The discovery of new knowledge to improve patient care and to prevent cardiovascular disease is the motivating force in everything the Texas Heart Institute does. THI is recognized nationally and internationally for its important contributions to the discovery of new knowledge, and support from the private sector has played a key role in making these advances possible. Physicians and scientists at THI work tirelessly to unfold the mysteries of nature and disease, to understand the mechanisms at work, and to envision solutions that will ultimately lead to effective treatments.
Global Leadership in Adult Stem Cell Research
The Stem Cell Center of the Texas Heart Institute at St. Luke's was first in the U.S to receive FDA approval for an adult stem cell clinical trial to treat patients with advanced heart failure. Stem cells were harvested from the patient’s bone marrow and injected directly into damaged but viable heart muscle with a special catheter. That study recently enrolled its 30th and final patient. The purpose of this randomized study is to validate that this form of therapy can improve heart muscle function and blood flow in patients with severe heart failure. Monitoring and follow-up of patients continues and Stem Cell Center physicians hope to publish their results soon.
It’s very significant that in the last year the Texas Heart Institute was one of five centers selected by the National Institutes of Health to study stem cell treatments for patients with cardiovascular disease. The National Heart, Lung and Blood Institute is providing a grant of $33.7 million over the next five years to support the new national consortium called the Cardiovascular Cell Therapy Research Network. The network represents the first U.S. federal funding for adult stem cell studies in which patients are treated with stem cells taken from their own bodies.
THI also received a second FDA-approved protocol where extracted bone marrow cells that highly express the enzyme aldehyde dehydrogenase are harvested by a procedure to create a highly purified stem cell population. These stem cells have the potential to build new blood vessels in damaged hearts, which could ultimately lead to better functional improvement in advanced heart failure patients.
Another important stem cell type is the mesenchymal cell. THI physicians and scientists have shown this stem cell improves recovery from heart attacks in animal models. Earlier this year, THI began the world’s first clinical trial to treat heart attack patients with precursor mesenchymal stem cells, taken from a young and very healthy individual, to prevent congestive heart failure, which many patients develop following a heart attack. These stem cells appear not to be rejected or cause inflammation when given to another human directly into the heart.
The Stem Cell Center is also conducting a study for peripheral vascular disease. These patients have severe blockages in the legs, they have exhausted all other treatments, and they are at risk of amputation. The stem cells are injected directly into the leg muscle.
The Texas Heart Institute has also been established as a NOGA Core Lab, the only one of its kind. The NOGA Cardiac Navigation System is a 3D-imaging method used to identify target sites for delivering stem cells to the heart by measuring electrical and mechanical function of the heart. The NOGA Core Lab helps other institutions analyze data and provide feedback about procedures used in stem cell research. The Stem Cell Center at THI is also a Site for Training Excellence in the NOGA procedure. Physicians from around the world travel to THI for hands-on training in the use of this intricate device.
Stem cell research is a relatively new discipline which is quickly evolving, as THI scientists in many different specializations of cardiovascular research incorporate stem cells into their studies. Stem cell therapy is a safe, promising treatment for patients with diseases of the heart and blood vessels. THI is committed to conducting research at all levels to determine the best approach for using stem cells to repair these tissues. Ideally, stem cell therapy may someday be used not only to treat these problems, but also to prevent them.
Unrivaled Experience with Mechanical Assist Devices
For more than 30 years, physician scientists at the Texas Heart Institute have amassed the world’s greatest experience in the development and use of ventricular assist devices (VADs) to sustain the failing circulation in patients with severe heart failure. Nearly 900 patients have received VADs since the research program began. More than a dozen different VADs are being studied in clinical trials, and even more are under development in preclinical studies.
While some of these pumps are for temporary use and deployed through the skin, others are surgically implanted and used as a bridge to heart transplantation. Patients with VADs can now be discharged home to await transplantation. While they are waiting, they lead fairly normal lives—a significant goal of this research. One VAD, developed and studied here, has been approved for permanent use (destination therapy) for patients in the United States.
A key area of research is the concept of using VADs to allow the patient’s heart to recover normal function. (See multimedia room for one patient's story.) This involves determining the right indicators that recovery has occurred, establishing testing methods to determine recovery and refining surgical methods to remove the VADs with minimal invasion. Over the last three years, seven patients supported on a long-term basis with a HeartMate II VAD have achieved recovery, allowing for the removal of their devices. THI physicians have conducted 76 HeartMate II implants since 2003, when the national HeartMate trial began.
Researchers are also working on the development of a total artificial heart that would deliver blood by continuous flow rather than pulsation. The pumps are smaller, less expensive and more reliable than the previous generation of total artificial hearts, and they can be implanted in adults of all sizes. To date, preclinical studies confirm the feasibility of supporting the circulation with dual continuous-flow pumps.
Understanding the Biomolecular Mechanisms for Cardiovascular Disease
THI scientists are paving the way for a new era of medicine by identifying genes and proteins that cause cardiovascular diseases. By identifying genetic risks, physician scientists can find promising treatments, isolate environmental threats, and assess how to modify human behavior to improve health.
Identifying the genes responsible for the diseases and the appropriate medical responses points to new hope in conquering heart and vascular diseases. THI scientists have identified four genes that are associated with heart attacks among 15,000 patients they have studied and they are currently evaluating other genes that may be associated with heart failure.
Many medical conditions result from flaws, or mutations, in one or more of a person’s genes. Mutations cause the protein encoded by that gene to malfunction. When a protein malfunctions, cells that rely on that protein’s function do not behave normally, causing problems for whole tissues or organs. Over the last decade, more than 100 mutations in a dozen genes have been identified in patients with hypertropic cardiomyopathy (HCM), a condition in which the heart muscle thickens, which can block or reduce the flow of blood throughout the body. HCM, which causes several varieties of heart problems—not the least of which is sudden death—affects an estimated 600,000 to 1.5 million Americans, or one in 500. Genetic information, in combination with clinical data, can be used to personalize disease management and predict the risk of sudden death in HCM patients. The same genetic techniques used in patients with HCM are also being used to study the identification of genes that cause premature heart attacks.
Physician scientists at THI want to be able to reduce a person's likelihood of developing cardiovascular disease based on his or her genetic profile, as well as on the individual's age, gender and lifestyle habits. They have already established a preliminary genetic profile, based on four genes that would enable individuals to adopt the habits most likely to reduce risk because different genes or gene combinations respond differently to changes in diet, exercise, smoking, alcohol consumption, or medications such as cholesterol-lowering drugs. And as more and more information comes to light, recommendations for lifestyle changes and new treatments will become available.
One study underway is the pursuit of treatment for carotid and peripheral arterial disease with the COX-1 gene, which promotes the development of new blood vessels. In pre-clinical models THI scientists have observed significantly improved blood flow with transfer of the COX-1 gene in combination with a tissue factor pathway inhibitor, which inhibits coagulation. These findings may eventually lead to an anti-clotting treatment that could be delivered locally or regionally without the systemic complications of coagulation seen with existing drugs.
Nonsurgical Treatment for Heart Disease
Texas Heart Institute physicians rank as world leaders in nonsurgical methods of treating heart disease. For example, it was THI physician scientists who identified unstable blockages (atherosclerotic plaques) in arteries—those likely to lead to heart attacks and strokes—by developing specially designed catheters to measure variations of temperatures in atherosclerotic plaques. Their studies concluded that the higher the temperature variations in a plaque, the greater the risk. Their studies also led to the creation of a very successful biotechnology company called Volcano and provide an opportunity to detect and treat patients at risk for heart attacks and strokes and to administer treatment before life-threatening episodes occur.
The Advanced Physiologic Monitoring department is investigating the use of temperature as a predictor in decompensated heart failure and coronary artery disease and the underlying science behind these phenomena. The data shows that there is a consistent and significant decline in core body temperature prior to decompensation towards death.
In a widely published study last year, THI scientists established that influenza can trigger heart attacks. Patients at risk of heart disease are already encouraged to get a flu vaccine every year. THI scientists recently discovered a new generation of anti-influenza agents that work by inhibiting a cellular motor protein that the influenza virus uses to infect healthy cells. They are currently studying cellular and molecular mechanisms underlying the inhibitory effect of these agents, and combining them with existing agents to see if they better protect against the proliferation of flu. Scientists are also exploring the anti-influenza effects of statin drugs.
Imaging the Heart
THI physicians are studying a new ultrasound imaging technique that can detect small differences in the heart’s contraction speeds, which cannot be detected by traditional ultrasound, so doctors can identify areas of myocardial dysfunction. Related technology analyzes contractility by detecting the speed at which heart muscle fibers shorten and lengthen. Scientists are also working to improve the diagnostic capabilities of computed tomography for assessing atherosclerotic plaques.
Electrophysiology—The Power Grid of the Heart
In pre-clinical studies, THI scientists are exploring how the parasympathetic nervous system affects arrhythmias in the heart. The parasympathetic nervous system, a branch of the autonomic nervous system, is responsible for slowing heart rate and increasing digestion and other activities when the body is at rest. Doctors are exploring the development of stem cells for conduction, reconstituting the atrioventricular node, the gatekeeper for electrical conduction between the upper and lower chambers of the heart. They are also conducting a study of how Botox, injected directly into the heart, affects arrhythmias. Yet another project aims to develop a device to prevent pneumothorax, a complication in which pulmonary air leaks into the pleural spaces of the heart.
THI physicians recently published a study of how weight loss products which cause arrhythmias are marketed over the Internet, even though they have been banned by the FDA. They are also exploring the effects of energy supplement drinks on heart rhythms. Other studies are using variabilities in pacing intervals to determine the geometric pattern of activation during arrhythmias. A simple mapping electrophysiology procedure can find how the arrhythmia is activating the heart and physicians can look for a pattern or response during the tachycardia.
THI physicians are exploring the use of MRI to define the anatomical setting which creates fibrillation. They are studying the use of an intra-atrial conduction relay to predict optimal settings for biventricular pacemakers. The study examines the timing of conduction between the top chambers of the heart to identify optimal settings for maximum cardiac output.
In prospective studies, doctors are looking at how the brain communicates with the heart in patients who are on dialysis for renal failure and have abnormal reflexes as a result. They are developing a scoring system that will predict post-operative afibrillation. The doctors are conducting prospective and retrospective studies to determine how often internal defibrillators deliver inappropriate shocks. The doctors are working with Rice University to study whether a digital respirometer in the nose can help minimize collateral damage during a procedure in which a catheter delivers radio frequency energy to create a scar to stop arrhythmias.
Updated June 2008
