Prognostic value of additional midwall late gadolinium enhancement in patients with ischemic cardiomyopathy

Abstract Background Although several studies have reported the additional presence of midwall late gadolinium enhancement (LGE) using cardiac magnetic resonance (CMR) in patients with ischemic cardiomyopathy (ICM), its prognostic value is not well established. Purpose To assess the prognostic value of the additional presence of midwall-LGE in a large cohort of patients with ICM and reduced left ventricular ejection fraction (LVEF). Methods Between 2008 and 2022, all consecutive patients referred for myocardial viability assessment using CMR with an history of ICM (≥70% stenosis in ≥1 epicardial coronary vessel on angiography and/or history of myocardial infarction and/or coronary revascularization) and LVEF <50% were included. Midwall-LGE was defined by non-ischemic LGE corresponding to non-specific myocardial fibrosis. All patients with a history of acute myocarditis and/or sub-epicardial LGE were excluded. The primary outcome was all-cause death. Nested Cox proportional hazard models were used to assess the prognostic value of additional midwall-LGE including its location (lateral and/or septal and other location) and extent (1 or ≥2 segments), above the presence of ischemic-LGE and traditional prognostic factors. The incremental prognostic value of midwall-LGE extent and location was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results Among the 6,082 included patients (65±12 years, 73% males), 702 (11.5%) had an additional midwall-LGE. During a median follow-up of 9 (IQR, 7-12) years, 652 (11%) patients died. The presence of midwall-LGE alone was strongly associated with the risk of death compared to patients without midwall-LGE (p<0.001, Figure 1A). Among these patients with midwall-LGE (N=702), survival curves showed an increased risk for midwall-LGE in lateral and/or septal location (p<0.001), for larger extent (p<0.001) and the presence of ischemic-LGE (p<0.001, Figure 1B). In this population with midwall-LGE (N=702), after adjustment for risk factors and extent of ischemic-LGE, midwall-LGE with septal and/or lateral location (adjusted HR: 2.6; 95%CI: 1.8-3.6) and extent ≥2 segments (adjusted HR: 2.6; 95%CI: 1.8-3.7, both p<0.001) were independently associated with all-cause death. A comprehensive LGE model combining all the characteristics of midwall-LGE showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.13; NRI=46%; IDI=19%, Chi-2 global=261, all p<0.05; LR-test p<0.001, Figure 2). Conclusion In a large cohort of ICM patients, the presence of an additional non-ischemic midwall-LGE is an independent prognosticator of all-cause death, particularly for larger extent or when present in the septal and/or lateral location.Prognostic value of midwall-LGEIncremental prognostic value