CLINICAL ABNORMALITIES OF THE HEART

(Table12-6)

Table 12-6 Cardiovascular signs and symptoms in patients with hyperthyroidism*

Physical examination	Hemodynamic changes	EKG/X-ray/Ultrasound
Tachycardia at rest	Cardiac output+	QT interval -
Pulse amplitude +	Myocardial contractility +	PR interval -
Systolic murmur	Systolic/diastolic function +	STsegm elev
Mitral valve prolapse	Systolic blood pressure +	Atrial fibrill.
1st heart sound +	Blood volume +	W-P-W syndr.
Possible 3rd heart sound	Venous resistance +	Contraction times -
Ankle swelling	Arterial resistance -
Unspecific symptoms, (palpitations dyspnea, chest pain)	Diastolic blood pressure -	Card. Hypertrophy
	Circulation time ++

*Modified from Kahaly GJ: The thyroid and the heart. Thyroid International 4,1998

The biochemical actions of thyroid hormone on the heart have been described in Chapter 10.

Thyrotoxicosis increases the demands on the heart both by chronotropic and inotropic alterations. Cardiac output is much increased on the basis of increased stroke volume and rapid heart rate.¹⁷³ It is possible that the metabolic efficiency of heart muscle is decreased. Irritability of the heart is increased. Investigation with stress echocardiography shows in hyperthyroidism impaired chronotropic, contractile, and vasodilatatory cardiovascular reserves, that are reversible upon conversion to euthyroidism^173a.

Mitral valve prolapse is reported to have been present in 43% of a series of thyrotoxic patients, whereas it was present in 18% of the control group.¹⁷⁴ This incidence may be due to increased adrenergic tone, autoimmunity, or the augmented cardiac output associated with thyrotoxicosis. Most patients with thyrotoxicosis are adults. Many, especially those with toxic nodular goiter, are in the 50- to 70-years age group, which has a relatively high incidence of organic heart disease anyway. (174a) Thus, it is not surprising that cardiac abnormalities are prominent among the symptoms of thyrotoxicosis. Frequent premature beats and paroxysmal tachycardia sometimes appear in thyrotoxic patients and may be disturbing to the patient. Atrial fibrillation occurs in thyrotoxicosis with or without previous heart disease. It may be episodic or may become fixed during the period of hyperthyroidism. Attempts to correct this arrhythmia to normal in-patients with persistent atrial fibrillation are usually unsuccessful while they are thyrotoxic. Once they have become euthyroid, the fibrillation may revert spontaneously or may be converted medically or by electroconversion. About two-thirds of patients undergo spontaneous reversion to sinus rhythm after receiving therapy for thyrotoxicosis, usually within a month. If fibrillation persists after the patient has been euthyroid for 4 months, spontaneous conversion is unlikely to occur.¹⁷⁵ It is wise to always evaluate thyroid function in clinically euthyroid patients with atrial arrhythmias with or without heart disease as in about 20% of patients TSH tests and/or FT4 point to an overactive thyroid and in 50% of these patients normal sinus rhythm resumes after treatment with antithyroid drugs.¹⁷⁶

Congestive heart failure is a frequent complication in those patients with thyrotoxicosis, who already have organic heart disease and is more prevalent with advancing age. ¹⁷⁷ These patients have mostly a toxic multinodular goiter. Low output congestive heart failure has also described in 25 patients with Graves’ disease with a mean age of 45 years. (177a) In fact, in the older age group, the cardiac symptoms may so dominate the clinical picture that the diagnosis of thyrotoxicosis may be overlooked. Careful attention should be given to this possibility in all patients with resistant congestive heart failure, especially if a goiter is found. Congestive heart failure may occur in patients who have no detectable preexisting organic heart disease.^178,179 It is not always possible to tell how much underlying heart disease is present in a patient with thyrotoxicosis who also has a disorder of rhythm, a cardiac murmur, or congestive heart failure, for all of these conditions may be encountered in thyrotoxicosis alone. It is frequently gratifying to note a return of the findings to normal when the thyrotoxicosis has been corrected.

Angina is worsened if already present, or may be induced de novo.¹⁸⁰ Evidence of myocardial lactate production when the heart is paced at an accelerated rate,¹⁸¹ and normal arteries on angiography after episodes of angina or infarction,¹⁸² have suggested that the changes in thyrotoxicosis are due to an imbalance between O2 demand and supply rather than arterial obstruction. This possibility is corroborated by the finding that coronary artery spasm of an otherwise normal vessel may occur during thyrotoxicosis. ^180,183 Histologic examination of the thyrotoxic heart only shows non-specific abnormalities like necrosis of isolated heart cells, small areas of fibrosis and round cell infiltration.¹⁸⁴

Generally, the cardiac changes found in Graves' disease are entirely reversible, except that longstanding atrial fibrillation due to hyperthyroidism is not always convertible after euthyroidism. It has become evident that even in the mildest forms of thyrotoxicosis subtle cardiac abnormalities may be present. Thus in patients with so-called "subclinical" thyrotoxicosis i.e. suppressed TSH and normal serum free T4 and T3, due to multinodular goiter or TSH-suppressive T4 treatment, mean basal 24h heart rate is increased, there is an augmented risk of atrial premature beats and atrial fibrillation, and left ventricular function and wall thickness are increased.^185-187 There is controversy whether TSH suppressive T4 treatment leads to functional cardiac abnormalities^168,188

The treatment of heart disease in the presence of thyrotoxicosis is no different from its treatment when thyrotoxicosis is absent, but may be more difficult. Rest, salt restriction, diuretic therapy, digitalization and administration of afterload reducers like angiotensin converting enzyme (ACE) inhibitors are in order. Larger than normal doses of digoxin are required, but there is probably no alteration in the ratio of toxic to therapeutic dosage. Atrial fibrillation may be controlled by digoxin, propranolol, or both. Electroconversion is usually successful only after thyrotoxicosis has been resolved for a few months¹⁹⁰.

Hyperthyroidism should be controlled as expeditiously as possible. Congestive heart failure is a contraindication to operation. Most patients with thyrotoxicosis and significant heart disease are now treated with RAI. This treatment may be preceded by a 3- to 6-month course of antithyroid drug therapy to deplete their glands of stored thyroid hormone, a program that lessens any chance of an exacerbation of the heart disease caused by a release of hormone from the gland. Administration of 131I followed by antithyroid drugs, and potassium iodide or ipodate, that also inhibit T4 to T3 conversion, may be used in severely ill patients in whom a prompt response is needed. This method is described in Chapter 11.

Propranolol has been used successfully in the control of tachycardia, and also in patients with congestive heart failure if tachycardia appeared to be adding substantially to the problem. In these instances, possible depression of myocardial contractility by the drug was outweighed by the benefit derived from controlling the rate. In such circumstances, one must proceed with caution and often digoxin should be added.

SUMMARY

In this chapter, a few of the important and characteristic complications of Graves' disease have been considered in some detail. When these complications occur, particular therapeutic problems arise and must be dealt with.

Thyroid storm, fortunately, is becoming rare. Formerly a complication appearing frequently after surgery on the incompletely prepared patient, it is now usually seen in patients with severe thyrotoxicosis who have neglected therapy or who have an added medical problem, such as an acute infection. Storm may be looked upon as a sudden and violent exacerbation of the signs and symptoms of thyrotoxicosis. Clinically, it is characterized by fever, extreme tachycardia, varied disorders of heart rhythm, and nervous hyperirritability rapidly progressing to exhaustion and often to coma. Mortality is high. A special form of thyroid storm is characterized by apathy and muscle weakness. It is no less serious.

The treatment of thyroid storm should include use of antithyroid drugs and iodide, and also general supportive measures such as cooling, oxygen, transfusions, repletion of electrolytes, nutritional repletion, antibiotics if indicated sedation, and adrenal corticoids. Control of many of the aspects of thyroid storm, especially tachycardia, may be achieved by the use of propranolol.

The infiltrative ophthalmopathy of Graves' disease (GO) usually occurs during a period of thyrotoxicosis, but may appear when there is no thyrotoxicosis or even when there is hypothyroidism. There is evidence that autoimmune mechanisms in the retroocular muscles stimulate preadipocytes and fibroblasts to production of glycosaminoglycans (Gags) leading to water retention and edema and ultimately fibrosis. The event responsible for retroocular autoimmune reactions is most probably the retrobulbar localized TSH-R as the primary antigen (possibly overexpressed) interacting with T cells directed against this antigen. In these autoimmune reactions circulating antibodies play a role as well. GO presents a therapeutic problem, sometimes of stupendous proportions. If simple local measures fail to halt the progress of the ophthalmopathy, glucocorticoids, surgical decompression of the orbits, or radiotherapy to the orbit may be required, and thyroid ablation may also be useful.

The curious deposits of a material rich in glycosaminoglycans in the skin of the lower legs and sometimes over the phalanges are discussed in some detail. This material is seen only in patients with Graves' disease and usually coincides with infiltrative ophthalmopathy. Its appearance has no direct relationship to the level of thyroid function.

Cardiac insufficiency in the course of toxic goiter is looked upon as the effect, in most instances at least of thyrotoxicosis on an already diseased heart. There may be younger patients who sustain permanent heart damage from severe thyrotoxicosis, and long-continued thyrotoxicosis in older age groups may be the only definable etiologic factor in congestive heart failure. The chief indication for treatment in cardiac insufficiency occurring in thyrotoxicosis is to abolish the thyrotoxicosis, but the usual cardiotonic, diuretic and sometimes vasodilatory measures should be employed as well.