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Monday, Feb. 26, 2018

The Rise & Fall (and Rise) of Cardiovascular Disease

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Since the early 20th century, of these medications represent continued development in two key areas of cardiovascular cardiovascular disease has been the leading cause of death in the United disease, and can be generally classified into States. Every year approximately 600,000 people in the United States die due to cardiovascular disease, accounting for one in every four deaths. With these numbers, it is difficult to appreciate that the treatment of cardiovascular disease represents one of the best modern success stories for biomedical research.

In the mid-1980’s, the number of people dying from cardiovascular disease nearly reached 800,000 per year. It was new classes of drugs and one of the following two categories: 1) drugs to treat increased cholesterol buildup in the arteries, and 2) drugs to prevent blood clotting.

High cholesterol represents a major risk factor for both heart attacks and strokes. The typical class of drug to treat high cholesterol, the statins, came on the market in 1987 and are credited with a large role in the reduction of cardiovascular disease risk over the following decades. Statins act advances in surgical interventions that by reducing the body’s ability to make led to a decline in the cardiovascular mortality rate over the following 30 years. This 25 percent drop in cardiovascular deaths from the 1980’s, giving the average American four more years of life expectancy, corresponded with a strong investment in biomedical research from the federal government. However, stagnant federal funding that doesn’t keep pace with inflation and reduced state support for the colleges and universities that perform this research currently threaten our biomedical workforce. Since 2014, the incidence of cardiovascular disease is on the rise again after decades of decline, suggesting a continued investment in biomedical research will be critical to maintaining the progress we have made in fighting this disease. At LSU Health Shreveport, we are at the forefront of this continued effort.

Treating Cardiovascular Disease

The U.S. Food and Drug Administration has approved a number of newer drugs to treat cardiovascular diseases. The majority cholesterol, but they do not affect dietary cholesterol and are often associated with negative side effects. The newer medications to battle high cholesterol are no longer made up of chemicals, but are instead biologically derived antibodies that target and inactivate a specific protein in the liver, resulting in enhanced clearance of bad cholesterol by the liver. These drugs reduce the combined incidence of heart attacks, stroke and death, while offering the convenience of taking the medication as a shot once or twice a month only. Another new drug instead targets inflammation driven by cholesterol buildup in the arteries. In a large clinical study, this drug was shown to decrease cardiovascular events, including death, in patients. It is expected that this drug will be sent to the U.S.

Food and Drug Administration soon for approval for use in the general population.

Many cardiovascular diseases are associated with enhanced risk of forming blood clots within the vessels, a primary cause of heart attacks and strokes. However, medications to reduce blood clots can leave a patient susceptible to bleeding, particularly following an injury. A common cause of blood clots is atrial fibrillation, a rapid and chaotic heart rhythm in the upper left chamber of the heart. New medications have shown promise in reducing clot formation in patients with atrial fibrillation with similar effectiveness as older drugs, but without the enhanced risk of bleeding associated with these older medications.

Surgical Treatments of Cardiovascular Disease

One of the key innovations with which the medical field is looking to drive a paradigm shift in the treatment of patients with clogged arteries is the bio-resorbable stent, or dissolving stent. Traditional stents are metal wire meshes that help prop open the blood vessels that supply blood to the heart, brain or legs. While they provide additional benefit compared to simply opening up the blood vessel with a balloon, the metal in the stents can cause vessel injury that leads to scarring and thickening of the vessel wall that eventually closes off the lumen (i.e., central opening of the vessel) and results in stent failure.

Drug-eluting stents contain drugs that are released over time and limit growth of the cells of the vessel wall, similar to chemotherapy, helping maintain the lumen of the vessel. However, the downside is that these drugs often significantly delay the healing of the vessel, enhancing the risk for clot formation months after stent implantation, and therefore increasing the risk of late heart attacks or strokes. Bio-resorbable stents function within clogged arteries similar to how casts are used to heal a broken bone. That is, they exist until the problem is solved and then they are gone. These stents, made up of a material that dissolves in two years, will allow the blood vessel to return to their natural shape and function. Although the first-generation bioresorbable stents did not perform as well as expected, experts in the field anticipate that, as the technology continues to advance, the benefits of newer bio-resorbable stents may outweigh any drawbacks.

The treatment options for cardiovascular diseases are slowly moving away from more invasive, major surgeries to minimally invasive procedures that are done through blood vessels in the leg. In the past, major surgeries were required to change a malfunctioning heart valve. However, these procedures have now been replaced by catheter-based approaches, where a self-expanding heart valve can be taken to its location in the heart through a catheter, and placed even in patients considered high risk for surgeries. A further advantage is that the necessary time for the hospital stay is also reduced.

Catheter-based ablation technology has revolutionized the treatment of heart rhythm problems and offers a complete cure for some arrhythmias that in the past have required patients to take medications for the rest of their lives. A study published in the New England Journal of Medicine clearly showed for the first time that, compared to medical management, catheter-based ablation for a rapid and chaotic heart rhythm called atrial fibrillation can dramatically decrease the risk of death in patients with heart failure. This procedure is offered at University Health and is performed by LSU Health Shreveport doctors.

In addition, there is ongoing intense research to find, or improve upon, technology that could provide clues to the source of arrhythmias in atrial fibrillation. This is critical because atrial fibrillation increases the risk for stroke. Even for patients who have failed all attempts to revert to normal rhythm and remain in atrial fibrillation, the last five years have brought relief in the form of numerous technological advances. If they are at high risk of bleeding from blood thinners, we can now implant a device to close off the part of the heart where the blood clots that give rise to stroke are formed. We can also regularize the heart by placing a special pacemaker that makes the heart contract as naturally as possible, and remove the electrical connection that takes the rapid and irregular atrial fibrillation heartbeats to the rest of the heart. Targeted treatment of heart rhythm problems by non-invasive cardiac ablations using nontraditional energy sources and by identifying key molecular players through biomedical research represent the future of heart rhythm management. Researchers around the globe, including here at LSU Health Shreveport, have been closely looking at molecular targets within the heart, the heart’s nerve supply and the brain-heart connection to better understand the origin of heart rhythm problems with the goal of developing treatment strategies that are specifically directed toward their origin.

Technological Advances in the Treatment of the Heart

Heart failure is a disease process where the muscle of the heart is weakened by lack of blood supply, prolonged stretch or increased workload leading to a reduced ability to pump blood to the rest of the body. Without proper care and treatment, patients with heart failure, just like patients with cancer, have a high risk of death. Newer technologies have now been implemented to address advanced heart failure even when medications fail. LSU Health Shreveport physicians, in collaboration with specialists from other institutions, are now able to take care of the “sickest of the sick” heart failure patients. This sometimes involves placing a mechanical pump to replace the work of the heart, thereby allowing people to lead a normal life for many more years. In addition, we can implant small micro-chips within the blood vessels of the heart and lungs to monitor the day-to-day fluid status in these patients, even when they are living in their homes miles away from the hospital. The data is then used by doctors to tailor the medication regimen for these patients on an ongoing basis.

In recent years, pacemakers have been progressively decreasing in size, and are now almost the size of a U.S. half-dollar coin. However, because they are connected to the heart by flexible wires going through blood vessels while the pacemaker battery sits in the shoulder region, there is a risk of pulling these wires loose in the first few weeks due to movement of the shoulders, and there is a lifelong risk of infection. Within the last year, doctors at LSU Health Shreveport have been implanting a new type of pacemaker that is the size of a vitamin capsule. This is placed directly inside the heart, thereby considerably decreasing the above risks. Substantial research is also under way in multipacemaker technology to treat heart rhythm problems. In a way, this system would re semble the natural conduction system of the heart by having multiple-site pacing where miniature pacemakers are placed in different chambers of the heart. Instead of wires connecting these pacemakers, they would be coordinated using Bluetooth® technology to generate a “natural” heart rhythm. In the near future, LSU Health Shreveport doctors will also place pacemakers to treat sleep disorders. This is a newly FDA-approved nerve stimulator that will stimulate the respiratory muscles in patients with a specific pattern of sleep apnea where the brain does not properly send signals to the respiratory muscles.

Biomedical Research and Cardiovascular Disease

While pharmaceutical companies often get credit for bringing drugs to market, much of the biomedical research conducted in this country is performed at state and private universities through funding from the National Institutes of Health (NIH). These NIH-funded research grants provide the university with education and training opportunities for its students and often result in patent applications filed on faculty research. Since pharmaceutical companies must invest billions to get drugs to market, much of the research in industry focuses on clinical studies rather than identifying novel drug targets. Therefore, the university research system represents the critical first step and acts as a major pipeline for discovering potential new treatments, with pharmaceutical companies then licensing the patents from universities to advance new therapies.

Research conducted at LSU Health Shreveport comprises all of the NIH-funded research in Caddo and Bossier parishes, with 21 active research grants bringing in over $10 million in annual funding. In addition, clinicians at LSU Health Shreveport perform a variety of clinical trials, providing Shreveport citizens with access to new treatments that are not available elsewhere. LSU Health Shreveport has a long-standing history of innovative research in cardiovascular disease, attracting scientists from around the country to establish their laboratories here in Shreveport. In 2013, the Center for Cardiovascular Diseases and Sciences (CCDS) was formed to leverage the state-of-the-art research facilities and diverse faculty expertise at LSU Health Shreveport toward the study of cardiovascular disease. The CCDS scientists are a nationally recognized group of 42 clinicians and basic scientists that bring in over $6 million in NIH funding for research on multiple aspects of cardiovascular disease, including heart attacks, stroke, heart failure, atrial fibrillation and peripheral artery disease. In addition, these scientists contribute to driving the future of cardiovascular research through their work with the NIH, the American Heart Association and the American Diabetes Association. This combination of basic biomedical research and clinical research will be instrumental in maintaining our success in the treatment of cardiovascular disease over the coming years.

Wayne Orr, PhD, is a professor in the Department of Pathology, Physiology and Cellular Biology & Anatomy at LSU Health Shreveport. He is the director of the Center for Cardiovascular Diseases and Sciences. Paari Dominic, MD, is an assistant professor in the Department of Internal Medicine, Division of Cardiology at LSU Health Shreveport. He is also an assistant director of the Center for Cardiovascular Diseases and Sciences.

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