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| Research Summary |
 Leading with the Heart Visionary scientists and physicians working together to bring translational research to the patient’s bedside with innovative treatments lead us to the heart of discovery. With unwavering passion, dedication and collaboration, the Texas Heart Institute remains the vanguard in the fight against heart disease. And what a war it is. Cardiovascular disease claims nearly 900,000 lives—more lives than the next five leading causes of death combined—each year in the U.S. alone. One in three Americans suffers from cardiovascular disease and associated costs are estimated at $432 billion in 2007. Discovery of new knowledge makes advances possible as we work to conquer cardiovascular disease.
Leading the World in Stem Cell Research
The Stem Cell Center’s research continues to expand rapidly. The Center is currently involved in a clinical trial using a patient’s own adult stem cells for treatment following a recent heart attack. Another study—the first of its kind in the U.S.—uses a patient’s stem cells for treatment of severe limb ischemia, in which the patients have exhausted all other options for treatment of the circulatory disease and are at risk of amputation. New, proprietary methods of processing stem cells are also being explored for the treatment of heart failure. Stem Cell Center physicians recently launched a collaborative study with colleagues in Spain to treat heart failure patients with stem cells derived from their adipose (fat) tissue. Most significantly, the Texas Heart Institute has been chosen as 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 will provide a grant of $33.7 million over the next five years to support the new national consortium called the Cardiovascular Cell Therapy Research Network (CCTRN). 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. As part of this network, THI will be treating a variety of cardiovascular conditions such as coronary artery disease or congestive heart failure. Physicians and scientists will explore the potential of stem cells taken from different sites in the body, including the bone marrow, circulating blood and muscle or adipose tissue. New techniques to process and deliver the stem cells in the body will be studied as well. Research continues at all levels to determine the best type of stem cell to use for heart repair and the best method of delivery, as well as to understand the biomolecular mechanisms involved in this treatment. Assisting the Failing Circulation
While some of these pumps are for temporary use and deployed percutaneously, like in an angioplasty, others are surgically implanted and used as a bridge to heart transplantation. Sixty patients have received the Jarvik 2000 left ventricular device, which is used as a bridge to transplantation. THI also has unrivaled experience with the Impella 2.5, a temporary heart assist device which supports patients who are in cardiogenic shock, in which insufficient circulation puts vital organs at risk of shutting down. THI also implanted its first MicroMed DeBakey heart assist device in recent months and the patient is recovering well at home. Many people are unaware that 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. THI typically sees about 30 patients with VADs on an outpatient basis at any given time. 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. This involves determining the right indicators that recovery has occurred, establishing testing methods to determine recovery and refining surgical methods to explant the VADs with minimal invasion. Over the last three years, five patients supported on a long-term basis with a HeartMate II VAD have achieved recovery, allowing for explanation of their devices. 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. Succeeding Against Failing Hearts
A recently completed study done at THI found that immunomodulatory therapy may be very helpful for treating patients with chronic heart failure. Immunomodulatory therapy involves drawing a small amount of a patient’s blood, mixing it with oxygen and ozone to stimulate the production of anti-inflammatory substances, and then injecting it back into the patient. Researchers have found that immunomodulatory therapy reduces the chronic inflammation that contributes to heart failure. Another study involves the use of small, implantable cardiac monitors to improve the care of patients with moderate to severe heart failure. The monitors continuously record blood pressures within the heart and transmit that information once a week to doctors. The transmitted information lets doctors know quickly whether a patient’s heart failure is getting worse. With this knowledge, doctors can change treatment strategies earlier, possibly helping patients avoid hospitalization. Physicians are currently studying internal defibrillators which provide remote monitoring of heart function in patients with heart failure. Trials of cardiac resynchronization therapy are also underway at THI. This therapy uses pacemaker devices to resynchronize (or coordinate) the conduction system within the heart’s lower chambers (the ventricles). Synchronizing the conduction system improves the efficiency of the heartbeat in patients with heart failure. New devices under study involve combined synchronization and defibrillation capabilities. Many patients with heart failure are at higher risk for complications during percutaneous coronary angioplasty (balloon angioplasty), a procedure performed by interventional cardiologists to open narrowed arteries in the heart. THI continues to evaluate whether it is helpful to use a miniature blood pump to support a patient’s circulation during high-risk procedures. THI also continues to see a large number of patients enrolling in a national database of heart failure patients. The database is designed to determine the best standards of treatment for patients with this serious condition. Another study is exploring the relationship between low core body temperature in patients with congestive heart failure and their risk for near-term morbidity and mortality. Predicting and Preventing Heart Attack and Stroke
Texas Heart Institute scientists are investigating new techniques to predict and identify patients at risk for heart attack and stroke. For many years, physicians have been testing patients’ blood levels for C-Reactive Protein (CRP) as a marker of inflammation and heart disease risk. Institute scientists are taking this concept a step further by investigating the specific actions of this protein on endothelial cells that line the inside of arteries. They have determined that CRP is more than a marker of inflammation, it is also the cause of inflammation within the arteries and is made locally in the injured arteries. CRP promotes the development of certain adhesive molecules on the endothelial cells that “attract” circulating inflammatory cells in the blood system. When the inflammatory cells attach themselves to the endothelial cells, they cause inflammation and the accumulation of substances that very often lead to the buildup and rupture of dangerous plaques. We now have the mechanistic insight to block the process in its early stages. In addition, Texas Heart Institute physicians have pioneered new techniques to identify and localize these “vulnerable plaques” with specially designed catheters that sense subtle differences in temperature changes within the vessel wall. Texas Heart Institute scientists and physicians are currently working together to develop the concept of the vulnerable patient. The long-term goal is to develop a noninvasive imaging procedure that detects these vulnerable plaques and that allows arteries throughout the body to be screened. By identifying a patient’s individual vulnerabilities in arterial plaques, blood and heart muscle tissue, physicians believe they will one day be able to precisely predict a person’s risk of heart attack within a 12-month period. New knowledge in this field could have a dramatic impact on preventive cardiology. Another project that has potential impact for millions of people is the role of influenza in contributing to cardiac events. The atherosclerosis team has previously shown that influenza infection resides in the arterial wall, acutely affects atherosclerotic plaques, and is associated with massive plaque inflammation and occasional plaque erosion. Last year, THI physicians successfully lobbied for the “American Heart Association/American College of Cardiology Guidelines for Secondary Prevention for Patients with Coronary and Other Atherosclerotic Vascular Disease” to include recommendations that all patients with cardiovascular disease receive an influenza vaccination as part of a comprehensive effort to avoid more cardiovascular complications. Developing Minimally Invasive Treatments In the cardiac catheterization laboratories (cath lab), doctors are making significant strides in testing new minimally invasive methods to treat a variety of cardiovascular ailments that could reduce the need for surgery. The advent of drug-coated stents to hold open arteries after angioplasty has significantly improved patient outcomes. Current studies seek to identify the most effective drug-coated stents and the most refined technology to deliver the treatment. Thoracic and abdominal aneurysms may also now be repaired with percutaneous (through the skin) interventions, and comparison studies of those technologies are underway. THI was one of the first heart centers in the country to use new technology in the percutaneous repair of abdominal aortic aneurysms. The technology involves implanting a tiny sensor between the aneurysm and the stent which occludes it. The sensor monitors blood pressure in the aneurysm and prevents the need for periodic CT scans during patient monitoring. Three studies are focusing on percutaneous repair of blocked carotid arteries in the neck with devices that protect the brain. Studies using percutaneous treatment of severely blocked veins in the legs are also underway. Another major innovation in the cath lab is the use of radiofrequency currents to treat atrial fibrillation, a type of arrhythmia that is a leading cause of stroke. This treatment, radiofrequency catheter ablation (RFCA), is as effective as the existing drug treatment, without the frequently occurring side effects associated with antiarrhythmic drugs. RFCA works by mapping and ablating (destroying) the triggers of atrial fibrillation.  With more than 1,000 heart transplants performed, THI physicians are unrivaled in their experience in this field, and our scientists are still refining their understanding of this lifesaving treatment. For the last 25 years of the heart transplantation program, our staff has been studying new drugs to prevent organ rejection, the long-term effects of these medications on other organ systems, and the effects of drug treatment for anemia in heart transplant recipients. Physicians are also pioneering new techniques and technology to reduce the invasiveness of cardiovascular surgery, including new robotic surgical procedures. Using the surgical robot, physicians have harvested vessels in the leg and chest for bypass, repaired heart valves, and performed closed-chest bypass operations, with dramatically reduced incisions and much faster recovery. Institute surgeons are also the world’s leaders in the treatment of aneurysms of the aorta, the large vessel that carries blood from the heart to other parts of the body. An aneurysm is a bulging, weakened section of an artery. THI surgeons have developed a multimodality approach to treat these dangerous lesions that has successfully decreased the incidence of paraplegia and paraparesis (partial paralysis) after surgery. This year, our surgeons also performed simultaneous percutaneous endovascular (within the vessel) repair of aneurysms in two different segments of the aorta. Ongoing research at the Institute suggests that an overproduction of an enzyme called matrix metalloproteinase may be responsible for the development and expansion of some types of aortic aneurysms. This potential link holds the promise of new and better treatments of these lesions. Improving Outcomes After Cardiovascular Surgery New methods to decrease mortality, morbidity, length of stay, disability, and discomfort during and after surgery encompass the global focus of our anesthesiology research, and we have become a leading center in exploring the influence of a patient’s genes on heart surgery risks. Several pharmacologic agents are being studied to improve surgical outcomes, including agents that reduce the inflammatory response to surgery, statins, and hormone therapy for women. The influence of diabetes and obesity on outcomes is of growing concern. Research to protect the brain during cardiac surgery with monitoring devices, pharmacologic agents that can minimize damage, and manipulation of brain temperature has been a long-standing focus of the department. New methods to minimize blood loss and blood transfusions are also being studied. Transferring Genes to Diseased Vessels Institute researchers are learning how to keep arteries and grafts open by transferring new genes, which have all of the information they need to make substances that protect from scarring, blood clotting and re-narrowing, to diseased vessels. Scientists have identified genetic variables which predispose some patients to negative effects of antiarrhythmic drugs so they are seeking to develop drug therapies based on individual genetics. Scientists are also looking at the differences in proteins expressed by healthy and diseased heart tissue—a science called proteomics. With this information, they will be able to diagnose some forms of heart diseases, develop new medications to treat heart failure, and, possibly, even prevent heart failure from occurring. The Heart Institute’s molecular biology laboratory has begun specifically to target congestive heart failure—a buildup of fluid in the lungs and other tissues caused by the heart’s weak pumping action—through the science of proteomics. Scientists are studying the complete protein profiles from tissue obtained from patients at all stages of heart failure. These studies will identify protein molecules that cause heart failure and identify those molecules that may be suitable targets for new or existing drug therapy. Knowing which proteins to target will allow physicians to treat all stages of heart failure more effectively. As part of THI’s emphasis on cardiac recovery after VAD support, our scientists are conducting proteomic analysis to better understand the mechanisms of cardiac recovery. Updated March 2007 |
The 
The lack of donor hearts prompted THI to begin translational research in the development of 
THI doctors and scientists can now offer patients with failing hearts a variety of options for improving their conditions. Our researchers are currently studying many different types of medicines that may improve heart function, reduce symptoms, and improve quality of life for 
Heart attacks are caused by plaques that rupture, leading to the acute development of a blood clot that obstructs the flow of blood to the heart. When strokes occur, blood clots obstruct the flow of blood to the brain.
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