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Serum dihydrotestosterone is associated with adverse myocardial remodeling in patients with aortic valve stenosis before and after aortic valve replacement

Authors

  • M. Schafstedde
  • J. Nordmeyer
  • F. Berger
  • C. Knosalla
  • P. Mertins
  • V. Regitz-Zagrosek
  • T. Kuehne
  • M. Kraus
  • S. Nordmeyer

Journal

  • American Journal of Physiology Heart and Circulatory Physiology

Citation

  • Am J Physiol Heart Circ Physiol 323 (5): H949-H957

Abstract

  • AIMS: Animal studies show a pivotal role of dihydrotestosterone (DHT) in pressure overload induced myocardial hypertrophy and dysfunction. The aim of our study was to evaluate the role of DHT levels and myocardial hypertrophy and myocardial protein expression in patients with severe aortic valve stenosis (AS). METHODS AND RESULTS: 43 patients (median age 68 (41-80) years) with severe AS and indication for surgical aortic valve replacement (SAVR) were prospectively enrolled. Cardiac magnetic resonance imaging including analysis of left ventricular muscle mass (LVM), fibrosis and function and laboratory tests including serum DHT levels were performed before and after SAVR. During SAVR left ventricular (LV) biopsies were performed for proteomic profiling. Serum DHT levels correlated positively with indexed LVM (LVMi, R=0.64, p<0.0001) and fibrosis (R=0.49, p=0.0065) and inversely with LV function (R=-0.42, p=0.005) in patients with severe AS. DHT levels were associated with higher abundance of the hypertrophy (moesin (R=0.52, p=0.0083)) and fibrosis (vimentin (R=0.41, p=0.039)) associated proteins from LV myocardial biopsies. Higher serum DHT levels preoperatively were associated with reduced LV function (ejection fraction: R=-0.34, p=0.035, circulatory efficiency: R=-0.46, p=0.012, global longitudinal strain: R=0.49, p=0.01) and increased fibrosis (R=0.55, p=0.0022) after SAVR. CONCLUSIONS: Serum DHT levels were associated with adverse myocardial remodeling and higher abundance in hypertrophy and fibrosis associated proteins in patients with severe AS. DHT may be a target to prevent or attenuate adverse myocardial remodeling in patients with pressure overload due to AS.


DOI

doi:10.1152/ajpheart.00288.2022