Redefining the histopathologic profile of acute aortic syndromes: Clinical and prognostic implications Ornella Leone, MD, Davide Pacini, MD, PhD, Alberto.

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Redefining the histopathologic profile of acute aortic syndromes: Clinical and prognostic implications Ornella Leone, MD, Davide Pacini, MD, PhD, Alberto Foà, MD, Anna Corsini, MD, Valentina Agostini, MD, Barbara Corti, MD, Luca Di Marco, MD, Alessandro Leone, MD, Massimiliano Lorenzini, MD, Letizia Bacchi Reggiani, MStat, Roberto Di Bartolomeo, MD, Claudio Rapezzi, MD The Journal of Thoracic and Cardiovascular Surgery Volume 156, Issue 5, Pages 1776-1785.e6 (November 2018) DOI: 10.1016/j.jtcvs.2018.04.086 Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 Microscopic images illustrating the most frequently found degenerative lesions. A and B, Aortic dissection in a patient with Marfan syndrome showing severe EFFL around the false lumen (arrows). A, Weigert Van Gieson, original magnification ×25; (B), detail of elastic fiber fragmentation (arrows). Weigert Van Gieson, original magnification ×100. C and D, Full-thickness aortic specimen with an area of elastic fiber rarefaction in the outer medial layer (C, arrow: Weigert Van Gieson, original magnification ×25); the detail shows thinning out of elastic fibers and enlarged spaces between them (D, Weigert Van Gieson, original magnification ×400). E and F, Examples of intralamellar-mucoid extracellular matrix accumulation. There is mild (E, ×100) to moderate (B, ×200) enlargement of intralamellar spaces containing bluish-pink mucoid material (hematoxylin–eosin stain). The Journal of Thoracic and Cardiovascular Surgery 2018 156, 1776-1785.e6DOI: (10.1016/j.jtcvs.2018.04.086) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 A and B, Aortic dissection samples from pure degenerative cases. A, A 45 year-old man with mild MD (hematoxylin–eosin, original magnification ×25). B, A 54-year-old man with bicuspid aortic valve and severe MD (B, Weigert Van Gieson stain, original magnification ×25). C and D, Aortic specimens from the mixed group. The dissection is above the atherosclerotic lesions, and the underlying media shows multifocal elastic fiber fragmentation (C, arrows) and translamellar (D, arrow) collagen increase (Azan Mallory trichrome, original magnification ×25). The Journal of Thoracic and Cardiovascular Surgery 2018 156, 1776-1785.e6DOI: (10.1016/j.jtcvs.2018.04.086) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Prevalence of atherosclerotic lesions according to age, ascending aorta diameter, gender, and DeBakey subtype. The Journal of Thoracic and Cardiovascular Surgery 2018 156, 1776-1785.e6DOI: (10.1016/j.jtcvs.2018.04.086) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Mortality (left) and major aorta-related events (right) of patients with type A AAS with degenerative (122 patients, green line) versus mixed (36 patients, blue line) histologic abnormalities. CI, Confidence interval. The Journal of Thoracic and Cardiovascular Surgery 2018 156, 1776-1785.e6DOI: (10.1016/j.jtcvs.2018.04.086) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Nonaorta-related events (left) and CV non–aorta-related events (right) of patients with type A AAS with degenerative (122 patients, green line) versus mixed (36 patients, blue line) histologic abnormalities. CI, Confidence interval. The Journal of Thoracic and Cardiovascular Surgery 2018 156, 1776-1785.e6DOI: (10.1016/j.jtcvs.2018.04.086) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Figure E1 Specimens of type A aortic dissection. A, Dissection involves 75% of circumference and the false lumen contains thrombosis; atherosclerotic plaques are visible in the intima (arrow). B, Aortic sample where dissection is more extensive (90% of circumference) and the aortic wall is extremely thinned. C and D, Extensive dissection and irregular intimal surface due to some whitish-yellow plaques (arrow). The Journal of Thoracic and Cardiovascular Surgery 2018 156, 1776-1785.e6DOI: (10.1016/j.jtcvs.2018.04.086) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Figure E2 Study flowchart. AAS, Acute aortic syndrome. The Journal of Thoracic and Cardiovascular Surgery 2018 156, 1776-1785.e6DOI: (10.1016/j.jtcvs.2018.04.086) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Figure E3 A, Severe focus of translamellar mucoid extracellular matrix accumulation in a degenerative group patient (hematoxylin–eosin stain, original magnification ×200). B, Medial fibrosis (ie, translamellar collagen increase), a distinctive lesion of the mixed group (Azan Mallory trichrome, original magnification ×200). C and D, laminar medial collapse. In the mixed group, this lesion was frequently found as a dense band of elastic fiber compaction bordering the lower margin of atherosclerotic plaques (C, arrow; Weigert Van Gieson, original magnification ×100); in degenerative patients, the lesion was frequently seen in the central areas of the medial layer above or on the same plane of the dissection (arrow) (Weigert Van Gieson, original magnification ×100). The Journal of Thoracic and Cardiovascular Surgery 2018 156, 1776-1785.e6DOI: (10.1016/j.jtcvs.2018.04.086) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Figure E4 The 6-year nonaorta-related events of type A AAS according to patients' CV risk profile. High CV risk means patients with history of coronary artery disease or stroke, or aged 40 years or older with at least 1 CV risk factor (hypertension, hypercholesterolemia, diabetes, current smoker). CI, Confidence interval. The Journal of Thoracic and Cardiovascular Surgery 2018 156, 1776-1785.e6DOI: (10.1016/j.jtcvs.2018.04.086) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions

Comparison between histologic features of degenerative alterations and atherosclerosis. The Journal of Thoracic and Cardiovascular Surgery 2018 156, 1776-1785.e6DOI: (10.1016/j.jtcvs.2018.04.086) Copyright © 2018 The American Association for Thoracic Surgery Terms and Conditions