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DEMA-CVN GIỚI THIỆU GIỚI THIỆU CÁC ĐỀ TÀI NGHIÊN CỨU KHOA HỌC TẠI HỘI NGHỊ NỘI KHOA TOÀN QUỐC TẠI THÀNH PHỐ HỒ CHÍ MINH THÁNG 7/ 2011 DEMA-CVN.COM Hue College of Medicine and Pharmacy Vietnam DEMA-CVN.COM DIABETIC CARDIOMYOPATHY Prof Nguyen Hai Thuy MD, PhD DEMA-CVN.COM Hue College of Medicine and Pharmacy Congestive heart failure in diabetic patient without CAD and HTN HbA1c : 8%, BP: 110/70 mmHg IVSd: 1.06 cm, IVSs: 1.23 cm LA: 4.29 cm, LVMI :180 g/m2, EF :20.5% What’s your diagnosis? DEMA-CVN.COM I.INTRODUCTION • Diabetes is observed in 15% to 25% of HF patients in major clinical trials • Among all patients hospitalized for heart failure, 25% to 30% patient have DM as a comorbid condition • In large-scale mortality trials, in HF patients with systolic dysfunction, diabetes was an independent risk factor for death DEMA-CVN.COM New England Journal of Medicine 1999; 341(12): 857-865 DEMA-CVN.COM • Framingham Study • SOLVD ( Studies of Left Ventricular Dysfunction) A direct association between DM and HF was first demonstrated Risk of developing symptomatic HF  2.4-fold in diabetic men  5-fold in diabetic women, Registry of 6791 patients with heart failure, 1310 diabetic patients were more likely to be hospitalized for HF exacerbation and more likely to die independent of coexisting hypertension or ischemic heart disease DEMA-CVN.COM DEMA-CVN.COM DM and younger HF study • Under 65 years old – Four fold in diabetic men – Eight fold in diabetic women • Gender-specific cardiovascular protective effects can be considered to be mitigated once overt diabetes develops in women W H Wilson Tang, MD, and James B Young, MD ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA, VOLUME 30 • NUMBER • DECEMBER 2001 DEMA-CVN.COM • Some diabetic patients not have obvious ischemic insults that lead to progressive HF • A number study challenged that Diabetic patients may have more diffuse and severe coronary insufficiency than nondiabetic patients • Every 1% increase in the baseline glycosylated hemoglobin level translates into a 15% increase in risk of developing HF DEMA-CVN.COM Metabolic modulators DEMA-CVN.COM Changing of metabolism in diabetic heart – would you accept them? ADP, adenosine diphosphate; ATP, adenosine triphosphate; CPT-1, carnitine palmitoyl transferase-1; FFA, free fatty acids DEMA-CVN.COM DEMA-CVN.COM AMPK Signaling is Activated by Exercise DEMA-CVN.COM DEMA-CVN.COM Cơ chế tác dụng metformin AMPK (Adenosine monophosphate activated protein kinase) ACC (Acetyl coa carboxylase) SREBP-1 (Sterol regulatory element binding protein-1) DEMA-CVN.COM Metabolic modulators • Trimetazidine, inhibits an enzyme involved in the βoxidation of NEFAs and has been shown to improve LVEF, NYHA functional class and QOL in patients with HF • Perhexiline has demonstrated substantial improvements in LVEF, ˙Vo2max and QOL, but is associated with a risk of hepatotoxicity and peripheral neuropathy • Ranolazine, reduces intracellular Na+ and diastolic Ca2+ overload, thus improving diastolic function, but it has been associated with prolongation of the QT DEMA-CVN.COM interval Metabolic modulators DEMA-CVN.COM FFAs are mobilized from adipose tissue to inhibit the uptake of glucose by muscle (including heart muscle) The result is hyperglycemia and increased insulin resistance Elevated FFAs also act on mitochondria (mito) to cause excess oxygen wastage with formation of ROS The consequences include mitochondrial and cellular dysfunction (ionic changes, increased cell calcium and sodium) Metabolic interventions decrease insulin resistance, hyperglycemia, and ROS formation to decrease the severity of heart failure DEMA-CVN.COM NEW THERAPEUTIC DIRECTIONS • PARP inhibitors • PARP which inhibits GAPDH (glyceraldehyde-3-phosphate dehydrogenase) This leads to the accumulation of glucose and other glycolytic intermediates prior to their entry into the Krebs cycle • These intermediaries activate a number of major transducers of hyperglycaemic damage In addition to the direct cytotoxic pathway regulated by DNA injury and PARP activation, • PARP also modulates the course of cardiovascular inflammation and injury by regulating the activation ofNF-κB and inducing over-expression of ET (endothelin)-1 and ET receptors Blocking PARP activity with two different competitive PARP inhibitors provides a ‗magic bullet‘ approach as it blocks activation of all the major pathways thought to mediate tissue DEMA-CVN.COM damage in diabetes DEMA-CVN.COM Congestive heart failure in diabetic patient before and after treating high doses of vitamin B1 at Hue University Hospital DEMA-CVN.COM Published October 2nd, 2010 in General Interest, Health, Health News, Health and Wellness, Heart, Life, Medical News, Nutrition, Popular ACS.org – Garlic oil has ―significant‖ potential for preventing cardiomyopathy, a form of heart disease that is a leading cause of death in people with diabetes, scientists have concluded in a new study Their report, which also explains why people with diabetes are at high risk for diabetic cardiomyopathy, appears in ACS‘ bi-weekly Journal of Agricultural and Food Chemistry Wei-Wen Kuo and colleagues : garlic might protect against heart disease , garlic oil possesses significant potential for protecting hearts from diabetes-induced cardiomyopathy,‖ DEMA-CVN.COM References • • • • • • • 1.Sajad A HAYAT∗, Billal PATEL†, Rajdeep S KHATTAR‡ and Rayaz A MALIK† Diabetic cardiomyopathy: mechanisms,diagnosis and treatment Clinical Science (2004) 107, 539–557 2.TK Mishra*, PK Rath**Diabetic Cardiomyopathy: Evidences, Pathophysiology, and Therapeutic ConsiderationsJournal, Indian Academy of Clinical Medicine Vol 6, No October-December, 2005 3.Indu G Poornima, Pratik Parikh, Richard P ShannonDiabetic Cardiomyopathy.The Search for a Unifying HypothesisCirculation Research March 17, 2006 4.Ding An and Brian RodriguesRole of changes in cardiac metabolism in development of diabetic cardiomyopathyAJP-Heart Circ Physiol • VOL 291 • OCTOBER 2006 5.Omar ASGHAR∗, Ahmed AL-SUNNI†, Kaivan KHAVANDI†, Ali KHAVANDI‡, Sarah WITHERS†, Adam GREENSTEIN†, Anthony M HEAGERTY† and Rayaz A MALIK†Diabetic cardiomyopathy.Clinical Science (2009) 116, 741–760 6.GF Gensini VENTRICULAR DYSFUNCTION AND DIABETIC CARDIOMYOPATHY:Where The Devil Comes From?.2011 7.AMERICAN DIABETES ASSOCIATION Standards of Medical Care in Diabetes— 2011 DEMA-CVN.COM Thank you for your attention DEMA-CVN.COM