1. How can nutrition help patients with cardiac diseases V. Biourge DVM PhD Dipl ACVN&ECVCN Health and Nutrition Scientific Director R&D, Royal Canin SAS, Aimargues, France Thanks to D. Elliott, DVM PhD Dip ACVIM&CVN Courtesy of V Chetboul

2. Nutrition and cardiac disease « Let food be thy medicine » Hippocrates (460-377 BC) Nutrition and cardiac disease Strong evidences in human medicine. Little support in veterinary medicine. Poor palatibility of the historical diet. Na content as the main emphasis. Importance of Nutrition Anorexia will not support recovery. Importance of a complete and balanced diet to support animal maintenance. Essential role of nutrients for normal cardiac function –Taurine, Carnitine, n-3 fatty acids, antioxidants, … Research & Development Confidential information - Mars Inc

3. Nutrition and cardiac disease Role of nutrition in cardiac disease: Provide nutrients and energy requirements. Pharmacological actions of nutrients. Slow progression of heart failure. Extend a symptom-free quality of life.

4. Energy Adapt energy to body weight and BCS Overweight cardiac patients cardiac workload and risk of congestive heart failure. Exercise intolerance. Weight reduction improves respiratory function Disproportional weight loss Patients with more advance disease. Predominate loss of lean body mass Cardiac cahexia: 54% of DCM cases LM Freeman

5. Cardiac Cachexia Royal Canin, Canine Clinical Encyclopedia, 2004

6. Cardiac Cachexia Pathophysiology Anorexia Metabolic alterations (cytokines) Increased energy expenditure Poor tissue perfusion Exacerbate weakness and exercise intolerance Catabolism of cardiac muscle may contribute to progression Associated with immune system dysfunction Royal Canin, Canine Clinical Encyclopedia, 2004

7. Cytokine dysregulation Dogs with heart failure have increased levels of TNF TNF correlates with severity of cardiac cachexia IL-I inversely correlates with survival Freeman et al, 1994 Freeman et al, 1998 R = -0.52 P = 0.02 Changes in IL-1 and Survival in 21 Dogs with DCM

8. Anorexia Causes of anorexia include Fatigue or dyspnea Medication toxicity Poor diet palatability Early management may help to reduce the risks of anorexia and cachexia Prevalence 33% of CHF dogs had only fair or poor appetite. 84% of dogs experience anorexia during disease. Dogs with DCM ate only 72-84% of expected caloric intake. Important reason influencing euthanasia decision. Food Intake in 21 dogs with DCM Freeman et al, 1994 Freeman et al, 1998

9. Promoting Food Intake Target: 70 -95 Kcal/kg 0,75 Highly palatable, energy dense foods Protein, Fat, Sodium Warm foods prior to feeding Texture Dry Vs Moist Assisted feeding Tube feeding

10. Protein Some cardiac diets are severely protein restricted to reduce metabolic stress No evidence to support this theory Protein restriction may contribute to Muscle loss and weakness Cardiac cachexia Exercise intolerance Poor quality of life Provide cardiac patients with adequate dietary protein – Dogs: > 50 g/1000 Kcal ME – Cats: 60-70 g/1000 Kcal ME AAFCO Royal Canin, Canine Clinical Encyclopedia, 2004

11. Taurine Essential a.a. in cats Beta -amino sulfonic acid H + 3 N - CH 2 - CH 2 - SO - 3 Not a part of proteins [Taurine] in cells very high Role: Intracellular osmolality Calcium concentration Transmembrane ion fluxes Positive inotrope Pion et al, 1987 250-500 mg/1000 kcal

12. Taurine Research & Development Confidential information - Mars Inc Low level of synthesisObligate losses

13. Taurine Taurine deficiency reported in dogs with DCM –American Cocker Spaniel –Portuguese Water Dog –Low or poorly available Met+Cys Certain lamb based diets Vegetarian diets Severely protein restricted diets Cardiac diets should contain supplemental taurine –250-500 mg/1000 Kcal ME Kittleson 1997; Freeman 2000, Torres 2000, Sanderson 2001

14. Carnitine Present in highest concentrations in the heart and skeletal muscles. Facilitates the transport of long chain fatty acids (LCFA) into the mitochondria –Normal heart obtains 60% of its energy from fatty acid oxidation Carnitine deficiency reported in Boxers, Doberman Pinchers, American Cocker Spaniels Patients often have normal plasma [carnitine] with low intramyocardial levels –?Membrane transporter defect Improvement within weeks of supplementation Carnitine may help improve myocardial energy production 50-100 mg/kg PO TID

15. L-arginine Essential amino acid for dogs and cats Precursor of nitric oxide (endothelium-derived relaxation factor) nitric oxide endothelial dysfunction peripheral blood flow exercise intolerance Arginine supplementation in humans with CHF has been reported to –Increase endothelial nitric oxide levels –Improve endothelium-dependent vasodilation –Improve cardiac output –Increase renal function –Improve exercise tolerance –Decrease dyspnea Cardiac diets should have adequate arginine –NRC RA = 0,88 g/1000Kcal –Cardiac diets = 3-5,6 g/1000 Kcal Wang et al, 1997

16. Fat Very good source of energy 9 Kcal/g Vs. 4 for Prot – CHO Essential components for life: phospholipids, sterols, ecosanoïds, … Source of essential fatty acids. -3 and -6 fatty acids Fish oils have been shown to decrease TNF and IL-1 in human patients Inhibition of pro-inflammatory arachadonic acid metabolites Direct inhibition on gene transcription Dogs 7% Cats 0%

17. -3 Polyunsaturated Fatty Acids Dogs with heart failure have low concentrations of EPA (c20:5n-3) and DHA (c22:6n-3) * * * P < 0.05 Freeman 1998 * P < 0.05 * * Fish oil supplementation –Increases EPA and DHA in dogs with DCM –Decreases arachidonic acid

18. -3 Polyunsaturated Fatty Acids Supplementation with fish oils –Reduced IL-1 and TNF in dogs with DCM –Improved cachexia and anorexia –Reduced arrhythmogenesis cytokines is associated with a lower risk of cardiac cachexia and increased survival of cardiac patients Freeman 1998

19. -3 Polyunsaturated Fatty Acids

20. Sodium Sodium restriction Reduce fluid retention Minimize congestion When should we institute sodium restriction? What level of restriction should we implement?

21. Pathogenesis of Na Retention in Heart Disease

22. Dietary sodium Research & Development Confidential information - Mars Inc

23. Dietary sodium Research & Development Confidential information - Mars Inc Royal Canin, Canine Clinical Encyclopedia, 2004

24. Sodium Rush et al, 2000 * = P<0.05 LA = standard left atrial dimension maxLA = maximum left atrial dimension; LVIDd/s = left ventricular internal dimension in diastole / systole * * * *

25. Sodium Activation of RAA system occurs early in cardiac disease –Increases ventricular preload and afterload –Cardiotoxic effects May be exacerbated by sodium restriction Severe restriction in association with ACE-inhibitor therapy in early cardiac disease could hasten progression Pedersen 1995

26. Potassium HypokalemiaHyperkalemia Diuretics e.g. furosemide Anorexia ACE-Inhibitors High K + diets Muscle weakness Arrhythmogenesis Digitalis toxicity Cardiac arrest NRC RA = 1,1 g/1000 kcal Cardiac diets = 1,8 – 2,0 g/1000 kcal

27. Potassium 60% of dogs on low sodium/potassium diet, furosemide, digoxin and captopril developed hyperkalemia Cardiac patients should receive a normal dietary K content 1-1,5 g/1000 Kcal Monitor serum potassium concentrations Roudebush 1994 Mark E Peterson, 2011

28. Magnesium Involved in –Carbohydrate and fatty acid metabolism –Protein and nucleic acid synthesis –Energy conversion –Cardiac and smooth muscle contractility Cardiac drugs (i.e. loop diuretics, digoxin) are associated with magnesium depletion

29. Magnesium 50% of Cavalier King Charles Spaniels with heart failure were magnesium deficient Hypomagnesemia is associated with –Hypertension, coronary artery disease –Congestive heart failure –Cardiac arrhythmias, decreased cardiac contractility –Muscle weakness Cardiac patients should receive diets with adequate magnesium concentrations Pedersen et al 1998 NRC RA = 100 mg/1000 kcal Cardiac diets = 100 – 320 mg/Mcal

30. B-Vitamins B-vitamins are water soluble – Diuresis Cats with cardiomyopathy have decreased concentrations of vitamin B 6 and B 12 B 12 correlates correlates with left atrial size –Involved in pathogenesis or promotion of heart disease in cats? *P < 0.05 * * Plasma Concentrations of Vitamins B 6 and B 12 in 27 Cats with Cardiomyopathy compared with 29 Healthy Cats McMichael et al 2000

31. Oxidative Stress Freeman et al, 1999 Heart failure class % of control MDA Vit E Vit C I II III IV Oxidative Stress and Antioxidant Concentrations in 18 Dogs With DCM * * ** * P < * P < 0.05 Vitamin E; r = -0.51, p = 0.03

32. Antioxidants Free radicals –Cytotoxic –Negative inotropes Free radical injury implicated in development and progression of –Coronary artery disease –Myocardial infarction –Cardiomyopathy

33. How Can Nutrition Help? High palatability &Maintain appetite & energy densityavoid cachexia Normal proteinRestriction may contribute contentto cachexia and muscle loss Taurine Beneficial in DCM? L-arginine Improved endothelium dependent vasodilatation Carnitine Improve myocyte energy production

34. w-3 PUFAReduced inflammatory cytokines, anorexia Reduced arrhythmogenesis How Can Nutrition Help? Moderate potassiumAvoids hypo & hyperkalaemia content Compatible with therapy Staged sodium Reduced sodium and restriction water retention Magnesium Avoids deficiency Antioxidants Combat oxidative stress B vitamins Avoids deficiency

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