Management of Combined CHF and CRF

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Management of Combined CHF and CRF

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

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