Acute effects of triiodothyronine replacement therapy in patients with chronic heart failure and low-T3 syndrome: a randomized, placebo-controlled study

Context. Low-Triiodothyronine (T3) syndrome is a predictor of poor outcome in patients with cardiac dysfunction. The study aimed to assess the short-term effects of synthetic L-T3 replacement therapy in patients with low-T3 syndrome and ischemic or non-ischemic dilated cardiomyopathy (DC). Design. Twenty clinically stable patients with ischemic (n=12) or non-ischemic (n=8) DC were enrolled. Ten patients (average age 72, range 66-77 years; median, 25-75 percentile) underwent 3-day synthetic L-T3 infusion (study group); the other 10 patients (average age 68, range 64-71 years) underwent placebo infusion (control group). Clinical examination, electrocardiography, cardiac magnetic resonance and bio-humoral profile (free thyroid hormones, thyrotropin [TSH], plasma renin activity, aldosterone, noradrenaline, N-Terminal-pronatriuretic peptide [NT-proBNP] and interleukin-6) were assessed at baseline and after 3-day synthetic L-T3 (initial dose: 20 mg/m2 body surface/day) or placebo infusion. Results. After T3 administration, free T3 concentrations increased until reaching a plateau at 24-48 h (3.43, 3.20-3.84 vs 1.74, 1.62-1.93 pg/ml, p=0.03) without side effects. Heart rate decreased significantly after T3 infusion (63; 60-66 vs 69, 60-76 bpm, p=0.008). Plasma noradrenaline (347; 270-740 vs 717, 413-808 pg/ml, p=0.009), NT-proBNP (3000, 438-4005 vs 3940, 528-5628 pg/ml, p=0.02) and aldosterone (175, 152-229 vs 231, 154-324 pg/ml, p=0.047) significantly decreased after T3 administration. Neurohormonal profile did not change after placebo infusion in the control group. After synthetic L-T3 administration, left-ventricular end-diastolic volume (142, 132-161 vs 133, 114-158 ml/m2 body surface, p=0.02) and stroke volume (40, 34-44 vs 35, 28-39 ml/m2 body surface, p=0.01) increased, while external and intracardiac workload did not change. Conclusions. In DC patients short-term synthetic L-T3 replacement therapy significantly improved neuroendocrine profile and ventricular performance. These data encourage further controlled trials with more patients and longer periods of synthetic L-T3 administration.