Takotsubo cardiomyopathy in a patient with lung adenocarcinoma.

Takotsubo cardiomyopathy (TC) is a rare and usually physical or emotional stress-induced clinical disorder characterized by transient left ventricular dysfunction and apical segment ballooning. Much is still unknown regarding risk factors and clinical relationships. Recently, an association between TC and malignancies has been proposed. We present a case of lung adenocarcinoma whose initial hospital admission was due to TC. We contribute this case report to the growing set of literature on the association between TC and malignancies.

INTRODUCTION

Takotsubo cardiomyopathy (TC), also called stress cardiomyopathy or apical ballooning syndrome, is a syndrome of reversible stress-induced cardiomyopathy associated with profound emotional or physical stress.[12] TC is characterized by transient left ventricular (LV) dysfunction with ischemia-like chest pain and ischemia-like electrocardiographic (ECG) changes and lack of any obstructive epicardial coronary artery disease observed at the time of emergent coronary angiography. LV wall motion abnormalities usually involve apical and/or midventricular myocardial segments with wall motion abnormalities extending beyond a single epicardial coronary distribution.[1]

Although several pathological mechanisms have been proposed, the precise pathophysiology of TC is still not entirely understood. Recently, an association between TC and malignancies has been proposed.[3] We present a case with lung adenocarcinoma whose initial hospital admission was due to TC.

CASE REPORT

A 59 year-old man without any history of cardiovascular disease was admitted to emergency service with the complaint of chest and back pain. ECG revealed sinus rhythm with a rate of 70/min, 2-3 mm ST elevations in V2 and V6 [Figure 1]. His blood pressure was 110/70 mmHg. He was on antihypertensive medication and smokes 20 cigarettes per day for more than 20 years. He was immediately taken into the cardiac catheterization laboratory with the diagnosis of acute anterior myocardial infarction. Coronary angiography demonstrated patent coronary arteries without significant stenosis. Ventriculography demonstrated systolic apical ballooning which is typical for TC [Figure 2]. Transthoracic echocardiography demonstrated apical akinesia with a dynamic LV outflow tract obstruction (peak resting gradient: 45 mmHg, peak gradient reaches to 177 mmHg and mean gradient to 81 mmHg with valsalva maneuver) [Figure 3]. ST elevations returned towards baseline and his complaints were improved progressively with medical treatment, which included antiplatelet agents and anticoagulation, beta adrenergic receptor blocker and renin-angiotensin system blocker agents. Troponin T level peaked at 0.71 ng/ml.

Figure 1

Twelve-lead electrocardiography samples of patient obtained at admission (a) and 2 days later (b)

Figure 2

Coronary angiography and left ventriculography of the patient

Figure 3

Transthoracic echocardiography images of the patient demonstrating left ventricular systolic apical ballooning (arrows) and left ventricular outflow tract obstruction

Patient had a cachectic appearance and had complaints of backache and dysphagia with weight loss of 25 kg during the last 12 months. Endoscopic examination revealed esophageal obstruction due to external compression. Computed tomography scan of the chest revealed a mass with 5 x 2.5 cm diameter at the level of right pulmonary upper lobe on the posterior segment, extending from retrotracheal to paravertebral space with bone invasion. There were also multiple mediastinal lymphadenopathies. Fine needle aspiration biopsy obtained from mass showed neoplastic cells and immunohistochemical analysis demonstrated that these cells were reactive with CK7, CK20, and TTF-1 antibodies. He was diagnosed with lung adenocarcinoma and whole body positron emission tomography (PET) demonstrated hypermetabolic subcarinal and paraosephageal lymphadenopathies and lytic/sclerotic lesions on thoracic vertebral bodies (T 3-4-5) and right sided ribs (from 4th to 9th), which were accepted as metastases.

Repeat transthoracic echocardiogram performed 10 days after admission revealed complete resolution of LV systolic dysfunction and disappearance of LV outflow gradient [Figure 4].

Figure 4

Repeat transthoracic echocardiography images of the patient 10 days after admission

DISCUSSION

TC usually mimics acute coronary syndrome and the most common abnormalities on the ECG are ST elevations on the precordial on the precordial leads.[4] Usually there is only a moderate rise in cardiac enzymes which is disproportionate with the size of the affected myocardium.[1] Dynamic LV outflow tract (LVOT) obstruction may occur in up to a fourth of TC subjects. Basal hypercontractility related venturi effect has been suggested as a cause of dynamic LVOT obstruction.[5] TC is a transient syndrome and resolution of symptoms with complete echocardiographic and clinical recovery is expected within 2 to 3 weeks of presentation. Our patient had complete recovery of cardiac symptoms and echocardiography performed 10 days after presentation revealed complete resolution of both wall motion abnormalities and dynamic LVOT obstruction.

Several pathophysiological mechanisms have been suggested for TC among them coronary artery vasospasm, coronary microcirculation dysfunction, and catecholamine overload.[2] Exposure to emotional or physical stress and increased sympathetic activity has been reported in most cases of TC. Excessive catecholamine production in patients with pheochromocytoma has also been shown to induce reversible LV dysfunction.[26]

Prognosis of TC seems favorable in the absence of significant underlying co-morbid conditions.[3] However, a high rate of concomitant malignancies were reported in a prospective TC registry[7] and Burgdorf- et al. investigated the prevalence of malignancies and long-term mortality in patients.[3] They evaluated 50 patients with TC and 50 age- and gender- matched control patients with acute anterior myocardial infarction (MI). They reported that 9 patients with TC (18%) and 3 patients with MI (6%) had a previous history of malignancy at the time of the index event. On follow-up, 7 malignancies were newly diagnosed in the TC group, whereas no new case of malignancy was found in the control group. These observations have suggested a possible association between malignancies and TC, which may be a result of paraneoplastic phenomena. A variety of malignancies were observed in patients with TC in their study, such as bronchial carcinoma, colorectal carcinoma, breast carcinoma, endometrial carcinoma, melanoma, bladder urothelial carcinoma, gastric carcinoma, and chronic lymphocytic leukemia. On the basis of these observations, Burgdorf et al. suggested to perform cancer screening in patients with TC.[8]

To the best of our knowledge, this is the first paper reporting TC in a patient with lung adenocarcinoma. The development of TC may be a result of paraneoplastic phenomena as previously suggested. Our patient had bone metastases causing backache and had complaints of dysphagia with weight loss of 25 kg during the past 12 months, which might also have constituted sufficient physical stress for the development of TC.

CONCLUSION

TC was the initial cause of hospital admission in our case with lung adenocarcinoma. We contribute this case report to the growing set of literature data regarding the presence of various concomitant malignancies in patients with TC. Further research is needed to elucidate the relationship between these diseases.