Bone Marrow Stem Cells Show Positive Results in Small Chronic AMI Trial

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For the first time, short-term improvements in regional cardiac function achieved by catheter-based injections of bone-marrow stem cells have been correlated with long-term reverse remodeling in patients with heart failure after acute myocardial infarction (AMI). Results of a small early-phase study appear online March 17, 2011, ahead of print in Circulation Research.

Investigators led by Joshua M. Hare, MD, of the University of Miami Miller School of Medicine (Miami, FL), studied 8 patients with previous AMI and a diagnosis of ischemic cardiomyopathy. After bone marrow aspiration, the patients underwent transendocardial injection (Helical Infusion Catheter; BioCardia, San Carlos, CA) of autologous bone marrow stem cells (mononuclear cells, n = 4; mesenchymal stem cells, n = 4) into the infarct and border zones. Cardiac MRI was conducted at baseline and 3, 6, and 12 months following the procedure.

Regional Improvements All Add Up

There were no serious adverse events. Ejection fraction and LV mass did not change, but peak strain measurements of contractility on cardiac MRI showed improved regional LV function in the treated infarct zone by 1 year after treatment (-8.1 ± 1.0 vs. -11.4 ± 1.3 at baseline; P = 0.04), a finding that demonstrated restored function to the level of the border zone. These improvements were apparent as early as 3 months and persisted at 6 and 12 months compared with baseline (P = 0.02, 0.013, and 0.029, respectively).

Cardiac MRI results at 1 year also demonstrated a decrease in end-diastolic volume (208.7 ± 20.4 mL vs. 167.4 ± 7.32 mL; P = 0.03) and a trend toward a decrease in end-systolic volume (142.4 ± 165 mL vs. 107.6 ± 7.4 mL; P = 0.06). A strong correlation was found between the changes in end diastolic and end systolic volume (P = 0.002), demonstrating parallel reductions in chamber volumes indicative of reverse remodeling. In addition, overall scar tissue size decreased by 18.3 ± 8.3% (P < 0.05), and heart size decreased by 15% to 20% on average.

Moreover, the improvements in infarct zone contractility strongly correlated with the changes in end diastolic volume and end systolic volume (P = 0.04 and 0.01, respectively).

The researchers conclude that “the early improvements in regional contractility of a treated infarct predicted later reverse remodeling.”

Bringing Scar Tissue Back from the Dead

According to Dr. Hare, very few cell therapy researchers have tried to restore function in the area of the infarct scar in chronic ischemic cardiomyopathy patients.

“I don’t think that’s ever been done before,” he told TCTMD in a telephone interview. “We’ve shown, I believe for the first time in humans, that you can definitively take a myocardial infarct scar that’s not moving and make the segment start to move again. These were completely dead segments. We inject the dead scar with the cells, and 3 months later the scar starts to move and is smaller, and then 6 months later, the entire ventricle has remodeled back to normal. It’s very exciting.”

Dr. Hare added that he believes the researchers have pinpointed the mechanistic basis for how the treatment works. “You inject the cells, and the cells reduce infarct size, so they reduce collagen and repopulate the tissue to some extent with new myocytes,” he said. “Then you get contractility restored in that zone, and that leads to reverse remodeling.”

Important Questions Remain

However, Warren Sherman, MD, of Columbia University Medical Center (New York, NY), cautioned that some important questions need to be answered to confirm the study results.

“Neither of the 2 cell types—especially the mononuclear cells—have, aside from a select few animal studies, been able to demonstrate reduction in infarct size when given in a chronic infarct model,” he told TCTMD in a telephone interview. “So if this holds up, and one would certainly hope that it does in a larger study, these would be quite important data.”

Dr. Sherman also noted that the catheter used to inject the stem cells does not have the capability of delivering cells precisely to an area like previous infarct tissue. “This is not a catheter that’s been known to be able to target central infarction injections any better than it can target any other area,” he said.

Improper MRI Use?

But the most important questions center around the imaging method, Dr. Sherman commented. For instance, the paper notes that some patients had “artifact distortion from delayed enhancement imaging from ICD leads. . . .”

“Up to this point in time, patients with ICD leads have been excluded from having MRIs altogether for fear the device will heat up,” Dr. Sherman said. “One of the more important observations might be that they can get patients through an MRI even in the presence of ICDs.”

In addition, because of the artifact distortion, the paper states that only 4 of the 8 patients had longitudinal assessment of scar size. “So to make claims about changes in scar size and contractility within the scar, which is one of the most striking observations they made, seems a little tenuous when you’re talking about 4 patients,” Dr. Sherman said.

Nevertheless, Dr. Hare was optimistic about what the research could mean for the field. “There’s been a sense of disappointment and the impression that [cell therapy] hasn’t worked,” he said. “I think this study breathes new life into the field. Clinicians should be excited and enthusiastic that with a lot of work, right around the corner is potentially an approvable therapy. Sometime this decade it looks like we’ll be able to do this in patients, if everything bears out in larger pivotal trials.”

“I would be ecstatic if that were the case,” Dr. Sherman commented, “genuinely.”

Study Details

The average age of the patients was 57.2 years, and the timing of the infarcts ranged from a maximum of 11 years to a minimum of 3 months prior to the study.

 

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Source:
Williams AR, Trachtenberg B, Velazquez DL, et al. Intramyocardial stem cell injection in patients with ischemic cardiomyopathy: Functional recovery and reverse remodeling. Circ Res. 2011;Epub ahead of print.

 

 

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