TAKOTSUBO CARDIOMYOPATHY WITH HYPERVASOPRESSINEMIA

Abstract

To the Editor: An 88-year-old woman presented with shortness of breath and appetite loss. Chest X-ray revealed significant right pleural effusion, and blood examination showed hyponatremia (119 mmol/L). She had no contributory medical history, and electrocardiography (ECG) was normal at admission. Findings on routine laboratory tests were not remarkable except for hyponatremia. The cytological examination of pleural effusion and chest computed tomography demonstrated that pleural metastasis of lung adenocarcinoma caused the effusion. Further blood examinations showed a high serum arginine vasopressin (AVP) concentration (25.0 pg/mL; normal range 0.3–3.5 pg/mL), low serum osmolality (246 mOsm/L), and high urine osmolality (625 mOsm/L). Her thyroid function and adrenal function were normal. Because of these results, she was diagnosed with syndrome of inappropriate secretion of antidiuretic hormone1 caused by high intrathoracic pressure due to marked pleural effusion. On her 14th hospital day, she suddenly complained of chest pain and chest oppression. ECG showed ST-segment elevation in the V3, V4, and V5 leads. She was diagnosed with acute ST-elevation myocardial infarction (STEMI) and transferred to the cardiovascular center. However, before coronary angiography (CAG) could be performed, chest pain and oppression disappeared, and we no longer found ST-segment elevation on ECG. There was no coronary artery atherosclerosis or spasm identified by CAG, and left ventriculography did not detect any abnormality. Blood examination after CAG showed no enzymatic evidence of myocardial necrosis. A diagnosis of Takotsubo cardiomyopathy2 was considered at this point. Follow-up ECG showed T-wave inversion in the V3, V4, and V5 leads on the 19th hospital day. On the 21st hospital day, the pleural effusion was drained and the intrathoracic pressure lowered. Blood examinations on the 30th hospital day showed a decrease in serum AVP concentration (1.5 pg/mL), increased serum osmolality (268 mOsm/L), decreased urine osmolality (339 mOsm/L), and normalization of serum sodium concentration (137 mmol/L). Many previous articles have reported that recurrence of Takotsubo cardiomyopathy is rare,2, 3 and this patient has not complained of chest pain and chest oppression since the initial episode. Takotsubo cardiomyopathy has cardiac symptoms that are difficult to distinguish from acute STEMI and is observed especially in women aged 60 and older.2 The patients diagnosed with Takotsubo cardiomyopathy complain of chest pain and chest oppression. ECG shows ST-segment elevation, and left ventriculography shows wall motion abnormalities, but CAG shows no evidence of obstructive atherosclerosis of the coronary arteries. Takotsubo cardiomyopathy is associated with several clinical events, such as subarachnoid hemorrhage,4 pheochromocytoma,5 Guillain-Barré syndrome,6 and mental stress.7 Although the pathophysiology and the reason for the strong elderly female predominance remain unknown, and accepted criteria for diagnosis have not been established, some hypotheses are suggested: catecholamine-mediated myocardial stunning, catecholamine-induced microcardiac artery spasm, and epicardial coronary artery spasm.2 AVP is a hormone produced in the cells located predominantly in the supraoptic and paraventricular hypothalamic nuclei, the axons of which terminate in the posterior lobe of the pituitary gland, and is well known as a antidiuretic hormone.8 There are three subtypes of receptors for AVP: V1a, V1b, and V2. AVP also functions as a vasoconstrictor and myocardial contractor through V1a receptors, which are located on vascular smooth muscle cells and cardiomyocytes.9 Because AVP causes peripheral vasoconstriction in the skin, skeletal muscles, gastrointestinal organs, fat tissue, renal arterioles, and coronary arteries, it is used as a vasoconstrictor to support blood pressure in refractory septic shock.10 This case showed hypervasopressinemia (20 times as high as normal level) before she was diagnosed with Takotsubo cardiomyopathy. Her blood pressure was always normal (108/66 mmHg), but it went up to 142/82 mmHg when she complained of chest pain. AVP may have been one of the causes of high blood pressure, working as a strong vasoconstrictor. Because of these results, this case can suggest a new hypothesis in the pathophysiology of Takotsubo cardiomyopathy; AVP may have induced microcardiovascular spasm, causing left ventricular wall motion abnormalities “Takotsubo cardiomyopathy.” Although Takotsubo cardiomyopathy is becoming recognized as a common heart disease, especially in elderly women, acceptable criteria for diagnosis are not established, and the pathophysiology remains unknown. More cases and studies are needed to ascertain the pathophysiology and management of this syndrome. We first demonstrated a relation between Takotsubo cardiomyopathy and hypervasopressinemia. Hypervasopressinemia may be an important trigger of reversible left ventricular dysfunction “Takotsubo cardiomyopathy.” Financial Disclosure: Norinaga Urahama's research has no financial and material support. None of the authors have any potential conflicts of interest associated with this study, and no authors have anything to disclose. Author Contribution: Norinaga Urahama participated in the study concept and design and contributed significantly to the treatment of the patient, acquisition of data, and preparation of manuscript. Hideki Nakashima, Hirokazu Kurose, and Tadatsugu Ohno treated the patient and prepared the manuscript. Sponsor's Role: No sponsor.