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CLINICAL RESEARCH: HEART FAILURE

Intravenous Iron Reduces NT-Pro-Brain Natriuretic Peptide in Anemic Patients With Chronic Heart Failure and Renal Insufficiency

Hospital Alemán, Buenos Aires, Argentina.

Manuscript received March 23, 2007; revised manuscript received July 3, 2007, accepted July 8, 2007.

^_* Reprint requests and correspondence: Dr. Jorge E. Toblli, School of Medicine, University of Buenos Aires, Department of Internal Medicine, Hospital Alemán, Av. Pueyrredon 1640, Buenos Aires (1118), Argentina. (Email: jorgetoblli{at}fibertel.com.ar).

Objectives: Our objective was to evaluate in a double-blind, randomized, placebo-controlled study possible modifications in NT-pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) levels together with clinical and functional parameters, in a group of anemic patients with chronic heart failure (CHF) and chronic renal failure (CRF) receiving intravenous iron therapy, without recombinant human erythropoietin (rhEPO), versus placebo.

Background: Chronic heart failure and CRF associated with absolute or relative iron deficiency anemia is a common problem. This situation is linked with a variable inflammatory status. Both NT-proBNP and CRP are recognized markers for left ventricular dysfunction and inflammatory status, respectively. In this double-blind, randomized, placebo-controlled study, modifications in NT-proBNP and CRP level and clinical and functional parameters, in anemic patients with CHF and CRF receiving intravenous iron therapy, without rhEPO, versus placebo were evaluated.

Methods: Forty patients with hemoglobin (Hb) <12.5 g/dl, transferrin saturation <20%, ferritin <100 ng/ml, creatinine clearance (CrCl) <90 ml/min, and left ventricular ejection fraction (LVEF) 35% were randomized into 2 groups (n = 20 for each). For 5 weeks, group A received isotonic saline solution and group B received iron sucrose complex, 200 mg weekly. Minnesota Living with Heart Failure Questionnaire (MLHFQ) and 6-min walk (6MW) test were performed. NT-pro brain natriuretic peptide and CRP were evaluated throughout the study. No patients received erythroprotein any time.

Results: After 6 months follow-up, group B showed better hematology values and CrCl (p < 0.01) and lower NT-proBNP (117.5 ± 87.4 pg/ml vs. 450.9 ± 248.8 pg/ml, p < 0.01) and CRP (2.3 ± 0.8 mg/l vs. 6.5 ± 3.7 mg/l, p < 0.01). There was a correlation initially (p < 0.01) between Hb and NT-proBNP (group A: r = –0.94 and group B: r = –0.81) and after 6 months only in group A: r = –0.80. Similar correlations were observed with Hb and CRP. Left ventricular ejection fraction percentage (35.7 ± 4.7 vs. 28.8 ± 2.4), MLHFQ score, and 6MW test were all improved in group B (p < 0.01). Additionally, group B had fewer hospitalizations: 0 of 20 versus group A, 5 of 20 (p < 0.01; relative risk = 2.33).

Conclusions: Intravenous iron therapy without rhEPO substantially reduced NT-proBNP and inflammatory status in anemic patients with CHF and moderate CRF. This situation was associated with an improvement in LVEF, NYHA functional class, exercise capacity, renal function, and better quality of life.

Abbreviations and Acronyms   6MW = 6-min walk   BMI = body mass index   CHF = chronic heart failure   CRF = chronic renal failure   CRP = C-reactive protein   Hb = hemoglobin   ISC = iron sucrose complex   IV = intravenous   LV = left ventricle/ventricular   LVEF = left ventricular ejection fraction   NT-proBNP = NT-pro-brain natriuretic peptide   NYHA = New York Heart Association   rhEPO = recombinant human erythropoietin   TSAT = transferrin saturation

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