Stefan Frantz, Ines Falcao-Pires, Jean-Luc Balligand, Johann Bauersachs, Dirk Brutsaert, Michele Ciccarelli, Dana Dawson, Leon J. de Windt, Mauro Giacca, Nazha Hamdani, Denise Hilfiker-Kleiner, Emilio Hirsch, Adelino Leite-Moreira, Manuel Mayr, Thomas Thum, Carlo G. Tocchetti, Jolanda van der Velden, Gilda Varricchi, Stephane Heymans

• Activation of the immune system in heart failure (HF) has been recognized for over 20 years. Initially, experimental studies demonstrated a maladaptive role of the immune system. However, several phase III trials failed to show beneficial effects in HF with therapies directed against an immune activation. Preclinical studies today describe positive and negative effects of immune activation in HF. These different effects depend on timing and aetiology of HF. Therefore, herein we give a detailed review on immune mechanisms and their importanceActivation of the immune system in heart failure (HF) has been recognized for over 20 years. Initially, experimental studies demonstrated a maladaptive role of the immune system. However, several phase III trials failed to show beneficial effects in HF with therapies directed against an immune activation. Preclinical studies today describe positive and negative effects of immune activation in HF. These different effects depend on timing and aetiology of HF. Therefore, herein we give a detailed review on immune mechanisms and their importance for the development of HF with a special focus on commonalities and differences between different forms of cardiomyopathies. The role of the immune system in ischaemic, hypertensive, diabetic, toxic, viral, genetic, peripartum, and autoimmune cardiomyopathy is discussed in depth. Overall, initial damage to the heart leads to disease specific activation of the immune system whereas in the chronic phase of HF overlapping mechanisms occur in different aetiologies.…