Tuesday November 15 2011
Heart failure causes the heart to pump blood less effectively
The Daily Telegraph reported that it may be possible for patients to use their own stem cells to repair the damage caused by heart attacks. The newspaper said that heart repair with stem cells could be the “biggest breakthrough in a generation”.
The news is based on a small safety trial that tested whether people with heart failure could have stem cells extracted from their heart, grown in a lab and safely injected back into the heart. The study, which is still in progress, found that the treatment did not lead to any negative effects in the year after treatment. Participants also saw improvements in heart function, scarring and quality of life compared with before treatment. A group of volunteers with heart failure who were not given the treatment showed no improvements in the symptoms of their heart failure.
This trial has shown another potential application for stem cells, which are at the forefront of medical research. However, the study was designed to look at safety rather than effectiveness, and was, accordingly, short and small. Given the limited nature of the trial, larger, longer trials will now be required to see whether these initially promising results can be replicated and whether the technique will prove safe and effective in the long-term.
Where did the story come from?
The study was funded by The University of Louisville Research Foundation and the US National Institutes of Health. It was carried out by the University of Louisville with lab work conducted by Brigham & Women's Hospital, a teaching hospital affiliated with Harvard Medical School. It was published in the peer-reviewed medical journal The Lancet.
The Daily Mail and The Daily Telegraph covered this study, with both highlighting that it was preliminary research that involved a small number of patients only.
What kind of research was this?
This was a phase 1 randomised controlled clinical trial that assessed the use of a form of stem cell therapy for people who had damage to their heart. Phase 1 trials recruit a small number of people and typically focus on the safety of a potential treatment rather than how effective it may be. The main outcome that the researchers were concerned with in this trial was short-term safety of the treatment, although, as a secondary measure, they also looked at the effectiveness of stem cell treatment compared with the recovery of members of the control group who did not undergo stem cell treatment or the injection process needed to introduce stem cells into the heart.
The adult heart contains cardiac stem cells that have the capability to develop into various types of cell found in the heart, including myocytes (heart muscle cells that contract when the heart beats), blood vessel cells and the muscle cells found in the blood vessels. Cardiac stem cells can also keep on dividing and replicating to replenish the heart’s supply of cardiac stem cells.
When a person’s heart tissue becomes damaged they can develop heart failure. Rather than meaning that their heart is about to stop beating or fail completely, the term means the heart can no longer pump enough blood round the body. The researchers wanted to see whether it was possible to extract stem cells safely from healthy areas of the heart and introduce them to damaged areas in people with heart failure. Earlier animal studies had shown that this technique could improve heart function in animal models of heart attack.
What did the research involve?
The study was called the Stem Cell Infusion in Patients with Ischemic Cardiomyopathy (SCIPIO) trial. The study recruited people who had experienced heart failure caused by lack of oxygen to their heart muscle cells. The participants had experienced a prior heart attack and their heart function was less or equal to 40%, as judged by an ultrasound investigation. They all had evidence of a scar on their heart tissue and had all received a type of operation called a heart artery bypass graft. In this procedure blood vessels are grafted around clogged and narrowed arteries in the heart to help maintain healthy blood flow. Only patients aged under 75 years were eligible to participate in this study.
The patients were randomised to receive either the stem cell treatment or no additional treatment after their bypass surgery. There were 16 people in the treatment group and seven people in the control group.
At the time the patients had undergone their bypass surgery a small sample (1g) of healthy heart tissue was extracted. The stem cells were isolated from the heart tissue and grown in a laboratory until the researchers had 1 million cells. The stem cells were injected into the damaged area of the heart through a catheter. The control group did not undergo this cardiac catheterisation.
The patients received ultrasound heart scans, laboratory tests and physical examinations prior to receiving the stem cell treatment. These tests were also performed on control participants. All participants were also asked to complete the Minnesota Living with Heart Failure Questionnaire to see how their condition affected their quality of life. All of these tests and measures were performed four and 12 months after the stem cell or control treatment. Where possible, a cardiac magnetic resonance imaging (MRI)scan was also performed at this time and a 24-hour heart monitor was worn one week and four weeks after the treatment to detect any heart rhythm problems.
What were the basic results?
The researchers reported that there were no side effects related to the stem cell treatment. The researchers analysed heart function in 14 of the patients treated with stem cells and all seven of the control patients. They looked at heart function in the treated group and found that it had improved from an average functioning level of 30.3% before treatment to 38.5% at four months after the treatment. However, the control group did not show an improvement in this period, with their heart function at 30.1% before treatment and 30.2% four months later. After one year the hearts of the stem cell patients were pumping higher volumes of blood than before treatment.
The researchers measured the area of damaged tissue before and after treatment using a cardiac MRI scan in seven patients that had received stem cell treatment. They found that at four months after treatment the area of the damaged tissue had decreased by 24%, and at one year it had decreased by 30%.
On average, quality of life scores improved beyond their initial level in the 16 patients treated with stem cells, but remained unchanged in the control group.
How did the researchers interpret the results?
The researchers say that their study demonstrated that heart stem cells can be isolated and grown from about 1g of heart tissue. They say that infusion of these stem cells back into the person that they were derived from does not lead to side effects for up to one year, and was associated with improvement in heart function, a decrease in heart scarring and an increase in quality of life compared with before treatment.
The researchers say that “although the primary purpose of our phase 1 trial was to assess the safety and feasibility of these cells, the treatment effects are very encouraging and compare favourably with previous trials of bone marrow cells” (another source of stem cells).
The researchers say that their results warrant follow-up studies for this treatment in patients with a poor outlook following heart failure that has been caused by damage of the heart tissue following blockage of blood flow.
This was a small, initial study designed to focus on the short-term safety of using a person’s own stem cells to treat heart failure caused by damage to their heart tissue. Rather than looking at how effective the treatment was, the study was set up to examine the short-term safety of using stem cells in this way. It has demonstrated the technique to be safe (at least over one year), and no treatment-related side effects were reported.
As a secondary outcome the research found that, compared with prior to treatment, the treatment improved some aspects of heart function, partially reduced heart tissue scarring and improved quality of life one year after treatment. The control group did not show these improvements over an equivalent length of time.
The study group was small, with just 16 receiving the stem cell treatment. A small study group is necessary in preliminary safety studies such as this. Also, as the trial looked at safety rather than effectiveness, there were not complete data on measures of effectiveness in all these patients. Overall, the small number of people examined in this safety trial means that the effectiveness of this treatment will have to be assessed through a larger trial to ensure that the observed effects were not due to chance.
The safety (and effectiveness) of the treatment was assessed for up to a year in this study and extended follow-up is needed to see if this treatment is safe in the longer term.
The study only included people under 75 years of age and who had a particular type of severe heart failure following heart attack. Further studies are needed to see if this treatment is suitable for other types of heart failure. Nevertheless, this preliminary study shows a promising application of this type of stem cell treatment.