Management of Combined CHF and CRF Ri 王薏茜 2003-06-23 CRF ↔ CHF (1) Average SCr of CHF patient : 1.5 mg/dl Mortality of CHF patients 40% sudden death 40% worsening CHF 20% others Cancer, COPD, infection… CRF ↔ CHF (2) CV disease in CRF patients At starting diaslysis 30-70% HTN 60% IHD 18-20% LVH 31-34% CHF CVD mortality: 5-50x(10-30x) more than in normal population Account for >50% of ESRD patient mortality CRF ↔ CHF (3) incidence CAD LVH CHF General population 5-12 20 5 Dialysis 40 75 40 Renal transplant 15 50 - CRF - 25-50 - No/1000pts/year 20-44 45-64 >65 CV death 43 76 179 After transplant 3.1 7.7 - Risk factors for CV diseases Normal population Related to uremia Related to dialysis Old age, male, race Hyper/hypo tension Hyper/hypo tension Hyperlipidemia Anemia Hypertension, DM Low HDL, High LDL Malnutrition homocysteinemia Hypertriglyceridemia Hypoalbuminemia Physical inactivity Lp(a) Low body mass index Family history Hyperparathyoidism Na water retention Menopause Ca X P Socioeconomic Uremic toxins status Oxidative stress Smoking Impaired gibrinosysis Infectous agents Insulin resistance Hymocysteine Thrombogenic factors Endothelialdysfunction Chronic inflammation Carbonyl stress Sleep apnea HTN in ESRD Strongest risk factor of LV hypertrophy For SCr = 3.3 ± 1.1 mg/dl Optimal BP: 3% High normal: 9% Stage 1 HTN (140-160): 34.4% Stage 2/3 HTN (160-200): 52.5% Mortality vs hypertension: J-shaped HTN in ESRD: mechanism Total sodium increase Plasma renin activity increase Noradrenergic hyperactivity Na/water retention AV fistula Anemia Hypotention in ESRD? BP<110: 4x increase in mortality Now suggested as a marker of ventricular systolic/diastolic dysfunction IHD in ESRD At starting dialysis: 18-20% with IHD Presentation Infarction: 56% Angina:82% CABG: 14% Angioplasyt: 1% With IHD Without IHD Progression to heart failure 24m 55m Mean survival time 44m 56m IHD in ESRD: risk factors Older age DM HTN Dyslipidemia Hypoalbuminemia Hyperhomocysteinemia: 83% of patients having levels higher than 90th percentile Associate with 7x increase in mortality Lp(a) LVH in ESRD Mechanism Re-expression of fetel Growth Factor/GFR Myocyte death, fibroblast growth (ESRD>DM, HTN) Interstitial fibrosis Diastolic dysfunction Intolerate to volume change (wall stiffness) Early reflection arrhythmia Independent prognostic factor for survival !! LVMI> 125 mg/m2: 25% (4-y) LVMI< 125 mg/m2: 55% LVEF<40%: odds ratio for mortality: 1.89 Survival in ESRD with/without LVH LVH in ESRD : prevalence In early renal dz (CCr>30ml/min) 65% eccentric hypertrophy 16% concentric hypertrophy In patients with CCr=10-30ml/min 26% concentric hypertrophy In dialysis pts (CCr<10ml/min) 44% eccentric 42-50% concentric LVH in ESRD: independent factors for LVH Hypertention BP ↑ 5mmHg: LVMI ↑10g/m2 Male gender BMI >25 Hb <10-12 Hb ↓ 0.5 mg/dl: LVMI ↑10g/m2 LVH in ESRD: hemodynamic mechanism Volume overload AV fistula Na/water retention Anemia Pressure overload Aotic wall/ventricular wall stiffness Atherosclerosis RAS overactivity: ACEI Dialysis: ∆ Ca(inotropic) and sympathetic tone LVH in ESRD: role of anemia When Hb<10-12 Reactive hemodynamic change Stroke volume ↑ Heart rate ↑ Odds ratio for CRF =1.32 / 0.5 Hb ↓ Odds ratio for ESRD = 1.46 / 1 Hb ↓ EPO? CHF in ESRD Epidemiology In starting dialysis 31% with CHF 25% develop CHF later Mortality 8.9% die of CHF/year Survival With CHF Without CHF 4-y survival 20% 60% Mean suvival 36 months (29m/45m) 62 months Survival in ESRD with/without CHF CHF in ESRD: factors Factors related to onset: Age DM Ischemic heart disease Factors related to recurrence: Ischemic heart disease Anemia Hypoalbuminemia hypertension D/D intrinsic myocardial dysfunction v.s. pure volume overload Echocardiography Radionuclide tecniques ANF and BNF(brain natriuretic factor): Stress receptor in atriumrelease of ANF, BNF Stress receptor in ventriclerelease of BNF NF receptors in kidney, adrenal glomerulose, vascular smooth muscle… Na excretion, vasodilatation, renin/aldosterone ↓,… ANF: associated more with volume overload BNF: associated more with ventricular dysfunction Management principles Preventive intervention should be initiated early in the first year of dialysis. Later treatment (CHF) has limited possibility of success. Management principles Major goal: treating underlying factors predispose to heart failure HTN, DM, hyperPTH, dyslipidemia, anemia Treatment of hemodynamic overload Pharmacologic therapy Diuretics Higher dose/ combine thiazide/ IF continuous use Monitor K+, regular supplement ACEI/Angiotensin Receptor Blockers: proven survival benefit, IHD↓,LVMI↓, GFR decline↓ If hyperkalemia/renal function↓: hydralizine + nitrate Side effect: anemia: EPO ↓, bone marrow ultilization of EPO↓ Beta-blocker: IHD, HTN, CHF Digoxin Cleared by kidney, NOT removed by dialysis Impact on symptom, functional capacity, hospitalized frequency, NOT on survival Management: aggressive correction of anemia CRA syndrome: cardio-renal-anemia Anemia CHF Damaged myocyte EPO production↓ Depress progenitor erythrocyte in bone marrow Interfere with RE system release of iron Management: aggressive correction of anemia 50% of CHF patients have Hb<12 66-80% of class IV CHF pts have Hb<12 Clinical trial in 2001 126 pts: anemic, CHF treatmtne-resistant, NYHA class 3-4 Target goal: keep Hb = 12.5-13 for 12.4 ± 8.2 m Mean: EPO 4000-5000 u if Hb<12.5 Keep serum ferritin>500ug/L, Sat>40% Management: aggressive correction of anemia 1-year Mortality in: Class 3-4 CHF patients: 30-50% This trial: 7.1% Management: intensive volume control Basis LVH accounts for large No of mortality in ESRD sBP elevation is the strongest risk factor for LVH Regression of LVH with BP control is well established Difficulty in controlling BP in ESRD pts, may be due to hidden volume expansion, which is out of reach of antihypertensive medications. Management: intensive volume control Effect of intensive hemodialysis on BP control Mean: 12h H/D per week, without antihypertensive drug As much UF as possible, without excess BP drop Dietary salt restriction 3 months of intensive volume control 12 months of follow up Management: intensive volume control sPB dBP BW CTI LA EDD ESD LVMI % Htc LVH Pre-HD 168 97 63.3 48 - - - - - 29.5 Post-HD 127 78 60.3 46 24.3 29.3 18.8 164 63 33.7 (3ms) 6ms 120 75 62.4 44 22.6 26.7 17.3 121 32 34.2 12ms 118 73 65.4 43 22.6 26.4 18.0 112 18 33.2 Avoid rapid volume shift Maintaining a low dry weight Regression of LVH, LVD, LV stiffness Conclusion CRF patients have a very high risk of develop CVD: HTN, LVH, IHD, CHF Account for more than 50% of ESRD patient mortality Management: risk reduction: anemia, BP control, volume management, medication toward symptoms: diuretics, digoxin, ACEI/ARBs, beta-blockers, correct dyslipidemia Proper dialysis Early intervention! Reference Seminars in dialysis 2003 vol 16(2):85-94 J of Nephrology 2002 15:655-60 Clinical nephrology 2002 vol 58 (supple1):s37-45 Ame J of Kidney diseases 2001 vol 38(4, supple1):s38-46 Peritoneal dialysis international. 2001 Vol 21(S3):s236-9 Seminars in nephrology. 2001 vol 21 (1):3-12 Thank you for your attention !
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