This Week in Circulation: the Long Reach of the N-Terminal of B-Type Natriuretic Peptide
High levels of the N-terminal fragment of the BNP prohormone (N-BNP) appear to be a powerful tool that foretells the mortality risk of patients who have acute coronary syndromes, according to researchers from Norway, Sweden, and the United Kingdom in a report that appears in this week’s issue of Circulation (Circulation. 2002;106:2913–2918).
The researchers led by Torbjørn Omland, MD, of the Department of Cardiology at the National Hospital in Oslo, Norway, obtained blood samples from 204 patients who were in the subacute phase of an ST-elevation myocardial infarction, 220 with non–ST-segment elevational myocardial infarction and 185 with unstable angina. After monitoring patients for an average of 51 months, 86 patients had died. The researchers found that median N-BNP levels were significantly lower in long-term survivors than in patients who died (442 vs 1306 pmol/L; P=0.0001). In a statistical analysis of the data, they found that N-BNP levels were more important in predicting the future of patients than Killip class, patient age, and left ventricular ejection fraction.
75th Scientific Sessions of the American Heart Association
Engineering Parts for Old Hearts
Chicago, Ill—With aged and failing hearts taking first place in the concerns of heart specialists worldwide, many researchers are searching for ways to shore up organs that cannot effectively fulfill their duties. As Valentin Fuster, MD, of Mount Sinai Medical Center in New York, told attendees at the November 17, 2002, session of the 75th Scientific Sessions of the American Heart Association (AHA), the aim is to develop new grafts, new stents, and to find ways to correct the defects that cause arrhythmias.
Todd McAlister, MD, of Cytograft Tissue Engineering in Novato, Calif, built his blood vessels out of fibroblasts grown in a sheet and then rolled together to mature and form the outer layer of the blood vessels. “We based our technique on sheet-based tissue engineering,” he said. “What makes this unique is that we can build mechanically viable blood vessels from the patient’s own cells.”
In other attempts to engineer organs from tissue, researchers have depended on a mechanical scaffold, he said. Their process uses no synthetic scaffold. “We believe one of the reasons for long-term failure (of these engineered organs) is inflammatory response to the synthetic scaffolds and their subsequent degradation,” said Dr McAlister.
“ We took cells from patients with advanced vascular disease,” said Dr McAllister. He said he and his colleagues have high hopes for the process because their products are built from the patient’s own cells, alleviating the need for immune suppression.
As he imagines the process, he said the blood vessels are built over a period of 14 weeks and are 20 to 25 cm long. He said they would be used in shunts for patients undergoing hemodialysis or in patients who have had one bypass procedure already and have no saphenous vein to use in another. Diabetic patients with multivessel disease would also be likely candidates for the technique, he said.
Douglas B. Cowan, PhD, of Harvard Medical School in Boston, Mass, was looking for an alternative to implanting a pacemaker in children with complete heart block. “With children with this condition, all you can do is implant a pacemaker. In very small children, you need to feed the wires through very small blood vessels, and if that is not possible, you put the leads outside the heart,” he said. “The leads have to be wound around inside the child. You get a lot of lead fractures and loss of leads. The batteries wear out after 5 to 7 years.”
In studies with rats, he used skeletal myoblasts and mixed them with a collagen matrix to position the cells and keep them intact. The mixture was implanted in the space between the atrium and the ventricle. They then demonstrated that an electrical current moves from cell to cell.
“We are at the embryonic stage in this research,” said Dr Cowan. “We are now looking at proof of principle.”
Cecilia Garcia, PhD, of the University of Texas Southwestern Medical Center in Dallas, Tex, described the development of a new tissue-engineered biodegradable stent for use in children. When they put their biodegradable sent seeded with cells from the patient to coat it in pigs and compared it with another stent without the autologous coating, they found that the tissue-engineered stent with the autologous cell coating maintained its lumen better and had less inflammation than the other.
“This area of tissue engineering is evolving and will be very significant in the near future,” she said.
Muscle and Bone Marrow Cells to Strengthen Hearts
Using skeletal muscle cells grown to hundreds of millions in culture to repair a heart damaged during an acute myocardial infarction may be the wave of the future for patients whose heart can no longer pump effectively, said Nabil Dib, MD, MSc, Director of the Cardiovascular Research at the Arizona Heart Institute in Phoenix.
Dr Dib enrolled 16 patients in his study of the technique—11 received coronary artery bypass surgery and 5 received a left ventricular assist device. “All patients had had a previous myocardial infarction, and all had contractility of heart function of less than 30%,” he said.
The skeletal muscle cells grown in the laboratory were injected into the scar tissue after the heart attack. A scan with magnetic resonance imaging, as well as with positron emission tomography scanning, revealed living tissue in the scar, he said. The transplants were safe in all the patients. He said he saw no significant adverse events in doses that ranged from 10 million to 300 million cells. One patient had an irregular heartbeat 7 days after the heart transplant, but it was treatable.
He said the technique was safe and the findings encouraging enough to proceed with larger trials that will determine if the cells aid heart function. “This therapy, if proven to work in the future, will clearly improve the quality of life for many patients and could replace heart transplants,” said Dr Dib.
In a similar study, Tomasz Siminiak, MD, PhD, Professor of Cardiology at the University School of Medical Science in Poznan, Poland, described his phase I trial of skeletal myoblast transplants in patients undergoing coronary artery bypass grafting. The cells were grown in culture and injected into the scar during the surgery, said Dr Siminiak.
Although it is too early to determine the true effect, he said some studies indicate that the injection improved some measurements of heart function.
In a departure from the earlier studies, Manuel Galinanes, MD, of the University of Leicester in the United Kingdom, along with his colleagues, obtained bone marrow from patients who were undergoing elective cardiac surgery. All of them had an area of scarred tissue that had been diagnosed before the operation.
Dr Galinanes and his colleagues injected the patients’ own bone marrow cells into the scar tissue of the heart. “We thought bone marrow cells had advantages over other cells,” he said. “They were ethically acceptable and there would be no need for immunosuppression. Bone marrow is readily available.”
The 14 patients in the study did well clinically. None died, and there were no heart attacks during the operation and no evidence of ventricular arrhythmia, he said. A stress echocardiogram used to examine the ability of the heart to contract 6 weeks and 10 months after the surgery demonstrated improvement in function, but only at the 10-month period, he said. The improvement was most effective when the patient received a CABG and bone marrow, he said.
Christof Stamm, MD, of Rostock University in Germany, used bone marrow stem cells in the treatment of patients who had had a myocardial infarction from 10 days to 3 months before they were referred for CABG. Their scar tissue had to be in an area that couldn’t be treated by CABG or by percutaneous intervention, although they would benefit from reperfusion in other parts of the heart.
The day before surgery, Dr Stamm and his colleagues took bone marrow from the patients’ hipbone. Cells were then selected on the basis of markers that identified them as potential stem cells. The stem cells were then purified.
Patients then underwent bypass grafting and received injections of as many as 5 million stem cells around the border of the scarred area.
All patients who underwent the procedure survived and were discharged to rehabilitation or to their homes. Dr Stamm said he had identified improvement in the ability of the heart to contract in 8 of the first 10 patients who underwent the procedure.
Awards at the Scientific Sessions
Douglas D. Schocken, MD, received the American Heart Association Chairman’s Award during the 75th Scientific Sessions opening session. The award, designed to honor individual excellence in volunteer service to the organization, was given to Dr Schocken in recognition of his leadership at various levels since he became involved with the AHA in 1983.
Dr Schocken is a Professor of Medicine at the University of South Florida College of Medicine and Professor in the Department of Epidemiology and Biostatistics at the University of Florida College of Public Health. Dr Shocken works locally with the chapter in Tampa, Fla, and with the Florida/Puerto Rico Affiliate. Nationally, he chaired the Advocacy Committee from 2000 to 2001, and has also chaired the Subcommittee on National Affairs and the Southeastern Regional Research Peer Review Consortium. He has also served on the Council on Geriatric Cardiology, including chairing the Finance and Membership committee.
Eugene Braunwald Academic Mentorship Award
Ronald M. Lauer, MD, received the Eugene Braunwald Academic Mentorship Award, which honors individuals whose academic careers have been marked by mentoring promising young academicians. Dr Lauer, Professor of Pediatrics and Epidemiology at the University of Iowa, was Director of Pediatric Cardiology at the school from 1968 until 1996. Soon after arriving in Iowa as director of the Division of Pediatric Cardiology, he established a training program that became a model for academic pediatric cardiology training. As principal investigator of a long-term study of early predictors of coronary heart disease—the Muscatine Study—Dr Lauer mentored many young faculty members from both clinical and epidemiologic fields through the early phases of their careers.
Basic Research Award
Richard Lifton, MD, Professor and Chair of the Department of Genetics at Yale University School of Medicine in New Haven, Conn, received the Basic Research Award at the Scientific Sessions this year. The Basic Research Prize was begun in 1990 to reward a researcher who is making outstanding contributions to the advancement of cardiovascular science and who currently heads an outstanding cardiovascular research laboratory.
Dr Lifton is a member of the American Heart Association’s Council for High Blood Pressure research and a recipient of that Council’s prestigious Novartis Award for Hypertension Research. Dr Lifton’s laboratory uses molecular genetic analysis to gain better understanding of the physiological processes that regulate cardiovascular function in people. The emphasis in the research is on the regulation of blood pressure. His studies have identified pathways that point the direction to the development of new drugs that will aid in the regulation of blood pressure.
Research Achievement Award
Victor McKusick, MD, a renowned genetics researcher, received the AHA’s Research Achievement Award during the opening session of its annual scientific meetings. Dr McKusick, University Professor of Medical Genetics at the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins University School of Medicine in Baltimore, Md, was honored for seminal contributions in cardiovascular medicine that have led to the discovery of the causes of heart diseases as well as shaping new treatments.
Dr McKusick is the author of more than 750 reports on the pathophysiology of human diseases and is Editor-in-Chief of Medicine, founding editor of Genomics, and author of 12 editions of Mendelian Inheritance in Man. He is senior author of the online Mendelian Inheritance in Man.