Canine Dilated Cardiomyopathy Research Articles

Diet-Mediated Dilated Cardiomyopathy in the Canine

Dilated cardiomyopathy (DCM) is a disease of the heart muscle resulting in decreased myocardial function and is the second most common myopathy in canine. Previously, canine dilated cardiomyopathy was considered to be an inherited disease among large and giant breeds, however, recent reports suggest a possible link between certain grain-free diets and this condition. Several investigations into the incidence of this condition in relationship to grain-free diet consumption have been conducted in recent years. The most recent research shows a static overall trend in the incidence of DCM despite a five-fold increase in the sales of grain-free pet foods. Inadequate intake of protein, taurine, and specific sulfur-containing amino acids may have a potential role in the development of DCM, as these nutrients are crucial for cardiac muscle development and function. However, significant research remains to be done on the topic to discern any potential definitive causation.

Oligosaccharides and diet-related dilated cardiomyopathy in beagles.

In 2018 the US Food and Drug Administration reported a potential link between grain-free, legume-containing dog foods and the development of canine dilated cardiomyopathy in atypical breeds. One hypothesis was that high oligosaccharide content in legumes reduced bioavailability of taurine, an amino acid with some previous links to canine dilated cardiomyopathy. To address this hypothesis, in the present study, 8 Beagle dogs consumed four diets: a husbandry commercial dental diet, and three test diets formulated with either 30% rice (control), 30% pea (grain-free) or 30% rice with the addition of 1% raffinose (the predominant oligosaccharide found in peas). The study was conducted in a randomized, crossover design with 5 week feeding periods. Measurement of basic health parameters (weight, body condition score, complete blood cell count, chemistry panel), plasma amino acids, cardiac biomarkers (plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac-specific troponin I), fecal bile acids and echocardiographic exams were completed pre-study after feeding the husbandry diet as well as after each test feeding period. Echocardiography showed 9-11% reduction in ejection fraction and 17- 20% greater left ventricular end systolic volume with the husbandry diet compared to both grain-containing test diets. Concentrations of plasma NT-proBNP were 1.3-2 times greater after the husbandry diet compared to the grain-based diet, with the oligosaccharide and pea-based diets showing intermediate levels. Plasma taurine levels were unchanged across diets, while plasma methionine levels were highest and cysteine/cystine levels were lowest after dogs ate the husbandry diet. Results indicate that raffinose in the diet is sufficient, but not required to see an increase NT-proBNP, but did not induce any changes in cardiac function after 5 weeks of feeding. Whether this could progress to reduction in cardiac function with longer term feeding is uncertain. A reduced cardiac function along with the greatest increase in NT-proBNP was observed after feeding the husbandry diet that contained the highest amount of insoluble fiber but did not contain legumes or oligosaccharide. Further research into the impact of insoluble fiber in the dental diet is needed to support these novel observations.

Effects of a 28-day feeding trial of grain-containing versus pulse-based diets on cardiac function, taurine levels and digestibility in domestic dogs.

In 2018, the US Food and Drug Administration reported a link between canine dilated cardiomyopathy (DCM) and grain-free diets. Evidence to support a link has emerged, but the specific ingredients responsible and the role of taurine or other causative factors remain unclear. We hypothesized dogs fed pulse-based, grain-free diets for 28 days will show decreased macronutrient digestibility, increased fecal bile acid excretion, and reduced plasma cystine, cysteine, methionine and taurine, causing sub-clinical cardiac or blood changes indicative of early DCM. Three diets were formulated using white rice flour (grain), whole lentil (grain-free), or wrinkled pea (grain-free) and compared to the pre-trial phase on a commercial grain-based diet. After 28 days of feeding each diet, the wrinkled pea diet impaired stroke volume and cardiac output, increased end-systolic ventricular diameter and increased plasma N-Terminal Pro-B-type Natriuretic Peptide (NT-ProBNP), albeit in a sub-clinical manner. Digestibility of some macronutrients and sulphur-containing amino acids, excluding taurine, also decreased with pulse-based compared to grain-based diets, likely due to higher fiber levels. Plasma taurine levels were unchanged; however, plasma methionine was significantly lower after feeding all test diets compared to the commercial diet. Overall, DCM-like changes observed with the wrinkled pea diet, but not lentil diet, after only 4 weeks in a breed not known to be susceptible support a link between pea-based diets and canine nutritionally-mediated DCM.

Canine Dilated Cardiomyopathy Secondary to Hypothyroidism: Review of 3 Clinical Cases

Canine dilated cardiomyopathy is characterized by ventricular systolic dysfunction with eccentric hypertrophy. Can be primary or secondary to other disorders such as hypothyroidism. Different cardiac changes, due to the inotropic and chronotropic alterations, can appear in these patients. Mainly affecting the left ventricle, although both ventricles may be affected. Electrocardiographic alterations may appear, as in the cases described, needing different therapeutic strategies for its control. Many times, we are able to achieve a complete resolution of the cardiac alterations once the hypothyroidism is stabilized, but this is not always possible, leaving permanent alterations.

Genetic Basis of Dilated Cardiomyopathy in Dogs and Its Potential as a Bidirectional Model.

Simple SummaryHeart disease is a leading cause of death for both humans and dogs. Inherited heart diseases, including dilated cardiomyopathy (DCM), account for a proportion of these cases. Human and canine patients with DCM suffer from an enlarged heart that can no longer pump efficiently, resulting in heart failure. This causes symptoms or clinical signs like difficulty breathing, irregular heartbeat, and eventually death. The symptoms or clinical signs of this disease vary in age of onset at the beginning of symptoms, sex predisposition, and overall disease progression. Despite the many similarities in DCM in both species, only a few candidate genes so far have been linked to this disease in dogs versus tens of genes identified in human DCM. Additionally, the use of induced pluripotent stem cells, or engineered stem cells, has been widely used in the study of human genetic heart disease but has not yet been fully adapted to study heart disease in dogs. This review describes the current knowledge on the genetics and subtypes of naturally occurring DCM in dogs, and how advances in research might benefit the dog but also the human patient. Additionally, a novel method using canine engineered stem cells to uncover unknown contributions of mistakes in DNA to the progression of DCM will be introduced along with its applications for human DCM disease modeling and treatment.Cardiac disease is a leading cause of death for both humans and dogs. Genetic cardiomyopathies, including dilated cardiomyopathy (DCM), account for a proportion of these cases in both species. Patients may suffer from ventricular enlargement and systolic dysfunction resulting in congestive heart failure and ventricular arrhythmias with high risk for sudden cardiac death. Although canine DCM has similar disease progression and subtypes as in humans, only a few candidate genes have been found to be associated with DCM while the genetic background of human DCM has been more thoroughly studied. Additionally, experimental disease models using induced pluripotent stem cells have been widely adopted in the study of human genetic cardiomyopathy but have not yet been fully adapted for the in-depth study of canine genetic cardiomyopathies. The clinical presentation of DCM is extremely heterogeneous for both species with differences occurring based on sex predisposition, age of onset, and the rate of disease progression. Both genetic predisposition and environmental factors play a role in disease development which are identical in dogs and humans in contrast to other experimental animals. Interestingly, different dog breeds have been shown to develop distinct DCM phenotypes, and this presents a unique opportunity for modeling as there are multiple breed-specific models for DCM with less genetic variance than human DCM. A better understanding of DCM in dogs has the potential for improved selection for breeding and could lead to better overall care and treatment for human and canine DCM patients. At the same time, progress in research made for human DCM can have a positive impact on the care given to dogs affected by DCM. Therefore, this review will analyze the feasibility of canines as a naturally occurring bidirectional disease model for DCM in both species. The histopathology of the myocardium in canine DCM will be evaluated in three different breeds compared to control tissue, and the known genetics that contributes to both canine and human DCM will be summarized. Lastly, the prospect of canine iPSCs as a novel method to uncover the contributions of genetic variants to the pathogenesis of canine DCM will be introduced along with the applications for disease modeling and treatment.

Dilatated Cardiomyopathy In Two Month Old Puppy

Background: Canine dilated cardiomyopathy (DCM) is a disease that results in a decreased ability of the cardiac contraction to generate pressure to pump blood through the vascular system. DCM is characterized by dilation of the ventricles with ventricular wall thinning. Purpose: The DCM case in Indonesia is rarely reported; therefore, this paper contains information about dilatated cardiomyopathy in a 2-month-old puppy. Case Analyze: A two-month-old local dog arrived with a complaint about coughing, loss of appetite, fatigue, and swelling on extremities, also having a history of seizures and bloody diarrhea. Physical examination shows that the patient breathes using abdominal type and polypnea, tachycardia pulse, pale mucose, and dehydration. Electrocardiogram result shows tachycardia sinus and abnormality in the depression of ST-segment. Radiography examination shows heart dilation and liquid accumulation in the thoracic cavity and abdomen. Hematology routine examination shows microcytic hyperchromic anemia, leucocytosis, and eosinophilia. Feces examination resulted in negative. Pathology anatomy examination show dilatated cardio, pulmonum hepatization, fluid accumulation in the thoracic cavity and abdomen cavity. Result: According to anamnesis, clinical examination, laboratory examination, and anatomy pathology examination can be concluded that the dog, in this case, is diagnosed with dilatated cardiomyopathy.

119 Awardee Talk: A Matter of the Heart: The Use of Pulses in Canine and Feline Nutrition

Abstract In the pet food industry, the popularity of plant-based protein sources has risen as consumer demand for grain-free and novel protein sources increase. However, minimal research has been conducted as regards use of pulses and their effects on acceptability and digestibility in canine and feline nutrition. In addition, market shift towards grain-free and pulse-rich diets has presented concerns about the suitability of pulses as viable protein sources. In July 2018, the FDA published a press release discussing a potential link between diets containing legumes and the development of dilated cardiomyopathy (DCM) in dogs. As such, part of our research program has focused on the 1) characterization of the macronutrient composition and protein quality of plant-based protein sources, 2) evaluation of the effects of plant-based protein sources in extruded canine and feline diets on macronutrient digestibility, and modulation of fecal microbiota and metabolites, and 3) determination of the longitudinal effects of high pulse inclusion in diets on taurine status in dogs. Pulse ingredients contained approximately 20% crude protein, and had methionine or tryptophan as the first-limiting amino acids using the precision-fed cecectomized rooster assay. When incorporated in canine and feline diets, pulses did not result in negative effects on macronutrient digestibility or fecal scores. However, shifts in fecal microbial and metabolites were observed in animals fed pulse-based in contrast with animal-based protein diets. The inclusion of 45% green lentils in extruded diets did not cause decreased plasma or whole blood taurine or methionine levels. Additionally, excess taurine was not depleted from these animals in the urine or feces. Taurine status was considered normal in these dogs, despite changes in fecal bile acid concentrations and microbiota. Although we are currently carrying out further research projects investigating potential association of pulse rich diets and canine DCM. Current research findings from our laboratory suggest the inclusion of pulses may not be the causative factor. The use of plant-based proteins as ingredients in canine and feline diets not only meet consumer demand but also provide a valuable, safe, and nutritionally adequate alternative to traditional protein sources.

Echocardiographic assessment of dilated cardiomyopathy in dogs

Dilated cardiomyopathy (DCM) is a frequent cause of cardiac disability, congestive heart failure (CHF), and arrhythmic death in dogs. The etiology of DCM is usually idiopathic/genetic, but some causes of a DCM phenotype are reversible. The disease is classified into preclinical (occult) and clinical (overt) stages; the latter stems from heart failure with reduced ejection fraction. DCM is further characterized by clinical, electrocardiographic, circulating biomarker, and imaging abnormalities. The diagnosis of clinical DCM with CHF is straightforward; however, identification of the preclinical stage can be challenging. Echocardiography is central to the diagnosis of both stages and characterized by left ventricular (LV) systolic dysfunction with progressive chamber dilation and variable enlargements of the left atrium and right-sided chambers. Left ventricular dilation is defined by increased LV end-diastolic volumes, areas, and internal dimensions normalized to body size or indexed to the aorta. Systolic dysfunction is characterized by decreased LV ejection fraction, increased end-systolic volume, and reduced shortening across minor and longitudinal LV axes. Dyssynchrony can confound the interpretation of linear indices of systolic function. A comprehensive echocardiogram in DCM includes two-dimensional and M-mode studies, spectral and tissue Doppler imaging, and potentially three-dimensional echocardiography and myocardial strain imaging. Echocardiographic findings should be interpreted within the context of identifiable risks and comorbidities, physical diagnosis, complementary diagnostic testing, and limitations of current reference intervals. Ambiguous examinations should be repeated. Specific echocardiographic criteria for the diagnosis of DCM are proposed to encourage discussion and additional outcome and breed-specific echocardiographic studies of canine DCM.

Investigation of diets associated with dilated cardiomyopathy in dogs using foodomics analysis

Dilated cardiomyopathy (DCM) is a disease of the heart muscle that affects both humans and dogs. Certain canine diets have been associated with DCM, but the diet-disease link is unexplained, and novel methods are needed to elucidate mechanisms. We conducted metabolomic profiling of 9 diets associated with canine DCM, containing ≥ 3 pulses, potatoes, or sweet potatoes as main ingredients, and in the top 16 dog diet brands most frequently associated with canine DCM cases reported to the FDA (3P/FDA diets), and 9 non-3P/FDA diets. We identified 88 named biochemical compounds that were higher in 3P/FDA diets and 23 named compounds that were lower in 3P/FDA diets. Amino acids, amino acid-derived compounds, and xenobiotics/plant compounds were the largest categories of biochemicals that were higher in 3P/FDA diets. Random forest analyses identified the top 30 compounds that distinguished the two diet groups with 100% predictive accuracy. Four diet ingredients distinguished the two diet groups (peas, lentils, chicken/turkey, and rice). Of these ingredients, peas showed the greatest association with higher concentrations of compounds in 3P/FDA diets. Moreover, the current foodomics analyses highlight relationships between diet and DCM in dogs that can identify possible etiologies for understanding diet-disease relationships in dogs and humans.

Diet associated canine dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a common cause of heart failure in the dog. Primary DCM is often a disease of exclusion, but inherited genetic breed dispositions have been reported. Secondary causes of DCM include toxins, nutritional deficiency, systemic and infectious disease. The number of dogs diagnosed with DCM has increased significantly in the last 20 years, and has been linked to the rise in popularity of boutique, exotic and grain-free, legume-rich diets. Veterinary cardiologists raised concerns as DCM was being reported in atypical breeds. Subsequently, the United States Food and Drug Agency released a statement in 2018 warning pet owners of the risks of grain-free and novel protein diets. It is assumed that the problem also occurs in the UK because these diets are popular here also. Contrary to primary causes of DCM, dogs have improved clinically and on echocardiograph when their diet has been changed and/or supplemented. No clear cause has yet been identified between these diets and DCM, but the potential reasons seem to be multifactorial and limited by a lack of understanding of the bioavailability, digestibility and metabolism of the novel proteins and legume-rich diets.

Corrigendum to: Review of canine dilated cardiomyopathy in the wake of diet-associated concerns.

Corrigendum to: Review of canine dilated cardiomyopathy in the wake of diet-associated concerns.

A commercial grain-free diet does not decrease plasma amino acids and taurine status but increases bile acid excretion when fed to Labrador Retrievers.

Grain-free diets tend to have greater inclusions of pulses in contrast to grain-based diets. In 2018, the Food and Drug Administration (FDA) released a statement that grain-free diets may be related to the development of canine dilated cardiomyopathy (DCM). However, all dog foods met regulatory minimums for nutrient inclusion recommended by the Association of American Feed Controls Official. In some FDA case reports, but not all, dogs diagnosed with DCM also had low concentrations of plasma or whole blood taurine; thus, we hypothesized that feeding these diets will result in reduced taurine status from baseline measures. The objective of this study was to determine the effects of feeding a grain-free diet to large-breed dogs on taurine status and overall health. Eight Labrador Retrievers (four males and four females; Four Rivers Kennel, MO) were individually housed and fed a commercial complete and balanced grain-free diet (Acana Pork and Squash formula; APS) for 26 wk. Fasted blood samples were collected prior to the start of the trial (baseline; week 0) and at weeks 13 and 26 for analyses of blood chemistry, hematology, plasma amino acids, and whole blood taurine. Urine was collected by free catch at weeks 0 and 26 for taurine and creatinine analyses. Fresh fecal samples were collected at weeks 0 and 26 for bile acid analyses. Data were analyzed using the GLIMMIX procedure with repeated measures in SAS (v. 9.4). Plasma His, Met, Trp, and taurine and whole blood taurine concentrations increased over the course of the study (P < 0.05). Urinary taurine to creatinine ratio was not affected by diet (P > 0.05). Fecal bile acid excretion increased after 26 wk of feeding APS to dogs. Despite the higher fecal excretion of bile acids, plasma and whole blood taurine increased over the 26-wk feeding study. These data suggest that feeding APS, a grain-free diet, over a 26-wk period improved taurine status in Labrador Retrievers and is not the basis for the incidence of DCM for dogs fed APS. Other factors that may contribute to the etiology of DCM should be explored.

Review of canine dilated cardiomyopathy in the wake of diet-associated concerns.

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.

Canine Dilated Cardiomyopathy: Diffuse Remodeling, Focal Lesions, and the Involvement of Macrophages and New Vessel Formation.

Dilated cardiomyopathy (DCM) is among the most common cardiac diseases in dogs. Its pathogenesis is not fully understood, but myocardial remodeling and inflammation are suspected to be involved. The present study aimed to characterize the pathological processes in canine DCM, investigating morphological changes in association with the expression of relevant cytokines and remodeling markers. The myocardium of 17 dogs with DCM and 6 dogs without cardiac diseases was histologically evaluated, and selected cases were further examined by immunohistochemistry, morphometry, and reverse transcription quantitative PCR. In DCM, the myocardium exhibited subtle but statistically significant diffuse quantitative changes. These comprised increased interstitial collagen deposition and macrophage numbers, as well as an overall reduced proportion of contractile tissue. This was accompanied by a significant increase in myocardial transcription of intracellular adhesion molecule (ICAM) 1, inflammatory cytokines, and remodeling enzymes. Laser microdissection showed that cardiomyocytes transcribed most relevant markers including ICAM-1, tumor necrosis factor α, transforming growth factor β (TGF-β), matrix metalloproteinase 2 (MMP-2), tissue inhibitor of MMP (TIMP) 1 and TIMP-2. In addition, there were multifocal cell-rich lesions characterized by fibrosis, neovascularization, macrophage infiltration, and cardiomyocyte degeneration. In these, macrophages were often found to express ICAM-1, TGF-β, and vascular endothelial growth factor; the former two were also expressed by cardiomyocytes. These results characterize the diffuse myocardial remodeling processes that occur in DCM. The observed multifocal cell-rich lesions might result from reduced tissue perfusion. Macrophages and cardiomyocytes seem to actively contribute to the remodeling processes, which ultimately lead to cardiac dilation and dysfunction. The precise role of the involved cells and the factors initiating the remodeling process still needs to be identified.

242 Effects of different carbohydrate sources on taurine status in healthy Beagle dogs

Abstract Consumption of grain-free (GF) diets has recently been linked to canine dilated cardiomyopathy in selected dog breeds. Soluble fiber present in GF carbohydrate sources may be contributing to taurine depletion, thus affecting heart health. The objective of this study was to evaluate the effects of different carbohydrate sources on taurine status in healthy Beagle dogs. Two practical diets sufficient in sulfur-amino acids and taurine were formulated with the same proportion of carbohydrate sources: a grain-based (GB) containing sorghum, millet, and spelt, and a GF containing peas, potatoes and tapioca starch. Twelve Beagle dogs were fed experimental diets for 4-wk in a randomized complete block design. The morning prior to feeding experimental diets (baseline) and two and four weeks after, markers of taurine metabolism were analyzed in blood, urine, and fresh fecal samples. Data were analyzed as a change from baseline in a repeated measures model by GLIMMIX (SAS, version 9.4) in which the main effects of time, diet, and their interaction were evaluated. Greater concentrations of taurine in plasma (158 vs. 117 nmol/mL) and whole blood (254 vs. 234 nmol/mL) were observed during experimental period compared to baseline. An increase in plasma methionine was also observed during experimental period compared to baseline (64 vs. 57nmol/mL). Dogs fed GF exhibited higher plasma taurine concentration compared to those fed GB (181 vs. 138 nmol/mL). There were no significant effects of diet, time, or their interaction on plasma cystine concentration, urinary taurine:creatinine ratio, or total fecal bile acid (BA) excretion (P &amp;gt; 0.05). However, dogs fed GF had greater fecal primary BA (26 vs 14%) as a proportion of total BA compared to those fed GB. This study suggests that GF diets do not impair taurine blood concentration, but the increased proportion of fecal primary BA may decrease recycling of taurine through enterohepatic circulation.

Diagnostic methods for the canine idiopathic dilated cardiomyopathy: A narrative evidence-based rapid review

Idiopathic dilated cardiomyopathy (DCM) is an important etiology of mortality and morbidity in dogs and its diagnosis relies on systolic dysfunction, chambers dilation, electrical instability and congestion. During the last decades veterinary cardiologists have been joining efforts to obtain diagnostic resources to correctly identify canine DCM in the preclinical stage. Unfortunately, most diagnostic resources have been used with the support of research with weak evidence, without high quality methodologies such as systematic reviews or meta-analysis. Therefore, the support of evidence-based medicine is tailored by empiricism and diagnostic criteria lose'out the ability to properly classify dogs suffering DCM. The presentation of the evidence in medicine is established by multiple sources and the most reliable source has been the presentation of evidence-based medicine from systematic reviews and meta-analysis. Rapid reviews can be interpreted as a pragmatic approach to systematic reviews and although a rapid review follows most of the critical steps of a systematic review to provide timely evidence, some components of a systematic review process are either simplified or omitted. The objective of this narrative evidence-based rapid review is twofold. First: To recognize and to stratify the level of evidence offered by rigorous selected papers about the diagnosis of DCM. Second: To classify the degree of clinical recommendation of the diagnostic resources available.

Intracoronary Gene Delivery of the Cytoprotective Factor Vascular Endothelial Growth Factor-B167 in Canine Patients with Dilated Cardiomyopathy: A Short-Term Feasibility Study.

Dilated cardiomyopathy (DCM) is a myocardial disease of dogs and humans characterized by progressive ventricular dilation and depressed contractility and it is a frequent cause of heart failure. Conventional pharmacological therapy cannot reverse the progression of the disease and, in humans, cardiac transplantation remains the only option during the final stages of heart failure. Cytoprotective gene therapy with vascular endothelial growth factor-B167 (VEGF-B167) has proved an effective alternative therapy, halting the progression of the disease in experimental studies on dogs. The aim of this work was to test the tolerability and feasibility of intracoronary administration, under fluoroscopic guidance, of VEGF-B167 carried by adeno-associated viral vectors in canine DCM patients. Ten patients underwent the gene delivery procedure. The intraoperative phase was well tolerated by all dogs. Clinical and echocardiographic assessments at 7- and 30-days post-procedure showed stable conditions compared to the pre-procedure phase. The results of this work indicate that intracoronary VEGF-B167 gene delivery is feasible and tolerated in dogs with DCM. Further monitoring/investigations are ongoing to evaluate the effects of this therapy on disease progression.

A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death.

The dog provides a large animal model of familial dilated cardiomyopathy for the study of important aspects of this common familial cardiovascular disease. We have previously demonstrated a form of canine dilated cardiomyopathy in the Doberman pinscher breed that is inherited as an autosomal dominant trait and is associated with a splice site variant in the pyruvate dehydrogenase kinase 4 (PDK4) gene, however, genetic heterogeneity exists in this species as well and not all affected dogs have the PDK4 variant. Whole genome sequencing of a family of Doberman pinchers with dilated cardiomyopathy and sudden cardiac death without the PDK4 variant was performed. A pathologic missense variant in the titin gene located in an immunoglobulin-like domain in the I-band spanning region of the molecule was identified and was highly associated with the disease (p < 0.0001). We demonstrate here the identification of a variant in the titin gene highly associated with the disease in this spontaneous canine model of dilated cardiomyopathy. This large animal model of familial dilated cardiomyopathy shares many similarities with the human disease including mode of inheritance, clinical presentation, genetic heterogeneity and a pathologic variant in the titin gene. The dog is an excellent model to improve our understanding of the genotypic phenotypic relationships, penetrance, expression and the pathophysiology of variants in the titin gene.

Special topic: The association between pulse ingredients and canine dilated cardiomyopathy: addressing the knowledge gaps before establishing causation.

In July 2018, the Food and Drug Administration warned about a possible relationship between dilated cardiomyopathy (DCM) in dogs and the consumption of dog food formulated with potatoes and pulse ingredients. This issue may impede utilization of pulse ingredients in dog food or consideration of alternative proteins. Pulse ingredients have been used in the pet food industry for over 2 decades and represent a valuable source of protein to compliment animal-based ingredients. Moreover, individual ingredients used in commercial foods do not represent the final nutrient concentration of the complete diet. Thus, nutritionists formulating dog food must balance complementary ingredients to fulfill the animal’s nutrient needs in the final diet. There are multiple factors that should be considered, including differences in nutrient digestibility and overall bioavailability, the fermentability and quantity of fiber, and interactions among food constituents that can increase the risk of DCM development. Taurine is a dispensable amino acid that has been linked to DCM in dogs. As such, adequate supply of taurine and/or precursors for taurine synthesis plays an important role in preventing DCM. However, requirements of amino acids in dogs are not well investigated and are presented in total dietary content basis which does not account for bioavailability or digestibility. Similarly, any nutrient (e.g., soluble and fermentable fiber) or physiological condition (e.g., size of the dog, sex, and age) that increases the requirement for taurine will also augment the possibility for DCM development. Dog food formulators should have a deep knowledge of processing methodologies and nutrient interactions beyond meeting the Association of American Feed Control Officials nutrient profiles and should not carelessly follow unsubstantiated market trends. Vegetable ingredients, including pulses, are nutritious and can be used in combination with complementary ingredients to meet the nutritional needs of the dog.

Heart-fatty acid binding protein in dogs with degenerative valvular disease and dilated cardiomyopathy

The study objective was to investigate heart-fatty acid binding protein (HFABP) concentrations in dogs with degenerative valvular disease (MVD) and dilated cardiomyopathy (DCM), and its potential as a prognostic factor. Plasma HFABP, N-terminal pro brain natriuretic peptide (NTproBNP) and serum cardiac troponin I (cTnI) levels were measured in 21 control dogs, 23 dogs with MVD and 13 dogs with DCM, with repeated sampling at 1 and 3 months after initial presentation. All dogs were followed up after 6 and 12 months to verify survival.Heart-fatty acid binding protein concentrations were significantly higher in dogs with MVD and DCM than controls at initial presentation, and after 1 month in dogs with MVD. For dogs with DCM, a significant reduction in HFABP levels over time was observed. Comparing ACVIM stages, highest HFABP concentrations were detected in ACVIM stage C dogs compared to stage B, with the lowest levels seen in controls, and a reduction over time in stage C dogs was present. Similarly, cTnI concentrations were higher in DCM and stage C in comparison to control dogs and reduced over time, while NTproBNP concentrations were only higher in diseased dogs at 1 month. Heart-fatty acid binding protein and cTnI levels at initial presentation and ACVIM disease stage were independent predictors of survival in a univariate analysis. The elevation of HFABP in dogs with MVD and DCM in comparison to controls, its association with disease severity, and its potential in predicting reduced survival, suggest that HFABP might be useful as marker for canine MVD and DCM.