Specific pre-clinical and clinical research objectives have been defined:

1. Identify renal drivers for HFpEF onset and progression in subgroups/clusters of HFpEF patients, taking patient-specific risk profiles into account.
   
   
2. Deepen our understanding of the mechanistic pathways involved in the pathogenic cross-talk between renal drivers, systemic inflammation, microvasculature, and cardiac cells leading to HFpEF, using dedicated ex vivo bioassays to assess patient material and in vivo small and large animal models.
   
   
3. Investigate the most promising therapeutic targets in newly developed and well-characterized state-of-the art rodent and porcine models of CKD-associated HFpEF, taking comorbidities into account.
   
   
4. Investigate the most promising therapeutic, diagnostic and prognostic candidate(s) in well-defined patient-groups by taking a stratified approach.

We expect that the results of this project will enhance our mechanistic insight in the renal drivers of HFpEF development and progression and will lead to the development of personalized diagnostic, prognostic and therapeutic solutions for HFpEF patients.

This multidisciplinary project will combine the expertise of clinicians, basic scientists and epidemiologists in the field of cardiology and nephrology. The project work packages are highly interconnected (Fig 3), and aim at:

Discovery and mechanistic studies of pathways, biomarkers and drug targets by strong interaction between clinical-epidemiologic studies (WP1) and mechanistic in vitro (WP2) and in vivo (WP3) studies;

Preclinical testing through in depth cause-effect studies, biomarker validation and drug target evaluation by interaction between WP2 and in vivo studies with dedicated CKD-HFpEF animal models (WP3);

Clinical testing of validated drug targets in well-defined patient groups (WP4) and validated biomarkers for the development of a prognosis model, requiring vital input from and providing input to WP1.

Because of the synergistic nature of RECONNEXT and the leads that have been discovered and tested in RECONNECT, work packages will run in parallel.

Societal impact is a major focus of RECONNEXT, and hence detailed valorization, implementation and dissemination plans have been designed. Ample experience is present among consortium PIs in these fields and the expertise within the consortium will be complemented with expert advice from the Dutch CardioVascular Alliance (DCVA). Particular attention is given to sex differences in cardiovascular disease through a close collaboration with the Queen of Hearts / DCVA IMPRESS consortium.

Young research talents are the cornerstones of successful research projects towards the future and the long-term driving force of innovation. RECONNEXT will identify, train, and stimulate valuable talent, that will encourage (inter)national research and translation perspectives. We aim to contribute to a new generation of multidisciplinary educated researchers and clinicians in the field of cardiovascular and renal-cardiac research. In RECONNEXT we will continue our dedicated program, containing the modules Training, Fellowships & grants, and Social interaction.

Click here for more information about our Talent program.

The RECONNEXT consortium has been selected and composed for its unique wide range of complementary expertise and synergistic mind-sets, combining the multidisciplinary expertise of leading cardiologists, nephrologists, general practitioners, epidemiologists and basic scientists. The consortium has access to a unique range of in vitro and in vivo experimental models and several unique patient cohorts, including patient cohorts coordinated by PI’s in our consortium. This multidisciplinary approach of RECONNEXT is pivotal, in view of increased evidence that HFpEF is a systemic multi-organ disease. The RECONNEXT research program is well embedded in the focus areas of the participating departments and institutions, ensuring structural embedding not only during the project but also thereafter. All PIs have the position and network to establish and extend such collaboration during this project and thereafter.

Our ambition is to expand our cooperation beyond our national boundaries. Already, the RECONNEXT meta-cohort encompasses international patient cohorts of cardiovascular and nephrology studies that are derived from multiple EU collaborations. In addition, all RECONNEXT PIs have solid leadership roles and access to EU consortia and cohorts. Collaborations with international initiatives to join forces with our consortium are more than welcome and are encouraged to contact us.