The National Heart, Lung, and Blood Institute convened a Working Group on September 19, 2005, in Bethesda, Maryland to identify clinical research opportunities and critical gaps in our knowledge about thoraco-abdominal aortic diseases in order to facilitate clinical detection and treatment of these diseases. The major objectives were to: (1) review the current state of basic research of thoraco-abdominal aortic diseases as it applies to future clinical applications; (2) identify basic science findings that are ready for translation into clinical research; (3) foster exchange of novel ideas to promote improved understanding of the temporal structural and mechanical changes that relate to disease progression of the thoraco-abdominal aorta; (4) identify research opportunities to improve clinical decision-making and health care delivery in order to optimize patient outcomes:, and (5) provide a prioritized set of novel research recommendations to the NHLBI that will direct its future research agenda and ultimately improve the diagnosis and treatment of diseases of the thoraco-abdominal aorta.
The Working Group members reviewed recent findings in basic research, clinical diagnosis, and treatment strategies related to diseases of the TAA. The discussion focused on the need for an improved understanding of the natural history of TAA diseases. There are few, if any, animal models of TAA disease. The Working Group thought that reliable animal models should be developed that replicate the etiology and pathogenesis of TAA diseases in humans. Members agreed that research using relevant animal models is an important intermediate step in the translation of results from basic science into clinical trials. In addition, the group stated that human TAA tissue must be collected and studied to evaluate gene and protein expression and elucidate histologic, biochemical, mechanical, and structural properties of TAA diseases.
The Working Group identified inadequate phenotyping in existing patient registries as a critical gap area. Full spectrum phenotyping was considered essential to advancing knowledge, and should include a comprehensive patient and family history and physical examination, as well as serial imaging studies such as echocardiograms, computerized tomography, and dynamic magnetic resonance imaging. The use of imaging to study the biomechanics of aneurysmal wall stress in the diseased TAA was also an area of interest.
Important gaps in our understanding of diseases of the TAA include: the potential benefits of endovascular repair of type B aortic dissection compared to optimal medical therapy; the benefits and risks of endovascular compared with surgical repair of TAA aneurysms; and the effects of medical therapies such as beta adrenergic blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers on expansion and outcome of aneurysms of the TAA. Randomized clinical trials were considered important mechanisms to develop new therapies for diseases of the TAA.
Understanding mechanisms of neurologic injury and spinal cord protection, in both surgical and endovascular repair, are needed to improve pharmacologic, endovascular and surgical treatment strategies in order to prevent paraplegia
- Support investigations of the natural history of diseases of the TAA, including extensive phenotyping of registry participants, as well as tissue collection for both genomic/proteomic investigation and for examination of tissue characteristics/orientation.
- Support a large multicenter clinical trial to compare optimal medical therapy to endovascular repair in acute uncomplicated type B dissection.
- Support investigations into the mechanisms of neurologic injury to the spinal cord during operations on the thoraco-abdominal aorta and explore techniques for spinal cord protection in the setting of both surgical and endovascular repair.
- Support a randomized clinical trial to compare optimal medical therapy, open surgical repair, or endovascular repair for the management of aneurysms of the TAA.
- Support a randomized clinical trial to identify optimal medical therapy for the treatment of small aneurysms of the TAA, early manifestations of aortic disease in susceptible individuals such as those with Marfan syndrome, and any aneurysm in non-surgical candidates. Optimal medical therapy could include beta adrenergic blockers, angiotensin receptor blockers or angiotensin converting enzyme inhibitors alone or in combination.
- Support the development of small animal models of thoracic and thoraco-abdominal aortic disease.
A summary of the workshop proceedings and recommendations will also be published in a peer-reviewed scientific journal. Anticipated publication date is 2006.
Suzanne Goldberg, R.N., M.S.N., NHLBI, NIH
Last updated: October 28, 2005