Repairing damaged hearts

Stem cell research shows promise in regenerating heart tissue


Barry Bucchioni figured he had nothing to lose. More than three decades of avoiding medical checkups and 40 years of smoking had finally caught up to him in 2001. At 52, he suffered congestive heart failure, and his heart was so enlarged from the strain of keeping blood pumping that it pressed on his lungs so he could barely breathe. Doctors at one hospital near his home in Cleveland, USA, put him on a heart transplant list, but cautioned that even if a suitable organ became available, his odds of survival were slim.

Then surgeons at the Cleveland Clinic Foundation gave him another option: the chance to be one of the first patients in the U.S. to undergo an experimental bypass surgery that involves transplanting muscle cells to the heart. The procedure, which at the time had been performed on only a few people in France, would take about a thimble-size sample of muscle cells from Bucchioni's arm muscle, grow them in a laboratory for a couple of weeks until they multiplied to become millions of cells and then inject them into his failing heart during coronary artery bypass surgery.

The doctors "didn't guarantee me anything,'' Bucchioni said recently, during a phone interview from his home in Cleveland. In fact, surgeons underscored that while the bypass surgery might improve blood flow to his heart, they didn't expect Bucchioni to recover fully. "They said that at best I'd still probably only feel about as good as I had five months before being diagnosed with congestive heart failure,'' he said.

Bucchioni decided that the procedure was worth the risk. "I didn't think it could hurt me, and I thought if it helps other people that is just fine,'' he said. "I thought I'd take the chance.''

On June 4, 2001, surgeons performed bypass surgery - an operation that grafts blood vessels from other parts of the body onto the heart to route blood around blockages. At the same time, they injected damaged areas of Bucchioni's heart with the healthy muscle cells harvested from his arm and grown in a lab.

Three months later, Bucchioni was well enough to return to his job repairing taxicabs. He no longer has symptoms of congestive heart failure - an improvement that his doctors are careful to attribute to the bypass surgery and continued medication, not necessarily to cell transplantation. Tests suggest the transplanted muscle cells are not harming his heart, but doctors can't say whether they are helping it either.

Whatever led to his improvement, Bucchioni is happy. "I have no shortness of breath,'' he said, noting that he has also quit smoking and adopted a healthier lifestyle. "I can run up the hill, and before, I had a problem walking half a block. It's worked out really well.''

Today, a variety of improved technologies and treatments - from defibrillators, which jolt a stopped heart back into action, to balloon angioplasty, which opens blocked arteries - help more people survive heart attacks than ever before.

But that improvement comes at a price. As more people survive their heart attacks, they often live with gradually weakening hearts since heart muscle dies during a heart attack.

Over time, the the damaged heart can become progressively weaker and flabby. As it struggles to maintain blood flow, it enlarges, a condition known as congestive heart failure that now strikes an estimated five million Americans each year.

"We now have a larger number of people surviving heart attacks with weakened hearts,'' said Robert Bonow, president of the American Heart Association. "That is what is helping to fuel the heart failure epidemic.''

While coronary artery bypass surgery and angioplasty can restore blood flow to the heart after a heart attack, scaffold-like devices called stents can keep arteries from collapsing once they've been opened and pacemakers thwart irregular heartbeats, none of these widely used treatments can revive heart cells that have already died from lack of oxygen.

"The problem is that when you have a heart attack, oftentimes the heart muscle is damaged,'' said John Fakunding, director of the heart research programme at the National Heart, Lung, and Blood Institute's Division of Heart and Vascular Diseases. "There's no real way to treat that muscle damage.''

That's why experts say that finding a way to help repair the heart is critical. Although medications can help control congestive heart failure, the condition is progressively debilitating. Frequently, heart transplants are the only treatment option. Trouble is, at best there are only a couple of thousand hearts available each year - far short of the number needed.

"If we could treat these people earlier,'' said Doris Taylor, assistant professor of medicine and surgery at Duke University Medical Center in Durham, North Carolina,USA, "we could positively affect the lives of millions of people.''

That's where cell transplantation may come in. Large muscles in the legs and arms contain some cells that are able to multiply and regrow muscle when it's damaged. That's how weight lifters can build big biceps. Bone marrow also includes cells that not only can multiply but also have the ability to change into different types of cells in the body. For this reason, researchers believe that transplanted muscle cells and bone marrow cells may have the potential to restore some function to a damaged heart, and maybe - and here even the strongest proponents urge caution - regenerate new heart muscle cells and grow new blood vessels inside the body.

"It's something that has really caught the imagination of the cardiovascular community,''
Fakunding said. "Everybody hopes it will really have major potential.''

At the American Heart Association's annual meeting in Chicago recently, the latest findings from several small studies continued to point to the promise of cell transplantation for repair of failing hearts and possibly treatment of peripheral artery disease, which involves blocked arteries in the legs.

Even so, this new approach is not without risk, as the French surgeon credited with performing the first heart cell transplantation just over two years ago cautioned.

Philippe Menasche, professor of cardiovascular surgery at the Georges Pompidou European Hospital in Paris reported that in his latest study of 10 people treated with cell transplantation and bypass surgery, four developed ventricular tachycardia, a potentially fatal abnormally rapid heartbeat that may be a result of the treatment. "Fortunately, no one died and they are all under control,'' he said.

But Menasche also noted that last year health officials in Europe halted a separate cell transplantation trial because of similar complications. In that trial, which did not involve Menasche, the cells were delivered by catheter directly into heart chambers rather than injected into ailing scarred heart tissue. One participant in Italy died. Critics question whether there was enough monitoring of patients to detect the arrythmias.

The trial that was halted underscores the many unknowns about this experimental procedure at a time when it is generating huge interest among cardiologists. "The clinicians that I talk to are as excited about this as I have heard them about anything,'' said Duke U