Details of a small clinical trial published in The Lancet on Tuesday reveal how scientists helped patients with hearts damaged by heart attack to re-grow healthy heart muscle and reduce scar tissue with an infusion of stem cells taken from the patients’ own hearts.
Leading international cardiologist and heart researcher Dr Eduardo Marbán, who is director of the Cedars-Sinai Heart Institute in Los Angeles and Mark S. Siegel Family Professor, is senior author of the study. He told the press what they saw in the trial:
“… challenges the conventional wisdom that, once established, scar is permanent and that, once lost, healthy heart muscle cannot be restored.”
In 2009, Marbán and his team had already shown it is possible, following a heart attack, to grow specialized stem cells from the patient’s own heart tissue (called cardiosphere-derived cells or CDCs), inject them back into the patient’s damaged heart, and see they reduce scars, increase muscle and boost cardiac function.
The purpose of the clinical trial (called CADUCEUS, short for CArdiosphere-Derived aUtologous stem CElls to Reverse ventricUlar dySfunction) was to assess the safety of such a procedure to repair damage in the left ventricle after a heart attack.
For the trial, which took place at two centres, the Cedars-Sinai Heart Institute and Johns Hopkins Hospital in Baltimore, the researchers enrolled 25 patients of average age 53, who had experienced heart attacks two to four weeks earlier.
Each patient underwent extensive imaging scans to locate and assess the severity of the scars caused by their heart attacks.
The heart attacks had left the patients with damage to their left ventricle, such that their “left ventricular ejection fraction” was between 20 and 45%, and on average, the scar tissue occupied 24% of left ventricular mass.
The patients were randomly allocated in a two to one ratio to either receive stem cell therapy or standard care (the controls). Standard care comprised conventional medical care for heart attack survivors, including prescription medicine and advice on exercise and diet.
The 17 patients assigned to receive stem cell therapy underwent a minimally invasive biopsy under local anesthetic. During this procedure, doctors inserted a catheter through a vein in the patient’s neck and removed small pieces of heart tissue, about half the size of a raisin.
Back in Marbán’s specialized lab at Cedars-Sinai, the researchers used the pieces of heart muscle to grow autologous CDCs.
When enough CDCs had grown (between 12 and 25 million of them), they re-introduced them into the patients’ coronary arteries. This was also done with a minimally invasive catheter procedure. By this time it was 1.5 to 3 months after their heart attacks.
The results showed that:
- No complications were reported within 24 hours of receiving infusions.
- By month 6, no patients had died, developed cardiac tumors or a major adverse cardiac event, although four patients in the CDC group had serious adverse events compared with one control.
- Imaging scans at month 6 showed that compared to controls, the CDC group had significant reductions in scar mass, increases in viable heart mass, regional contractility, and regional systolic wall thickening.
- At month 12 the CDC group showed average of 50% reduction in their heart attack scars (from 24% to 12%) while the controls did not show any reduction.
- However, changes in end-diastolic volume, end-systolic volume, and left ventricular ejection fraction did not differ between groups at month 6.
“While the primary goal of our study was to verify safety, we also looked for evidence that the treatment might dissolve scar and regrow lost heart muscle.”
“This has never been accomplished before, despite a decade of cell therapy trials for patients with heart attacks. Now we have done it. The effects are substantial, and surprisingly larger in humans than they were in animal tests,” he added.
Dr Shlomo Melmed, dean of the Cedars-Sinai medical faculty and the Helene A and Philip E. Hixon Chair in Investigative Medicine, describes the study as a “paradigm shift” in heart attack care.
“In the past, all we could do was to try to minimize heart damage by promptly opening up an occluded artery. Now, this study shows there is a regenerative therapy that may actually reverse the damage caused by a heart attack,” said Melmed.
The trial was part of a phase I investigative study approved by the Food and Drug Administration (FDA) in the US. Funding came from the US National Heart, Lung, and Blood Institute and Cedars-Sinai Board of Governors Heart Stem Cell Center.
The method for growing CDCs in the lab was developed by Marbán when he was on the faculty of Johns Hopkins University, who have now filed for an intellectual property patent and licensed it to a company in which Marbán has a financial interest. However, that company did not provide funds for the study.
Written by Catharine Paddock PhD