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Conversation

Dr. Mario C. Deng

Photography by Juliane Backmann

The internationally recognized physician and researcher takes the reins as medical director of UCLA’s Advanced Heart Failure, Mechanical Circulatory Support and Heart Transplant Program.

WHILE A MEDICAL STUDENT AT THE UNIVERSITY OF BERLIN IN 1977, Mario C. Deng, M.D., was working the nightshift in the resuscitation center, when his team sought to transfer a dying 45- year-old heart-failure patient more than 5,500 miles to Stanford University, one of only three centers in the world performing heart transplants at the time. The man died before he could receive a new heart, but the experience had a lasting impact on Dr. Deng, who went on to become an internationally recognized leader in the field.

On April 1, 2011, Dr. Deng arrived at UCLA as medical director of the Advanced Heart Failure, Mechanical Circulatory Support and Heart Transplant Program at Ronald Reagan UCLA Medical Center.

Born and raised in Berlin and Hamburg, Germany, Dr. Deng spent his senior year of high school in Southern California as part of an international-student-exchange program. He returned to Germany for medical school and trained in internal medicine and cardiology. In 1992, he came back to California to complete a postdoctoral fellowship in heart transplantation/molecular cardiology at Stanford University. He then served as medical director of the Interdisciplinary Heart Failure and Heart Transplant Program at Muenster University in Germany before moving to Columbia University Medical Center in New York City in 2000, where he was director of cardiac-transplantation research for more than a decade prior to coming to UCLA.

In Germany, and then at Columbia, Dr. Deng conceived of and pioneered one of the seminal recent advances in heart transplantation, in close collaboration with UCLA and other leading academic U.S. heart-transplant centers: the first FDA-cleared blood test to rule out cardiac rejection, known as the Allomap test. The genomics-based test has greatly reduced the number of invasive cardiac biopsies required by heart-transplant recipients.

Dr. Mario C. WengDr. Deng spoke with UCLA Medicine contributor Dan Gordon about his career, his humanistic perspective on patient care and about his vision for UCLA’s Advanced Heart Failure, Mechanical Circulatory Support and Heart Transplant Program.

How did the Allomap test come about, and what has its development meant for heart-transplant patients?

Dr. Deng: When I arrived at Columbia University, we asked questions based on work we had done, both at Stanford and in Europe, on the interaction between the immune system and the cardiovascular system. For 30 years, every heart-transplant center had been using heart-muscle biopsy with an invasive heart catheter to rule out heart-transplant rejection. We learned, through a large study involving collaboration among 20 of the largest U.S. heart-transplant centers and a biotech company, Expression Diagnostics in San Francisco, that we could determine the absence of rejection by drawing the recipient’s white blood cells and subjecting these cells to gene-expression profiling with DNA microarray technology, which had become increasingly available during the years before the Human Genome Project was completed in 2001. This finding led to Clinical Laboratory Improvement Amendments approval in 2005 and FDA clearance in 2008 of the Allomap test, which is now used in many U.S. transplant centers to rule out rejection in stable heart-transplant patients coming in for their routine follow-up visits. In April 2010, we reported in the New England Journal of Medicine that it has led to a reduction of biopsies by at least 25 percent. Besides its scientific merit, this is a major advance from the patients perspective because it is less invasive, i.e., less risky and painful.

Where is your research focused now?

Dr. Deng: At the invitation of the National Institutes of Health, we are using a similar design to conduct the first pilot studies for a clinical problem that all of us encounter in the advanced-heart-failure population: multi-organ dysfunction syndrome. This syndrome, unfortunately, occurs in very-ill patients in the intensive care units for different reasons, for example, after a very-advanced-heart-failure patient has a surgical intervention such as mechanical-circulatory-support device implantation. A fraction of these patients die without ever leaving the hospital, and no one has a good grasp of how to predict this clinical course before a heart surgery takes place, or even early after surgery but before it becomes a clinical problem. The concept of our work in recent years, just as we did with the Allomap test, is to utilize the information carried by white blood cells to predict if and when this process will occur to alter the impact of the multiorgan-dysfunction syndrome.

All of our studies take place in a framework of systems biology, because the relationship between the white blood cells’ gene products, the organ function and the whole person is not a simple one. It’s translational bench-to-bedside research involving a multidisciplinary team, which is what we assembled in our research lab at Columbia and what we will be expanding at UCLA.

What drew you to UCLA?

Dr. Deng: There were both personal and professional attractions. For one, my wife, Federica Raia, and I love the Californian spirit of exploration. I grew up in Germany, but at age 16, I was privileged to live in the United States as part of the Youth for Understanding International Student Exchange program. I came to Southern California, was placed with a family, who I consider my American Family, in Garden Grove and graduated from Bolsa Grande High School in 1972. I went with my American brother to Disneyland and the drive-in movies and surfed, and I fell in love with the culture and the international-cultural-exchange perspective. Twenty years later, I came back to the United States to train in the sub-specialization of heart failure, transplant and molecular cardiology at Stanford University, where many of the heart-transplantation concepts had been developed. As a result, I associated California with the spirit of exploring novel concepts and testing boundaries.

I knew and had always admired the UCLA organ-transplant and heart-failure program – both its outcomes and its team-oriented approach. Most important, I felt that the vision of the hospital CEO, Dr. David Feinberg, and the medical school dean, Dr. A. Eugene Washington, were well-aligned with mine.

What is that vision?

Dr. Deng: The core of my clinical convictions is that high-tech modern medicine can be practiced in a humanistically sound way only if we empower patients and their families to make decisions, and that we physicians see ourselves not as gods or goddesses – the sole possessors of knowledge and truth – but as consultants in our patients’ decision-making process. I believe that at the center of anything we do in medicine is the encounter between a person who has an illness and seeks professional help and a health professional who has a white coat on but is also a human being. These two meet, and within this encounter everything unfolds. I listen to you as the patient, clearly communicate different options for you based on my expertise and experience, and empower you as the patient to make an appropriate decision, in consultation with your family and other second opinions. I would never say, “Either you have a heart transplant or you will die,” because eventually we all will die, and no matter how white our coat is, none of us can predict with certainty what is going to happen. Everything we do within the specialized field of advanced heart failure – including education, training, translational research and collaboration with other healthcare providers in the region – should take place within the framework of these humanistic, patient-centered values.

How does this patient-centered approach play out in the clinical landscape for advanced-heart-failure patients, in particular, given the shortage of organs available for transplant?

Dr. Deng: Our goal is to recommend to our advancedheart- failure patients various options in answer to their question: “Doc, which treatment concept gives me the best chance of growing old and living a good quality of life?” I will be working closely with my colleagues in the Ahmanson-UCLA Cardiomyopathy Center, the Ahmanson/UCLA Adult Congenital Heart Disease Center and the Division of Cardiothoracic Surgery to meet the needs of patients along the continuum of heart failure. In the Greater Los Angeles Area, there are roughly 100,000 to 200,000 people with heart failure, and of them, at least 10,000 have advanced heart failure. The number of donor organs for heart transplantation is 100-200 a year, leaving at least 9,800 persons who have to be treated in other ways. Mechanical circulatory support is a rapidly evolving therapy with which I have been intimately involved in Europe long before coming to the United States. Currently, the number of patients with lifetime-assist heart pumps is already similar to the number of patients with a heart transplant. In 10 years, we will probably have a fourthor fifth-generation device with completely implantable assist heart pumps that stay in the body 10-to-20 years, along with a transcutaneous belt energy transformer and a very low risk of infection. With that advance, similar to the evolution of pacemakers over the last 50 years, another 1,000 to 2,000 of these persons may choose to have a mechanical-circulatory-support device for their lifetime. But many of these individuals may opt to live a life with less aggressive treatment options. For example, in 2008, my American father was 82 and in advanced heart failure, and he was asked if he wanted a lifetimeassist heart pump. After careful discussions and deliberations, he opted to live with his own heart as long as it would carry him. He spent a beautiful holiday season with his family and passed away one week later. That kind of informed-patient preference has to be respected.

How can the program best position itself to be able to meet patient needs and preferences?

Dr. Deng: Obviously, if someone opts to have a heart transplant, UCLA – with a tradition of more than 25 years and having recently been ranked by the U.S. government as the nation’s top-quality heart-transplant program – must continue to deliver world-class outcomes through its clinical teams, as well as continue to be a leader in discovery through its basic-science teams. We will also be rapidly expanding our lifetimemechanical- support program to offer more options for people who make that choice. Assist heart pumps are moving rapidly from bulky, crisis-intervention treatments toward small, completely implantable devices that allow patients to return to a fairly normal life. We will take on the challenge to develop a network with community cardiology providers who are an integral part of a lifelong-care continuum for these patients after their devices are implanted.

And finally, if after being evaluated, patients opt to have a less-aggressive treatment plan, as my American father did, we need to provide what is usually termed palliation care. What it really means is a focus on quality of life not just at the end of life but during the entire continuum of the illness, in conjunction with the family and community, as part of a broader vision.

We also have a responsibility to play a leadership role in creating what the current administration and healthcare discourse has termed accountable healthcare organizations. The outcome measure should not be how many transplants we do or how many assist devices we implant. Instead, it should be how these 10,000- to-20,000 patients in the region with advanced heart failure are treated in an evidence-based-medicine way that respects their personal choices, their humanity and their dignity. Part of this vision for our Dr. Dengprogram at UCLA is that we will be working very closely with cardiologists, primary-practice offices and community hospitals in the Greater Los Angeles Area and beyond, guaranteeing their indispensible active role and responsibility in the healthcare continuum. That’s a vision that should be owned not just by UCLA but by all of us who provide care in the region.

Reflecting back to when you were first starting in this field, what are the most striking advances that have been made?

Dr. Deng: Starting with the development in medical therapies, there has been a more complete understanding of what the dysfunction in heart failure is about – not seeing it only on the isolated organ level, but also taking the person as a complex, dynamic system and treating him or her accordingly. The field of mechanical circulatory support has been rapidly advancing over the last 20 years. We have moved to more evidencebased, less-invasive types of assist heart pumps that are smaller, more durable and allow the patient much more freedom to move about. And finally, in heart transplantation, I think one of the most important advances is the introduction of non-invasive monitoring based on molecular white blood cell gene-expression testing. Not only does this procedure expose patients to fewer of the invasive heart-muscle biopsies, but now we are also using this gene-expression profiling approach to safely down-titrate immunosuppression therapy, thereby reducing their side effects.

Where do you derive the most personal satisfaction from your work in this field?

Dr. Deng: To have had the underlying vision and to have been intimately involved with the implementation of the first-in-history genomic heart-transplantation test is certainly very rewarding. But the most rewarding moments for me are those times when I am interacting with my patients in a way that connects us as two individuals – not white coat and patient, but two human beings. This interaction is the spirit in which we must conduct our high-tech modern medicine.

 





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