It is a part of the heart that most people have never pondered, let alone heard of, in their lives. But the left atrial appendage – a physical trait that all humans share – is worth knowing about because it is involved in the vast majority of strokes. Now, a prestigious new grant obtained by a team from the USF Health Morsani College of Medicine and Tampa General Hospital could significantly enhance preventive treatments.

Thanks to the innovative work of Dr. Hiram Bezerra, professor at the USF Health Morsani College of Medicine and director of the TGH Interventional Cardiology Center of Excellence, the $460,000 grant could lead to key improvements of an existing procedure to block the opening to the left atrial appendage (LAA) in certain patients who are at high risk for stroke. And it ultimately could deliver safer, faster, and more effective results for patients.

This marks the first time a National Institutes of Health R01 grant – designed to support advanced, hypothesis-driven research projects with strong preliminary data – has been awarded to USF Health’s Division of Cardiology Sciences in the Morsani College of Medicine.

“I think this is reflective of the journey we are on to become a national presence in the forefront of cardiology,” said Dr. Guilherme Oliveira, chief of the division and Ed C. Wright Professor and Chair of Cardiovascular Research, as well as co-director of the USF Heart Institute for Research. Dr. Oliveira also is vice president and chief of the Tampa General Hospital Heart & Vascular Institute.

“This has never been done here before – the ability to get an R01 grant for our division that basically is developing a new technology – with potential clinical applications going all the way from basic pre-clinical engineering of an innovation and taking it all the way to the bedside,” said Dr. Oliveira. “And I think it’s very telling of where we are with the type of talent we’ve been able to attract to USF and Tampa General.”

In this case, the grant, three years in the works, will allow Dr. Bezerra and his team to produce a better, more streamlined approach for dealing with the left atrial appendage – an area in the heart’s left atrium akin to a little pocket. While the structure may help lower pressure in the atrium, it also is possible for blood to pool there in patients with atrial fibrillation, a type of irregular heartbeat, and raises the risk of a clot that could travel to the brain.

“The actual magical aspect of it, and what we are trying to achieve, is a therapy that is offered for stroke prevention,” said Dr. Bezerra. “More than 90 percent of strokes originate from the left atrial appendage chamber. And by occluding the left atrial appendage, you will prevent a stroke in a population prone to have one – the atrial fibrillation, or AFib, population.”

Those suffering from AFib experience an array of symptoms that include an irregular heartbeat, a racing heart, shortness of breath, fatigue and chest pain. People with the condition are some five times more likely to suffer a stroke than those without it – with some 12 million in the U.S. estimated to have AFib by 2030.

“The patients we are targeting have AFib and for some reasons are not a good candidate for the standard preventive therapy of blood thinners,” Dr. Bezerra added. “The next treatment in line is occluding the left atrial appendage. And we are talking about hundreds of thousands of patients in the United States.”

The primary device in the U.S. used to block the left atrial appendage is called the Watchman, manufactured by Boston Scientific, with some doctors employing the Amplatzer Amulet heart device from Abbott. In the current protocol, a patient typically receives a transesophageal echocardiogram two weeks ahead of the procedure to examine the structure and functioning of the heart and evaluate the size of the appendage.

This allows doctors to plan the procedure and select the device. Patients commonly receive general anesthesia for the procedure, which again involves a transesophageal echocardiogram as a real-time guide. In most cases, patients return home the next day.

“But we are pushing to implement a workflow that is less resource intense, and that we believe is actually safer to do,” Bezerra said.

The grant proposed that patients will not have to undergo general anesthesia for the procedure, and a single cardiac MRI would be employed, allowing a patient to just come in once and not have to undergo a separate pre-imaging appointment. The scanner on the day of the procedure would perform the sizing to determine the best device to use. And it would also allow for improved visibility in real-time guidance during the procedure – providing live, higher-resolution images than the current method affords.

“It will all be done with a single modality,” Dr. Bezerra explained. “In addition, the patient is awake. There is no additional cost of the intracardiac echo, or the inconvenience of general anesthesia. And it increases the chances of a patient to go home the same day.”

Dr. Bezerra wrote the grant to be tied specifically to the Watchman because it is more frequently used. But ultimately, replicating the procedure on a different device would not be difficult to achieve. The grant includes a pre-clinical stage at Cleveland’s Case Western University followed by a clinical phase at USF Health and Tampa General. He estimates that it could be available for use on USF Health patients at TGH in three years.

“The plan is for me now to make a few trips to Cleveland, when it’s time for the animal experiments and to help facilitate that,” Dr. Bezerra said. “The next step will be testing for MRI compatibility and starting basic engineering work. A lot of bench and pre-clinical work still needs to take place before we can offer it to patients.”

Dr. Oliveira put it in perspective: “This is the holy grail of grants – where you go, as I said, from a bench concept and have a grant that will support the development of that product all the way to the bedside. It is not easy to do outside of the industry.”

The research also will be a natural fit for work that other physicians, such as Dr. Bibhu Mohanty, already are doing at USF and TGH to advance stroke care, Dr. Bezerra said. Dr. Mohanty, an associate professor in Internal Medicine at the College of Medicine, is an interventional cardiology specialist.

“This grant will complement our very active multidisciplinary neurocardiac program led by Dr. Mohanty in close collaboration with Neurology and Electrophysiology,” Dr. Bezerra said. “With the addition of this translation grant, USF/TGH will continue to be on the very cutting edge of stroke prevention.”

Story by Dave Scheiber for USF Health News.

USF Health’s cardiovascular team of faculty, researchers, doctors, nurses, physical therapists, pharmacists and public health professionals continue to develop top-quality research, education and state-of-the-art clinical care to make life better for patients suffering with heart disease. To learn more, click here.

Heart disease is the leading cause of death in the United States. According to American Heart Association (AHA), more than 6 million adults currently live with heart disease.

The number of people living with the condition is only expected to rise. AHA data shows that, by 2030, more than 8 million people could be diagnosed with heart disease.

The numbers are alarming. But, taking basic daily steps may help prevent or reduce heart disease and heart attack.

USF Health medical experts on cardiovascular disease weigh in – providing ten things people can do to keep their heart healthy. They suggest to:

Exercise daily

Vishal Parikh, MD, fellow of the Department of Cardiovascular Sciences at USF Health Morsani College of Medicine, says moderate exercise for at least 30 minutes a day can lower the risk of obesity, high blood pressure, high cholesterol and diabetes.

Quit smoking

Smoking increases the risk of heart disease and heart attack, says Amy Alman, PhD, assistant professor in the Department of Epidemiology and Biostatistics at the USF College of Public Health. “So, say no to smoking,” says Dr. Alman.

Maintain a healthy diet

“A bad diet can put a strain to your heart,” says Ponrathi Athilingam, PhD, assistant professor of cardiology at USF College of Nursing. She suggests considering healthy foods such as fruits, vegetables, whole grains, fish, poultry, lean meats, and nuts to help lower the risk of heart disease. She also recommends eating foods with low trans-fat, saturated fat or sodium.

Manage stress

Dr. Parikh says that stress adds strain to the heart. Constant stress causes behaviors that increase heart disease risks including smoking, excessive alcohol, physical inactivity and lack of sleep. So, he says, “It’s important for people to identify triggers and practice relaxing techniques such as meditation. Something just as simple as laughing may help combat stress.

Advanced genomic monitoring/testing

Kevin Sneed, PharmD, dean of the USF College of Pharmacy, said advanced genomic testing and monitoring, which provides an assessment of cardiovascular genes, helps detect any genetic abnormalities early. “This type of technology would provide awareness, and, most of all, give information for a more targeted intervention to prevent future complications,” says Dr. Sneed.

Maintain a balanced weight

Excessive weight gain increases the risk of cardiovascular disease. According to Center for Disease Control and Prevention, weight gain leads to high cholesterol, high blood pressure and diabetes. “To keep the body in check, remain physically active and, above all, consume whole foods rather than processed foods,” says Mary Soliman, PharmD, assistant professor at USF College of Pharmacy.

Get regular exams

USF Health cardiovascular experts suggest that having regular heart screenings is important – checking the heart rate, blood pressure, body fat and blood sugar. They believe regular screenings keep people informed, which ultimately help prevent heart disease.

Know family history  

Knowing about the family history is important. Having a relative or family member suffering from heart disease, greatly increases one’s risk. “If you have a family history of heart disease or a personal history of heart health risk factors (smoking, obesity, high blood pressure and cholesterol), you may just need to be more diligent in monitoring your heart health,” says Gregory M. Gutierrez, PhD, assistant professor at the USF Health School of Physical Therapy and Rehabilitation Sciences.

Maintain a healthy lifestyle

Keeping an overall healthy lifestyle is the secret to a healthy heart. USF Health experts all agree that lifestyle is key to lowering the risk of heart disease. Exercising, eating healthy, avoiding smoking and second hand-smoking and managing stress, lead to better heart health.

What women need to do

Heart disease causes, symptoms and outcomes may be different in women than in men, says Theresa Beckie, PhD, professor and cardiovascular health researcher at USF College of Nursing and Department of Cardiovascular Sciences in the USF Health Morsani College of Medicine. “Women represent a particularly high-risk phenotype. So, women, especially young women, need to pursue aggressive measures to reduce risks with daily physical activity, a healthy dietary pattern, and stress management,” says Dr. Beckie.

Jerome Breslin studies what happens when the endothelial barrier is breeched by traumatic injury and inflammation

Traumatic injury is the leading cause of death among people ages 1 to 44 in the United States. The body’s inflammatory response accompanying massive injury can severely complicate the resuscitation of trauma victims, worsen clinical outcomes and often lead to multiple organ failure.

In his laboratory at the USF Health Morsani College of Medicine, Jerome Breslin, PhD, and colleagues study microvascular hyperpermeability, that is, the “excessively leaky” small blood vessels that are a hallmark of systemic inflammation.  Their aim is to find new, more effective ways to treat trauma and prevent early death, but their work also has implications for the treatment of lymphedema, wound healing and arteriosclerosis.

Jerome Breslin, PhD, can do live imaging of vascular endothelial cells under a microscope that he helped build.

In particular, Dr. Breslin, an associate professor in the Department of Molecular Pharmacology and Physiology, looks at what happens when the protective barrier of endothelial cells forming an interface between circulating blood and tissues outside the blood vessel network is compromised by traumatic injury and inflammation.

Leaky blood vessels: The soaker hose analogy

“These capillaries are like soaker hoses used to water plants, that leak out fluid carrying proteins and other nutrients in addition to delivering oxygen to surrounding tissue,” Dr. Breslin said. “In patients who have undergone trauma or major surgery, blood pressure drops in part because the wall of the hose becomes too leaky. There is less fluid in the blood vessels and more flowing out into nearby tissues, which can cause damage and impair the function of some organs.”

In addition to investigating ways to prevent excessive blood vessel leakage, Dr. Breslin’s lab focuses on how to return the leaked fluid back into the blood by the lymphatic vessels.  As a result, his team spends a lot of time studying the pumping function of the lymphatic system, which manages fluid levels in the body. Swelling, or edema, occurs when it fails to drain off excess fluid.

Dr. Breslin’s work is currently supported by two National Institutes of Health RO1 grants totaling more than $2 million.

Dr. Breslin with two undergraduate students who conduct research in his laboratory: Andrea Burgess (American Physiological Society IOSP Summer Fellow) and Sara Spampinato, center (NIH Diversity Grant recipient).

 Dr. Breslin comments on his approach to research problems.

The most recent award from the NIH’s National Institute of General Medical Sciences focuses on testing whether a class of drugs that activate the S1P1 receptor may keep blood vessels from leaking too much and stabilize blood pressure following trauma.

In this project, Dr. Breslin will use the first rat model combining alcohol intoxication and hemorrhagic shock to induce excessive leakiness in small blood vessels. He will evaluate whether fluid containing sphingosine-1-phosphate (S1P) reduces the blood vessel permeability, thereby restoring normal blood pressure and fluid balance. If so, Dr. Breslin said, drugs similar to S1P, a bioactive lipid that prevents cell death, may offer a more effective way for paramedics and physicians to resuscitate trauma patients than the standard IV fluid therapy now administered.  That standard fluid resuscitation protocol works particularly poorly in alcohol-intoxicated victims suffering major blood loss, a significant portion of all trauma cases coming through emergency rooms, he said.

With the second award, a competitive renewal from the NIH’s National Heart, Blood and Lung Institute, Dr. Breslin and colleagues are studying the molecular and cellular mechanisms that may regulate and resolve microvascular leakage following inflammation caused by traumatic injury.

Dr. Breslin points to a human heart valve suspended in a test tube solution. His group plans to study the microvessels within heart valves.

Unexpected finding leads to “new way of thinking”

Previous work by his group using live imaging of vascular endothelial cells under a microscope demonstrated that when the edges of these cells make contact with their neighboring cells they appear very active and are constantly remodeling, or changing shape — rapidly opening up holes at cell junctions and then closing back up. This finding, published in the journal PLOS One, countered one of the conventional theories that endothelial cells were more rigid at the junctions where they connect and adopted a contracted state during inflammation.

“It was an unexpected finding that changed our thinking about how these cells behaved,” Dr. Breslin said.

This led the researchers to begin to question the prevailing view about the role actin stress fibers — threadlike structures involved in cell stability, adhesion and movement — play in disrupting the endothelial barrier function.

Further preclinical studies by Dr. Breslin and others over several years showed that in response to an inflammatory agent actin stress fibers cause endothelial cells to spread out, not contract, at the junctions. The USF researchers published evidence in the American Journal of Physiology: Cell Physiology that actin stress fiber formation may be a reaction to, rather than a cause of, reduced integrity of the endothelial barrier that protects against excessive fluid leakage.

Earlier this year, Dr. Breslin was first author on a study appearing in the Journal of the American Heart Association showing that the signaling protein Rnd3 reduced leakage of small blood vessels when delivered a new way in a rat model of hemorrhagic shock. The researchers suggested Rnd3 (or analog drugs) might offer an anti-inflammatory treatment to repair the endothelial barrier compromised by prolonged and uncontrolled inflammation.

  Dr. Breslin talks about his most exciting experiment

//www.youtube.com/watch?v=lm2ag8m1QqQ

Live imaging of endothelial microvascular cells at 600x magnification shows the dynamic movement of the protruding cell edges (local lamellipodia). Videoclip courtesy of Jerome Breslin, PhD. 

Heart Institute, former mentor a draw to USF

Dr. Breslin joined USF in 2012 from Louisiana State University Health Sciences Center in New Orleans, where he was an assistant professor of physiology.  He received his PhD in pharmacology and physiology from Rutgers University – New Jersey Medical School in Newark, NJ.  His postdoctoral training was conducted at both Texas A&M and the School of Medicine at the University of California Davis, where he was mentored by Sarah Yuan, MD, PhD, the chair of Molecular Pharmacology at Physiology at Morsani College of Medicine who is nationally recognized for her translational research on the regulation of microcirculation.

The opportunity to be part of a growing university, join core faculty who will help build a Heart Institute advancing bench-to-bedside cardiovascular research, and work again with Dr. Yuan attracted him to USF Health, Dr. Breslin said.

“Dr. Yuan was a great mentor to me when I was a postdoctoral fellow,” he said. “This has reopened our scientific collaborations and now we’re mentoring a student together.”

Dr. Breslin, center, with some members of his laboratory.

  His advice to emerging scientists

Dr. Breslin is a fellow of the American Physiological Society Cardiovascular Section and a member of The Microcirculatory Society and the American Heart Association.  He is associate editor of the journal Microcirculation and a member of the editorial board of PLOS One.  He has authored or co-authored nearly 40 articles in peer-reviewed journals.

Dr. Breslin serves on two NIH special emphasis panels, one on lymphatics and another for the Intramural Postdoctoral Research Associate Program.  He is also a grant reviewer for the Association of American Medical Colleges (AAMC) Innovations in Research and Research Education Awards.

Something you may not know about Dr. Breslin

To help pay for tuition while earning his master’s degree in biology, Dr. Breslin worked as a park ranger in Somerset County, N.J, for a couple of summers.

No stranger to outdoor activities, including camping, as a teen Dr. Breslin attained the rank of Eagle Scout, the highest achievement in the Boy Scouting program.  His connection with scouting continues today as committee chair for his 13-year-old son’s Boy Scout troop.

Dr. Breslin’s Scouting experiences included learning wilderness survival skills, such as how to build a shelter from scratch in the woods or navigating a group of boys through the wilderness without a map and compass, or a smartphone for that matter. They were instrumental, he said, in helping him develop the resourcefulness and leadership skills he hopes to impart to the emerging scientists he mentors in his laboratory

In case you’re wondering, one of the most challenging of the merit badges he earned as a Boy Scout: bugling.

Photos and audioclips by Sandra C. Roa, USF Health Communications and Marketing

TAMPA, FL (April 18, 2012) — The Hillsborough County Board of County Commissioners today approved $2 million to help support equipment and space for the USF Health Heart Institute,  joining the state in funding the project.   Gov. Rick Scott approved $6.9 million in state funding Tuesday to support the initial design of the new institute.

The combined $8.9 million in state and county funding will allow USF Health to move ahead as one of the nation’s leaders in cardiovascular care, with a special focus on genomics-based personalized medicine.

“This is a forward-looking action on the part of the governor and our Hillsborough County Commissioners, and we thank them for it,” said USF President Judy Genshaft. “We’re also grateful for the support of Florida legislators and the leadership of Florida House Speaker Designate Will Weatherford.”

“We thank  Will Weatherford, our legislative leaders, the governor and Commissioner Mark Sharpe for recognizing the power of an entrepreneurial academic health center in growing the economy and the health of the state and Tampa Bay region,” said Dr. Stephen K. Klasko, CEO of USF Health and dean of the Morsani College of Medicine.  “We believe that the technology developed here will herald a new day and that USF Health will be able to partner with the best industry and academic partners throughout the world to develop these new personalized and genetic approaches to health.”

The Hilllsborough County agreement calls for $2 million over five years for the institute,  a key part of helping USF Health and the Tampa Bay community to create a health care innovation hub and expand the region’s growing reputation as a medical destination.

USF Health already has committed nearly $25 million in resources for genomics-based personalized medicine, including funding of research equipment and facilities, as well as the recruitment of two top physicians. They are Dr. Leslie Miller, chair of the Department of Cardiovascular Sciences, and Dr. Steve Liggett, a nationally prominent researcher who will become director of the Personalized Medicine Institute.

“Personalized medicine for heart and other diseases, which is based on an individual patient’s DNA, is the future of medicine and will allow us to tailor treatments,” said Dr. Liggett, who will join USF in June as vice dean for personalized medicine at the Morsani College of Medicine and USF Health associate vice president for personalized medicine. “We can put into place the current known genetic signatures, and discover those that are desperately needed, with the formation of this institute at USF Health. This places the State of Florida, and the Tampa Bay Area, as a leader, and not a follower, in the most advanced health care and research in the world.”

Cardiovascular disease accounts for 40 percent of all hospitalizations and deaths in Florida.  State costs for cardiovascular care are projected to increase to $17 billion a year by 2020. The USF Health Heart Institute can help with research that will help identify those at greatest risk for heart disease, allowing practitioners to treat them earlier; improve the knowledge of how an individual’s genetics can better guide drug treatments and dosage; and find new therapeutic treatments based on genetic discoveries.

“Cardiovascular disease is now the biggest health risk not only to the residents of Tampa Bay or the nation, but in the world. The State has made a major investment that recognizes the imperative to address this growing problem,” said USF Health Cardiovascular Sciences Chair Dr. Miller.  “The creation of a new Heart Institute at USF is a critical step toward saving lives by finding new diagnostic tools such as use of genomic markers of disease that will allow earlier detection and better prevention, as well as develop new and improved therapies such as stem cell and gene therapy to improve outcomes. USF Health is committed to solving health care problems today.”

The American College of Cardiology has selected the USF Health Heart Institute as a partner to conduct the first trial linking genomic screening with a clinical database of millions of patients with cardiovascular disease. The ACC also recently named the USF Health Center for Advanced Medical Learning and Simulation (CAMLS)  as its first-ever Center of Excellence in Education and Training.

USF Health will also partner in this new project with the Florida Hospital Pepin Heart Institute, which is located at Florida Hospital Tampa, a new part of the Adventist Health System.  USF Health and Pepin plan to collaborate on research and clinical trials.

“Gov. Scott’s approval of this funding is great news for the heart institute,” said Tom Pepin, founding philanthropist of the Florida Hospital Pepin Heart Institute. “Patients across Florida and beyond will benefit from better cardiovascular care because of the research and care improvements being made through our partnership.”

Starting the Institute shows how USF Health works to act as an entrepreneurial academic center, Dr. Klasko said.

“This is a great example of growing our own biomedical start-up,” Dr. Klasko said. “Instead of recruiting a center, we’re creating one. Most importantly, this is the future of health care, and we’ll have it right here in Tampa Bay.”

-USF Health-

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a global research university ranked 50^th in the nation by the National Science Foundation for both federal and total research expenditures among all U.S. universities.

Media contact:
Lisa Greene, (813) 974-4312 or  lgreene@health.usf.edu

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