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Thyroid Disease and the Heart Heart 2000;84:455–460 production of T3, owing to hypersecretion by GENERAL CARDIOLOGY the thyroid gland, and an increase in the peripheral monodeiodination of T4, which Heart: first published as 10.1136/heart.84.4.455 on 1 October 2000. Downloaded from leads to profound changes in the cardiovas- Thyroid disease and the heart cular system through both nuclear and non- nuclear actions at the cellular level.1 A D Toft, N A Boon The interrelation between the direct and Endocrine Clinic, and Department of Cardiology, Royal Infirmary, indirect actions of T3 on the peripheral circu- 455 Edinburgh, UK lation and the heart is shown in fig 1.2 Myocar- dial contractility is increased as a result of a change in the synthesis of myosin heavy chain ardiologists encounter thyroid disor- protein from the â to the á form, increased ders frequently. Hyperthyroidism transcription of the calcium ATPase gene, and Ccauses and may present with atrial enhanced calcium and glucose uptake. These fibrillation, while hypothyroidism is a risk changes make contraction less eYcient and factor for coronary artery disease. Moreover, increase heat production. Afterload is reduced, the use of amiodarone may precipitate a variety with a reduction of as much as 50–70% in sys- of thyroid disorders, and severe heart disease, temic vascular resistance, caused by the direct such as left ventricular failure or acute myocar- eVects of T3 and the indirect eVects of excess dial infarction, can cause confusing distur- lactate production (increased tissue thermo- bances in thyroid function tests. genesis) on vascular smooth muscle. Blood flow, particularly to skin, muscle, and heart, is Hyperthyroidism therefore greatly increased. The preload of the heart rises because blood volume is expanded owing to increases in the serum concentrations Hyperthyroidism is a common condition with a prevalence of approximately 1%; it aVects pre- of angiotensin converting enzyme and erythro- dominantly women aged 30–50 years and is poietin, with resultant increases in renal usually (70%) caused by Graves’ disease which sodium absorption and red cell mass. is characterised by diVuse goitre, orbitopathy, Hyperthyroidism is characterised by a high pretibial myxoedema, and the presence of left ventricular ejection fraction (LVEF) at rest stimulating thyrotrophin (TSH) receptor anti- but, paradoxically, by a significant fall during body in the serum. Most of the remaining cases exercise. Restoration of euthyroidism is accom- (20%) are caused by autonomous production panied by the anticipated rise in LVEF on of thyroid hormones by a nodular goitre. exercise at the same workload and heart rate.3 This reversible “cardiomyopathy” could ex- Effects of thyroid hormones on the plain the reduced exercise tolerance of patients cardiovascular system with hyperthyroidism. Rather than being an http://heart.bmj.com/ Correspondence to: intermediate state between normal left ven- DrADToft, Endocrine The thyroid secretes two active hormones: thy- Clinic, Royal roxine (T4) which is a prohormone and tricular function and left ventricular dysfunc- Infirmary, Edinburgh tri-iodothyronine (T3) which acts as the final tion at rest, the failure of LVEF to increase on EH3 9YW, UK mediator. In hyperthyroidism there is excessive exercise is perhaps better viewed as a conse- quence of the additional burden of exercise induced increase in afterload on a heart performing near its maximum capacity. The characteristic tachycardia is caused by a on October 1, 2021 by guest. Protected copyright. combination of more rapid diastolic depolari- sation and shortening of the action potential of the sinoatrial cells. The refractory period of the atrial cells is also shortened which may explain the well known propensity to atrial fibrillation. There is a complex interaction between thy- roid hormones and the adrenergic system, and many of the clinical features of hyperthy- roidism such as tachycardia, increased pulse pressure, and tremor resemble the heightened â adrenergic state of phaeochromocytoma. However, serum and urinary catecholamine concentrations are normal or even low in hyperthyroidism, and there is no good evidence of greater sensitivity to catecholamines despite an increased density of â1 adrenoceptors in cardiac muscle. It may well be that thyroid hormones and catecholamines act independ- Figure 1. Effects of hyperthyroidism on the cardiovascular system and the ently at the cellular level but share a signalling possible outcomes. TBV, total blood volume; LVEDV, left ventricular end diastolic pathway. This would explain why non-selective volume; LVESV, left ventricular end systolic volume; SV stroke volume; SVR â adrenoceptor antagonists, such as pro- systemic vascular resistance; CO, cardiac output; ↑ increased; ↓ decreased. Solid arrows indicate direct effects, and dashed arrows potential outcomes. pranolol or nadolol, improve but do not abolish *Features for which T3 is directly responsible. many of the symptoms of hyperthyroidism. www.heartjnl.com Education in Heart Clinical features A Most patients with hyperthyroidism complain I aVR V1 V4 of palpitations and breathlessness on exertion, Heart: first published as 10.1136/heart.84.4.455 on 1 October 2000. Downloaded from although symptoms such as weight loss in the presence of a normal or increased appetite, heat intolerance, and irritability tend to pre- II aVL V2 V5 dominate. Established angina may become 456 worse and may, exceptionally, be a new development. Myocardial ischaemia is presum- ably caused by the increased demands of the thyrotoxic myocardium. However, coronary III aVF V3 V6 spasm may be an additional factor and myocardial infarction can occur in the absence of significant atheroma.4 The ECG is usually normal but in severe hyperthyroidism there Rhythm strip: II may be impressive ST-T wave changes in the 25 mm/sec; 1 cm/mV absence of ischaemic chest pain (fig 2). Characteristically there is a sinus tachycardia of approximately 100 per minute with a good LOC 00000–0000 F 40 11797 volume, often collapsing pulse, and a wide pulse pressure. The apex beat is forceful, flow murmurs are common, and there may be a B bruit over the enlarged thyroid gland. Mild I aVR C1 C4 ankle oedema is common but is rarely caused by cardiac failure and is, in part, a manifesta- tion of the reduced day:night ratio of urinary II aVL C2 C5 sodium excretion by the kidneys. Overt cardiac failure is uncommon in hyper- thyroidism and usually occurs in the context of rapid atrial fibrillation in an elderly patient with III aVF C3 C6 pre-existing ischaemic or valvar heart disease. Nevertheless, high output failure is a rare but recognised complication of severe thyrotoxico- II sis. Atrial fibrillation LOC 00000–0000 Speed: 25 mm/sec Limb: mm/mV Chest: 10 mm/mV F 50~ 0.5 – 100 Hz W 05744 A variety of atrial and ventricular tachycardias Figure 2. (A) ECG in a 48 year old woman in whom there was an exacerbation have been described in hyperthyroidism, but of hyperthyroidism 72 hours after treatment with iodine131. (B) The pronounced ST http://heart.bmj.com/ the most common arrhythmia is atrial fibrilla- changes slowly resolved and the tracing was normal three months after the tion. In unselected series 10–15% of patients patient became euthyroid. with thyrotoxicosis were in atrial fibrillation at presentation; however, the prevalence is prob- ably falling because the widespread availability example, a low serum TSH was associated with of accurate tests of thyroid function means that a threefold increase in the incidence of atrial hyperthyroidism is now diagnosed at an earlier fibrillation among clinically euthyroid elderly stage in its natural history. Atrial fibrillation is subjects, 28% of whom developed atrial fibril- on October 1, 2021 by guest. Protected copyright. rare in patients under 40 years of age unless lation during 10 years of follow up.7 there is longstanding severe thyrotoxicosis or Sixty per cent of patients with hyperthyroid coexistent structural heart disease. The preva- atrial fibrillation will revert spontaneously to lence increases with age and is higher in men sinus rhythm within a few weeks of restoration such that in the authors’ experience 50% of of normal tests of thyroid function; approxi- hyperthyroid males over the age of 60 are in mately half of the remainder will respond to atrial fibrillation at presentation. DC cardioversion if serum TSH concentra- In one series, 13% of patients with “idio- tions are normal or raised at the time of the pathic” or “lone” atrial fibrillation attending a procedure. Failure to achieve stable sinus cardiology clinic were found to have overt or rhythm is most likely in those in whom the subclinical hyperthyroidism; the discovery of diagnosis of hyperthyroidism has been delayed. atrial fibrillation, in the absence of an obvious These are usually patients with mild hyperthy- cause, should therefore prompt a request for roidism caused by a small multinodular goitre thyroid function testing.5 Atrial fibrillation may be the dominant in whom only serum T3 may be elevated (T3 feature of hyperthyroidism in older patients toxicosis) and in whom other useful diagnostic and is not necessarily accompanied by pro- features, such as ophthalmopathy or major nounced elevation of the serum concentrations weight loss, are missing. of T3 and T4. Increases of thyroid hormones Hyperthyroid atrial fibrillation is typically within their respective reference ranges associ- resistant to digoxin, caused in part by an ated with a suppressed serum TSH concentra- increase in the renal clearance and the apparent tion (subclinical hyperthyroidism) may be suf- volume of distribution of the drug. It is often ficient to trigger atrial fibrillation in susceptible necessary to add a non-selective â adrenocep- individuals.6 In the Framingham study, for tor antagonist to achieve adequate rate control. www.heartjnl.com Education in Heart Anticoagulation the low serum concentrations of thyroid Systemic embolisation is increased in hyper- hormones are associated with a decrease in thyroid atrial fibrillation, but the risk is diYcult cardiac output, heart rate, stroke volume, and Heart: first published as 10.1136/heart.84.4.455 on 1 October 2000.
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