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SUMMER ISSUE 2004

DOCTORS OF CEDARS-SINAI

FINDING THE ANSWERS TOGETHER.

HEART

DISEASE 21ST-CENTURY SOLUTIONS Life is everything.


.DOCS

VITAL SIGNS: A LETTER FROM THE EDITOR

ISSUE NUMBER 2, SUMMER 2004

AT HOME ON THE

NEWEST 2 VITAL SIGNS: Letter from Shlomo Melmed, MD, Director of the Burns and Allen Research Institute.

3 NEW FRONTIERS: Alfredo Trento, MD, moving the science of heart transplantation light-years ahead.

4 CARDIAC INSIGHT: P.K. Shah, MD, revolutionizing the treatment of heart disease.

WELCOME In this second issue of .DOCS we focus on the heart. As pioneers of innovative approaches to cardiac care, hypertension, and acute myocardial infarction, Cedars-Sinai has been a leader in the fight against heart disease, America’s greatest health concern. Cardiac care has always been a major focus at Cedars-Sinai. In more than 40 years of providing excellence in diagnostics and therapeutics, the Cedars-Sinai heart programs have gained an international reputation. Our work reflects a wide spectrum of clinical experience, including basic molecular events involved in cardiac disease, open-

heart surgery, the implementation of advanced imaging, and the advancement of translational research. This issue of .DOCS highlights the work of four talented physicians: Prediman K. Shah, MD, and his visionary research on a drug with the potential to revolutionize the treatment of heart disease; Daniel Berman, MD, who is advancing cardiac imaging through the development of artificial intelligence systems; Alfredo Trento, MD, and his cutting-edge mitralvalve heart surgery; and Peng-Sheng Chen, MD, who is breaking new ground in the field of arrhythmia research. As you read this issue of .DOCS, I know -2-

you will share the pride we all feel in the achievements of these innovative physician scientists and their teams who are keeping Cedars-Sinai on the cutting edge of cardiac investigation and care.

6 CURING HEART DISEASE: Daniel Berman, MD, merging artificial intelligence and cardiac imaging.

7 ARRHYTHMIAS: Peng-Sheng Chen, MD, pioneering arrhythmia research.

SHLOMO MELMED, MD Director, Burns and Allen Research Institute Senior Vice President, Academic Affairs

8 SCIENCE AND HUMANITY: Donor profile: Harold and Eleanor Foonberg.

FRONTIERS In the early 1980s, a resident at the University of Pittsburgh showed an unusual ability for surgical innovation. It brought him to the attention of Cedars-Sinai. “At that time,” Alfredo Trento, MD, remembers, “heart transplantation was an uncommon procedure. We were the pioneers. Before then, it was considered very experimental.” With his reputation for innovation, Dr. Trento was invited by Cedars-Sinai to head its new heart transplant program. His program was not only successful, it put the Medical Center at the forefront of the transplantation field. More than 15 years later, Dr. Trento continues to lead Cedars-Sinai’s transplantation program. He and his team perform more than 30 procedures annually, making the Medical Center among the ten busiest transplant centers in the country. One of the newest procedures is the implantation of a Cardiac Assist Device (CAD), which was initially used as a temporary measure until a donor heart became available. However, recent CAD technology has proven to be so effective, it is now being developed as a “destination” therapy. As a permanent solution, the Cardiac Assist Device enables a patient to be treated -3-

immediately upon diagnosis. Considering the average time a transplant candidate spends waiting for a donor organ is at least six months, permanent CAD devices are nothing short of a revolution. As CAD technology comes into regular clinical use, Cedars-Sinai has been approved by Medicare to be among a select group of medical facilities nationwide able to administer this procedure. One of the most important breakthroughs is Dr. Trento’s own minimally invasive mitral-valve surgery. Poised to eclipse the accepted treatment of replacing a defective heart valve with an artificial one, this mitral-valve surgery actually helps the heart heal itself and is expected to be the next wave in cardiac care. But even this is not Dr. Trento’s greatest ambition. “My ultimate goal,” he says, “is to expand our programs to include a new Heart Failure Center where all aspects of end-stage heart failure will be treated.” Until the new Heart Failure Center becomes a reality, Dr. Trento’s current program is setting a national standard for creativity and excellence, while clearly demonstrating the possibilities for his next innovation in heart care.


INSIGHT

HAS NO BOUNDARIES On the table next to the desk in P.K. Shah, MD’s office is an object of contemplation. It’s not one of those small waterfalls in a bowl or a picture of a tropical sunset. It’s a model of the human heart. As Dr. Shah would be the first to point out, “The heart is the center of the universe.” For the past 27 years, his unique focus and dedication have served him well as Director of Cedars-Sinai’s Division of Cardiology, one of the nation’s leading heart care centers. It has also prompted him to seek out other physician-scientists and researchers throughout the world with similar expertise and creativity. It is a mission that connected him with researchers at the University of Milano working under the guidance of Dr. Cesare Sitori in the early 1980s who had made a fascinating discovery. A man from the small town of Limone in Northern Italy was found to have an unusual combination of elements in his blood. While he demonstrated very low levels of HDL cholesterol, the “good” cholesterol that protects arteries from plaque buildup, he also exhibited extremely high levels of triglicerides, a bad form of fat in the blood that can lead to deposits in the arteries. This combination normally increases the risk of cardiovascular disease. But this man had healthy arteries. Taking their studies to others in Limone, researchers then tested nearly 1,000 inhabitants. Among those tested, 40 subjects shared a similar lipid abnormality. Through the use of local church records, it was discovered that each shared a common ancestor, and all of them shared a certain genetic mutation. This mutation or genetic abnormality produces a protein, Apo-A-1 milano, that -4-

becomes part of the HDL cholesterol, and offers amazing benefits to the heart. At Cedars-Sinai, in 1992, Dr. Shah and his colleagues began to research the applications of Apo-A-1 milano. They discovered that when Apo-A-1 milano was injected intravenously, it could reduce the buildup of cholesterol plaque inside the arteries. Further testing demonstrated that Apo-A-1 milano could stop the progressive plaque buildup, in addition to shrinking or reversing preexisting arterial deposits. Sanjay Kaul, MD, member of Dr. Shah’s research team, also was able to prove that local injections of recombinant Apo-A-1 milano prohibited the growth of scar tissue around coronary artery stents. But perhaps the most stunning result was that a single large dose of Apo-A-1 milano could remove not only cholesterol, but also inflammation from arterial plaque within two days, sending the cholesterol out from the arteries and to the liver for disposal from the body. Based on Dr. Shah’s work at Cedars-Sinai, and that of Dr. Cesare Sitori in Milan, Phase 1 clinical trials of Apo-A-1 milano were conducted that showed it to be safe to test on humans. A Phase 2 trial was completed in 2003, which showed that plaque in the human coronary artery shrank after five weekly injections of Apo-A-1 milano. Additional clinical trials including a Phase 3 trial are in the planning stages, and Dr. Shah hopes to have the revolutionary treatment available within the next four years, after FDA approval. It takes an uncommon mind to sift through all the complex issues of heart disease, America’s number-one health concern, and isolate the potential applications of a particular genetic abnormality found in the descendants of a small Italian village. But if you spent as much time contemplating the human heart as Dr. Shah, it’s easy to understand how he is helping to bring hope to hundreds of thousands of those suffering from heart disease.

ATHEROSCLEROSIS RESEARCH CENTER

Our scientists are breaking new ground in treating heart disease. They are developing a vaccine for the prevention of heart disease that may become a routine part of childhood vaccination programs. The team is finding new genes that could explain why some arteries become clogged with cholesterol plaque and others do not — leading to new ways of preventing arterial plaque buildup. By donating to the Research Center, you will receive named recognition and help them continue their important work. $100,000 to $5,000,000 ENDOWED CHAIRS IN CARDIAC AND THORACIC SURGERY

Giving at this level will endow a lasting succession of prominent cardiac scholar-surgeons within this prestigious appointment. $1,500,000 ENDOWED FELLOWSHIPS FOR CARDIAC RESEARCH

Our world-renowned cardiac fellowship program prepares outstanding young doctors to be the cardiac pioneers of tomorrow. Endowing these Fellowships will enable our scientists and clinicians to achieve lifesaving advances in the prevention, diagnosis, and treatment of heart disease. $1,000,000 CARDIOTHORACIC OPERATING ROOM OF THE 21ST CENTURY

Cedars-Sinai is blending the finest surgical devices in the world with our own technological breakthroughs to create the Cardiothoracic Operating Room of the 21st Century, ready to be named in your or your family’s honor. $1,000,000 HEART DISEASE RESEARCH LABORATORIES

By making a gift to name a major heart research laboratory, you can provide a permanent, state-of-the-art scientific setting for Cedars-Sinai’s most advanced cardiac research in promising areas, including: using stem cells to regenerate damaged heart muscle; the role of blood thinners in heart failure; hormone-replacement therapy for women with heart disease; new treatments for congestive heart failure; and new gene-based therapies to prevent the development of arterial plaque and to reverse existing plaque buildup. $600,000 (per lab) CARDIAC IMAGING RESEARCH

We are world leaders in developing noninvasive techniques for early detection of heart disease. Our research team is developing breakthrough software that will revolutionize the clinical applications of major cardiac diagnostic devices: magnetic resonance imaging, computed tomography, positron emission tomography, and other diagnostic technologies. A gift at this level will enable this research to continue. $50,000 and up PILOT RESEARCH GRANTS

A “modest” pilot research grant in your name can provide the seed money that creates a major, long-term research project, which in turn leads to significant breakthroughs. Pilot grants are a powerful tool in fighting heart disease. $25,000 and up For giving opportunities in the heart disease arena, please contact Alice Holzman (310) 423-3665 -5-


HEART

DISEASE: CAN WE MAKE IT EASIER

TO CURE THAN THE COMMON COLD?

Daniel Berman, MD, Director of CedarsSinai’s Cardiac Imaging and Nuclear Cardiology Division has posed a visionary question: What if heart disease could be stamped out? The breakthrough work he and his team of scientists and researchers are achieving at the new Cardiac Imaging Research Center is making the elimination of heart disease a reality for thousands of CedarsSinai patients each year. Dr. Berman’s formula for success has a stunning simplicity: early detection and treatment of disease in the arteries can prevent development of actual heart disease. Dr. Berman states, “The therapies we have now are so powerful, we can stop the disease before it ever becomes obstructive. All we have to do is to detect it and treat it in its initial stages. Our goal is to maximize the ability of noninvasive imaging technologies to detect and ultimately prevent coronary heart disease.” Led since the 1970s by Dr. Berman and Dr. John Friedman, the Cardiac Imaging Research Center (CIRC) at Cedars-Sinai has created a dynamic new diagnostic approach in which several modalities for diagnosis are combined to create powerful new treatment opportunities. -6-

During the past 15 years, the Cardiac Imaging Research Center (CIRC) has compiled a comprehensive database of nuclear cardiology and clinical information for over 20,000 individuals who have then been tracked over time. By relating the initial observations to patient outcomes, the doctors have been able to define the way in which testing can be used to determine the most beneficial treatment for individual patients. The research of the CIRC team is widely credited as being the most influential in the country in shaping the way in which noninvasive testing is used to guide patient-management decisions.

the quest to making this valuable test available to the patients who need it,” states Dr. Berman.

Dr. Berman brought other cardiac imaging specialists to the CIRC, so the interpretive skills of the readers could be at the same level as the advanced technology with which they were working. “We attracted some of the world ’s best scientists in cardiac image processing, beginning with Guido Germano, PhD , leading to the development of the world-class Artificial Intelligence in Medicine (AIM) program at Cedars-Sinai,” Dr. Berman states. By bringing together the team of computer scientists and cardiologists with expertise in cardiac imaging and outcomes analysis, an innovative partnership between CIRC and the Artificial Intelligence in Medicine (AIM) team was formed.

In 2004, through another generous donation, Cedars-Sinai will acquire a new PET/CT, a scanner combining the latest in Positron Emission Tomography (PET) scanners and CT scanners in the same machine. PET/CT, already recognized as a powerful tool for cancer, is likely to play a prominent role in cardiac diagnosis as well. Dr. Berman states, “PET/CT may make noninvasive coronary angiography a practical reality, by allowing us to detect plaques in the artery walls, see if they are obstructing the lumen, and determine the importance of the obstruction — all at one time.”

In 1998, the CIRC team added cardiac computerized tomography (CT) to their imaging armamentarium, with its high-resolution images enabling them to measure the calcium deposits, that are the earliest direct markers for plaque buildup in the coronary arteries. “We can now identify these early indicators 15-20 years before clinical heart disease develops, allowing effective therapies to start at an early stage,” Dr. Berman notes. With the generous support of the Eisner Foundation, the CIRC team has developed a database of clinical and CT data on over 10,000 patients and has undertaken two large scale clinical trials of thousands of subject to determine the usefulness of the coronary calcium and how it relates to the nuclear cardiology and clinical information. “Our data promises to play an important role in

In 2003, a dedicated cardiac MRI was added to the CIRC, and new imaging cardiologists and scientists with specialized expertise in cardiac MRI were recruited to Cedars-Sinai, creating a center of excellence in cardiac MRI. Dr. Berman calls MRI “the sleeping giant” of all the new technologies. “It has the potential to do everything,” he says as he opens his laptop to reveal high-resolution MRI images of a woman’s beating heart.

Dr. Berman envisions a proposed new building for the CIRC as a place of unparalleled innovation. “Proximity is key to innovation,” he says, looking forward to a time when AIM and CIRC will be housed together, in a location adjacent to the clinical cardiac scanners. “With the AIM team, the research coordinators, the CIRC physicians and the clinical imaging being spread all over the Medical Center, we cannot come close to reaching our creative potential,” Dr. Berman notes. “Half the people who die from heart disease don ’t even know they have it,” Dr. Berman points out, “We envision a world-class Cardiac Imaging Research Center to complement a Center that can transform the potential of these new technologies into clinical realities for all those who need them.”

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ARRHYTHMIAS: UNLOCKING THE CURE BY UNDERSTANDING THE CAUSE When Peng-Sheng Chen, MD, talks about the interdependence of the atria and ventricles in the heart, it becomes clear that they are inextricably linked. A malfunction in one of the chambers affects the entire organ, creating rhythm disturbances. These irregularities are called cardiac arrhythmias. One kind of arrhythmia, atrial fibrillation, occurs when the two upper chambers of the heart beat more quickly than the ones beneath. This uneven circulation results in a form of blood stagnation that can induce a stroke. Fibrillation of the lower ventricles is an even more serious condition, and affects over 100,000 Americans on an annual basis. This rhythm results in sudden cardiac death unless an electrical shock terminates it within several minutes. The causes of ventricular fibrillation are not yet fully understood and current therapies are limited. As the Pauline and Harold Price Chair in Cardiac Electrophysiology Research, Dr. Chen is focusing his work on the mechanisms that cause atrial and ventricular fibrillation. His teams are also studying the phenomenon of cardiac nerve sprouting, an abnormality commonly found in the central nervous system. As one of the first physicianresearchers in the nation to observe a relationship between nerve sprouting and cardiac disorders, they have already produced a new understanding of arrhythmias and another example of CedarsSinai’s standard of excellence.


Harold and Eleanor Foonberg

Harold Foonberg remembers a time when a family member had become ill and sought care at another hospital. His condition become so critical that doctors had given up hope. But Harold didn’t believe in giving up. He insisted his brother-in-law be transferred to Cedars-Sinai, and after a few weeks in intensive care, he was on his way to a full recovery. “Because of Cedars-Sinai,” Harold remembers, “someone in my family is still here.” Harold and his wife, Eleanor, have a special place in their hearts for the Cedars-Sinai family. In 1982, he became involved in the Cedars-Sinai Diabetes Tennis Tournament, and in the late 1990s, became its chair. Under Harold’s stewardship, the Tournament broke all prior fund-raising records and in the next three years, raised in excess of $2.5 million. Because those with diabetes are three to four more times at risk for heart disease, his involvement with the tennis tournament was understandable. His own heart condition had been treated by Dr. P.K. Shah, Director of the Medical Center’s Division of Cardiology. In gratitude, Harold donated funds to further Dr. Shah’s important research, and because of his generosity, the cardiology waiting room has been named in his and his wife’s honor. “The Medical Center has made incredible strides in so many areas,” Harold notes, “I’m just happy I could help.”

Life is everything.

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