Recently, we have shown in a retrospective study that induction of heart-reactive autoantibodies (HRA) in the wake of acute decompensation of heart failure was associated with a worse clinical prognosis. To confirm these data and to obtain a better understanding of the immunological processes triggered by decompensation of heart failure, we initiated the prospective ‘Acute Heart Failure-Immunomonitoring Cohort Study’ (AHF-ImmunoCS) following AHF patients for 18 months after index hospitalisation including serial collection of biomaterials. Determining HRA by indirect immunofluorescence for the first 28 enrolled patients confirmed de novo induction in 27% of patients (previously published by our group: 32%) six months after the index hospitalisation. Moreover, for 13% of patients we detected HRA already six weeks after acute decompensation. In parallel to determining HRA by indirect immunofluorescence, we established bead-based assays using recombinantly expressed antigens like Myosin Heavy Chain 6 and 7, Troponin I as well as Tropomyosin 1. We determined antibody binding to beads coated with different amounts of antigen by flow cytometry allowing us not only to quantify reactivities to these defined autoantigens, but also to estimate antibody affinity. Comparing baseline samples to samples obtained six weeks and six months after acute decompensation of heart failure showed clear changes in reactivity to these autoantigens, with great interindividual differences between patients. Future correlation of HRA and defined autoantibody quality and quantity with clinical outcome should pinpoint to novel biomarkers for the clinical course of acute heart failure and, ideally, lead to the development of immunomodulatory interventions. This study was supported by a grant from the DFG (SFB1525 - project C05).