Dilated cardiomyopathy and chronic cardiac inflammation: Pathogenesis, diagnosis and therapy

Abstract

Dilated cardiomyopathy (DCM) is typically defined by left ventricular dilation and systolic dysfunction in the absence of a clear precipitant. Idiopathic disease is common; up to 50% of patients with DCM have no cause found despite imaging, genetic and biopsy assessments. Treatment remains focused on managing symptoms, reducing the risk of sudden cardiac death and ameliorating the structural and electrical complications of disease progression. In the absence of aetiologyspecific treatments, the condition remains associated with a poor prognosis; mortality is approximately 40% at 10 years. The role of immunemediated inflammatory injury in the development and progression of DCM was first proposed over 30 years ago. Despite the subsequent failures of three large clinical trials of immunosuppressive treatment (ATTACH, RENEWAL and the Myocarditis Treatment Trial), evidence for an abnormal adaptive immune response in DCM remains significant. In this review, we summarise and discuss available evidence supporting immune dysfunction in DCM, with a specific focus on cellular immunity. We also highlight current clinical and experimental treatments. We propose that the success of future immunosuppressive treatment trials in DCM will be dependent on the deep immunophenotyping of patients, to identify those with active inflammation and/or an abnormal immune response who are most likely to respond to therapy.

Dapagliflozin protects against dilated cardiomyopathy progression by targeting NLRP3 inflammasome activation

“…In DCM, the NLRP3 inflammasome is activated and mediates pathogenic pyroptosis (Zeng et al 2020). Therefore, targeting NLRP3 inflammasome activation and related pathways may be a With the activation of the NLRP3 inflammasome, IL-1β and IL-18 are released, which may trigger and amplify inflammation and lead to cardiac injury in DCM (Harding et al 2022). Doxorubicin also activated the NLRP3 inflammasome in H9C2 cells (Tavakoli Dargani and Singla 2019).…”

Identification of cuproptosis-related biomarkers in dilated cardiomyopathy and potential therapeutic prediction of herbal medicines

“…In recent years as the pathological mechanisms of DCM have been investigated, the role of abnormal immune cells in ventricular remodelling has been revealed, and the role of immune-mediated inflammatory injury in the progression of DCM has been confirmed by several studies (Harding et al, 2023). Therefore, we analyzed the differences between the immune cells of DCM and healthy control Cardiac tissue.…”

Pathogenic pathways and therapeutic targets of inflammation in heart diseases: A focus on Interleukin‐1

“…In patients with DCM, a large body of evidence supports the concept that inflammation and dysregulation of the immune system are important in the pathogenesis of DCM either as a primary event or as a disease modifier. 121 Indeed, a viral infection could represent the trigger for the development of HF followed by an (auto)immune activation in the myocardium, 122 with a role played by the myeloid differentiation factor (MyD88)/IL-1 signalling in the bone marrow 123 and an altered ratio of IL-1/IL-1 receptor antagonist. 124 The role of IL-1 was largely investigated in DCM.…”