Effects of darbepoetin alpha on right and left ventricular systolic and diastolic function in anemic patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.
BACKGROUND
Anemia is a frequent condition in chronic heart failure (CHF) that affects adversely long-term cardiac outcomes. We sought to investigate the effects of recombinant human erythropoietin analogue darbepoetin alpha on left (LV) and right ventricular (RV) function and neurohormonal activation in patients with CHF and anemia.


METHODS
Thirty-two CHF patients (New York Heart Association class II-III, LV ejection fraction [EF] <40%, hemoglobin level <12.5 g/dL, serum creatinine level <2.5 mg/dL) were randomized (2:1) to receive either a 3-month darbepoetin alpha regimen at 1.5 microg/kg every 20 days plus oral iron (n = 21) or placebo plus oral iron (n = 11). Echocardiographic indices of LV systolic and diastolic function and RV function, plasma B-type natriuretic peptide (BNP) and 6-minute walked distance were assessed at baseline and posttreatment.


RESULTS
Regarding LV function, only treatment with darbepoetin alpha caused a significant improvement in LVEF (F = 22.001, P < .001), end-systolic wall stress (F = 4.934, P = .034), mitral annulus systolic displacement (F = 6.710, P < .015), isovolumic relaxation time (F = 4.909, P = .035), and E/e ratio (F = 7.833, P = .009). The RV systolic pressure (F = 7.715, P = .009) as well as tricuspid annulus systolic displacement and RVEF (F = 9.264, P = .005) were significantly improved only in the darbepoetin alpha group. Darbepoetin alpha had also alpha beneficial effect on New York Heart Association class (F = 14.586, P = .001), plasma BNP (F = 14.781, P = .001), and 6-minute walk test (F = 19.926, P < .001), whereas these parameters did not significantly change in the placebo-treated patients.


CONCLUSIONS
Darbepoetin alpha improves both LV and RV performance and exercise capacity and counteracts neurohormonal activation in CHF patients with anemia. The drug effects on LV diastolic function, RV function, and LV end-systolic wall stress, in particular, are novel findings, with a potential important contribution to patients' symptomatic improvement.
Parissis
John T
JT
Second Department of Cardiology and Heart Failure Unit, University of Athens Medical School, Attikon University Hospital, Athens, Greece.
Kourea
Kallirrhoe
K
Panou
Fotios
F
Farmakis
Dimitrios
D
Paraskevaidis
Ioannis
I
Ikonomidis
Ignatios
I
Filippatos
Gerasimos
G
Kremastinos
Dimitrios Th
DT
D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D002311:Cardiomyopathy, Dilated / Q000150:complications; D000068256:Darbepoetin alfa; D004359:Drug Therapy, Combination; D004452:Echocardiography; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017079:Exercise Tolerance; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D006397:Hematinics / Q000494:pharmacology / Q000627:therapeutic use*; D006439:Hemodynamics; D006801:Humans; D007279:Injections, Subcutaneous; D016037:Single-Blind Method; D016277:Ventricular Function, Left / Q000187:drug effects*; D016278:Ventricular Function, Right / Q000187:drug effects*
D006397:Hematinics; D004921:Erythropoietin; D000068256:Darbepoetin alfa