Encouraging Signs Follow Muscle Cell Transplantation Into Damaged Hearts

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Pilot study paves way for larger trials of treatment to repair scarring after heart attacks.

December 17, 2003

(BETHESDA, MD)—In the first trial of its type, a study of five patients with severe heart failure following heart attacks indicates that a minimally invasive technique for transplanting muscle cells into damaged hearts appears feasible and may offer benefits, according to the Dec. 17, 2003 issue of the Journal of the American College of Cardiology.

“These five patients provide preliminary results which show a favorable trend toward better functioning of the heart. Safety remains an issue, although we didn’t encounter any adverse events in our initial five patients,” said Pieter C. Smits, MD, PhD from the Erasmus Medical Center in Rotterdam, The Netherlands.

The researchers collected thigh muscle cells from each patient by biopsy. The skeletal myoblasts were isolated and cultured until hundreds of millions of the patient’s own myoblasts were available for transplantation into his or her damaged heart muscle. By threading a catheter similar to the type used for angioplasty through blood vessels into the heart, the researchers injected the myoblasts into scarred heart muscle tissue.

All the cell transplantation procedures were uneventful, and no serious adverse events occurred during follow-up. Since each patient’s own muscle cells were used, there was no need for treatment to suppress transplant rejection. One patient received an implantable cardioverter-defibrillator after transplantation because of asymptomatic episodes of ventricular tachycardia. Compared with baseline, the left ventricular ejection fraction (a measure of the heart’s ability to pump blood) increased from 36 percent (± 11 percent) to 41 percent (± 9 percent) after three months (p = 0.009) and then 45 percent (± 8 percent) after 6 months (p = 0.23).

Dr. Smits pointed out that this study was designed to look just at feasibility and safety of the muscle cell transplants, and larger studies will have to be done to gather reliable evidence of effectiveness.

“It is promising, but still I think we need to be very cautious,” Dr. Smits said.

The researchers also noted that some patients in more recent tests and other similar experiments have suffered arrhythmias (potentially hazardous irregular heartbeats) following transplantation of muscle cells. However, heart failure itself puts patients at higher risk for arrhythmias.

“It is difficult to say whether the arrhythmias are a result of these cell injections or are a result of the natural course of the disease in these patients. Larger, randomized trials are needed to get answers to this crucial question,” Dr. Smits said.

In an editorial in the journal, Raj R. Makkar, MD and colleagues from the Cedars-Sinai Medical Center and UCLA in Los Angeles praised the report. Dr. Makkar called it a very exciting feasibility study.

“I have to commend the authors on the methodology. They used multiple ways of looking at left ventricular function. The data are very exciting, and I think the authors need to be congratulated for a small, but very carefully done study. At the same time, I think future trials with myoblasts should focus a lot more on the possibility of arrhythmias occurring with this particular therapy,” Dr. Makkar said.

The editorial authors wrote that, for now, studies of this sort of cell transplantation to treat heart failure should be restricted to patients who have implantable cardioverter-defibrillators (ICDs) to protect them against a potential risk of arrhythmias. Dr. Smits and his colleagues are recruiting patients with ICDs for their follow-up studies.

“The beauty of this study is that even though it was small, it was done in the catheterization lab and it was a standalone therapy, nothing else was done, no angioplasty or other therapy that would change or improve the left ventricular function, so you can more confidently say that whatever was seen was actually because of cell therapy,” Dr. Makkar added.

James S. Forrester, MD, FACC from the Cedars-Sinai Medical Center in Los Angeles, who was not connected to either this study or editorial, said the work offers a vision of future treatments for heart failure following a heart attack.

“If you had asked me a few years ago if I thought you could inject muscle cells or stem cells into a damaged heart and have them survive, let alone improve cardiac function, I would have thought you were off your rocker. But that’s exactly what we are seeing. That doesn’t mean it’s ready for prime time, because we need a lot more experience with safety. We also need to define what type of cells and what methods of delivery are best. But this report certainly gives us a hope,” Dr. Forrester said.

The American College of Cardiology, a 29,000-member nonprofit professional medical society and teaching institution, is dedicated to fostering optimal cardiovascular care and disease prevention through professional education, promotion of research, leadership in the development of standards and guidelines, and the formulation of health care policy.

The American College of Cardiology (ACC) provides these new reports of clinical studies published in the Journal of the American College of Cardiology as a service to physicians, the media, the public, and other interested parties. However, statements or opinions expressed in these reports reflect the view of the author(s) and do not represent official policy of the ACC unless stated so.

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