Introduction: Thyroid hormones play a central role in the regulation of the cardiovascular system. Heart failure with preserved ejection fraction (HFpEF) is responsible for more than 50% of all heart failure cases and its main pathophysiological alteration is diastolic dysfunction. Diminished thyroid function is known to predominantly impair diastolic function, however the thyroid hormone status in HFpEF remains largely unknown.
Methods: We evaluated an animal model of HFpEF, ZSF1 Obese rats (ZSF1-Ob, n=13), and their control group, ZSF1 Lean rats (ZSF1-Ln, n=11), with serial echocardiography followed by invasive hemodynamic recordings and tissue collections at 20 weeks. Serum TSH was quantified by ELISA. Thyroxine (T4) and triiodothyronine (T3) were quantified in serum, left ventricle and visceral adipose tissue by radioimmunoassay (RIA).
Results: At 20 weeks of age, ZSF1-Ob group developed HF with diastolic dysfunction, as shown by an increased E/E on echocardiography, a prolonged time constant of isovolumetric relaxation, an elevated end-diastolic pressure and upward shifted end-diastolic pressure-volume relationship on invasive hemodynamic evaluation. Serum levels of thyroid hormones were significantly decreased in ZSF1-Ob rats (T3: 5.96±4.65 vs 35.85±9.39 ng/dL in ZSF1-Ln, P<0.001; T4: 1.51±0.64 vs 3.49±1.35 μg/dl in ZSF1-Ln, P<0.001), while the levels of serum TSH were not significantly different between the two groups (0.65±0.38 ng/ml in ZSF1-Ln vs 0.79±0.57 ng/ml in ZSF1-Ob, P=0.531). Left ventricle levels of thyroid hormones were significantly decreased in ZSF1-Ob rats (T3: 3.87±0.85 vs 10.51±7.91 ng/g in ZSF1-Ln, P=0.012; T4: 0.99±0.43 vs 2.02±0.60 ng/g in ZSF1-Ln, P=0.016). The levels of T3 and T4 in visceral adipose tissue were not significantly different between the two groups.
Conclusion: We observed a decrease in serum and myocardial thyroid hormone levels in an animal model of HFpEF. This may contribute to impaired diastolic function and, therefore, may constitute an interesting therapeutic target in HFpEF.
20 - 23 May 2017
European Society of Endocrinology