T cells in acute and chronic myocarditis: from diagnosis to treatment

Figure 1. T cell activity at the nexus of myocardial inflammatory disease. Immune checkpoint inhibition attenuates processes that limit the activity of heart-specific T cells (‘brakes off’), whereas stimulatory signals from antigenic mimicry or global immune activation during infection or vaccination enhance and accelerate tissue-destructive T cell activity (‘accelerator on’)

Figure 2. Activation and control of heart-specific T cells. (A) T cells undergo education in the thymus and circulate as naive T cells through lymph nodes. Upon activation, they clonally expand and migrate as effector T cells to peripheral tissues. (B) In the thymus, T cells are educated to distinguish self from non-self. Recognition of self-peptides presented by medullary thymic epithelial cells (mTECs), such as the cardiac protein myosin heavy chain 7 (MYH7), triggers apoptosis. Due to the lack of thymic expression, T cells specific for the cardiac protein myosin heavy chain 6 (MYH6) escape the thymus. (C) In heart-draining lymph nodes, MYH6-specific T cells are activated by recognizing the MYH6–MHC complex on dendritic cells and receiving costimulatory signals (CD28-CD80/CD86 interaction). Concomitant antigen presentation via MHC class I and II activated CD8+ T cells, with CD4+ T cells providing help via interleukin-2 (IL-2). Following activation and expansion, effector T cells migrate to the heart. (D) Re-encountering cardiac antigens in the heart, effector T cells induce cardiomyocyte damage. CD4+ T cells release interferon-gamma (IFN-γ) to activate inflammatory macrophages, which in…

Figure 3. Clinical characterization of myocarditis. Patients with acute myocarditis can present with a range of symptoms, with 3%–9% progressing to acute fulminant myocarditis, characterized by its rapid onset and progression of symptoms. Following the resolution of acute symptoms, patients enter the post-episodic phase which can lead to one of three outcomes: resolution, chronic myocarditis, or recurrent myocarditis. Recurrent myocarditis requires more than one acute episode requiring hospitalization. Chronic myocarditis is persistent cardiac inflammation lasting for more than 30 days from the initial onset of symptoms. Resolution is defined as complete recovery, including symptom relief, biomarker normalization, and resolution of structural abnormalities

Figure 4. Overview algorithm for the diagnosis and management of acute myocarditis based on 2025 ESC guidelines. CRP, C-reactive protein; CK-MB, creatinine kinase MB; NT-BNP, N-terminal-B-type natriuretic peptide; ECG, electrocardiogram; TTE, transthoracic echocardiogram; CAD, coronary artery disease; LVEF, left ventricular ejection fraction; ICU, intensive care unit; CMR, cardiac magnetic resonance; GDMT, guideline-directed medical therapy; MCS, mechanical circulatory support