A case of congestive heart failure due to reversible dilated cardiomyopathy caused by hyperthyroidism.

Abstract: Thyrotoxicosis is an uncommon cause of low-output congestive heart failure. The case of a 41-year-old male who presented with severe symptomatic congestive heart failure, and was subsequently diagnosed with dilated cardiomyopathy secondary to hyperthyroidism, is presented. The cause of his hyperthyroidism was Graves disease. Despite an initial left ventricular systolic ejection fraction of 20% and evidence of global hypokinesis on echocardiography, treatment with antithyroid agents led to rapid improvement in his clinical status and normalization of his ejection fraction. The proposed mechanisms underlying the development of systolic dysfunction in thyrotoxicosis are discussed, and the literature on similar cases previously reported is reviewed.

Key Words: congestive heart failure, dilated cardiomyopathy, hyperthyroidism, thyrotoxicosis.

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Thyrotoxicosis is commonly associated with a hyperdynamic circulatory state, which can lead to high output congestive heart failure. A case of dilated cardiomyopathy/low-output congestive heart failure due to hyperthyroidism that was reversed with treatment of thyrotoxicosis is presented. The pathophysiologic mechanisms are discussed, and similar cases reported in the literature are reviewed.

Case Report

A 41-year-old, previously healthy male presented with a two-week history of fatigue, palpitations, orthopnea, and paroxysmal nocturnal dyspnea. There was no history of chest pain or fever, but he had noticed recent heat intolerance, frequent bowel movements, and an unintentional 10 to 15 lb weight loss over the previous 3 months. There was no previous history of cardiorespiratory problems, hypertension, diabetes, or risk factors for coronary artery disease. The patient was a nonsmoker and drank alcohol socially. On examination he was afebrile, the respiratory rate was 30/min and the blood pressure was 100/60 mm Hg with a regular pulse of 110 bpm. He had mild bilateral proptosis, lid retraction and lid lag, and the thyroid gland was diffusely enlarged at about 40 g (normal 15-20 g). The cardiovascular examination was remarkable for a jugular venous pressure of 10 cm above the sternal angle, a displaced point of maximal impulse, an S3 and bilateral pitting edema. There were bilateral crackles on chest examination. The neurologic examination demonstrated tremor of the outstretched extremities, diffuse hyperreflexia (3/4) and evidence of proximal muscle weakness (4/5). Chest radiograph revealed cardiomegaly, bilateral air space disease, peribronchial cuffing, and pleural effusions compatible with pulmonary edema. Electrocardiogram showed sinus tachycardia with nonspecific ST-T wave changes. A transthoracic echocardiogram demonstrated left ventricular enlargement with global left ventricular systolic dysfunction, hypokinetic right ventricle, and moderate bi-atrial enlargement. There was diffuse global hypokinesia, and the estimated ejection fraction was 20%. Laboratory investigations were significant for normal electrolytes, renal function, and cardiac enzymes. The total thyroxine was 17.8 [micro]g/dL (4.2-13), total T3 192 ng/dL (55-170), free T4 was 3.5 ng/dL (0.7-1.5), thyroid-stimulating hormone was less than 0.03 U/L (0.5-5.0) and thyroid-stimulating immunoglobulin was elevated at 20.7 U/L (negative < 1.0). The [I.sup.131] uptake was elevated at 71% at 2 hours and 78% at 24 hours, and was uniform in distribution, consistent with diffuse toxic goiter. The patient had a myocardial perfusion single photon emission computed tomography study which did not demonstrate any abnormality of myocardial perfusion.

The diagnosis of dilated cardiomyopathy likely secondary to thyrotoxicosis was made, and the patient was treated with digoxin, diuretics, angiotensin-converting enzyme inhibitor, high dose propylthiouracil, glucocorticoids, and [beta]-adrenergic antagonists. The patient's condition subsequently improved, and a repeat systolic ejection fraction 1 month later on a myocardial perfusion single photon emission computed tomography study was 51%. He was subsequently treated with [I.sup.131], after which he became hypothyroid and is currently on levothyroxine replacement. The repeat echocardiogram showed normal left ventricular systolic and diastolic function with no evidence of valvular/wall motion abnormalities.

Discussion

The effects of thyroid hormone on the cardiovascular system are myriad and include an increase in inotropy, chronotropy, and preload, and a reduction in afterload. (1-2) Hyperthyroidism commonly causes a sustained hyperkinetic circulatory state resulting both from the direct effect of thyroid hormone on cardiac contractility and rate, as well as an indirect effect on peripheral circulation leading to increased blood volume and vasodilation. The development of a "high-output" heart failure in untreated thyrotoxicosis is well recognized and is also known to occur in other conditions, including Paget disease of the bone, beri beri, and severe anemia. (3) There has, however, been evidence of a "low-output" congestive heart failure with reduced systolic ejection fraction occurring in hyperthyroidism as well. The pathophysiology of this low-output heart failure is unclear. It has been hypothesized that thyroid hormone, which translocates to the nucleus of the cardiac cells, may alter the expression of certain cardiac proteins--including myosin heavy chain and sarcoplasmic reticulum adenosine triphosphatase in the cardiac myocytes--and lead to contractile dysfunction. (4) Another proposed etiology is the presence of chronic tachycardia in thyrotoxicosis, leading to tachycardia-related cardiomyopathy. Chronic tachycardia is speculated to cause myocardial cell energy depletion, abnormalities in myocyte alignment, and abnormal calcium handling. (5) Thyrotoxicosis has also been shown to prevent the rise of left ventricular ejection fraction during exercise. (6) Cardiac atrophy, akin to the skeletal muscle atrophy due to altered protein composition, has also been proposed to cause dilated cardiomyopathy in thyrotoxicosis. In autopsy studies of humans and animals with hyperthyroidism, left ventricular dilation and congestive heart failure have been reported in the absence of other forms of heart disease, and interstitial and perivascular fibrosis, myocardial hypertrophy, necrosis, and cell edema have been reported histologically. (7)

There have been other reports in the literature of low-output, reversible congestive heart failure caused by hyperthyroidism. Umpierrez et al (8) published a study of a series of seven patients with hyperthyroidism and congestive heart failure in which the mean left ventricular systolic ejection fraction increased from 28 to 55% after treatment of thyrotoxicosis. The ejection fraction normalized in 5 patients, and an improvement from severe to mild systolic dysfunction was noted in the other two patients. Goldman et al described a 56-year-old patient with heart failure who was noted to have global left ventricular hypokinesis and an ejection fraction of 35%, which increased to 55% in 3 weeks after the treatment of the patient's hyperthyroidism. (8) Kantharia et al (9) reported a 52-year-old female with congestive heart failure and global hypokinesis with an ejection fraction of 30% at admission that improved to 58% with the treatment of her thyroid disease. Riaz et al (10) also presented three case reports of reversible dilated cardiomyopathy due to thyrotoxicosis. Other investigators have also reported cases of low-output congestive heart failure associated with thyrotoxicosis. (11-13) In general, the heart failure is reversible and responds dramatically to the treatment of hyperthyroidism, and most patients described have had complete normalization of their cardiac abnormality, and have been able to discontinue medication for congestive heart failure.

The patient discussed in this report, in retrospect, had symptoms consistent with hyperthyroidism for approximately 3 months before his presentation with heart failure. Despite clinical and echocardiographic evidence of severe left ventricular dysfunction at presentation, the patient responded dramatically to appropriate antithyroid therapy, and had complete normalization of his left ventricular function. He is currently 2 years post-treatment, and remains asymptomatic and in excellent health on levothyroxine supplementation only.

Conclusion

Thyrotoxicosis is an uncommon cause of low-output congestive heart failure and dilated cardiomyopathy. Although the exact pathophysiologic mechanism is not clear, it should be considered in the differential diagnosis, as the heart failure is potentially reversible with restoration of the euthyroid state.

The significant problems we face cannot be solved at the same level of
thinking we were at when we created them.
--Albert Einstein

Accepted January 8, 2004.

References

1. Woebker KA. Thyrotoxicosis and the heart. N Eng J Med 1992;327:94-98.

2. Polikar R, Burger AG, Scherrer U, et al. The thyroid and the heart. Circulation 1993;88:631-637.

3. DeGroot WJ, and Leonard JJ. Hyperthyroidism as a high output state. Am Heart J 1970;79:265-275.

4. Rohrer DK, Hartong R, Dillman WH. Influence of thyroid hormone and retinoic acid on slow sarcoplasmic reticulum Ca+ ATPase and myosin heavy chain gene expression in cardiac myosites. J Biol Chem 1991;266:8636-8646.

5. Cruz FE, Cheriex EC, Smeets JL. Reversibility of tachycardia induced cardiomyopathy after cure of incessant supraventricular tachycardia. J Am Coll Cardiol 1990;16:739-744.

6. Forfar JC, Muir AI, Sawers SA, et al. Abnormal left ventricular function in hyperthyroidism. N Eng J Med 1982;307:1165-1170.

7. Sandler G, Wilson GM. The production of cardiac hypertrophy by thyroxine in the rat. Q J Exp Physiol 1949;44:282.

8. Umpierrez GE, Challapalli S, Patterson C. Congestive heart failure due to reversible cardiomyopathy in patients with hyperthyroidism. AM J Med Sci 1995;310:99-102.

9. Kantharia BK, Richards HB, Battaglia J. Reversible dilated cardiomyopathy: an unusual case of thyrotoxicosis. AM Heart J 1995;129:1030-1032.

10. Riaz K, Forker AD, Isley WL, et al. Hyperthyroidism: curable cause of congestive heart failure. CHF 2003;9:40-46.

11. Watanabe E, Ohsawa H, Noike H, et al. Dilated cardiomyopathy associated with hyperthyroidism. Int Med 1995;34:762-767.

12. Goldman LE, Sahlas DJ, Sami M. A case of thyrotoxicosis and reversible systolic cardiac dysfunction. Can J Cardiol 1999;15:811-814.

13. Baurlein EJ, Chakklo CS, Kessler KM. Reversible dilated cardiomyopathy due to thyrotoxicosis. Am J Cardiol 1992;70:132.

RELATED ARTICLE: Key Points

* Thyrotoxicosis can lead to low-output congestive heart failure secondary to dilated cardiomyopathy.

* Treatment of thyrotoxicosis often leads to reversal of heart failure and complete normalization of ejection fraction.

* Although uncommon, thyrotoxicosis should be considered in the differential diagnosis of congestive heart failure.

Hasnain M. Khandwala, MD, FRCPC

From the Department of Medicine, Division of Endocrinology, University of Saskatchewan, Saskatoon, SK, Canada.

Reprint requests to Hasnain M. Khandwala, MD, FRCPC, Room 3654, Division of Endocrinology, Royal University Hospital, 103 Hospital Drive, Saskatoon, SK, S7N 0W8, Canada. Email: [e-mail]