Supplementary Material for: Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling

<b><i>Background:</i></b> Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T<sub>3</sub>) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, atrial electromechanical function and POAF. <b><i>Methods:</i></b> Thirty-nine patients with sinus rhythm and no history of atrial fibrillation or thyroid disease undergoing cardiac surgery were prospectively enrolled. Serum concentrations of thyrotropin, free (F) and total (T) thyroxine (T<sub>4</sub>) and T<sub>3</sub>, reverse (r)T<sub>3</sub>, 3-iodothyronamine (3-T<sub>1</sub>AM) and 3,5-diiodothyronine (3,5-T<sub>2</sub>) were measured preoperatively, complemented by evaluation of echocardiographic and electrophysiological parameters of cardiac function. Holter-ECG and telemetry were used to screen for POAF for 10 days following cardiac surgery. <b><i>Results:</i></b> Seven of 17 patients who developed POAF demonstrated nonthyroidal illness syndrome (NTIS; defined as low T<sub>3</sub> and/or low T<sub>4</sub> syndrome), compared to 2 of 22 (p < 0.05) patients who maintained sinus rhythm. In patients with POAF, serum FT<sub>3</sub> concentrations were significantly decreased, but still within their reference ranges. 3,5-T<sub>2</sub> concentrations directly correlated with rT<sub>3</sub> concentrations and inversely correlated with FT<sub>3</sub> concentrations. Furthermore, 3,5-T<sub>2</sub> concentrations were significantly elevated in patients with NTIS and in subjects who eventually developed POAF. In multivariable logistic regression FT<sub>3</sub>, 3,5-T<sub>2</sub>, total atrial conduction time, left atrial volume index and Fas ligand were independent predictors of POAF. <b><i>Conclusion:</i></b> This study confirms reduced FT<sub>3</sub> concentrations in patients with POAF and is the first to report on elevated 3,5-T<sub>2</sub> concentrations in cardiac NTIS. The pathogenesis of NTIS therefore seems to involve more differentiated allostatic mechanisms.