NEW YORK — Intramyocardial delivery of bone marrow stem cells during coronary artery bypass grafting conferred additional benefits in ejection fraction and perfusion beyond that seen with the surgery alone in two small studies, Dr. Gustav Steinhoff reported at a conference on cell therapy and cardiovascular diseases.
The first was a phase I trial that included 15 patients with chronic ischemia resulting from previous myocardial infarction. Their mean age was 63 years, and all were male and had moderate to severe symptoms of coronary artery disease, including reduced exercise capacity and chest pain.
All patients first underwent bone marrow aspiration, and from the aspirate, CD133+ cells were isolated. CD133+ cells are a subset of CD34+ hematopoietic progenitor cells that have been found to improve myocardial function in animal models and to increase vascular differentiation, Dr. Steinhoff said.
The following day coronary artery bypass grafting (CABG) was done and the CD133+ cells were injected into an area of myocardial perfusion defect.
Among patients in this first trial, the average left ventricular ejection fraction (EF) evaluated echocardiographically increased significantly, from 39% to 50% at 6 months, and to 48% at 18 months. Left ventricular end systolic volume also decreased significantly, from 92 mL to 66 mL at 6 and 18 months, while end diastolic volume decreased from 144 mL to 121 mL at 6 months and to 127 mL at 18 months (J. Thorac. Cardiovasc. Surg. 2007;133:717–25).
All patients tolerated the procedure well, and there were no serious adverse events related to the treatment. One patient died of a stroke 9 months later.
The remaining 14 have survived for up to 5 years, for a total of 739 patient-years, said Dr. Steinhoff of the department of cardiac surgery, University of Rostock (Germany).
The promising results of the phase I study prompted Dr. Steinhoff and his colleagues to perform a phase II trial that included 55 patients who were randomized to stem cell therapy plus CABG or CABG alone. In this study, the mean age also was 63 years, and three-quarters of the patients were male. Disease severity was similar to that seen in the phase I trial.
Among patients who had the cell treatment, left ventricular EF increased from 37% to 47% at 6 months, while in the CABG-only patients it increased from 38% to 41% at 6 months. The difference between the groups was statistically significant, he said.
Moreover, gains in perfusion seen on single-photon emission CT scans were “long standing and impressive in many patients,” Dr. Steinhoff said. In one patient, perfusion had virtually normalized by 6 months, he noted.
Mean follow-up time now is 41 months in the cell therapy group and 39 months in the control CABG-only group. There have been two deaths in each group, for a mortality rate of 5.7% in the cell therapy group and 10% in the control group, Dr. Steinhoff said.
Additionally, two patients in the cell therapy group subsequently underwent percutaneous transluminal coronary angioplasty. Among the control patients, one has had a pulmonary embolism and another experienced cardiac decompensation.
“We concluded that safety and clinical feasibility was shown in the phase I trial, and that the phase II trial supported the safety and suggested clinical activity. We are now proceeding with a phase III trial scheduled to begin this year,” he said.
A total of 142 patients whose EF is 25%–30% will be enrolled, and the primary end point will be left ventricular EF at 6 months measured by cardiac magnetic resonance imaging.
But much remains to be done in the final development of this treatment, Dr. Steinhoff cautioned. Further efforts must include clarifying patient selection, assessing whether patients with worse preoperative left ventricular function derive more benefits, and confirming the long-term safety of the procedure.
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