Cardiac Remodeling in Aortic and Mitral Valve Disease - a Simulation Study with Clinical Validation

Research output: Contribution to journalArticle


BACKGROUND: Remodeling is an important long-term determinant of cardiac function throughout the progression of heart disease. Numerous biomolecular pathways for mechanosensing and transduction are involved. However, we hypothesize that biomechanical factors alone can explain changes in myocardial volume and chamber size in valve disease.

METHODS: A validated model of the human vasculature and the four cardiac chambers was used to simulate aortic stenosis, mitral regurgitation and aortic regurgitation. Remodeling was simulated with adaptive feedback preserving myocardial fiber stress and wall shear stress in all four cardiac chambers. Briefly, the model used myocardial fiber stress to determine wall thickness and cardiac chamber wall shear stress to determine chamber volume.

RESULTS: Aortic stenosis resulted in the development of concentric left ventricular hypertrophy. Aortic and mitral regurgitation resulted in eccentric remodeling and eccentric hypertrophy, with more pronounced hypertrophy for aortic regurgitation. Comparisons with published clinical data showed the same direction and similar magnitudes of changes in end-diastolic volume index and left ventricular diameters. Changes in myocardial wall volume and wall thickness were within a realistic range both in stenotic and regurgitant valvular disease.

CONCLUSIONS: Simulations of remodeling in left-sided valvular disease support, in both a qualitative and quantitative manner, that left ventricular chamber size and hypertrophy are primarily determined by preservation of wall shear stress and myocardial fiber stress.


  • Elira Maksuti
  • Berend E Westerhof
  • Martin Ugander
  • Dirk W Donker
  • Marcus Carlsson
  • Michael Broome
External organisations
  • Karolinska University Hospital
  • Karolinska Institutet
  • University Medical Center Utrecht
  • Vrije Universiteit Amsterdam
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems
Original languageEnglish
Pages (from-to)1377-1389
JournalJournal of Applied Physiology
Issue number5
Publication statusPublished - 2019 Feb 7
Publication categoryResearch