Late Gadolinium Enhancement CMR for Detecting Myocardial Injury after Oncotherapy: Correlation with Left Ventricular Function

Late Gadolinium Enhancement CMR for Detecting Myocardial Injury after Oncotherapy: Correlation with Left Ventricular Function | 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 Late Gadolinium Enhancement CMR for Detecting Myocardial Injury after Oncotherapy: Correlation with Left Ventricular Function Xi Liu, Yue Gao, Zhen Wang, Wei-Feng Yan, Rui Shi, Chun-Xiao Zheng, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7780372/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 Clinically, cardiotoxicity defined by reduced left ventricle ejection fraction (LVEF) in tumor therapy could miss the onset of tissue-level myocardial changes. In this study, we aimed to use late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) to evaluate myocardial injury in patients receiving oncotherapy, and to investigate the effect of LGE and other clinical factors on LV function. Material and method This study included 108 cancer patients and 60 healthy controls examined by CMR imaging. Patients were assigned to the LGE-negative (LGE−, n = 80) and LGE-positive groups (LGE+, n = 28). The LV functional parameters and myocardial strain parameters, were compared among the three subgroups. Associations between variables were evaluated via Pearson or Spearman correlation analyses. Further, the association between risk factors and LVEF was determined via multivariate linear regression analysis. Results The LVEF and peak strain (PS) in all directions were significantly lower in the patients with LGE than in those without (all p < 0.05). There were moderate to high correlations between circumferential peak diastolic strain rate (PDSR), peak systolic strain rate (PSSR), PS, and LVEF in the patients with cancer (r = 0.54, r = -0.63, r = 0.82, respectively; p < 0.001). Multivariate linear regression analysis revealed independent associations between 1) N-terminal-pro B-type natriuretic peptide and radial, circumferential and longitudinal PS (β = −0.419, β = 0.407, β = 0.327, respectively; p < 0.001), 2) troponin T and circumferential PDSR (β = 0.342, p < 0.001) and between 3) the LGE extent (LGE%, 5SD) and circumferential PS (β = 0.297, p < 0.001). Conclusion The presence of LGE was an important risk factor for LV dysfunction in patients receiving cancer therapy, and the circumferential strain reduction is the predominant mechanism of LV dysfunction. cancer therapy-related cardiotoxicity cardiovascular magnetic resonance late gadolinium enhancement myocardial strain Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Significant advancements in cancer therapeutics, including conventional chemotherapy, immunotherapy, targeted therapy, radiotherapy, and therapeutic combinations, have led to improved long-term survival in patients with cancer, however, these therapeutic options are potentially cardiotoxic. Cancer survivors are at higher risk than the general population for developing cardiac disease, which is the leading cause of noncancer-related mortality in cancer survivors (1,2). Timely and accurate identification of cancer therapy-related cardiotoxicity, which poses a formidable challenge for oncologists and cardiologists, is crucial to enable the targeted use of cardioprotective interventions and/or to introduce alternative treatment strategies (3). Although cancer therapy-related cardiotoxicity has received increased attention in recent years, previous studies of cancer therapy-related cardiotoxicity and causative factors have been oversimplified and failed to reflect the complex pathophysiological differences. In routine clinical practice, cancer patients usually receive multiple cancer drug treatments, with the potential for cardiotoxic effects from interactions among the different therapy modalities. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging provides tissue characterization and enables detection of myocardial fibrosis and/or edema associated with cardiotoxic therapy (4,5). There are currently limited data on LGE detection of cardiotoxicity in patients receiving cancer-related treatment, and some studies have obtained conflicting results. Therefore, this study aimed to use LGE to characterize myocardial damage in a somewhat diverse population that included several cancer types and treatment regimens. We also investigated the effect of LGE and other clinical factors on left ventricular (LV) function. Material and Methods Study population We conducted a retrospective study of patients with various cancer who were referred for clinical CMR for suspected cardiotoxicity between June 2018 and March 2025. The inclusion criteria were age >18 years and had received at least one antitumor treatment (including conventional chemotherapy, immunotherapy, targeted therapy, or radiotherapy). The exclusion criteria were pre-existing symptomatic heart failure (NYHA Class III or IV), a history of myocardial infarction, or chronic arrhythmia such as atrial fibrillation, incomplete medical records, or inadequate CMR studies. Besides, 2 cancer patients with coronary heart disease were excluded from the study cohort due to extensive ischemic LGE caused by silent myocardial infarction. We also included 60 age- and sex-matched normal controls who underwent CMR. The exclusion criteria were clinical evidence of cancer, cardiovascular disease, or other systemic disease or inadequate CMR studies. This retrospective study was approved by the Institutional Review Board, which waived the requirement for written informed consent. Clinical data extraction Detailed clinical data were extracted from the electronic medical records. We collected the following data: demographic characteristics, vital signs, cancer treatments, previous cardiovascular history, cardiovascular risk factors, and cardiac biomarkers including serum N-terminal pro–B-type natriuretic peptide (NT-pro BNP) and troponin T. We then counted the number of cardiovascular disease risk factors (known coronary artery disease, hypertension, diabetes mellitus, smoking, or elevated cholesterol) to enable calculation of a cardiovascular disease score (range: 0–5). MR protocol The CMR examinations were performed on 3T scanner (Tim Trio/Skyra, Siemens, Erlangen, Germany) with standard image acquisitions. The data included cine images acquired with a balanced steady-state free-precession sequence (TR: 2.9/3.4 ms; TE：1.25 /1.3 ms; flip angle: 50/40°; slice thickness: 8 mm; field of view: 319 × 249/339 × 284 mm 2 ; matrix size 256 × 166/256 × 144), and LGE imaging using a T1-weighted inversion recovery turbo FLASH sequence (TR：650/500 ms; TE: 1.43/ 1.24 ms, flip angle: 50 /40°, slice thickness: 8 mm, field of view: 340×255/340×233 mm 2 , matrix size: 256×192/ 256×125) conducted for 10–15 min after intravenous administration of gadolinium-based contrast agent. Image analysis All CMR imaging data were analyzed by an experienced radiologist (>8 years of experience in interpreting CMR) using commercially available software (cvi42 version 5.11.2, Circle Cardiovascular Imaging Inc., Calgary, Canada). The LV function parameters, including the end diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV), and ejection fraction (EF), as described in a previous study were acquired (6).To analyze the LV myocardial strain, the short- and long-axis two-chamber and four-chamber slices of the cine images were loaded into the tissue-tracking module, as described in our previous study (6). The LV global strain parameters, including radial, circumferential, and longitudinal peak strain (PS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR) were estimated automatically. LGE was visually identified as positive (LGE+) if there were hyperintense regions within the myocardium in the short- or long-axis views. In addition, for LGE quantification, the extent of LGE based on the signal threshold analysis was performed using sequential short axis LGE images. LGE lesion was evaluated semi-quantitatively as above the five-fold standard deviation (5SD) of the remote reference myocardium that demonstrated the lowest signal intensity (Figure 1). The LGE extent was calculated as the ratio of the LGE lesion volume to the total LV myocardium volume. Statistical analysis SPSS software (version 23.0), GraphPad Prism software (version 8.0.1), and R software (R studio version 1.4.1717) were used to perform the statistical analyses.Categorical variables are presented as numbers (percentages) and compared by performing Fisher’s exact or Chi-squared tests. Continuous variables are presented as means ± standard deviations or as medians and interquartile ranges. Normality was evaluated by performing the Kolmogorov–Smirnov test, and the homogeneity of variance was assessed by performing Levene’s test. Comparative analyses were repeated in subgroups after stratification of the study cohort into three categories (control, cancer patients without LGE, and cancer patients with LGE) by performing one-way analysis of variance, followed by Bonferroni post hoc correction or its nonparametric equivalent (Kruskal–Wallis test), as appropriate. Associations between variables were investigated by performing Pearson or Spearman correlation analyses. Furthermore, univariate factors of p < 0.1 were then included in the stepwise multivariate analysis. NT-pro BNP was log-transformed before inclusion in the regression analysis. Values ofp <0.05 were accepted as indicating statistical significance. Results Baseline characteristics The final study cohort comprised 108 patients with cancer who received potentially cardiotoxic therapy and 60 healthy controls. On CMR images, LGE was identified in 28/108 (25.93%) of the patients with cancer. The patients with cancer without and with LGE were assigned to the LGE-negative (LGE−) group (n = 80) and LGE-positive (LGE+) group (n = 28). The baseline characteristics of the study population were presented in Table 1 . Table 1 Baseline Characteristics of Control Individuals, Cancer Patients without or with LGE normal n = 60 Patients (LGE-) n = 80 Patients (LGE+) n = 28 Age, y 55.00(49.00, 63.00) 62.00(50.00, 67.00) 60.00(53.00, 71.00) Male gender, n (%) 26(43.33%) 41(51.25%) 19(67.85%) BMI, kg/m 2 23.52 ± 3.15 22.52 ± 3.75 23.42 ± 3.01 Heart rate, bpm 74.60(66.91, 78.27) 79.96(71.34, 94.09) 85.07(75.14, 95.38) * Diastolic BP (mmHg) 125.75 ± 15.42 1119.57 ± 16.14 121.32 ± 18.76 Systolic BP (mmHg) 77.16 ± 9.98 77.51 ± 11.48 83.67 ± 14.85 * CV risk factors Smoking, n (%) - 23(28.75%) 8(28.57%) Hypertension, n (%) - 20(25.00%) 7(25.00%) Diabetes, n (%) - 13(16.25%) 4(14.29%) Hyperlipidemia, n (%) - 7(8.75%) 3(10.71%) Coronary artery disease, n (%) - 7(8.75%) 5(17.86%) CVD score, n (%) - 42/17/11/9/1/0 14/6/4/3/1/0 Biomarker NT-pro BNP, pg/ml - 154.0(49.0, 455.0) 256.0(49.0,743.0) † Troponin T, pg/ml - 21.00(7.1, 59.4) 41.33(18.7, 99.1) † Cancer treatment Anthracyclines, n (%) - 14(17.50%) 2(7.14%) Targeted agents, n (%) - 24(30.00%) 19(67.86%) † ICIs, n (%) - 26(32.50%) 9(32.14%) Antimetabolic, n (%) - 23(28.75%) 8(28.57%) Antimicrotubule agents, n (%) - 36(45.00%) 7(25.00%) Alkylating agents, n (%) - 62(77.50%) 15(53.57%) † Chest radiotherapy, n (%) - 17(21.25%) 7(25.00%) Note: Data given as the mean ± SD, n (%), or median (25th to 75th percentile), *p < 0.05 vs controls; † p < 0.05 vs patients without LGE. BMI: body mass index; BP: blood pressure; CV: cardiovascular; CVD: cardiovascular disease; NT-pro BNP, N-terminal pro–B-type natriuretic peptide; ICIs, immune checkpoint inhibitors. Pre-existing coronary heart disease was present in 11.11% of the patients with cancer. However, there were no significant differences in coronary artery disease, other cardiovascular risk factors, or cardiovascular disease score between the two groups. We observed that NT-pro BNP and troponin T were significantly higher in the LGE + group than in the LGE − group (256.0(49.0,743.0) vs. 154.0(49.0, 455.0); 41.33(18.7, 99.1) vs. 21.00(7.1, 59.4); respectively; p < 0.05). There were no significant differences in the cancer type or whether it was combined with metastasis among the two subgroups. The proportion of patients with a therapeutic regimen that included targeted therapy was significantly higher in the LGE + group than in the LGE − group (67.86% vs. 30.00%). However, the proportion of patients whose therapeutic regimens were > 3 was lower in the LGE + than in the LGE − groups (16.67% vs 41.77%). CMR imaging results Our results showed that 28 (25.93%) patients with cancer exhibited abnormal LGE. On CMR images, LGE mainly occurred at midmyocardium and/or subepicardial of the LV (23/28, 82.14%), and the distribution of LGE did not fit a single profile, including focal pattern, multiple and diffuse pattern (Fig. 2 ). Table 2 presents the data on the functional and strain parameters of the LV of the control subjects, LGE − group, and LGE + group. The LVEF values were lower in the LGE + and LGE − groups than in the healthy controls (all p < 0.05), and LVEF was significantly lower in the LGE + group than in the LGE− (p < 0.05). The prevalence of LV systolic dysfunction (LVEF < 55%) was significantly higher in the LGE + group than in the LGE − group (60.71% vs. 23.75%, p < 0.05). Compared with the normal controls, the LV radial, circumferential and longitudinal PS of patients with LGE and those without LGE significantly impaired (all p < 0.05). The LV radial, circumferential, and longitudinal PS were significantly lower in the LGE + group than in the LGE − group (all p < 0.05). Besides, the LV longitudinal, circumferential, and radial PDSR also were significantly lower in the patient groups than in the controls (all p < 0.05). Only the LV radial and circumferential PSSR were significantly lower in the LGE + group than in the LGE − group and control subjects (all p < 0.05) (Fig. 3 ). Table 2 CMR Parameters between Normal Individuals, Cancer Patients without or with LGE normal n = 60 Patients (LGE-) n = 80 Patients (LGE+) n = 28 LVEDVI, ml/m 2 72.10(64.82–79.44) 70.86(57.45,82.51) 69.39(60.22,78.99) LVESVI, ml/m 2 24.22(19.99–28.14) 24.26(20.03,32.77) 27.50(23.70,36.67) LVSVI, ml/m 2 46.18(41.27–52.14) 41.71(34.25,47.99) * 36.86(27.35,47.51) * LVEF, % 65.85(62.61–70.15) 62.62(56.34,67.94) * 53.43(46.86,64.20) *† PS (%) Radial 40.11(34.32–44.17) 32.11(24.51,41.74) * 27.11(12.71,30.48) *† Circumferential -21.27(-23.00-(-19.55) -19.70(-21.66, -16.40) * -16.35(-19.26, -10.13) *† Longitudinal -15.57(-17.85-(-13.59) -13.00(-14.66, -9.15) * -10.02(-12.57, -6.41) *† PSSR (1/s) Radial 2.18(1.97–2.67) 2.20(1.54,2.82) 1.51(1.00,2.38) *† Circumferential -1.10(-1.21-(-0.96) -1.08(-1.35, -0.86) -0.96(-1.16, -0.66) *† Longitudinal -0.83(-0.98-(-0.71) -0.81(-0.98, -0.63) -0.67(-0.89, -0.53) PDSR (1/s) Radial -3.01(-3.71-(-2.34) -2.17(-2.66, -1.53) * -1.63(-2.46, -1.27) * Circumferential 1.43(1.25-(1.58) 1.11(0.87,1.30) * 1.07(0.75,1.27) * Longitudinal 1.03(0.89–1.27) 0.80(0.59,0.99) * 0.71(0.56,0.85) * LVEF<55% (n,%) 19(23.75%) 17(60.71%) † Note: Data given as the median (25th, 75th percentile), *p < 0.05 vs controls; † p < 0.05 vs patients without LGE. LV, left ventricular; end diastolic volume; ESV, end systolic volume; SV, stroke volume; EF, ejection fraction; I, indexed to BSA; PS, Peak Strain; PSSR, Peak Systolic Strain Rate; PDSR, Peak Diastolic Strain Rate. Correlation between the clinical data and CMR parameters In the multivariate analysis the factors that could potentially influence LV strain, including age, sex, BMI, systolic blood pressure, cardiovascular risk factors, cardiac biomarker, therapeutic regimens, and the LGE extent were adjusted. Multivariate linear regression analysis revealed that NT-pro BNP was independently associated with the radial, circumferential and longitudinal PS (β = −0.419, β = 0.407, β = 0.327, respectively; p < 0.001) (Table 3 ). The NT-pro BNP was independently associated with the circumferential PSSR (β = 0.362, p < 0.001) (Table S1 ). In addition, the troponin T was independently associated with the circumferential PDSR (β = 0.342, p < 0.001) (Table S2) (Fig. 4 ). The LGE extent was independently associated with circumferential PS (β = 0.297, p < 0.001). No significant correlations between cardiovascular risk factors and LV strain parameters were found. Table 3 Multivariate linear regression of factors associated with left ventricle peak strain Radial PS Circumferential PS Longitudinal PS Univariable Multivariable Univariable Multivariable Univariable Multivariable r p β p r p β p r p β p Age 0.640 0.510 -0.009 0.926 -0.031 0.754 Male gender -0.073 0.453 0.067 0.493 -0.027 0.778 BMI 0.026 0.791 -0.093 0.338 0.024 0.804 Systolic BP 0.128 0.186 0.200 0.038 -0.207 0.008 -0.012 0.898 LGE%(5SD) -0.282 0.003 -0.187 0.030 0.410 < 0.001 0.297 < 0.001 0.304 0.001 0.237 0.010 NT-pro BNP & -0.459 < 0.001 -0.419 < 0.001 0.500 < 0.001 0.407 < 0.001 0.383 < 0.001 0.327 < 0.001 Troponin T 0.175 0.070 -0138 0.101 -0.189 0.050 -0.122 0.132 -0.111 0.252 Smoking 0.083 0.393 -0.126 0.192 -0.083 0.395 Hypertension -0.054 0.582 0.019 0.846 0.095 0.330 Diabetes 0.218 0.023 0.231 0.006 -0.208 0.031 -0.136 0.080 -0.142 0.143 Hyperlipidemia -0.002 0.983 0.037 0.701 0.033 0.746 Prior coronary artery disease -0.071 0.466 0.054 0.580 -0.008 0.938 Anthracyclines -0.129 0.183 0.098 0.314 0.024 0.808 Targeted agents -0.265 0.006 -0.145 0.089 0.262 0.006 0.127 0.120 0.208 0.031 0.100 0.295 Immune checkpoint inhibitor 0.072 0.457 -0.088 0.367 -0.113 0.246 Antimetabolic 0.036 0.708 -0.062 0.521 0.083 0.391 Antimicrotubule agents 0.074 0.466 -0.123 0.203 -0.032 0.739 Alkylating agents 0.144 0.137 -0.227 0.018 -0.166 0.035 -0.012 0.898 Chest radiotherapy 0.073 0.454 -0.084 0.386 -0.045 0.646 Note: Factors with p < 0.1 in the univariable analysis were included in the multivariable analysis. & NT-proBNP is log-transformed before being included in the regression analysis Pearson correlation analysis was used to examine the correlations between LV strain parameters and LVEF (Fig. 5 ). There were moderate to high correlations between circumferential PDSR, PSSR, PS, and LVEF in the patients with cancer (r = 0.54, r = -0.63, r = -0.82, respectively; p < 0.001). The radial PDSR, PSSR, and PS were weak to moderately associated with LVEF (r = -0.62, r = 0.46, r = 0.72, respectively; p < 0.001). While, weak to moderate correlations between longitudinal PDSR, PSSR, PS, and LVEF in the patients with cancer were found (r = 0.35, r = -0.32, r = -0.57, respectively; p < 0.001). Discussion The current clinical diagnosis of cardiotoxicity is mainly based on the variable cutoff values of LVEF in different imaging modalities (7,8). In one of the criteria, cardiotoxicity based on LVEF was defined as a decrease > 10% in asymptomatic patients to a final value of < 55% or a decrease ≥ 5% in symptomatic patients to a final value of < 55% (9). However, LVEF may not be sufficiently sensitive to detect early myocardial injury, and reductions may reflect the systemic changes associated with cardiotoxicity after significant damage. More than half of patients do not fully recover from depressed LVEF after treatment for cardiotoxicity evaluated by LVEF (10,11). Early detection of cardiotoxicity and timely initiation of cardioprotective therapy may help reverse its course. Reportedly, early cardiotoxicity is histologically characterized by myocardial edema and inflammation (12,13), and eventually myocardial and extracellular fibrosis (14), both of which can be manifested as LGE. Previous study had demonstrated that the presence of LGE may reflect irreversible myocardial injury, and that patients with LGE also had a significantly increased chance of subsequent cardiac events (15). In the current study, although there were no significant differences in the cardiovascular risk factors between the LGE − and LGE + cohorts, the prevalence of LGE was relatively high (25.93%). Our study did not exclude patients at higher risk for cardiovascular factors, which provides greater generalizability in real-world routine clinical practice. In patients treated with anthracyclines and/or trastuzumab, LGE was present in only a minority of patients (16,17). Unlike those in previous studies, our subjects were physician referred patients with cancer for CMR primarily to assess suspected cardiotoxicity. While, the presence of LGE can be as high as 42% to 74% in patients with confirmed ICI-associated myocarditis, especially with a mid-myocardial pattern (18,19). Besides, in a study of patients with ibrutinib-associated cardiotoxic, more than 50% of patients exhibited LGE (20). We speculated that the variation in the prevalence of LGE reflected the cohort of patients with cancer who were referred for CMR, LGE is a characteristic manifestation of myocardial injury caused by cancer treatment. Our data also showed that LGE was highest in the patients with a therapeutic regimen that included targeted therapy. Trastuzumab is a typical targeted therapy that causes type II cardiotoxicity; it is rarely used alone and is often applied sequentially or concurrently as adjuvant cancer therapy, which may increase susceptibility to myocardial injury (7). In this study, LVEF was significantly lower in the patients with LGE than in those without. Therefore, we recommend LGE as an adjunct diagnostic indicator in addition to LVEF for diagnosing tumor treatment-related cardiotoxicity and as a clinical decision-making aid. Recently, myocardial strain analysis based on feature-tracking CMR has become a sensitive method for detecting subclinical myocardial dysfunction that does not require additional MR sequences, and can help in the early initiation of preventive cardiac strategies (21). The global longitudinal strain (GLS) has been recommended by cardio-oncology guidelines for imaging evaluation of cardiotoxicity, defining a relative GLS decline of > 15% during cancer treatment as cancer therapy–related cardiac dysfunction (CTRCD) (22). Our results showed that the LV global strain parameters of patients with cancer decreased to different degrees. However, among the correlations between the strain parameters and LVEF in patients with cancer, the highest were for the circumferential strain parameters, indicating that circumferential strain reduction is probably the predominant mechanism related to LV dysfunction. Furthermore, the circumferential strain is the most reliable and reproducible measure of myocardial deformation (23). A previous study showed that changes in global circumferential strain could help predict declines in LVEF for at least 2 years after treatment in cancer survivors (24). Narayan et al. also found that global circumferential strain was the strongest predictor of cardiotoxicity (25). Overall, our results suggest that global circumferential strain (GCS) is a more reliable indicator than GLS for cardiotoxicity. In this study, the radial, circumferential and longitudinal PS were significantly lower in the LGE + group than in the LGE − group, while the LGE extent was independently associated with circumferential PS. This is consistent with the LGE distribution that reflects myocardial injury in the current study, which mainly occurred at the midmyocardium and/or subepicardial of the LV. Contraction of subendocardial muscle fibers mainly leads to longitudinal shortening of the myocardium, and contraction of subepicardial muscle fibers mainly causes circumferential shortening of the myocardium, both of which contribute to radial thickening of myocardium (26). The fibers in the midmyocardium were circumferentially oriented, which implies that the midmyocardium was responsible for the circumferential strain (26,27). This results provide further evidence that the circumferential contraction of myocardium might be the most depressed in patients with cancer who received cardiotoxic therapy. In addition to imaging, elevation of cardiac biomarkers can help with recognition of cardiotoxicity. An elevated natriuretic peptide level often represents hemodynamic congestion (28). Our study revealed that NT-pro BNP was independently associated with PS in all directions. In addition, the NT-pro BNP was independently associated with circumferential PSSR, consistent with previous research showing NT-pro BNP as a biomarker for preclinical systolic dysfunction (11). Our results also showed that troponin T was independently associated with circumferential PDSR, suggesting that troponin T may be a biomarker for diastolic dysfunction. In general, an elevated troponin is a marker of myocardial injury (28). Previous studies have shown that elevated troponin levels appeared to identify patients who did not recover from LVEF after chemotherapy (29). These findings further support the importance of monitoring NT-pro BNP and troponin T levels in patients receiving cancer treatment. Furthermore, the monitoring of cardiac biomarkers could provide additional indicators to identify patients at risk of cardiac injury and stratify patients for treatment effectiveness. Diagnostic accuracy could be improved by combining multiple imaging and cardiac biomarkers. This should contribute to early detection and treatment of cancer therapy-related cardiotoxicity. Identifying the presence and severity of cardiotoxicity is essential in determining whether a patient can safely resume cancer therapy, thus profoundly influencing future oncological treatment decisions. Clinically, cardiotoxicity defined by reduced LVEF in tumor therapy could miss the onset of tissue-level myocardial changes and subclinical dysfunction. This study used CMR found that the combination of LGE, circumferential strains, and biomarkers could help clinicians diagnose myocardial injury that truly represents cardiotoxicity. Developing a practical clinical score based on cardiac imaging and biomarkers to determine the cancer therapy-cardiotoxicity risk will help clinicians make decisions regarding the surveillance frequency and indication for cardio-protection. However, further long-term follow up of this study’s cohort is needed to establish this score. Our study has several limitations. First, this was a retrospective investigation, we only included patients referred clinically for CMR for suspected cardiotoxicity rather than all patients with cancer, which may have introduced selection bias. This patient sample also explains the higher prevalence of LGE in this study than in other reported studies. Second, we did not determine the presence and extent of cardiotoxicity by myocardial biopsy; however, because of its invasiveness, potential for sampling error, and risk of serious complications, biopsy is now rarely performed. Third, long-term follow up data are not yet available; therefore, the precise prognostic significance of LGE and LV strain changes remains to be determined. Future studies are required to determine if these patients with LGE experience higher rates of cardiovascular events. Conclusion The present study investigated the role of CMR for diagnosis of cancer patients with suspected cardiotoxicity in routine clinical practice. This study revealed that the presence of LGE was independently associated with circumferential PS in patients received oncotherapy, and the circumferential strain reduction is the predominant mechanism of LV dysfunction. LGE and circumferential strains could help clinicians diagnose myocardial injury that indicates cancer therapy-cardiotoxicity, which will help clinicians make decisions regarding the surveillance frequency and indication for cardio-protection. Abbreviations CMR cardiac magnetic resonance LGE late gadolinium enhancement LV left ventricle PS peak strain PDSR peak diastolic strain rate PSSR peak systolic strain rate NT-pro BNP N-terminal pro–B-type natriuretic peptide EDV end diastolic volume ESV end systolic volume SV stroke volume EF ejection fraction I indexed to BSA ICIs immune checkpoint inhibitors Declarations Supplementary information Supplementary data associated with this article can be found in the online version. Author contributions ZGY and YSS designed the study and contributed to revising the manuscript. XL contributed to drafting and revising the manuscript. YG performed statistical analysis. YG, ZW, WFY and RS collected clinical data and analyzed data. CXZ, BZ and YL collected clinical data and interpreted the results. All authors read and approved the final manuscript. Funding This work was supported by the National Natural Science Foundation of China (82102022), and 1-3-5 project for disciplines of excellence of West China Hospital, Sichuan University (ZYGD23019). Data availability The datasets used in this study are available from the corresponding author upon request. Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki. Ethical approval for this clinical study was obtained from the Biomedical Research Ethics Committee of West China Hospital, Sichuan University. The requirement for informed consent from patients was waived due to the retrospective nature of this study. Clinical trial number: not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. References Strongman H, Gadd S, Matthews A, Mansfield KE, Stanway S, Lyon AR et al. 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Can J Cardiol. 2016; 32: 211–216. Alvarez-Cardona JA, Zhang KW, Mitchell JD, Zaha VG, Fisch MJ, Lenihan DJ. Cardiac Biomarkers During Cancer Therapy: Practical Applications for Cardio-Oncology. JACC CardioOncol. 2020;2(5):791-794. Zardavas D, Suter TM, Van Veldhuisen DJ, Steinseifer J, Noe J, Lauer S, et al. Role of Troponins I and T and N-Terminal Prohormone of Brain Natriuretic Peptide in Monitoring Cardiac Safety of Patients with Early-Stage Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Receiving Trastuzumab: A Herceptin Adjuvant Study Cardiac Marker Substudy. J Clin Oncol. 2017;35:878–884. Additional Declarations No competing interests reported. Supplementary Files SupplementaryDatatables.docx Cite Share Download PDF Status: Posted 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. 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3","display":"","copyAsset":false,"role":"figure","size":777922,"visible":true,"origin":"","legend":"\u003cp\u003eDifferences in LV global, radial, circumferential, and longitudinal PS (A1–A3), PSSR (B1–B3), and PDSR (C1–C3) among the healthy controls, patients with cancer who were LGE−, and patients with cancer who were with LGE+, * \u003cem\u003ep\u003c/em\u003e\u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"Fig.3.png","url":"https://assets-eu.researchsquare.com/files/rs-7780372/v1/41df05280ea1437406328c70.png"},{"id":94224875,"identity":"f85e311c-9a0a-420f-8d1a-1480c25c002f","added_by":"auto","created_at":"2025-10-23 19:24:43","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":230822,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation of NT-pro BNP (was log-transformed) with the circumferential PSSR (A), and troponin T with the circumferential PDSR (B) in cancer patients.\u003c/p\u003e","description":"","filename":"Fig.4.png","url":"https://assets-eu.researchsquare.com/files/rs-7780372/v1/144ddfcfa0aafa62a67e0fe2.png"},{"id":94224203,"identity":"d76af460-9491-460a-8528-f5e38471dfd9","added_by":"auto","created_at":"2025-10-23 19:16:43","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":393334,"visible":true,"origin":"","legend":"\u003cp\u003eHeatmap shows relationship between LV global strain parameters in all directions and LVEF.\u003c/p\u003e","description":"","filename":"Fig.5.png","url":"https://assets-eu.researchsquare.com/files/rs-7780372/v1/88f08b520cb720f7d151c58d.png"},{"id":97122156,"identity":"69cf26c9-4b8d-48ef-a0cc-f9e10ed48774","added_by":"auto","created_at":"2025-12-01 07:55:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4895172,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7780372/v1/df1ba2ff-46cd-4a51-8af1-64f7070d8e07.pdf"},{"id":94224876,"identity":"d76a624c-f5a9-4a68-b882-cecf603a1ba9","added_by":"auto","created_at":"2025-10-23 19:24:43","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":29664,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryDatatables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7780372/v1/53d98b5e71c34abb9703917d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Late Gadolinium Enhancement CMR for Detecting Myocardial Injury after Oncotherapy: Correlation with Left Ventricular Function","fulltext":[{"header":"Background","content":"\u003cp\u003eSignificant advancements in cancer therapeutics, including conventional chemotherapy, immunotherapy, targeted therapy, radiotherapy, and therapeutic combinations, have led to improved long-term survival in patients with cancer, however, these therapeutic options are potentially cardiotoxic. Cancer survivors are at higher risk than the general population for developing cardiac disease, which is the leading cause of noncancer-related mortality in cancer survivors (1,2). Timely and accurate identification of cancer therapy-related cardiotoxicity, which poses a formidable challenge for oncologists and cardiologists, is crucial to enable the targeted use of cardioprotective interventions and/or to introduce alternative treatment strategies (3). Although cancer therapy-related cardiotoxicity has received increased attention in recent years, previous studies of cancer therapy-related cardiotoxicity and causative factors have been oversimplified and failed to reflect the complex pathophysiological differences. In routine clinical practice, cancer patients usually receive multiple cancer drug treatments, with the potential for cardiotoxic effects from interactions among the different therapy modalities.\u003c/p\u003e\u003cp\u003eLate gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging provides tissue characterization and enables detection of myocardial fibrosis and/or edema associated with cardiotoxic therapy (4,5). There are currently limited data on LGE detection of cardiotoxicity in patients receiving cancer-related treatment, and some studies have obtained conflicting results. Therefore, this study aimed to use LGE to characterize myocardial damage in a somewhat diverse population that included several cancer types and treatment regimens. We also investigated the effect of LGE and other clinical factors on left ventricular (LV) function.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted a retrospective study of patients with various cancer who were referred for clinical CMR for suspected cardiotoxicity between June 2018 and March 2025. The\u0026nbsp;inclusion criteria were age \u0026gt;18 years and had received at least one antitumor treatment (including conventional chemotherapy, immunotherapy, targeted therapy, or radiotherapy). The exclusion criteria were\u0026nbsp;pre-existing symptomatic heart failure (NYHA Class III or IV), a history of myocardial infarction, or chronic arrhythmia such as atrial fibrillation, incomplete medical records,\u0026nbsp;or inadequate CMR studies. Besides, 2 cancer patients with coronary heart disease were excluded from the study cohort due to extensive ischemic LGE caused by silent myocardial infarction.\u0026nbsp;We also included 60 age- and sex-matched normal controls who underwent CMR. The exclusion criteria were clinical evidence of cancer, cardiovascular disease, or other systemic disease or\u0026nbsp;inadequate CMR studies. This retrospective study was approved by the Institutional Review Board, which waived the requirement for written informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical data extraction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDetailed clinical data were extracted from the electronic medical records. We collected the following data: demographic characteristics, vital signs, cancer treatments, previous cardiovascular history, cardiovascular risk factors, and cardiac biomarkers including serum N-terminal pro–B-type natriuretic peptide (NT-pro BNP) and troponin T. We then counted the number of cardiovascular disease risk factors (known coronary artery disease, hypertension, diabetes mellitus, smoking, or elevated cholesterol) to enable calculation of a cardiovascular disease score (range: 0–5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMR protocol\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe CMR examinations were performed on 3T scanner (Tim Trio/Skyra, Siemens, Erlangen, Germany) with standard image acquisitions. The data included cine images acquired with a balanced steady-state free-precession sequence (TR: 2.9/3.4 ms; TE：1.25 /1.3 ms; flip angle: 50/40°; slice thickness: 8 mm; field of view: 319 × 249/339 × 284 mm\u003csup\u003e2\u003c/sup\u003e; matrix size 256 × 166/256 × 144),\u0026nbsp;and LGE imaging using a T1-weighted inversion recovery turbo FLASH sequence\u0026nbsp;(TR：650/500 ms; TE: 1.43/ 1.24 ms, flip angle: 50 /40°, slice thickness: 8 mm, field of view: 340×255/340×233 mm\u003csup\u003e2\u003c/sup\u003e, matrix size: 256×192/ 256×125) conducted for 10–15 min\u0026nbsp;after intravenous administration of gadolinium-based contrast agent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImage analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll CMR imaging data were analyzed\u0026nbsp;by an experienced radiologist\u0026nbsp;(\u0026gt;8 years of experience in interpreting CMR)\u0026nbsp;using commercially\u0026nbsp;available\u0026nbsp;software (cvi42 version 5.11.2, Circle Cardiovascular Imaging Inc., Calgary, Canada).\u0026nbsp;The LV function\u0026nbsp;parameters, including the end\u0026nbsp;diastolic volume (EDV), end systolic volume (ESV), stroke volume (SV), and ejection fraction\u0026nbsp;(EF), as described in a previous study were acquired (6).To analyze the LV myocardial strain, the\u0026nbsp;short- and long-axis two-chamber and four-chamber slices\u0026nbsp;of the cine images were loaded into the\u0026nbsp;tissue-tracking module, as described in our previous study (6).\u0026nbsp;The\u0026nbsp;LV global\u0026nbsp;strain parameters, including radial, circumferential, and longitudinal peak strain (PS), peak systolic strain rate (PSSR), and peak diastolic strain rate (PDSR) were estimated automatically.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLGE was visually identified as positive (LGE+) if there were hyperintense regions within the myocardium in the short- or long-axis views.\u0026nbsp;In addition, for LGE quantification, the extent of LGE based on the signal threshold analysis was performed using sequential short axis LGE images. LGE lesion was evaluated semi-quantitatively as above the five-fold standard deviation (5SD) of the remote reference myocardium that demonstrated the lowest signal intensity (Figure 1). The LGE extent was calculated as the ratio of the LGE lesion volume to the total LV myocardium volume.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSPSS software (version 23.0), GraphPad Prism software (version 8.0.1), and R software (R studio version 1.4.1717) were used to perform the statistical analyses.Categorical variables are presented as numbers (percentages) and compared by performing Fisher’s exact or Chi-squared tests. Continuous variables are presented as means ± standard deviations or as medians and interquartile ranges. Normality was evaluated by performing the Kolmogorov–Smirnov test, and the homogeneity of variance was assessed by performing Levene’s test. Comparative analyses were repeated in subgroups after stratification of the study cohort into three categories (control, cancer patients without LGE, and cancer patients with LGE) by performing one-way analysis of variance, followed by Bonferroni post hoc correction or its nonparametric equivalent (Kruskal–Wallis test), as appropriate. Associations between variables were investigated by performing Pearson or Spearman correlation analyses. Furthermore, univariate factors of\u0026nbsp;p\u0026nbsp;\u0026lt; 0.1 were then included in the stepwise multivariate analysis. NT-pro BNP was log-transformed before inclusion in the regression analysis. Values ofp \u0026lt;0.05 were accepted as indicating statistical significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003eBaseline characteristics\u003c/h2\u003e\u003cp\u003eThe final study cohort comprised 108 patients with cancer who received potentially cardiotoxic therapy and 60 healthy controls. On CMR images, LGE was identified in 28/108 (25.93%) of the patients with cancer. The patients with cancer without and with LGE were assigned to the LGE-negative (LGE\u0026minus;) group (n\u0026thinsp;=\u0026thinsp;80) and LGE-positive (LGE+) group (n\u0026thinsp;=\u0026thinsp;28). The baseline characteristics of the study population were presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\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\u003eBaseline Characteristics of Control Individuals, Cancer Patients without or with LGE\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003enormal\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;60\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePatients (LGE-)\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;80\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePatients (LGE+)\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;28\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\u003eAge, y\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55.00(49.00, 63.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62.00(50.00, 67.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e60.00(53.00, 71.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMale gender, n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26(43.33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41(51.25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19(67.85%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI, kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23.52\u0026thinsp;\u0026plusmn;\u0026thinsp;3.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22.52\u0026thinsp;\u0026plusmn;\u0026thinsp;3.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23.42\u0026thinsp;\u0026plusmn;\u0026thinsp;3.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHeart rate, bpm\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74.60(66.91, 78.27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e79.96(71.34, 94.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e85.07(75.14, 95.38) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDiastolic BP (mmHg)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e125.75\u0026thinsp;\u0026plusmn;\u0026thinsp;15.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1119.57\u0026thinsp;\u0026plusmn;\u0026thinsp;16.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e121.32\u0026thinsp;\u0026plusmn;\u0026thinsp;18.76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSystolic BP (mmHg)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e77.16\u0026thinsp;\u0026plusmn;\u0026thinsp;9.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77.51\u0026thinsp;\u0026plusmn;\u0026thinsp;11.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e83.67\u0026thinsp;\u0026plusmn;\u0026thinsp;14.85 \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCV risk factors\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23(28.75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8(28.57%)\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\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20(25.00%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7(25.00%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13(16.25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4(14.29%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHyperlipidemia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7(8.75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3(10.71%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCoronary artery disease, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7(8.75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5(17.86%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCVD score, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42/17/11/9/1/0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14/6/4/3/1/0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBiomarker\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNT-pro BNP, pg/ml\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e154.0(49.0, 455.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e256.0(49.0,743.0) \u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTroponin T, pg/ml\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.00(7.1, 59.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e41.33(18.7, 99.1) \u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCancer treatment\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnthracyclines, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14(17.50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2(7.14%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTargeted agents, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24(30.00%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19(67.86%) \u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eICIs, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26(32.50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9(32.14%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntimetabolic, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23(28.75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8(28.57%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntimicrotubule agents, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36(45.00%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7(25.00%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlkylating agents, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62(77.50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15(53.57%) \u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChest radiotherapy, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17(21.25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7(25.00%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: Data given as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, n (%), or median (25th to 75th percentile), *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs controls; \u003csup\u003e\u0026dagger;\u003c/sup\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs patients without LGE. BMI: body mass index; BP: blood pressure; CV: cardiovascular; CVD: cardiovascular disease; NT-pro BNP, N-terminal pro\u0026ndash;B-type natriuretic peptide; ICIs, immune checkpoint inhibitors.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePre-existing coronary heart disease was present in 11.11% of the patients with cancer. However, there were no significant differences in coronary artery disease, other cardiovascular risk factors, or cardiovascular disease score between the two groups. We observed that NT-pro BNP and troponin T were significantly higher in the LGE\u0026thinsp;+\u0026thinsp;group than in the LGE\u0026thinsp;\u0026minus;\u0026thinsp;group (256.0(49.0,743.0) vs. 154.0(49.0, 455.0); 41.33(18.7, 99.1) vs. 21.00(7.1, 59.4); respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). There were no significant differences in the cancer type or whether it was combined with metastasis among the two subgroups. The proportion of patients with a therapeutic regimen that included targeted therapy was significantly higher in the LGE\u0026thinsp;+\u0026thinsp;group than in the LGE\u0026thinsp;\u0026minus;\u0026thinsp;group (67.86% vs. 30.00%). However, the proportion of patients whose therapeutic regimens were \u0026gt;\u0026thinsp;3 was lower in the LGE\u0026thinsp;+\u0026thinsp;than in the LGE\u0026thinsp;\u0026minus;\u0026thinsp;groups (16.67% vs 41.77%).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eCMR imaging results\u003c/h3\u003e\n\u003cp\u003eOur results showed that 28 (25.93%) patients with cancer exhibited abnormal LGE. On CMR images, LGE mainly occurred at midmyocardium and/or subepicardial of the LV (23/28, 82.14%), and the distribution of LGE did not fit a single profile, including focal pattern, multiple and diffuse pattern (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents the data on the functional and strain parameters of the LV of the control subjects, LGE\u0026thinsp;\u0026minus;\u0026thinsp;group, and LGE\u0026thinsp;+\u0026thinsp;group. The LVEF values were lower in the LGE\u0026thinsp;+\u0026thinsp;and LGE\u0026thinsp;\u0026minus;\u0026thinsp;groups than in the healthy controls (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and LVEF was significantly lower in the LGE\u0026thinsp;+\u0026thinsp;group than in the LGE\u0026minus; (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The prevalence of LV systolic dysfunction (LVEF\u0026thinsp;\u0026lt;\u0026thinsp;55%) was significantly higher in the LGE\u0026thinsp;+\u0026thinsp;group than in the LGE\u0026thinsp;\u0026minus;\u0026thinsp;group (60.71% vs. 23.75%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Compared with the normal controls, the LV radial, circumferential and longitudinal PS of patients with LGE and those without LGE significantly impaired (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The LV radial, circumferential, and longitudinal PS were significantly lower in the LGE\u0026thinsp;+\u0026thinsp;group than in the LGE\u0026thinsp;\u0026minus;\u0026thinsp;group (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Besides, the LV longitudinal, circumferential, and radial PDSR also were significantly lower in the patient groups than in the controls (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Only the LV radial and circumferential PSSR were significantly lower in the LGE\u0026thinsp;+\u0026thinsp;group than in the LGE\u0026thinsp;\u0026minus;\u0026thinsp;group and control subjects (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\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\u003eCMR Parameters between Normal Individuals, Cancer Patients without or with LGE\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003enormal\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;60\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePatients (LGE-)\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;80\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePatients (LGE+)\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;28\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\u003eLVEDVI, ml/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e72.10(64.82\u0026ndash;79.44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e70.86(57.45,82.51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e69.39(60.22,78.99)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLVESVI, ml/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e24.22(19.99\u0026ndash;28.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e24.26(20.03,32.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e27.50(23.70,36.67)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLVSVI, ml/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e46.18(41.27\u0026ndash;52.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e41.71(34.25,47.99) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e36.86(27.35,47.51) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLVEF, %\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e65.85(62.61\u0026ndash;70.15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e62.62(56.34,67.94) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e53.43(46.86,64.20) \u003csup\u003e*\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePS (%)\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRadial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e40.11(34.32\u0026ndash;44.17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e32.11(24.51,41.74) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e27.11(12.71,30.48) \u003csup\u003e*\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCircumferential\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-21.27(-23.00-(-19.55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-19.70(-21.66, -16.40) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-16.35(-19.26, -10.13) \u003csup\u003e*\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLongitudinal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-15.57(-17.85-(-13.59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-13.00(-14.66, -9.15) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-10.02(-12.57, -6.41) \u003csup\u003e*\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePSSR (1/s)\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRadial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.18(1.97\u0026ndash;2.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.20(1.54,2.82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.51(1.00,2.38) \u003csup\u003e*\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCircumferential\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-1.10(-1.21-(-0.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-1.08(-1.35, -0.86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.96(-1.16, -0.66) \u003csup\u003e*\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLongitudinal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.83(-0.98-(-0.71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-0.81(-0.98, -0.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.67(-0.89, -0.53)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePDSR (1/s)\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\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRadial\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-3.01(-3.71-(-2.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-2.17(-2.66, -1.53) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.63(-2.46, -1.27) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCircumferential\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.43(1.25-(1.58)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.11(0.87,1.30) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.07(0.75,1.27) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLongitudinal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.03(0.89\u0026ndash;1.27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.80(0.59,0.99) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.71(0.56,0.85) \u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLVEF\u0026lt;55% (n,%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19(23.75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e17(60.71%) \u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eNote: Data given as the median (25th, 75th percentile), *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs controls; \u003csup\u003e\u0026dagger;\u003c/sup\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs patients without LGE. LV, left ventricular; end diastolic volume; ESV, end systolic volume; SV, stroke volume; EF, ejection fraction; I, indexed to BSA; PS, Peak Strain; PSSR, Peak Systolic Strain Rate; PDSR, Peak Diastolic Strain Rate.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation between the clinical data and CMR parameters\u003c/h2\u003e\u003cp\u003eIn the multivariate analysis the factors that could potentially influence LV strain, including age, sex, BMI, systolic blood pressure, cardiovascular risk factors, cardiac biomarker, therapeutic regimens, and the LGE extent were adjusted. Multivariate linear regression analysis revealed that NT-pro BNP was independently associated with the radial, circumferential and longitudinal PS (β = \u0026minus;0.419, β\u0026thinsp;=\u0026thinsp;0.407, β\u0026thinsp;=\u0026thinsp;0.327, respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The NT-pro BNP was independently associated with the circumferential PSSR (β\u0026thinsp;=\u0026thinsp;0.362, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). In addition, the troponin T was independently associated with the circumferential PDSR (β\u0026thinsp;=\u0026thinsp;0.342, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table S2) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The LGE extent was independently associated with circumferential PS (β\u0026thinsp;=\u0026thinsp;0.297, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant correlations between cardiovascular risk factors and LV strain parameters were found.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariate linear regression of factors associated with left ventricle peak strain\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"15\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eRadial PS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c10\" namest=\"c7\"\u003e\u003cp\u003eCircumferential PS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"4\" nameend=\"c15\" namest=\"c12\"\u003e\u003cp\u003eLongitudinal PS\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eUnivariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eMultivariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003eUnivariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u003cp\u003eMultivariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e\u003cp\u003eUnivariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c15\" namest=\"c14\"\u003e\u003cp\u003eMultivariable\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eβ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eβ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003eβ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.640\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.510\u003c/p\u003e\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\u003cp\u003e-0.009\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.926\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-0.031\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.754\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale gender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.073\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.453\u003c/p\u003e\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\u003cp\u003e0.067\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.493\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-0.027\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.778\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.026\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.791\u003c/p\u003e\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\u003cp\u003e-0.093\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.338\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.804\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSystolic BP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.128\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.186\u003c/p\u003e\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\u003cp\u003e0.200\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.038\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e-0.207\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-0.012\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.898\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLGE%(5SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.282\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.187\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.030\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.410\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.297\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.304\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e\u003cp\u003e0.237\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e0.010\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNT-pro BNP \u003csup\u003e\u0026amp;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.459\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.419\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.500\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.407\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.383\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e\u003cp\u003e0.327\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\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\u003eTroponin T\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.175\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.070\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0138\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.101\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-0.189\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.050\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e-0.122\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.132\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-0.111\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.252\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.083\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.393\u003c/p\u003e\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\u003cp\u003e-0.126\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.192\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-0.083\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.395\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\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\u003e-0.054\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.582\u003c/p\u003e\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\u003cp\u003e0.019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.846\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.095\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.330\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.218\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.023\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.231\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-0.208\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e-0.136\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.080\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-0.142\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.143\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHyperlipidemia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.983\u003c/p\u003e\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\u003cp\u003e0.037\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.701\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.033\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.746\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrior coronary artery disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.071\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.466\u003c/p\u003e\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\u003cp\u003e0.054\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.580\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-0.008\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.938\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnthracyclines\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.129\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.183\u003c/p\u003e\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\u003cp\u003e0.098\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.314\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.808\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTargeted agents\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.265\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.145\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.089\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.262\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.127\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.120\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.208\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c14\"\u003e\u003cp\u003e0.100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u003cp\u003e0.295\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImmune checkpoint inhibitor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.072\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.457\u003c/p\u003e\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\u003cp\u003e-0.088\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.367\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-0.113\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.246\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntimetabolic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.036\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.708\u003c/p\u003e\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\u003cp\u003e-0.062\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.521\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.083\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.391\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntimicrotubule agents\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.074\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.466\u003c/p\u003e\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\u003cp\u003e-0.123\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.203\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-0.032\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.739\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlkylating agents\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.144\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.137\u003c/p\u003e\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\u003cp\u003e-0.227\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e-0.166\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.035\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-0.012\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.898\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChest radiotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.073\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.454\u003c/p\u003e\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\u003cp\u003e-0.084\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.386\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-0.045\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.646\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"15\"\u003eNote: Factors with p\u0026thinsp;\u0026lt;\u0026thinsp;0.1 in the univariable analysis were included in the multivariable analysis.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"15\"\u003e\u003csup\u003e\u0026amp;\u003c/sup\u003e NT-proBNP is log-transformed before being included in the regression analysis\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003ePearson correlation analysis was used to examine the correlations between LV strain parameters and LVEF (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). There were moderate to high correlations between circumferential PDSR, PSSR, PS, and LVEF in the patients with cancer (r\u0026thinsp;=\u0026thinsp;0.54, r = -0.63, r = -0.82, respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The radial PDSR, PSSR, and PS were weak to moderately associated with LVEF (r = -0.62, r\u0026thinsp;=\u0026thinsp;0.46, r\u0026thinsp;=\u0026thinsp;0.72, respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). While, weak to moderate correlations between longitudinal PDSR, PSSR, PS, and LVEF in the patients with cancer were found (r\u0026thinsp;=\u0026thinsp;0.35, r = -0.32, r = -0.57, respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe current clinical diagnosis of cardiotoxicity is mainly based on the variable cutoff values of LVEF in different imaging modalities (7,8). In one of the criteria, cardiotoxicity based on LVEF was defined as a decrease\u0026thinsp;\u0026gt;\u0026thinsp;10% in asymptomatic patients to a final value of \u0026lt;\u0026thinsp;55% or a decrease\u0026thinsp;\u0026ge;\u0026thinsp;5% in symptomatic patients to a final value of \u0026lt;\u0026thinsp;55% (9). However, LVEF may not be sufficiently sensitive to detect early myocardial injury, and reductions may reflect the systemic changes associated with cardiotoxicity after significant damage. More than half of patients do not fully recover from depressed LVEF after treatment for cardiotoxicity evaluated by LVEF (10,11). Early detection of cardiotoxicity and timely initiation of cardioprotective therapy may help reverse its course. Reportedly, early cardiotoxicity is histologically characterized by myocardial edema and inflammation (12,13), and eventually myocardial and extracellular fibrosis (14), both of which can be manifested as LGE. Previous study had demonstrated that the presence of LGE may reflect irreversible myocardial injury, and that patients with LGE also had a significantly increased chance of subsequent cardiac events (15).\u003c/p\u003e\u003cp\u003eIn the current study, although there were no significant differences in the cardiovascular risk factors between the LGE\u0026thinsp;\u0026minus;\u0026thinsp;and LGE\u0026thinsp;+\u0026thinsp;cohorts, the prevalence of LGE was relatively high (25.93%). Our study did not exclude patients at higher risk for cardiovascular factors, which provides greater generalizability in real-world routine clinical practice. In patients treated with anthracyclines and/or trastuzumab, LGE was present in only a minority of patients (16,17). Unlike those in previous studies, our subjects were physician referred patients with cancer for CMR primarily to assess suspected cardiotoxicity. While, the presence of LGE can be as high as 42% to 74% in patients with confirmed ICI-associated myocarditis, especially with a mid-myocardial pattern (18,19). Besides, in a study of patients with ibrutinib-associated cardiotoxic, more than 50% of patients exhibited LGE (20). We speculated that the variation in the prevalence of LGE reflected the cohort of patients with cancer who were referred for CMR, LGE is a characteristic manifestation of myocardial injury caused by cancer treatment. Our data also showed that LGE was highest in the patients with a therapeutic regimen that included targeted therapy. Trastuzumab is a typical targeted therapy that causes type II cardiotoxicity; it is rarely used alone and is often applied sequentially or concurrently as adjuvant cancer therapy, which may increase susceptibility to myocardial injury (7). In this study, LVEF was significantly lower in the patients with LGE than in those without. Therefore, we recommend LGE as an adjunct diagnostic indicator in addition to LVEF for diagnosing tumor treatment-related cardiotoxicity and as a clinical decision-making aid.\u003c/p\u003e\u003cp\u003eRecently, myocardial strain analysis based on feature-tracking CMR has become a sensitive method for detecting subclinical myocardial dysfunction that does not require additional MR sequences, and can help in the early initiation of preventive cardiac strategies (21). The global longitudinal strain (GLS) has been recommended by cardio-oncology guidelines for imaging evaluation of cardiotoxicity, defining a relative GLS decline of \u0026gt;\u0026thinsp;15% during cancer treatment as cancer therapy\u0026ndash;related cardiac dysfunction (CTRCD) (22). Our results showed that the LV global strain parameters of patients with cancer decreased to different degrees. However, among the correlations between the strain parameters and LVEF in patients with cancer, the highest were for the circumferential strain parameters, indicating that circumferential strain reduction is probably the predominant mechanism related to LV dysfunction. Furthermore, the circumferential strain is the most reliable and reproducible measure of myocardial deformation (23). A previous study showed that changes in global circumferential strain could help predict declines in LVEF for at least 2 years after treatment in cancer survivors (24). Narayan et al. also found that global circumferential strain was the strongest predictor of cardiotoxicity (25). Overall, our results suggest that global circumferential strain (GCS) is a more reliable indicator than GLS for cardiotoxicity.\u003c/p\u003e\u003cp\u003eIn this study, the radial, circumferential and longitudinal PS were significantly lower in the LGE\u0026thinsp;+\u0026thinsp;group than in the LGE\u0026thinsp;\u0026minus;\u0026thinsp;group, while the LGE extent was independently associated with circumferential PS. This is consistent with the LGE distribution that reflects myocardial injury in the current study, which mainly occurred at the midmyocardium and/or subepicardial of the LV. Contraction of subendocardial muscle fibers mainly leads to longitudinal shortening of the myocardium, and contraction of subepicardial muscle fibers mainly causes circumferential shortening of the myocardium, both of which contribute to radial thickening of myocardium (26). The fibers in the midmyocardium were circumferentially oriented, which implies that the midmyocardium was responsible for the circumferential strain (26,27). This results provide further evidence that the circumferential contraction of myocardium might be the most depressed in patients with cancer who received cardiotoxic therapy.\u003c/p\u003e\u003cp\u003eIn addition to imaging, elevation of cardiac biomarkers can help with recognition of cardiotoxicity. An elevated natriuretic peptide level often represents hemodynamic congestion (28). Our study revealed that NT-pro BNP was independently associated with PS in all directions. In addition, the NT-pro BNP was independently associated with circumferential PSSR, consistent with previous research showing NT-pro BNP as a biomarker for preclinical systolic dysfunction (11). Our results also showed that troponin T was independently associated with circumferential PDSR, suggesting that troponin T may be a biomarker for diastolic dysfunction. In general, an elevated troponin is a marker of myocardial injury (28). Previous studies have shown that elevated troponin levels appeared to identify patients who did not recover from LVEF after chemotherapy (29). These findings further support the importance of monitoring NT-pro BNP and troponin T levels in patients receiving cancer treatment. Furthermore, the monitoring of cardiac biomarkers could provide additional indicators to identify patients at risk of cardiac injury and stratify patients for treatment effectiveness. Diagnostic accuracy could be improved by combining multiple imaging and cardiac biomarkers. This should contribute to early detection and treatment of cancer therapy-related cardiotoxicity.\u003c/p\u003e\u003cp\u003eIdentifying the presence and severity of cardiotoxicity is essential in determining whether a patient can safely resume cancer therapy, thus profoundly influencing future oncological treatment decisions. Clinically, cardiotoxicity defined by reduced LVEF in tumor therapy could miss the onset of tissue-level myocardial changes and subclinical dysfunction. This study used CMR found that the combination of LGE, circumferential strains, and biomarkers could help clinicians diagnose myocardial injury that truly represents cardiotoxicity. Developing a practical clinical score based on cardiac imaging and biomarkers to determine the cancer therapy-cardiotoxicity risk will help clinicians make decisions regarding the surveillance frequency and indication for cardio-protection. However, further long-term follow up of this study\u0026rsquo;s cohort is needed to establish this score.\u003c/p\u003e\u003cp\u003eOur study has several limitations. First, this was a retrospective investigation, we only included patients referred clinically for CMR for suspected cardiotoxicity rather than all patients with cancer, which may have introduced selection bias. This patient sample also explains the higher prevalence of LGE in this study than in other reported studies. Second, we did not determine the presence and extent of cardiotoxicity by myocardial biopsy; however, because of its invasiveness, potential for sampling error, and risk of serious complications, biopsy is now rarely performed. Third, long-term follow up data are not yet available; therefore, the precise prognostic significance of LGE and LV strain changes remains to be determined. Future studies are required to determine if these patients with LGE experience higher rates of cardiovascular events.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe present study investigated the role of CMR for diagnosis of cancer patients with suspected cardiotoxicity in routine clinical practice. This study revealed that the presence of LGE was independently associated with circumferential PS in patients received oncotherapy, and the circumferential strain reduction is the predominant mechanism of LV dysfunction. LGE and circumferential strains could help clinicians diagnose myocardial injury that indicates cancer therapy-cardiotoxicity, which will help clinicians make decisions regarding the surveillance frequency and indication for cardio-protection.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCMR \u0026nbsp; \u0026nbsp; cardiac magnetic resonance\u003c/p\u003e\n\u003cp\u003eLGE \u0026nbsp; \u0026nbsp; \u0026nbsp;late gadolinium enhancement\u003c/p\u003e\n\u003cp\u003eLV \u0026nbsp; \u0026nbsp; \u0026nbsp; left ventricle\u003c/p\u003e\n\u003cp\u003ePS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;peak strain\u003c/p\u003e\n\u003cp\u003ePDSR \u0026nbsp; \u0026nbsp; peak diastolic strain rate\u003c/p\u003e\n\u003cp\u003ePSSR \u0026nbsp; \u0026nbsp; \u0026nbsp;peak systolic strain rate\u003c/p\u003e\n\u003cp\u003eNT-pro \u0026nbsp; \u0026nbsp;BNP N-terminal pro–B-type natriuretic peptide\u003c/p\u003e\n\u003cp\u003eEDV \u0026nbsp; \u0026nbsp; \u0026nbsp;end diastolic volume\u003c/p\u003e\n\u003cp\u003eESV \u0026nbsp; \u0026nbsp; \u0026nbsp;end systolic volume\u003c/p\u003e\n\u003cp\u003eSV \u0026nbsp; \u0026nbsp; \u0026nbsp; stroke volume\u003c/p\u003e\n\u003cp\u003eEF \u0026nbsp; \u0026nbsp; \u0026nbsp; ejection fraction\u003c/p\u003e\n\u003cp\u003eI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; indexed to BSA\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eICIs \u0026nbsp; \u0026nbsp; \u0026nbsp;immune checkpoint inhibitors\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eSupplementary information\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupplementary data associated with this article can be found in the online version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZGY and YSS designed the study and contributed to revising the manuscript. XL contributed to drafting and revising the manuscript. YG performed statistical analysis. YG, ZW, WFY and RS collected clinical data and analyzed data. CXZ, BZ and YL collected clinical data and interpreted the results. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the National Natural Science Foundation of China (82102022), and 1-3-5 project for disciplines of excellence of West China Hospital, Sichuan University (ZYGD23019).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used in this study are available from the corresponding author upon 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 conducted in accordance with the Declaration of Helsinki. Ethical approval for this clinical study was obtained from the Biomedical Research Ethics Committee of West China Hospital, Sichuan University. The requirement for informed consent from patients was waived due to the retrospective nature of this study.\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable.\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 no competing interests.\u003c/p\u003e"},{"header":"References ","content":"\u003col\u003e\n\u003cli\u003eStrongman H, Gadd S, Matthews A, Mansfield KE, Stanway S, Lyon AR et al. Medium and long-term risks of specific cardiovascular diseases in survivors of 20 adult cancers: a population-based cohort study using multiple linked UK electronic health records databases. 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JACC: CardioOncology. 2020; 2: 270\u0026ndash;292.\u003c/li\u003e\n\u003cli\u003eLiu X, Gao Y, Guo YK, Xia CC, Shi R, Jiang L et al. Cardiac magnetic resonance T1 mapping for evaluating myocardial fibrosis in patients with type 2 diabetes mellitus: Correlation with left ventricular longitudinal diastolic dysfunction. Eur Radiol. 2022; 32: 7647\u0026ndash;7656.\u003c/li\u003e\n\u003cli\u003ePlana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M 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. European Heart Journal - Cardiovascular Imaging. 2014; 15: 1063\u0026ndash;1093.\u003c/li\u003e\n\u003cli\u003eČelutkienė J, Pudil R, L\u0026oacute;pez-Fern\u0026aacute;ndez T, Grapsa J, Nihoyannopoulos P, Bergler-Klein J et al. Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC). Eur J Heart Fail. 2020; 22: 1504\u0026ndash;1524.\u003c/li\u003e\n\u003cli\u003eThavendiranathan P, Negishi T, Somerset E, Negishi K, Penicka M, Lemieux J et al. Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy. J Am Coll Cardiol. 2021;77(4):392-401.\u003c/li\u003e\n\u003cli\u003eKhan AA, Ashraf A, Singh R, Rahim A, Rostom W, Hussain M et al. Incidence, time of occurrence and response to heart failure therapy in patients with anthracycline cardiotoxicity. Intern Med J. 2017; 47: 104\u0026ndash;109.\u003c/li\u003e\n\u003cli\u003eFei HW, Ali MT, Tan TC, Cheng KH, Salama L, Hua L et al. Left ventricular global longitudinal strain in HER‐2 + breast cancer patients treated with anthracyclines and trastuzumab who develop cardiotoxicity is associated with subsequent recovery of left ventricular ejection fraction. Echocardiography. 2016; 33: 519\u0026ndash;526.\u003c/li\u003e\n\u003cli\u003eThavendiranathan P, Wintersperger BJ, Flamm SD, Marwick TH. Cardiac MRI in the assessment of cardiac injury and toxicity from cancer chemotherapy: A systematic review. Circ: Cardiovascular Imaging. 2013; 6: 1080\u0026ndash;1091.\u003c/li\u003e\n\u003cli\u003eGal\u0026aacute;n-Arriola C, Lobo M, V\u0026iacute;lchez-Tschischke JP, L\u0026oacute;pez GJ, de Molina-Iracheta A, P\u0026eacute;rez-Mart\u0026iacute;nez C et al. Serial magnetic resonance imaging to identify early stages of anthracycline-induced cardiotoxicity. J Am Coll Cardiol. 2019; 73: 779\u0026ndash;791.\u003c/li\u003e\n\u003cli\u003eShanbhag SM, Greve AM, Aspelund T, Schelbert EB, Cao JJ, Danielsen R et al. Prevalence and prognosis of ischaemic and non-ischaemic myocardial fibrosis in older adults. Eur Heart J. 2019; 40: 529\u0026ndash;538.\u003c/li\u003e\n\u003cli\u003eKuruvilla S, Adenaw N, Katwal AB, Lipinski MJ, Kramer CM, Salerno M. Late gadolinium enhancement on cardiac magnetic resonance predicts adverse cardiovascular outcomes in nonischemic cardiomyopathy: A systematic review and meta-analysis. Circ: Cardiovascular Imaging. 2014; 7: 250\u0026ndash;258.\u003c/li\u003e\n\u003cli\u003eModi K, Joppa S, Chen KA, Athwal PSS, Okasha O, Velangi PS et al. Myocardial damage assessed by late gadolinium enhancement on cardiovascular magnetic resonance imaging in cancer patients treated with anthracyclines and/or trastuzumab. Eur Heart J Cardiovasc Imaging. 2021; 22: 427\u0026ndash;434.\u003c/li\u003e\n\u003cli\u003eMaestrini V, Cheang MH, Kotwinski P, Rosmini S, Lloyd G, Kellman P et al. Late anthracycline-related cardiotoxicity in low-risk breast cancer patients. J Am Coll Cardiol. 2017; 69:2573\u0026ndash;5.\u003c/li\u003e\n\u003cli\u003eZhang L, Awadalla M, Mahmood SS, Nohria A, Hassan MZO, Thuny F et al. Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis. Eur Heart J. 2020; 41: 1733\u0026ndash;1743.\u003c/li\u003e\n\u003cli\u003eMahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol. 2018; 71: 1755\u0026ndash;1764.\u003c/li\u003e\n\u003cli\u003eBuck B, Chum AP, Patel M, Carter R, Nawaz H, Yildiz V et al. Cardiovascular magnetic resonance imaging in patients with ibrutinib-associated cardiotoxicity. JAMA Oncol. 2023; 9: 552\u0026ndash;555.\u003c/li\u003e\n\u003cli\u003eFischer K, Obrist SJ, Erne SA, Stark AW, Marggraf M, Kaneko K et al. Feature tracking myocardial strain incrementally improves prognostication in myocarditis beyond traditional CMR imaging features. JACC: Cardiovasc Imaging. 2020; 13: 1891\u0026ndash;1901.31\u003c/li\u003e\n\u003cli\u003eLyon AR, L\u0026oacute;pez-Fern\u0026aacute;ndez T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J et al. 2022 ESC guidelines on cardio-oncology developed in collaboration with the european hematology association (EHA), the european society for therapeutic radiology and oncology (ESTRO) and the international cardio-oncology society (IC-OS). Eur Heart J. 2022; 43: 4229\u0026ndash;4361.\u003c/li\u003e\n\u003cli\u003eCannizzaro MT, Inserra MC, Passaniti G, Celona A, D\u0026apos;Angelo T, Romeo P et al. Role of advanced cardiovascular imaging in chemotherapy-induced cardiotoxicity. Heliyon. 2023; 9: e15226.\u003c/li\u003e\n\u003cli\u003eSuerken CK, D\u0026apos;Agostino RB Jr, Jordan JH, Mel\u0026eacute;ndez GC, Vasu S, Lamar ZS et al. Simultaneous left ventricular volume and strain changes during chemotherapy associate with 2‐year postchemotherapy measures of left ventricular ejection fraction. J Am Heart Assoc. 2020; 9: e015400.\u003c/li\u003e\n\u003cli\u003eNarayan HK, French B, Khan AM, Plappert T, Hyman D, Bajulaiye A et al. Noninvasive measures of ventricular-arterial coupling and circumferential strain predict cancer therapeutics\u0026ndash;related cardiac dysfunction. JACC: Cardiovasc Imaging. 2016; 9: 1131\u0026ndash;1141.\u003c/li\u003e\n\u003cli\u003eOmar AMS, Vallabhajosyula S, Sengupta PP. Left ventricular twist and torsion: Research observations and clinical applications. Circ: Cardiovascular Imaging. 2015; 8: e003029.\u003c/li\u003e\n\u003cli\u003eKim SA, Park SM, Kim MN, Shim WJ. Assessment of left ventricular function by layer-specific strain and its relationship to structural remodelling in patients with hypertension. Can J Cardiol. 2016; 32: 211\u0026ndash;216.\u003c/li\u003e\n\u003cli\u003eAlvarez-Cardona JA, Zhang KW, Mitchell JD, Zaha VG, Fisch MJ, Lenihan DJ. Cardiac Biomarkers During Cancer Therapy: Practical Applications for Cardio-Oncology. JACC CardioOncol. 2020;2(5):791-794.\u003c/li\u003e\n\u003cli\u003eZardavas D, Suter TM, Van Veldhuisen DJ, Steinseifer J, Noe J, Lauer S, et al. Role of Troponins I and T and N-Terminal Prohormone of Brain Natriuretic Peptide in Monitoring Cardiac Safety of Patients with Early-Stage Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Receiving Trastuzumab: A Herceptin Adjuvant Study Cardiac Marker Substudy. J Clin Oncol. 2017;35:878\u0026ndash;884. \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":"cancer therapy-related cardiotoxicity, cardiovascular magnetic resonance, late gadolinium enhancement, myocardial strain","lastPublishedDoi":"10.21203/rs.3.rs-7780372/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7780372/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eClinically, cardiotoxicity defined by reduced left ventricle ejection fraction (LVEF) in tumor therapy could miss the onset of tissue-level myocardial changes. In this study, we aimed to use late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) to evaluate myocardial injury in patients receiving oncotherapy, and to investigate the effect of LGE and other clinical factors on LV function.\u003c/p\u003e\u003ch2\u003eMaterial and method\u003c/h2\u003e\u003cp\u003eThis study included 108 cancer patients and 60 healthy controls examined by CMR imaging. Patients were assigned to the LGE-negative (LGE\u0026minus;, n\u0026thinsp;=\u0026thinsp;80) and LGE-positive groups (LGE+, n\u0026thinsp;=\u0026thinsp;28). The LV functional parameters and myocardial strain parameters, were compared among the three subgroups. Associations between variables were evaluated via Pearson or Spearman correlation analyses. Further, the association between risk factors and LVEF was determined via multivariate linear regression analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe LVEF and peak strain (PS) in all directions were significantly lower in the patients with LGE than in those without (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). There were moderate to high correlations between circumferential peak diastolic strain rate (PDSR), peak systolic strain rate (PSSR), PS, and LVEF in the patients with cancer (r\u0026thinsp;=\u0026thinsp;0.54, r = -0.63, r\u0026thinsp;=\u0026thinsp;0.82, respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Multivariate linear regression analysis revealed independent associations between 1) N-terminal-pro B-type natriuretic peptide and radial, circumferential and longitudinal PS (β = \u0026minus;0.419, β\u0026thinsp;=\u0026thinsp;0.407, β\u0026thinsp;=\u0026thinsp;0.327, respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), 2) troponin T and circumferential PDSR (β\u0026thinsp;=\u0026thinsp;0.342, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and between 3) the LGE extent (LGE%, 5SD) and circumferential PS (β\u0026thinsp;=\u0026thinsp;0.297, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThe presence of LGE was an important risk factor for LV dysfunction in patients receiving cancer therapy, and the circumferential strain reduction is the predominant mechanism of LV dysfunction.\u003c/p\u003e","manuscriptTitle":"Late Gadolinium Enhancement CMR for Detecting Myocardial Injury after Oncotherapy: Correlation with Left Ventricular Function","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-23 19:16:38","doi":"10.21203/rs.3.rs-7780372/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":"cf0cd119-88c8-4e39-a0ec-c5fc5961968f","owner":[],"postedDate":"October 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-01T07:55:04+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-23 19:16:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7780372","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7780372","identity":"rs-7780372","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}