Clinical characteristics and outcomes of cardiomyopathies related to immune-mediated diseases

AIMS: Dilated cardiomyopathy (DCM) encompasses genetic and acquired aetiologies, yet the impact of immune-mediated mechanisms remains unclear. This study investigates the clinical characteristics and outcomes of immune-mediated DCM (ID-CMP). METHODS: From the Maastricht Cardiomyopathy registry, 194 patients with ID-CMP were compared with 678 non-immune DCM controls over a median follow-up of 5.2 (3.7-10.7) years. ID-CMP was categorized into autoimmune-mediated (adaptive immunity dysfunction), autoinflammatory-driven (innate immunity dysfunction), and mixed-pattern (MHC Class I associations and autoinflammatory components). Patients with features of >1 category were classified as overlapping-CMP. Echocardiographic and genetic data were collected. Cox regression assessed major adverse cardiovascular events (MACE: cardiac mortality, heart failure hospitalization, life-threatening arrhythmias). Left ventricular ejection fraction (LVEF) trajectories were analysed using linear mixed-effects models. Findings were validated in an independent cohort of 201 ID-CMP patients. RESULTS: ID-CMP was associated with a higher risk of MACE [HR: 1.68 (1.1-2.5), P = .012] after adjustment for age, sex, and baseline LVEF, confirmed in an external validation cohort [HR:2.40 (1.6-3.5), P < .001]. LVEF was lower in ID-CMP during the first year but converged with non-immune DCM thereafter (P0-1year = .018; P>1year = ns). Outcomes did not differ among ID-CMP subtypes. Inflammation on EMB was related to worse clinical outcome [HR:2.0 (1.1-3.6), P = .017]. Pathogenic DCM gene variants were equally frequent in ID-CMP and non-ID-CMP patients (22% vs 20%, P = ns). CONCLUSION: ID-CMP patients have a higher risk of MACE despite similar LVEF trajectories, as confirmed in a validation cohort. Cardiac immune cell infiltration suggests an inflammatory substrate independent of genetics.