HFNEF HFNEF. Heart failure with normal ejection fraction, HFNEF Diastolic heart failure, DHF. CHARM-Preserved Trial 2 NYHA class II-IV

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1. 2. 3. Heart failure with normal ejection fraction, HFNEF Diastolic heart failure, DHF relatively preserved systolic left ventricular function 1 LVEF < 40% HFNEF HFNEF CHARM-Preserved Trial 2 NYHA class II-IV BNP level 2007 HFNEF 3 HFNEF LVEF LV end-diastolic volume LVEDV natriuretic peptides 3

LVEDVI, left ventricular end-diastolic volume index; mpcw, mean pulmonary capillary wedge pressure; LVEDP, left ventricular end-diastolic pressure; s, time constant of left ventricular relaxation; b, constant of left ventricular chamber stiffness; TD, tissue Doppler; E, early mitral valve flow velocity; E', early TD lengthening velocity; NT-proBNP, N- terminal pro-brain natriuretic peptide; BNP, brain natriuretic peptide; E/A, ratio of early (E) to late (A) mitral valve flow velocity; DT, deceleration time; LVMI, left ventricular mass index; LAVI, left atrial volume index, Ard, duration of reverse pulmonary vein atrial systole flow; Ad, duration of mitral valve atrial wave flow. Paulus WJ. Novel strategies in diastolic heart failure. Heart 2010;96:1147-53. 1. HFNEF VO2max < 14ml/kg/min < 300 4 99 9

2. LVEF 50% LVEDV index <97 ml/m2 LVEDV LVEF 72 HFNEF LVEF 3. wedge pressure mpcw > 12 mmhg LVEDP > 16 mmhg > 48ms b > 0.27 tissue doppler E/ E' > 15 E = early mitral valve flow velocity; E' = tissue Doppler early diastolic lengthening velocity E/E' 8~15 1. 50 E/A < 0.5 deceleration time > 280 ms Ard- Ad > 30 ms Ard: duration of atrial reverse pulmonary vein flow velocity; Ad: duration of atrial mitral valve flow velocity 2. LAVI > 40 ml/m2 LVMI 122 g/m2 > 149 g/m2 3. 4. brain natriuretic peptide BNP N-terminal-proBNP NT-proBNP BNP BT-proBNP HFNEF HFNEF HFNEF guideline HFNEF BNP < 100 pg/ml NTproBNP < 120 pg/ml BNP LVED volume index < 76 ml/m2 LAVI < 29 ml/m2 LVMI: female < 96 g/m2; male < 116 g/m2 tissue Doppler shortening velocity > 6.5 cm/s E/E' > 8 HFNEF 20 CHARM-Alternative study I-PRESERVE 4 HFNEF ARB 5

Paulus WJ. Novel strategies in diastolic heart failure. Heart 2010;96:1147-53. remodeling SHF eccentric LV mass/ volume HFNEF concentric LV SHF microfilaments HFNEF SHF VS HFNEF or DHF 6 99 9

ACEI PREAMI trial LVEF > 40% NYHA class I-II 8 mg perindopril eccentric LV HFNEF concentric 5 Aronow enalapril AMI LVEF > 50% hydralazine+isosorbide dinitrate eccentric LV a cardiothoracic ratio > 0.55 or an echocardiographic LV end-diastolic dimension index > 2.7 cm/m2 PEP-CHF study DHF ACEI 6 70 LVEF > 40% LA LV mitral flow Doppler velocity OPTIMISE-HF registry 76% 62% DHF ACEIs 60-90 diastolic heart failure 1. 2. ramipril 3. irbesartan ACEI or ARB NTproBNP mitral annular velocity S systolic E' early diastolic ALLHAT trial 7 chlorthalidone lisinopril DHF SHF presymptomatic DHF or SHF DHF ARB LV mitral flow velocity Doppler evidence of diastolic LV dysfunction Losartan hydrochlorothiazide valsartan TDI evidence of diastolic LV dysfunction valsartan TDI E' early diastolic mitral annular lengthening velocity DHF ARB CHARM-preserved trial 3023 DHF candesartan ARB 56% 23% 7

DHF DHF CHARM-preserved LV mass /LV volume 1.4 1.3 DHF 1.7 Irbesartan I-PERSERVE trail Hong Kong diastolic heart failure study irbesartan DHF I-PERSERVE 60% 88% 30% DHF ACEI ARB -blocker DHF Dobre registry 43% remodeling eccentric DHF concentric HFNEF SWEDIC trial wall motion score dyskinetic mitral or pulmonary venous flow velocity Doppler HFNEF carvedilol diastolic indices aldosterone antagonist HFNEF spironolactone DHF 25 mg strain strain rate digoxin SHF DHF digoxin verapamil statin DHF 8 Statin DHF ACEI ARB Statin SHF CORONA trail DHF HFNEF DHF SHF DHF free fatty acid 8 99 9

ACE angiotensin converting enzyme gene insertion polymorphism 9 ACE deletion deletion polymorphism AT1R gene ACEI 10 DHF References 01. Paulus WJ. Novel strategies in diastolic heart failure. Heart 2010;96:1147-53. 02. Persson H, Lonn E, Edner M, et al. Diastolic dysfunction in heart failure with preserved systolic function: need for objective evidence:results from the CHARM Echocardiographic Substudy- CHARMES. J Am Coll Cardiol 2007;49:687-94. 03. How to diagnose diastolic heart failure. European Study Group on Diastolic Heart Failure. Eur Heart J 1998;19:990-1003. 04. Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med 2008;359:2456-67. 05. van Heerebeek L, Borbely A, Niessen HW, et al. Myocardial structure and function differ in systolic and diastolic heart failure. Circulation 2006;113:1966-73. 06. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008;29:2388-442. 07. Davis BR, Kostis JB, Simpson LM, et al. Heart failure with preserved and reduced left ventricular ejection fraction in the antihypertensive and lipid-lowering treatment to prevent heart attack trial. Circulation 2008; 118:2259-67. 08. Fukuta H, Sane DC, Brucks S, Little WC. Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report. Circulation 2005;112:357-63. 09. Wu CK, Luo JL, Wu XM, et al. A propensity scorebased case-control study of renin-angiotensin system gene polymorphisms and diastolic heart failure. Atherosclerosis 2009;205:497-502. 10. Wu CK, Luo JL, Tsai CT, et al. Demonstrating the pharmacogenetic effects of angiotensin-converting enzyme inhibitors on long-term prognosis of diastolic heart failure. Pharmacogenomics J 2010;10:46-53. 9