Biventricular Takotsubo Cardiomyopathy in Graves Hyperthyroidism

ABSTRACT:Graves hyperthyroidism is commonly seen in clinical practice and Takotsubo stress cardiomyopathy is an increasingly recognized cardiac complication of physical or emotional stress. We report the rare case of a patient with Graves hyperthyroidism that was complicated by severe biventricular takotsubo cardiomyopathy, which was demonstrated on heart catheterization. After appropriate pharmacologic treatment of her hyperthyroidism, she had complete resolution of her cardiomyopathy. 

J INVASIVE CARDIOL 2014;26(3):E35-E36

Key words: biventricular Tako-tsubo, Graves hyperthyroidism

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Hyperthyroidism is a common disorder with an overall prevalence of approximately 1.3%; however, increased rates are seen among elderly women.¹ Takotsubo or stress cardiomyopathy is also seen most commonly in postmenopausal women and has been described as an unusual complication of Graves hyperthyroidism.^2,3 Our report describes a case of atypical Takotsubo cardiomyopathy characterized by biventricular apical ballooning and pulmonary hypertension in the setting of Graves thyrotoxicosis. The patient’s cardiomyopathy resolved after treatment of her hyperthyroidism was initiated with methimazole. This case serves as an example of an atypical presentation of a rare but serious complication of Graves disease, which is almost always reversible when proper treatment of the underlying condition is initiated. To the best of our knowledge, this is the first reported case of biventricular Takotsubo cardiomyopathy in the setting of Graves hyperthyroidism.

Case Report. A 36-year-old African-American woman with past medical history of well-controlled HIV infection, hypertension, end-stage renal disease, and chronic pancreatitis presented with a 1-month history of epigastric pain, nausea with frequent vomiting, and hyperdefecation with a 35 lb weight loss. She was admitted for a presumed exacerbation of her chronic pancreatitis. Her admission electrocardiogram (ECG) was notable for new T-wave inversions in the precordial leads. A myocardial perfusion scan performed 3 weeks earlier was negative for ischemia and showed normal left ventricular systolic function. Thyroid studies after admission revealed an undetectable TSH and free T4 of 2.92 ng/dL (0.58-1.64). Ultrasound of the thyroid revealed no nodules, normal echogenicity, and diffusely increased vascularity. Thyroid stimulating immunoglobulins were elevated at 423% of normal, confirming the diagnosis of Graves hyperthyroidism. The day after admission, the patient developed pressure-like substernal chest pain and ECG changes were noted with increasingly deep symmetrical T-wave inversions in the precordial leads (Figure 1). Troponin-T was trended and was never elevated. Transthoracic echocardiogram revealed a large area of left and right ventricular apical akinesis with left ventricular ejection fraction of 25 ± 5% (Video 1). Left and right heart catheterization was performed and showed large areas of severe apical akinesis of both the left and right ventricles with hyperkinetic base, severe pulmonary hypertension, and angiographically normal coronary arteries (Videos 2 and 3). Pharmacologic therapy with methimazole, carvedilol, and lisinopril was initiated. The patient saw improvement in her gastrointestinal symptoms and she was discharged. Repeat echocardiography 6 weeks later showed normal left and right ventricular size and function with complete resolution of biventricular apical ballooning (Videos 4 and 5). Follow-up thyroid function tests, also obtained 6 weeks later, revealed a normalized free T4 of 1.27 ng/dL, although TSH was still suppressed at <0.01 mcIU/mL (0.27-4.32).

Discussion. While our patient had multiple potential etiologies for her cardiomyopathy, the pattern of ventricular dysfunction with apical akinesis and hyperkinetic base in the setting of non-diseased coronary arteries was most consistent with Takotsubo cardiomyopathy. The patient’s HIV infection was well-controlled on a stable antiretroviral regimen for over a year, which makes HIV-related cardiomyopathy or drug effect less likely. Dilated cardiomyopathy, likely a rate-related phenomenon, is a well-described complication of hyperthyroidism, but the expected pattern of myocardial dysfunction would be more consistent with other forms of dilated cardiomyopathy, not a classic Takotsubo pattern as seen in our patient.^4-6 Although Graves hyperthyroidism is a frequently encountered clinical entity and Takotsubo cardiomyopathy is an increasingly recognized complication of physical or emotional stress, the two have infrequently been associated.³

This patient’s presentation with right ventricular involvement of her Takotsubo cardiomyopathy makes her presentation even more unusual. A number of case series have assessed patients with Takotsubo cardiomyopathy for right ventricular involvement and it appears that this occurs in approximately one- third of cases.^7-10

Commonly recognized cardiovascular sequelae of hyperthyroidism include hypertension, sinus tachycardia, atrial fibrillation, and high or normal output heart failure.^11,12 Although many of the complications of hyperthyroidism mimic a hyperadrenergic state, circulating plasma catecholamine concentrations are usually normal or decreased in hyperthyroidism.¹³ Among the postulated mechanisms for the pathogenesis of Takotsubo cardiomyopathy is catecholamine excess causing microvascular spasm or dysfunction or by direct myocardial toxicity.^14,15 Furthermore, elevated levels of thyroid hormone may increase tissue responsiveness to catecholamines by way of increased catecholamine receptor density.¹³ Although many variants of Takotsubo cardiomyopathy have been observed, the most common presentation is with left ventricular ballooning. Supporting the hypothesis that Takotsubo cardiomyopathy is a catecholamine-induced state is the observation that beta-adrenoreceptor density is greatest in the apical myocardium, the area most frequently affected in Takotsubo cardiomyopathy.¹⁶ This observation could also provide a pathophysiologic link between hyperthyroidism and Takotsubo cardiomyopathy, which was observed in this patient. It has also been postulated that thyroid-stimulating antibodies, which are elevated in Graves disease, may directly affect the myocardium since most cases of Takotsubo cardiomyopathy seen in hyperthyroidism have been seen in the setting of Graves disease.¹⁷

Right ventricular involvement in Takotsubo cardiomyopathy is an important prognostic indicator. Case series have demonstrated that patients with right ventricular involvement tend to have a lower left ventricular ejection fraction, increased incidence of pleural effusions, longer hospitalizations, and more severe CHF symptoms, with a greater likelihood of necessitating invasive therapies such as intraaortic balloon pump.^7,12,18

Conclusion. Although serious complication rates are higher among patients with right ventricular involvement, similar ventricular function recovery rates have been observed. To our knowledge, this is the first reported case of thyrotoxicosis causing severe biventricular Takotsubo cardiomyopathy that completely reversed after successful treatment.

References

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From the ¹Department of Internal Medicine and ²Department of Cardiology, Madigan Army Medical Center, Tacoma Washington.

Disclaimer: The views expressed are those of the authors and do not reflect the official policy of the Department of the Army, the Department of Defense or the United States Government.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted August 13, 2013, provisional acceptance given August 19, 2013, final version accepted September 16, 2013.

Address for correspondence: Matthew Perkins, MD, Madigan Army Medical Center, Internal Medicine PGY-3, 9040 Fitzsimmons Blvd, Tacoma, WA 98431. Email: matthew.j.perkins.mil@mail.mil or daschachter@gmail.com