Thyroid hormone and "cardiac metamorphosis": potential therapeutic implications.

Recent research has revealed novel actions of thyroid hormone (TH) on the heart which may be of important physiological and therapeutic relevance. TH, apart from its "classical" actions on cardiac contractility and heart rhythm, appears to regulate various intracellular signaling pathways related to stress responses and cardiac remodelling. Accumulating experimental evidence suggests that changes in TH may constitute an important component in the pathophysiology of heart failure. In fact, TH seems to be a "switch" for the fetal cardiac phenotype. Changes in the TH-thyroid hormone receptor axis are also evident in patients with heart failure and associated with impaired cardiac function and increased mortality. More importantly, experimental and clinical studies demonstrate that TH can limit ischaemic injury, attenuate cardiac remodeling and improve cardiac hemodynamics. TH analogs have already been developed and may allow exploitation of the TH-thyroid hormone receptor in clinical practice. At present, the therapeutic potential and efficacy of TH in the treatment of cardiac diseases await evaluation in large clinical trials.