title: Circulating endothelial progenitor cells as a predictor of response to cardiac resynchronization therapy: the missing piece of the puzzle?
abstract: BACKGROUND
  It would be important to better identify heart failure (HF) patients most likely to respond to cardiac resynchronization therapy (CRT). Because endothelial progenitor cells (EPCs) play a crucial role in the maintenance of vascular endothelium integrity, we hypothesize that patients who have higher circulating EPCs levels have greater neovascularization potential and are more prone to be responders to CRT.
  
  
  METHODS
  Prospective study of 30 consecutive patients, scheduled for CRT. Echocardiographic evaluation was performed before implant and 6 months after. Responders to CRT were defined as patients who were still alive, have not been hospitalized for HF management, and demonstrated ≥15% reduction in left ventricular end-systolic volume (LVESV) at the 6-month follow-up. EPCs were quantified before CRT, from peripheral blood, by flow cytometry using five different conjugated antibodies: anti-CD34, anti-KDR, anti-CD133, anti-CD45, and anti-CXCR4. We quantified five different populations of angiogenic cells: CD133(+) /CD34(+) cells, CD133(+) /KDR(+) cells, CD133(+) /CD34(+) /KDR(+) cells, CD45(dim) CD34(+) /KDR(+) cells, and CD45(dim) CD34(+) /KDR(+) /CXCR4(+) cells.
  
  
  RESULTS
  The proportion of responders to CRT at the 6-month follow-up was 46.7%. Responders to CRT presented higher baseline EPCs levels than nonresponders (0.0003 ± 0.0006% vs 0.0001 ± 0.0002%, P = 0.04, for CD34(+) /CD133(+) /KDR(+) and 0.0006 ± 0.0005% vs 0.0003 ± 0.0003%, P = 0.009, for CD45(dim) CD34(+) /KDR(+) /CXCR4(+) cells). In addition, baseline levels of CD45(dim) CD34(+) /KDR(+) /CXCR4(+) cells were positively correlated with the reduction of LVESV verified 6 months after CRT (r = 0.497, P = 0.008).
  
  
  CONCLUSIONS
  High circulating EPCs levels may identify the subset of HF patients who are more likely to undergo reverse remodeling and benefit from CRT. Addition of EPCs levels assessment to current selection criteria may improve the ability to predict CRT response.
authors.affiliation: Cardiology Department, Coimbra Hospital and University Center, Coimbra, Portugal; Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Natália
authors.initials: N
authors.lastname: António
authors.forename: Ana
authors.initials: A
authors.lastname: Soares
authors.forename: Tiago
authors.initials: T
authors.lastname: Carvalheiro
authors.forename: Rosa
authors.initials: R
authors.lastname: Fernandes
authors.forename: Artur
authors.initials: A
authors.lastname: Paiva
authors.forename: Miguel
authors.initials: M
authors.lastname: Ventura
authors.forename: João
authors.initials: J
authors.lastname: Cristóvão
authors.forename: Luís
authors.initials: L
authors.lastname: Elvas
authors.forename: Lino
authors.initials: L
authors.lastname: Gonçalves
authors.forename: Luís A
authors.initials: LA
authors.lastname: Providência
authors.forename: Carlos Fontes
authors.initials: CF
authors.lastname: Ribeiro
authors.forename: Guilherme Mariano
authors.initials: GM
authors.lastname: Pego
mesh_terms: D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D066026:Endothelial Progenitor Cells / Q000473:pathology*; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000473:pathology* / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods*; D018579:Patient Selection; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
keywords: cardiac resynchronization therapy; endothelial progenitor cells; responders