LVH-Voltage Discordance and Myocardial Dysfunction in Wild-Type Transthyretin Cardiomyopathy: A Prospective Cohort Study.

BACKGROUND: In wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM), increased left ventricular wall thickness reflects amyloid infiltration rather than myocyte hypertrophy, and QRS voltage may not rise proportionally. Whether this electrical-anatomical discordance marks myocardial dysfunction and adverse outcomes within established disease is uncertain. METHODS: We prospectively enrolled 220 consecutive patients with newly diagnosed wtATTR-CM in a single-centre cohort. LVH-voltage discordance was defined as maximum LV wall thickness ≥12 mm with a Sokolow-Lyon voltage < 3.5 mV. The primary outcome was absolute global longitudinal strain (GLS); secondary outcomes included impaired GLS (< 16%), serial GLS change, and clinical events. RESULTS: Discordance was present in 41.8%. Absolute GLS was lower with discordance (13.4 ± 2.8% vs. 17.3 ± 3.5%), including after multivariable adjustment (β -2.21, 95% CI -3.04 to -1.39; p< 0.001), without interaction by rhythm (p = 0.52). Impaired GLS was more prevalent (81.5% vs. 35.2%; adjusted prevalence ratio 1.66, 95% CI 1.28-2.15). The continuous QRS amplitude-to-wall-thickness index correlated with absolute GLS (ρ = 0.35; p< 0.001). Over a median 16.0 months, discordance was associated with cardiovascular death or first heart failure hospitalization (adjusted HR 3.88, 95% CI 1.43-10.52) and first heart failure hospitalization (adjusted HR 3.48, 95% CI 1.08-11.18); mortality estimates were imprecise. Among 142 patients with serial imaging, adjusted annual GLS decline was greater with discordance (-0.65 vs. -0.31 percentage points/year). CONCLUSIONS: In established wtATTR-CM, LVH-voltage discordance was associated with worse baseline GLS, a less favorable longitudinal GLS trajectory, and HF-related outcomes. It may provide a simple marker for within-disease phenotyping, but these findings require external validation.