Inflammatory cardiomyopathy is defined as myocarditis in association with cardiac dysfunction and ventricular remodelling 1,2. Despite extensive research and improved diagnosis and understanding of the pathogenesis of inflammatory cardiomyopathy, this disorder is still associated with a poor prognosis when complicated by left ventricular (LV) dysfunction, heart failure (HF) or arrhythmia 3. Furthermore, fulminant myocarditis, a rare, sudden and severe cardiac inflammation, is one of the main causes of cardiogenic shock in young adults 4,5. Prompt diagnosis and specific treatment strategies are needed to reduce mortality and the need for heart transplantation in these patients 4,5. Many questions remain unanswered regarding the pathogenesis of inflammatory cardiomyopathy and the role of the viral infection, the immune system, the host genetic background and the environment in disease progression and prognosis. These gaps in knowledge highlight the need for advanced experimental systems that can better model the human immune system and the need to improve the characterization and classification of the patients, for example, with the use of phenomapping and phenomics, which involve detailed evaluation of immune status, viral presence and/or other biomarkers. In this Review, we discuss the available evidence and identify the gaps in our understanding of the pathogenesis, diagnosis, treatment and prognosis of myocarditis and inflammatory cardiomyopathy, appraise the available animal and cell models of these conditions and propose future directions for the field. We discuss the role

Fibroblasts, which are traditionally recognized as a quiescent cell responsible for extracellular matrix production, are more and more appreciated as an active key player of the immune system. This review describes how fibroblasts and immune cells reciprocally influence the pathogenesis of fibrosis. An overview is given how fibroblasts are triggered by components of the innate and adaptive immunity on the one hand and how fibroblasts modulate immune cell behaviour via conditioning the cellular and cytokine microenvironment on the other hand. Finally, latest insights into the role of cardiac fibroblasts in the orchestration of inflammatory cell infiltration in the heart, and their impact on heart failure, are outlined.

Purpose of ReviewWith the intention to summarize the currently available evidence on the pathophysiological relevance of inflammation in heart failure, this review addresses the question whether inflammation is a cause or consequence of heart failure, or both.Recent FindingsThis review discusses the diversity (sterile, para-inflammation, chronic inflammation) and sources of inflammation and gives an overview of how inflammation (local versus systemic) can trigger heart failure. On the other hand, the review is outlined how heart failure-associated wall stress and signals released by stressed, malfunctioning, or dead cells (DAMPs: e.g., mitochondrial DNA, ATP, S100A8, matricellular proteins) induce cardiac sterile inflammation and how heart failure provokes inflammation in various peripheral tissues in a direct (inflammatory) and indirect (hemodynamic) manner. The crosstalk between the heart and peripheral organs (bone marrow, spleen, gut, adipose tissue) is outlined and the importance of neurohormonal mechanisms including the renin angiotensin aldosteron system and the ß-adrenergic nervous system in inflammation and heart failure is discussed.SummaryInflammation and heart failure are strongly interconnected and mutually reinforce each other. This indicates the difficulty to counteract inflammation and heart failure once this chronic vicious circle has started and points out the need to control the inflammatory process at an early stage avoiding chronic inflammation and heart failure. The diversity of inflammation further addresses the need for a tailored characterization of inflammation enabling differentiation of inflammation and subsequent target-specific strategies. It is expected that the characterization of the systemic and/or cardiac immune profile will be part of precision medicine in the future of cardiology.