Identification of Subclinical Myocardial Dysfunction in Breast Cancer Patients With Metabolic Syndrome After Cancer Related Comprehensive Therapy

Identification of Subclinical Myocardial Dysfunction in Breast Cancer Patients With Metabolic Syndrome After Cancer Related Comprehensive Therapy | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Identification of Subclinical Myocardial Dysfunction in Breast Cancer Patients With Metabolic Syndrome After Cancer Related Comprehensive Therapy Feng Zhang, Siyuan Wang, Siying Liang, Chao Yu, Sufang Li, Hong Chen, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-129387/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Breast cancer patients with metabolic syndrome have an increased risk of cardiovascular disease. These patients are more prone to suffer from cardiotoxicity after anti-cancer therapy. Patients after completion of cancer related comprehensive therapy, who show normal myocardial function, may already have subclinical myocardial dysfunction. We sought to evaluate the subclinical myocardial dysfunction in breast cancer patients with metabolic syndrome after cancer related comprehensive therapy. Methods : In this study, 45 breast cancer patients with metabolic syndrome after completion of cancer related comprehensive therapy and 45 non-breast cancer patients with metabolic syndrome were enrolled. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were measured using echocardiogram. Results : All the patients have normal LVEF. However, nine breast cancer patients (20%) had GLS that was lower than -17%, while all the non-cancer patients have normal GLS. Breast cancer patients with metabolic syndrome had a decrease of GLS and LVEF, compared with non-cancer patients with metabolic syndrome. Furthermore, we found that decrease of age was associated with reduction of LVEF, and that use of trastuzumab for 1 year was a significant factor that associated with reduction of GLS. Conclusions : Breast cancer patients with metabolic syndrome after completion of cancer related comprehensive therapy suffered from subclinical myocardial dysfunction. GLS should be routinely performed to early identify subclinical myocardial damage of patients, in order to prevent the cardiotoxicity of cancer related comprehensive therapy. Trial registration : the Medical Ethics Committee of Peking University People’s Hospital, 2018PHB032-02, Registered 23 November 2018, http://www.chictr.org.cn/showproj.aspx?proj=35202 Cardiac & Cardiovascular Systems Subclinical Myocardial Dysfunction Breast Cancer Metabolic Syndrome Cancer Related Comprehensive Therapy Figures Figure 1 Figure 1 Figure 1 Background The incidence of metabolic syndrome has increased year by year with the unhealthy lifestyle. Previous study has estimated that 24.5% Chinese subjects over 15 years old had suffered from metabolic syndrome [ 1 ]. Recently several studies have shown that metabolic syndrome is involved in the occurrence, recurrence and metastasis of breast cancer, thus affecting the prognosis of breast cancer patients [ 2 ]. In China, there are a large number of breast cancer patients with metabolic syndrome, especially those with abdominal obesity. It is known that patients with metabolic syndrome have an increased risk of cardiovascular disease [ 3 ]. Furthermore, most of these breast cancer patients need to have cancer-related comprehensive therapy, including chemotherapy, targeted therapy, and radiotherapy, which may result in the further damage of their myocardium. Recent studies have shown that chemotherapy, targeted therapy and radiotherapy in breast cancer patients can cause injury of the myocardium. Use of anthracyclines, one of most widely used chemotherapeutic drug, can lead to acute and chronic toxic damage to myocardium [ 4 ]. In addition, trastuzumab is often used in combination in HER2 or ErbB2 positive breast cancer patients. Although trastuzumab improves clinical outcomes by targeting the tumor, trastuzumab also causes an increased risk of cardiovascular adverse events, the most common of which is the left ventricular systolic dysfunction [ 5 ]. Furthermore, radiation therapy for left breast cancer can also cause cardiotoxicity, including cardiac insufficiency, due to its radiation to the heart [ 6 ]. The European Society of Cardiology have defined that cancer therapeutic related cardiac dysfunction (CTRCD) is that the reduction of left ventricle ejection fraction (LVEF) is over 10% or LVEF is decreased to a value below 50% [ 7 ]. However, the decrease of LVEF that can be detected by echocardiogram may occur after sever damage of myocardium in patients. In more than half of these patients, left ventricular dysfunction has been permanently impaired and cannot be restored [ 8 ]. It was found that measurement of GLS using two-dimensional speckle tracing echocardiography (STE) can detect early change of left ventricular function, thus predicting the occurrence of CRTCD [ 9 ]. However, due to the insufficient understanding of GLS, it is not routinely used in cancer patients [ 10 ]. In this study, we aim to evaluate the cardiotoxicity of patients by both LVEF and GLS, together. Rare studies focused on the cardiotoxicity of cancer related therapy in patients with metabolic syndrome. Therefore, our study observed the cardiac function in breast cancer patients with metabolic syndrome, compared with that in non-cancer patients with metabolic syndrome. We aimed to find the subclinical myocardial dysfunction of these patients and related risk factors, so as to early prevent cardiotoxicity in these patients. Methods Study design and population In our study ( www.chictr.org.cn Identifier: ChiCTR1900022108), 45 breast cancer patients with metabolic syndrome who were admitted to Breast Center of Peking University People’s Hospital from November 2018 to February 2019 were consecutively enrolled. The inclusion criteria were: (1) Patients were ≥ 18 and ≤ 60 years old; (2) Patients were diagnosed with stage I-III breast cancer; (3) Patients have completed breast cancer surgery, chemotherapy, targeted therapy, and radiotherapy in Breast Center. (4) Patients had a body weight change of less than 10% in the past 6 months. (5) Patients had a waist circumference ≥ 80 cm with at least one abnormal indicator, including high blood glucose, high blood pressure and dyslipidemia. The exclusion criteria included: (1) Patients have heart, liver or kidney related diseases; (2) Patients have history of other caner. Age, height, weight, radiotherapy, targeted therapy and chemotherapy regimen, and cardiovascular risk factors were collected for each patient. Meanwhile, serum type B natriuretic peptide (BNP) and troponin I (TnI) were also collected. In addition, 45 non-cancer patients with metabolic syndrome were enrolled as matches. The inclusion criteria were (1), (4), (5), that the same with breast cancer patients, and no history of cancer, as well as no heart, liver, and kidney related disease. Image acquisition All patients were examined by transthoracic echocardiography and contrast-enhanced echocardiography using GE95. All echocardiographic exams were performed by the same technician using the same machine. All images were interpreted by the same cardiologist. Contrast-enhanced echocardiography for left ventricular opacification (LVO) was used to improve the accuracy of quantitative assessment of LVEF. LVEF was calculated by the two-plane Simpson method. GLS was measured in all patients. The specific measurement is as follows. When the images were collected, we made an optimization of the gain, compress, and time-gain compensation controls to get clear appearance of the left ventricle. Then apical views (4,2 and 3 chambers) were collected using high frame rate (> 50 frames/s). The GLS was measured, and the boundary tracking was optimized by manual corrections. The images of each patient had no or just one segment of poor display. All participants provided written informed consent. The study was approved by the Medical Ethics Committee of Peking University People’s Hospital. Statistical analysis Continuous variables were represented by mean ± standard deviation. Categorical variables were expressed by percentage of patients in each group. Categorical variables were compared using Person’s chi-square test. Continuous variables were compared using independent sample t test. Multiple linear regression was used to analyzed the risk factors related to GLS and LVEF. P < 0.05 was considered to have statistical significance. All the analyses were performed by SPSS 20.0 software. Results Baseline characteristics of the 45 breast cancer patients with metabolic syndrome and the 45 non-cancer patients with metabolic syndrome are shown as Table 1 . The mean age of breast cancer patients was 49 years old. The mean BMI of breast cancer patients was 27.8 kg/m 2 . There are no significant differences in age, BMI, waist circumference and cardiovascular risk factors between breast cancer patients and non-cancer patients. All of the breast cancer patients with metabolic syndrome showed TnI and BNP levels within normal range. Table 1 Baseline characteristics Breast cancer patients with metabolic syndrome Non-cancer patients with metabolic syndrome P value Demographics Age (years) 49 ± 8 52 ± 10 0.442 BMI (kg/m 2 ) 27.8 ± 3.2 27.3 ± 2.6 0.674 Waist circumference (cm) 92.6 ± 7.4 93.2 ± 8.3 0.542 Cardiovascular risk factors Coronary heart disease 0 0 Hypertension 9 (20%) 11 (24%) 0.342 High blood glucose 13 (29%) 15 (33%) 0.573 Dyslipidemia 26 (58%) 24 (53%) 0.483 Beta-blockers 2 (4%) 3 (7%) 0.231 ACE inhibitors 3 (7%) 2 (4%) 0.323 Vital sign Systolic blood pressure (mmHg) 122 ± 18 125 ± 15 0.673 Diastolic blood pressure (mmHg) 78 ± 10 76 ± 11 0.523 Cholesterol level (mmol/L) Total cholesterol 4.88 ± 0.97 5.02 ± 1.14 0.734 LDL-c 3.11 ± 0.79 3.15 ± 0.98 0.634 TG 1.82 ± 1.00 1.79 ± 1.15 0.667 Fasting glucose (mmol/L) 5.4 ± 0.97 5.56 ± 1.03 0.782 Breast cancer side Left 22 (49%) - Right 22 (49%) - Both 1 (2%) - Comprehensive therapy Chemothrapy 45(100%) Anthracycline use 31 (69%) - Trastuzumab use 20 (44%) - Both of anthracycline and trastuzumab 11 (24%) - Left-side radiotherapy 16 (36%) - Values as mean ± SD, or n (%). LDL-c = low density lipoprotein cholesterol; TG = triglyceride All patients have normal LVEF. However, four breast cancer patients with metabolic syndrome had LVEF that was lower than 60%, while no non-cancer patients with metabolic syndrome had LVEF that was lower than 60%. Furthermore, among the breast cancer patients with metabolic syndrome, nine patients (20%) had GLS that lower than − 17%, which is the normal lower limit of GLS. In contrast, there was no abnormality of GLS in the non-cancer patients with metabolic syndrome. In addition, we found that the breast cancer patients with metabolic syndrome had a decrease of GLS and LVEF (GLS: -19.95 ± 2.98%, LVEF 67.19 ± 5.92%), compared with the non-cancer patients with metabolic syndrome (GLS − 21.53 ± 2.32%,LVEF 70.63 ± 3.24%) (Fig. 1 A, B). Multivariate linear regression analysis was performed to identify possible factors that affected LVEF and GLS in breast cancer patients. Age, BMI, use of anthracycline, use of trastuzumab and left-side radiotherapy were included. We found that age was a significant factor that affected LVEF (Table 2 ). Specifically, decrease of age was associated with decrease of LVEF. Moreover, use of trastuzumab was a significant factor that associated with reduction of GLS (Table 3 ). Table 2 Multivariate analysis for LVEF in breast cancer patients with metabolic syndrome after treatment Factor β SE P value Age 0.328 0.127 0.014 BMI 0.343 0.270 0.211 Anthracycline -0.020 2.073 0.992 Trastuzumab -1.442 1.901 0.453 Left-side radiotherapy 2.133 1.802 0.244 Table 3 Multivariate analysis for GLS in breast cancer patients with metabolic syndrome after treatment Factor β SE P value Age 0.014 0.076 0.855 BMI -0.222 0.154 0.160 Anthracycline 0.767 1.194 0.525 Trastuzumab 2.489 1.107 0.031 Left-side radiotherapy 0.578 1.077 0.595 Discussion In this study, we observe the subclinical myocardial dysfunction of breast cancer patients with metabolic syndrome after completion of cancer related comprehensive therapy. We measured LVEF and GLS in these patients, compared those with non-cancer patients with metabolic syndrome, and identified risk factors that may be associated with subclinical myocardial dysfunction. Our main findings are as follows: (1) Breast cancer patients with metabolic syndrome after completion of cancer related comprehensive therapy have decreased LVEF and GLS, compared to those without cancer, even though their LVEF are all within normal range; (2) Decreased age is the risk factor of LVEF reduction in breast cancer patients with metabolic syndrome, while use of trastuzumab is associated with the reduction of GLS. Our study used both LVEF and GLS to observe the myocardial injury of breast cancer patients with metabolic syndrome. LVEF is the regular method to be used in evaluation of myocardial function in cancer patients with tumor-related therapy. In contrast, echocardiography-based myocardial strain is a novel way to detect subclinical dysfunction of left ventricle. GLS may be a more sensitive predictor of toxicity of heart, compared to LVEF. This may be explained by following reasons. Chemotherapy may affect just certain segments of left ventricle, resulting in the early reduction of GLS. Other region of left ventricle may have compensatory enhanced movement, leading to unchanged LVEF [ 11 ]. In addition, LVEF may be affected by many other conditions including preload, heart rate, and et al [ 12 ]. Tracing process is often used in measurement of LVEF. In contrast, GLS may adopt more accurate measurement through STE (Specking Tracking Echocardiogram). Therefore, 2014 ASE/EACVI Expert Consensus recommend that GLS can be used to early detect subclinical dysfunction of left ventricle in the patients with chemotherapy [ 13 ]. Indeed, we observed that a reduction of GLS in the breast cancer patients with metabolic syndrome after treatment, and that 9 breast cancer patients with normal EF, however, had GLS below normal lower limit, indicating that GLS can be effective in finding early subclinical myocardial dysfunction [ 14 , 15 ]. In addition, the average time after the completion of cancer related comprehensive therapy of the breast cancer patients in our study was 33 months. Although TnI, BNP and LVEF of these patients were in the normal range, 20% of these patients had an abnormal GLS, suggesting that the subclinical myocardial injury may persist for a long time after completion of anti-cancer therapy. Therefore, GLS should be used to monitor the early myocardial injury over a long period of time even after completion of cancer related comprehensive therapy. In our study, we found that the reduction of age was associated with LVEF reduction. Previous studies have shown that age > 65 years is a risk factor for cardiotoxicity of cancer therapy [ 16 ]. However, we found that LVEF reduction more easily occurred in younger patients. This may due to the fact that the average age of the patients in our study was 49 years old, with the youngest being 34 years old. Similarly, some studies have shown that the incidence of cardiotoxicity was elevated in younger patients. It was also found in a study with patients younger than 41 years old that there was a 6-fold increased risk of death resulting from cardiovascular diseases in patients treated for Hodgkin’s Disease before age 21, and that this elevated mortality decreased with increase of age [ 17 ]. The higher risks in patients treated at a younger age may be explained by a cardiovascular tissue that more vulnerable to cancer related therapy. In addition, the average age of patients treated with both anthracycline and trastuzumab in our study was 43 years old, while the average age of the other patients were 51 years old. This indicates that more younger patients received chemotherapy containing anthracycline plus targeted therapy in our study, while older patients chose non-combination therapy of anthracycline and trastuzumab. This may also explain the association of the reduction of age with LVEF reduction. Our study found that trastuzumab can cause a decrease in GLS, which has been confirmed by many other studies. The mechanism of GLS reduction induced by trastuzumab is that it binds to HER-2 receptor of myocardial cells, which leads to the imbalance of Bcl-xL and Bcl-sL and sequential activation of mitochondrial apoptotic pathway. These result in myocardial injury and the decrease of GLS. Myocaridal injury induced by trastuzumab, which is classified as type II CTRCD, leads to indirect cell injury and may be partly recovered after withdrawal of trastuzumab [ 5 ]. We do not find a relationship between use of anthracycline and cardiotoxicity. This may be explained by that the cumulative dosage of anthracycline for all patients that receive anthracycline therapy in our study is 400 mg/m 2 , which is below the waning dose of cardiotoxicity [ 18 ]. In addition, the number of patients in our study is small, and large-scale studies are still needed to further verify. In our study, we did not find the effect of left side-radiotherapy on the LVEF and GLS, which may be related to the use of intensity-modulated radiation therapy (IMRT) in our breast center. IMRT is a new radiotherapy technology that can reduce adverse events of radiotherapy [ 19 ]. IMRT allows for the radiation dose to conform more precisely to the three-dimensional (3-D) shape of the breast cancer by modulating the intensity of the radiation bean in multiple small volumes. IMRT also allows higher radiation doses to focused on the tumor while minimizing the dose to surrounding normal critical structures, including heart. Previous studies have shown that IMRT could effectively reduce clinical toxicities compared with conventional breast radiotherapy [ 20 , 21 ]. We included patients with metabolic syndrome in our study, and found that breast cancer comprehensive therapy caused subclinical myocardial dysfunction, compared with those without anti-cancer therapy. The metabolic syndrome has become a world-wide problem. The metabolic syndrome includes abdominal obesity, hyperlipidemia, hypertension and hyperglycemia. Previous studies have shown that obesity is associated with progression of breast cancer, due to the augmented level of enzyme aromatase and increased production of estrogen caused by obesity [ 22 , 23 ]. At the same time, patients with metabolic syndrome have a higher risk of cardiovascular disease. Obesity has been found to be a risk factor for cardiotoxicity of anthracyclines and trastuzumab in breast cancer patients [ 24 ]. Although we dose not found a correlation of obesity with GLS or LVEF, further study with large scale of people is needed to be designed to confirm this correlation. Limitations There are several limitations of our studies. Firstly, our study is a single center, cross-sectional study, although consecutive patients were enrolled in our study. Secondly, the number of the patients in our study is small. Thirdly, we investigated patients with different time point after completion of treatment, possible resulting in a loss of data with change of GLS and LVEF. Therefore, further studies with large scale of people are needed. Conclusions we found that breast cancer patients with metabolic syndrome after cancer related comprehensive treatment have a reduction of GLS and LVEF. GLS should be routinely performed to early identify subclinical myocardial damage of patients, in order to prevent the cardiotoxicity of cancer related comprehensive therapy. Abbreviations LVEF: left ventricular ejection fraction; GLS: global longitudinal strain; BNP: type B natriuretic peptide; TnI: troponin I Declarations Acknowledgements Not applicable Authors’ contributions FZ, SW and TZ concept and designed the study. FZ and SL analyzed the data. FZ and drafted the manuscript. SL, CY, SL, HC revised the manuscript. TZ and SW final approved the manuscript. Funding This study was supported by the National Natural Science Foundation of China (81400265) Availability of data and materials The datasets during and/or analysed during the current study available from the corresponding author on reasonable request. Ethics approval and consent to participate The study was approved by the Medical Ethics Committee of Peking University People’s Hospital (2018PHB032-02) and was registered by Chinese Clinical Trial Registry (ChiCTR1900022108). Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. 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Zhu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsElEQVRIiWNgGAWjYJACZoYKBhk2opXzgLWcYeAhUQtjG5gmEtjzL2D+XDjPjodPIsfsAUONTTRhWyQeMBjP3JbMwyaRY27AcCwtt4GwlgMMybzbmEFazCQYGw4Tp+Uw75x6UrTwNzA28zYcJkXLDQZmZp5jx3nYeJ6VSSQQ4xf2/gPMn3lqquXk25O3SXyosSGshUEi/wOEIZDAwJBAUDkI8B9AZ4yCUTAKRsEoQAMAsjMw+qjwSPUAAAAASUVORK5CYII=","orcid":"","institution":"Peking University People's Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Tiangang","middleName":"","lastName":"Zhu","suffix":""}],"badges":[],"createdAt":"2020-12-15 21:05:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-129387/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-129387/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":4474030,"identity":"454c63df-cceb-4f3f-8815-06e348c8f6b7","added_by":"auto","created_at":"2020-12-23 14:25:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":18202,"visible":true,"origin":"","legend":"LVEF (A) and GLS (B) in breast cancer patients with metabolic syndrome and non-cancer patients with metabolic syndrome","description":"","filename":"Onlinefigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-129387/v1/8df2b95dd98b82810e6aa390.png"},{"id":4342589,"identity":"7e0c091f-8837-4a18-8694-96bb5b16505f","added_by":"auto","created_at":"2020-12-17 18:00:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":18202,"visible":true,"origin":"","legend":"LVEF (A) and GLS (B) in breast cancer patients with metabolic syndrome and non-cancer patients with metabolic syndrome","description":"","filename":"Onlinefigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-129387/v1/e16c689c405137490a5e7430.png"},{"id":4342587,"identity":"0e4e822f-8605-43d2-ba3f-ae82e59014e6","added_by":"auto","created_at":"2020-12-17 18:00:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":18202,"visible":true,"origin":"","legend":"LVEF (A) and GLS (B) in breast cancer patients with metabolic syndrome and non-cancer patients with metabolic syndrome","description":"","filename":"Onlinefigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-129387/v1/4e48eef871aa9edf3d0818e2.png"},{"id":13634550,"identity":"b775ec6e-7d9c-4da4-a820-c9960daaad69","added_by":"auto","created_at":"2021-09-17 08:32:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":429452,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-129387/v1/e2a34c64-235f-49e9-b1c3-f16b0a7e2777.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eIdentification of Subclinical Myocardial Dysfunction in Breast Cancer Patients With Metabolic Syndrome After Cancer Related Comprehensive Therapy\u003c/p\u003e","fulltext":[{"header":"Background","content":" \u003cp\u003eThe incidence of metabolic syndrome has increased year by year with the unhealthy lifestyle. Previous study has estimated that 24.5% Chinese subjects over 15\u0026nbsp;years old had suffered from metabolic syndrome [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Recently several studies have shown that metabolic syndrome is involved in the occurrence, recurrence and metastasis of breast cancer, thus affecting the prognosis of breast cancer patients [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In China, there are a large number of breast cancer patients with metabolic syndrome, especially those with abdominal obesity. It is known that patients with metabolic syndrome have an increased risk of cardiovascular disease [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Furthermore, most of these breast cancer patients need to have cancer-related comprehensive therapy, including chemotherapy, targeted therapy, and radiotherapy, which may result in the further damage of their myocardium.\u003c/p\u003e \u003cp\u003eRecent studies have shown that chemotherapy, targeted therapy and radiotherapy in breast cancer patients can cause injury of the myocardium. Use of anthracyclines, one of most widely used chemotherapeutic drug, can lead to acute and chronic toxic damage to myocardium [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In addition, trastuzumab is often used in combination in HER2 or ErbB2 positive breast cancer patients. Although trastuzumab improves clinical outcomes by targeting the tumor, trastuzumab also causes an increased risk of cardiovascular adverse events, the most common of which is the left ventricular systolic dysfunction [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Furthermore, radiation therapy for left breast cancer can also cause cardiotoxicity, including cardiac insufficiency, due to its radiation to the heart [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe European Society of Cardiology have defined that cancer therapeutic related cardiac dysfunction (CTRCD) is that the reduction of left ventricle ejection fraction (LVEF) is over 10% or LVEF is decreased to a value below 50% [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, the decrease of LVEF that can be detected by echocardiogram may occur after sever damage of myocardium in patients. In more than half of these patients, left ventricular dysfunction has been permanently impaired and cannot be restored [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It was found that measurement of GLS using two-dimensional speckle tracing echocardiography (STE) can detect early change of left ventricular function, thus predicting the occurrence of CRTCD [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, due to the insufficient understanding of GLS, it is not routinely used in cancer patients [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In this study, we aim to evaluate the cardiotoxicity of patients by both LVEF and GLS, together.\u003c/p\u003e \u003cp\u003eRare studies focused on the cardiotoxicity of cancer related therapy in patients with metabolic syndrome. Therefore, our study observed the cardiac function in breast cancer patients with metabolic syndrome, compared with that in non-cancer patients with metabolic syndrome. We aimed to find the subclinical myocardial dysfunction of these patients and related risk factors, so as to early prevent cardiotoxicity in these patients.\u003c/p\u003e "},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003eStudy design and population\u003c/h2\u003e\n\u003cp\u003eIn our study (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e\u003ca href=\"http://www.chictr.org.cn/showproj.aspx?proj=35202\" target=\"_blank\"\u003ewww.chictr.org.cn\u003c/a\u003e\u003c/span\u003e\u003c/span\u003e Identifier: ChiCTR1900022108), 45 breast cancer patients with metabolic syndrome who were admitted to Breast Center of Peking University People\u0026rsquo;s Hospital from November 2018 to February 2019 were consecutively enrolled. The inclusion criteria were: (1) Patients were \u0026ge;\u0026thinsp;18 and \u0026le;\u0026thinsp;60\u0026nbsp;years old; (2) Patients were diagnosed with stage I-III breast cancer; (3) Patients have completed breast cancer surgery, chemotherapy, targeted therapy, and radiotherapy in Breast Center. (4) Patients had a body weight change of less than 10% in the past 6\u0026nbsp;months. (5) Patients had a waist circumference\u0026thinsp;\u0026ge;\u0026thinsp;80\u0026nbsp;cm with at least one abnormal indicator, including high blood glucose, high blood pressure and dyslipidemia. The exclusion criteria included: (1) Patients have heart, liver or kidney related diseases; (2) Patients have history of other caner. Age, height, weight, radiotherapy, targeted therapy and chemotherapy regimen, and cardiovascular risk factors were collected for each patient. Meanwhile, serum type B natriuretic peptide (BNP) and troponin I (TnI) were also collected. In addition, 45 non-cancer patients with metabolic syndrome were enrolled as matches. The inclusion criteria were (1), (4), (5), that the same with breast cancer patients, and no history of cancer, as well as no heart, liver, and kidney related disease.\u003c/p\u003e\n\u003ch2\u003eImage acquisition\u003c/h2\u003e\n\u003c/div\u003e\n\u003cp\u003eAll patients were examined by transthoracic echocardiography and contrast-enhanced echocardiography using GE95. All echocardiographic exams were performed by the same technician using the same machine. All images were interpreted by the same cardiologist. Contrast-enhanced echocardiography for left ventricular opacification (LVO) was used to improve the accuracy of quantitative assessment of LVEF. LVEF was calculated by the two-plane Simpson method. GLS was measured in all patients. The specific measurement is as follows. When the images were collected, we made an optimization of the gain, compress, and time-gain compensation controls to get clear appearance of the left ventricle. Then apical views (4,2 and 3 chambers) were collected using high frame rate (\u0026gt;\u0026thinsp;50 frames/s). The GLS was measured, and the boundary tracking was optimized by manual corrections. The images of each patient had no or just one segment of poor display.\u003c/p\u003e\n\u003cp\u003eAll participants provided written informed consent. The study was approved by the Medical Ethics Committee of Peking University People\u0026rsquo;s Hospital.\u003c/p\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003eStatistical analysis\u003c/h2\u003e\n\u003cp\u003eContinuous variables were represented by mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Categorical variables were expressed by percentage of patients in each group. Categorical variables were compared using Person\u0026rsquo;s chi-square test. Continuous variables were compared using independent sample t test. Multiple linear regression was used to analyzed the risk factors related to GLS and LVEF. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to have statistical significance. All the analyses were performed by SPSS 20.0 software.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eBaseline characteristics of the 45 breast cancer patients with metabolic syndrome and the 45 non-cancer patients with metabolic syndrome are shown as Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age of breast cancer patients was 49\u0026nbsp;years old. The mean BMI of breast cancer patients was 27.8\u0026nbsp;kg/m\u003csup\u003e2\u003c/sup\u003e. There are no significant differences in age, BMI, waist circumference and cardiovascular risk factors between breast cancer patients and non-cancer patients. All of the breast cancer patients with metabolic syndrome showed TnI and BNP levels within normal range.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eBaseline characteristics\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBreast cancer patients with metabolic syndrome\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNon-cancer patients with metabolic syndrome\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDemographics\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.442\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.674\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWaist circumference (cm)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e92.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e93.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.542\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCardiovascular risk factors\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCoronary heart disease\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHypertension\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (20%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (24%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.342\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHigh blood glucose\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13 (29%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15 (33%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.573\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDyslipidemia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26 (58%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24 (53%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.483\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBeta-blockers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.231\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eACE inhibitors\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (4%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.323\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVital sign\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSystolic blood pressure (mmHg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e122\u0026thinsp;\u0026plusmn;\u0026thinsp;18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e125\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.673\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDiastolic blood pressure (mmHg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e78\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e76\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.523\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCholesterol level (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal cholesterol\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.88\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.734\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLDL-c\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.634\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTG\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.82\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.79\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.667\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFasting glucose (mmol/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.782\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBreast cancer side\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLeft\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22 (49%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRight\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22 (49%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBoth\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eComprehensive therapy\u003c/p\u003e\n\u003cp\u003eChemothrapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45(100%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAnthracycline use\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31 (69%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTrastuzumab use\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20 (44%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBoth of anthracycline and trastuzumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (24%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLeft-side radiotherapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (36%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003eValues as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, or n (%).\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003eLDL-c\u0026thinsp;=\u0026thinsp;low density lipoprotein cholesterol; TG\u0026thinsp;=\u0026thinsp;triglyceride\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll patients have normal LVEF. However, four breast cancer patients with metabolic syndrome had LVEF that was lower than 60%, while no non-cancer patients with metabolic syndrome had LVEF that was lower than 60%. Furthermore, among the breast cancer patients with metabolic syndrome, nine patients (20%) had GLS that lower than \u0026minus;\u0026thinsp;17%, which is the normal lower limit of GLS. In contrast, there was no abnormality of GLS in the non-cancer patients with metabolic syndrome. In addition, we found that the breast cancer patients with metabolic syndrome had a decrease of GLS and LVEF (GLS: -19.95\u0026thinsp;\u0026plusmn;\u0026thinsp;2.98%, LVEF 67.19\u0026thinsp;\u0026plusmn;\u0026thinsp;5.92%), compared with the non-cancer patients with metabolic syndrome (GLS \u0026minus;\u0026thinsp;21.53\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32%,LVEF 70.63\u0026thinsp;\u0026plusmn;\u0026thinsp;3.24%) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eA, B).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMultivariate linear regression analysis was performed to identify possible factors that affected LVEF and GLS in breast cancer patients. Age, BMI, use of anthracycline, use of trastuzumab and left-side radiotherapy were included. We found that age was a significant factor that affected LVEF (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Specifically, decrease of age was associated with decrease of LVEF. Moreover, use of trastuzumab was a significant factor that associated with reduction of GLS (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eMultivariate analysis for LVEF in breast cancer patients with metabolic syndrome after treatment\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFactor\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026beta;\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSE\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.328\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.127\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.014\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.343\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.270\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.211\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAnthracycline\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-0.020\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.073\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.992\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTrastuzumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-1.442\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.901\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.453\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLeft-side radiotherapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.133\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.802\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.244\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eMultivariate analysis for GLS in breast cancer patients with metabolic syndrome after treatment\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eFactor\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u0026beta;\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSE\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eP value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.014\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.076\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.855\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBMI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e-0.222\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.154\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.160\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAnthracycline\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.767\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.194\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.525\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTrastuzumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.489\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.107\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.031\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLeft-side radiotherapy\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.578\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.077\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.595\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":" \u003cp\u003eIn this study, we observe the subclinical myocardial dysfunction of breast cancer patients with metabolic syndrome after completion of cancer related comprehensive therapy. We measured LVEF and GLS in these patients, compared those with non-cancer patients with metabolic syndrome, and identified risk factors that may be associated with subclinical myocardial dysfunction.\u003c/p\u003e \u003cp\u003eOur main findings are as follows: (1) Breast cancer patients with metabolic syndrome after completion of cancer related comprehensive therapy have decreased LVEF and GLS, compared to those without cancer, even though their LVEF are all within normal range; (2) Decreased age is the risk factor of LVEF reduction in breast cancer patients with metabolic syndrome, while use of trastuzumab is associated with the reduction of GLS.\u003c/p\u003e \u003cp\u003eOur study used both LVEF and GLS to observe the myocardial injury of breast cancer patients with metabolic syndrome. LVEF is the regular method to be used in evaluation of myocardial function in cancer patients with tumor-related therapy. In contrast, echocardiography-based myocardial strain is a novel way to detect subclinical dysfunction of left ventricle. GLS may be a more sensitive predictor of toxicity of heart, compared to LVEF. This may be explained by following reasons. Chemotherapy may affect just certain segments of left ventricle, resulting in the early reduction of GLS. Other region of left ventricle may have compensatory enhanced movement, leading to unchanged LVEF [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In addition, LVEF may be affected by many other conditions including preload, heart rate, and et al [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Tracing process is often used in measurement of LVEF. In contrast, GLS may adopt more accurate measurement through STE (Specking Tracking Echocardiogram). Therefore, 2014 ASE/EACVI Expert Consensus recommend that GLS can be used to early detect subclinical dysfunction of left ventricle in the patients with chemotherapy [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Indeed, we observed that a reduction of GLS in the breast cancer patients with metabolic syndrome after treatment, and that 9 breast cancer patients with normal EF, however, had GLS below normal lower limit, indicating that GLS can be effective in finding early subclinical myocardial dysfunction [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition, the average time after the completion of cancer related comprehensive therapy of the breast cancer patients in our study was 33 months. Although TnI, BNP and LVEF of these patients were in the normal range, 20% of these patients had an abnormal GLS, suggesting that the subclinical myocardial injury may persist for a long time after completion of anti-cancer therapy. Therefore, GLS should be used to monitor the early myocardial injury over a long period of time even after completion of cancer related comprehensive therapy.\u003c/p\u003e \u003cp\u003eIn our study, we found that the reduction of age was associated with LVEF reduction. Previous studies have shown that age\u0026thinsp;\u0026gt;\u0026thinsp;65\u0026nbsp;years is a risk factor for cardiotoxicity of cancer therapy [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. However, we found that LVEF reduction more easily occurred in younger patients. This may due to the fact that the average age of the patients in our study was 49\u0026nbsp;years old, with the youngest being 34\u0026nbsp;years old. Similarly, some studies have shown that the incidence of cardiotoxicity was elevated in younger patients. It was also found in a study with patients younger than 41\u0026nbsp;years old that there was a 6-fold increased risk of death resulting from cardiovascular diseases in patients treated for Hodgkin\u0026rsquo;s Disease before age 21, and that this elevated mortality decreased with increase of age [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The higher risks in patients treated at a younger age may be explained by a cardiovascular tissue that more vulnerable to cancer related therapy. In addition, the average age of patients treated with both anthracycline and trastuzumab in our study was 43\u0026nbsp;years old, while the average age of the other patients were 51\u0026nbsp;years old. This indicates that more younger patients received chemotherapy containing anthracycline plus targeted therapy in our study, while older patients chose non-combination therapy of anthracycline and trastuzumab. This may also explain the association of the reduction of age with LVEF reduction.\u003c/p\u003e \u003cp\u003eOur study found that trastuzumab can cause a decrease in GLS, which has been confirmed by many other studies. The mechanism of GLS reduction induced by trastuzumab is that it binds to HER-2 receptor of myocardial cells, which leads to the imbalance of Bcl-xL and Bcl-sL and sequential activation of mitochondrial apoptotic pathway. These result in myocardial injury and the decrease of GLS. Myocaridal injury induced by trastuzumab, which is classified as type II CTRCD, leads to indirect cell injury and may be partly recovered after withdrawal of trastuzumab [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. We do not find a relationship between use of anthracycline and cardiotoxicity. This may be explained by that the cumulative dosage of anthracycline for all patients that receive anthracycline therapy in our study is 400\u0026nbsp;mg/m\u003csup\u003e2\u003c/sup\u003e, which is below the waning dose of cardiotoxicity [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In addition, the number of patients in our study is small, and large-scale studies are still needed to further verify.\u003c/p\u003e \u003cp\u003eIn our study, we did not find the effect of left side-radiotherapy on the LVEF and GLS, which may be related to the use of intensity-modulated radiation therapy (IMRT) in our breast center. IMRT is a new radiotherapy technology that can reduce adverse events of radiotherapy [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. IMRT allows for the radiation dose to conform more precisely to the three-dimensional (3-D) shape of the breast cancer by modulating the intensity of the radiation bean in multiple small volumes. IMRT also allows higher radiation doses to focused on the tumor while minimizing the dose to surrounding normal critical structures, including heart. Previous studies have shown that IMRT could effectively reduce clinical toxicities compared with conventional breast radiotherapy [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe included patients with metabolic syndrome in our study, and found that breast cancer comprehensive therapy caused subclinical myocardial dysfunction, compared with those without anti-cancer therapy. The metabolic syndrome has become a world-wide problem. The metabolic syndrome includes abdominal obesity, hyperlipidemia, hypertension and hyperglycemia. Previous studies have shown that obesity is associated with progression of breast cancer, due to the augmented level of enzyme aromatase and increased production of estrogen caused by obesity [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. At the same time, patients with metabolic syndrome have a higher risk of cardiovascular disease. Obesity has been found to be a risk factor for cardiotoxicity of anthracyclines and trastuzumab in breast cancer patients [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Although we dose not found a correlation of obesity with GLS or LVEF, further study with large scale of people is needed to be designed to confirm this correlation.\u003c/p\u003e "},{"header":"Limitations","content":" \u003cp\u003eThere are several limitations of our studies. Firstly, our study is a single center, cross-sectional study, although consecutive patients were enrolled in our study. Secondly, the number of the patients in our study is small. Thirdly, we investigated patients with different time point after completion of treatment, possible resulting in a loss of data with change of GLS and LVEF. Therefore, further studies with large scale of people are needed.\u003c/p\u003e "},{"header":"Conclusions","content":" \u003cp\u003ewe found that breast cancer patients with metabolic syndrome after cancer related comprehensive treatment have a reduction of GLS and LVEF. GLS should be routinely performed to early identify subclinical myocardial damage of patients, in order to prevent the cardiotoxicity of cancer related comprehensive therapy.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eLVEF: left ventricular ejection fraction; GLS: global longitudinal strain; BNP: type B natriuretic peptide; TnI: troponin I\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFZ, SW and TZ concept and designed the study. FZ and SL analyzed the data. FZ and drafted the manuscript. SL, CY, SL, HC revised the manuscript. TZ and SW final approved the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the National Natural Science Foundation of China (81400265)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets during and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Medical Ethics Committee of Peking University People\u0026rsquo;s Hospital (2018PHB032-02) and was registered by Chinese Clinical Trial Registry (ChiCTR1900022108).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\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"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLi R, Li W, Lun Z, Zhang H, Sun Z, Kanu J, Qiu S, Cheng Y, Liu Y. Prevalence of metabolic syndrome in Mainland China: a meta-analysis of published studies. BMC Public Health 2016;16(1):296-305.\u003c/li\u003e\n\u003cli\u003ePothiwala P, Jain SK, Yaturu S. Metabolic syndrome and cancer. Metab Syndr Relat Disord. 2009;7(4):279-288.\u003c/li\u003e\n\u003cli\u003eZeller M, Steg PG, Ravisy J, Lorgis L, Laurent Y, Sicard P, Janin-Manificat L, Beer JC, Makki, H, Lagrost AC. Relation between body mass index, waist circumference, and death after acute myocardial infarction. Circulation. 2008;118(5):482-490.\u003c/li\u003e\n\u003cli\u003eMenna P, Minotti G, Salvatorelli E. Cardiotoxicity of Targeted Cancer Drugs: Concerns, \"The Cart Before the Horse,\" and Lessons from Trastuzumab. Curr Cardiol Rep. 2019;21:33.\u003c/li\u003e\n\u003cli\u003eNemeth BT, Varga ZV, Wu WJ, Pacher P. Trastuzumab cardiotoxicity: from clinical trials to experimental studies. Br J Pharmacol. 2016;174(21):3727-3748.\u003c/li\u003e\n\u003cli\u003eRaghunathan D, Khilji MI, Hassan SA, Yusuf SW. Radiation-Induced Cardiovascular Disease. Curr Atheroscler Rep. 2017;19(5):22.\u003c/li\u003e\n\u003cli\u003eZamorano JL, Lancellotti P, Rodriguez MD, Aboyans V, Asteggiano R, Galderisi M, Habib G, Lenihan DJ, Lip GYH, Lyon AR. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(36):2768-2801.\u003c/li\u003e\n\u003cli\u003eSantoro C, Arpino G, Esposito R, Lembo M, Paciolla I, Cardalesi C, Simone G, Trimarco B, Placido SD, Galderisi M. 2D and 3D strain for detection of subclinical anthracycline cardiotoxicity in breast cancer patients: a balance with feasibility. Eur Heart J Cardiovasc Imaging. 2017;18(8):930-936.\u003c/li\u003e\n\u003cli\u003eGeyer H, Caracciolo G, Abe H, Wilansky S, Carerj S, Gentile F, Nesser HJ, Khandheria B, Narula J, Sengupta PP. Assessment of myocardial mechanics using speckle tracking echocardiography: fundamentals and clinical applications. J Am Soc Echocardiogr. 2010;23(4):351-369.\u003c/li\u003e\n\u003cli\u003eSawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Tan TC, Cohen V, Banchs J, Carver JR, Wiegers SE, et al. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging. 2012;5(5):596-603.\u003c/li\u003e\n\u003cli\u003eSawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Cohen V, Gosavi S, Carver JR, Wiegers SE, Martin RP, et al. Early detection and prediction of cardiotoxicity in chemotherapy-treated patients. Am J Cardiol. 2011;107(9):1375-1380.\u003c/li\u003e\n\u003cli\u003eWeinberg BA, Conces DJ, Jr., Waller BF. Cardiac manifestations of noncardiac tumors. Part II: Direct effects. Clin Cardiol. 1989;12(6):347-354.\u003c/li\u003e\n\u003cli\u003ePlana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, Ganame J, Sebag IA, Agler DA, Badano LP, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2014;15(10):1063-93.\u003c/li\u003e\n\u003cli\u003eOng G, Brezden-Masley C, Dhir V, Deva DP, Chan KW, Chow CM, Thavendiranathan D, Haq R, Barfett JJ, Petrella TM, et al. Myocardial strain imaging by cardiac magnetic resonance for detection of subclinical myocardial dysfunction in breast cancer patients receiving trastuzumab and chemotherapy. Int J Cardiol 2018;261:228-233.\u003c/li\u003e\n\u003cli\u003eLaufer-Perl M, Derakhshesh M, Milwidsky A, Mor L, Ravid D, Amrami N, Sherez J, Keren G, Topilsky Y, Arbel Y. Usefulness of Global Longitudinal Strain for Early Identification of Subclinical Left Ventricular Dysfunction in Patients With Active Cancer. Am J Cardiol 2018;122(10):1784-1789.\u003c/li\u003e\n\u003cli\u003eShenoy C, Klem I, Crowley AL, Patel MR, Winchester MA, Owusu C, Kimmick GG. Cardiovascular complications of breast cancer therapy in older adults. Oncologist. 2011;16(8):1138-1143.\u003c/li\u003e\n\u003cli\u003eAleman BM, van den Belt-Dusebout AW, Klokman WJ, Van't Veer MB, Bartelink H, van Leeuwen FE. Long-term cause-specific mortality of patients treated for Hodgkin's disease. J Clin Oncol. 2003;21(18):3431-3439.\u003c/li\u003e\n\u003cli\u003eGianni L, Herman EH, Lipshultz SE, Minotti G, Sarvazyan N, Sawyer DB. Anthracycline cardiotoxicity: from bench to bedside. J Clin Oncol. 2008;26(22):3777-3784.\u003c/li\u003e\n\u003cli\u003eDayes I, Rumble RB, Bowen J, Dixon P, Warde P. Intensity-modulated radiotherapy in the treatment of breast cancer. Clin Oncol (R Coll Radiol). 2012;24(7):488-498.\u003c/li\u003e\n\u003cli\u003eHarsolia A, Kestin L, Grills I, Wallace M, Jolly S, Jones C, Lala M, Martinez A, Schell S, Vicini FA. Intensity-modulated radiotherapy results in significant decrease in clinical toxicities compared with conventional wedge-based breast radiotherapy. Int J Radiat Oncol Biol Phys. 2007;68(5):1375-1380.\u003c/li\u003e\n\u003cli\u003eHurkmans CW, Cho BC, Damen E, Zijp L, Mijnheer BJ. Reduction of cardiac and lung complication probabilities after breast irradiation using conformal radiotherapy with or without intensity modulation. Radiother Oncol. 2002;62(2):163-171.\u003c/li\u003e\n\u003cli\u003eCalle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625-1638.\u003c/li\u003e\n\u003cli\u003eBraun S, Bitton-Worms K, LeRoith D. The link between the metabolic syndrome and cancer. Int J Biol Sci. 2011;7(7):1003-1015.\u003c/li\u003e\n\u003cli\u003eCheraghi Z, Ayubi E, Doosti-Irani A. Obesity As a Risk Factor for Anthracyclines and Trastuzumab Cardiotoxicity in Breast Cancer: Methodologic Issues to Avoid Misinterpretation in the Meta-Analysis. J Clin Oncol. 2016;35(8):923.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"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":"Subclinical Myocardial Dysfunction, Breast Cancer, Metabolic Syndrome, Cancer Related Comprehensive Therapy","lastPublishedDoi":"10.21203/rs.3.rs-129387/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-129387/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Breast cancer patients with metabolic syndrome have an increased risk of cardiovascular disease. These patients are more prone to suffer from cardiotoxicity after anti-cancer therapy. Patients after completion of cancer related comprehensive therapy, who show normal myocardial function, may already have subclinical myocardial dysfunction. We sought to evaluate the subclinical myocardial dysfunction in breast cancer patients with metabolic syndrome after cancer related comprehensive therapy.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: In this study, 45 breast cancer patients with metabolic syndrome after completion of cancer related comprehensive therapy and 45 non-breast cancer patients with metabolic syndrome were enrolled. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were measured using echocardiogram.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: All the patients have normal LVEF. However, nine breast cancer patients (20%) had GLS that was lower than -17%, while all the non-cancer patients have normal GLS. Breast cancer patients with metabolic syndrome had a decrease of GLS and LVEF, compared with non-cancer patients with metabolic syndrome. Furthermore, we found that decrease of age was associated with reduction of LVEF, and that use of trastuzumab for 1 year was a significant factor that associated with reduction of GLS.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Breast cancer patients with metabolic syndrome after completion of cancer related comprehensive therapy suffered from subclinical myocardial dysfunction. GLS should be routinely performed to early identify subclinical myocardial damage of patients, in order to prevent the cardiotoxicity of cancer related comprehensive therapy.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e: the Medical Ethics Committee of Peking University People’s Hospital, 2018PHB032-02, Registered 23 November 2018, \u003c/p\u003e\u003cp\u003ehttp://www.chictr.org.cn/showproj.aspx?proj=35202\u003c/p\u003e","manuscriptTitle":"Identification of Subclinical Myocardial Dysfunction in Breast Cancer Patients With Metabolic Syndrome After Cancer Related Comprehensive Therapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-12-17 18:00:29","doi":"10.21203/rs.3.rs-129387/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":"78b8b54d-088d-4a02-a656-1bcf79016036","owner":[],"postedDate":"December 17th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":1520310,"name":"Cardiac \u0026 Cardiovascular Systems"}],"tags":[],"updatedAt":"2020-12-23T14:22:39+00:00","versionOfRecord":[],"versionCreatedAt":"2020-12-17 18:00:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-129387","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-129387","identity":"rs-129387","version":["v1"]},"buildId":"GqpaHPwrfC8PjnIFayRh5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}