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

Background and Aims Dilated cardiomyopathy (DCM) encompasses diverse etiologies, including genetic and acquired factors, 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 to 678 non-immune DCM (nonID-CMP) controls over a median follow-up of 5.2 [3.7–10.7] years. ID-CMP was further categorized into three groups: autoimmune-mediated (AImm-CMP, linked to adaptive immunity dysfunction), autoinflammatory-driven (AInfl-CMP, associated with innate immunity dysfunction), and a mixed-pattern group (Mixed-CMP, with MHC I class associations and autoinflammatory components). Patients exhibiting features of more than one category were classified separately as the overlapping-CMP (Ovr-CMP) group. Echocardiographic and genetic data were collected. Cox regression assessed major adverse cardiovascular events (MACE: cardiac mortality, heart failure hospitalization, life-threatening arrhythmias). LVEF trajectories were analyzed using linear mixed-effects ANOVA. Findings were validated in an independent cohort of 201 patients with ID-CMP. Results ID-CMP was associated with a higher risk of MACE (HR 1.68 [1.1–2.5], p=0.012) after adjustment for age, sex, and baseline LVEF, which was confirmed in an external validation cohort (HR 2.40 [1.6-3.5], p<0.001). ID-CMP patients had worse LVEF in the first year compared to nonID-CMP patients, but this difference resolved over time (p0-1years=0.018; p>1year=ns). Subgroup analyses showed no significant differences in the composite endpoint or cardiac mortality across the subtypes of ID-CMP, indicating similar clinical outcomes. Inflammation on EMB was also related to worse clinical outcome (HR 2.0 [1.1-3.6], p=0.017). Pathogenic gene variants in DCM-associated genes were identified in 22% of ID-CMP patients, which was comparable to the 20% in non-ID-CMP patients (p=ns). Conclusions Patients with ID-CMP have a higher risk of MACE despite similar LVEF trajectories, as also confirmed in a validation cohort. Significant cardiac immune cell infiltration suggests an inflammatory substrate independent of genetic factors.