Introduction

Thyrotoxicosis is a condition which occurs when there is an elevated level of thyroid hormones in the circulation and tissues.¹ This in turn could significantly affect the cardiovascular system and cause various complications that impact individuals' health by dysregulating metabolic rate and placing higher demands on the heart.² The cardiovascular problems associated with thyrotoxicosis are often termed cardio-thyrotoxic syndrome.¹ Thyrotoxicosis can arise from several underlying causes, including an overactive thyroid, commonly observed in in hyperthyroidism, thyroiditis, or excessive intake of external thyroid hormones.³ Common causes include Graves' disease, toxic multinodular goitre, and toxic adenoma.^2,3 Additionally, some incidences result from external factors, such as unintentional or deliberate intake of excessive thyroid hormones, a condition known as thyrotoxicosis factitia, which is linked with the use of diet pills, contaminated food sources such as ground beef, or accidental overdoses of thyroid medication ⁴.

Thyroid hormones play a fundamental role in cardiovascular regulation, and thyrotoxicosis places significant strain on the heart, often resulting in various cardiac complications.¹ Individuals with thyrotoxicosis face an elevated risk of developing disorders such as atrial fibrillation, congestive heart failure, cardiomyopathy, and electrocardiographic abnormalities, including atrioventricular nodal block.⁵ Typically, systolic blood pressure is elevated due to increased cardiac output, leading to altered hemodynamic stability. Additionally, thyrotoxicosis has been associated with a hypercoagulable state, marked by elevated levels of coagulation factors, heightening the risk of thromboembolic events, including transient intracardiac thrombi.⁶ Moreover, spasms of coronary arteries can lead to ischaemic events even in individuals with structurally normal coronary arteries.⁷ These cardiovascular manifestations contribute to the increased morbidity and mortality associated with thyrotoxicosis, proving the importance of early detection and management.¹

Pathophysiology of thyrotoxicosis and cardiovascular outcomes

Thyrotoxicosis impacts the cardiovascular performance through several mechanisms. The overproduction of thyroid hormones directly affects heart muscle, resulting in increased cardiac output, reduced systemic vascular resistance, and a hyperdynamic state.¹ Clinically, this manifests as palpitations, tachycardia and irregular rhythms, such as atrial fibrillation, which can increase stress on the heart and, in severe cases, lead to cardiac failure. The phenomenon is often referred to as "thyrotoxic cardiomyopathy".⁸ Thyroid hormones, especially triiodothyronine, bind to receptors on cardiac myocytes, enhancing their contractility and relaxation. In excess, it leads to an elevated heart rate and stroke volume, thereby influencing cardiac performance.⁹ Furthermore, excess thyroid hormone heightens the heart's sensitivity to epinephrine, increasing heart rate and contractility through Beta-Adrenergic receptor sensitisation.¹⁰ Additionally, thyroid hormones can promote vasodilation, relaxation of smooth muscle in blood vessels, by activating the renin-angiotensin-aldosterone system, which lowers systemic vascular resistance and allows blood to circulate more freely. ^{5, 10}

Key cardiovascular complications of thyrotoxicosis

Excessive levels of thyroid hormones profoundly affect cardiac function, increasing metabolic demand and disrupting normal hemodynamic, leading to various complications such as arrhythmias, hypertension, heart failure, and thromboembolic events. However, it's important to note that many of these complications are reversible through proper regulation of thyroid hormone levels.¹¹ The following article outlines the key cardiovascular complications associated with thyrotoxicosis, highlighting the urgent need for early detection, effective management strategies, and the potential for positive outcomes.

Atrial fibrillation and other cardiac arrhythmias

Atrial fibrillation (AF) is one of the most prevalent and serious cardiovascular complications of thyrotoxicosis.¹² Excess thyroid hormones enhance beta-adrenergic receptor activity, increasing the sinoatrial (SA) node's automaticity and shortening the refractory period in atrial myocytes.¹³ This dysregulation predisposes individuals to irregular and rapid atrial electrical activity, culminating in AFn.^12,13,14 Additionally, the persistent tachyarrhythmia associated with AF can lead to ventricular dysfunction and heart failure, especially in patients with pre-existing structural heart disease.¹³ In some instances, ventricular arrhythmias and supraventricular tachycardias may also arise, further complicating the cardiovascular burden.^{15, 16} Given the risks linked to AF, the management of thyrotoxicosis-related arrhythmias often necessitates the use of beta-blockers and anticoagulation therapy. ^{12, 13,15,16}

Hypercoagulability and thromboembolic events

Thyrotoxicosis is characterised by a hypercoagulable state, which elevates the risk of thromboembolic complications, including deep vein thrombosis (DVT), pulmonary embolism (PE), and ischemic stroke.¹⁴ This prothrombotic tendency can be attributed to increased coagulation factors such as von Willebrand factor, fibrinogen, and factor VIII, along with reduced fibrinolysis and endothelial dysfunction.²⁰ The risk of thromboembolic events is especially pronounced in patients with atrial fibrillation, where blood stasis in the left atrium can facilitate thrombus formation.¹⁴ Consequently, anticoagulation therapy may be advisable for individuals with persistent atrial fibrillation and additional risk factors, by established guidelines for stroke prevention in individuals affected by hyperthyroidism.^{14, 20}

Systolic hypertension and vascular dysfunction

Individuals with thyrotoxicosis frequently exhibit isolated systolic hypertension, characterised by an elevated systolic blood pressure (SBP) while the diastolic blood pressure (DBP) remains within a normal or low range.¹⁷ This phenomenon arises from the vasodilatory effects of thyroid hormones, which reduce systemic vascular resistance (SVR) while enhancing cardiac contractility and stroke volume. A notable feature of hypertension due to thyrotoxicosis is the enlarged pulse pressure, which is the difference between SBP and DBP and may contribute to increased arterial stiffness over time.¹⁸ Persistent systolic hypertension can impose additional stress on the left ventricle, potentially leading to left ventricular hypertrophy and diastolic dysfunction.^17,18 Furthermore, individuals with pre-existing hypertension may experience a deterioration of their condition, driven by the heightened adrenergic activity associated with thyrotoxicosis.¹⁹ Medications such as beta-blockers can be employed to manage blood pressure fluctuations and mitigate the cardiovascular risks linked to elevated thyroid hormone levels.¹⁷ Administering calcium channel blockers, via parenteral routes, is to be avoided due to the possible adverse effects of reducing blood pressure leading to hypotension and cardiovascular failure.¹⁸

Heart failure: high-output and low-output states

Thyrotoxicosis has a significant effect on the way the heart functions, which results in two distinct types of heart failure, high output and low output, depending on the progression of the disease and the presence of underlying cardiac conditions.²¹ High-output heart failure occurs in the initial stages of thyrotoxicosis and is generally recognised to be due to enhanced cardiac contractility, tachycardia and elevated cardiac output. With the manifestation of cardiac failure, physical symptoms may become more apparent, such as shortness of breath on exertion (paroxysmal), oedema of the periphery, or effort intolerance. Prolonged strain on the cardiac muscles thus leads to ventricular structural changes, contractile fatigue, and systolic dysfunction with a decrease in ejection fraction and a decrease in cardiac function leading to low-output heart failure.²² When thyrotoxicosis is combined with pre-existing (e.g., ischemic or valvular) heart disease, this functional decompensation may be more readily demonstrated as acute (often life-threatening) heart failure. Maintenance of euthyroidism is essential to improve the hemodynamics in thyrotoxic heart failure and to prevent further heart damage.²¹

Cardiomyopathy and left ventricular hypertrophy

Persisting high thyroid levels can lead to thyrotoxic cardiomyopathy. This condition leads to changes in the heart muscle's make-up and its function.¹⁰ Elevated levels of thyroid hormones increases the oxygen demand of the, causing more stress, and altering the ability of cardiac cells to handle calcium. These pathological changes lead to left ventricular hypertrophy, fibrosis of the myocardium, and diastolic dysfunction. In chronic cases, the heart chambers could lead to permanent dilation (dilated cardiomyopathy) and lead to worse heart failure with reduced ejection fraction. But, with early diagnosis and treatment options, this condition can often be rectified, reinforcing the importance of early diagnosis and thyroid function stabilisation.²²

Coronary artery spasm and angina

Although there is no evidence of a causal relationship between thyrotoxicosis and coronary artery disease (CAD), elevated thyroid hormone levels can lead to coronary artery spasm, causing angina symptoms despite normal arterial function. The mechanism of this is thought to be due to changes in the lining of the arteries, elevated sympathetic stress, and a heightened response to vasoconstrictive stimuli.²³ The need for more oxygen caused by elevated contractility of the heart and continuous tachycardia can lead to worsening ischemic presentations. In some individuals with hyperthyroidism, acute coronary syndrome (ACS) may develop, particularly in patients predisposed to atherosclerosis of the coronary arteries. The management of ischaemic chest pain caused by thyrotoxicosis requires normalising the serum thyroid hormone, beta blocker, and the use of drugs that alter vascular reactivity (eg, calcium-channel blockers and nitrates) to minimise the risk of coronary artery spasms.²⁴ 

Summary

Thyrotoxicosis attributes a significant threat to cardiovascular health, including arrhythmias, hypertension, heart failure, and thromboembolic events. The substantial impact of elevated thyroid hormones on heart function demands early diagnosis and effective treatment to reduce cardiovascular risks. As many of these complications are reversible with proper management of thyroid hormone, initiation of early and focused therapies such as antithyroid medications, beta-blockers, along with more definitive treatment approaches such as radioactive iodine ablation or thyroidectomy, are essential in improving patient outcomes and maintaining long-term heart health.