Targeting myocardial remodelling to develop novel therapies for heart failure: A position paper from the Working Group on Myocardial Function of the European Society of Cardiology

Guido Tarone, Jean Luc Balligand, Johann Bauersachs, Angela Clerk, Leon De Windt, Stephane Heymans, Denise Hilfiker-Kleiner, Emilio Hirsch, Guido Iaccarino, Ralph Knöll, Adelino F. Leite-Moreira, André P. Lourenço, Manuel Mayr, Thomas Thum, Carlo G. Tocchetti

Research output: Contribution to journalArticlepeer-review

Abstract

The failing heart is characterized by complex tissue remodelling involving increased cardiomyocyte death, and impairment of sarcomere function, metabolic activity, endothelial and vascular function, together with increased inflammation and interstitial fibrosis. For years, therapeutic approaches for heart failure (HF) relied on vasodilators and diuretics which relieve cardiac workload and HF symptoms. The introduction in the clinic of drugs interfering with beta-adrenergic and angiotensin signalling have ameliorated survival by interfering with the intimate mechanism of cardiac compensation. Current therapy, though, still has a limited capacity to restore muscle function fully, and the development of novel therapeutic targets is still an important medical need. Recent progress in understanding the molecular basis of myocardial dysfunction in HF is paving the way for development of new treatments capable of restoring muscle function and targeting specific pathological subsets of LV dysfunction. These include potentiating cardiomyocyte contractility, increasing cardiomyocyte survival and adaptive hypertrophy, increasing oxygen and nutrition supply by sustaining vessel formation, and reducing ventricular stiffness by favourable extracellular matrix remodelling. Here, we consider drugs such as omecamtiv mecarbil, nitroxyl donors, cyclosporin A, SERCA2a (sarcoplasmic/ endoplasmic Ca2 + ATPase 2a), neuregulin, and bromocriptine, all of which are currently in clinical trials as potential HF therapies, and discuss novel molecular targets with potential therapeutic impact that are in the pre-clinical phases of investigation. Finally, we consider conceptual changes in basic science approaches to improve their translation into successful clinical applications.

Original languageEnglish
Pages (from-to)494-508
Number of pages15
JournalEuropean Journal of Heart Failure
Volume16
Issue number5
DOIs
Publication statusPublished - 2014

Keywords

  • Adaptive hypertrophy
  • Cardiac remodelling
  • Cardiomyocyte survival
  • Contractility
  • Heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

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