Bone marrow dysfunction in chronic heart failure patients

Abstract

To investigate whether chronic heart failure (CHF) is associated with a general dysfunction of the haematopoietic compartment. Methods and results: Bone marrow was obtained during coronary artery bypass graft surgery from 20 patients with CHF (age 67 ± 6 years, 75 NYHA class ≥ III, LVEF 32 ± 6), and 20 age-and gender-matched control patients with normal cardiac function. CD34+ haematopoietic progenitor cells were isolated and cultured with increasing doses of erythropoietin (0.02-10 IU/mL, EPO), myeloid growth factors or a mix of both. After 14 days, burst forming units erythroid (BFU-E), and granulocyte or monocyte colony forming units (CFU-G, CFU-M, respectively) were counted. Apoptosis and erythropoietin-receptor (EPO-R) density were quantified by flow cytometry. Throughout the EPO dose range, the CD34+ cells from CHF patients produced a two-fold lower number of BFU-E colonies compared with controls (P = 0.02). The resistance to EPO was associated with markedly increased apoptosis during erythroid differentiation in CHF patients compared with controls [5.3 (2.9-8.1) vs. 1.5 (0.8-3.4), P = 0.01]. Erythropoietin-receptor expression was, however, comparable between CHF patients and controls and the anti-apoptotic cytokine interleukin-3 did not rescue erythropoiesis. In the myeloid cultures, the number of CFU-G and CFU-M colonies was also two-fold lower in CHF patients compared with controls (both P < 0.01). In the mixed-culture assay, myelopoiesis and erythropoiesis were reduced to a similar magnitude in CHF patients. The impaired clonogenic potential was independently associated with clinical and biochemical severity of CHF, but not with the presence of anaemia. Conclusion: Chronic heart failure is associated with profound and general bone marrow dysfunction, simultaneously affecting multiple haematopoietic lineages. © 2010 The Author.