Cardioprotection and Thyroid Hormones in the Clinical Setting of Heart Failure

Abstract

Ischemic heart disease is the main cause of morbidity and mortality worldwide and is becoming more widespread with population aging. Cardioprotection is a dynamic process characterized by mechanisms related to myocardial damage and activation of protective factors. Targeting these processes could be attractive as a new therapeutic strategy in the evolution of post-ischemic heart failure (HF). In this context, the role of thyroid hormone (TH)-mediated cardioprotection is supported by a number of findings regarding the modulation of neuroendocrine systems, inflammatory and oxidative stress status, pro-survival intracellular pathways, and epigenetic factors, its effects on cardiac angiogenesis, structure, and function and on the preservation of mitochondrial function and morphology, and its beneficial effects on cell growth and redifferentiation. Moreover, the numerous effects of TH on the heart involve genomic mechanisms, which include cardiac differentiation during the perinatal period and non-genomic action, directed toward the maintenance of cardiovascular homeostasis. This evidence suggests that there is an opportunity to treat HF patients with TH. This review is mainly focused on the clinical evidence of the role of the thyroid system in the complex setting of HF.

Low Free Triiodothyronine Level as a Predictor of Cardiovascular Events and All-Cause Mortality in Patients Undergoing Hemodialysis: The DREAM Cohort

“…Thus, our results can be explained by the confounding effects of prior CVD and NT-proBNP. Considering the effect of T3 on cardiac function 9,14,15) , the observed cross-sectional inverse association between FT3 and NT-proBNP may indicate the causal effect of a lower FT3 on a higher NT-proBNP. If so, low FT3 status might play a causative role in the pathogenesis of increased CVD risk to some extent.…”

“…Suppressed conversion of T4 to T3 could be protective against wasting as it reduces energy expenditure in tissues. In contrast, since T3 has cardioprotective functions 9,14) , low T3 status may induce hypofunction of the heart and further deteriorate the cardiovascular health. As recently reviewed in detail 14) , T3 regulates the expression of genes which are relevant to cell growth, differentiation, and metabolism by binding to thyroid hormone receptors and in the nucleus.…”

“…Although low T3 syndrome may represent "adaptation" to severe disease conditions in order to avoid wasting 12) , it may also play a pathophysiologic role in the worsening of the severe conditions 13) . Since thyroid hormones were shown to have cardioprotective properties 9,14,15) , a low T3 status itself could further deteriorate cardiac function. In fact, T3 replacement was shown to improve cardiac performance in a randomized controlled study of patients with heart failure and low T3 syndrome 15) .…”

“…It is still a matter of debate whether low T3 syndrome should be treated or not 9,12,14,29) . Low T3 syndrome (nonthyroidal illness, euthyroid sick syndrome) has been regarded as "adaptation" to wasting caused by severe illness such as cardiac and adjusted for the four major demographic factors including age, sex, duration of hemodialysis, and DKD or not (Table 4).…”

Associations of Thyroid Hormones and Resting Heart Rate in Patients Referred to Coronary Angiography

“…Moreover, the link between thyroid hormones within the reference range and RHR may also support considerations to be cautious with thyroid hormone replacement therapy in older patients at relatively high cardiovascular risk [31]. By contrast, there is also evidence suggesting some beneficial cardiovascular effects of thyroid hormone replacement in NTIS such as in patients with myocardial infarction or heart failure warranting further RCTs to test these hypotheses [32][33][34]. Apart from this, our findings may also pave the way for further studies to evaluate whether monitoring RHR may be a useful tool for guiding treatment decisions regarding antithyroid drug titration in patients with hyperthyroidism and for the potential detection of a (re-) emerging hyperthyroidism [35,36].…”