• Top
• Background
• Methods
• Results
• Conclusion

Background

Bone marrow-derived mononuclear cell (BM-MNC) transplantation into the myocardium has been proposed as a new therapy for ischemic heart failure (HF). Successful cellular therapy for HF using myoblast transplantation has been reported previously but malignant arrhythmias (MA) were an issue. We investigated the safety of BM-MNC transplantation into the myocardium for MA.

Methods

A prospective study to evaluate the safety of autologous BM-MNC transplantation in patients with severe ischemic HF not amenable to myocardial revascularization was conducted. Bone marrow was harvested from the iliac crest and BM-MNCs were selected by Ficoll gradient. Hibernating myocardium areas were targeted using electromechanical mapping in catheter-based subendocardial injections (MyoStar, Cordis, Miami Lakes, FL, USA). All patients were evaluated for MA, number of premature ventricular contractions (PVC) and QT dispersion using a 24-hour Holter test at baseline, immediately after the procedure and then after 8 weeks. Perfusion tests to quantify the left ventricular (LV) ischemic mass and echocardiograms to evaluate the ejection fraction (EF) were performed at baseline and then repeated at 8 weeks.

Results

Fourteen patients (12 males, 56.9 ± 10 years) with severe HF (LV EF 30 ± 6%) were enrolled. All patients had triple-vessel disease and 64% had previous myocardial revascularization. A total of 30 × 10⁶ BM-MNC were injected at 15 sites. All patients were discharged from hospital 48 hours after the procedure. The estimated LV ischemic area on MIBI SPECT was measured by per-centual of myocardial defect reverse, 14.8 ± 15% of LV mass at baseline that was reduced to 5 ± 11% (P = 0.009) at 8 weeks after procedure. EF increased 16% (P = 0.03) at 8 weeks. The number of PVC was reduced at 24 hours (483 ± 4598 versus 236 ± 6243, P = not significant) and at 8 weeks (483 ± 4598 versus 191 ± 1236, P = not significant). No MA were documented at 24 hours or at 8 weeks. QT dispersion decreased from 63 ± 24 ms at baseline to 54 ± 16 ms (P = 0.3) at 2 months of follow-up.

Conclusion

BM-MNC transplantation into myocardium of patients with severe heart failure was safely performed and short term follow-up suggests electrical stability as observed by a decrease in the QT dispersion, maintenance in the number of PVC and an absence of MA. Possible mechanisms may be due to ischemic LV mass reduction and improvement in myocardium contractility.

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