February 10, 2005

BIRMINGHAM, AL — Despite huge gains in treating and preventing many forms of heart disease, congestive heart failure remains a stubborn, steady killer.

But perhaps not for long.

The National Institutes of Health has picked UAB as one of just five institutions nationwide — and the only university in the Southeast — to lead a massive, national research assault on congestive heart failure, the most unremitting diagnosis in heart disease.

Over the next five years, UAB will receive $18 million from the NIH to fund a Specialized Center of Clinically Oriented Research, or SCCOR, program, focusing specifically on heart failure research. SCCOR programs are clinically oriented, collaborative research programs, and the grant underscores UAB’s worldwide preeminence in cardiovascular research. NIH announced the grant Thursday. The Cleveland Clinic, Washington University, University of Cincinnati and Columbia University are the other four designated heart failure SCCOR centers.

The University of Alabama at Birmingham (UAB) SCCOR will bridge the efforts of a host of researchers who will combine their expertise and resources to more fully understand how and why heart failure occurs.

Researchers — from basic scientists to cardiologists — will then use an integrative approach to develop new strategies for treatment and prevention. UAB will also collaborate with electrical engineers and veterinarians from Auburn University (AU).

Heart failure affects more than 4.7 million people in the United States and includes more than 500,000 new cases each year. Research investments during the past 30 years have largely targeted deaths from ischemic heart disease. As a result, survival rates after heart attacks due to coronary artery disease have significantly improved. In 1963 there were 3,000 centenarians living in the United States and the number has grown to 60,000 in 2004. However, as patients live longer, doctors are now confronted with a new and more debilitating type of heart disease — heart muscle disease or heart failure. The only known cure for this is heart transplantation, but because only a limited number of donor hearts are available each year, heart transplantation cannot be the solution to the ever-increasing burden presented by chronic heart failure. The UAB SCCOR targets three types of heart failure that are very difficult to treat using standard therapy. These include medication resistant hypertension, diabetes, and valvular heart disease.

The Science of SCCOR

The main research goal is to unravel the mechanisms of left ventricle enlargement associated with heart failure in three distinctive forms of heart disease. Preliminary research has shown these three types of heart disease are resistant to standard medical treatment. “Understanding these mechanisms could lead to new treatments for those living with chronic heart disease,” said Louis J. Dell’Italia, M.D., UAB’s primary SCCOR program director, professor of medicine in cardiovascular diseases and the department of physiology and biophysics, and Elmer and Glenda Harris Endowed Chair holder.

Ahsan Husain, Ph.D., professor of physiology with joint appointments in the departments of physiology and biophysics and medicine and co-director of the UAB Center for Heart Failure Research (CHFR), will serve as primary co-director of the UAB SCCOR program.

The three groups of heart patients SCCOR researchers will study – those with heart valve disease, those with medication resistant hypertensive heart disease and those with diabetic heart disease (or disease of the heart muscle and its blood vessels) — account for greater than 50 percent of patients with heart failure.

“If we can understand heart failure in relation to these three major categories of heart muscle disease and develop new ways to treat it, then we could make a significant impact on the care of the increasing number of patients living with heart failure,” Dell’Italia said.

Heart Failure

Heart failure is a chronic condition and the eventual consequence of living with a diseased or malfunctioning and enlarged heart. The left ventricle (LV) is the main pumping chamber of the heart and is responsible for pumping oxygenated blood out of the heart and to the rest of the body.

When the heart’s pumping mechanisms do not function properly — caused by a variety of reasons such as birth defects, viruses, obstructed or narrowed arteries, and chronic diseases like diabetes or high blood pressure — the volume of blood in the LV increases and forces the heart to work harder. Thus, over time, as the LV chamber enlarges, the muscles that form the walls of the chamber grow thicker. This response is just like any other body muscle in response to an increased workload.

However, there is a cost of this incessant increase in workload with each beat of the heart. Eventually, the heart fails as a pump resulting in increased pressure within the LV, which causes a backup of blood in the lungs and one of the cardinal symptoms of heart failure, shortness of breath. Finally, as the heart muscle fails completely, other organs, like the kidney and liver, begin to shut down from lack of oxygenated blood.

Although enlargement of the left ventricle is the common result of heart failure, it happens in response to different factors, depending on the underlying cause of disease.

“Our approach in each of these three separate situations of heart disease considers the underlying causes, which have distinct mechanistic and functional consequences,” Dell’Italia said. “Therefore, we believe that in order to develop new, targeted drug therapies, we must understand and account for these unique causes and differences. That is our goal with all three of the SCCOR projects and the reason why the NIH requires SCCOR programs to focus on both clinical and basic scientific issues.”

Collaboration Within and Without

In addition to the three study projects, the SCCOR program has a system of core collaborators — groups of researchers who process data from all three projects for consistency. The core areas provide state-of-the-art technology, foster interactions between investigators, accelerate the pace of research, help translate basic research findings to clinical applications and ensure a productive research effort.

"In addition to consistency of data, the idea of the core set-up is to get the best person for the job. It makes more sense for engineers to study the geometry of the heart and for cardiologists to relate these findings to patient symptoms and treatment,” Dell’Italia said. “We have pathologists studying tissues, basic scientists studying cells in the lab, and veterinarians treating and studying dogs with heart failure.

“As a bonus, an undertaking of this magnitude will also help sick animals living with heart failure, like dogs — particularly because of our partnership with Auburn,” he added.

“This grant represents the culmination of many years of work to establish UAB as a global leader in clinically oriented research,” Dell’Italia said. “UAB was built on the concept of collaboration … on the idea of pooling all available resources within an academic environment in which basic scientists and doctors form bridges that allow them to see the big picture and to actually live the ‘bench-to-bedside’ approach.”

For veterinary medicine, this research has direct clinical implications because mitral valve disease is more common than all other canine heart diseases combined.

“Working with UAB, we have developed new therapeutic strategies to immediately apply that information to improve the quality of life of dogs with heart disease,” said Dr. Ray Dillon, Jack Rash Professor of Medicine and the principal investigator on the project in AU’s College of Veterinary Medicine. “When we started some of these projects 10 years ago, we had to send the MRI data to an engineering group in New Zealand for computer analysis.”

The image data will be sent to Tom Denney, professor of electrical and computer engineering in AU’s Samuel Ginn College of Engineering, for analysis. Denney has developed techniques for quantitatively measuring how much the heart muscle contracts and other indicators of cardiac health from cardiac MRI data. This analysis, combined with serial MRI scans, is expected to revolutionize the understanding of the heart’s response to disease.

Please note: We are the University of Alabama at Birmingham. Use UAB on second reference. We are not to be confused with the University of Alabama, a separate, independent campus in Tuscaloosa, Alabama.

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Image Size: 1,200 pixels by 1,680 pixels (4.0" by 5.6") Resolution: 300 dpi Format: JPEG (RGB) File Size: 1,161 KB Download Now! Caption: Louis J. Dell’Italia, M.D. (pictured), UAB’s primary SCCOR program director, professor of medicine in cardiovascular diseases and the department of physiology and biophysics, and Elmer and Glenda Harris Endowed Chair holder.

Image Size: 900 pixels by 1,261 pixels (3.0" by 4.2") Resolution: 300 dpi Format: JPEG (RGB) File Size: 928 KB Download Now! Caption: Ahsan Husain, Ph.D. (pictured), professor of physiology with joint appointments in the departments of physiology and biophysics and medicine and co-director of the UAB Center for Heart Failure Research (CHFR), will serve as primary co-director of the UAB SCCOR program.