Large-scale CMR-ECGI uncovers an association between diffuse myocardial fibrosis and prolonged whole-heart repolarisation in older adults

Background Myocardial extracellular volume (ECV) by cardiovascular magnetic resonance (CMR) quantifies diffuse interstitial fibrosis, but its relationship to non-invasive epicardial electrophysiology in older adults is unknown. We investigated associations between global and segmental ECV and electrocardiographic imaging (ECGI) repolarisation biomarkers in the MyoFit46 older-age cohort. Methods In ~500 participants, we tested cross-sectional associations between global ECV and ECGI biomarkers using Gaussian linear model (or generalized linear model with log link). Multivariable models sequentially adjusted for sex (Model 1), sex plus left ventricular (LV) ejection fraction and LV mass index (Model 2), and additionally resting heart rate (Model 3A). Interaction models assessed effect modification by LV ejection fraction (Model 3B) and LV mass index (Model 3C). Segment-level analyses used linear mixed-effects models to evaluate within-heart associations between segmental ECV and ECGI metrics, with random intercepts for participant and AHA segment. Results Higher global ECV was associated with prolonged ECGI repolarisation timing. In univariable model, global ECV was associated with longer median LV repolarisation time (RT; β=1.67 ms per 1% ECV, 95% CI 0.60–2.73, p=0.002) and longer median LV activation–recovery interval (ARI; β=1.45 ms per 1% ECV, 95% CI 0.42–2.48, p=0.006). Heart-rate–corrected ARI (Fridericia) remained associated (β=1.33 ms per 1% ECV, 95% CI 0.40–2.26, p=0.005). Global associations persisted after adjustment for sex, LV ejection fraction, and LV mass index (e.g., RT β=5.26–4.07 ms per 1 SD higher ECV across Models 1–3A; p=0.002–0.010; ARI β=4.58–3.55 ms per 1 SD higher ECV; p=0.006–0.020), with similar findings for Fridericia-corrected metrics. Segmental mixed-effects analyses showed no significant within-heart associations between segmental ECV and ECGI metrics. Conclusions In older adults, higher global myocardial ECV is independently associated with prolongation of ECGI-derived ventricular repolarisation biomarkers (RT and ARI), consistent with diffuse fibrosis influencing whole-heart repolarisation dynamics. The absence of segment-level associations suggests the observed coupling primarily reflects between-person differences in diffuse substrate burden rather than detectable within-heart spatial covariation at the 16-segment level.