Takotsubo Cardiomyopathy Can Occur in Patients with Apathetic Hyperthyroidism

Dear Editor:

Takotsubo cardiomyopathy (TC) is a transient, severe, but reversible myocardial stunning with a clinical presentation mimicking acute myocardial infarction. It almost always occurs in elderly women and is usually precipitated by an emotional or physical stressful event. Hyperthyroidism is one of medical conditions that have been associated with TC, but this association has rarely been reported (1), and apathetic hyperthyroidism had never been reported as a cause of TC. We report the clinical case of a female patient with TC associated with apathetic hyperthyroidism due to Graves' disease.

A 70-year-old female patient was admitted to the emergency department with chest pain present for several hours. She had no history of cardiovascular disease, but there was a family history of premature coronary disease. She also reported asthenia and muscle weakness for several weeks. On admission, she presented features of hemodynamic shock. The electrocardiogram showed ST-segment elevations suggestive for myocardial infarction in the apical and lateral leads. Cardiac troponin and BNP levels were elevated. She was transferred rapidly to the catheterization laboratory, but coronary angiography did not demonstrate any lesion (no stenosis or spasm). Interestingly, ventriculography showed a decreased left ventricular ejection fraction (LVEF) with the characteristic apical ballooning of TC (Fig. 1).

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FIG. 1.

Left ventriculogram showing the typical features of apical ballooning characteristic of Takotsubo cardiomyopathy.

Supportive therapy was implemented and her cardiogenic shock improved, but her asthenia and muscle weakness persisted. Several days later, her clinical course was complicated by atrial fibrillation requiring intravenous amiodarone therapy. Thyroid function tests performed on samples drawn before amiodarone introduction showed overt hyperthyroidism: thyrotropin (TSH), 0.01 mIU/L (reference rage [RR] 0.27–5); free thyroxine, 38 pmol/L (RR 11–23); and free triiodothyronine, 7 pmol/L (RR 3–6.9). A thyroid ultrasound showed a hypervascularized goiter, and TSH receptor antibodies were positive, confirming the diagnosis of Graves' disease.

The patient was treated with carbimazole and potassium perchlorate in addition to continuing beta-blocker therapy, and she fully recovered within one month. The electrocardiogram alterations and her LVEF returned to normal. Thyroid function tests also improved.

The clinical features of TC in the setting of hyperthyroidism may have been reported before the description of the Takotsubo syndrome in 1991. In 1988, Bergeron et al. described a 68-year-old woman with exogenous thyrotoxicosis who experienced a severe reversible myocardial ischemic event (2). At presentation, there was a large apical dyskinetic region on echocardiography and myocardial scintigraphy. Cardiac catheterization, which was done after restoring euthyroid state, showed no stenosis or spasm, and the patient's LVEF had returned to normal. The clinical course of this patient is typical for TC. However, the authors might have missed the typical picture of apical ballooning because catheterization was not done at initial presentation.

The exact pathophysiology of TC remains unclear, with many proposed hypotheses. The most widely accepted theory is the catecholamine excess theory where supraphysiologic levels of catecholamines could trigger a switch in the coupling of beta-2 adrenoreceptors from Gs to Gi protein. This “stimulus trafficking” would lead to decreased contractility. A higher density of beta-adrenoreceptors in the apex could explain the typical apical akinesia. Thyroid hormones have stimulatory effects on beta-adrenoreceptor signaling pathways (modest increase in the number of receptors), but they also target several proteins that mediate cell functions regulated by beta-adrenergic signaling. Thus, even if catecholamine levels are not increased in hyperthyroidism, their action is amplified, and this amplification can result in a hyper-responsive state to even minimal stimulation (stress).

Another theory, the autoimmune theory, could be particularly relevant in hyperthyroidism-associated TC. As most published cases have been observed in patients with autoimmune thyroid disease, some authors have proposed that TC is not a complication of thyrotoxicosis per se but a specific complication of autoimmune thyrotoxicosis (3). However, the recent publication of some cases associated with exogenous thyrotoxicosis and radioiodine-induced thyroiditis argues against this theory, but this needs to be confirmed/invalidated by a larger number of cases and longer follow-up.

This case illustrates that TC may occur in patients with apathetic hyperthyroidism and might represent the first major manifestation of an apathetic or mildly symptomatic form of thyrotoxicosis. It is very important to diagnose hyperthyroidism as a cause of TC, as failure to correct hyperthyroidism would lead to recurrence (4) and could impact prognosis. As the mean age of patients with TC is 68 years and as hyperthyroidism may be associated with minimal symptoms in the elderly, this emphasizes that TSH should be determined in all patients presenting with acute coronary syndrome and typical finding of TC, as well as those presenting with unexplained cardiac failure.

In conclusion, hyperthyroidism-associated TC is a rare entity essentially affecting elderly women, who almost always present a history of autoimmune thyroid disease. Clinical features of hyperthyroidism are not always obvious in these patients. A TSH determination is therefore warranted in every patient with unexplained TC, especially in the elderly.