1. Schwertz, Dorie W. PhD, RN, FAAN

Article Content

Every year, the American Heart Association (AHA) publishes a list of the top 10 research advances in the areas of heart disease and stroke.1 This list, released on the last day of the year, describes achievements that have the potential to greatly improve the cardiovascular health of individuals and communities. The 2001 advances range from studies that substantially move forward our understanding of fundamental cardiovascular physiologic and pathophysiologic processes at the cellular and molecular level to research that confirms the outcomes of preventive interventions.


This issue of The Journal of Cardiovascular Nursing (18:1) consists of 10 short articles that review each of the research advances of 2001. The top 10 list includes (in order of priority from the AHA) the following:


1. Drug-coated stents prevent artery reblockage


2. Implantable left ventricular assist devices (LVADs) treat heart failure


3. Implantable heart shows promise


4. Tissue engineering grows new heart parts


5. Gene therapy (with vascular endothelial growth factor [VEGF]) reduces angina


6. Cholesterol-lowering drugs benefit high-risk populations even when the low-density lipoprotein (LDL) level is normal


7. New genetic predictors of cardiovascular disease (CVD)


8. Cell transplants offer promise for stroke recovery


9. Nurture and nature associated with type 2 diabetes


10. Passive smoking is not so passive for arteries



The goal of this issue is to describe the research that contributed to these achievements, provide some insight into why these topics were considered among the top 10 advances, and describe the promise and potential these advances have for significantly impacting cardiovascular health in the future.


As the year 2002 progresses, the advances continue to generate interest, excitement, and optimism. But research goes in fits and starts, and few outstanding research achievements evolve without running into controversy, frustration, and failure. Therefore, while the articles in this issue highlight achievements, failures and struggles have not been overlooked. Overall, however, each of these advancements has greatly informed the body of cardiovascular research and has generated and directed more focused future studies.


The first of the top 10 advances is the development of drug-eluting stents to prevent reblockage of coronary arteries after stenting. The development of drug-eluting stents appears on first glance to be nothing but a meteoric and dramatic success story. However, there are elements of luck, along with brilliance and hard work in most success stories. This breakthrough was empirically based on previous research defining the role of smooth muscle cell proliferation in pathophysiologic neointimal hyperplasia. The concept behind drug-eluting stents was to locally deliver anti-proliferative drugs, inhibit cell proliferation, and thereby eliminate reblockage of stented arteries. The results of the RAVEL and ELUTES clinical trials demonstrated that coating stents with the anti-proliferative drugs sirolimus (Rapamycin) or paclitaxel dramatically reduced in-stent restenosis to near zero in simple de novo lesions. There was some luck in the choice of the anti-proliferative drug because not all drugs that inhibit cell proliferation worked to stop restenosis. Preliminary results from further trials of drug-eluting stents in 2002 continue to be promising. In fact, recently Heartwire ( reported: "The US Centers for Medicare and Medicaid Services has created new hospital reimbursement rules for drug-eluting stents before the devices themselves have even received FDA [Food and Drug Administration] approval."2


LVADs for end-stage heart failure was listed as the second research advance. The relatively small implanted device supports circulation when the natural heart is unable to maintain adequate perfusion. The device can serve as replacement therapy or as a bridge to transplant, and research exploring the role of the LVAD as a potential bridge to recovery is in progress. Patients treated with the device live longer and may have a better quality of life than those treated with drugs and medical monitoring. In the second article of this issue, Cianci and colleagues describe the assist device and discuss the current and potential applications of the LVAD from their own perspective (working with patients with LVADs) and from a review of other clinical trials.


The AbioCor artificial heart made headlines in 2001 and continues to make headlines in 2002. Unlike one of the first artificial hearts, the Jarvik-7, that was implanted in Barney Clarke in 1982 and had attachments to external components through holes in the chest, the AbioCor device is totally implantable. This third article, written by a nurse who works at the bedside of patients who received this heart, provides some developmental history of the totally implantable heart and a technical description of the device itself, as well as an outline of the degree of success in terms of patient outcome after implant. While each death of one of the "unselfish [horizontal ellipsis] pioneers and heroes" who enroll in these trials could be thought of as a failure, the knowledge gained by each trial translates into improving technology with the hope of one day developing an implantable artificial heart that will provide relief from end-stage heart failure.


The first trial to transfer a gene into a human for CVD therapy involved introducing the LDL receptor into the liver of a patient with familial hypercholesterolemia in 1992. Since then hundreds of clinical trials of gene therapies have been conducted, and the results have begun to answer challenges inherent in this type of therapy including identifying candidate genes, finding minimally invasive methods of gene delivery, increasing duration of gene expression, and lessening toxicities and side effects. To date, only 1% of these trials have reached phase III clinical trials. The public successes and failures of gene therapy trials have shaped opinions and motivated government regulation. In 2001, the AHA listed "Gene therapy (with VEGF-2) reduces angina" as the fifth of the top 10 research advances based on early findings from a placebo-controlled, double-blind, randomized trial showing VEGF gene therapy reduced angina in subjects with severe angina. VEGFs are vascular endothelial growth factors that play key roles in the formation of new blood vessels from preexisting vessels. Merkle and Montgomery discuss the physiology of VEGF as well as the achievements and tribulations of the gene therapy trials. Overall, the results move the science of gene therapy forward and may provide hope for those living with angina.


If heart parts (such as valves and blood vessels) could be engineered out of living cells, the major disadvantages associated with mechanical or bioprosthetic replacement parts (such as thrombosis, limited durability, infection, rejection, etc) could be overcome. If a heart part using a person's own cells could be developed, not only would these disadvantages be eliminated but also the part could be placed in an infant with congenital heart disease and grow with the child into adulthood. Perry and Roth describe advances in tissue engineering of heart valves and blood vessels over the last decade. They describe sources of cells that may successfully be used in tissue engineering such as progenitor and stem cells. The use of fetal stem cells has raised ethical questions; however, multipotent progenitor and stem cells have been shown to exist in bone marrow, peripheral blood, and umbilical cord blood. The authors of this article and other investigators are working to develop the use of these cells in bioengineered tissues. The results of their studies foretell great promise for valve, blood vessel, and heart muscle cell replacement.


The eighth of the top 10 research advances "Cell transplants offer promise for stroke recovery" has some commonalities with advances in tissue engineering and thus is discussed out of sequence. Stroke is the leading cause of disabilities in adults. Currently, little can be done to recover function once brain cells have been terminally damaged by a stroke. However, the recent findings that stem cells can develop into mature brain cells in stroke-damaged rat brains and even reduce stroke-induced disability have generated tremendous excitement. The article by Savitz and colleagues reviews sources of cells that may be used for brain transplantation including the authors' own work with neural progenitor cells. Debate about use of embryonic stem cells has directed researchers to look for other cell sources that might proliferate and differentiate in a controlled manner, reconstruct neural circuits, and recover brain function. An immortalized cell line, bone marrow stromal cells, and umbilical cord blood cells are potential candidates. Similar to the efforts toward use of cells in bioengineered heart parts, cell transplants into the brain to recover function shows promise but "much work lies ahead" to reap full potential in both fields.


In 2001, the National Cholesterol Education Program (NCEP) released clinical practice guidelines for the evaluation and management of elevated cholesterol in adults (Adult Treatment Panel [ATP] III). These outcome-based guidelines take a more comprehensive and aggressive approach to identification and treatment of high-risk patients than had been previously recommended. In addition, even though not actually published until 2002, results of the Heart Protection Study (HPS), the largest randomized study of a 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA) inhibitor and antioxidants in persons with high risk for CVD, were being reported. The results of this study showed daily simvastatin therapy significantly reduced major adverse cardiovascular events in high-risk populations (ie, those with diabetes, non-coronary occlusive disease, etc) and also in women, persons over age 70, and those with LDL below 116 mg/dL. These findings have such enormous implications for prevention of CVD that the AHA named "Cholesterol-lowering drugs benefit high-risk populations even when LDL is normal" as the sixth of the top 10 research advances of 2001. Braun and Davidson discuss the results of the HPS and the ATP III guidelines and provide recommendations for management of high-risk patients.


The seventh of the top 10 advances highlights the discovery of genes that are involved in the development of CVD. The presence of these genes in individuals and families will aid in predicting premature disease and may provide an opportunity for preventive strategies. In one of the largest genotyping studies ever attempted, investigators found variations in the genes for thrombospondins (a family of matrix proteins associated with growth of blood vessels, the blood vessel's response to oxidized LDL, and blood clotting) could, depending on the variant, either significantly increase risk or provide protection from CVD. Mutations in other genes were found to be associated with Dunnigan-type familial lipodystrophy (a disease that causes a six fold risk of coronary artery disease) and with familial Wolff-Parkinson-White syndrome. These findings were made possible by the use of a high-throughput technology called microarray genotyping (DNA chip technology). Cheek and Cesan describe this new "chip" technology, focusing on the investigation that linked thrombospondin gene variants with CVD.


Maybe we really can change our habits-exercise, eat right, and thereby prevent serious disease. This appears to be true to a great extent in the case of type 2 diabetes. As described in the ninth article by Quinn, recent evidence suggests that environmental and behavioral factors may have a greater role in the development of type 2 diabetes than was previously thought. Clearly, genotype sets the biologic stage for this disease, but recent studies underscore the potency of behavioral and environmental contributions to its manifestation. This realization validates the theory that manipulation of these factors could decrease the phenotypic expression of the disease in high-risk genotype groups. The finding has implications for the prevention of this increasingly prevalent disease.


Since 1984, indirect evidence has suggested that passive smoking, defined as exposure to sidestream smoke from burning cigarettes and mainstream smoke exhaled by the smoker, is associated with heart disease. Mechanisms by which passive smoke exposure causes CVD include increasing platelet aggregation, reducing oxygen transport, and initiating arterial endothelial damage, which can lead to restricted flow and atherosclerosis. However, in 2001, a well-controlled experimental investigation by Otsuka and colleagues directly demonstrated passive smoking alters endothelial function in coronary arteries and alters coronary flow reserve in healthy young adults. This definitive study, and its potential impact on prevention of CVD, was the basis on which the AHA chose this research advance as one of the top 10 for 2001. Ahijevych and Wewers review experimental and epidemiologic work on passive smoking and suggest that appropriate assessment of passive exposure to smoke and public health initiatives to eliminate exposure to passive smoke are needed.


The top 10 research advances for 2001, as determined by the AHA, range from achievements grounded in the Human Genome Project and molecular biologic techniques to results of pivotal experimental studies and clinical trials that provide an empirical basis for prevention and treatment of CVD. The spectrum of advances described in this issue illustrates the level of sophistication of scientific inquiry inherent in the pursuit of eradication of heart disease today. The advances demonstrate the evolution of cardiovascular science from the bench to bedside. It is important that cardiovascular nurses and all health care professionals caring for patients with CVD make an effort to stay informed with regard to the science that affects their practice. One of the goals of developing this special issue was to make the task of understanding the latest advances a little easier. I thank the many expert contributors from multiple disciplines for their work in achieving this goal.


-Dorie W. Schwertz, PhD, RN, FAAN


Associate Professor Medical Surgical Nursing, Adjunct Professor of Pharmacology




1. American Heart Association. American Heart Association's top 10 research advances for 2001 include heart devices, cell transplants and drug-eluting stents [news release]. Dallas, Tex: AHA; December 31, 2001. [Context Link]


2. Shelley Wood. Medicare services ready to reimburse hospitals for drug-eluting stents. Available at: Accessed August 1, 2002. [Context Link]