy (DCM) has been considered to be primarily an inherited disease, with higher prevalence in specific dog breeds (Dukes-McEwan et al., 2003; Sammarco, 2008). However, other causes of DCM include specific nutrient deficiencies (Freeman et al., 2001; Backus et al., 2003) and concurrent diseases, such as endocrine (Karlapudi et al., 2012; Janus et al., 2014), myocarditis, and chronic tachycardia (Calvert et al., 1997). Recently, there has been concern regarding the relationship of diets with specific characteristics, such as, but not limited to, grain-free diets and those containing legumes, novel protein diets, and those produced by small manufacturers to DCM in dogs (Freeman et al., 2018); however, no definitive link has been established at this time.
In order to better understand the disease process, a knowledge of the incidence, clinical manifestations, diagnostics, and potential treatments is required. Research studies must be carried out evaluating one variable at a time, while mitigating sampling bias of data collected, to effectively identify potential new causes of DCM (Simundić, 2013). Additionally, robust statistical designs that look at the effect of single dietary components, in controlled environments, with robust outcomes related to metabolism will allow for an understanding of potential disease etiology. This review covers the various etiologies known to cause DCM in dogs, including genetics, hypothyroidism, myocarditis, chronic tachycardia, and certain known dietary deficiencies (Phillips and Harkin, 2003; Sanderson, 2006; Wess et al., 2010b; Beier et al., 2015; Hallman et al., 2019; Vollmar et al., 2019). It also includes other potential diet-associated etiologies that have been recently suggested (Santilli et al., 2017).
Incidence
Information regarding the incidence of DCM in the dog population is limited. Up to 75% of all cardiovascular disease in the dog is chronic degenerative valve disease (Kvart and Häggström, 2000; Kahn, 2005). The second most common heart disease (and most common primary myocardial disease) in the dog is reported to be DCM. According to the Veterinary Medical Database (Sisson et al., 2000) from 1986 to 1991, 0.5% of the dogs evaluated at U.S. referral-hospitals were diagnosed with DCM. Moreover, a U.S. veterinary teaching hospital study that included all dogs evaluated in that hospital between 1995 and 2010 (90,004) reported a DCM incidence rate of 0.4%. Interestingly, a subset of dogs from the same study that only included dogs with an inherited disease (27,254 cases) observed an incidence rate of 1.3% in this specific group (Bellumori et al., 2013). In a European study, 1.1% of the dog population seen at veterinary hospitals were diagnosed with DCM (Fioretti and Delli, 1988). It can be hypothesized that the occurrence of DCM may be different in the general dog population since dogs presented to veterinary hospitals (including referral institutions) are only a subset and may not be representative of the overall dog population (Redfield et al., 1993). If one considers the estimated total number of dogs in the United States equals 77,000,000 (AVMA, 2019), the published incidence studies (Fioretti and Delli, 1988; Sisson et al., 2000) suggest that a minimum of 308,000 to 1,001,000 dogs in the United States have DCM at any given time. In June 2019, the Food and Drug Administration (FDA) released a public statement that 560 dogs were reported with potential diet-related DCM (FDA, 2019a). If the report was accurate, these 560 cases would represent 0.05% to 0.1% of dogs in the United States with DCM.
DCM has historically been an inherited, genetically linked condition. Published surveys, in North America, reported a higher incidence of DCM in Doberman Pinschers, Irish Wolfhounds, Great Danes, Boxers, and American Cocker Spaniels (Dukes-McEwan et al., 2003). Other breeds, such as Bulldogs (Meurs, 2003), Golden Retrievers, and Saint Bernards, have also been reported to have a higher incidence of DCM (Backus et al., 2003, 2006; Fascetti et al., 2003; Belanger et al., 2005; Vollmar et al., 2013). Additionally, European sources reported a higher incidence in Airedale Terriers, Doberman Pinschers, Newfoundlands, Scottish Deerhounds, and English Cocker Spaniels (Meurs, 2010). Typically, DCM in dogs is more prevalent in males than in females (Oyama, 2015). More specifically, Doberman Pinschers have a reported incidence rate of 50% in males and 33% in females (Oyama, 2015), while Irish Wolfhounds have an overall breed incidence of 25%. DCM is also a disease of middle aged to older dogs (Oyama, 2015); there are cases of juvenile DCM reported in Portuguese Water Dog puppies (Sleeper et al., 2002).
The incidence of DCM resulting from other disease states (hypothyroid disease, myocarditis, chronic tachycardia) is poorly understood. DCM related to low taurine levels has been noted in Cocker Spaniels (Kittleson et al., 1997; Egenvall et al., 2006), Golden Retrievers (Belanger et al., 2005; Kaplan et al., 2018), and foxes (Moise et al., 1991), though the incidence is unknown.
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