Myocardial scar burden, not mechanical dyssynchrony or strain, dictates recovery potential in HFrEF: a CMR study

Background Prediction of myocardial recovery in patients with heart failure with reduced ejection fraction (HFrEF) remains a clinical challenge. Despite the potential of cardiac magnetic resonance (CMR) to assess both mechanics and tissue characterization, the relative importance of scarring versus dyssynchrony in predicting this transition is not well defined. Purpose This study aimed to evaluate and compare the performance of baseline CMR parameters, including late gadolinium enhancement (LGE) and myocardial strain, in predicting the transition from HFrEF to heart failure with improved ejection fraction (HFimpEF). Methods We enrolled 416 patients with HFrEF with a mean baseline left ventricular ejection fraction (LVEF) of 33.3 ± 6.5%. All participants underwent baseline CMR imaging. HFimpEF was defined as a follow-up LVEF ≥ 40% with an absolute increase of ≥10%. Parameters included LGE mass, global longitudinal strain (GLS), global circumferential strain (GCS), LV remodeling index (LVRI), and left ventricular mechanical dyssynchrony (LV-MD). Results During a median follow-up of 13.2 months, 243 patients (58.4%) achieved HFimpEF. Compared to patients with persistent HFrEF (n=173), recovered patients were younger (56.57 ± 11.62 vs. 59.12 ± 10.42 years; P = 0.022), and exhibited significantly lower baseline LGE mass (3.69 vs. 12.68 g; P < 0.001), higher LVRI (0.56 vs. 0.49; P < 0.001) and better myocardial deformation (GLS: -8.11% vs. -6.71%, P < 0.001; GCS: -11.38% vs. -9.93%, P = 0.002). Baseline LVEF and LV-MD showed no significant differences. Univariate logistic regression identified LGE mass (OR: 0.933; P < 0.001), LVRI (OR: 1.081 per 0.01 increase; P < 0.001), GLS (OR: 0.896; P < 0.001), and GCS (OR: 0.925; P < 0.001) as significant predictors of recovery, whereas LV-MD was not. However, receiver operating characteristic (ROC) analysis confirmed LGE mass as the superior predictor (AUC: 0.742), significantly outperforming LVRI (AUC: 0.690), GCS (0.593), GLS (0.585), and LV-MD (0.529). Conclusions Myocardial scar burden, quantified by LGE mass, is the primary determinant of recovery potential in HFrEF. Conversely, mechanical dyssynchrony and strain offer limited prognostic value for LVEF improvement. These results suggest that quantitative LGE assessment could help clinicians identify patients most likely to experience myocardial recovery.