Thyroid hormone and cardiac disease: from basic concepts to clinical application.

Nature's models of regeneration provide substantial evidence that a natural healing process may exist in the heart. Analogies existing between the damaged myocardium and the developing heart strongly indicate that regulatory factors which drive embryonic heart development may also control aspects of heart regeneration. In this context, thyroid hormone (TH) which is critical in heart maturation during development appears to have a reparative role in adult life. Thus, changes in TH -thyroid hormone receptor (TR) homeostasis are shown to govern the return of the damaged myocardium to the fetal phenotype. Accordingly, thyroid hormone treatment preferentially rebuilds the injured myocardium by reactivating developmental gene programming. Clinical data provide further support to this experimental evidence and changes in TH levels and in particular a reduction of biologically active triiodothyronine (T3) in plasma after myocardial infarction or during evolution of heart failure, are strongly correlated with patients morbidity and mortality. The potential of TH to regenerate a diseased heart has now been testing in patients with acute myocardial infarction in a phase II, randomized, double blind, placebo-controlled study (the THiRST study).