Researchers at the Texas Heart Institute in Houston tested mononuclear bone marrow cell transplant injections in patients with severe ischemic heart failure -- the first such study in a severely ill population. There are few treatment options for patients with end-stage ischemic heart failure, according to the study's lead author Emerson C. Perin, M.D., Ph.D., a clinical assistant professor of medicine at Baylor College of Medicine at the University of Texas Health Science Center in Houston.
Previous laboratory research has shown that mononuclear cells taken from bone marrow then injected into human tissue can promote growth in oxygen-deprived tissue. Mononuclear cells can differentiate into tissue and new blood vessels, and secrete a wide variety of proteins and growth factors, said Perin, who is also director of new cardiovascular interventional technology at the Texas Heart Institute.
Treated patients had better blood flow and could walk longer on treadmill tests than controls. They also reported less chest pain and were able to breathe better.
"To have the sustained ability to exercise at six months is significantly different than the controls. They're functional and they have their lives back," Perin said.
Researchers conducted a controlled, open label, non-blinded study of 20 patients (average age 58) with severe heart failure.
Eleven patients received injections in the left ventricle of their heart with their own mononuclear cells. The procedure involved extracting 50 milliliters of bone marrow and isolating the mononuclear cells. Using a guided imaging and mapping system, researchers carefully aimed the cells into the areas of the heart with blocked blood flow. The procedure takes about an hour and a half.
The nine patients in the control group received no treatment.
Patients were monitored on treadmill tests and had blood tests to see if the stem cells caused inflammation.
Researchers measured "reversible defects" (live heart muscle tissue that's not getting enough blood flow) and "fixed defects" (dead tissue that has become scar tissue) at baseline, two and six months.
In the treatment group, the total reversible defect made up about 15 percent of the tissue at baseline. That was reduced to an average 4.5 percent at two months and 8.8 percent at six months. Among controls, reversible defects increased from an average 10 percent at baseline to 32 percent at two and six months.
"There wasn't significant change in the amount of scar tissue between the two groups. The scar didn't change or get worse in the treated group, and the area that lacked blood flow got better in the treatment group," Perin said.
Oxygen consumption (VO2 max) and the body's ability to exercise are directly related to how well the heart can pump. "Patients who have a VO2 max of less than 14 are generally near death. A lot of the patients in this trial were close to that number at the beginning of the study," Perin said.
Patients in the treatment group started with an average VO2 max of 18ml/Kg/min (milliliters per kilogram per minute) and the control group had 17.7ml/Kg/min. The treatment group went up to 23ml/Kg/min in the first two months while the controls were at an average 18ml/Kg/min. At six months, the treatment group averaged 24ml/Kg/min, while the control group was at 17ml/Kg/min.
Metabolic equivalents (METs), which also relate to the heart's function on a treadmill, rose for the treatment group from an average 5 at baseline to 7 at six months. The control group, which started at an average MET of 5, finished the study at 4.9.
Blood tests taken at six months revealed no evidence of significant inflammation.
"The group as a whole was severely limited in their physical capacity or activity at baseline and now the treated group are leading pretty active lives, Perin said. "One of the participants in the treatment group was in his apartment building during a blackout and had to walk up eight flights of stairs. He did it, and it wasn't a problem."
Perin warned that these results need confirmation in a placebo-controlled, blinded and randomized trial. "This is the first step. It's incredible to see that this is a safe procedure with sustained improvement," he said. "It's the impetus we need to go forward ."
Co-authors are Hans F. Dohmann, Radovan Borojevic, Suzana A. Silva, Andre L. Sousa, Guilherme V. Silva, Claudio T. Mesquita, Luciano Belem, Fernando O Rangel, Joao A. Assad, Antonio C. Carvalho, Isabel Rossi, Hans J. Dohmann, and James T. Willerson.
Note: Presentation time is 9 a.m. EST, Wednesday, Nov. 12, 2003.
Note: This abstract will be featured in a news conference.