Risk factors for Takotsubo Syndrome Following Cardiac Surgery: A Case–Control Study

Risk factors for Takotsubo Syndrome Following Cardiac Surgery: A Case–Control Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Risk factors for Takotsubo Syndrome Following Cardiac Surgery: A Case–Control Study Yun Seok Kim, Ju Yong Lim This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-131034/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 May, 2021 Read the published version in Journal of Cardiac Surgery → Version 1 posted You are reading this latest preprint version Abstract Background: Takotsubo syndrome following cardiac surgery is a rare occurrence. However, early diagnosis is essential to prevent treatment which could increase the left ventricular outflow tract pressure gradient in patients with Takotsubo syndrome, and lead to cardiogenic shock. Therefore, our study aimed to identify the incidence of Takotsubo syndrome after cardiopulmonary bypass and the associated risk factors and prognosis. Methods: We retrospectively studied 5,773 patients who underwent cardiopulmonary bypass between February 2007 and July 2017. Among these, Takotsubo syndrome was diagnosed in 52 (0.9%). To evaluate the risk factors for Takotsubo syndrome, 104 of the remaining 5,721 patient were randomly selected as the control group (1:2 ratio). Univariate and multivariate logistic regression analyses were used for risk factor analysis. Results: Majority of patients (69.2%) in the Takotsubo syndrome group underwent mitral valve surgery, compared to 32.7% in the control group. The following risk factors of Takotsubo syndrome were identified: atrio-ventricular valve surgery (odds ratio (OR),10.5; 95% confidence interval (CI), 2.6-42.5; P=0.001); and the immediate postoperative use of epinephrine (OR, 3.3; 95%CI, 1.0-10.7; P=0.05) and dobutamine (OR, 4.8; 95%CI, 1.72-13.3; P=0.003). Hypertension was a significant protective factor against Takotsubo syndrome following cardiac surgery (OR, 0.22; 95%CI, 0.06-0.73; P=0.01). Conclusions: Takotsubo syndrome following cardiac surgery is rare. Immediate postoperative use of epinephrine and doputamine, as well as atrio-ventricular valve surgery were factors associated with the development of Takotsubo syndrome. Cardiac & Cardiovascular Systems Cardiothoracic Surgery Takotsubo Cardiomyopathy Cardiac Surgery Postoperative management Figures Figure 1 Background Takotsubo syndrome was first described in Japan in 1991 ( 1 ). The term ‘Takotsubo’ in traditional Japanese means ‘octopus trap with a wide base’ ( 2 ). Owing to the shape of the left ventricle, Takotsubo syndrome is also sometimes referred to as ampullary-shaped cardiomyopathy. Although the pathophysiology of Takotsubo syndrome is not fully understood yet, sympathetic over-activation, excessive catecholamine release, and coronary microcirculatory dysfunction, induced by emotional or physical stress, have been suggested as important contributing factors ( 3 – 5 ). Certain types of surgeries may act as a physiological stressor, triggering Takotsubo syndrome ( 6 ). In 2007, Itoh et al. ( 7 ) reported on Takotsubo syndrome following cardiac surgery (mitral valve repair), leading the authors to suggest that myocardial stunning, caused by cardiopulmonary bypass, might be a cause of Takotsubo syndrome ( 7 ). Takotsubo syndrome preceded by cardiac surgery, however, is a very rare occurrence with only a few cases having been reported in the literature. Despite the low prevalence of Takotsubo syndrome after cardiac surgery, accurate diagnosis of the syndrome, and its differential diagnosis from low cardiac output syndrome following cardiac surgery, is essential as the use of catecholamines and beta-receptor agonists may increase the left ventricular outflow tract (LVOT) pressure gradient in patients with Takotsubo syndrome and lead to cardiogenic shock ( 8 ). In addition, catastrophic complications, such as ventricular tachycardia (3.0%) or ventricular rupture (0.2%), may occur without proper management based on early detection of Takotsubo syndrome ( 9 ). However, early detection of Takotsubo syndrome is challenging due to the rarity of the syndrome and lack of knowledge about the associated risk factors. Therefore, our aim in this study was to identify the risk factors and prognosis of Takotsubo syndrome after cardiopulmonary bypass.. Methods Study population From February 2007 to July 2017, a total of 9,037 consecutive cardiac surgeries were performed at Asan Medical Center, Seoul, Korea. Among these cases, 3,264 patients who were diagnosed with coronary artery disease pre-operatively or who underwent heart transplantation were excluded. Of the remaining 5,773 patients, Takotsubo syndrome was revealed postoperatively in 52 patients (0.9%). To perform a case-control study, we randomly selected 104 patients of the remaining 5,721 patients (without Takotsubo syndrome) as the control group (with a 2:1 ratio to the Takotsubo syndrome) to identify risk factors. The analysis of risk factors was performed retrospectively. The study was approved by the Institutional Review Board of Asan Medical Center and the requirement for informed consent was waived (IRB number: 2017 − 1144) owing to the retrospective design of our study. Data Collection Takotsubo syndrome was diagnosed based on the criteria of the Mayo clinic ( 6 , 10 ). ECG was performed every day postoperatively during hospitalization. Cardiac enzymes were routinely checked every day until those decreased to a normal range. Transthoracic echocardiography (TTE) was routinely performed at least 4-days after surgery and performed immediately if patients showed unstable vital signs. Once Takotsubo syndrome was diagnosed, follow-up TTE was performed on a daily or weekly basis, depending on the severity of LV dysfunction. All TTE was reviewed by dedicated cardiologists of our institute. Statistical Analysis Statistical analyses were performed using R program (version 3.1.2). Data are expressed as the mean ± standard deviation for continuous variables, with categorical variables reported as a count and percentage. Comparison between the Takotsubo syndrome group and the control group was performed using Student’s t -test or the Mann-Whitney U -test for continuous variables and the Chi-squared or Fisher’s exact test for categorical variables. For all analyses, a P-value < 0.05 was considered statistically significant. Univariable logistic regression analyses were performed to identify risk factors for Takotsubo syndrome in the entire study cohort. Clinical relevant variables with a P < 0.15 on univariable analysis were included in a multivariable analysis, using a backward elimination method to retain predictive variables. Results Baseline Characteristics The baseline characteristics for the Takotsubo syndrome and control groups are summarized in Table 1 . The mean interval from the cardiac surgery to the diagnosis of Takotsubo syndrome was 5.0 ± 4.5 days. The mean age was similar in both groups, but with a greater proportion of females in the Takotsubo syndrome than control group (P = 0.08). In the Takotsubo group, the majority of patients (69.2%) had undergone mitral valve operation, compared to 32.7% in the control group (p < 0.05). With regard to intra-operative variables, the time of cardiopulmonary bypass or aortic cross-clamping was comparable between the two groups. Of note, vasoactive inotropic agents, with the exception of vasopressin, were used in a greater proportion of patients in the Takotsubo syndrome than control group (P < 0.05). The length of intensive care unit (ICU) stay and the rate of early mortality were similar in both groups. Table 1 Clinical characteristics between groups Takotsubo (N = 52) Control (N = 104) Total (N = 156) p-value Age, years 55.8 ± 14.4 58.2 ± 15.1 57.4 ± 14.9 0.35 Female, N (%) 39 (75.0) 62 (59.6) 101 (64.7) 0.08 Hypertension, N (%) 5 (9.6) 38 (36.5) 43 (27.6) 0.001 Diabetes mellitus, N (%) 4 (7.7) 11 (10.6) 15 (9.6) 0.77 Hemodialysis, N (%) 0 1 (1.0) 1 (0.6) 1.00 Cerebrovascular accident, N (%) 0 1 (1.0) 1 (0.6) 1.00 Laboratory findings Hemoglobin, g/dL 12.2 ± 1.9 12.5 ± 2.0 12.4 ± 2.0 0.30 Creatinine, mg/dL 1.2 ± 2.1 1.2 ± 1.7 1.2 ± 1.8 0.89 Albumin, g/dL 3.5 ± 0.7 3.7 ± 0.5 3.6 ± 0.6 0.04 Electrocardiography 0.005 Sinus rhythm, N (%) 18 (40.0) 57 (66.3) 75 (57.3) Atrial fibrillation, N (%) 23 (51.1) 28 (32.6) 51 (38.9) Permanent pacemaker, N (%) 4 (8.9) 1 (1.2) 5 (3.8) Preoperative ventilator, N (%) 1 (1.9) 2 (1.9) 3 (1.9) 1.00 Preoperative inotropes, N (%) 2 (3.8) 2 (1.9) 4 (2.6) 0.85 LVEF, N (%) 57.2 ± 9.1 59.5 ± 9.6 58.7 ± 9.5 0.15 Type of operation < 0.001 Aortic valve, N (%) 6 (11.5) 32 (30.8) 38 (24.4) Mitral valve, N (%) 36 (69.2) 34 (32.7) 70 (44.9) Aortic and mitral valve, N (%) 4 (7.7) 9 (8.7) 13 (8.3) Tricuspid valve, N (%) 4 (7.7) 4 (3.8) 8 (5.1) Aorta, N (%) 1 (1.9) 17 (16.3) 18 (11.5) Others, N (%) 1 (1.9) 8 (7.7) 9 (5.8) CPB time, min; mean (± SD) 172.3 ± 66.7 163.8 ± 113.5 166.7 ± 99.9 0.53 ACC time, min; mean (± SD) 106.5 ± 49.1 100.5 ± 55.9 102.6 ± 53.6 0.54 Immediate postoperative VIA * Epinephrine, N (%) 15 (28.8) 12 (11.5) 27 (17.3) 0.01 Norepinephrine, N (%) 24 (46.2) 28 (26.9) 52 (33.3) 0.02 Dopamine, N (%) 24 (46.2) 69 (66.3) 93 (59.6) 0.02 Dobutamine, N (%) 23 (44.2) 17 (16.3) 40 (25.6) < 0.001 Vasopressin, N (%) 1 (1.9) 2 (1.9) 3 (1.9) 1.00 Ventilator duration 2.1 ± 3.5 2.0 ± 5.0 2.0 ± 4.6 0.83 ECMO, N (%) 1 (2.0) 0 1 (0.6) 0.71 ICU stay; mean (± SD) 8.0 ± 15.2 4.3 ± 8.1 5.5 ± 11.1 0.11 Early mortality, N (%) 2 (3.8) 8 (7.7) 10 (6.4) 0.58 ACC, aortic cross clamp; CPB, cardiopulmonary bypass; ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit; LVEF, left ventricular ejection fraction; VIA, vasoactive inotropic agent. *Vasoactive inotropic agent administered on the day of surgery. Troponin-I was increased up to mean value of 108.4 ± 118.8 ng/ml and newly developed electrocardiographic abnormalities (ST-segment changes or T-wave inversion) were documented in 94% (n = 49) of the patients. In the Takotsubo group, the left ventricular systolic function was recovered to normal values on echocardiography at a mean duration of 7.1 ± 1.3 months after diagnosis (Fig. 1 ). Univariable and multivariable analyses to identify risk factors of Takotsubo syndrome following cardiac surgery On univariable analyses, female sex, pre-operative atrial fibrillation and/or pacemaker insertion were identified as risk factor for Takotsubo syndrome. Atrio-ventricular valve surgery, such as mitral and tricuspid valve surgery, was also identified as a significant risk factor for Takotsubo syndrome (Odds ratio (OR), 5.61; 95% confidence interval (CI), 2.11–14.9; P = 0.001). Immediate postoperative use of vasoactive inotropic agents was also a risk factor for Takotsubo syndrome. Hypertension was identified as a preventive factor against Takotsubo syndrome (OR, 0.18; 95%CI; 0.06–0.46; P = 0.001). On multivariable analysis, the following variables were retained as independent risk factors for Takotsubo syndrome: Atrio-ventricular valve surgery (OR, 10.5; 95%CI, 2.6–42.5; P = 0.001), and the immediate postoperative use of epinephrine (OR, 3.3; 95%CI, 1.0-10.7; P = 0.05) and dobutamine (OR, 4.8; 95%CI, 1.72–13.3; P = 0.003). Hypertension was retained as a significant protective factor against Takotsubo syndrome (OR, 0.22; 95%CI, 0.06–0.73; P = 0.01). These findings are summarized in Table 2 . Table 2 Risk analysis for Takotsubo syndrome following cardiac surgery Univariable analysis Multivariable analysis Preoperative variables OR 95% CI p-value OR 95% CI p-value Age, years 0.98 0.96–1.01 0.34 Sex (female) 2.03 0.98–4.37 0.06 Diabetes mellitus 0.70 0.18–2.18 0.56 Hypertension 0.18 0.06–0.46 0.001 0.22 0.06–0.73 0.01 Ventilator support 1.00 0.04–10.67 > 0.99 Inotropic support 2.04 0.23–17.41 0.48 LVEF 0.97 0.94–1.01 0.16 Arrhythmia Atrial fibrillation 2.60 1.21–5.66 0.01 Permanent pacemaker 12.6 1.73–256.5 0.03 Hemoglobin 0.91 0.77–1.08 0.30 Creatinine 0.98 0.79–1.18 0.89 Albumin 0.52 0.29–0.92 0.03 Operative variables Type of operation Atrio-ventricular valve 5.61 2.11–14.93 0.001 10.54 2.63–42.54 0.001 Others 0.94 0.27–3.22 0.92 CPB time 1.00 1.00–1.00 0.53 ACC time 1.00 0.99–1.01 0.53 Postoperative use of VIA Epinephrine 3.11 1.33–7.39 0.009 3.36 1.04–10.73 0.05 Norepinephrine 2.33 1.16–4.69 0.02 Vasopressin 1.00 0.05–10.68 1.00 Dopamine 0.43 0.22–0.85 0.02 Dobutamine 4.06 1.92–8.76 < 0.001 4.84 1.72–13.35 0.003 ACC, aortic cross clamp; CPB, cardiopulmonary bypass; LVEF, left ventricular ejection fraction; VIA vasoactive inotropic agent. Discussion To the best of our knowledge, this is the first case-control study to report Takotsubo syndrome after cardiac surgery. We also identified that of the patients who developed Takotsubo syndrome, 69.2% had undergone mitral valve surgery. We identified atrio-ventricular valve surgery, and the immediate postoperative use of epinephrine or dobutamine as specific risk factors for Takotsubo syndrome following cardiac surgery. Our findings are consistent with those previously reported. In the literature, 14 cases of Takotsubo syndrome after cardiac surgery have been reported, with the majority of these cases (n = 10, 71.4%) occurred after mitral valve surgery ( 2 , 7 , 11 – 22 ). Like all other surgeries, cardiac surgery can cause emotional and/or physiological stress which may trigger Takotsubo syndrome. In addition, cardiopulmonary bypass needed during cardiac surgery induces a systemic inflammatory response which may also cause coronary microvascular dysfunction and excessive catecholamine release ( 7 ). Direct manipulation and incision of the heart also increases its vulnerability to catecholamine-induced cardiac toxicity ( 21 ). We note, however, that the reason why Takotsubo syndrome occurs more frequently after mitral valve surgery than other cardiac surgery is unknown. Several differential diagnoses for Takotsubo syndrome have previously been presented. Of these, papillo-annular discontinuity after mitral valve replacement, which leads to a spherical LV and, thus, decreases LV systolic function, should be differentiated from ‘transient’ Takotsubo syndrome ( 12 , 23 ). Other causes of myocardial stunning after cardiac surgery, such as suboptimal myocardial protection or coronary air embolism, should also be considered as differential diagnoses of Takotsubo syndrome. These differential diagnoses should be identified intra-operatively, using transesophageal echocardiography, based on the characteristic echocardiographic finding of Takotsubo syndrome, namely apical ballooning that extends beyond a single coronary territory ( 15 ). In 2008, Takotsubo syndrome, induced by pharmacological stress (epinephrine infusion), was first described by Wong et al. ( 11 ). In the following year, Abraham at al. reported that exogenous catecholamines and beta-receptor agonists (epinephrine, dobutamine), like endogenous catecholamines, could induce Takotsubo syndrome ( 24 ). Previous findings that excessive release of catecholamine may cause Takotsubo syndrome ( 3 , 4 ) are convincing and are consistent with our own results that immediate postoperative use of epinephrine and dobutamine as risk factors for Takotsubo syndrome following cardiac surgery. Previous reports on the occurrence of Takotsubo syndrome after cardiac surgery indicated that, in most cases, the syndrome developed several minutes to several days after the release of cross-clamping ( 2 , 7 , 11 , 12 , 14 – 22 ). Of note, Ohata et al. did report on a case of Takotsubo syndrome that developed 1-month after aortic valve replacement in a 70-year-old female ( 13 ). In our study, intra-operative transesophageal echocardiography was performed in all cases, with TTE routinely performed at least 4 days after surgery. We do note that in the case of unstable vital signs, or if the patient complained of chest discomfort, TTE was immediately performed. The median interval between the cardiac surgery and the diagnosis of Takotsubo syndrome in our study cohort was 4.0 (Interquartile range, 3.0–5.0) days. Therefore, our imaging protocol would have been appropriate to detect Takotsubo syndrome in most cases. Takotsubo syndrome has been known to occur mostly in elderly women ( 25 ). Ueyama et al. reported that, in rats, the use of estradiol might be protective against LV dysfunction induced by emotional stress ( 26 ). In the present study, there were more female patients in Takotsubo group (75.0%) than in control group (59.6%), although this difference was not significant (P = 0.08). However, female sex was identified as a risk factor for Takotsubo syndrome after cardiac surgery on univariable analysis, but was not retained as an independent risk factor on multivariable analysis. Characteristically, Takotsubo syndrome is a transient heart failure syndrome ( 27 ), with a mortality rate of 3.2% having been reported in a previous case-summary study ( 25 ). The mortality rate of Takotsubo syndrome after cardiac surgery in our study cohort was 3.8% and, thus, was comparable to previously published data. Of note, the mortality rate in the Takotsubo group (3.8%) was similar to that in the control group (7.7%; P = 0.58). Madias reported a low prevalence of diabetes mellitus among patients with Takotsubo syndrome ( 28 ). Based on this finding, Madias suggested that diabetic autonomic neuropathy and decreased catecholamine release might have protective effect against Takotsubo syndrome. Madias did report that the prevalence of hypertension in patients with Takotsubo syndrome was comparable to that in the general population. In contrast, in our study, the prevalence of hypertension was lower in the Takotsubo syndrome than control group, while the prevalence of diabetes mellitus was similar between the two groups. In our multivariable analysis, hypertension was identified as having a protective factor against Takotsubo syndrome after cardiac surgery. It is possible that anti-hypertensive medications, such as beta-receptor antagonists, taken before cardiac surgery may lower the risk of Takotsubo syndrome following cardiac surgery. However, data about anti-hypertensive medications prescribed to the patients in our study cohort by their primary-care physician could not be accurately identified and, thus, analysis of the plausible protective role of anti-hypertensive medications was not possible. Limitations This study is a retrospective observational study of patients enrolled from a single center. Although we did use a case-controlled design, in the absence of randomization, effects of selection or detection bias cannot be denied. In addition, due to the retrospective design of the study, the causal relationship between the development of Takotsubo syndrome and the use of epinephrine or dobutamine could not be determined. Finally, we could not completely exclude confounding effect of medications taken pre-operatively, a factor which should be assessed in subsequent, larger, cohort studies. Conclusions Takotsubo syndrome occurred in about 1% of patients who underwent cardiac surgery under cardiopulmonary bypass. Immediate postoperative use of epinephrine and doputamine, as well as atrio-ventricular valve surgery were factors associated with the development of Takotsubo syndrome after cardiac surgery. The resulting left ventricular dysfunction was reversible in the majority of patients, without an increase in the rate of mortality. The findings of our study will need to be verified in a larger, multi-center, prospective studies. Abbreviations ECG, electrocardiography ICU, intensive care unit LV, left ventricle LVOT, left ventricular outflow tract TTE, transthoracic echocardiography Declarations Ethics approval and consent to participate This study was approved and informed consent was waivered by the Institutional Review Board of Asan Medical Center (IRB number: 2017-1144). Consent to publication Not applicable. Availability of data and materials The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This study was supported by a grant from the Asan Institute for Life Sciences and Corporate Relations of Asan Medical Center, Seoul, Korea. The funding body had no role in the design of the current study and collection, analysis, and interpretation of data and in writing the manuscript. Authors’ contributions JY and YS have made substantial contributions to the acquisition, analysis, interpretation of data. JB have designed the study and interpreted the data. All authors have approved the submitted version. Acknowledgement Not applicable. References Dote K, Sato H, Tateishi H, Uchida T, Ishihara M. Myocardial stunning due to simultaneous multivessel spasm; review of five cases [in Japanese]. J Cardiol. 1991;21:203–14. Chiariello GA, Bruno P, Colizzi C, Crea F, Massetti M. Takotsubo cardiomyopathy following cardiac surgery. J Card Surg. 2016;31:89–95. 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Cite Share Download PDF Status: Published Journal Publication published 16 May, 2021 Read the published version in Journal of Cardiac Surgery → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-131034","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":6692247,"identity":"87cf1c91-66cd-4b86-b48f-45cfde806615","order_by":0,"name":"Yun Seok Kim","email":"","orcid":"https://orcid.org/0000-0002-2817-557X","institution":"Keimyung University Dongsan Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yun","middleName":"Seok","lastName":"Kim","suffix":""},{"id":6692248,"identity":"672fea31-420a-4d05-97bc-5935e6ad6226","order_by":1,"name":"Ju Yong Lim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIiWNgGAWjYDACZubGAwwFEgz87M0HgFwJGSK0MDYcYDCQYJDsOZYA0sJDhDVgLQwMBjdyDEBcwlp024FafhhYRBscyPn86kaNBQ8D++GjG/BpMTvM2HCwx0Aid+aBs9usc44BHcaTlnaDkJYDPEAtfQd7txnnsAG1SPCYEdRy8A9QS8NhnmfGOf+I1HIYZMuEYzzMj3PbiNUiA/JLD5sZc26fBA8bQb+cP3zw4ZuKutx++cePP+d8q5PjZz98DK8WZMAmASaJVQ4CzB9IUT0KRsEoGAUjBwAAryhMcER42UYAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-2864-1630","institution":"The Catholic University of Korea College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Ju","middleName":"Yong","lastName":"Lim","suffix":""}],"badges":[],"createdAt":"2020-12-17 21:27:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-131034/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-131034/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1111/jocs.15626","type":"published","date":"2021-05-16T21:07:24+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":4419274,"identity":"793c0e94-ecc4-42ab-9ef6-2d31d49678dd","added_by":"auto","created_at":"2020-12-21 18:03:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":449160,"visible":true,"origin":"","legend":"Echocardiographic findings of Takotsubo syndrome. Transthoracic echocardiography showing apical ballooning with decreased left ventricular (LV) systolic function (ejection fraction, 35%) on postoperative day 4 (A). Seven days later, LV systolic function had normalized (ejection fraction, 55%) and apical ballooning is no longer observable (B).","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-131034/v1/8e6cae7ab2505d64938a2842.png"},{"id":20040624,"identity":"e671538e-6527-4a4e-acad-219af31ebf99","added_by":"auto","created_at":"2022-04-06 21:07:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":874083,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-131034/v1/a202c54c-0b15-4503-81b4-4c13766d7d5a.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eRisk factors for Takotsubo Syndrome Following Cardiac Surgery: A Case–Control Study\u003c/p\u003e","fulltext":[{"header":"Background","content":" \u003cp\u003eTakotsubo syndrome was first described in Japan in 1991 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The term \u0026lsquo;Takotsubo\u0026rsquo; in traditional Japanese means \u0026lsquo;octopus trap with a wide base\u0026rsquo; (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Owing to the shape of the left ventricle, Takotsubo syndrome is also sometimes referred to as ampullary-shaped cardiomyopathy. Although the pathophysiology of Takotsubo syndrome is not fully understood yet, sympathetic over-activation, excessive catecholamine release, and coronary microcirculatory dysfunction, induced by emotional or physical stress, have been suggested as important contributing factors (\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCertain types of surgeries may act as a physiological stressor, triggering Takotsubo syndrome (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In 2007, Itoh et al. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) reported on Takotsubo syndrome following cardiac surgery (mitral valve repair), leading the authors to suggest that myocardial stunning, caused by cardiopulmonary bypass, might be a cause of Takotsubo syndrome (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Takotsubo syndrome preceded by cardiac surgery, however, is a very rare occurrence with only a few cases having been reported in the literature. Despite the low prevalence of Takotsubo syndrome after cardiac surgery, accurate diagnosis of the syndrome, and its differential diagnosis from low cardiac output syndrome following cardiac surgery, is essential as the use of catecholamines and beta-receptor agonists may increase the left ventricular outflow tract (LVOT) pressure gradient in patients with Takotsubo syndrome and lead to cardiogenic shock (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In addition, catastrophic complications, such as ventricular tachycardia (3.0%) or ventricular rupture (0.2%), may occur without proper management based on early detection of Takotsubo syndrome (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). However, early detection of Takotsubo syndrome is challenging due to the rarity of the syndrome and lack of knowledge about the associated risk factors. Therefore, our aim in this study was to identify the risk factors and prognosis of Takotsubo syndrome after cardiopulmonary bypass..\u003c/p\u003e "},{"header":"Methods","content":" \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eFrom February 2007 to July 2017, a total of 9,037 consecutive cardiac surgeries were performed at Asan Medical Center, Seoul, Korea. Among these cases, 3,264 patients who were diagnosed with coronary artery disease pre-operatively or who underwent heart transplantation were excluded. Of the remaining 5,773 patients, Takotsubo syndrome was revealed postoperatively in 52 patients (0.9%). To perform a case-control study, we randomly selected 104 patients of the remaining 5,721 patients (without Takotsubo syndrome) as the control group (with a 2:1 ratio to the Takotsubo syndrome) to identify risk factors. The analysis of risk factors was performed retrospectively. The study was approved by the Institutional Review Board of Asan Medical Center and the requirement for informed consent was waived (IRB number: 2017\u0026thinsp;\u0026minus;\u0026thinsp;1144) owing to the retrospective design of our study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData Collection\u003c/h2\u003e \u003cp\u003eTakotsubo syndrome was diagnosed based on the criteria of the Mayo clinic (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). ECG was performed every day postoperatively during hospitalization. Cardiac enzymes were routinely checked every day until those decreased to a normal range. Transthoracic echocardiography (TTE) was routinely performed at least 4-days after surgery and performed immediately if patients showed unstable vital signs.\u003c/p\u003e \u003cp\u003eOnce Takotsubo syndrome was diagnosed, follow-up TTE was performed on a daily or weekly basis, depending on the severity of LV dysfunction. All TTE was reviewed by dedicated cardiologists of our institute.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using R program (version 3.1.2). Data are expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation for continuous variables, with categorical variables reported as a count and percentage. Comparison between the Takotsubo syndrome group and the control group was performed using Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test or the Mann-Whitney \u003cem\u003eU\u003c/em\u003e-test for continuous variables and the Chi-squared or Fisher\u0026rsquo;s exact test for categorical variables. For all analyses, a P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Univariable logistic regression analyses were performed to identify risk factors for Takotsubo syndrome in the entire study cohort. Clinical relevant variables with a P\u0026thinsp;\u0026lt;\u0026thinsp;0.15 on univariable analysis were included in a multivariable analysis, using a backward elimination method to retain predictive variables.\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":" \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eBaseline Characteristics\u003c/h2\u003e \u003cp\u003eThe baseline characteristics for the Takotsubo syndrome and control groups are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean interval from the cardiac surgery to the diagnosis of Takotsubo syndrome was 5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5 days. The mean age was similar in both groups, but with a greater proportion of females in the Takotsubo syndrome than control group (P\u0026thinsp;=\u0026thinsp;0.08). In the Takotsubo group, the majority of patients (69.2%) had undergone mitral valve operation, compared to 32.7% in the control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). With regard to intra-operative variables, the time of cardiopulmonary bypass or aortic cross-clamping was comparable between the two groups. Of note, vasoactive inotropic agents, with the exception of vasopressin, were used in a greater proportion of patients in the Takotsubo syndrome than control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The length of intensive care unit (ICU) stay and the rate of early mortality were similar in both groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics between groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTakotsubo\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;52)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;104)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;156)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.8\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.2\u0026thinsp;\u0026plusmn;\u0026thinsp;15.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57.4\u0026thinsp;\u0026plusmn;\u0026thinsp;14.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (75.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (59.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101 (64.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (36.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43 (27.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (10.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemodialysis, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebrovascular accident, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory findings\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin, g/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine, mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin, g/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElectrocardiography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSinus rhythm, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 (66.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75 (57.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrial fibrillation, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (51.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (32.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51 (38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePermanent pacemaker, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative ventilator, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative inotropes, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEF, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of operation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAortic valve, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38 (24.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMitral valve, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (69.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (32.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70 (44.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAortic and mitral valve, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid valve, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAorta, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (16.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCPB time, min; mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e172.3\u0026thinsp;\u0026plusmn;\u0026thinsp;66.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e163.8\u0026thinsp;\u0026plusmn;\u0026thinsp;113.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e166.7\u0026thinsp;\u0026plusmn;\u0026thinsp;99.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACC time, min; mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e106.5\u0026thinsp;\u0026plusmn;\u0026thinsp;49.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100.5\u0026thinsp;\u0026plusmn;\u0026thinsp;55.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e102.6\u0026thinsp;\u0026plusmn;\u0026thinsp;53.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmediate postoperative VIA\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpinephrine, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (28.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (11.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNorepinephrine, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (26.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e52 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDopamine, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69 (66.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93 (59.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDobutamine, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (44.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (16.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (25.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVasopressin, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentilator duration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eECMO, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU stay; mean (\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEarly mortality, N (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eACC, aortic cross clamp; CPB, cardiopulmonary bypass; ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit; LVEF, left ventricular ejection fraction; VIA, vasoactive inotropic agent. *Vasoactive inotropic agent administered on the day of surgery.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTroponin-I was increased up to mean value of 108.4\u0026thinsp;\u0026plusmn;\u0026thinsp;118.8\u0026nbsp;ng/ml and newly developed electrocardiographic abnormalities (ST-segment changes or T-wave inversion) were documented in 94% (n\u0026thinsp;=\u0026thinsp;49) of the patients.\u003c/p\u003e \u003cp\u003eIn the Takotsubo group, the left ventricular systolic function was recovered to normal values on echocardiography at a mean duration of 7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3 months after diagnosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eUnivariable and multivariable analyses to identify risk factors of Takotsubo syndrome following cardiac surgery\u003c/h2\u003e \u003cp\u003eOn univariable analyses, female sex, pre-operative atrial fibrillation and/or pacemaker insertion were identified as risk factor for Takotsubo syndrome. Atrio-ventricular valve surgery, such as mitral and tricuspid valve surgery, was also identified as a significant risk factor for Takotsubo syndrome (Odds ratio (OR), 5.61; 95% confidence interval (CI), 2.11\u0026ndash;14.9; P\u0026thinsp;=\u0026thinsp;0.001). Immediate postoperative use of vasoactive inotropic agents was also a risk factor for Takotsubo syndrome. Hypertension was identified as a preventive factor against Takotsubo syndrome (OR, 0.18; 95%CI; 0.06\u0026ndash;0.46; P\u0026thinsp;=\u0026thinsp;0.001). On multivariable analysis, the following variables were retained as independent risk factors for Takotsubo syndrome: Atrio-ventricular valve surgery (OR, 10.5; 95%CI, 2.6\u0026ndash;42.5; P\u0026thinsp;=\u0026thinsp;0.001), and the immediate postoperative use of epinephrine (OR, 3.3; 95%CI, 1.0-10.7; P\u0026thinsp;=\u0026thinsp;0.05) and dobutamine (OR, 4.8; 95%CI, 1.72\u0026ndash;13.3; P\u0026thinsp;=\u0026thinsp;0.003). Hypertension was retained as a significant protective factor against Takotsubo syndrome (OR, 0.22; 95%CI, 0.06\u0026ndash;0.73; P\u0026thinsp;=\u0026thinsp;0.01). These findings are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRisk analysis for Takotsubo syndrome following cardiac surgery\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnivariable analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eMultivariable analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative variables\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.96\u0026ndash;1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.98\u0026ndash;4.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.18\u0026ndash;2.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.06\u0026ndash;0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.06\u0026ndash;0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentilator support\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.04\u0026ndash;10.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInotropic support\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.23\u0026ndash;17.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.94\u0026ndash;1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArrhythmia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrial fibrillation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.21\u0026ndash;5.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePermanent pacemaker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.73\u0026ndash;256.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.77\u0026ndash;1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.79\u0026ndash;1.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.29\u0026ndash;0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOperative variables\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of operation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrio-ventricular valve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.11\u0026ndash;14.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.63\u0026ndash;42.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.27\u0026ndash;3.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCPB time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00\u0026ndash;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACC time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.99\u0026ndash;1.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative use of VIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpinephrine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.33\u0026ndash;7.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.04\u0026ndash;10.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNorepinephrine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.16\u0026ndash;4.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVasopressin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.05\u0026ndash;10.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDopamine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.22\u0026ndash;0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDobutamine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.92\u0026ndash;8.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.72\u0026ndash;13.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eACC, aortic cross clamp; CPB, cardiopulmonary bypass; LVEF, left ventricular ejection fraction; VIA vasoactive inotropic agent.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e "},{"header":"Discussion","content":" \u003cp\u003eTo the best of our knowledge, this is the first case-control study to report Takotsubo syndrome after cardiac surgery. We also identified that of the patients who developed Takotsubo syndrome, 69.2% had undergone mitral valve surgery. We identified atrio-ventricular valve surgery, and the immediate postoperative use of epinephrine or dobutamine as specific risk factors for Takotsubo syndrome following cardiac surgery. Our findings are consistent with those previously reported. In the literature, 14 cases of Takotsubo syndrome after cardiac surgery have been reported, with the majority of these cases (n\u0026thinsp;=\u0026thinsp;10, 71.4%) occurred after mitral valve surgery (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR12 CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Like all other surgeries, cardiac surgery can cause emotional and/or physiological stress which may trigger Takotsubo syndrome. In addition, cardiopulmonary bypass needed during cardiac surgery induces a systemic inflammatory response which may also cause coronary microvascular dysfunction and excessive catecholamine release (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Direct manipulation and incision of the heart also increases its vulnerability to catecholamine-induced cardiac toxicity (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). We note, however, that the reason why Takotsubo syndrome occurs more frequently after mitral valve surgery than other cardiac surgery is unknown.\u003c/p\u003e \u003cp\u003eSeveral differential diagnoses for Takotsubo syndrome have previously been presented. Of these, papillo-annular discontinuity after mitral valve replacement, which leads to a spherical LV and, thus, decreases LV systolic function, should be differentiated from \u0026lsquo;transient\u0026rsquo; Takotsubo syndrome (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Other causes of myocardial stunning after cardiac surgery, such as suboptimal myocardial protection or coronary air embolism, should also be considered as differential diagnoses of Takotsubo syndrome. These differential diagnoses should be identified intra-operatively, using transesophageal echocardiography, based on the characteristic echocardiographic finding of Takotsubo syndrome, namely apical ballooning that extends beyond a single coronary territory (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn 2008, Takotsubo syndrome, induced by pharmacological stress (epinephrine infusion), was first described by Wong et al. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In the following year, Abraham at al. reported that exogenous catecholamines and beta-receptor agonists (epinephrine, dobutamine), like endogenous catecholamines, could induce Takotsubo syndrome (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Previous findings that excessive release of catecholamine may cause Takotsubo syndrome (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) are convincing and are consistent with our own results that immediate postoperative use of epinephrine and dobutamine as risk factors for Takotsubo syndrome following cardiac surgery. Previous reports on the occurrence of Takotsubo syndrome after cardiac surgery indicated that, in most cases, the syndrome developed several minutes to several days after the release of cross-clamping (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19 CR20 CR21\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Of note, Ohata et al. did report on a case of Takotsubo syndrome that developed 1-month after aortic valve replacement in a 70-year-old female (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). In our study, intra-operative transesophageal echocardiography was performed in all cases, with TTE routinely performed at least 4\u0026nbsp;days after surgery. We do note that in the case of unstable vital signs, or if the patient complained of chest discomfort, TTE was immediately performed. The median interval between the cardiac surgery and the diagnosis of Takotsubo syndrome in our study cohort was 4.0 (Interquartile range, 3.0\u0026ndash;5.0) days. Therefore, our imaging protocol would have been appropriate to detect Takotsubo syndrome in most cases.\u003c/p\u003e \u003cp\u003eTakotsubo syndrome has been known to occur mostly in elderly women (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Ueyama et al. reported that, in rats, the use of estradiol might be protective against LV dysfunction induced by emotional stress (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). In the present study, there were more female patients in Takotsubo group (75.0%) than in control group (59.6%), although this difference was not significant (P\u0026thinsp;=\u0026thinsp;0.08). However, female sex was identified as a risk factor for Takotsubo syndrome after cardiac surgery on univariable analysis, but was not retained as an independent risk factor on multivariable analysis.\u003c/p\u003e \u003cp\u003eCharacteristically, Takotsubo syndrome is a transient heart failure syndrome (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e), with a mortality rate of 3.2% having been reported in a previous case-summary study (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). The mortality rate of Takotsubo syndrome after cardiac surgery in our study cohort was 3.8% and, thus, was comparable to previously published data. Of note, the mortality rate in the Takotsubo group (3.8%) was similar to that in the control group (7.7%; P\u0026thinsp;=\u0026thinsp;0.58). Madias reported a low prevalence of diabetes mellitus among patients with Takotsubo syndrome (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Based on this finding, Madias suggested that diabetic autonomic neuropathy and decreased catecholamine release might have protective effect against Takotsubo syndrome. Madias did report that the prevalence of hypertension in patients with Takotsubo syndrome was comparable to that in the general population. In contrast, in our study, the prevalence of hypertension was lower in the Takotsubo syndrome than control group, while the prevalence of diabetes mellitus was similar between the two groups. In our multivariable analysis, hypertension was identified as having a protective factor against Takotsubo syndrome after cardiac surgery. It is possible that anti-hypertensive medications, such as beta-receptor antagonists, taken before cardiac surgery may lower the risk of Takotsubo syndrome following cardiac surgery. However, data about anti-hypertensive medications prescribed to the patients in our study cohort by their primary-care physician could not be accurately identified and, thus, analysis of the plausible protective role of anti-hypertensive medications was not possible.\u003c/p\u003e "},{"header":"Limitations","content":" \u003cp\u003eThis study is a retrospective observational study of patients enrolled from a single center. Although we did use a case-controlled design, in the absence of randomization, effects of selection or detection bias cannot be denied. In addition, due to the retrospective design of the study, the causal relationship between the development of Takotsubo syndrome and the use of epinephrine or dobutamine could not be determined. Finally, we could not completely exclude confounding effect of medications taken pre-operatively, a factor which should be assessed in subsequent, larger, cohort studies.\u003c/p\u003e \u003c/div\u003e "},{"header":"Conclusions","content":" \u003cp\u003eTakotsubo syndrome occurred in about 1% of patients who underwent cardiac surgery under cardiopulmonary bypass. Immediate postoperative use of epinephrine and doputamine, as well as atrio-ventricular valve surgery were factors associated with the development of Takotsubo syndrome after cardiac surgery. The resulting left ventricular dysfunction was reversible in the majority of patients, without an increase in the rate of mortality. The findings of our study will need to be verified in a larger, multi-center, prospective studies.\u003c/p\u003e "},{"header":"Abbreviations","content":" \u003cp\u003eECG, electrocardiography\u003c/p\u003e \u003cp\u003eICU, intensive care unit\u003c/p\u003e \u003cp\u003eLV, left ventricle\u003c/p\u003e \u003cp\u003eLVOT, left ventricular outflow tract\u003c/p\u003e \u003cp\u003eTTE, transthoracic echocardiography\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved and informed consent was waivered by the Institutional Review Board of Asan Medical Center (IRB number: 2017-1144).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by a grant from the Asan Institute for Life Sciences and Corporate Relations of Asan Medical Center, Seoul, Korea. The funding body had no role in the design of the current study and collection, analysis, and interpretation of data and in writing the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJY and YS have made substantial contributions to the acquisition, analysis, interpretation of data. JB have designed the study and interpreted the data. All authors have approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDote K, Sato H, Tateishi H, Uchida T, Ishihara M. Myocardial stunning due to simultaneous multivessel spasm; review of five cases [in Japanese]. J Cardiol. 1991;21:203\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChiariello GA, Bruno P, Colizzi C, Crea F, Massetti M. 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Thorac Cardiovasc Surg. 2011;59:500\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamane K, Hirose H, Reeves GR, Marhefka GD, Silvestry SC. Left ventricular dysfunction mimicking Takotsubo cardiomyopathy following cardiac surgery. J Heart Valve Dis. 2011;20:471\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang LW, Jansz PC, Baron DW. Delirium and Takotsubo cardiomyopathy following cardiac surgery. Anaesth Intensive Care. 2013;41:437\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi S, Koerner MM, El-Banayosy A, Soleimani B, Pae WE, Leuenberger UA. Takotsubo's syndrome after mitral valve repair and rescue with extracorporeal membrane oxygenation. Ann Thorac Surg. 2014;97:1777\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi JH, Oh ID, Shin E, Lee S, Jeon JM, Kim HT, et al. Extracorporeal membrane oxygenation for Takotsubo cardiomyopathy that developed after mitral valve replacement. Acute Crit Care. 2020;35:51\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePergolini A, Zampi G, Casali G, Madeo A, Visconti CL, Cipullo PL, et al. Takotsubo syndrome after mitral valve replacement: case report and brief review of the literature. J Cardiothorac Vasc Anesth. 2015;29:431\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoldfine H, Aurigemma GP, Zile MR, Gaasch WH. Left ventricular length-force-shortening relations before and after surgical correction of chronic mitral regurgitation. J Am Coll Cardiol. 1998;31:180\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbraham J, Mudd JO, Kapur N, Klein K, Champion HC, Wittstein IS. Stress cardiomyopathy after intravenous administration of catecholamines and beta-receptor agonists. J Am Coll Cardiol. 2009;53:1320\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDonohue D, Movahed MR. Clinical characteristics, demographics and prognosis of transient left ventricular apical ballooning syndrome. Heart Fail Rev. 2005;10:311\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUeyama T, Hano T, Kasamatsu K, Yamamoto K, Tsuruo Y, Nishio I. Estrogen attenuates the emotional stress-induced cardiac response in the animal model of Tako-Tsubo (ampulla) cardiomyopathy. J Cardiovasc Pharmacol. 2003;42(Suppl 1):117\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLyon AR, Bossone E, Schneider B, Sechtem U, Citro R, Undewood SR, et al. Current state of knowledge on Takotsubo syndrome: a position statement from the task force on Takotsubo syndrome of the Heart Failure Association on the European Society of Cardiology. Eur J Heart Fail. 2016;18:8\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMadias JE. Low prevalence of diabetes mellitus in patients with Takotsubo syndrome: a plausible 'protective\u0026rsquo; effect with pathophysiologic connotations. Eur Heart J Acute Cardiovasc Care. 2016;5:164\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Takotsubo Cardiomyopathy, Cardiac Surgery, Postoperative management ","lastPublishedDoi":"10.21203/rs.3.rs-131034/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-131034/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Takotsubo syndrome following cardiac surgery is a rare occurrence. However, early diagnosis is essential to prevent treatment which could increase the left ventricular outflow tract pressure gradient in patients with Takotsubo syndrome, and lead to cardiogenic shock. Therefore, our study aimed to identify the incidence of Takotsubo syndrome after cardiopulmonary bypass and the associated risk factors and prognosis.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe retrospectively studied 5,773 patients who underwent cardiopulmonary bypass between February 2007 and July 2017. Among these, Takotsubo syndrome was diagnosed in 52 (0.9%). To evaluate the risk factors for Takotsubo syndrome, 104 of the remaining 5,721 patient were randomly selected as the control group (1:2 ratio). Univariate and multivariate logistic regression analyses were used for risk factor analysis. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eMajority of patients (69.2%) in the Takotsubo syndrome group underwent mitral valve surgery, compared to 32.7% in the control group. The following risk factors of Takotsubo syndrome were identified: atrio-ventricular valve surgery (odds ratio (OR),10.5; 95% confidence interval (CI), 2.6-42.5; P=0.001); and the immediate postoperative use of epinephrine (OR, 3.3; 95%CI, 1.0-10.7; P=0.05) and dobutamine (OR, 4.8; 95%CI, 1.72-13.3; P=0.003). Hypertension was a significant protective factor against Takotsubo syndrome following cardiac surgery (OR, 0.22; 95%CI, 0.06-0.73; P=0.01).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eTakotsubo syndrome following cardiac surgery is rare. Immediate postoperative use of epinephrine and doputamine, as well as atrio-ventricular valve surgery were factors associated with the development of Takotsubo syndrome.\u003c/p\u003e","manuscriptTitle":"Risk factors for Takotsubo Syndrome Following Cardiac Surgery: A Case–Control Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-12-21 18:00:46","doi":"10.21203/rs.3.rs-131034/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0277be75-614c-4aff-a645-2052a8b8e700","owner":[],"postedDate":"December 21st, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":1555642,"name":"Cardiac \u0026 Cardiovascular Systems"},{"id":1555643,"name":"Cardiothoracic Surgery"}],"tags":[],"updatedAt":"2022-04-06T21:07:24+00:00","versionOfRecord":{"articleIdentity":"rs-131034","link":"https://doi.org/10.1111/jocs.15626","journal":{"identity":"journal-of-cardiac-surgery","isVorOnly":true,"title":"Journal of Cardiac Surgery"},"publishedOn":"2021-05-16 21:07:24","publishedOnDateReadable":"May 16th, 2021"},"versionCreatedAt":"2020-12-21 18:00:46","video":"","vorDoi":"10.1111/jocs.15626","vorDoiUrl":"https://doi.org/10.1111/jocs.15626","workflowStages":[]},"version":"v1","identity":"rs-131034","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-131034","identity":"rs-131034","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}