Z02 - Multilevel human HFpEF phenotyping

The central aim of Z02 is to build a unique cohort of 400 HFpEF patients that allows a CRC-wide deep mechanistic and molecular patient phenotyping. Phenotyping will not only include the cardiovascular system, but also skeletal muscle, kidney, and adipose tissue, including metabolism, microbiome, proteome and inflammasome, thereby, focusing on systemic triggers associated with HFpEF. Besides robust clinical data, Z02 will generate a unique human HFpEF biorepository including blood, serum, urine and tissue obtained from heart, skeletal muscle and adipose tissue biopsies, as well as gut microbiome samples. Z02 will also get access to similarly phenotyped patient data from matched patients at riks for HFpEF (N=400, pre-HFpEF), and with HFmrEF and HFrEF (N=180). Follow-up in all cohorts will allow understanding of the dynamic nature of the syndrome.

Graphical Abstract: 400 HFpEF patients will be recruited, undergo deep phenotyping and follow-up. We will use matched preHFpEF patients (BeLOVE) and HFrEF patients (TYPE-HF) for comparison. Biosampling will include  blood, stool, urine, and tissue (cardiac, skeletal muscle, adipose tissue). Data and biosamples will be used and analyzed in Z02 and several subprojects. Specific tests including invasive hemodynamics and advanced MRI imaging will be done in subsets of patients. All resulting data will be inserted and curated in the CRC REDCap database and made available to Z03 (Eils, Kuehne) for advanced bioinformatics analysis. We will organize a stringent communication and  training strategy within Z02 and subprojects involved in the use of patient data and material, and build a clinical knowledge base (SHEPHERD- clinical). Structured patient and public communication and education is also part of the project.