MEDIA: The MEtabolic Road to DIAstolic Heart Failure

Background

More than 50% of heart failure (HF) patients present without a major deficit of left ventricular (LV) systolic function and are presumed to suffer from diastolic HF (DHF) because diastolic LV distensibility is usually impaired in these patients. The vast majority (~80%) of DHF patients is exposed to metabolic risk factors and the rising incidence of DHF therefore mirrors the current epidemics of obesity and type 2 diabetes.

Objectives

The MEDIA consortium (19 partners, 12 countries, 16 academic partners, 3 sme) investigates:

- how metabolic derangements contribute to DHF;

- how diagnostic algorithms for DHF can be improved by assessing metabolic risk;

- how correction of metabolic risk or of metabolic risk induced cardiac abnormalities can open new therapeutic perspectives for DHF.

The project consortium will, within the context of 7 RTD work packages:

- Expose animal models of DHF to intense metabolic risk in order to accelerate DHF development;

- Perform mechanistic studies in cardiomyocytes derived from DHF animal models or from DHF patients. Because of the acquired nature of metabolic risk, these studies will focus on posttranslational modifications of proteins and on epigenetic control of hypertrophy development. Their relevance for global LV function will also be appraised;

- Perform mechanistic studies on myocardial collagen synthesis, which is enhanced by metabolic risk;

- Execute a phase II trial in DHF with cardiac specific antifibrotic therapy.

- Explore the use of biomarkers as premorbid identifiers of DHF in existing cohorts of patients exposed to metabolic risk;

- Prospectively test biomarkers and arterial stiffening, which is accelerated by metabolic risk, for their diagnostic potential in a large DHF cohort;

- Assess myocardial metabolic substrate preference with modern imaging techniques and improve diastolic LV dysfunction through modified substrate utilization in a phase II trial.

Expected Results

- Identification of metabolic risk related mechanisms as future therapeutic targets for DHF;

- Improved diagnostic algorithms for DHF through inclusion of biomarkers and arterial stiffness tests;

- Novel DHF treatments consisting of modified myocardial substrate utilization and myocardial antifibrotic therapy.