Whole-Blood Copper Concentrations in Patients with Atrial Fibrillation According to Amiodarone Use: An Exploratory Study

Background: Trace elements are essential for cardiovascular physiology, and their systemic imbalance has been linked to cardiovascular diseases and pharmacological therapies. However, the relationship between amiodarone therapy and whole-blood elemental profiles in patients with atrial fibrillation (AF) remains unclear. Objectives: This exploratory study evaluated whole-blood elemental concentrations in AF patients with and without amiodarone treatment. Methods: This single-center observational study included 51 AF patients (32 males, 62.8%; median (Q1–Q3) age of 71 (60–76) years) referred for catheter ablation. Whole-blood concentrations of 12 elements were compared in the amiodarone (n =18) and non-amiodarone (n = 33) subgroups. A subgroup analysis restricted to patients with predefined comorbidities was performed. Results: After correction for multiple comparisons, patients receiving amiodarone had higher copper and cobalt concentrations and lower rubidium concentrations (q = 0.01, 0.02, and 0.04, respectively). Amiodarone use remained associated with higher copper concentration after multivariable adjustment (B = 86.3 µg/L, 95% CI 25.3–147.3; p = 0.007), with a similar bootstrap estimate. Adjusted associations for cobalt and rubidium were not statistically significant in the full sample. Among patients with predefined comorbidities, the differences in copper, cobalt, and lead remained significant after correction. Conclusions: Amiodarone use was associated with higher whole-blood copper concentrations after adjustment for selected demographic and clinical characteristics. This association may partly reflect underlying cardiovascular disease burden, although the contributions of disease characteristics and treatment exposure remain uncertain. These findings are hypothesis-generating and do not establish causality.