Ultrasound Waves, Bone Marrow Cells Show Promise in Heart Failure Patients
But experts caution that larger studies of combined treatment are needed
Tuesday, April 16, 2013
The therapy is still experimental, and experts said much more work is needed. But they also said the results, reported in the April 17 issue of the Journal of the American Medical Association, are promising.
The study, which included about 100 patients, added a new twist to a therapy heart disease researchers have been trying for about a decade -- using immature cells from patients' own bone marrow to try to aid damaged heart muscle.
There has been some success in helping recent heart attack sufferers. Overall, research suggests the cell therapy can cut the risk of a repeat heart attack, and even prolong people's lives.
But it has not worked as well for chronic heart failure -- where the heart's pumping ability declines over time, causing fatigue, breathlessness and fluid build-up in the legs. In the United States, close to 6 million adults have heart failure, often developing it after a heart attack first damages the heart muscle.
One theory on the limited results for heart failure is that patients' bone marrow cells are not retained in the heart for a long enough time.
So in the new study, German researchers first "pre-treated" patients with so-called shock wave therapy, which applies high-dose ultrasound to the chest. For patients, the experience is similar to having a diagnostic ultrasound of the heart, said senior researcher Dr. Andreas Zeiher, of Goethe University in Frankfurt.
One day after the shock wave therapy, patients' hearts were infused with a dose of their own bone marrow cells.
The idea, Zeiher explained, is that the shock waves might spur the heart to churn out chemicals that attract more bone marrow cells to the damaged portion of heart muscle.
After four months, his team found, there was a 3 percent increase in the patients' left ventricular ejection fraction -- the percentage of blood pushed out of the heart with each contraction.
That's a "decent" improvement, said Dr. Eduardo Marban, director of the Cedars-Sinai Heart Institute in Los Angeles. And it's possible it could translate into long-term benefits -- like a lower risk of a repeat heart attack or longer life, according to Marban.
But, he said, larger studies are needed to prove that.
"This is a feasibility and efficacy study," Marban explained. He added that neither shock waves nor bone marrow cells are approved treatments for heart failure. "You're not going to be able to go to your doctor and ask for this."
Dr. Gregg Fonarow, a professor of cardiovascular medicine and science at the University of California, Los Angeles, agreed that caution is in order.
"Whether these findings can be reproduced, and whether there is any clinical benefit that will result from this approach, will require subsequent, well-designed clinical trials," said Fonarow.
The findings are based on 103 patients who'd developed chronic heart failure after a heart attack. Zeiher's team randomly assigned 81 patients to receive shock wave therapy; afterward, 42 of them received an infusion of bone marrow cells, while 39 were given a cell-free "placebo" infusion.
The remaining 21 patients received placebo shock wave therapy. (A cushion was placed over the chest so the ultrasound waves could not reach the heart.) They did, however, get a real infusion of bone marrow cells.
Four months later, patients who'd received the combination therapy were faring best: On average, the percentage of blood being pushed out of the heart's main pumping chamber ticked up 3 percent.
That's "modest," the researchers acknowledged, but it compared with no significant change in the other patients.
The combination-therapy group also had fewer heart-related "events," such as heart rhythm problems, hospitalization for heart failure, repeat heart attacks or strokes. There were 32 such complications among the 42 patients, versus 18 among the 21 patients who received only bone marrow cells.
Now, one of the big questions is whether the improved heart function fades with time, Zeiher said. Repeat treatments may be necessary.
"In principle," Zeiher said, "that can be very easily performed, because the procedure itself is rather simple and -- most importantly -- safe."
Marban agreed that, based on years of research experience, bone marrow cell therapy does seem to be safe.
It's not clear, though, exactly how it works. Early on, some researchers suggested that transplanted bone marrow cells actually generate new heart muscle. But studies since then have failed to show that's true.
The "best guess," Marban said, is that the bone marrow cells secrete certain growth factors that improve the heart's ability to contract.
Right now, the standard treatments for heart failure include medications that lighten the heart's workload and moderate exercise. But researchers are looking for new ways to improve the heart's pumping ability, or even regenerate the damaged muscle.
Marban and his colleagues are studying the use of heart stem cells -- primitive cells within the heart that are, in theory, capable of generating new heart muscle.
The current study was funded by Goethe University. Zeiher and a co-researcher are founders of a company, t2cure, focused on regenerative therapies for heart disease.