Unraveling hidden culprits for the cardiac arRHYTHMia burden: Modulation of immunoINflammation and inter-cellular SIGnaling as targets for novel tHerapeuTic approaches (Acronym: RHYTHM-INSIGHT)

The occurrence of severe arrhythmic events is an unsolved medical burden. Briefly, arrhythmias arise from the interplay of substrate alterations and abrupt emergence of triggers. Based on Units' interdisciplinary expertise and coordinator’s long-standing experience in arrhythmogenesis, we identified clinically relevant settings to be investigated: A) Immunoinflammatory conditions and the occurrence of brady- and tachy-arrhythmias B) Cardiac remodelling resulting in non-homogenous impulse generation and propagation. We will join efforts focusing on ill-explored mediators: i) autoantibodies and cytokines, based on previous clinical data, and ii) the interplay of suitable channel-modifying mechanisms. We found on the recognized reputation of participants in specific fields: redox state and altered calcium homeostasis; mediators as H2S, carbonic anhydrase and monoamine-oxidases, glucocorticoids and GILZ; emerging arrhythmogenic substrates as fatty-fibrotic infiltration. The combination of reliable methods, sound preexisting background and rational hypothesis will drive us to well-defined proofs of concept on novel therapeutic targets, aimed to test unconventional “antiarrhythmic” strategies, acting on channel-modifying pathways and redox/metabolic or ionic imbalance.