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Prevalence of Anemia in selected HF studies StudyPopulationn Definition of anemia Prevalence AL-Ahmad etal.(4) LV dysfunction+/- symptoms,clinical.

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Presentation on theme: "Prevalence of Anemia in selected HF studies StudyPopulationn Definition of anemia Prevalence AL-Ahmad etal.(4) LV dysfunction+/- symptoms,clinical."— Presentation transcript:

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7 Prevalence of Anemia in selected HF studies StudyPopulationn Definition of anemia Prevalence AL-Ahmad etal.(4) LV dysfunction+/- symptoms,clinical trial 6,563 Hct<35%4% Tanner etal.(7) Tertiary care HF clinic 193Hb<1215% Ezekowitz etal(8) New HF diagnosis,claims data 12,065 MD defined(ICD9 codes) 17% Mozaffarian etal(5) Severe chronic HF,clinical trial 1,130 Hct < 37.6%20% Horwich etal(9) Heart transplant referrals single center 1,061 Hb<13men,<12Women 30% Kosiborod etal(10) Medicare patients,claims data 2,281 Hct ≤ 37% 48% Felker etal(38) Acute decompensated HF,clinical trial 949Hb < 13 men, < 12 women 49% Silverbergetal(6) Chronic HF,single center study 142Hb < 1255%

8 The frequency of anemia in stable treated chronic C.H.F. (defined as Hb < 12.5/g. varied from 9.1% (NYHA1) to 79.1% (NYHA4) (SILVERBERG Ds etal,JACC,2000) NYHA1 0% NYHA2 36.4% NYHA3 52.0% NYHA4 65.9% (Wisniacki N, Hevt,2001) NYHA1 7% NYHA2 9% NYHA3 17% NYHA4 26% (Tanner etal,Jnt.J.Cardiol,2002)

9 We have reached a ceiling of benefit with regards to neurohormonal blockade. (Mehra etal,JACC,2003)

10 Anemia: has recently been recognized as a potentially novel therapeutic target in patients with heart failure. (FELKER et al,JACC,2004)

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13 Causes of anaemia in C.H.F. (1)Iron or folate or B12 defeciency. (2) Bone marrow dysfunction caused by low output failure. (Chatterjee B etal,E.H.F.,2000) (3) High TNF alpha : (a)Direct bone marrow depression. (b) Induction of EPO insensitivity. (c) Interference with release &utilization of iron. (SILVERBERG etal,JACC,2000) (4)Down regulation of EPO by ACE-I. (Volpe M etal,A.J. Cardiol,1994)

14 Anemia signs and symptoms

15 Lower HB was associated with an: (1) Impaired hemodynamic profile (2) Higher BUN and creatinine. (3) Lower albumin. (4) Lower B.M.I. (5) Worsened symptom ; functional status. (6) Worsened survival. (HORWICH etal,JACC,vol 39 No.11,2002)

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21 Cardio-renal anemia syndrome Heart failure Kidney Bone Marrow Anemia Low RBC production EPO resistance Low perfusion RAS activation High sympathetic tone ACE inhibitor therapy Ischemia Apoptosis LVH High sympathetic tone Hemodilution Vasocns triction (Felker JACC,vol 44, No.5,2004) Relative decrease in EPO TNF-alpha perfusion Malnutrition

22 Kalpan-Meier survival analysis for the entire COHORT by QUARTILE of HEMOGLOBIN(Hb) LEVEL (Afler Horwich etal JACC,2002) % Survival

23 One year survival in patients with hear failure according to the hematocrit(%) level. Each lower hematocrit leads to greater year morbidity (Kosiborod etal,2003)

24 Cumulative risk of death in patients with versus without anemia Nikolsky etal.Anemia and primary angioplasty outcomes(CADI LLAC)

25 Rates of survival (A) and disabling stroke (B) at 1 year in patients undergoing percutaneous coronary intervention for acute myocardial infarction stratified by baseline anemia and gender. Nikolisky etal.Anemia and primary angioplasty outcomes (CADLLAC)

26 Association of anemia and outcome in selected HF studies StudyPopulationOutcomeAdjusted hazard/odds ratio Unit change Al-Ahmed et al.(4) LV dysfunction+/- symptoms,clinical trial Mortality1.0271% Hct Ezekawitz et al.(8) New HF diagnosis,claims data Mortality1.34Anemic vs. not Horwich et al.(9) Heart transplant referrals,single-center Mortality1.131g/dl HB Kosiborod et al.(10) Medicare patients,claims data Mortality1.021%Hct Mozaffarian et al.(5) Severe HF,clinical trial Mortality1.031%Hct Felker et al.(38) Acute HF,clinical trialDeath or rehospitalization 1.121g/dl Hb

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34 Erythropoietin 1985 Recombinant human (rh) EPO 1989 FDA approved 1990 DARBEPOETIN –alpha (longer half life) Dosing and monitoring of EPO-alpha and darbepoietin-alpha Locatelli etal, amJkidney Dis 2002 EPO-alphaDarbepoetin-alpha Dose(s.c.)80-120 U/kg/week0.45mg/kg/week Interval(recommended) Divided 2x/weekWeekly Interval rangeUp to once every 2-3 weeks Up to monthly MonitoringEvery 2 weeks untill stable ;then monthly Dose adjustment(25%-50%) Every 2 weeksmonthly

35 The hematological and clinical data of the 26 CHF patients at onset and at the end of the intervention period InitialFinal Hematocrit,vol%30.14 +/-3.1235.9+/-4.22 Hemoglobin,g%10.16 +/-0.9512.1+/-1.21 Serum ferritin,mg/liter177.07 +/-113.80346.73+/-207.4 Serum iron,mg%60.4 +/-16.074.8+/-20.7 %iron saturation20.5 +/-6.0426.14+/-5.23 Serum creatinine,mg%2.59 +/-0.772.73+/- 1.55 LVEF,%27.7 +/-4.835.4+/-7.6 No.hospitilization/patient2.72 +/- 1.210.22+/-0.65 Systolic BP,mm Hg127.1+/- 19.4128.9+/-26.4 Diastolic BP mm Hg73.9 +/-9.974.0+/-12.7 NYHA(0-4)3.66 +/-0.472.66+/-0.70 (AFTER SILVERBERG etal, JACC, 2000 )

36 17.9 CHF +/- CRF S.C. EPO + J.V iron sucrose. HB 2.2 g/dl in 1 Y. NYHA 3.89 2.53 LVEF 34.8% 39.8% (SILVERBERG DS etal,Nephrol Dial transplant,2003)

37 Evaluation of inadequate rHu EPO response (Bradly M.Denher etal.,Nephrology,2004) Inadequate EPO response TSAT < 20% Ferritin < 100 ng/ml Replace iron TSAT > 20% Ferritin > 100ng/ml Exclude: 1. Occult Gi blood loss 2.infection/inflammation 3.Ostetis fibrosa 4. Aluminium toxicity 5.Hemoglobinopathy 6.B12,folate deficiency 7.Multiple myeloma 8.Malnutrition 9.Hemolysis

38 Potential benefits and risks of treating anemia in heart failure (Felker etal.,JACC,2004) Potential benifitsPotential risks Improved oxygen deliveryIncresased thrombosis Improved exercise tolerancePlatelet activation Attenuate adverse remodelingHypertension AntiapoptoticEndothelial activation Improved QOL Decrease in hospitalization Improved survival

39 The optimal target HB has not been well established. Normalization by EPO + iron dextran increased risk of C.V.events compared to a lower Hematocrit TARGET. (Due to rheoloogical and/or Prooxidant effect of J.V. iron dextran) (Furuland etal,Nephrol Dial, transplant,2003)

40 Current HF guidelines provide no specific recommendation for evaluation or treatment of anemia. (Hunt etal,JACC,2001,Renime etal EHJ,2001)

41 Proverbial wisdom counsels against risk and change. But sitting ducks fare worst of all. (MASON COOLEY)

42 is common in CHF. It correlates with the severity of CHF It leads to higher morbidity and mortality. Correction of improves prognosis and decrease mortality. Optimal % has not been defined.

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