New Stem Cell Therapies Promising in Severe Heart Disease

SAN FRANCISCO, CALIF.—Transendocardial injection of stem cells derived from adipose tissue appeared to be safe in patients with chronic ischemic heart disease, according to 18-month results of the first-in-man PRECISE trial.

Follow-up revealed no periprocedural complications and no evidence of cell therapy-related adverse events (see Figure), Francisco Fernandez-Avilés, MD, PhD, of Hospital General Universitario Gregorio Marañón, Madrid, Spain, said at TCT 2011. “Improvements in functional capacity and myocardial perfusion, as demonstrated by [metabolic equivalents], VO₂max and SPECT suggests potential efficacy of these cells, which should be explored in a larger trial,” he added

PRECISE was a double blind, placebo-controlled trial involving 27 patients with chronic ischemic heart disease with HF, angina, or both, who were not eligible for percutaneous or surgical revascularization. The patients were randomized  to treatment with adipose-derived stem and regenerative cells (Celution 800; Cytori Therapeutics) or placebo. The stem cell treatment utilizes a process that withdraws fat tissues from the abdomen, separates regenerative cells and reinjects them into the patient’s heart, all at the patient’s bedside. Patients in the placebo arm were given the same procedure, but placebo was injected in place of stem cells.

At 18 months, metabolic equivalents and peak oxygen consumption were greater in the stem cell-treated group compared with the control group (P=.03 for each comparison).

Adipose tissue provides an abundant supply of stem cells. The stromal layer of adipose tissue contains multipotent stem cells which, as shown in this trial, can be isolated and prepared in high numbers in 2 to 3 hours while electromechanical mapping of the left ventricle is performed. These data show that adipose-derived stem cells can be harvested in relatively large amounts with minimal morbidity, Fernandez-Avilés said.

C-Cure trial

In another study presented at TCT 2011, Jozef Bartunek, MD, PhD, of Cardiovascular Center Aalst in Belgium, reported the safety and feasibility of cardiopoietic mesenchymal stem cells in patients with chronic ischemic cardiomyopathy.

Researchers tested the efficacy and safety of C-Cure, a first-in-class lineage-specified stem cell product developed for the treatment of HF. The phase 2, multicenter, prospective, open-label study randomized patients to active treatment with guided cardiopoietic cells or optimal standard of care.

During a median follow-up of about 1 year, 13 cell-treated and 14 control patients remained free from any arrhythmic episodes. A total of 101 episodes were recorded, with no differences in incidence of atrial fibrillation or ventricular tachycardia between the groups. Of note, three episodes of ventricular fibrillation requiring ICD therapy occurred in the control group; none were observed in the cell-treated group.

Baseline cardiac structure and function, as measured by LV volumes and ejection fraction, were similar between the cell-treated and control groups. At 6-month follow-up, a trend toward a larger reduction of end-diastolic volume was observed in cell-treated patients (239.2 ml vs. 228.1 ml) compared with controls. The reduction of end-systolic volume was also significantly larger in cell-treated patients (171.4 ml vs. 167.3 ml; P=.010). Consistent with changes in volumes, LVEF remained unchanged in controls, whereas a significant increase of more than 5% was noted in the cell-treated group at follow-up, as compared with baseline. Although not powered, this change in cell-treated patients translated into a relative improvement of 18%, Bartunek said.

To address whether improved cardiac function had a clinical correlate, researchers monitored performance on a 6-minute walk distance test.  At follow-up, 6-minute walk distance improved significantly in cell-treated patients while it decreased in controls. The actual gain in 6-minute walk distance in the cell-treated group was, on average, as high as 50 meters vs. a decline of almost 20 meters in the control group.