Acute Heart Failure: A New Paradigm. Role of Micronutrients

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1 Acute Heart Failure: A New Paradigm Role of Micronutrients Professor John GF Cleland University of Hull Kingston-upon-Hull United Kingdom Conflict of Interest: I have received funding from NUMICO, a manufacturer of neutriceuticals

2 Survival After Discharge for Patients Admitted with Heart Failure National Audit England & Wales % 25% 50% In-patient mortality Age <75 years 5% Age >75 years 16% Survival time (days post-discharge) Age yrs Age yrs Age yrs Age >=85 yrs

3 What are Micronutrients? Nutrients needed in small quantities (<~100µg/day) Minerals: Boron, Cobalt, Chloride, Chromium, Copper, Fluoride, Iodine, Iron, [Magnesium], Manganese, Molybdenum, Selenium, Zinc Vitamins: A, B1-12, Choline, C, D, E & K, Carotenoids, Flavonoids & Lycopenes Essential amino acids Isoleucine, Leucine, (Arginine), Lysine, Methionine, [L- Carnitine], (Cysteine), Phenylalanine, Threonine, (Glutamine), Tryptophan, (Glycine), Valine, (Proline), Organic Acids and Carbohydrates Acetic, Citric, Lactic, Malic Acids, Creatine, Taurine, Inositol Co-enzyme Q10 Essential Fatty Acids (Vitamin F) ά-linolenic (Ω-3), Linoleic (Ω-6), PUFA, Lauric (saturated), and Palmitoleic (monosaturated), Arachidonic Acid

4 Role of Micronutrients Pathophysiology of Deficiency Consequence of heart failure Cause of heart failure Therapy Prevention Physiological restoration Pharmacological (supra-physiological) Sniper (Silver-Bullet) Shotgun Blunderbuss

5 Reasons for Micronutrient Deficiency in Heart Failure Reduced Intake Poor Diet Quantity Quality Reduced absorption Sunlight Reduced Assimilation/Conversion Statins block synthesis of endogenous Q10 Aspirin may impair mitochondrial respiratory chain and conversion of arachidonic acid to vasodilator prostaglandins Increased Wastage Gut Urine Diuretics

6 Micronutrients Vasodilatation Enhanced Energy Substrate Improved Energy Utlilisation Myocardial Protection Reduction in Arrhythmias

7 7-Dehydrocholesterol Promyelocyte to monocyte differentiation IL-2, γifn and TNF-α, IL-4 and IL-10 production, transplant rejection Improved cardiac contractility, LVEF Circulating vitamin D 3 Pancreatic islet cell insulin release 25-hydroxylase -ve 25 (OH) vitamin D 3 1-hydroxylase -ve Vitamin D receptor Increased muscle strength and reduced fall frequency Vasodilatation 1, 25 (OH)2 vitamin D 3 Calcium absorption, renin angiotensin suppression Parathyroid hormone (PTH) The pleiotropic effects of vitamin D and their potential importance in heart failure Calcium absorption Inhibited if dietary calcium sufficient Calcium absorption Inhibition of PTH release PTH Calcium loading, oxidative stress peripheral blood mononuclear cell activation

8 Sir John Hunter The Father of Modern Scientific Medicine But why think, why not try the experiment? Conclusion of a letter to Edward Jenner (leading to the discovery of vaccination for smallpox) 2nd August 1775

9 Wet Beri-Beri Discovery of Thiamine Takaki Kanehiro 1884 Japanese Naval Cadets : Christiaan Eijkman, Sir Frederick Hopkins, Casimir Funk Pathophyiology Vasodilation High output heart failure Peripheral oedema Treatment Intravenous replacement Only available preparation in UK is Pabrinex - 250mg of thiamine & Vitamin C, Nicotinamide, Pyridoxine and Riboflavin. Improvement with hours But vasoconstriction in the presence of primary cardiac disorder can lead to paradoxical exacerbation

10 Thiamine deficiency in 33% of those admitted with worsening CHF (v 12% in controls (p =0.007). Thiamine deficiency was related to Urine thiamine loss Lack of thiamine supplements

11 Thiamine for the treatment of acute decompensated heart failure. Smithline HA. Am J Emerg Med 2007;25:124 6

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15 CORONA (Rosuvastatin v Placebo in Chronic Heart Failure with Reduced LVEF) Outcome According to Tertiles of Plasma Co-enzyme Q10 Lowest

16 Chronic Supplementation in Chronic HF Co-enzyme Q10 Morisco et al patients followed for one year HF Hospitalisation (n = 73 v 118, P < 0.001).

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18 Chronic Supplementation in Chronic HF L-Carnitine & Propionyl-L-Carnitine CEDIM Trial 2,330 patients post-mi (stopped due to low event rate) HR = 0.61, 95% CI , p = Improved LV remodelling Ferrari EHJ 1999

19 Circulation. 1994;89:

20 RCTs of Chronic Supplementation in Chronic HF Creatine Arginine D-Ribose Iron Vitamin C Folic Acid PUFA Multi-nutrient

21 What would A Study of Micronutrients in AHFS Look Like? Haemodynamics? Symptoms? speed or completeness of resolution) Short-term prognosis? Starting point of a long-term outcome trial? Interventions Increase availability and utilisation of carbohydrates rather than fatty acids Prevent cellular acidosis Improve mitochondrial function & ATP production Improve calcium handling Off-load the failing heart Reduce arrhythmias