Program Structure

2014-07-08 Reconnect Schema 1_A_2 (clean)

Heart failure with preserved ejection fraction: Role of the microvasculature

Therapies that improve clinical outcome in patients with HFrEF are less effective in patients with HFpEF. Characteristics of patients with HFpEF are also different from HFrEF. Together with a wealth of experimental data this suggests that the pathogenesis of HFpEF is different from that of HFrEF, and thus requires a more tailored approach.

Whereas in HFrEF direct injury to the cardiomyocyte and replacement of dead cardiomyocytes by fibrotic tissue plays a major role, in HFpEF myocardial remodelling and dysfunction are driven by microvascular dysfunction and rarefaction.

Recent studies have identified a causal relationship between the onset of microvascular dysfunction, systemic inflammation, and cardiomyocyte dysfunction and survival in HFpEF. These three biological compartments are strongly influenced by systemic and metabolic risk factors. CKD, even in mild stages, leads to metabolic and systemic derangements that introduce an activated systemic inflammatory state, which may lead to cardiomyocyte stiffening, hypertrophy and interstitial fibrosis via cross-talk between the microvascular and cardiomyocyte compartments.

Infographic 4: Summary of selection target criteria in WP2: Drug and biomarker targets for further evaluation in WP3-5 will be selected on criteria that are defined in each individual sub-WPs of WP2. To accommodate WPs downstream, WP2 will start simultaneously with analysis of the biased renal drivers (described in WP1) and non-biased discovery of new renal factors that are specific for CKD-HFpEF patient.

Infographic 5: Workflow of WP 2.4: Transcriptional and epigenetic microvascular response to CKD-associated factors in patient plasma. LV: left ventricle. IHC: immuno-histochemistry.