Impact of the Extent, Pattern, and Location of Replacement Myocardial Fibrosis on Clinical Outcomes in Aortic Regurgitation

Aims The prognostic significance of late gadolinium enhancement (LGE)-detected replacement myocardial fibrosis in aortic regurgitation (AR) remains incompletely understood. This study aims to explore the association between the extent, pattern, and location of LGE and clinical outcomes in patients with chronic AR. Methods and results Between 2010 and 2024, consecutive patients with moderate-to-severe AR and no significant coronary artery stenosis who underwent contrast-enhanced cardiac magnetic resonance (CMR) were included. The primary endpoint was major adverse cardiovascular events (MACE), defined as cardiovascular mortality, heart transplantation, or rehospitalization for heart failure. The association between LGE characteristics and MACE was evaluated. Overall, 363 patients (mean age 52.6 ± 14.2 years; 54 female) were included. Over a median follow-up of 56.6 months, 73 patients experienced MACE. LGE was present in 200 patients (55.1%). An LGE extent threshold of 2.6% provided robust risk stratification, yielding the highest C-index of 0.797, a likelihood ratio chi-square of 97.30, and the lowest Akaike information criterion of 681.06. Furthermore, predominant subendocardial-involved LGE was present in 13.5% of LGE-positive patients and was independently associated with MACE after adjusting for LGE extent (HR 3.028; 95% CI 1.216-7.539; P = 0.017). Kaplan-Meier analysis demonstrated that patients with both LGE extent >2.6% and predominant subendocardial-involved LGE pattern were at the highest risk of MACE. Conclusions In AR, an LGE extent > 2.6% predicts MACE better than LGE presence alone. Furthermore, non-ischemic predominant subendocardial-involved LGE is independently associated with MACE. The coexistence of both features further amplifies the risk of MACE.