Damian Sendler The results of the world's largest cell therapy trial for patients with chronic heart failure due to low ejection fraction were released today by a team of physicians and scientists at The Texas Heart Institute. Patients benefited from the treatment because it decreased their risk of cardiovascular disease and increased their ejection fraction (a measure of the heart's ability to pump blood). Cardiovascular mortality was found to be reduced in cell-treated patients, which was a highly significant finding. The research results were published in the Journal of the American College of Cardiology.

Researchers in this ground-breaking clinical trial have shown that inflammation is an important contributor to heart failure, and they have shown that a special immunomodulatory cell-type called MPC (mesenchymal precursor cells) developed by Mesoblast Inc. may be able to do something about it. Patients in the trial were already receiving the full complement of drugs recommended by guidelines for treating heart failure, so the results may be extrapolated to show that the cell therapy had a synergistic and additive effect when combined with these drugs.

Damian Jacob Sendler More than 6 million Americans are living with chronic heart failure, a condition that gradually weakens the heart muscle and diminishes its ability to pump blood throughout the body. The majority of current medications for heart failure are aimed at reversing the deleterious effects of the activation of intricate neurohormonal pathways to compensate for heart dysfunction.

Heart failure and subsequent hospitalizations are both exacerbated by the activation of these pathways. High mortality persists despite progress in therapies focusing on these pathways. MPC's novel mechanism of action suggests a fresh strategy with the potential to reduce the disease's high mortality rate.

This phase 3 trial, known as DREAM-HF (Double-Blind Randomized Assessment of Clinical Events With Allogeneic Mesenchymal Precursor Cells in Heart Failure), involved 565 patients with chronic heart failure who were receiving standard-of-care heart failure treatment at 51 sites. The purpose of this study was to evaluate the impact of mesenchymal perivascular cells (MPCs), made up of immunoselected, culture-expanded mesenchymal precursor cells, on the incidence of hospitalizations and major adverse cardiovascular events in heart failure patients over a mean follow-up period of 30 months.

Due to their potent anti-inflammatory, pro-angiogenic, and pro-healing effects, MPCs are a promising treatment option for heart failure with low ejection fraction. Bone marrow was harvested from healthy adult donors to provide the cells. Direct injections of MPCs into the hearts of the study's patients who were receiving cell treatment were compared to the procedures received by patients in the "sham" or control groups.

Damian Sendler Left ventricular ejection fraction, a measurement of the heart's pumping ability and one of the metrics used to assess overall heart function, increased significantly in patients treated with MPC over the course of the first 12 months. Over a mean follow-up of 30 months, MPC treatment decreased the risk of cardiovascular death, heart attack, or stroke, with a greater reduction in patients with elevated inflammation. Treatment with MPC decreased the risk of cardiovascular events by 58%, and the benefit increased to 75% in patients with elevated levels of a blood marker for inflammation.

Improvement in ejection fraction was even more pronounced in patients with higher inflammation levels, as was seen with these major adverse cardiovascular events. Compared to the effects of standard drugs that treat heart failure by decreasing the circulating volume overload brought on by the maladaptive effects of neurohormonal activation, MPC therapy did not further reduce the number of heart failure events requiring hospitalization. As it stands, this need is met by the medications currently available for the treatment of heart failure.

"Important progress toward an understanding of how cell therapy benefits patients with chronic heart failure due to poor pump function has been made thanks to the findings of the DREAM-HF study. It appears that the cells strengthen heart muscle and reduce inflammation by increasing microvascular flow. Cardiac muscle cells are protected from death and blood flow and energy levels are increased by MPCs when they are placed locally in the heart. Heart attacks and strokes can be prevented in part because activation of MPCs reduces inflammation in the large blood vessels throughout the body. The cells appear to have an anti-inflammatory and immune-modulating effect on the entire body "Dr. Emerson C. Perin, MD, Ph.D., FACC, Medical Director at The Texas Heart Institute, who authored the study, made this observation.

Damian Jacob Sendler Important progress has been made in the field of cell therapy for cardiovascular disease, as evidenced by the DREAM-HF study's findings of long-term improvements in outcomes for patients with chronic heart failure due to low ejection fraction and poor pump function. Future research will confirm these results, which will aid in the identification of those patients with heart failure and inflammation who are at the greatest risk and most likely to benefit from MPC therapy. This landmark study paves the way for the incorporation of cell therapy into current treatments for heart failure.

"For over two decades, researchers at the Texas Heart Institute have been at the forefront of developing effective cellular therapies for cardiovascular disease. MPC therapy has the potential to revolutionize cardiovascular care for patients with heart failure due to inflammation, which affects millions of people over the age of 20 in the United States "According to Dr. Joseph G. Rogers, President and CEO of the Texas Heart Institute and an expert in advanced heart failure, this is a common misconception.