While preliminary, the results of the prospective randomized trial indicate that a minimally invasive approach to cell therapy is feasible for the estimated 40 percent of heart failure patients whose disease is unrelated to coronary blockages and who therefore cannot benefit from bypass procedures. Moreover, the experience so far suggests the novel stem-cell approach may be a viable treatment for these and other heart failure patients, reported Dr. Patel, director of clinical cardiac cell therapies at the McGowan Institute.
All 15 of the patients who received stem cell injections had some degree of improvement, some with dramatic results, while the conditions essentially remained unchanged in the 15 randomized to receive injections of their own blood serum.
"It is remarkable the level of improvement we've seen in these patients, who came to us with no other medical or surgical options available to them. However, we don't yet fully understand how these cells work, whether they differentiate to become heart muscle cells or cells that promote vessel growth, or whether they serve as homing signals to other cells and substances that help with repair," explained Dr. Patel.
The study took place at centers in South America. The research team obtained the necessary institutional and government health agency approval and each patient provided informed consent.
All 30 patients enrolled had severe heart failure (New York Heart Association heart failure classifications III and IV) with ejection fraction rates of less than 35 percent. Ejection fraction is a standard measure of heart function and is determined by the total amount of blood that the left ventricle pumps out per heart beat. A patient with good heart function has an ejection fraction of at least 55 percent.
Patients were scheduled to undergo the minimally invasive procedure but were unaware whether they would receive their own bone marrow stem cells or their own serum. Regardless, while under general anesthesia, each patient had bone marrow harvested from their hipbones. The cells believed to have the greatest therapeutic benefit, CD34+ cells, were isolated from the bone marrow and either injected into the hearts of patients randomized for therapy or placed in frozen storage if the patients were randomized to the control group. These patients received the same number of injections into the heart - about 25 to 30 - as the patients in the treatment group but instead of containing their stem cells, the injections were loaded with their serum. Neither group experienced any significant side effects or complications, including abnormal heart rhythms, which had been associated with other stem cell trials.
Prior to the study, the two groups had comparable ejection fraction rates. The treatment study group had an average rate of 26 percent, with the range between 21 and 34 percent, and the control group averaged 27 percent, with the range being 22 to 34 percent. Yet six months later, those receiving stem cells improved to an average rate of 46 percent, the lowest rate of improvement going up to 38 and the highest climbing to 52 percent. By comparison, the control patients average went up one percentage point, to 27, with a range between 22 and 31, indicating that some had worsening heart function.
With a six-month follow-up period now complete, the patients who had been randomized to receive the placebo treatment are now eligible to receive their own bone-marrow stem cells that had been kept frozen.
Last April, Dr. Patel reported the results of a trial looking at stem cell therapy given in conjunction with beating-heart bypass surgery for patients whose hearts were damaged by heart attack or chronic coronary disease. That study involving 20 patients also demonstrated the potential benefits of using a patient's own bone marrow-derived stem cells to treat their ischemic heart disease.
Dr. Patel and his colleagues are in discussions with the U.S. Food and Drug Administration and hope to receive the agency's approval to conduct a trial at the University of Pittsburgh that would involve giving stem cells to patients who are being implanted with heart assist devices. When a donor heart becomes available for transplantation, the native heart would be removed, allowing researchers the rare opportunity to look at the heart in its entirety and to more closely examine the effects of the stem cells.
If approved, the protocol will be performed under the umbrella of the newly established Center for Cardiovascular Cellular Therapy, a collaboration that includes the McGowan Institute, the University of Pittsburgh School of Medicine's department of surgery, the University of Pittsburgh Schools of the Health Sciences and the University of Pittsburgh Medical Center. The center will encompass clinical and research programs focused on the use of stem cells as an adjuvant treatment for a wide array of heart failure patients and for those with peripheral vascular disease.
In addition to Dr. Patel, co-authors of the current research include Federico Benetti, M.D., and Luis Geffner, M.D., of the Benetti Foundation in Rosario, Argentina; Roberto Paganini, M.D. and Daniel Brusich, M.D., of Asociacion Espanola Primera de Socorros Mutos in Montevideo, Uruguay; Robert L. Kormos of the University of Pittsburgh's McGowan Institute; and Harold C. Urschel, Jr., M.D., of Baylor University Medical Center in Dallas.