**6. Future perspectives and therapeutic implications**

Despite available treatment guidelines, the recent progress in conventional pharmacotherapy, and promising novel device-based therapeutic approaches, the outcome of patients suffering from heart failure remains unsatisfactory. This has stimulated the search for causal treatment strategies aiming to block or neutralize factors thought to play a role in heart failure progression.

In a large number of neurologic, rheumatologic, and endocrine disorders autoimmune phenomena have been recognised as main disease-causing factors. Their relevance in human heart disease and failure, however, still need to be substantiated (Jahns et al., 2006; Fu, M., 2008) although preliminary clinical data suggest that the presence of certain cardiac aabs clearly worsens the prognosis of patients with idiopathic DCM (Störk et al., 2006). Therapeutic strategies known from other autoimmune disorders, such as application of peptide-ligands (for multiple sclerosis (Warren et al., 2006)) or immunoadsorption of disease-causing aabs (for myasthenia gravis (Tzartos et al., 2008)) might thus also offer treatment options for a variety of human cardiac disorders.

In this regard, recent *in vitro* experiments with functionally active receptor-aabs isolated from a smaller number of DCM-patients indicate, that aab-induced adrenoceptor activation might be abrogated by incubation with epitope-mimicking peptides (Nikolaev et al., 2007; Jahns et al. 2010). Although clinical *in vivo* data with epitope-derived antibody-scavengers are still lacking, the latter *in vitro* findings together with the results from the ETiCS study should stimulate further research in the field of specifically antibody-directed therapeutic strategies.

In addition to established anti-adrenergic drugs like cardioselective beta-blockers such strategies might comprise (a) the aforementioned epitope-derived peptides as antibodyscavengers (Jahns et al., 2010), (b) an elimination of functionally active cardiac aabs by selective or non-selective immunoadsorption (studies currently under way (Felix & Staudt, 2008; Müller et al., 2008)), or (c) the direct targeting/suppression of autoantibody-producing B cells and/or plasma-cells themselves (Neubert et al., 2008).

At least in animal models of antibody-induced immune-cardiomyopathy and –nephropathy some of these novel therapeutic approaches have already been successfully applied (Jahns et al., 2005; Matsui et al., 2006; Neubert et al., 2008; Jahns et al., 2010). Hence, the results from the clinical (diagnostic) ETiCS study might also furnish a basis for and accelerate further pre-clinical development of such novel therapeutic approaches and agents targeting at cardio-noxious aabs, and –hopefully– for a faster transfer into clinical practice. Moreover, by initiating a joint venture of the leading European research institutes in the field of cardiac autoimmunity, ETiCS could equally serve as a starting point for future common efforts to further understand and therapeutically modulate the immune system with respect to immune-mediated (post-inflammatory) human cardiac disorders.
