title: Maladaptive remodeling is associated with impaired survival in women but not in men after aortic valve replacement.
abstract: OBJECTIVE
  The purpose of this study was to test whether adaptive or maladaptive remodeling is associated with survival in women and men after aortic valve replacement (AVR).
  
  
  BACKGROUND
  Women with isolated aortic valve stenosis (AS) develop more concentric left ventricular hypertrophy (LVH) than men in similar disease states. We recently reported less up-regulation of profibrotic genes at AVR and faster LVH regression post-operatively in women than in men, suggesting that there are sex differences in the adaptation to pressure overload and its regression.
  
  
  METHODS
  The study cohort included 128 patients (age 70.0 ± 9.6 years, 49% women) undergoing AVR for AS. Echocardiography was obtained before and 4.0 ± 1.6 years after surgery. Factor analysis was used to classify LVH as adaptive (combining smaller left ventricular [LV] mass/diameters and greater relative wall thicknesses) or maladaptive. Myocardial tissue samples from the LV septum were obtained during AVR to analyze cardiac fibrosis and associated key molecular regulators.
  
  
  RESULTS
  Before AVR, LVH was classified as adaptive in 62% of women and 45% of men (p < 0.050). Four years after AVR, adaptive LVH was observed in 75% of women and 49% of men (p < 0.031). At surgery, more cardiac fibrosis was present in men compared with women (p < 0.05). Higher levels of transforming growth factor beta 1 (p < 0.01), SMAD2 phosphorylation (p < 0.001), and periostin expression (p < 0.05) were found in men than in women. Women with maladaptive LVH had worse survival than women with adaptive LVH (p < 0.050), whereas the pattern of LVH did not affect survival in men (p < 0.307).
  
  
  CONCLUSIONS
  Women more frequently exhibit adaptive LV remodeling with less fibrosis than men. Maladaptive LVH is associated with worse survival in women. Thus, sex should be considered as a strong modulating factor when management of patients with AS is discussed.
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany. Electronic address: george@docpetrov.info.
authors.forename: George
authors.initials: G
authors.lastname: Petrov
authors.affiliation: DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany; Institute of Gender in Medicine and Center for Cardiovascular Research, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Dworatzek
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany.
authors.forename: Tabea Marie
authors.initials: TM
authors.lastname: Schulze
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Dandel
authors.affiliation: DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany; Institute of Gender in Medicine and Center for Cardiovascular Research, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Kararigas
authors.affiliation: DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany; Institute of Gender in Medicine and Center for Cardiovascular Research, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Shokufeh
authors.initials: S
authors.lastname: Mahmoodzadeh
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Knosalla
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.affiliation: Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany; Institute of Gender in Medicine and Center for Cardiovascular Research, Charité Universitaetsmedizin Berlin, Berlin, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Regitz-Zagrosek
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000000981:diagnostic imaging / Q000601:surgery*; D001024:Aortic Valve Stenosis / Q000150:complications / Q000000981:diagnostic imaging / Q000401:mortality / Q000601:surgery*; D015415:Biomarkers / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis; D005163:Factor Analysis, Statistical; D005260:Female; D005355:Fibrosis; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D051900:Smad3 Protein / Q000032:analysis; D016019:Survival Analysis; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D016896:Treatment Outcome; D014463:Ultrasonography; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; C497790:SMAD3 protein, human; D051900:Smad3 Protein; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1
keywords: aortic valve replacement; aortic valve stenosis; cardiac fibrosis; gender; hypertrophy regression; sex; survival