SMART – System Medicine of heart failure

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SMART - Systems Medicine of heart failure

FMER, PI: Vera Regitz-Zagrosek, 2015-2018

Partners: DHZB, MDC, Charite, Hasso Plattner Institute, Bayer Technology Services GmbH

 

SMART aims to establish individualized strategies for the prevention and Management of heart failure (HF) by early detection of the physiological, genomic, proteomic, and hemodynamic mechanisms that lead from one common cause of ventricular dysfunction (pressure overload) to maladaptive remodelling and irreversible HF. To cope with the complexity of HF, SMART will interrelate models describing the interplay between genome, proteome and cell function, regulating hormones, tissue composition and hemodynamic whole organ function up to a whole body description of a patient and patient cohorts.

To achieve the ultimate goals of demonstrating proof-of-concept tools for predicting disease evolution and the efficacy of treatment in a given Patient, SMART will:

  • Apply a modelling framework that couples multi-scale mechanistic models with in-depth genome/proteome, cell physiology and whole organ (biomechanical and fluid dynamic) models.
  • Subsequently, investigate methods validity and relevance for "quantitative prediction" of treatment outcome in a clinical proof-of-concept trial (demonstrator) of patients with aortic valve stenosis (n=60 patients, 2 trial arms). •
  • More specifically, the demonstrator will investigate the pathophysiological response to surgical aortic valve replacement and adjunctive pharmacological treatment with angiotensin receptor blockers (ARB).