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Myocardial Function

Position papers and consensus documents from the ESC Working Group on Myocardial Function

Basic Science

Targeting myocardial remodelling to develop novel therapies for heart failure

Authors: 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 and Carlo G. Tocchetti

Reference: Article first published online: 17 MAR 2014; DOI: 10.1002/ejhf.62

Summary: 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.

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How to study the right ventricle in experimental models?

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

Reference: Article first published online: 23 FEB 2014; DOI: 10.1002/ejhf.66

Summary: The right ventricle has become an increasing focus in cardiovascular research. In this position paper, we give a brief overview of the specific pathophysiological features of the right ventricle, with particular emphasis on functional and molecular modifications as well as therapeutic strategies in chronic overload, highlighting the differences from the left ventricle. Importantly, we put together recommendations on promising topics of research in the field, experimental study design, and functional evaluation of the right ventricle in experimental models, from non-invasive methodologies to haemodynamic evaluation and ex vivo set-ups.

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Towards a re-definition of “cardiac hypertrophy” through a rational characterization of left ventricular phenotypes

Authors: Ralph Knöll, Guido Iaccarino, Guido Tarone, Denise Hilfiker-Kleiner, Johann Bauersachs, Adelino F. Leite-Moreira, Peter H. Sugden, and Jean-Luc Balligand

Reference: European Journal of Heart Failure (2011); Doi:10.1093/eurjhf/hfr071; First Published on line: 27 June  2011

Summary: Many primary or secondary diseases of the myocardium are accompanied with complex remodelling of the cardiac tissue that results in increased heart mass, often identified as cardiac ‘hypertrophy’. Although there have been numerous attempts at defining such ‘hypertrophy’, the present paper delineates the reasons as to why current definitions of cardiac hypertrophy remain unsatisfying. Based on a brief review of the underlying pathophysiology and tissue and cellular events driving myocardial remodelling with or without changes in heart dimensions, as well as current techniques to detect such changes, we propose to restrict the use of the currently popular term ‘hypertrophy’ to cardiac myocytes that may or may not accompany the more complex tissue rearrangements leading to changes in shape or size of the ventricles, more broadly referred to as ‘remodelling’. We also discuss the great potential of genetically modified (mouse) models as tools to define the molecular pathways leading to the different forms of left ventricle remodelling. Finally, we present an algorithm for the stepwise assessment of myocardial phenotypes applicable to animal models using well-established imaging techniques and propose a list of parameters most suited for a critical evaluation of such pathophysiological phenomena in mouse models. We believe that this effort is the first step towards a much auspicated unification of the terminology between the experimental and the clinical cardiologists. 

Read the Press Release related to this position paper: ESC calls for renaming of term cardiac hypertrophy  

"We hope that clarifying the terminology will help foster communication between different investigators in the field and act as an impetus to increase research in cardiac remodelling,” says Jean-Luc Balligand, from the Université Catholique de Louvain (Brussels, Belgium), past-chair of the Myocardial Function working group.

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Cardiovascular side effects of cancer therapies

A Position Statement From The Heart Failure Association Of The European Society Of Cardiology And The Working Group On Myocardial Function Of The European Society Of Cardiology 

Authors: Thomas Eschenhagen, Thomas Force, Michael S. Ewer, Gilles W. de Keulenaer, Thomas M. Suter, Stefan D. Anker, Metin Avkiran, Evandro de Azambuja, Jean-Luc Balligand, Dirk L. Brutsaert, Gianluigi Condorelli, Arne Hansen, Stephane Heymans, Joseph A. Hill, Emilio Hirsch, Denise Hilfiker-Kleiner, Stefan Janssens, Steven de Jong, Gitte Neubauer, Burkert Pieske, Piotr Ponikowski, Munir Pirmohamed, Mathias Rauchhaus, Douglas Sawyer, Peter H. Sugden, Johann Wojta, Faiez Zannad and Ajay M. Shah

Reference: Eur J Heart Fail (2010) 13 (1): 1-10

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