(2) (P 6.8 mg/dl) (pre-esrd) ( (congestive heart failure, CHF) ) E/A (reverse) 60% [1-2]

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1 (P 6.8 mg/dl) (cardiovascular ( ) disease, CVD) (pre-esrd) ( (congestive heart failure, CHF) ) (hypertension) (coronary artery disease, CAD) [5] (systolic dysfunction) (left ventricular ejection fraction, LVEF) 40% 80% % (diastolic dysfunction) 28% E/A (reverse) 60% [1-2] [6] Nixon (end-stage renal disease, ESRD) (ultrafiltration, UF) [3] 40% [7] (coronary artery disease, CAD) 75% (left ventricular hypertrophy, LVH) (2) (Ca 8 mg/dl) 36% [4] (chronic kidney (1) ( -adrenergic stimulation) (2) disease, CKD) (stiffness) (afterload) (multiple risk factors) (isolated systolic hypertension, ISH) (3) (stiffer heart) (4) 4,024 (cardiac (prevalence) output, CO) (neurohormonal stimulation) (perfusion [5] (1) (albumin) pressure) (hypoalbuminemia) (renin-angiotensin-aldosterone, RAA) 150

2 (arginine vasopressin, AVP) (a) (b) (fluid overload) [8] camp (c) (d) (prothrombotic factor) (e) (f) (hyperparathyroidism) (g) (angiotensinogen) (angiotensin I) (LVH) (angiotensin-converting enzyme, ACE) (angiotensin II, AII) 93% (vasoconstrictor) (aldosterone) (cardiac remodelling) ( 1) (LV dilation) 42% (1) (2) (3) Foley 48% ( hyp erlipi de mia ) (hyperhomocystinemia)

3 60 100% (primary goal) (renaovascular disease) Foley 432 (percutaneous catheter intervention, PCI) [9] (coronary artery bypass graft, CABG) (heart transplantation) 1. (underyling etiology) 2. Zager 5, mmhg 4. [10] 5. (1) (ACE inhibitors) (diuretics) (digitalis) (2) (AII receptor blockers, ARBs) [15] (3) (vasodilators) Hydralazine isosorbide dinitrite [11-12] (4) (CAD) (aldosterone antagonist) spironolactone (Aldactone ) ( 83%) (5) dobutamine (phosphodiesterase [13] inhibitors) (6) (dilated cardiomyopathy, (carnitine) (PTH)DCM) ( -blockers) (7) [14] (ischemic heart disease, IHD) 152

4 (optimal dialysis) 4 g/dl (folic acid) (cardiac (homocysteine) echo) (dry weight) (ACEIs) ( -blocker Carvedilol) [4] (secondary hyperparathyroidism) (hyperlipidemia) (Diuretics) (atherosclerosis) (glomerular filtration rate, GFR) (renal anemia) (loop diuretics) (subcutaneous injection, SC) (recombinant human erythropoietin, rhu-epo) (fluid overload) thiazide (continuous drip) (natriuresis) (LV mass) [16] spironolactone (preload) (afterload) (extracellular matrix) (degradation) [19-22] ( 30%) (dry weight) [17- (hyperkalemia) 18] (shorter interdialytic phase) ( ) 5% (AV fistula) (Digoxin) (high cardiac output) ( L/min) 153

5 (angioedema) (ARBs) (Af with RVR) (apresoline) (nitrate) (1) (2) (3) (AII type 1 receptor blockers, (4) 30% ARBs) ARBs RAA AT 1 quinidine ACEI ARBs ACEI (add on therapy) [15] ARBs (ACEIs) (stroke) ACEIs RAA (regression) (baroreceptor) (bradykinin) (NO) ( ) (Beta-blockers) RAA ACEI (diastolic filling time) ( u p - regulation) ( -agonist) HOPE [23] ACEI Londan ACEI (LVH) ACEI (CCB) 12 ACEI (LV mass) Metoprolol ACEI (100 mg) 1/4 (25 mg) ACEI (systolic dysfunction) (renoprotection) (NYHA classes II-IV) ACEI 10 ( ) 20% Carvedilol ( 1, 2 1) Carvedilol (anti-oxidation) 154

6 (anti-atherogenic) Carvedilol [24-25] Carvedilol 114 (dilated cardiomyopathy, DCM) (LVEF) 35% (LV volume) [26] (very low dose) (JACC) Carvedilol (6.25 ) 85 90% [27] 40% (PSVT) ( ) 1. Taffet GE, Teasdale TA, Bleyer AJ, Kutka NJ, Luchi NJ: Survival of elderly men with Congestive heart failure. Age Aging 1992; 21: Weintraub NL, Chaitman BR: Newer concepts in the medical management of patients with congestive heart failure. Clin Cardiol 1993; 16: Al-Ahmad A, Sarnak MJ, Salem DN, Konstam MA: Cause and management of heart failure in patients with chronic renal disease. Semin Nephrol 2001; 21: Levey AS, Beto JA, Coronado BE, et al: Special report, controlling the epidemic of cardiovascular disease in chronic renal disease: What do we know? What do we need to learn? Where do we go from here? Am J Kidney Dis 1998; 32: Stack AG, Bloembergen WE: A cross-sectonal study of the prevalence and clinical correlates of congestive heart failure among inicident US dialysis patient Am J Kidney Dis 2001; 38: Richard BD, Mary JR, Welty Thomas K, et al: Congestive heart failure despite normal left ventvicular systolic function in a population-based sample: The strong heart study. Am J Cardiol 2000; 86: Nixon JV, Mitchell JH, Mc Phaul JJ, et al: Effect of hemodialysis on left ventricular function, dissociation of changes in filling volume and in contractile state. J Clin Invest 1983; 71: Francis GS, Goldsmith SR, Levine TB, Olivari MT, Cohu JN: The neuro humoral axis in congestive heart failure. Ann Intern Med 1984; 101: Foley RN, Parfrey PS, Havnetl JD, et al: Impact of hypertension on cardiomyopathy, morbidity and mortality in end stage renal disease. Kidney Int 1996; 49: Zager PG, Nikolic J, Brown RH, et al: "U" curve association of blood pressure and mortality in hemodialysis patients. Kidney Int 1998; 54: Kronenberg F, Utermann G, Dieplinger H: Lipoprotein in renal disease. Am J Kidney Dis 1996; 27: Becker BN, Himmelfarb J, Henrich WL, et al: Reassessing the cardiac risk profile in chronic hemodialysis patients: A hypothesis on the role of oxidant stress and other non-traditional risk factors. J Am Soc Nephrol 1997; 8: Bostom AG, Lathrop L: Hyperhomocysteinemia in end-stage renal disease: Prevalence, etiology, and potential relationship to arteriosclerotic outcomes. Kidney Int 1997; 52: Block GA, Hulbert-Shearon TE, Levin NW, et al: Association of serum phosphate and calcium X phosphorous product with mortality risk in chronic hemodialysis patients: A national study. Am J Kidney Dis 1998; 31: Cohn JN, Tognoni G (the Valsartan Heart Failure Trial 155

7 Investigators): A randomized trial of the angiotensin receptor blocker valsartan in chronic heart failure. N Engl J Med 2001; 345: Silverberg DS, Wexler D, Blum M, et al: The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol 2000; 23: Wizeman V, Kramer W: Choice of ESRD treatment strategy according to cardiac status. Kidney Int 1988; 33: S Wizeman V, Timio M, Alpert MA, et al: Options in dialysis therapy: Significance of cardiovascular findings. Kidney Int 1993; 40: S Faiez Z, Brigithle D, Francois A: Treatment of congestive heart failure: Interfering the aldosterone-cardiac extracellular matrix relationship. Circulation 2001; 38: Francois A, Faiez Z, Brigitte D, Alfonso P, Bertram P: Limitation of excessive extracellular matrix tuvnover may contribute to survival benefit of epironolactone therapy in patients with congestive heart failure: Insights from the Randomized Aldactone Evaluation Study (RALES). Circulation 2000; 102: Korkmaz, ME, Mderrisoglu H, Ulucan M, Ozin B: Effects of spironolactone on heart rate varibility and left ventricular systolic function in severe ischemic heart failure. Am J Cardiol 2000; 86: Pitt B, Zannad F, Remme WJ, et al: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341: Yusuf S, Sleight P, Pogue J, et al: Effects of angiotensinconverting enzyme inhibitor, ramipril, on cardiovascular event in high-risk patients (The Heart Outcomes Prevention Evaluation study investigators). N Engl J Med 2000; 342: Packer M, Bristow MR, Cohn JN, et al: The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996; 334(21): Packer M, Coats AJ, Fowler MB, et al: Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001; 344(22): Cice G, Ferrara L, Benedetto AD, et al: Dilated cardiomyopathy on dialysis patients-beneficial effects of carvedilol: A double-blind placebo-controlled trial. J Am Coll Cardiol 2001; 37: CIBIS Investigation and Committees: A randomized trial of α-blockade in heart failure: The cardiac insufficiency Bisoprolol study. Am Heart Assoc Inc. 1994; 90: ; 39: ( ) 1997: 33: Dorminak P: Pharmacotherapeutic strategy in heart failure. Clin Nephrol 2002; 58: S Henning L: Clinical studies on the therapy of heart failure using ACE-inhibitors and AT1-receptor blockers-dose combination treatment make sense? Clin Nephrol 2002; 58: S7- S Manjunath GU, Leuey AS, Sarmk MJ: How can the cardiac death rate be reduced in dialysis patients? Semin Dialysis 2002; 15:

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