Scientists are a step closer to harnessing a technique that “literally mends broken hearts”, according to the Daily Express. The newspaper says that the simple procedure “uses patients’ own cells to regrow muscle damaged by a heart attack”.
This story is based on an early-stage trial that examined the safety of using stem cells to heal the scars and cardiac tissue damage experienced after a heart attack. In the study researchers recruited patients who had recently had a heart attack and took a sample of healthy tissue from their hearts. They then used the tissue to grow stem cells that could turn into any type of heart cell and injected them directly into the hearts of 17 patients. Next they assessed the safety of the treatment over 12 months and compared the results from these patients with those from eight patients who received standard care. The researchers determined that the approach was safe. They speculated that there may be some interesting clinical results, such as a reduction in scar tissue and an increase in new heart tissue. However, as this was a trial of the technique’s safety, the effectiveness of the process will need to be examined in further studies.
This small, early-stage study identified a potential application of stem cells for the treatment of heart attacks, but a great deal of additional research is required to see whether or not this therapy will literally mend broken hearts.
Where did the story come from?
The study was carried out by researchers from Cedars-Sinai Heart Institute, the EMMES Corporation and The Johns Hopkins University in the US. It was funded by the US National Heart, Lung and Blood Institute, and the Cedars-Sinai Board of Governors Heart Stem Cell Center.
The study was published in the peer-reviewed medical journal The Lancet.
Despite some contradictory reporting on the degree of scarring reduction, the research was covered appropriately by the media, with The Daily Telegraph, BBC, Daily Mail and Daily Express all reporting that this was an early-stage study designed to investigate the safety of the procedure. The Daily Telegraph also mentioned the need for further research to determine the long-term implications of the study.
What kind of research was this?
This was a small phase I clinical trial designed to assess the safety of using stem cells found within the heart as a treatment for repairing the damage experienced following a heart attack. Such small, early-stage studies are required to ensure that a procedure is safe and feasible before larger studies to assess the effectiveness of the treatment are started.
Although stem cells can be obtained from a variety of sources, the stem cells used to treat this study’s participants were derived from their own bodies rather than embryos or foetal tissue. Treating a person using their own stem cells may provide an effective therapy as the cells are not at risk of being rejected. This study used a type of stem cell called a cardiac-derived cell (CDC), which is found in a layer on the surface of the heart. These particular stem cells can grow, or differentiate, into any type of cell found within the heart tissue.
What did the research involve?
Researchers recruited 31 patients who had had a heart attack within the previous 30 days, 25 of whom were included in the study’s final set of analyses. These patients were randomly allocated to receive either cardiac-derived cells (CDC) or standard care.
All of the patients had shown a reduction in a measure called the ‘left ventricular ejection fraction’ (LVEF). The left ventricle is one of four chambers of the heart, and is responsible for pumping oxygenated blood from the heart to the rest of the body. LVEF is a measure of the amount of blood the left ventricle is able to pump in one heart contraction.
The researchers took a sample of healthy heart tissue from the patients in the group allocated to receive CDC treatment. They used this tissue to grow CDCs, which were later injected directly back into the particular artery that had been involved in their heart attacks. This injection occurred between 1.5 and 3 months after the heart attack.
Participants in both the CDC and the standard care group had been given a scan using magnetic resonance imaging (MRI) at the start of the study, which provided an image of heart damage following their heart attack but before treatment. Researchers followed up the progress of the participants two weeks after the start of the study, then again at one, two, three, six and twelve months. The researchers assessed several safety measures at these follow-up points, including any instances of death immediately following the CDC injection, sudden or unexpected death, and a range of heart-related safety outcomes such as another heart attack, the development of new tumours of the heart and being admitted to hospital for heart failure.
Although this was primarily a trial assessing safety, the researchers also collected data on a range of relevant clinical factors in order to form a preliminary idea of whether the treatment might prove effective or feasible. This included conducting additional MRIs at six and twelve months to determine the extent of heart damage, scarring and the amount of healthy heart tissue in the left ventricle.
The researchers then compared the proportion of patients in each group who experienced any of the study’s predefined negative outcomes. They also compared the degree of heart scarring and the amount of healthy heart tissue between the two groups.
What were the basic results?
The researchers found that no patients in the CDC group experienced complications during the cell injection procedure or in the day after. The researchers further determined that:
- At six and twelve months, there was no significant difference between the two groups in the proportion of patients who experienced a serious adverse event (CDC group: 24%, standard care group: 13%, p=1.00).
- There were no deaths in either group, and no patients were admitted to hospital for heart failure or for another heart attack. No patients were found to have developed heart tumours.
When assessing preliminary effectiveness data, the researchers found that:
- At baseline (the start of the study) the average scar size (proportion of the left ventricle that was scarred) was 24% in both groups.
- The proportion of the left ventricle that was scarred did not significantly change in the standard care group between the start of the study and six months (difference in size: 0.3%, p=0.894), but significantly decreased in the group given CDC treatment (difference in size: -7.7%, p<0.0001).
- At twelve months, patients treated with standard care still did not experience a significant difference in scar size from the start of the study (difference in size -2.2%, p=0.452), while the CDC-treated group had a decrease in scar size of 12.3% (p=0.001).
- Similarly, at six months, the standard care group showed no significant difference in the amount of healthy left ventricle tissue (mass difference 0.9g, p=0.703), but this significantly increased in the CDC group (mass difference 13.0g, p=0.001). This pattern held at 12 months.
- No patients in either group demonstrated significant changes in LVEF at six months.
How did the researchers interpret the results?
The researchers conclude that the results of this safety trial offer a preliminary indication that it may be possible to regenerate heart tissue that has been damaged during a heart attack. They say that the apparent ability of CDCs to reduce both the amount of scarring and to generate new heart tissue is promising, but requires further research.
This was a small, early-stage clinical trial that was designed to assess the safety and feasibility of using adult cardiac-derived stem cells to treat patients who have suffered a heart attack. While it has helped support the safety of the technique, it is too early to tell whether this will be a viable and effective treatment. The study should be seen as leading the way to larger trials of the technique, rather than directly supporting its use in an everyday medical setting.
The study’s analysis looked at data from just those participants who successfully completed the trial according to the original criteria laid down by the researchers (25 of the 31 patients randomised). While this approach is commonly used to assess the safety of a treatment, it is not the best approach for assessing effectiveness. Further trials designed to determine the effectiveness of the technique will need to be larger and in their data analysis they will need to include all participants who started the trial, not just those who adhered to particular rules or procedures. Analysing all participants is of paramount importance during trials of effectiveness (which are typically larger than safety trials), as it allows researchers to assess factors such as whether patients will realistically be able to complete a treatment if it is given in a clinical setting.
Based on this initial study, it is unclear how the CDCs might regenerate a heart damaged by a heart attack. Additionally, it is still not known whether such a ‘repaired’ heart will affect cardiac functioning in a significant manner. The researchers say that although there were reductions in scar size after CDC treatment, there was not significant improvement in cardiac function, as measured by LVEF. The reasons for this are unclear.
While this study was a randomised controlled trial, its primary aim was to assess the safety of the procedure and it is too small to provide much indication of whether or not the therapy will work. Like a similar safety trial published last year, the study indicates that treating patients who have recently had a heart attack with CDCs is safe, and research can move on to larger phase II trials. Phase II studies are designed to determine the effectiveness of a therapy in a highly controlled setting. Phase III trials are larger still, and are required to confirm the safety and effectiveness findings of the previous studies. It is only once a therapy or treatment has found significant results in each of these phases that it can move on to be used in wider patient populations. This process can take many years, and is by no means certain.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
The Daily Telegraph, 14 February 2012
BBC News, 14 February 2012
Daily Mail, 14 February 2012
Daily Express, 14 February 2012
Links to the science
The Lancet, Early Online Publication, February 14 2012