FOCUS-HF: The first US randomized blinded controlled trial of transendocardial injection of bone marrow mononuclear cells in chronic severe ischemic heart failure patients

BACKGROUND: We described the initial experience of transendocardial (TE) bone-marrow derived mononuclear cell (BMMNC) injection in ischemic heart failure(IHF) pts. In the present study we evaluated BMMNC TE injection in severe IHF pts in a randomized blinded fashion. METHODS: :30 pts with IHF (NYHA/CCS III/IV) with no option for revascularization were randomized (2:1) into treatment (TE injection of 30x106 BMMNC) or controls (C) (mock injection). Cell function analyses were perfomed. Primary endpoint of safety, and efficacy endpoints (NOGA, Echo,SPECT, perfusion MRI, MVO2) were evaluated at baseline, 3 and 6 mo f/u. Comparisons were made by repeated measures ANOVA or Mann-Whitney U test. RESULTS: There were no major peri-procedural complications. At 3 mos 1 treated pt had a NSTEMI. Overall treated (T) pts had functionally compromised BMMNC progenitor compartments. T pts had a mean of 18±14 mesenchymal colony forming units (CFU-F) per 106 BMMNC (nl>30). T pts <60 y had significantly higher CFU-F than older pts (27±17 creatinine clearance and left ventricular systolic function, the odds ratio for mortality were 3.07 (95% confidence interval [CI], 1.25-7.53, p<0.01), 3.89 (95%CI, 1.22-12.34, p<0.02) and 21.66 (95%CI, 3.12-150.0, p<0.002) for mild, moderate and severe RV dysfunction respectively, as compared to normal RV function group. Figure 1 depicts the Kaplan-Meier cumulative probability for mortality curves for each group. CONCLUSIONS: There is a graded independent association between the severity of RV dysfunction after AMI and long-term mortality. Even a mild dysfunction is associated with an increase in risk of death.