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Takotsubo cardiomyopathy caused by acute respiratory stress from extubation

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Introduction
Takotsubo cardiomyopathy (TCM) is known as psychological and physical stress-induced cardiomyopathy accompanied by transient systolic dysfunction of the left ventricular apex. [1] Intensive care unit (ICU) patients are exposed to overstress during treatment and therefore are potentially at risk for TCM. Precise diagnosis and prompt treatment for it are thus required because Editor: N/A. Written informed consent was obtained from the patient for publication of this report and accompanying images.
Authors' contributions: Mainly KT, ST, RI, MN, and OU treated the patient; KO and AT collaborated in the patient's management; KS and TF performed cardiac catheterization; KT designed and drafted the manuscript; NI, KU, and AT reviewed and revised the manuscript.
Supplemental Digital Content is available for this article.
The authors report no conflicts of interest.
TCM sometimes results in lethal heart failure or cardiac shock, [2] especially in ICU patients. Herein, we report a case of TCM induced by acute respiratory stress including extubation.

Case report
An 86-year-old man was hospitalized in emergency department with a diagnosis of pneumonia because of an influenza A virus/ bacteria mixed infection and had been already treated with an anti-influenza agent in our department (Fig. 1A). He had an extensive medical history including hypertension, diabetes mellitus, pulmonary tuberculosis, and hydrocephalus, and a surgical history involving partial pulmonary resection for lung cancer. He was administered antibiotics immediately after admission, but his respiratory condition rapidly deteriorated. Oxygen was given at the rate of 12 L/min by face mask with a reservoir. His arterial blood gas (ABG) examination showed a PaO 2 of 58.0 Torr (normal, 80.0-100), a PaO 2 /fraction of inspiratory oxygen ratio (P/F ratio) of 61.1, and a PaCO 2 of 28.5 Torr (normal, 35.0-45.0). Hence, he was intubated and managed strictly with broad-spectrum antibiotics and mechanical ventilation in the ICU. As his respiratory condition smoothly recovered, he was extubated on ICU day 4. ABG analysis showed a PaO 2 of 129.7 Torr, (P/F ratio of 324.3) and a PaCO 2 of 39.1 Torr under the rate of 4 L/min O 2 flow via face mask. However, his respiratory condition redeteriorated, with pink foamy sputum appearing about half a day after extubation. Also, his decreasing blood pressure required support by administration of catecholamine such as dopamine and noradrenaline. The chest x-ray revealed pulmonary edema ( Fig. 1B and C). High O 2 flow was again given at the rate of 15 L/min, but his ABG analysis remained at a PaO 2 of 91.7 Torr (P/F ratio of 91.7) and a PaCo 2 of 37.2 Torr, and so he was reintubated. At the same time, the electrocardiogram (ECG) pattern clearly changed ( Fig. 2A and  com/MD/B987). Based on these findings, a diagnosis of TCM after extubation was made. Deep inverted T waves appeared widely from chest and limb leads on the ECG at 48 hours after cardiac catheterization (Fig. 4A). Nadirs of the inverted T waves steadily rose under treatment with catecholamine for left ventricular dysfunction, diuretics for pulmonary edema, and anticoagulants for prevention of thrombogenesis (Fig. 4). As the respiratory condition improved, reextubation was done at ICU day 11. Although slight T-wave inversions still remained 3 weeks later on the ECG (Fig. 4C), his cardiovascular hemodynamics was stable, without administration of catecholamine at ICU day 8. The patient was discharged from the ICU at ICU day 15. The patient was subsequently treated for pneumonia after leaving the ICU but suffered from repetitive aspiration pneumonia and was finally transferred to another hospital at hospital day 111.

Discussion
TCM was first reported in 1989 in a pheochromocytoma patient as impaired reversible LV motion. [3] Possible onset mechanisms of TCM include spastic coronary microcirculatory disturbance, catecholamine cardio-injuries, and neurogenic stunning myocardium [4][5][6] ; however, controversy remains regarding them. TCM is  thought to be induced by psychological stresses such as depression, anxiety, alcohol and drug abuses, and even mental disorders caused by disasters such as earthquake. [7][8][9] Physical stresses including subarachnoid hemorrhage, acute respiratory distress syndrome, and acute exacerbation of chronic obstructive pulmonary disease can be also indicated as risk factors for TCM. [10] Namely, many ICU inpatients have potentially high risk for TCM. In our present case, acute respiratory stress owing to pneumonia and extubation probably induced TCM. Also, a relatively high PEEP (8-cmH 2 O) cancellation after extubation might have contributed to it. TCM should be diagnosed promptly and managed carefully because it sometimes causes lethal conditions such as cardiogenic shock, left ventricular outflow tract obstruction, heart failure, arrhythmia, thrombogenesis or cardiac rupture. [2] ECG is one of the most versatile and easiest tools in the clinical situation. STsegment depression in lead aVR without ST-segment elevation in lead V1 is a typical ECG finding for the acute phase of TCM, [11] but it is not often revealed. In the present case, an abnormal Q wave and flat T wave were detected (Fig. 2B). Hence, it is important to suspect TCM without overlooking the various ECG pattern changes and to perform promptly a subsequent echocardiogram and cardiac catheterization.
TCM therapy is still empirical. [12] Fortunately, in the present case, the cardiovascular hemodynamics was relatively stable with administration of catecholamine, and the patient recovered from TCM without serious complications following administration of only diuretics and anticoagulants. Although generally TCM has a relatively good prognosis, clinicians should consider the possibility of TCM in intensive care patients not to delay management of this disorder.

Conclusion
TCM should be considered especially under the situation of intensive care, and prompt diagnosis should be followed by appropriate management because delay management of this disorder sometimes induces lethal complications.