Bone marrow dysfunction in chronic heart failure patients

Eur J Heart Fail. 2010 Jul;12(7):676-84. doi: 10.1093/eurjhf/hfq061. Epub 2010 Apr 28.


Aims: 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 >or= 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis / physiology
  • Bone Marrow / physiopathology*
  • Cell Count
  • Cell Differentiation / physiology
  • Erythroid Precursor Cells / cytology
  • Female
  • Flow Cytometry
  • Granulocyte-Macrophage Progenitor Cells / cytology
  • Heart Failure / physiopathology*
  • Hematopoiesis / physiology
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Male
  • Middle Aged
  • Receptors, Erythropoietin / analysis


  • Receptors, Erythropoietin