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In this CRC, the different subprojects are investigating diverse mechanistic causes of heart failure (HF) that can lead to potentially different HF subtypes. In this Z03 subproject, the data and information obtained in the preclinical and clinical CRC subprojects (areas A, B as well as Z01 and Z02) will be pooled, analyzed, and the data modeled to identify and interpret differences and commonalities that exist across different HF subtypes. Thus, Z03 supports the CRC not only by providing an overarching data analysis and interpretation level, but its information and findings will also help the CRC subprojects to interpret their own results and enable adjustment of experimental designs.
Graphical Abstract: The figure illustrates the interaction between work done towards the phenomaps and the data driven (AI) and numerical modelling components for the clinical and preclinical experiments. The integration of multidimensional data from the whole organ, tissue and cell level (by imaging, sensor, lab, omics) together with data-driven mechanistic modelling will provide a more complete picture of HFpEF for the individual animal studies and in exploring human HFpEF subforms. In addition, the modelling concepts enable mechanistic reasoning and thus a linkage of preclinical models with appropriate clinical subgroups that can explain differences and similarities between models and subgroups on a functional basis. With this information, the project is expected to enhance current knowledge concerning the main triggers of HFpEF subgroups and, in turn, in a clinical context to better predict the course of the disease and to develop appropriate precision therapy concepts adapted to individual patient characteristics.
Schafstedde M, Nordmeyer J, Berger F, Knosalla C, Mertins P, Ziehm M, Kirchner ML, Regitz-Zagrosek V, Kuehne T, Kraus M, Nordmeyer S. Serum dihydrotestosterone levels are associated with adverse myocardial remodeling in patients with severe aortic valve stenosis before and after aortic valve replacement. Am J Physiol Heart Circ Physiol. 2022 Nov 1;323(5):H949-H957. doi: 10.1152/ajpheart.00288.2022. Epub 2022 Oct 7. PMID: 36206048; PMCID: PMC9621711.