Guest Editorial - Douglas E. Vaughan, M.D.

Poised for the future

Editor’s Note:  This guest editorial was written in 2007 by Douglas Vaughan, M.D., who in 2008 became chair of the Department of Medicine at Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital.

Douglas E. Vaughan, M.D.
Director, Vanderbilt Division of Cardiovascular Medicine
C. Sidney Burwell Professor of Medicine
Professor of Pharmacology
Published: October, 2007

Photo by Dean Dixon
More rapidly, perhaps, than has any other field of medicine, the treatment of heart disease has been transformed by extraordinary advances in basic and clinical science.

One of the best examples of the impact of research is in the management and treatment of patients with acute MI (myocardial infarction, or heart attack).

The evidence for many of the standard treatments that we routinely apply today, including beta-blockers, acute reperfusion therapy, statins and angiotensin-converting enzyme (ACE) inhibitors can be attributed to the investigative efforts and leadership of Eugene Braunwald, M.D., who is profiled in this issue of Lens.

This issue also will examine two other areas of active research that have been conceptually informed and motivated by Braunwald’s ground-breaking work—mechanisms of coronary thrombosis (clotting in the coronary arteries), and new treatments to improve cardiac function after a heart attack.

These advances are examined from the perspective of researchers at Vanderbilt University Medical Center, a microcosm of the breadth and depth of research and cross-disciplinary collaborations that are revolutionizing heart disease treatment and prevention around the world.

Investigators at Vanderbilt, for example, have pioneered numerous advances in cardiovascular research, including fundamental insights into the metabolism of prostaglandins and other eicosanoids, the molecular biology of blood pressure regulation, and the molecular mechanisms of cardiac arrhythmias.

Many of these studies have been conducted in the Clinical Research Center, one of the first of its kind in the country and also one of the most productive in terms of the volume of CRC-related research papers that are published each year.

Another example is the Vanderbilt Heart and Vascular Institute, which in 2005 joined cardiology, cardiac surgery and vascular surgery under one roof.

The institute provides a new opportunity to improve the ways we interact, and to increase the efficiency and quality of what we do. It achieves a real partnership between the providers, whether they are physicians, nurse practitioners or nurses, and the hospital that was not possible before.

In 2006, the National Heart, Lung, and Blood Institute (NHLBI) designated Vanderbilt, along with the Cleveland Clinic and the University of Pennsylvania, as a Specialized Center of Clinically Oriented Research (SCCOR) in Hemostatic and Thrombotic Diseases.

The Vanderbilt SCCOR grant will allow investigators from throughout the medical center to investigate why patients with obesity, insulin resistance and type 2 diabetes are at greater risk for arterial thrombosis and premature coronary disease.

It is critical for us to understand the mechanisms of these phenomena if we are to prevent effectively coronary events in these increasingly prevalent populations.

Over the last several years, no area of cardiovascular science has been more exciting or controversial than the area of stem cell biology. Do we have the capacity to regenerate cardiac tissue and function with resident stem cells in the myocardium (heart muscle) or from cells derived from the blood, bone marrow, or other sources?

As part of the newly formed Cardiac Cell Therapy Research Network, another NHLBI initiative, we recently began testing the efficacy of bone marrow-derived cells for the treatment of patients with acute MI and for patients with chronic left ventricular dysfunction.

Our working group includes basic scientists with expertise in cardiac development and stem cell biology, and a rather remarkable group of physicians from interventional cardiology, bone marrow harvesting and transplantation, cardiovascular imaging, cardiac surgery, electrophysiology and heart failure.

Fusion of two images of the heart—a computerized, tomographic (CT) angiograph and a myocardial perfusion image (MPI).
Courtesy of Murray Mazer, M.D., associate professor of Radiology and Radiological Sciences, Vanderbilt University Medical Center
The confluence of technology, pharmacology, surgery and genetics also is being applied to the identification and prevention of abnormal heart rhythms (arrhythmias) that are a frequent cause of sudden cardiac death. At Vanderbilt, for example, Dan Roden, M.D., and his colleagues are scanning the human genome for gene variants that put people at higher risk for fatal heart arrhythmias.

These examples illustrate how hypotheses about disease that emerge from basic science discoveries can be tested in the clinic and, conversely, how clinical observations can lead to entirely new and unexpected hypotheses. With current and anticipated developments at the cellular and molecular level, including knowledge of the human genome, future opportunities for continuing these advances are enormous.

There are numerous challenges to maintaining this momentum, however.

Cardiovascular research is an extremely expensive activity. The diminishing margins in health care in this country eventually will impact the ability of Vanderbilt and other academic medical centers to invest in research. Federal budget limitations already are affecting cardiovascular research and the training of new investigators.

Here again, Vanderbilt scientists are playing an important role.

Rose Marie Robertson, M.D., the first Vanderbilt faculty member to serve as president of the American Heart Association, has been the association’s chief science officer since 2003. She and NHLBI director Elizabeth “Betsy” Nabel, M.D., discuss the current state of research funding, the evolving mission of the institute and the value of public-private partnerships in this issue of Lens.

Betsy and I were fellows together at the Brigham and Women’s Hospital in Boston. Her vision and leadership have re-invigorated cardiovascular research nationally. She gives us the confidence that critically important areas of investigation will thrive in the years ahead, and that we will be able to continue to make progress in the fight against this nation’s leading disease killer.

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