Takotsubo cardiomyopathy resulting in left ventricle thrombus

Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy, was initially described in Japanese patients in 1991.¹ This syndrome is associated with stressful events such as the death of a loved one, domestic abuse, catastrophic medical diagnoses, postoperative stress, devastating financial losses, natural disasters, and termination of long-standing relationships. Such stressful situations are associated with increased output of catecholamine by the sympathetic nervous system, suggesting surges in this chemical compound may have a critical role in the genesis of stress-induced cardiomyopathy.

Apical segments of the left ventricle are depressed in patients with takotsubo cardiomyopathy, which results in compensatory hyperkinesis of the basal segments and ballooning of the apex during systole. The syndrome frequently mimics acute coronary syndrome (ACS) and is often accompanied by reversible left ventricular apical ballooning in the absence of clinically significant coronary artery disease. Although most patients regain left ventricular function and make a full recovery, some do not, and a case of death from myocardial rupture has been reported.² A rare complication of takotsubo cardiomyopathy is left ventricular thrombus, with only 5 such cases having been reported in the literature.^3-6 We report an additional case of this complication in a postmenopausal woman who was successfully treated with anticoagulation therapy.

Case report

A 67-year-old woman with a history of hypertension and mild asthma presented to our institution for further evaluation after receiving a diagnosis of takotsubo cardiomyopathy. The syndrome began while she was attending a sporting event, during which she developed nausea and chest discomfort. Her symptoms continued throughout the night, and she experienced shortness of breath, jaw fullness, and right arm numbness and tingling the following morning.

The patient presented to the emergency department, where a 12-lead echocardiogram showed ST-segment elevation in leads V₃ through V₆, with inverted T waves in leads II, III, and aVF. Her cardiac troponin T peaked at 2.3 ng/mL (normal, 0-0.10 ng/mL). Cardiac catheterization showed normal coronary arteries, but she experienced a spasm of the left circumflex artery that resolved upon administration of intracoronary nitroglycerin and nicardipine (Cardene). Left ventricle angiography was consistent with takotsubo syndrome. Her hospital course was unremarkable, and she was discharged with the following once-daily oral medications: lisinopril (Prinivil), 2.5 mg; carvedilol (Coreg), 6.25 mg; triamterene and hydrochlorothiazide (Maxzide, Dyazide), 37.5 mg; and aspirin, 325 mg.

Eight days after the initial event, the patient was asymptomatic, but she presented to our institution for a second opinion. An echocardiogram showed an apical aneurysm and a 0.75 x 0.96-cm pedunculated left ventricular thrombus (Figure 1). She was admitted to the hospital and anticoagulation therapy with heparin and warfarin (Coumadin) was initiated. The patient was dismissed on hospital day 5 with the following oral medications: carvedilol, 6.25 mg (administered twice daily); lisinopril, 2.5 mg (administered twice daily); triamterene and hydrochlorothiazide, 37.5 mg (administered once daily); and warfarin (dosage was adjusted to maintain an international normalized ratio between 2.5 and 3.5). An echocardiogram performed at 1-month followup showed complete resolution of the thrombus and a normal ejection fraction (Figure 2).

More than 80% of takotsubo cardiomyopathy cases occur in postmenopausal women (mean age, 65—72 years).⁷ Some institutions estimate the syndrome to occur in approximatey 1 of 30 patients undergoing catheterization.⁸ In 2006, Pillière and associates reported a prevalence of 0.7% in a large urban area.⁹ The authors estimated that roughly 12,250 patients in the United States could present with takotsubo syndrome annually. Dhar and colleagues reported a prevalence of less than 2%.¹⁰ The best estimates suggest that 0.7% to 2.2% of patients presenting with suspected ACS have symptoms and ECG findings consistent with stress-induced cardiomyopathy.¹¹

Prognosis and complications

Patients with takotsubo cardiomyopathy generally have a good prognosis, with most making a complete recovery several weeks after receiving conservative treatment.^3,12 The mortality rate is estimated to be 1%, and the recurrence rate is estimated to be 8% or less.¹⁰ Complications include mitral regurgitation, ventricular tachycardia, ventricular fibrillation, ventricular free wall rupture, and left ventricular mural thrombus.

Our literature search identified 5 case reports of left ventricular mural thrombus formation occurring as a complication of takotsubo syndrome.^3-6 Of the 5 reports, 4 were written in English, and all reported complete resolution of the thrombus with warfarin therapy. The mechanism for the thrombus formation may be blood stasis in the region of the akinetic segment of the left ventricle.³

Management

Management of takotsubo cardiomyopathy is based on the patient’s overall condition. No controlled studies have provided data that define optimal medical management, but reasonable treatment includes standard therapy for left ventricular dysfunction, including antiplatelet agents, angiotensin-converting enzyme inhibitors, and beta blockers to prevent excessive sympathetic activity.¹³ Anticoagulant medications may be considered to prevent apical thrombus formation.¹³

Conclusion

Increased awareness of takotsubo cardiomyopathy will result in more frequent diagnosis. A better understanding of this disorder would be beneficial to optimize treatment in these patients. Prospective studies are needed to determine the incidence of this syndrome more accurately, to ascertain the long-term prognosis on the basis of the clinical features and echocardiographic and angiographic findings, and to elucidate the specific pathophysiologic mechanisms responsible for the syndrome’s development.