Heart failure has emerged as an enigma in cardiovascular medicine. In contrast to the overall trend of decreasing death rates attributable to heart disease and stroke, the prevalence of heart failure and the resultant death toll are greater than ever before. Moreover, the improved diagnostic, preventive, and therapeutic methods now available for most cardiac disorders have barely made a dent in the prognosis for patients with heart failure. Despite reversal of symptoms, standard treatment for heart failure is associated with only a modest improvement in survival. Transplantation remains the only effective therapy for patients with severe end-stage disease, and that option is very much limited by a shortage of donor organs.
To those of us who are committed to alleviating the health burden of cardiovascular disease in the nation, heart failure represents at once the best, most pressing research opportunity and the worst, most difficult clinical problem. Its increasing prevalence accentuates the gulf between our accomplishments, which have been substantial in improving the nation's cardiovascular health, and the work that is still needed.
Annual heart failure death rates in the United States tripled between 1974 and 1994, and the morbidity from this disease, which leaves patients exhausted and bedridden, is staggering. Ironically, the upward trend in heart failure is likely an undesired outcome of advances in reducing mortality from coronary heart disease, hypertension, and stroke. More Americans than ever before are surviving with what heretofore would have been fatal heart disorders, and these survivors, as well as the elderly population in general, are at high risk for heart failure. Of the nearly 5 million patients afflicted with heart failure, 75% are older than 65 years of age. As the population ages—research advances and medical intervention notwithstanding—we can expect the problem to worsen.
Independent of the growing clinical problem of heart failure, an explosion of new information—derived from molecular and cellular biological and genetic engineering techniques—has fundamentally altered traditional definitions of normal health and disease of the heart and vasculature. That heritable and environmental factors are major determinants of health and disease has been an important tenet from the beginning of modern medicine. New techniques and the resulting data are delineating cellular and subcellular processes and the manner in which they are altered during the life cycle (ie, embryonic morphogenesis, development, normal adulthood, aging, and disease states). Molecular definition of cellular processes has been demonstrated, and these approaches provide extraordinary opportunities.
The biomedical research community is rapidly becoming aware of the extent of the health threat posed by heart failure and the extent of the new opportunities that exist to attack the problem. An example is the American Heart Association–supported scientific conference on the Molecular Biology of the Normal, Hypertrophied, and Failing Heart that was held last August in Snowbird, Utah. The meeting convened a stellar group of laboratory and clinical scientists attempting to apply cutting-edge basic approaches to the human conditions of heart failure. One clear message from this meeting is that advances against heart failure are most likely to arise from collaborations across scientific disciplines. The complexities of heart failure are such that a complete working model would require a knitting together of singular insights from outstanding investigators with varied expertise.
During the past several years, the National Heart, Lung, and Blood Institute (NHLBI) has intensified its efforts with respect to heart failure research. In 1992, the NHLBI convened a Task Force on Research in Heart Failure to identify new opportunities and chart a course for future research endeavors. The task force released a broad but comprehensive plan of objectives in 1994 (see the September 1994 issue of Circulation) that laid the groundwork for, among other endeavors, establishment of five Specialized Centers of Research in heart failure.
Recognizing the ever-evolving nature of the scientific enterprise, the NHLBI followed up the Task Force with a Special Emphasis Panel (SEP) on Heart Failure Research. The SEP met May 20, 1996, and was given the charge to focus on new strategies and capitalize on the latest innovations, needs, and opportunities in the field. Its deliberations and major recommendations appear in this issue of Circulation.
Despite the grave and growing problems associated with heart failure, participants in the SEP found much reason for optimism that we may soon have a better understanding of how to treat and, eventually, prevent this devastating condition. Bright new directions are highlighted by several developments.
• Transgenic mouse models of enhanced cardiac performance are now available to enable identification of protein and molecular targets for drug or molecular therapy.
• Xenotransplants from large, transgenic animals, genetically altered to produce organs compatible with humans, are becoming feasible.
• Cell transplants of cardiac myocytes may provide the basis for improved cardiac function. This fast-moving area of research holds promise for providing healthy cells to replace or supplement dysfunctional ones in a failing heart. This strategy may also one day offer the possibility of genetically altering donor cells for such desirable characteristics as enhanced contractile performance or secretion of beneficial neurohumoral agents.
• Novel gene vector development is actively being pursued to bring the promise of gene therapy closer to practice.
• Identification of endogenous regulators contributing to pathological conditions is occurring at an increased pace. Because of efforts such as the Rat Genome Project and Human Genome Project, investigators are able to identify optimal targets for study that are likely to have a significant impact on the progression of heart failure.
An important focus of the discussion during the SEP—and a concern that reverberates within the NHLBI and in the biomedical community—is the variety of obstacles that may slow, if not block, progress. As highlighted at the above-mentioned Snowbird conference, a major concern is inadequate communication and/or cross-training particularly between basic science investigators and physician investigators. If the readers of this article come away with only one message, it should be the following: The brightest opportunities to solve this major public health threat will never come to fruition unless the new technological wizards in the laboratory join forces with the healers at the bedside who so desperately need help in caring for the heart failure patient. Modern science has provided the tools, but only by combining and integrating our talents can we meet the challenge of fixing the failing heart. If we work together, there is much hope that one day heart failure will be added to our list of cardiovascular research triumphs.
- Copyright © 1997 by American Heart Association