Effects of thyroid hormones on the heart

Vargas‐Uricoechea, Hernando; Bonelo-Perdomo, Anilza; Sierra‐Torres, Carlos H.

doi:10.1016/j.arteri.2014.07.003

Cited by 115 publications

(130 citation statements)

References 64 publications

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“…4 Also noted are elevations in both C-reactive protein and homocysteine (Table 2). 1,5 Thyroid hormones affect endothelial functions mediated by thyroid hormone receptor (THR)-α 1 and THR-β. Activation of THR-α 1 increases coronary blood flow, decreases coronary resistance in mouse models, and increases production of nitric oxide in endothelial and vascular smooth muscle cells.…”

Section: Cardiometabolic Changes In Hypothyroidismmentioning

confidence: 99%

Hypothyroidism and the Heart

Udovcic

Pena

Patham

et al. 2017

Methodist DeBakey Cardiovascular Journal

241

165

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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...

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Section: Cardiometabolic Changes In Hypothyroidismmentioning

confidence: 99%

Hypothyroidism and the Heart

Udovcic

Pena

Patham

et al. 2017

Methodist DeBakey Cardiovascular Journal

241

165

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“…Other possible hemodynamic changes include an increased systemic vascular resistance, pericardial effusion, endothelial dysfunction, impaired relaxation and increased ventricular filling time, ventricular asynchrony, QT prolongation with risk of Torsades de Pointes, heart failure, and cardiogenic shock [13,[16][17][18]. The development of overt heart failure is rare, however, owing to decreased oxygen consumption in cardiac myocytes during the hypothyroid state [14].…”

Section: Discussionmentioning

confidence: 99%

“…Thyroid hormone binds to intracellular thyroid hormone receptors (TR), which then bind to thyroid hormone response elements (TRE) in regulatory regions of specific genes [14]. Of the numerous receptor isoforms TRalpha1 is the isoform most significantly expressed in the heart, regulating genes corresponding to contractility, conduction, pacemaker automaticity, and cellular growth [14]. In a relative absence of thyroid hormone, as in hypothyroidism, TRs act along with co-repressors to silence genetic expression and shut off transcription.…”

Section: Discussionmentioning

confidence: 99%

Differential reversibility in heart failure due to hypothyroidism: A series of contrasting cases with review of literature

Roberto¹,

Aung²,

Agarwal³

et al. 2016

IJCRI

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International Journal of Case Reports and Images (IJCRI) is an international, peer reviewed, monthly, open access, online journal, publishing high-quality, articles in all areas of basic medical sciences and clinical specialties.Aim of IJCRI is to encourage the publication of new information by providing a platform for reporting of unique, unusual and rare cases which enhance understanding of disease process, its diagnosis, management and clinico-pathologic correlations.IJCRI publishes Review Articles, Case Series, Case Reports, Case in Images, Clinical Images and Letters to Editor. Website: www.ijcasereportsandimages.comDifferential reversibility in heart failure due to hypothyroidism:A series of contrasting cases with review of literature E. Samuel Roberto, Thein Aung, Ajay Agarwal, Roberto J. Colón ABSTRACT Introduction: Ranking third as a leading cause of heart failure in the United States, dilated cardiomyopathy (DCMP) affects 5 in 100,00 adults with an eight-year mortality rate between 70-80%. In the setting of hypothyroidism, DCMP is unique due to its potential reversibility with medical therapy. Thyroid hormone affects cardiac physiology and intracellular calcium regulation via SERCA2 and phospholamban, with concentrations of phospholamban most numerous in the ventricles. Administration of thyroid hormone can restore contractile function. However, the relationship between disease timeline and reversibility in DCMP due to hypothyroidism has not been previously described. Case Series: A 65-year-old Caucasian male presented with new onset severe dyspnea and fatigue. Thyroid-stimulating hormone was markedly elevated. Following levothyroxine therapy, his dilated cardiomyopathy reversed and returned to normal within six months. LVEF improved from 15-45% with decreased chamber dilation. A 60-year-old Caucasian female presented minimally responsive in overt heart failure due to myxedema coma. History revealed chronically uncontrolled hypothyroidism. TSH was significantly elevated. Following prolonged hospitalization and intravenous levothyroxine therapy, her clinical status began to reverse. LVEF improved from 10-25%, with decreased chamber dilation. Conclusion:Once the underlying mechanism of heart failure was addressed, the cases displayed varying recovery of contractility following thyroid hormone replacement. This may suggest that with longer duration of uncontrolled disease and consequent cardiac structural remodeling, the reversibility diminishes into irreversibility. These cases underscore the need to identify and treat early any contributing hypothyroidism in the setting of new onset dilated cardiomyopathy, as reversibility may be at stake.

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“…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.…”

Section: Role Of Thyroid Hormone In Energy Homeostasismentioning

confidence: 99%

Hypothyroidism and the Heart

Osuna

Udovcic

Sharma

2017

Methodist DeBakey Cardiovascular Journal

132

123

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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...

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Effects of thyroid hormones on the heart

Cited by 115 publications

References 64 publications

Hypothyroidism and the Heart

Hypothyroidism and the Heart

Differential reversibility in heart failure due to hypothyroidism: A series of contrasting cases with review of literature

Hypothyroidism and the Heart

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