Coronary artery disease
Safety and Feasibility of Transendocardial Autologous Bone Marrow Cell Transplantation in Patients With Advanced Heart Disease

https://doi.org/10.1016/j.amjcard.2005.09.132Get rights and content

The present report contains the final results of a Phase I study that evaluated the feasibility, safety, and potential efficacy of intramyocardial injection of autologous bone marrow (BM) in “no-option” patients with refractory angina and myocardial ischemia. Twenty-seven patients underwent electromechanic mapping-guided transendomyocardial injections (n = 12, 0.2 ml each) of unfractionated autologous BM cells directed to ischemic, noninfarcted myocardial territory. Patients were injected with 28 ± 27 × 106/ml nucleated cells containing 2.2 ± 1.4% CD34+ cells. The autologous BM injection procedure was successful in all patients and was associated with no adverse events. At 3 months, the Canadian Cardiovascular Society angina score (3.2 ± 0.5 vs 2.0 ± 0.91, p = 0.001) and treadmill exercise duration (418 ± 136 vs 489 ± 142 seconds, p = 0.017) had improved significantly. The stress-induced ischemia score within the injected territories (118 segments) had also improved (2.2 ± 0.8 vs 1.7 ± 1.1, p <0.001). At 1 year, the clinical improvement was sustained, although 5 patients had undergone revascularization procedures. The number of total injected nucleated cells (CD45+), progenitor cells (CD34+), and the magnitude of secreted vascular endothelial growth factor and macrophage chemoattractant protein-1 by cultured BM cells failed to predict the clinical response. In conclusion, the 3- and 12-month study results have indicated the safety of catheter-based transendocardial delivery of autologous BM cells in patients with advanced symptomatic ischemic heart disease and may suggest sustained potential efficacy. The cellular and humeral characteristics of autologous BM cells did not predict the clinical response, underscoring the advisability of additional mechanistic exploration.

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Patient population

This was a nonrandomized, open-label, multicenter study. All patients underwent maximally tolerated medical therapy before the baseline assessment. Patients were eligible for this study if they met all the following inclusion criteria: (1) Canadian Cardiovascular Society (CCS) angina class III to IV; (2) ≥1 major epicardial vascular conduit with >70% obstruction and supplying the myocardial territory with reversible myocardial ischemia on dual-isotope single-photon emission computed tomographic

Patients

Patient characteristics are listed in Table 1. The average number of surgical and percutaneous revascularization procedures per patient was 1.5 ± 0.7 and 4.0 ± 4.0, respectively.

Bone marrow

Cell viability was ≥97% in all patients. The filtered BM had no clots or bone spicules, had normal morphology, and stained negative for bacteria. The BM aspiration and processing time was approximately 2.5 hours. The injected BM contained 28 ± 28 × 106/ml CD45+ cells (4 to 109 × 106/ml). The cell composition is detailed

Discussion

The main study results support the safety and feasibility of direct, transendocardial autologous BM injection in patients with advanced coronary artery disease. The study results also suggest the potential efficacy, with clinical benefit sustained to 1 year.

The results of the present study extend our preliminary observations,5 underscoring the intermediate-term safety of autologous direct intramyocardial BM cell injections. During the first 6 months after the autologous BM injection, 4 patients

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  • Cited by (0)

    This research was supported by grants from the Cardiovascular Research Institute, Washington, DC, and the Cardiovascular Research Foundation, New York, New York, and a grant from MediVas LLC, San Diego, California.

    Dr. Fuchs, Kornowski, Leon, and Epstein are minor shareholders in a startup company dedicated to the field of cell therapy for angiogenesis.

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