Thyroid Disease and the Heart

The positive chronotropic effect of thyroid hormones derives mainly from a direct action of T3 on genes regulating cardiac-pacemaker activity.

“The positive chronotropic effect derives mainly from a direct action of T3 on the genes that regulate the activity of the cardiac-pacemaker.”

At the cardiac level, stimulation of β-type thyroid-hormone receptors up-regulates calcium-dependent ATPase pumps of the endoplasmic reticulum and reduces expression of Phospholamban, resulting in increased myocardial relaxation and a positive inotropic effect.

“At the cardiac level, stimulation of the β-type thyroid-hormone receptors determines an up-regulation of the calcium-dependent ATPase pumps of the endoplasmic reticulum and a reduced expression of the Phospholamban protein resulting in an inhibitory action.”

At the peripheral level, stimulation of α-1 thyroid receptors on endothelial and smooth muscle cells reduces peripheral resistance, causing a decrease in diastolic pressure.

“At the peripheral level, the stimulation of the α-1 thyroid receptors, expressed by the endothelial and smooth muscle cells of the vessels, reduces peripheral resistance causing a decrease in diastolic pressure [1, 6].”

Patients with overt hyperthyroidism experience atrial fibrillation at a rate ranging from 10 to 25%, with higher percentages in males over 60 years and in those with higher free T4 values.

“Patients with overt hyperthyroidism, at a rate ranging from 10 to 25%, experience atrial fibrillation (AF) with even higher percentages in males over 60 years of age and in those with higher free T4 (FT4) values.”

T3 induces an increase in expression of β1-adrenergic receptors on myocardiocytes, increasing myocardial sensitivity to catecholamines, while simultaneously inhibiting cardiac expression of catalytic isoforms of adenylate-cyclase, keeping the endocellular response unchanged.

“Indeed, T3 induces an increase in the expression of β1-adrenergic receptors on myocardiocytes, increasing myocardial sensitivity to the action of catecholamines, as it simultaneously inhibits the cardiac expression of the catalytic isoforms of adenylate–cyclase, keeping the endocellular response unchanged [1, 6].”

Only 5% of subjects with thyrotoxicosis under the age of 60 have atrial fibrillation.

“Conversely, only 5% of subjects with thyrotoxicosis under the age of 60 have AF [1, 6].”

Tachyarrhythmia associated with hemodynamic alterations in hyperthyroidism is often the cause of high-rate heart failure, especially in patients with concomitant risk factors.

“The presence of tachyarrhythmia associated with the previously described hemodynamic alterations is often the cause of high-rate heart failure, especially in patients with concomitant risk factors [1, 6].”

At the renal level, reduced perfusion from peripheral vasodilation activates the renin-angiotensin-aldosterone system, with sodium-retentive action and increased circulating volume.

“At the renal level, this effect leads to a reduced perfusion with consequent activation of the renin–angiotensin–aldosterone system (to which a direct effect of T3 via thyroid β-1 receptors probably also contributes) with a sodium-retentive action and an increase in circulating volume [1, 6].”

Thyrotoxicosis determines an imbalance of coagulative homeostasis towards hypercoagulability and reduced fibrinolysis, characterized by increased circulating levels of factor VIII, IX, fibrinogen and Von Willebrand factor.

“thyrotoxicosis determines an imbalance of coagulative homeostasis towards a state of hypercoagulability and reduced fibrinolysis characterized by an increase in the circulating levels of factor VIII, IX, fibrinogen and Von Willebrand factor [1, 6]”

A role of catecholaminergic stimulation in the positive chronotropic effect of thyroid hormones seems unlikely.

“Although a role of cathecolaminergic stimulation has been hypothesized, this seems unlikely.”