Endomyocardial biopsy in a patient with hemorrhagic pheochromocytoma presenting as inverted Takotsubo cardiomyopathy
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- Iio, K., Sakurai, S., Kato, T. et al. Heart Vessels (2013) 28: 255. doi:10.1007/s00380-012-0247-4
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A 29-year-old female patient presented with shock and dyspnea due to heart failure and pulmonary edema. Echocardiography indicated excessive contraction limited to the left ventricular apex and akinesis of the basal and middle ventricle, which were confirmed by emergency left ventriculography. The finding was diagnostic of inverted Takotsubo cardiomyopathy. An abdominal computed tomography scan showed a tumor in the left adrenal gland with a central low-density area, and the plasma and urinary catecholamines were strikingly elevated. Taken together, these findings suggested the presence of a hemorrhagic pheochromocytoma. A myocardial biopsy in the very acute stage on the day of admission revealed neutrophilic infiltration and contraction-band necrosis, which was indistinguishable from the previously reported pathology in the acute phase of idiopathic Takotsubo cardiomyopathy without pheochromocytoma. The diagnosis of pheochromocytoma in this case was confirmed 7 weeks later by surgical removal of the left adrenal gland with massive hemorrhage at the center of the pheochromocytoma. The marked similarity of the endomyocardial pathology between this case and cases with idiopathic Takotsubo cardiomyopathy strongly points to catecholamine excess as a common causality for Takotsubo cardiomyopathy with or without pheochromocytoma.
KeywordsPheochromocytomaTakotsubo cardiomyopathyEndomyocardial biopsyShock
Pheochromocytoma is a rare but clinically important tumor composed of chromaffin cells that produce, store, and release catecholamines, with potentially life-threatening complications. While the classic triad of pheochromocytoma is an episodic headache, diaphoresis, and palpitations [1, 2], unusual presentations including hypotension, acute cardiogenic shock, pulmonary edema, and sudden death have also been reported [2, 3]. In addition, cardiomyopathy characterized by transient hypokinesis of the basal and mid-ventricular segments with sparing of the apical contraction, i.e., so-called inverted Takotsubo cardiomyopathy [4–8], a variant of Takotsubo cardiomyopathy [9–13], have been reported in patients with pheochromocytoma. Takotsubo cardiomyopathy per se is a potentially fatal condition, which can even cause ventricular septal perforation and septal dissection . We report here the case of a young woman with a pheochromocytoma presenting with shock and severe pulmonary edema with inverted Takotsubo cardiomyopathy. Pathological findings in the myocardium in this patient in the very acute phase were indistinguishable from those reported in idiopathic Takotsubo cardiomyopathy.
A 29-year-old woman presented at the emergency department with shock and severe dyspnea. She gave a history of occasional palpitations while walking for the past 2 years. Approximately 1 year previously, she had experienced palpitations lasting as long as 30 min. Her electrocardiogram (ECG) showed normal sinus rhythm with a heart rate of 73 beats/min and transient ST depression on II, III, aVF, V3 through V6. Her palpitations progressed, occurring even at rest, to several times a week. An hour before her arrival at the hospital, she collapsed after having a sudden onset of palpitations, nausea, vomiting, dyspnea, dizziness, and high-left backache. She looked pale and severely dyspneic, and was assessed as a 10 on the Glasgow Coma Scale 10 (E2V3M5). Her blood pressure was 122/91 mmHg, heart rate 129 beats/min with a body temperature of 35.4 °C, respiratory rate 52 breaths/min, and oxygen saturation 66 % on 3 l oxygen by nasal cannula. Copious amounts of pink foamy secretion were present, resulting in her being intubated.
Intravenous administration of dopamine hydrochloride (DOA), 250 μg/min and dobutamine (DOB), 150 μg/min (3.75 μg/kg/min) was started, and intra-aortic balloon pumping (IABP) support was given to maintain hemodynamic conditions.
Plasma and urinary catecholamine levels
On the 4th day after admission, echocardiography showed improvement in abnormal contraction in the basal and middle segments of the left ventricle. The LVEF improved to 35.8 % and the lung edema was cleared (Fig. 2b). The IABP support was withdrawn. Dopamine hydrochloride and DOB were tapered, and discontinued on the 10th hospital day. Viral antibodies against adenovirus, coxsackievirus A16, B1, B2, B3, B4, B5, and B6, echovirus 6 and 8, and cytomegalovirus were all negative. With an oral α1-blocker, doxazosin, 1.5 mg/day, the patient recovered uneventfully during her month-long hospital stay.
It is a clinical challenge to correctly diagnose and manage patients with pheochromocytoma in crisis . The clinical presentation, medical history, and discovery of an adrenal tumor on the CT scan together lead us to strongly suspect the presence of pheochromocytoma in our patient. Elevated plasma and urinary catecholamines on the 2nd day, likely due to episodic discharge of the hormones from the tumor, and the accumulation of 131I-metaiodobenzylguanidine in the tumor were compatible with the diagnosis later confirmed by surgical pathology. We believe that the patient’s pulmonary edema was the result of a combination of the abnormally elevated permeability of the pulmonary vascular bed and myocardial damage caused by a catecholamine excess. Hemodynamic data obtained on the day of admission support this hypothesis. The clinical course illustrates the importance of intensive cardiocirculatory support immediately after the crisis onset. Normal plasma concentration of NT-proBNP has been shown to be a predictor of favorable prognosis in idiopathic Takotsubo cardiomyopathy , which was also the case in our patient. Although the elevation of serum inflammatory markers was recently found in patients with idiopathic Takotsubo cardiomyopathy , such markers were not present in this case.
In the diagnostic guidelines for Takotsubo cardiomyopathy [24, 25], the presence of pheochromocytoma is listed as an exclusion criterion. “Inverted” Takotsubo cardiomyopathy was first described by Ennezat et al.  in 2005 as a possible variant form of Takotsubo cardiomyopathy, characterized by excessive contraction of the left ventricular apex and akinesia of the left ventricular base and midportion. The cardiac contour in our case was compatible with the description of inverted Takotsubo cardiomyopathy given as a variant in the guidelines for Takotsubo cardiomyopathy proposed by Prasad et al. , although this variant does not feature in the guidelines put forward by Japanese researchers . Catecholamine excess has been recognized as a major underlying mechanism for “idiopathic” Takotsubo cardiomyopathy.
An endomyocardial biopsy in the current case obtained on the day of the attack showed nonlymphocytic infiltration, together with negativity in the viral antibodies, and so excluded the possibility of viral myocarditis. Importantly, the histological evidence for similarity between idiopathic (i.e., without pheochromocytoma) Takotsubo cardiomyopathy and the pheochromocytoma-associated inverted Takotsubo cardiomyopathy was obtained, namely, neutrophilic infiltration and diffuse contraction-band necrosis were present in our patient. Contraction-band necrosis is commonly found in idiopathic Takotsubo cardiomyopathy, especially in the acute phase [27, 28]. As far as we are aware, this is the first report on endomyocardial biopsy findings during the very acute stage of pheochromocytoma-associated Takotsubo cardiomyopathy. Taken together, it is likely that the two conditions, idiopathic Takotsubo cardiomyopathy and pheochromocytoma-associated (inverted) Takotsubo cardiomyopathy, share a virtually indistinguishable pathogenesis. Diagnosis of pheochromocytoma was made early in the course of the disease, which is also an uncommon experience.
The occurrence of a pheochromocytoma crisis with hemorrhaging into the tumor and development of severe pulmonary edema is in line with previous reports [2, 29–31]. Although the frequency of germline mutations in apparently sporadic cases with pheochromocytoma is reportedly as high as about 25 % , we found no such germline mutation in our patient. The prevalence of genetic mutation in patients with Takotsubo cardiomyopathy or inverted Takotsubo cardiomyopathy associated with pheochromocytoma has never been investigated, and warrants further study.
We reported a case of cardiogenic shock and pulmonary edema due to a pheochromocytoma crisis. The patient survived with intensive cardiopulmonary care. Acute hemorrhage in the tumor with a surge of catecholamines was considered the cause of heart failure and pulmonary edema. At the very acute stage, inverted Takotsubo cardiomyopathy with a pathological finding indistinguishable from that reported in patients with idiopathic Takotsubo cardiomyopathy was present. This is the first such report in a patient with pheochromocytoma-associated Takotsubo cardiomyopathy.
The authors thank Dr Hiroyuki Uchiyama for providing invaluable suggestions during the acute-phase management, Dr Yoshihiko Ikeda for constructive discussion regarding pathology, and Dr Osamu Ishizuka for providing the 131I-metaiodobenzylguanidine scintigraphy image and the photograph of the resected tumor. We are also grateful to Professor Hau C. Kwaan, Northwestern Medical Faculty Foundation, Chicago, and Robert Pastorek for editorial assistance.