Graded MESA-LVH as a marker of left ventricular electrical remodeling: spectrum-based diagnosis, prognosis analysis

BACKGROUND: Emerging evidence suggests that electrocardiographic (ECG) voltage reflects left ventricular electrical remodeling (LVER) beyond left ventricular hypertrophy (LVH), with independent clinical and prognostic significance. OBJECTIVE: To determine whether graded increases in QRS amplitude provide diagnostic and prognostic information for cardiac magnetic resonance (CMR)-defined LVH. METHODS: We analyzed 4644 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) with paired ECG and CMR. CMR-LVH was defined as left ventricular (LV) mass index >91 g/m² in men and >77 g/m² in women. ECG indices included Sokolow-Lyon, Cornell voltage, Peguero-Lo Presti, RaVL, and MESA-LVH(SV1 + SV2 + RV5). Likelihood ratios (LR) were calculated at matched specificities. Hazard ratios (HR) for all-cause mortality, major adverse cardiovascular events (MACE), and their composite were estimated adjusting for clinical covariates and CMR-LVH. RESULTS: CMR-LVH prevalence was 28.6%; 763 deaths and 639 MACE occurred. MESA-LVH combined a coherent monotonic gradient with the widest dynamic range of the indices tested, with LR- ≈ 0.6 at <30 mm and LR+ ≈ 3, 5, 10 at ≥40, ≥50, ≥60 mm, respectively. After CMR-LVH adjustment, MESA-LVH ≥50 mm predicted MACE (HR 1.41), and ≥60 mm predicted MACE (HR 2.08) and, less robustly, death-or-MACE (HR 1.61). The MACE signal was confined to heart-failure hospitalization (HR 4.21 at ≥60 mm), which remained associated after adjustment for continuous LV mass index (HR 2.73, 95% CI 1.34-5.56). CONCLUSIONS: Graded MESA-LVH provides the broadest diagnostic-prognostic spectrum for QRS amplitude interpretation; at its upper range it predicted MACE after adjustment for binary CMR-LVH, and heart-failure hospitalization even after adjustment for continuous LV mass index, reinforcing the LVER paradigm.