TRANSLATING T3 TREATMENT OF HEART FAILURE FROM BENCH TO BEDSIDE: FINALLY, A SAFE TREATMENT/MONITORING PROTOCOL THAT SHOULD WORK!
A. Martin Gerdes, Ph.D., New York Institute of Technology, Old Westbury, NY, USA
The idea of treating heart failure with thyroid hormones (THs) is not new. Unfortunately, cardiovascular clinical studies mostly using TH analogs at excessive doses demonstrated an increased incidence of arrhythmias and have largely deterred further studies. At the heart of the problem, no one has clearly demonstrated potential benefits using a therapeutic TH treatment/monitoring protocol that can be safely translated to humans. Over the past few years, our lab has investigated the pathophysiological consequences of low oral doses of T3 in animal models of diabetic cardiomyopathy (DM), myocardial infarction (MI), and hypertension. In each model, a T3 dose that produced mild feedback inhibition of T4 and/or TSH was used with insignificant changes in serum T3. Cardiac tissue T3 levels were depressed in untreated rats and restored to normal with T3 in all disease models. Results were remarkable. T3 prevented decline in LV function and arteriolar remodeling in DM. T3 treatment of MI dramatically improved LV systolic and diastolic function, reduced sensitivity to arrhythmia induction, increased myocyte survival, and reduced the incidence of RV hypertrophy, suggesting improved pulmonary function. One year of T3 treatment in Spontaneously Hypertensive Heart Failure rats did not affect the degree of hypertension but improved diastolic function and tended to reduce fibrosis. No adverse effects were observed in any T3 treated model. It appears that re-expression of the fetal gene program, ubiquitous in diseases leading to heart failure and also hypothyroidism, may reflect low cardiac tissue T3 levels. In conclusion, safe restoration of low cardiac T3 levels in heart diseases leading to heart failure may lead to dramatic improvement in cardiac function and remodeling. The approach employed in these studies provides a safe and effective treatment/monitoring protocol that should be easily translatable to humans.