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• W3014536746 abstract "Central MessageAortic regurgitation results in increased inflammation and medial degeneration of the proximal aorta independent of aortic diameter.See Article page XXX. Aortic regurgitation results in increased inflammation and medial degeneration of the proximal aorta independent of aortic diameter. See Article page XXX. Aortic diameter has traditionally been used to determine the timing for elective surgical repair of ascending aortic aneurysms to avoid the risks of dissection and rupture.1Hiratzka L.F. Creager M.A. Isselbacher E.M. Svensson L.G. Nishimura R.A. Bonow R.O. et al.Surgery for aortic dilatation in patients with bicuspid aortic valves: a statement of clarification from the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.J Am Coll Cardiol. 2016; 67: 724-731Crossref PubMed Scopus (79) Google Scholar The extracellular matrix is crucial to maintaining the integrity and size of the aortic wall. The degradation of the extracellular matrix is controlled by processes involving matrix metalloproteinases and their tissue inhibitors, which are secreted by vascular smooth muscle cells, fibroblasts, and endothelial cells. Wall shear stress (WSS) alters regional and radial wall stress, which can result in abnormal areas of extracellular matrix hemostasis in the ascending aorta. Abnormal valve-mediated flow dynamics, which can occur in patients with aortic stenosis (AS) and aortic regurgitation (AR), result in regional differences in WSS that affect the stress placed on individual endothelial cells in the intimal layer. These altered blood flow patterns predispose to aortic dilatation and aneurysm formation, which ultimately result in dissection and rupture.2Pasta S. Rinaudo A. Luca A. Pilato M. Scardulla C. Gleason T.G. et al.Difference in hemodynamic and wall stress of ascending thoracic aortic aneurysm with bicuspid and tricuspid aortic valve.J Biochem. 2013; 46: 1729-1738Google Scholar,3Guzzardi D.G. Barker A.J. van Ooij P. Malaisrie S.C. Puthumana J.J. Belke D.D. et al.Valve-related hemodynamics mediate human bicuspid aortopathy: insights from wall shear stress mapping.J Am Coll Cardiol. 2015; 66: 892-900Crossref PubMed Scopus (221) Google Scholar Gross and colleagues4Gross T.M.S. Lindner D. Ojeda F.M. Neumann J. Grewal N. Kuntze T. et al.Comparison of microstructural alterations in the proximal aorta between aortic stenosis and regurgitation.J Thorac Cardiovasc Surg. 2020; ([In press])Google Scholar describe the differences in flow patterns, gene expression, and histology in the proximal aorta in patients with AS and AR undergoing aortic valve replacement with and without proximal aortic surgery. Patients with connective tissue disorders, endocarditis, and those requiring urgent surgery for dissections or ruptures were excluded. Magnetic resonance imaging was used to assess aortic diameter and turbulent flow patterns. Segments of the ascending aorta associated with altered WSS were analyzed for inflammatory markers (ie, VCAM1), gene expression of extracellular matrix proteins (ie, COL1A1 and ELN), and evidence for fibrosis, elastin fragmentation, and cystic medial necrosis on histological tissue sections. Patients with AR exhibited increased expression of inflammation (ie, COL1A1) and histologic expression of medial degeneration compared with patients with AS. When valve morphology was compared in patients with AR, patients with tricuspid valve morphology had increased markers of cystic medial necrosis, but no difference in inflammatory markers. These findings were accentuated in patients with aortic diameters >4 cm. The authors hypothesize that abnormal retrograde flow in AR patients alters the WSS on intimal endothelial cells and predisposes to dilatation and aneurysm formation. In their study, the mean proximal aortic diameter in all patients with AR was significantly higher than in patients with AS (5.2 cm vs 4.3 cm; P < .001). These results are similar to those reported by Heng and colleagues,5Heng E. Stone J.R. Kim J.B. Comparative histology of aortic dilatation associated with bileaflet versus trileaflet aortic valves.Ann Thorac Surg. 2015; 100: 2095-2101Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar who found more histological abnormalities in the aortas of patients with tricuspid aortic valves (TAV) versus bicuspid aortic valves (BAV).5Heng E. Stone J.R. Kim J.B. Comparative histology of aortic dilatation associated with bileaflet versus trileaflet aortic valves.Ann Thorac Surg. 2015; 100: 2095-2101Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar Roberts and colleagues6Roberts W.C. Vowels T.J. Ko J.M. Comparison of the structure of the aortic valve and ascending aorta in adults having aortic valve replacement for aortic stenosis versus for pure aortic regurgitation and resection of the ascending aorta for aneurysm.Circulation. 2011; 123: 896-903Crossref PubMed Scopus (79) Google Scholar studied elastin fiber loss in aortas >4.5 cm. Only 10% of patients with AS had moderate-to-severe elastin fragmentation compared with 50% of patients with AR.6Roberts W.C. Vowels T.J. Ko J.M. Comparison of the structure of the aortic valve and ascending aorta in adults having aortic valve replacement for aortic stenosis versus for pure aortic regurgitation and resection of the ascending aorta for aneurysm.Circulation. 2011; 123: 896-903Crossref PubMed Scopus (79) Google Scholar The inadequacy of aortic diameter alone to predict aortic dissections was demonstrated by Kreibech and colleagues7Kreibich M. Rylski B. Czerny M. Pingpoh C. Siepe M. Beyersdorf F. et al.Type A aortic dissection in patients with bicuspid aortic valve aortopathy.Ann Thorac Surg. 2020; 109: 94-101Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar in a series of patients undergoing surgery for acute type A dissections. Predissection aortas were <5.5 cm in 96% of TAV patients and <5 cm in 76% of all BAV patients. Therefore, <5% of all TAV patients and <25% of all BAV patients would meet current guidelines for elective repair of the ascending aorta.1Hiratzka L.F. Creager M.A. Isselbacher E.M. Svensson L.G. Nishimura R.A. Bonow R.O. et al.Surgery for aortic dilatation in patients with bicuspid aortic valves: a statement of clarification from the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.J Am Coll Cardiol. 2016; 67: 724-731Crossref PubMed Scopus (79) Google Scholar If aortic diameter alone is insufficient to predict dissection or rupture, what other parameters can be followed to prevent these devastating complications? Matrix metalloproteinases,8Wu J. Song H.-F. Li S.-H. Guo J. Tsang K. Tumiati L. et al.Progressive aortic dilation is regulated by miR-17-associated miRNAs.J Am Coll Cardiol. 2016; 67: 2965-2977Crossref PubMed Scopus (39) Google Scholar MiR-17 related messenger RNAs,8Wu J. Song H.-F. Li S.-H. Guo J. Tsang K. Tumiati L. et al.Progressive aortic dilation is regulated by miR-17-associated miRNAs.J Am Coll Cardiol. 2016; 67: 2965-2977Crossref PubMed Scopus (39) Google Scholar transforming growth factor beta,9Maredia A.K. Greenway S.C. Verma S. Fedak P.W.M. Bicuspid aortic valve associated aortopathy: update on biomarkers.Curr Opin Cardiol. 2018; 33: 134-139Crossref PubMed Scopus (8) Google Scholar stimulator of interferon genes,10Luo W. Wang Y. Zhang L. Ren P. Zhang C. Li Y. et al.Critical role of cytosolic DNA and its sensing adaptor STING in aortic degeneration, dissection, and rupture.Circulation. 2020; 141: 42-66Crossref Scopus (22) Google Scholar and receptors for advanced glycation end products, have all been associated with extracellular matrix degradation and derangements of elastin and collagen fibers in the wall of aortic dissections. WSS cannot be directly measured and must be determined from computational modeling, such as finite element analysis, which has been used to quantify WSS in arteries.11Natsome K. Shiiya N. Takehara Y. Sugiyama M. Satoh H. Yamashita K. et al.Characterizing saccular aortic arch aneurysms from the geometry-flow dynamics relationship.J Thorac Cardiovasc Surg. 2017; 153: 1413-1420Abstract Full Text Full Text PDF Scopus (14) Google Scholar Further refinements will be needed in magnetic resonance imaging equipment to assess extracellular matrix degradation. This will include 4-dimensional flow imaging for enhanced visualization of transvalvular flow and specific magnetic resonance imaging sequences for more detailed information regarding the degree of fibrosis and inflammatory activity of the aortic wall. Combining measurements of WSS with biomarkers of inflammation and extracellular matrix degradation may ultimately improve our ability to predict aortic events and determine the timing for prophylactic aorta replacement. However, before these biomarkers and imaging studies can be incorporated into current guidelines, larger, adequately powered, prospective studies from aortic centers of excellence will be needed. Nevertheless, studies such as those by Gross and colleagues4Gross T.M.S. Lindner D. Ojeda F.M. Neumann J. Grewal N. Kuntze T. et al.Comparison of microstructural alterations in the proximal aorta between aortic stenosis and regurgitation.J Thorac Cardiovasc Surg. 2020; ([In press])Google Scholar strongly suggest that when determining the risk for dissection and rupture in patients with AR, size may not matter. Comparison of microstructural alterations in the proximal aorta between aortic stenosis and regurgitationThe Journal of Thoracic and Cardiovascular SurgeryPreviewWe aimed to analyze the association among flow patterns, gene expression, and histologic alterations of the proximal aorta in patients with aortic valve disease. Full-Text PDF" @default.
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• W3014536746 title "Commentary: Determining the risk for dissection and rupture in patients with aortic regurgitation—size may not matter" @default.
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