Effect of Hypothyroidism on Force and Kinetics in End-stage Failing Human Myocardium

Abstract

Introduction The relationship between hypothyroidism and the occurrence and progression of heart failure (HF) had an increase interest over the past years. The low T3 syndrome, characterized by reduced T3 in the presence of normal thyroid stimulating hormone (TSH) and free T4 concentration, is a strong predictor of all-cause mortality in HF patients. Still, the impact of hypothyroidism on the contractility properties of failing human heart is unknown. Therefore, the goal of our study was to investigate the hypothyroidism in heart failure using ex-vivo force of contraction and kinetics assessments in left ventricular intact human myocardial muscle preparations. Methods Uniform linear trabeculae were dissected from three groups: (1) non-failing hearts (n=9), (2) failing hearts without underling thyroid dysfunction (n=9), and (3) failing hearts with hypothyroidism (n=9). These muscles were transferred into a custom-made setup where the three main physiological modulators that regulate the contractile strength, length-dependent activation, frequency-dependent activation, and β-adrenergic stimulation were assessed under near-physiological conditions. Clinical information for all patients with HF and hypothyroidism in our study revealed that these patients were receiving levothyroxine treatment. Results Hypothyroidism did not show any additional significant impact on the force of contraction and kinetics of contraction/relaxation different than the recognized alterations usually detected in such parameters in any end-stage failing heart without underlying thyroid dysfunction. Conclusions We suggest the usefulness of levothyroxine treatment in repressing the myocardial alterations of hypothyroidism and limiting them to those caused by HF syndrome itself in our study. Absence of statistical difference between TSH levels of patients with HF and hypothyroidism and TSH levels of patients with HF and no thyroid dysfunction reflects the efficiency and accuracy of the thyroid hormone doses used in treating these patients. More studies are still needed to explore the full potential of the therapeutic use of thyroid hormones in treating HF associated with hypothyroidism.