Abstract
We report a patient with Takotsubo cardiomyopathy associated with thyrotoxicosis. This has been reported only six times to date (Supplementary Table S1, Supplementary Data are available online at
A 66-year-old woman without primary heart disease was admitted to the hospital with nausea, vomiting, fatigue, and palpitations. Physical examination on admission showed a blood pressure of 165/95 mm Hg, a regular pulse of 130 beats per minute, and a temperature of 37.7°C. No anemia, jaundice, or exophthalmos were observed. Serum chemistries showed only an elevated glucose level. The electrocardiogram showed a sinus tachycardia of 140 per minute (Supplementary Fig. S1). Chest radiography showed no signs of pulmonary venous congestion or cardiomegaly. Creatine kinase and c-Troponin were elevated: 231 U/L (normal: <145) and 0.88 μg/L (normal: <0.03), respectively. Echocardiography showed apical hypokinesis and a diminished left ventricular ejection fraction of 40%. Left ventricular end diastolic dimension and wall thickness were normal, and no valvular disease was detected. A diagnostic heart catheterization was performed. Coronary angiography showed no stenotic lesions (Supplementary Fig. S2A, B). On left ventriculography, apical hypokinesis was seen with a typical apical ballooning of a Takotsubo pattern (Supplementary Fig. S2C, D).
Urinary catecholamine levels were elevated with adrenaline 17.7 nmol/mmol creatinine (normal <7) and noradrenaline 101.6 nmol/mmol creatinine (normal <60). Serum concentrations of thyrotropin, free thyroxine, and triiodothyronine were 0.005 mU/L (normal: 0.4–4.0 mU/L), >77.2 pmol/L (normal:8–26 pmol/L), and 6.1 nmol/L (normal:1.2–3.0 nmol/L), respectively. Thyrotropin-receptor antibodies were elevated and confirmed Graves' disease. Treatment included metoprolol, enalapril, heparin, and methimazole as the anti-thyroid medication.
The clinical symptoms and tachycardia resolved within 24 hours, and thyroid function tests normalized and became stable after ∼1 month. Repeat echocardiography after 1 month showed complete resolution of the apical hypokinesis and a normalization of the left ventricular ejection fraction.
Takotsubo cardiomyopathy is a reversible condition that has been recently recognized among patients with symptoms and signs of acute myocardial infarction. It is characterized by the absence of coronary stenosis and by a left ventricle that takes the shape of a Japanese octopus fishing pot (called tako-tsubo) with a narrow neck and a round bottom (1). This type of cardiomyopathy is usually preceded by an episode of emotional or physical stress, which has fuelled the hypothesis that catecholamine release plays a role in the pathophysiology of this condition. Its pathogenesis is not well understood, but four mechanisms have been postulated (2).
The first theory ascribes the syndrome to epicardial coronary artery spasm with stunning. However, this seems unlikely, because the levels of cardiac enzymes are rather low in Takotsubo cardiomyopathy, the electrocardiogram changes are atypical, and there is a discrepancy between coronary perfusion and ventricular involvement. Finally, no spasms have been observed. A second proposed mechanism is coronary microvascular impairment. Microvascular changes may be involved, but causality has not yet been proved. The third postulated mechanism is cardiotoxicity due to catecholamine excess, especially adrenaline. Finally, it has been postulated that the myocardium is stunned from a neurogenic source. The apical myocardium contains a higher concentration of adrenoceptors, and apical ballooning may reflect toxic high local concentrations of sympathetic catecholamines causing cellular rupture and decreased beta-adrenoceptor responsiveness. Since most patients with Takotsubo cardiomyopathy are postmenopausal women, low estrogens probably also play a role in its development, but the mechanism is unknown.
Clinically, hyperthyroidism mimics a state of adrenergic excess. However, plasma catecholamine levels are usually low to normal in hyperthyroidism, and the sensitivity of the heart to adrenergic stimulation does not seem to be enhanced in hyperthyroidism (3). Consequently, the occurrence of Takotsubo cardiomyopathy in hyperthyroidism does not seem to be primarily caused by catecholamine toxicity, but it may be the result of a common downstream mechanism in the myocardium not mediated by the beta-adrenergic receptor (4). The cause of the catecholamine excess in our patient was not clear. A catecholamine-producing tumor was not found, and recent stressful, emotional events were not reported by the patient.
Treatment of Takotsubo cardiomyopathy is supportive and not evidence based. Beta-blockers (with or without alpha-blockade) and angiotensin-converting enzyme inhibitors are usually given. When congestive heart failure is present, diuretics are needed. The prognosis is usually good. A complete recovery is expected within 4 to 8 weeks as occurred in our patient.
In conclusion, our case shows that when Takotsubo cardiomyopathy is found, thyroid function tests should be ordered, as thyrotoxicosis is a rare, but now well described, underlying condition that requires separate treatment. Should not studies be performed to determine the true incidence and prevalence of thyrotoxicosis in patients with Takotsubo cardiomyopathy?
Footnotes
Disclosure Statement
The authors declare that no competing financial interests exist.