Background

This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone-marrow cells in patients with end-stage ischemic heart disease could promote neovascularization and improve perfusion and myocardial contractility.

Methods and results

Twenty-one patients were enrolled into this prospective, non-randomized, open-label, controlled study (first 14, treatment; last seven, control). Baseline evaluations included complete clinical and laboratory evaluations, exercise stress (ramp treadmill), two-dimensional Doppler echocardiogram, SPECT perfusion scan, and 24-hour Holter monitoring. Bone-marrow mononuclear cells were harvested, isolated, washed, and resuspended in saline for injection by NOGA catheter (15 injections of 0.2 cm³). Electromechanical mapping (EMM) was used to identify viable myocardium (unipolar voltage ≥ 6.9 mV) for treatment. Patients underwent 2-month noninvasive and 4-month invasive (treatment group only) follow-up using standard protocols and the same procedures as baseline. Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups; only creatinine and BNP levels varied in laboratory evaluations. At 2 months, there was a significant reduction in total reversible defect within the treatment group and between the treatment and control groups (P = 0.02) on quantitative SPECT analysis. At 4 months, there was improvement in ejection fraction from a baseline of 20% to 29% (P = 0.003) and a reduction in ESV (P = 0.03) in the treated patients. EMM revealed significant mechanical improvement of the injected segments (P < 0.0005).

Conclusions

In patients with chronic, ischemic heart failure, EMM technology was used to target viable, hibernating myocardium for transendocardial delivery of autologous bone-marrow mononuclear cells. At follow-up, treated patients had significantly improved myocardial perfusion and contractility.