Mesenchymal stem cell therapy has helped reduce mortality, the number of heart attacks, and strokes among patients suffering from chronic NYHA functional class II and III heart failure with reduced ejection fraction.
Chronic heart failure is a condition in which the heart cannot pump blood properly, as a result of which organs and tissues suffer, resulting in organs and tissues a lack of oxygen and nutrients. In heart failure with a reduced ejection fraction (HFrEF), the heart muscle increases and weakens, leading to a decrease in pumping ability and the accumulation of fluid of the body tissues. Inflammation plays an important role in the progression of heart failure over time.
The new study, presented at a virtual session of the American Heart Association on November 13-15, 2021, looked at the effects of mesenchymal stem cells (MSCs) in the heart to fight inflammation and treat chronic heart failure.
Scientists have hypothesized that a single injection of MSCs from healthy adult donors in addition to guideline-directed medical therapy (GDMT) for heart failure will reduce the number of hospitalizations for heart failure cases and reduce the number of heart attacks, strokes, and/or deaths.
“Cell therapy has the potential to change how we treat heart failure. This study addresses the inflammatory aspects of heart failure, which go mostly untreated, despite significant pharmaceutical and device therapy development. Our findings indicate stem cell therapy may be considered for use in addition to standard guideline therapies”, – says Emerson C. Perin, M.D., Ph.D., study’s lead author, director of the Center for Clinical Research, and medical director of the Texas Heart Institute, Houston.
The “Randomized Trial of Targeted Transendocardial Delivery of Mesenchymal Precursor Cells in High-Risk Chronic Heart Failure Patients with Reduced Ejection Fraction”, also called the DREAM-HF trial, is the largest study of stem cell therapy in people with heart failure to date.
This multi-center, randomized, sham-controlled, double-blind study enrolled 537 patients (mean age 63 years, 20% women) with heart failure and reduced ejection fraction of the left ventricle, the main pumping chamber.
Chronic heart failure was determined using New York Heart Association (NYHA) functional classification system. The system places patients in one of four categories based on how limited they are in physical activity. Grade I heart failure means no limitation of physical activity, and grade IV heart failure means the inability to perform any physical activity without discomfort.
The participants were randomly divided into two groups: 261 patients received an injection of 150 million mesenchymal stem cells directly into the heart using a catheter. The remaining 276 adults underwent a similar procedure but with the introduction of a placebo. The mesenchymal stem cells for testing were obtained from healthy adult donors.
Study participants were discharged from the hospital the day after the procedure and followed up by scientists for an average of 30 months. First of all, the researchers wanted to determine if stem cell treatment would affect the likelihood of participants returning to the hospital with worsening heart failure. Patients were also monitored for heart attacks, strokes, mortality, and highly sensitive C-reactive protein (CRP) levels, a blood indicator that signals inflammation.
While the researchers did not notice a decrease in hospital admissions after stem cell treatment, they did notice several other significant results:
- Those who received stem cell therapy experienced a 65% reduction in the likelihood of attacks of non-fatal heart attacks and strokes throughout the study period;
- Participants with high levels of inflammation (CRP levels of at least 2 mg/L) were 79% less likely to have a heart attack or fatal stroke after stem cell treatment;
- Stem cell therapy reduced deaths from heart disease by 80% in people with high levels of inflammation and less severe class II heart failure.
“We were impressed to learn that stem cell treatment effects were additive to current standard heart failure treatments”, – says Perin. “For the first time, the known anti-inflammatory mechanism of action of these cells may be linked to a cause-and-effect benefit in heart failure. The stem cells acted locally in the heart, and they also helped in blood vessels throughout the body.”
Perin and his colleagues believe that further research is needed to understand better the mechanism of the effect of mesenchymal stem cells on the progression of heart failure. There is also a need to define a strategy to help patients get the most out of this treatment.