Determinants of functional recovery after myocardial infarction of patients treated with bone marrow-derived stem cells after thrombolytic therapy.
OBJECTIVE
To assess the determinants of functional recovery in patients with ST-elevation myocardial infarction (STEMI) treated initially with thrombolysis, followed by percutaneous coronary intervention and intracoronary injection of bone marrow-derived stem cells (BMC).


METHODS
A randomised, placebo-controlled, double-blind study (substudy of FINCELL).


METHODS
Two tertiary cardiac centres.


METHODS
78 patients with STEMI randomly assigned to receive either intracoronary BMC (n=39) or placebo (n=39) into the infarct-related artery.


METHODS
Thrombolysis a few hours after symptom onset, percutaneous coronary intervention and intracoronary injection of BMC 2-6 days later.


METHODS
Efficacy of the BMC treatment was assessed by measurement of the change of global left ventricular ejection fraction (LVEF) from baseline to 6 months after STEMI. Various predefined variables (eg, the levels of certain natriuretic peptides and inflammatory cytokines) were analysed as determinants of improvement of LVEF.


RESULTS
In the BMC group, the most powerful determinant of the change in LVEF was the baseline LVEF (r=-0.58, p<0.001). Patients with baseline LVEF at or below the median (< or = 62.5%) experienced a more marked improvement in LVEF (+12.7 + or - 12.5 %units, p<0.001) than those above the median (-0.8 + or - 6.3 %units, p=0.10). Elevated N-terminal probrain natriuretic peptide (p<0.001) and N-terminal proatrial natriuretic peptide (p=0.052) levels were also associated with improvement in LVEF in the BMC group but not in the placebo group.


CONCLUSIONS
The global LVEF recovers most significantly after intracoronary infusion of BMC in patients with the most severe impairment of LVEF on admission. The baseline levels of natriuretic peptides seem also to be associated with LVEF recovery after BMC treatment. Trial registration ClinicalTrials.gov number, NCT00363324.
Miettinen
Johanna A
JA
University of Oulu, Department of Internal Medicine. P.O. Box 5000 (Kajaanintie 50), FIN-90014 University of Oulu, Oulu, Finland. johanna.miettinen@oulu.fi
Ylitalo
Kari
K
Hedberg
Pirjo
P
Jokelainen
Jari
J
Kervinen
Kari
K
Niemelä
Matti
M
Säily
Marjaana
M
Koistinen
Pirjo
P
Savolainen
Eeva-Riitta
ER
Ukkonen
Heikki
H
Pietilä
Mikko
M
Airaksinen
K E Juhani
KE
Knuuti
Juhani
J
Vuolteenaho
Olli
O
Mäkikallio
Timo H
TH
Huikuri
Heikki V
HV
D000368:Aged; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000628:therapy*; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D020127:Recovery of Function; D013318:Stroke Volume / Q000502:physiology; D015912:Thrombolytic Therapy
D015415:Biomarkers; D015850:Interleukin-6; C099254:N-terminal proatrial natriuretic peptide; D010446:Peptide Fragments; D011498:Protein Precursors; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor