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Texas Heart Institute
Discovery - the creation of knowledge - is the foundation of Texas Heart Institute's mission. With research programs in cardiology, cadiovascular surgery, anesthesiology and pathology, Texas Heart Institute is recognized nationally and internationally for important contributions to the battle against cardiovascular disease. Institute physicians and scientists direct research efforts ranging from artificial hearts to gene therapy. Here are some examples of how the Texas Heart Institute is revolutionizing the understanding, prevention and treatment of heart disease. Keeping Arteries Open
Aiding the Failing Heart Institute researchers have been working for years on implantable pumps that have sustained patients who otherwise would have died while awaiting a donor heart for cardiac transplantation. The ultimate goal is to provide an alternative to cardiac transplantation for patients with congestive heart failure. Recently, physicians and scientists at the Texas Heart Institute discovered that a patient's heart muscle seems to recover during assist pump support. Indeed, pumps have been removed in several patients without the need for subsequent transplantation. Additional studies are necessary to confirm this finding and to learn how to further promote the process to reduce the length of implantation. Vascular Gene Therapy Healthy arteries and arterial venous bypass grafts continuously release substances designed to prevent blood clots, arteriosclerosis, and excessive scarring, which may cause vascular obstruction. These substances include prostacyclin, nitric oxide, tissue plasminogen activator, and tissue factor pathway inhibitor. In the presence of arteriosclerosis, high plasma cholesterol levels, diabetes, or hypertension, an artery or a graft stops producing these protective substances. Similarly, if the vessel is injured during surgery, angioplasty, or stent placement, it no longer releases these substances. As a result, the organ or limb that originally received blood from the involved vessel has little defense against blood clots and obstructive scarring. Drug treatments are not very effective against this problem, and they entail possible side effects such as prolonged bleeding in patients taking anticoagulants (blood thinners). A revolutionary new option for keeping arteries and grafts open is gene therapy. With this approach, physicians can transfer to the diseased vessel a gene that contains all the information the vessel needs in order to resume the production of protective substances. This genetic information is given locally–that is, only where it is needed (at the involved vascular site). The genetic code (gene) is transferred into the vascular wall by a gene vehicle (gene vector). In animal experiments, researchers at the Texas Heart Institute's Wafic Said Molecular Cardiology and Gene Therapy Research Laboratory have used an attenuated (mutilated) virus (which can neither multiply nor spread through the body) to transfer into diseased arteries and grafts the genes that produce prostacyclin and tissue factor pathway inhibitor. A single application of these genes to the target vessel during balloon angioplasty or coronary bypass surgery increases that vessel's ability to produce prostacyclin or tissue factor pathway inhibitor. Within 24 hours after the gene transfer, the damaged blood vessel begins to produce these substances, thereby protecting itself from blood clotting, scarring, and further obstruction (restenosis). These beneficial effects are also observed in animals with arteriosclerosis. More recently, researchers at the Wafic Said Molecular Cardiology and Gene Therapy Research Laboratory have shown that a newly discovered gene (called E2F-1) can reduce restenosis after angioplasty and can inhibit the progression of arteriosclerosis by inducing the "gentle" death (apoptosis) of vascular smooth muscle cells. These cells, which normally regulate vascular tone, proliferate after angioplasty or stenting and cause scarring and narrowing of the involved vessels. Developing a Mechanical Heart Each year in the United States alone, between 50,000 and 70,000 people could benefit from a heart transplant. Since only about 2,000 donor hearts are available, scientists at the Texas Heart Institute are in the final stages of testing a battery-powered implantable total artificial heart. The artificial heart completely replaces the natural heart and consists of two pumping chambers, a power system and control electronics. Surgeons expect to begin clinical trials at the Texas Heart Institute within the next two years. Preventing Heart Attacks Scientists and physicians at the Texas Heart Institute have discovered that dangerous plaques in human arteries that are likely to interfere with blood flow and lead to heart attacks and strokes evidence a slight increase in temperature. This is a unique discovery at the Texas Heart Institute and one that is likely to be extremely important in the prevention of heart attacks in humans. In more recent work, researchers have also shown these dangerous plaques have a different pH than the remainder of the plaque. Thus, two characteristics of human atherosclerotic plaques - part of the plaque is warmer and part of the plaque is more acidic - should help in the prediction of heart attacks and strokes. In complementary studies, researchers have also shown that brief heating of the human atherosclerotic plaque for approximately fifteen minutes at temperatures of 41-42 degrees Centigrade causes the inflammatory cells responsible for plaque rupture and blood clot development to undergo a gentle death—one in which they simply go to sleep. Medically, this is referred to as apoptosis. Researchers and physicians have been constructing catheters for humans that use infrared heat detection and other heat detection systems. In the coming months, scientists plan to identify unstable plaques with temperature and pH differences and treat them with local heating to determine if this will prevent subsequent heart attack and strokes. It should also be emphasized that the ability to detect unstable plaques will allow physicians to use other treatments to prevent heart attacks and strokes. Included in the substances that will be administered to such plaques are different forms of gene therapy to reduce inflammation and blood clotting. Scientists and physicians are optimistic about these studies and the focus on prevention of heart attacks is very much in keeping with the mission of the Texas Heart Institute in trying to prevent as well as treat major cardiovascular disease. Promoting New Blood Vessel Growth in the Heart Physicians and scientists at the Texas Heart Institute, in conjunction with other institutions, have been involved in attempting to promote new blood vessel growth in the heart, i.e. angiogenesis, by the local administration of vascular endothelial growth factor (VEGF). Preliminary evidence suggests this is the means to promote new blood vessel growth in the heart and also in the peripheral circulation. In studies that will be done in the coming months, more patients will be treated with this approach to determine if such treatment results in enough new vessel growth to protect the patient from heart attacks and its consequences and reduce the need for coronary artery bypass surgery, angioplasty or stents. Scientists have also been using fibroblast growth factor (FGF) as another means to promote blood vessel growth in experimental studies with the belief it may be applied to human hearts in the future. In addition to FGF serving as an angiogenic factor, one may be able to use FGF for gene transfer into injured heart muscle cells to promote blood vessel growth and treat heart failure and other cardiovascular problems. Work is ongoing in this area in various experimental systems in the laboratories of the Texas Heart Institute. In complementary studies, Texas Heart Institute physicians and scientists are also involved in the development of new catheters for injection of growth factors into the heart without opening the chest. Laboratory experiments have already demonstrated the benefits of this technique. Improving Treatments for Children Many techniques and technologies in cardiovascular medicine and surgery are designed for adult patients and are impossible or impractical for use in children. Institute bioengineers are collaborating with pediatric surgeons at Texas Children's Hospital to develop improved techniques as well as a small efficient blood pump for open-heart surgery in children, including newborns. Researchers are conducting laboratory studies to demonstrate the effectiveness and readiness of these innovations for clinical use. Using Space-Age Technology
A similar technology - called percutaneous transmyocardial laser revascularization, or PTMR - is being performed without surgery by cardiologists. Texas Heart Institute physicians again have been among the leaders in the application of this new technology. Providing Expert Instruction Texas Heart Institute is a primary training site for new cardiovascular technologies. More than 100 different groups of physicians and other health care professionals throughout the U.S. and the world have received expert instruction and hands-on laboratory training with new techniques and devices, such as heart assist pumps and laser revascularization. Improving Diagnosis and Treatment Cardiologists
at the Texas Heart Institute are helping to pioneer the use of a new
diagnostic
modality of three-dimensional imaging that maps the electrical activity
and
motion of the beating heart. This exciting technology provides new
insights into
the progression of heart disease and serves as a navigational tool to
guide
physicians during delicate procedures. Numbered among these procedures
are
tissue ablation (destruction of tissue causing heart rhythm
abnormalities),
laser revascularization (creation of channels for blood flow in the
heart
muscle) and site-specific delivery of drugs (for example, gene therapy
to treat
blockages in coronary arteries). In addition to clinical applications,
current
efforts by Institute staff include laboratory and clinical research to
help
refine the technology and identify new applications.
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Physicians at the
Texas Heart Institute continue to work with various interventional
devices
directed at maintaining adequate blood flow of human coronary arteries,
especially after they have received angioplasty and other forms of
interventional therapy. Specifically, researchers and physicians have
been
delivering radiation into the artery following angioplasty and the
placement of
a stent. Preliminary work suggests that such local radiation may
prevent the
renarrowing of the artery requiring the patient to have a second
interventional
procedure or surgery. Although preliminary results are very
promising,
additional studies are needed.
