CMR-ECGI reveals occult electrical remodeling related to myocardial fibrosis in aging populations (MyoFit46)

Background Myocardial fibrosis increases with age and is linked to conduction abnormalities and ventricular arrhythmia, yet its functional electrophysiological consequences in the aging heart remain incompletely understood.1-6 We investigated the relationship between myocardial fibrosis by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging and non-invasive electrophysiological phenotypes derived from CMR-guided electrocardiographic imaging (ECGI) in older adults.7-9 Methods In MyoFit46 (NCT 05455125), the cardiac sub-study of the National Survey of Health and Development, older participants prospectively underwent combined 3 Tesla CMR and ECGI. Global and segmental left ventricular (LV) LGE burden was quantified (using 3 and 5 standard deviation methods, 3SD/5SD), and its association with ECGI-derived measures of voltage, activation, and repolarization was assessed using regression for global analyses and mixed-effects models for segmental analyses. Models were adjusted for sex, body mass index (BMI) and indexed global LV mass or segmental LV mass as appropriate. Results Among 386 participants (76.8±0.8 years, 56% male), increasing segmental LGE burden was independently associated with marked attenuation of ECGI-derived QRS voltage (-0.30 mV per log1p-unit increase in LGE3SD mass; 95% CI: -0.44 to -0.17; p<0.001, Table 1). In contrast, conventional 12-lead ECG voltage showed only weak or absent associations (Figure 1), particularly among individuals with normal surface ECG voltage. ECGI voltage demonstrated a clear stepwise reduction across increasing LGE tertiles, revealing an electro-anatomical substrate not captured by standard ECG (Figure 1). Greater LGE burden was also associated with reduced dispersion and lower spatial gradients of both activation and repolarization at segmental and global LV levels, consistent with altered electrical organization in fibrotic myocardium (Table 1). Conclusions In the largest CMR-ECGI study of older adults to date, myocardial fibrosis was associated with ECGI-defined voltage attenuation and reduced activation and repolarization heterogeneity, changes that remained largely occult on standard ECG. These findings suggest that ECGI, but not conventional surface ECG can resolve age-related replacement fibrosis which reshapes the electrophysiological substrate, supporting the potential value of combined CMR-ECGI for improved characterization of arrhythmic risk in the aging heart.