Diet and canine dilated cardiomyopathy

Introduction

Dilated cardiomyopathy (DCM) is an idiopathic functional abnormality of the myocardium causing left ventricular systolic dysfunction, cardiac chamber dilation and/or ventricular tachyarrhythmias. Definitive breed predispositions exist for the Doberman Pinscher, Great Dane, Standard Schnauzer and Irish Wolfhound, where a pattern of inheritance and/or genetic mutations are described (Figure 1). As in cats, diet-associated DCM in dogs is also well-described, with clusters of cases being reported in the 1990s and into the first decade of this century; these were mainly characterized by taurine deficiency and were linked to diets low in protein or that contained lamb and/or rice 1,2,3. Several studies at that time investigated possible risk factors, which primarily appeared to negatively impact the dog’s ability to synthesize adequate taurine to meet its metabolic needs 4,5,6.

After resulting modifications to various commercial diets, including those formulated to be lower in protein for management of specific diseases, diagnosis of DCM in dogs of non-genetically predisposed breeds apparently occurred only occasionally until late 2016, when clinicians began noticing more cases. The United States Food and Drug Administration (FDA) announced an investigation into the potential connection between diet and canine DCM in July 2018 and this was followed by updates in February and June 2019. The most recent update in September 2020 included over 1,100 reports of canine DCM suspected to be related to diet, in particular those marketed as grain-free and especially with diets containing legumes such as lentils and peas. This report also included detailed follow-up on a subset of the affected dogs, which showed that dietary change, most often together with taurine supplementation, resulted in complete or partial disease reversal 7.

Unsubstantiated claims that grains cause allergies and other negative health outcomes in dogs and cats have contributed to the popularity of grain-free pet foods. However, there is no evidence of an inherent safety risk of grains for pets, nor any medical or nutritional indication for grain-free diets per se. Descriptive and investigative research by multiple groups is ongoing or published, although the role of specific dietary characteristics in diet-associated DCM linked to grain-free foods remains unclear.

Clinical findings and diagnostic guidelines

While DCM can be occult (asymptomatic), clinical signs may include coughing, dyspnea, tachypnea, syncope, and occasionally ascites. A soft systolic murmur consistent with mitral valve regurgitation and/or a gallop sound (S₃) may be auscultated at the left apex. A tachyarrhythmia of sinus, supraventricular or ventricular origin may be noted. In some cases, a murmur or an arrhythmia may be the first sign of the occult form of the disease, and this should not be overlooked. Since primary valvular disease is relatively uncommon in young or middle-aged large breed dogs, and the detection of DCM before the development of congestive heart failure (CHF) may be beneficial in the long-term management of the case, identification of any new murmur, gallop, or tachyarrhythmia in suspect breeds may warrant a thorough cardiac work-up (Figure 2).

Many dogs with DCM have normal electrocardiograms (ECGs), but in some cases atrial and/or ventricular enlargement patterns (R > 3.0 mV Lead II for the left ventricle) may be noted. Chamber enlargement patterns in dogs are specific but not sensitive findings, as many DCM cases have relatively normal ECG complex measurements. Sinus tachycardia, atrial fibrillation or ventricular arrhythmias are common (Figure 3). In some cases, ventricular tachyarrhythmias can develop before any ventricular dilation or systolic dysfunction. Routine Holter monitoring may help detect these, and this technique has become a mainstay of the screening process for this disease, particularly in breeding populations.

If the disease is diagnosed in the early stages, radiographic findings may be subtle. Therefore, depending on the stage of the disease, thoracic radiographs can be within normal limits or may indicate atrial and ventricular enlargement (typically left) with or without pulmonary venous distension and pulmonary edema (Figure 4). Biatrial and biventricular enlargement may be noted in some cases. Echocardiography is not only the diagnostic test of choice for diagnosing canine DCM, it is also an important test for occult disease. Findings in the patient with overt disease should include left (and sometimes right) atrial and ventricular dilation and decreased systolic function.

Cardiac biomarkers are currently a major area of research for identification of occult heart disease. NT-proBNP is released when the ventricles are dilated, hypertrophic or subjected to increased wall stress or stretch, and concentrations of NT-proBNP are typically increased in dogs with CHF and can be used to help diagnose or exclude CHF in dogs with cough or dyspnea. NT-proBNP may also be helpful in the identification of occult disease, but the frequency of false positives is a concern. Additionally, cardiac troponin-I is a cardiac biomarker that, when elevated, is consistent with occult cardiomyopathy, and although this test is specific for DCM, it is not sensitive enough to identify all cases. Interestingly, a recent study involving four breeds of apparently healthy dogs showed that cardiac troponin-I was elevated in those eating diets labeled as grain-free when compared to those that were fed a grain-inclusive diet 8.

Potential risk factors for diet-associated DCM

Various factors, including taurine deficiency, are postulated to have a role in recent cases of diet-associated DCM. However, many cases do not have taurine assessments performed as part of the work-up, or when tested, are shown not to have low plasma and/or whole blood taurine concentrations. It should be noted that most clinical cases of diet-associated canine DCM are identified once cardiac dysfunction is apparent, which may or may not be accompanied by CHF, and sulfur amino acid metabolism – and in particular taurine kinetics – under those circumstances have not been characterized. The disconnect between the results of taurine status assessments and clinical changes in the cardiac muscle may also be due to other factors. For example, it should be recognized that taurine has long been used as a readily analyzed marker for sulfur amino acid adequacy and, indirectly, the adequacy of general methyl donor status. However, other markers or assessments may enable a more complete clinical picture. Additional research is necessary to investigate the possible role of taurine in canine DCM, as well as fully characterize the interrelationships of other potential factors or nutrients that likely influence this disease.

Certain dietary characteristics have been linked to many cases of canine DCM, and notably in relation to particular ingredients. Specific ingredients such as peas or lentils, which are commonly used in grain-free diets, appear to be largely over-represented. Several studies have identified grain-free diets as a risk factor in this disease, but the reason for these findings is unclear 8,9,10,11. Legumes are a source of starch as well as significant amounts of fiber and protein; however, they are limited in sulfur amino acids, and some contain anti-nutritional factors that negatively impact protein digestibility and amino acid bioavailability. Proper manufacturing processes, including adequate cooking times and temperatures, are expected to largely destroy such anti-nutritional factors, but these procedures must be well defined by the manufacturer for any particular ingredient combination. In addition, some amino acids (especially lysine, cysteine, and methionine) undergo non-enzymatic reactions during processing that can result in decreased bioavailability even without negative effects on global protein digestibility. In summary, many characteristics of pet food impact the overall dietary amino acid balance as well as the microbiome 12. These are all likely to influence availability and utilization of sulfur-containing metabolites, pathway intermediates, methyl donors such as choline, and enzyme co-factors such as vitamins.

Commercial pet foods and DCM risk

Without a complete understanding of the underlying mechanisms, it is difficult to define specific recommendations for product modifications that will help prevent canine diet-associated DCM. Many balanced pet food products have been successfully formulated over the years using a range of ingredients, including potatoes and legumes, to provide the necessary protein and starch. However, it is apparent that commercial foods must better address the diversity of the canine population, so that all diets meet the needs of the many dogs that are not “average” in terms of energy and nutrient requirements. In addition, in vivo testing is essential, since amino acid bioavailability cannot be estimated by chemical analysis of the food 13.

Many manufacturers have initiated taurine supplementation in grain-free dog diets, with the implication or even assertion that this strategy will prevent DCM. However, this masks the ability to assess for poor sulfur amino acid bioavailability or deficiency. Although it is not unreasonable to add taurine to some diets where the protein level is intentionally restricted (such as in some veterinary therapeutic diets), maintenance of taurine adequacy in dogs is probably most appropriately accomplished by increasing the concentration of bioavailable methionine and cysteine 14. The use of high-quality, digestible protein sources and/or supplementation with purified methionine is recommended, together with consideration for overall amino acid balance and adequate provision of methyl donors necessary for metabolism of sulfur amino acids 15.

Assessment of suspected cases

Individualized nutritional assessment is a critical aspect of management of any patient. Evaluation of the complete diet along with the medical history, patient status, and physical examination findings will inform diagnostic and therapeutic plans, including dietary options. Current and historical body weights, body condition scores, and muscle condition scores should all be taken into account.

Whole blood and plasma taurine concentrations should be measured in all dogs (and cats) with DCM, given that low concentrations are very good indicators of disease risk and of nutritional inadequacy, even if additional factors may also influence the development of the condition 16. Due to the high-taurine content of granulocytes and platelets, sample clotting or hemolysis can result in falsely increased plasma taurine concentrations; however, whole blood taurine concentration is not confounded by these sampling and handling effects. As such, when plasma taurine concentrations are low, a diagnosis of taurine deficiency can be made; however, whole blood taurine concentrations may be used to substantiate a diagnosis of taurine deficiency when plasma concentrations are normal or equivocal. In addition, whole blood taurine concentrations are only slightly altered after meal consumption, whereas the plasma concentration may change substantially depending on taurine status and the composition of the pre-sampling meal relative to the longer-term diet.

Management recommendations

A dietary change is recommended if it is suspected of playing a role in the development of heart disease, especially if there is a large discrepancy between the predicted and actual calorie requirement. Notably, the FDA report from 2020 described disease resolution or improvement with diet change, and two recent studies have shown that dogs fed grain-free or non-traditional diets when diagnosed with DCM have prolonged survival times and improvement of heart function once a diet change is instituted as part of therapy 9,11. For owners that wish to discontinue commercial pet food entirely, it is recommended to pursue the formulation of a customized home-cooked diet recipe through consultation with a board-certified veterinary nutritionist. Internet or book recipes are not advised due to documented problems with adequacy and outdated strategies for disease management.

In the United States, any suspected diet-associated cases of dilated cardiomyopathy (regardless of diet history) should be reported to the FDA. For Doberman Pinschers, genetic testing is available (through North Carolina State University and other establishments) which may help elucidate the etiology, but it should be remembered that more than one cause in an individual dog is possible.

Administration of angiotensin converting enzyme (ACE) inhibitors may be beneficial for the dog with early ventricular dilation, with or without systolic dysfunction. A major study in Doberman Pinschers with ventricular dilation showed that this drug prolongs the time period before the onset of CHF 17. Although this study was limited to evaluation of one breed, the use of ACE inhibitors (e.g., enalapril at 0.5 mg/kg PO q12H) for other breeds with occult DCM may be considered. The same study also showed that once a certain level of heart enlargement and systolic dysfunction is reached, Doberman Pinschers benefit from oral pimobendan therapy (~0.3 mg/kg PO q12H) which prolongs the time to onset of CHF 17. Pimobendan is an inodilator drug that exerts its action through phosphodiesterase III inhibition and calcium sensitization. In the authors’ practice, all dogs with occult cardiomyopathy receive both pimobendan and an ACE-inhibitor, with or without dietary change and taurine supplementation depending on breed, blood taurine levels, and diet history. Therapy for dogs with DCM and CHF is expanded to add furosemide (and often spironolactone) on top of the existing pimobendan and ACE-inhibitor treatment, with the treatment regime being frequently modified to address ventricular arrhythmias or atrial fibrillation as needed.

Taurine supplementation is safe and is specifically indicated in cases with confirmed deficiency (500-1500 mg per dog q12H). Carnitine supplementation can also be considered (50 mg/kg q8H), but the indication and benefits are difficult to assess, and it can be costly. Additionally, omega-3 fatty acids may be beneficial in cardiac disease, with a suggested total dose of 125 mg EPA+DHA/kg^0.75/day. Note that, when calculating the total intake, the clinician should consider the fatty acid contributions from all sources, including the base diet and any supplements.

Many dogs with diet-associated DCM improve with appropriate therapy including diet change and nutritional supplementation, and in some cases the improvement can be quite significant, including reversal of CHF and even successful withdrawal of medications. This degree of reversibility is similar to that seen in cats, and is one defining feature of diet-associated (compared to hereditary) canine DCM.

Conclusion

Although the possible links between diet and canine dilated cardiomyopathy (DCM) are currently far from clear, there is ample evidence to support that certain nutritional factors influence the disease. Any animal presenting with a heart murmur, gallop, or tachyarrhythmia should undergo a thorough cardiac work-up, including a detailed diet history and whole blood taurine measurements. Early intervention in dogs found to have DCM using appropriate therapy and – where indicated – dietary changes can have a significant effect on the outcome of such cases.