Management of Combined

CHF and CRFRi 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

Old age, male, race Hyperlipidemia Hypertension, DM homocysteinemia Physical inactivity Family history Menopause Socioeconomic stat

us Smoking Infectous agents

Related to uremia Hyper/hypo tension Anemia Low HDL, High LDL Hypertriglyceridemia Lp(a) Hyperparathyoidism Ca X P Uremic toxins Oxidative stress Impaired gibrinosysis Insulin resistance Hymocysteine Thrombogenic factors Endothelialdysfunction Chronic inflammation Carbonyl stress Sleep apnea

Related to dialysis Hyper/hypo tension Malnutrition Hypoalbuminemia Low body mass index Na water retention

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 predi

spose 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: cardi

o-renal-anemia Anemia CHF

Damaged myocyte EPO production↓ Depress progenitor eryt

hrocyte in bone marrow Interfere with RE syste

m 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 establi

shed Difficulty in controlling BP in ESRD pts, may be d

ue 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

Avoid rapid volume shift Maintaining a low dry weight Regression of LVH, LVD, LV stiffness

sPB dBP BW CTI LA EDD ESD LVMI %LVH

Htc

Pre-HD 168 97 63.3 48 - - - - - 29.5

Post-HD(3ms)

127 78 60.3 46 24.3 29.3 18.8 164 63 33.7

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

Conclusion CRF patients have a very high risk of develop CV

D: 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/AR

Bs, 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, supple

1):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 !