Acute Effects of Triiodothyronine (T₃) Replacement Therapy in Patients with Chronic Heart Failure and Low-T₃Syndrome: A Randomized, Placebo-Controlled Study

Abstract

Context: Low-T 3 syndrome is a predictor of poor outcome in patients with cardiac dysfunction. The study aimed to assess the short-term effects of synthetic L-T 3 replacement therapy in patients with low-T 3 syndrome and ischemic or nonischemic dilated cardiomyopathy (DC).Design: A total of 20 clinically stable patients with ischemic (n ϭ 12) or nonischemic (n ϭ 8) DC were enrolled. There were 10 patients (average age 72 yr, range 66 -77; median, 25-75th percentile) who underwent 3-d synthetic L-T 3 infusion (study group); the other 10 patients (average age 68 yr, range 64 -71) underwent placebo infusion (control group). Clinical examination, electrocardiography, cardiac magnetic resonance, and bio-humoral profile (free thyroid hormones, TSH, plasma renin activity, aldosterone, noradrenaline, N-terminal-pro-B-Type natriuretic peptide, and IL-6) were assessed at baseline and after 3-d synthetic L-T 3 (initial dose: 20 g/m 2 body surface⅐d) or placebo infusion.Results: After T 3 administration, free T 3 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 ϭ 0.03) without side effects. Heart rate decreased significantly after T 3 infusion (63, 60 -66 vs. 69, 60 -76 beats per minute; P ϭ 0.008). Plasma noradrenaline (347; 270 -740 vs. 717, 413-808 pg/ml; P ϭ 0.009), N-terminal pro-B-Type natriuretic peptide (3000, 438-4005 vs. 3940, 528-5628 pg/ml; P ϭ 0.02), and aldosterone (175, 152-229 vs. 231, 154 -324 pg/ml; P ϭ 0.047) significantly decreased after T 3 administration. Neurohormonal profile did not change after placebo infusion in the control group. After synthetic L-T 3 administration, left-ventricular end-diastolic volume (142, 132-161 vs. 133, 114 -158 ml/m 2 body surface; P ϭ 0.02) and stroke volume (40, 34 -44 vs. 35, 28 -39 ml/m 2 body surface; P ϭ 0.01) increased, whereas external and intracardiac workload did not change. Conclusions:In DC patients, short-term synthetic L-T 3 replacement therapy significantly improved neuroendocrine profile and ventricular performance. These data encourage further controlled trials with more patients and longer periods of synthetic L-T 3 administration. (J Clin Endocrinol

Early and Short-term Triiodothyronine Supplementation Prevents Adverse Postischemic Cardiac Remodeling: Role of Transforming Growth Factor-β1 and Antifibrotic miRNA Signaling

“…Furthermore, clinical studies have shown that levels of T3 have a positive correlation with ejection fraction (EF%) in ST-elevation myocardial infarction (STEMI) patients at 48 h from the index event (22). Consistently, treatment of Low-T3S exerts cardioprotective effects in both humans and animal models and may be a novel option for treatment of cardiac disease (23)(24)(25)(26)(27)(28)(29)(30).…”

Thyroid Hormone and Coronary Artery Disease: From Clinical Correlations to Prognostic Implications

“…Only an appropriately designed, large-scale, longitudinal study, coupled with smaller studies aimed at investigating potential pathophysiological mechanisms, would be able to confirm such a hypothesis. However, considering that hypothyroidism increases the risk of CAD and that T3 therapy has proven benefits in diverse forms of heart disease, 11,12 any reduction in fT3 should not be viewed simply as an innocent bystander in cardiovascular disease.…”

The renin–angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations

“…Emdin et al (2004) also reported that PRA and aldosterone levels were significantly higher in heart failure patients than in healthy subjects and showed a significant linear increase from controls through to patients with severe heart failure, while T 3 and FT 3 levels were significantly decreased in heart failure patients. However, subsequent studies reported normal PRA and aldosterone values in heart failure patients (Pingitore et al 2008, Fontana et al 2012, and Pingitore et al (2008) found a significant decrease in plasma aldosterone but no change in PRA after T 3 infusion.…”