Medical Device Daily Associate

Researchers at the Minneapolis Heart Institute Foundation said they have launched a study to examine whether administration of stem cells to first-time heart attack patients can prevent the development of congestive heart failure (CHF).

The study protocol calls for patients with acute myocardial infarctions to be admitted to either the University of Minnesota (Minneapolis) or to Abbott Northwestern Hospital (also Minneapolis) – with which the Minneapolis Heart Institute has an affiliation – through its nationally recognized Level 1 heart attack program, which allows patients to undergo immediate angioplasty and stenting.

Patients will then undergo bone marrow aspiration and harvesting of their stem cells three to seven days later, which will be followed by an intra-coronary infusion of the isolated stem cells on the same day.

Of the 60 patients in this new study, 45 patients will have their stem cells infused through a catheter in the region of their heart attack, and 15 will receive a placebo. Patients in the placebo group will receive cell therapy six months following their heart attack.

The study is intended to look exclusively at patients with moderate to large heart attacks, putting them at risk of developing CHF.

CHF diagnosis is the leading cause of hospitalization in the U.S. and is responsible for more than 50,000 deaths a year. Currently, heart transplantation is the only available cure.

Each year more than one million Americans have their first heart attack, putting them at risk of developing CHF as a result of cardiac cell death and scar formation which results in diminished pumping ability of the heart and leads to exercise intolerance and fluid retention.

However, researchers believe that patients' own bone marrow-derived stem cells, which are capable of secreting a variety of growth and survival factors, can improve cardiac function after a heart attack and fend off the development of CHF.

To date, several clinical trials in Europe have demonstrated the safety and feasibility of using adult stem cells for cardiac repair following acute myocardial infarction, but in most of the studies the heart attacks were small and therefore much less likely to lead to the development of CHF.

“Europe and Asia started doing these [types of studies] a couple of years ago . . . but there's been nothing published or completed [on stem cells in CHF], just because the regulatory issues and the hurdles are a little bit higher,” Jay Traverse, MD, a cardiologist with the Minneapolis Heart Institute and principal investigator for the study told Medical Device Daily.

He also noted that the studies done outside the U.S. were carried out on patients “with pretty small infarcts [and] they're ejection fractions were only mildly decreased.” In other words, patients in these trials “were not likely to go on to develop congestive heart failure, which is really the group of patients that needs this type of therapy.”

Traverse noted that this “first-of-its-kind study” in the U.S. is randomized and placebo-controlled, involving 60 patients with moderate to large anterior infarctions who will receive an intra-coronary infusion of their own stem cells or placebo. All patients will receive standard treatment including aspirin, beta-blockers, ACE inhibitors and statins.

The study, which is funded by the Minneapolis Heart Institute Foundation, the Abbott Northwestern Hospital Foundation and the National Institutes of Health (NIH; Bethesda, Maryland), is being conducted following FDA trial approval this past September.

Traverse said that investigators for the trial – which has enrolled six patients since it began back in November – hope to get at least a “several percent retention” of the stem cells in the heart, which could add up to a “couple million cells setting up shop in the area of the infarct.”

While he said that the best way found thus far to get the cells into the heart has been a direct injection via a needle at the end of a catheter (studies have shown at least a 10% retention of cells with this method), that was not a viable option in the case of the patients involved in this study. The problem is that everyone was a bit anxious about sticking a needle into an area that has already had an infarct. He said the more direct injection approach has only been used on chronic ischemia patients who have already undergone bypass and angioplasty with a scarred over infarct that have no other options.

The use of what Traverse called a “true placebo,” something not found in most of the European and Asian studies, is another important aspect of this study. “I think we've learned over the years. . . that if you don't have a placebo you tend to get patients who know they got the drug and say they feel a lot better,” but who have in fact not really improved all that much at all.

Placebo patients undergo the same procedure including the aspiration and harvesting procedures and have a solution that looks fairly identical to the stem cells infused into their artery.

Traverse said he expects complete enrollment of the trial to take at least another year, but that the process could be sped up if the expensive cost of the stem cell process could be offset with more extensive NIH funding. With the added funding he said the trial could be opened up to the whole Twin Cites area. For now though, the patients are only coming from the University of Minnesota and Abbott Northwestern. The goal of the study, according to Traverse, is to reduce the development of CHF with the therapy.

“What we're hoping is that these stem cells will help salvage a lot of the cells that were injured from the infarction that would normally go on to die.” As for possible cell regeneration, he noted that while the issue “is still up in the air,” he said European studies that have started with a superior patient ejection fraction (EF) showed close to a 10% improvement in that clinical measurement.

“We're starting out with an average EF of about 40%. It would be great if patients' ejection fractions would improved up to 50% or so, but we don't know if that's going to be possible or not.” The patients will be followed for two years following treatment, with MRI used to determine if the therapy reduces scarring and improves cardiac function.

Traverse told MDD, “If we can prove that using adult stem cells can reduce the development of CHF, many people could potentially benefit from this study."

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