Hypothyroidism is a commonly encountered clinical condition with variable prevalence. It has profound effects on cardiac function that can impact cardiac contractility, vascular resistance, blood pressure, and heart rhythm. With this review, we aim to describe the effects of hypothyroidism and subclinical hypothyroidism on the heart. Additionally, we attempt to briefly describe how hypothyroid treatment affects cardiovascular parameters. Thyroid hormone activation of THR-β induces angiogenesis by initiating the mitogen-activated protein kinase pathway. 4 Severe hypothyroidism can also cause pericardial effusion. Though the mechanism is unclear, increased capillary permeability and reduced lymphatic drainage from the pericardial space have been suggested. 4 Hypothyroidism can also be associated with a decrease in insulin sensitivity due to downregulation of glucose transporters and direct effects on insulin secretion and clearance. 6Heart Failure and HypothyroidismAs described earlier, hypothyroidism can affect cardiac contractility, which is often diastolic in nature, and impair cardiac muscle relaxation. Associated diastolic hypertension and sometimes-coexistent coronary artery disease further affect myocardial diastolic function.7 Cardiac echocardiography has demonstrated impaired relaxation in patients with overt and subclinical hypothyroidism. In addition, early impaired relaxation has been demonstrated by prolongation of the isovolumetric relaxation time and reduction in the E/A ratio in subclinical hypothyroidism.8 The E/A ratio is a ratio of early to late ventricular filling velocities, and a reduced E/A ratio signifies diastolic dysfunction from impaired relaxation. Consequently, it results in a state of low cardiac output with decreased heart rate and stroke volume. It is well known that protein-rich pericardial and/or pleural effusion often occurs in hypothyroidism as a result of increased vascular permeability. In advanced heart failure and shortly after myocardial infarction, the conversion of T4 to T3 decreases. Since T3 is the main regulator of gene expression in myocardial muscle, this decrease has been thought to affect myocardial contractility and remodeling.7 Low free T3 levels also have been associated with increased mortality in patients with heart disease. Arrhythmia and HypothyroidismIt is well known that hyperthyroidism is associated with atrial fibrillation (AF). Similarly, hypothyroidism is associated with increased cardiovascular risk factors as well as subclinical and diagnosed cardiovascular disease, both of which are thought to predispose one to AF. However, the relationship between hypothyroidism and AF was evaluated in the Framingham Heart Study and was not found to be statistically significant. 10 The QT interval is often prolonged in hypothyroidism due to prolonged ventricular action potential.11 This is indicative of increased ventricular irritability and in turn can lead to acquired Torsades de pointes. Varying degrees of atrioventricular block and low QRS complexes a...

Thyroid hormones greatly impact energy homeostasis in the heart, and excess thyroid hormone leads to a hypermetabolic state. The thyroid gland produces two hormones, thyroxine (T4) and triiodothyronine (T3). The major form of thyroid hormone is thyroxine, which acts mostly as a prohormone. 1 The set point for thyroid hormone production and secretion by the thyroid gland is regulated by the hypothalamic thyrotropin-releasing hormone (TRH), which stimulates the production and secretion of thyroid stimulating hormone (TSH) that, in turn, controls thyroid hormone concentrations. Most of T4 is converted to biologically active T3 through the removal of an iodide by deiodinases. While there are three types of deiodinases, most of the circulating T3 is derived from Type 1; Type 1 activates thyroid hormone by converting T4 to active T3, and it deactivates thyroid hormone by converting T4 to inactive reverse T3 (rT3) or to T2.2 It is important to note that there is no significant intracellular deiodinase activity in cardiac cells; therefore, the heart relies mainly on the action of T3 since that is the hormone transported into the myocyte.3 Both T4 and T3 circulate in the blood almost entirely (> 95%) bound to thyroxine-binding globulin and a family of other hormone-binding proteins. The remaining unbound T3 is transported through a variety of membrane transport proteins and subsequently to the cell nucleus to regulate expression of selected genes. 4 Molecular Mechanisms of Thyroid Hormone ActionThe intracellular cardiac effects of thyroid hormone are exerted by two mechanisms: genomic and nongenomic. Several of the main effects are exerted through genomic actions, which consist of T3 linking to nuclear receptors that bind to thyroid-responsive elements (TREs) in the promoter of target genes. 5 There are several key myocyte-specific genes regulated by this mechanism (Table 1). 3 Binding of thyroid hormone to these TREs can either activate or repress gene expression, thereby regulating the expression of specific messenger RNA and translated proteins and producing different tissue-specific responses. Importantly, thyroid hormone-regulated genes are also involved in structural and regulatory proteins, and long-term exposure to high T3 levels can increase the synthesis of cardiac proteins, leading to cardiac hypertrophy and dysfunction. Extranuclear nongenomic activities provoke rapid changes in the cardiac myocyte plasma membrane and cytoplasmic organelles. These include changes in sodium, potassium, and calcium ion channels; changes in actin cytoskeleton polymerization; and changes to the intracellular signaling pathways in the heart and smooth muscle cells.Both genomic and nongenomic mechanisms act together to regulate cardiac function and cardiovascular hemodynamics.2 For example, they upregulate expression of the sarcoplasmic reticulum calcium-activated ATPase and downregulate phospholamban expression, thereby enhancing myocardial relaxation. They also increase expression of the more rapid contractile isoforms of the myo...