Maladaptive remodeling is associated with impaired survival in women but not in men after aortic valve replacement

JACC Cardiovasc Imaging. 2014 Nov;7(11):1073-80. doi: 10.1016/j.jcmg.2014.06.017. Epub 2014 Oct 8.

Abstract

Objectives: 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.

Keywords: aortic valve replacement; aortic valve stenosis; cardiac fibrosis; gender; hypertrophy regression; sex; survival.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aortic Valve / diagnostic imaging
  • Aortic Valve / surgery*
  • Aortic Valve Stenosis / complications
  • Aortic Valve Stenosis / diagnostic imaging
  • Aortic Valve Stenosis / mortality
  • Aortic Valve Stenosis / surgery*
  • Biomarkers / analysis
  • Cell Adhesion Molecules / analysis
  • Factor Analysis, Statistical
  • Female
  • Fibrosis
  • Heart Valve Prosthesis Implantation / adverse effects*
  • Heart Valve Prosthesis Implantation / mortality
  • Humans
  • Hypertrophy, Left Ventricular / diagnostic imaging
  • Hypertrophy, Left Ventricular / etiology
  • Hypertrophy, Left Ventricular / metabolism
  • Hypertrophy, Left Ventricular / mortality
  • Hypertrophy, Left Ventricular / physiopathology*
  • Male
  • Middle Aged
  • Phosphorylation
  • Prospective Studies
  • Risk Factors
  • Sex Factors
  • Smad3 Protein / analysis
  • Survival Analysis
  • Time Factors
  • Transforming Growth Factor beta1 / analysis
  • Treatment Outcome
  • Ultrasonography
  • Ventricular Function, Left*
  • Ventricular Remodeling*

Substances

  • Biomarkers
  • Cell Adhesion Molecules
  • POSTN protein, human
  • SMAD3 protein, human
  • Smad3 Protein
  • TGFB1 protein, human
  • Transforming Growth Factor beta1