Cardiac electrical remodeling in Graves' disease: insights from global ventricular repolarization indices.

Background: Thyroid hormone excess can affect cardiac electrical activity through several mechanisms, yet its relationship with ventricular repolarization remains incompletely understood. Standard electrocardiographic intervals primarily characterize the overall duration of repolarization, whereas newer ECG-derived indices may provide additional information on its spatial and temporal heterogeneity. A better understanding of these alterations may be clinically relevant in light of emerging evidence linking circulating thyroid hormone levels with sudden cardiac death. Objectives: The aim of this study was to identify electrocardiographic parameters of ventricular repolarization that exhibit the most pronounced alterations in patients with Graves' disease, thereby characterizing the pattern of repolarization changes associated with thyroid hormone excess. Methods: We conducted an observational analysis comparing individuals with patients with Graves' disease with age- and sex-matched euthyroid controls. Ventricular repolarization was assessed using QT, QTc, JT, JTc, Tp-e, and Tp-e-based ratios. Group differences and discriminatory performance were evaluated using non-parametric tests and ROC analysis. Independent associations with hyperthyroidism were examined using multivariable logistic regression with entropy balancing and internal bootstrap validation. Results: Compared with controls, patients with Graves' disease showed higher Tp-e values and Tp-e-derived ratios, consistent with greater heterogeneity of ventricular repolarization. Conversely, the raw QT and JT intervals were reduced, while their rate-corrected counterparts (QTc and JTc) showed only limited differences that varied according to the correction method. Among the evaluated ECG measures, Tp-e/QT provided the strongest separation between the groups, yielding an AUC of 0.92 (95% CI 0.84-0.97), with a sensitivity of 83% and specificity of 86% at a threshold of ≥0.24. After multivariable adjustment, Tp-e/QT remained independently related to overt hyperthyroidism (OR 1.75 for each 0.01 increment, 95% CI 1.31-2.34; p < 0.001). Heart rate was also independently associated with hyperthyroidism (OR 1.05 per 1-bpm increase, 95% CI 1.00-1.10; p = 0.046). Conclusions: In patients with Graves' hyperthyroidism, ventricular repolarization appears to be characterized by greater electrical heterogeneity without a consistent increase in overall repolarization duration. Tp-e-derived measures may capture these abnormalities more effectively and provide additional information beyond standard ECG repolarization indices.