Understanding the structural features of symptomatic calcific aortic valve stenosis: A broad-spectrum clinico-pathologic study in 236 consecutive surgical cases

Daniela Galli, Roberta Manuguerra, Rodolfo Monaco, Laura Manotti, Matteo Goldoni, Gabriella Becchi, Cecilia Carubbi, Giulia Vignali, Nicola Cucurachi, Tiziano Gherli, Francesco Nicolini, Roberto Lorusso, Marco Vitale, Domenico Corradi*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: With age, aortic valve cusps undergo varying degrees of sclerosis which, sometimes, can progress to calcific aortic valve stenosis (AVS). To perform a retrospective clinico-pathologic investigation in patients with calcific AVS.

Methods: We characterized and graded the structural remodeling in 236 aortic valves (200 tricuspid and 36 bicuspid) from patients with calcific AVS (148 males; average 72 years); possible relationships between general/clinical/echocardiographic characteristics and the histopathologic changes were explored. Twenty autopsy aortic valves served as controls. In 40 cases, we also tested the immunohistochemical expression of metalloproteinases and cytokines, and characterized the inflammatory infiltrate. In 5 cases, we cultured cusp stem cells and explored their potential to differentiate into osteoblasts/adipocytes.

Results: AVS cusps showed structural remodeling as severe fibrosis (100%), calcific nodules (100%), neoangiogenesis (81%), inflammation (71%), bone metaplasia with or without hematopoiesis (6% and 53%, respectively), adipose metaplasia (16%), and cartilaginous metaplasia (7%). At multivariate analysis, AVS degree and interventricular septum thickness were the only predictors of remodeling (barring inflammation). All the tested metalloproteinases (except MMP-13) and cytokines were expressed in AVS cusps. Inflammation mainly consisted of B and T lymphocytes (CD4+/CD8+ cell ratio 3:1) and plasma cells. AVS changes were mostly different from typical atherosclerosis. Cultured mesenchymal cusp stem cells could differentiate into osteoblasts/adipocytes.

Conclusions: Structural remodeling in AVS is peculiar and considerable, and is related to the severity of the disease. However, the different newly formed tissues-where "valvular interstitial cells" play a key role-and their wellknown slow turnover suggest a reverse structural remodeling improbable. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)364-374
Number of pages11
JournalInternational Journal of Cardiology
Publication statusPublished - 1 Feb 2017


  • Aortic valve stenosis
  • Structural remodeling
  • Histopathology
  • Valvular interstitial cells
  • Osseous metaplasia


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