The innate immune system in chronic cardiomyopathy: a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC

Abstract

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 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.

A giant mystery in giant cell myocarditis: navigating diagnosis, immunosuppression, and mechanical circulatory support

“…The pathologic diagnosis of GCM requires exclusion of other causes of myocarditis including infectious diseases, amyloidosis, and sarcoidosis. GCM pathophysiology is linked to a T‐cell‐mediated process, characterized by infiltration of cardiomyocytes by lymphocytes, histocytes, multinucleated giant cells, eosinophils with necrosis of cardiomyocytes, and notable absence of granulomas …”

“…GCM pathophysiology is linked to a T-cell-mediated process, characterized by infiltration of cardiomyocytes by lymphocytes, histocytes, multinucleated giant cells, eosinophils with necrosis of cardiomyocytes, and notable absence of granulomas. 1,4,[11][12][13] Saltykow first described GCM in 1905, and the role of immunosuppression was reported in 1987. 14,15 There are no prospective clinical trials to guide management of this rare disease; however, retrospective reports and case series suggest maintenance immunosuppressive therapy with or without induction.…”

Low‐level transcutaneous vagus nerve stimulation attenuates cardiac remodelling in a rat model of heart failure with preserved ejection fraction

“…Inflammation and fibrosis represent the major mechanisms underlying cardiac remodelling in HFpEF (Franssen et al., ; Frantz et al., ; Paulus & Tschope, ). Comorbidities, such as ageing, obesity, hypertension and diabetes induce a systemic pro‐inflammatory state, which leads to recruitment of macrophages and monocytes into the heart.…”

“…Hospitalizations related to HFpEF are increasing and outcomes of patients with HFpEF are poor, yet no treatment has been shown to decrease morbidity and mortality (Butler et al., ; Fonarow et al., ). Recent animal and human studies suggest that a systemic proinflammatory state, produced by comorbidities, including ageing and hypertension, plays a central role in the development of HFpEF (Franssen et al., ; Frantz et al., ; Paulus & Tschope, ). This proinflammatory state leads to left ventricular (LV) fibrosis, diastolic dysfunction and HFpEF (Paulus & Tschope, ).…”

Heart Failure Association position papers – a new way to advance the field

“…Other topical issues covered including cancer in HF by the cardio‐oncology sub‐committee, and a proposed taxonomy of heart and brain interactions complicating HF by the Heart and Brain Sub‐Committee as well as a practical guidance paper from the Study Group on Peripartum Cardiomyopathy . There were also important papers from our translational scientist colleagues, including one from the Translational Research Committee on the autonomic nervous system as a therapeutic target in HF, and two from the affiliated Working Group on Myocardial Function, one covering an integrative translational approach to study HFpEF and a second on the innate immune system in chronic cardiomyopathy . The HFA has never looked stronger.…”