title: Osseous and chondromatous metaplasia in calcific aortic valve stenosis.
abstract: BACKGROUND
  Aortic valve replacement for calcific aortic valve stenosis is one of the more common cardiac surgical procedures. However, the underlying pathophysiology of calcific aortic valve stenosis is poorly understood. We therefore investigated the histologic findings of aortic valves excised for calcific aortic valve stenosis and correlated these findings with their associated clinical features.
  
  
  RESULTS
  We performed a retrospective analysis on 6685 native aortic valves excised for calcific stenosis and 312 prosthetic tissue aortic valves with calcific degeneration at a single institution between 1987 and 2013. Patient demographics were correlated with valvular histologic features diagnosed on formalin-fixed, decalcified, and paraffin embedded hematoxylin and eosin stained sections. Of the analyzed aortic valves, 5200 (77.8%) were tricuspid, 1473 (22%) were bicuspid, 11 (0.2%) were unicuspid, and 1 was quadricuspid. The overall prevalence of osseous and/or chondromatous metaplasia was 15.6%. Compared to tricuspid valves, bicuspid valves had a higher prevalence of metaplasia (30.1% vs. 11.5%) and had an earlier mean age of excision (60.2 vs. 75.1 years old). In addition, the frequency of osseous metaplasia and/or chondromatous metaplasia increased with age at time of excision of bicuspid aortic valves, while tricuspid aortic valves showed the same incidence regardless of patient age. Males had a higher prevalence of metaplasia in both bicuspid (33.5% vs. 22.3%) and tricuspid (13.8% vs. 8.6%) aortic valves compared to females. Osseous metaplasia and/or chondromatous metaplasia was also more common in patients with bicuspid aortic valves and concurrent chronic kidney disease or atherosclerosis than in those without (33.6% vs. 28.3%). No osseous or chondromatous metaplasia was observed within the cusps of any of the prosthetic tissue valves.
  
  
  CONCLUSIONS
  Osseous and chondromatous metaplasia are common findings in native aortic valves but do not occur in prosthetic tissue aortic valves. Bicuspid valves appear to have an inherent proclivity for metaplasia, as demonstrated by their higher rates of osseous metaplasia and/or chondromatous metaplasia both overall and at earlier age compared to tricuspid and prosthetic tissue aortic valves. This predilection could be due to aberrant hemodynamic forces on bicuspid valves, as well as intrinsic genetic changes associated with bicuspid valve formation. Aortic valve interstitial cells may play a central role in this process. Calcification of prosthetic tissue valves is most likely a primarily dystrophic phenomenon.
authors.affiliation: Department of Pathology, Brigham and Woman's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Torre
authors.affiliation: Department of Pathology, Brigham and Woman's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Hwang
authors.affiliation: Department of Pathology, Brigham and Woman's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Padera
authors.affiliation: Department of Pathology, Brigham and Woman's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: rmitchell@rics.bwh.harvard.edu.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Mitchell
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: VanderLaan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000002:abnormalities* / Q000473:pathology* / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000453:epidemiology / Q000473:pathology* / Q000601:surgery; D000082882:Bicuspid Aortic Valve Disease; D001900:Boston / Q000453:epidemiology; D002114:Calcinosis / Q000453:epidemiology / Q000473:pathology* / Q000601:surgery; D005260:Female; D006349:Heart Valve Diseases / Q000453:epidemiology / Q000473:pathology* / Q000601:surgery; D006350:Heart Valve Prosthesis; D019918:Heart Valve Prosthesis Implantation / Q000295:instrumentation; D006801:Humans; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors
keywords: Bicuspid; Calcific aortic valve stenosis; Calcification; Osseous chondromatous metaplasia; Tricuspid