Low Triiodothyronine Syndrome as a Powerful Predictor of Death in Heart Failure

Thyroid hormone (TH) has a critical role in cardiovascular homeostasis under both physiological and pathological conditions. THs, in particular the biologically active triiodothyronine (T3), modulate cardiac contractility, heart rate, diastolic function, and systemic vascular resistance through genomic, and nongenomic-mediated effects. In heart failure (HF), the main alteration of thyroid function is referred to as "low-T3 syndrome," characterized by a reduction in serum T3 with normal levels of thyroxine (T4) and thyrotropin (thyroid-stimulating hormone, TSH). This syndrome, which affects approximately one-third of patients with more severe HF, is commonly interpreted as an adaptive factor minimizing the catabolic phenomena of illness. However, this interpretative hypothesis is now questioned: experimental data have shown potential negative effects of the low-T3 state in the progressive deterioration of cardiac function and myocardial remodeling in HF. In addition, prognostic studies have shown that T3 levels are a strong predictor of mortality in HF patients, also adding prognostic power to conventional cardiac parameters. All these data, together with the evidence of some benefit of administration of synthetic THs administration to HF patients in pilot studies, indicate that placebo-controlled prospective studies are now needed in order to better define the safety and prognostic effects of long-term treatment with synthetic THs in HF.