Two-dimensional Speckle Tracking Echocardiography in Chemotherapy-Induced Cardiotoxicity in Females with Breast Cancer

Two-dimensional Speckle Tracking Echocardiography in Chemotherapy-Induced Cardiotoxicity in Females with Breast Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Two-dimensional Speckle Tracking Echocardiography in Chemotherapy-Induced Cardiotoxicity in Females with Breast Cancer Ahmed A Fawzy, Khaled A El-Menyawi, Walid M Sallam, Mohamed E Zahran This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3484121/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Mar, 2024 Read the published version in Cardio-Oncology → Version 1 posted 7 You are reading this latest preprint version Abstract Background Cancer and cardiovascular diseases are the main causes of mortality worldwide. Although the incidence of cancer is rising, modern comprehensive management including surgery, chemotherapy, and radiotherapy led to decreased mortality, but also different cardiovascular complications. Conventional EF measurement fails to detect subtle changes in LV function, so a more sensitive tool is needed. Methods The study included 101 asymptomatic female patients with newly diagnosed breast cancer who received anthracycline ± trastuzumab-based chemotherapy regimen. A comprehensive echocardiographic examination was performed before receiving the chemotherapy (T0), at 3 months (T1), and at 6 months after (T2). All patients had pre-treatment normal LV EF. Cardiotoxicity was defined as a decrease in EF > 10% from baseline value to EF 5% in symptomatic patients “according to the cardiac review and evaluation committee (CREC)”. Results CTRCD occurred in 24 patients (25.5%) while RV systolic dysfunction was more common occurring in 37 patients (39.4%). LV GLS at (T1) (cut-off value <-15% with relative 12.5% reduction from the baseline value) was a strong predictor of CTRCD, but combining LV GLS with RV GLS & RV FWLS was the strongest (AUC = 0.947, sensitivity = 91.67%, specificity = 90%). Conclusion Chemotherapy induces biventricular changes with more prevalent deterioration in RV values. Low LV & RV strain values at baseline together with reduction of these values after chemotherapy treatment can predict later CTRCD development. Combining LV GLS with RV GLS & FWLS values at (T1) is the strongest predictor of subsequent CTRCD. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Introduction Breast cancer is the most common cancer among females worldwide, and it is ranked as the fifth leading cause of cancer death ( 1 ) . Anthracyclines and HER-2 inhibitor (Trastuzumab) are the mainstays of chemotherapy for breast cancer and although they prolonged survival in patients, they led to cardiac toxicity which ranges from mild asymptomatic decrease in EF to clinically overt form of heart failure. Anthracyclines lead to cardiotoxicity in a dose-dependent manner with a 5% incidence of heart failure with an average cumulative dose of 400 mg/m 2 , but it can reach up to 48% with an average cumulative dose of 700 mg/m 2 ( 2 ) . Conversely, Trastuzumab-induced cardiotoxicity is not dose-dependent and is thought to be due to changing the expression of genes responsible for DNA repair and mitochondrial function leading to impaired systolic function ( 3 ) . Traditional follow-up of chemotherapy patients was done by LV EF measurement together with clinical surveillance of heart failure symptoms. Despite the prognostic value of EF measurement, it lacks sensitivity to detect early changes in myocardial function ( 4 ) . This is due to pitfalls including inadequate LV apex visualization, the need for geometrical assumption for calculations, and the variability of measurements ( 5 ) . Because of the aforementioned causes, LVEF reduction is often detected late with failure to recover in 58% of the cases ( 6 ) . Hence, there is a growing interest in identifying the earliest markers of myocardial impairment that can predict subsequent drops in EF. LV strain parameters measurement was used for early assessment of myocardial changes ( 7 ) and LV GLS was adopted by ASE/EACVI expert consensus to be used for follow-up during the chemotherapy treatment ( 8 ) . There is a lack of literature about the effect of chemotherapy on RV function and strain parameters, whether LV changes precede RV changes or the opposite. Also, it`s questionable if changes in GLS values for the RV could predict LV EF drop or not. In this study, we aimed to study changes in LV & RV mechanics during the chemotherapy treatment and detect the strongest predictor of subsequent cardiotoxicity. Methodology This is an observational prospective study that included 101 asymptomatic female patients who were scheduled to receive chemotherapy for breast cancer during the period from April 2021 to December 2022. Exclusion criteria included history of previous chemotherapy or radiotherapy, reduced LV EF < 50%, a history of coronary artery disease, patients with severe valvular disease or primary cardiomyopathy, history of medical diseases affecting right ventricular function, and patients with Atrial Fibrillation or with permanent pacemakers. All patients received anthracycline (doxorubicin or epirubicin) in 3-week cycles for an average of 3–4 cycles. HER-2 (Human Epidermal growth factor Receptor-2) inhibitor (Trastuzumab) was administered in some patients and none of the study population received concurrent anthracyclines and Trastuzumab. Traditional cardiovascular risk factors such as hypertension, diabetes, chronic kidney disease, smoking, hypothyroidism, and obesity (BMI) were recorded in our study population. All patients were informed about the study and informed consent was obtained. This study was approved by Ain-shams University's ethical committee & complied with the ethical guidelines of the 1975 declaration of Helsinki as revised in 2008. * The baseline visits All patients underwent thorough history-taking regarding demographic data, previous oncological therapy, and cardiovascular risk factors. Hypertension was defined as patients taking antihypertensive treatment or patients with Systolic BP ≥ 140 mmHg or Diastolic BP ≥ 90 mmHg based on the mean of two or more properly measured seated blood pressure readings on two or more occasions ( 9 ) . Patients with HbA1C ≥ 6.5% or at least two fasting glucose levels ≥ 126 mg/dL or in use of oral hypoglycemic drugs and/or insulin were classified as diabetics ( 10 ) . Chronic kidney disease was defined as kidney damage or glomerular filtration rate < 60 ml/min/1.73 m2 for 3 months or more ( 11 ) . Data regarding the chemotherapy regimen and received doses were obtained from patients` files. * Two dimensional transthoracic Echocardiography (TTE) Resting ECG-gated transthoracic echocardiography was performed for all patients. Patients were imaged in the left lateral decubitus position using a General Electric (GE) Vingmed Ultrasound Vivid 5 or Vivid 7 system. Full 2D, M-mode, and Doppler images in standard precordial apical and parasternal views were stored and digitally recorded for subsequent analysis. Each measurement was taken from the average of 3 continuous cardiac cycles. Left atrial (LA) diameter, LV end-systolic dimension (LVESD), LV end-diastolic dimension (LVEDD), and LV wall thickness were measured in the parasternal long-axis view. LV diastolic function was assessed by Mitral inflow pattern (E/A ratio), E velocity deceleration time, annular tissue Doppler curves (e`/a`), and E/e` ratio. LVEF was calculated using modified Simpson`s method and cardiotoxicity was defined as a decrease in EF > 10% from baseline value to EF 5% in symptomatic patients “as defined by the cardiac review and evaluation committee (CREC)” ( 12 ) . RV systolic function was assessed using systolic TV annular excursion velocity (S`). The lower reference value of S’ was set as 10 cm/s. All the measurements were performed and reported according to the recommendations of the American Society of Echocardiography ( 13 ) . * Measurement of myocardial strain The standard three apical views together with the parasternal short axis view at the level of insertion of the papillary muscles were used to obtain LV strain values (LV longitudinal (GLS), circumferential (GCS), and radial (GRS)) and the focused RV apical four-chamber view for global longitudinal peak RV systolic strain (RV GLS) and longitudinal peak systolic strain of the RV free wall (RV FWLS) ( 14 ) . Three consecutive heart cycles were recorded and averaged. The frame rate was set between 60 and 80 frames per second; these settings were recommended to combine temporal resolution with adequate spatial definition and to enhance the feasibility of the frame-to-frame tracking technique. Offline analysis was performed using the commercially available software (EchoPAC; GE Medical Systems). Segments of the LV with inadequate image quality were excluded from the analysis due to the presence of acoustic shadows, image artifacts, reverberations, or poor quality in the trace of the points by manual evaluation. The RV peak systolic global longitudinal strain (RVGLS) was measured from all 6 RV myocardial segments from an apical 4-chamber view (3 segments of the free wall plus 3 segments of the interventricular septum) while the RV free wall peak systolic longitudinal strain (RVFWLS) was obtained from the 3 RV free wall segments only. Both were measured because in RVGLS the interventricular septum is measured taking into consideration that it might partially reflect changes in the left ventricle as the septum is shared by both ventricles. While measuring RVFWLS focus is only on the RV-free wall and does not include the contribution of the septum; however, it doesn`t consider potential changes that may occur in the RV septum. * The follow-up visits Patients were asked to follow up after 3 and 6 months from the start of the chemotherapy. In every follow-up visit, revision of the chemotherapy regimen and proper clinical assessment for symptoms and signs of heart failure were done. Echocardiographic imaging (conventional and 2D-STE) was repeated, and the same study parameters were recorded. Patients in the 3-month follow-up visits who met the definition of CTRCD received the proper anti-failure treatment according to the latest ESC guidelines in 2021. * Statistical analysis All data were plotted into tables and statistically studied. All statistical analyses were performed with SPSS software (version 12.0, SPSS Inc., Chicago, Illinois). Quantitative variables were expressed as mean ± standard deviation and compared by Student's t-test , whereas qualitative variables were expressed by their frequencies and percentages, and compared by the chi-square test. A p-value < 0.05 was considered statistically significant. Univariate and multivariate linear regression analysis were used with demographic and echocardiographic data introduced into the regression model to identify the independent predictors of cardiotoxicity. A receiver operator characteristic (ROC) analysis was used to detect the best cut-off values in strain values with the highest sensitivity and specificity for the prediction of future cardiotoxicity. Results In the current study, 101 female patients diagnosed with non-metastatic breast cancer were initially recruited. Six patients were lost to follow-up, and 1 patient died before the first follow-up visit after 3 months, so finally we have 94 patients included in the statistical analysis at the follow-up visits. * Patient Characteristics and Chemotherapy regimens The baseline demographic and clinical data of the study population are summarized in Table (1). The mean age of the study population was 48.75 ± 10.07 years old. Diabetes Mellitus was the most prevalent CV risk factor in our population, present in 34 patients representing 33.7% of the total population. None of the patients was an active smoker. The mean BSA of the study population was 1.83 ± 0.18 Kg/m2. Table (1) Demographic data and characteristics of the studied patients Total no. = 101 Gender Female 101 (100.0%) Age Mean ± SD 48.75 ± 10.07 Range 20–70 BSA Mean ± SD 1.83 ± 0.18 Range 1.5–2.3 Diabetes Mellitus No 67 (66.3%) Yes 34 (33.7%) Hypertension No 73 (72.3%) Yes 28 (27.7%) Chronic Kidney Disease No 100 (99.0%) Yes 1 (1.0%) Thyroid Disorders Normal 97 (96.0%) Hypothyroid 4 (4.0%) All patients received an anthracycline-based chemotherapy regimen (doxorubicin “Adriamycin” or epirubicin) in addition to cyclophosphamide. Forty-nine patients received Trastuzumab as shown in Table (2). Table (2) Chemotherapy regimen details among the studied patients Total no. = 101 Chemotherapy Regimen AC 46 (45.5%) EC 55 (54.5%) Cumulative Dose of Doxorubicin (mg/m2) Mean ± SD 435.40 ± 45.13 Range 370–552 Cumulative Dose of Epirubicin (mg/m2) Mean ± SD 731.85 ± 73.04 Range 600–896 Trastuzumab No 52 (51.5%) Yes 49 (48.5%) AC regimen: Adriamycin (doxorubicin) + cyclophosphamide, EC regimen: Epirubicin + cyclophosphamide * Incidence of Cancer Therapy Related Cardiac Dysfunction (CTRCD), Right ventricular dysfunction At the end of the follow-up period, CTRCD occurred in 24 patients, 11 patients (45.8%) after 3 months (T1) and 13 (54.2%) after 6 months (T2). In these patients, none showed cardiac-related symptoms. Interestingly, Right ventricular dysfunction (defined as RV S`<10 cm/s) was more common occurring in 37 patients representing 39.4% of the study population. 18 patients had Right ventricular dysfunction at T1 and 19 patients at T2. * CTRCD vs non-CTRCD cases at baseline echocardiography The baseline parameters present in Table (3) showed that CTRCD cases had lower mean EF at baseline, but this was not statistically significant when assessed by Simpson`s method. The mean LV GLS was − 18.85 ± 1.56% in non-CTRCD cases and − 17.58 ± 1.28% in CTRCD cases which was statistically significant. LV GCS was also statistically different while LV GRS didn`t achieve statistical significance. RV S`, RV GLS, and RV FWLS were lower in CTRCD cases and this was statistically significant. Table (3) Comparison between cases with and without CTRCD regarding ECHO parameters at baseline Baseline Without CTRCD With CTRCD Test value P-value Sig. No. = 70 No. = 24 LVEDD Mean ± SD 47.14 ± 4.12 48.42 ± 3.59 -1.348• 0.181 NS Range 39–55 44–56 LVESD Mean ± SD 30.73 ± 3.25 32.67 ± 3.23 -2.527• 0.013 S Range 23–37 28–40 LA AP diameter Mean ± SD 35.59 ± 4.11 35.96 ± 2.77 -0.412• 0.681 NS Range 26–45 30–42 Diastolic function Normal 16 (22.9%) 1 (4.2%) 4.214* 0.040 S Grade I 54 (77.1%) 23 (95.8%) Grade II 0 (0.0%) 0 (0.0%) Grade III 0 (0.0%) 0 (0.0%) EF by M-mode Mean ± SD 63.67 ± 3.94 61.29 ± 3.28 2.660• 0.009 HS Range 58–74 54–68 EF by Simpson`s method Mean ± SD 60.21 ± 2.80 59.29 ± 3.50 1.304• 0.195 NS Range 52–68 53–68 RV S` Mean ± SD 12.89 ± 0.86 12.42 ± 0.83 2.325• 0.022 S Range 11–15 11–14 GLS % Mean ± SD -18.85 ± 1.56 -17.58 ± 1.28 -3.603• 0.001 HS Range -22 – -16 -21 – -16 GCS % Mean ± SD -24.34 ± 1.77 -23.21 ± 1.86 -2.647• 0.010 S Range -27.6 – -21 -26.6 – -20.9 GRS % Mean ± SD 45.91 ± 6.55 43.76 ± 6.83 1.370• 0.174 NS Range 33.8–58.8 37.2–55.2 RVGLS % Mean ± SD -23.20 ± 1.04 -22.68 ± 0.92 -2.170• 0.033 S Range -27 – -21.6 -25 – -21.6 RV FWLS % Mean ± SD -25.47 ± 1.20 -24.83 ± 0.96 -2.354• 0.021 S Range -30 – -23 -27 – -23 *: Chi-square test; •: Independent t-test * CTRCD vs non-CTRCD cases at 3-month follow-up echocardiography Table (4) shows the difference regarding baseline echocardiography parameters between CTRCD cases and non-CTRCD cases. LV EF, LV GLS, and LV GCS were lower in CTRCD cases in a statistically significant value. LV GRS was also lower in CTRCD cases, but not statistically significant. RV S`, RV GLS & RV FWLS were lower with a statistical significance in CTRCD cases. Table (4) Comparison between cases with and without CTRCD regarding ECHO parameters after 3 months After 3 months Without CTRCD With CTRCD Test value P-value Sig. No. = 70 No. = 24 LVEDD Mean ± SD 47.84 ± 3.87 50.88 ± 4.50 -3.173• 0.002 HS Range 40–56 43–58 LVESD Mean ± SD 31.79 ± 3.43 37.42 ± 4.36 -6.464• 0.000 HS Range 25–39 29–46 LA Mean ± SD 36.53 ± 3.45 37.83 ± 2.87 -1.664• 0.099 NS Range 28–45 32–45 Diastolic degree Normal 11 (15.7%) 1 (4.2%) 2.140* 0.143 NS Grade I 59 (84.3%) 23 (95.8%) Grade II 0 (0.0%) 0 (0.0%) Grade III 0 (0.0%) 0 (0.0%) EF M mode Mean ± SD 62.07 ± 4.06 52.50 ± 5.65 8.974• 0.000 HS Range 55–74 35–60 EF Simpson`s method Mean ± SD 59.13 ± 2.53 49.54 ± 5.63 11.356• 0.000 HS Range 54–65 35–59 RV S` Mean ± SD 12.74 ± 1.29 9.42 ± 0.97 11.515• 0.000 HS Range 9–15 8–11 GLS % Mean ± SD -17.80 ± 1.88 -13.54 ± 1.91 -9.539• 0.000 HS Range -22 – -13 -19 – -9 GCS % Mean ± SD -24.37 ± 1.73 -21.83 ± 2.51 -5.488• 0.000 HS Range -28 – -21 -26 – -15 GRS % Mean ± SD 45.00 ± 6.28 42.08 ± 8.03 1.825• 0.071 NS Range 32–58 26–57 RV GLS% Mean ± SD -22.14 ± 2.92 -15.38 ± 2.57 -10.101• 0.000 HS Range -26 – -13 -24 – -12 RV FWLS % Mean ± SD -24.36 ± 3.18 -17.13 ± 2.42 -10.163• 0.000 HS Range -28 – -15 -26 – -14 *: Chi-square test; •: Independent t-test * Changes in LV and RV echocardiographic parameters at T0, T1 and T2 The following figures show the temporal changes in LV and RV mechanics in both CTRCD and non-CTRCD cases. * Predicting a subsequent CTRCD development On the univariate logistic regression analysis model, baseline LV GLS (<-18%), LV GCS (<-23.9%), RV GLS (<-22.6%), and RV FWLS (<-24%) were predictors of CTRCD occurrence as shown in table (5) . At the 3-month follow-up visit, LV GLS (<-15% with a relative reduction of 12.5% from the baseline) together with RV GLS (<-18%) and RV FWLS (<-19%) were predictors of later CTRCD development. A multivariate regression model showed that the relative reduction of LV GLS of 12.5% at 3 months from baseline was an independent predictor for the development of CTRCD as shown in Table (5). Table (5) Univariate and multivariate logistic regression analysis for factors associated with CTCRD after 6 months Univariate Multivariate P-value Odds ratio (OR) 95% C.I. for OR P-value Odds ratio (OR) 95% C.I. for OR Lower Upper Lower Upper Diabetes Mellitus 0.000 6.750 2.445 18.637 – – – – Trastazumab 0.006 4.241 1.500 11.989 – – – – Baseline LVESD > 33 0.040 2.857 1.050 7.772 – – – – Diastolic function grade I 0.070 6.815 0.853 54.461 – – – – EF by M-mode < = 60 0.010 3.710 1.360 10.123 – – – – RV S` <=13 0.073 4.098 0.878 19.123 – – – – GLS % <= -18 0.001 9.333 2.546 34.214 – – – – GCS % <= -23.9 0.014 3.385 1.274 8.995 – – – – RVGLS % <= -22.6 0.018 3.172 1.214 8.288 – – – – RV FWLS % 33 0.000 10.217 3.128 33.375 – – – – EF M mode < = 58 0.000 33.889 9.408 122.069 – – – – EF Simpson`s method < = 55 0.000 82.500 18.904 360.046 – – – – GLS % <= -15 0.000 85.250 16.803 432.517 – – – – RVGLS % <= -18 0.000 178.250 21.115 1504.785 – – – – RV FWLS % <= -19 0.000 207.000 24.136 1775.303 – – – – GLS change < = 12.5% 0.000 207.000 24.136 1775.303 0.000 198.000 23.046 1701.117 RVGLS change < = 21.74% 0.000 198.000 23.046 1701.117 – – – – RVFWLS change < = 24% 0.000 207.000 24.136 1775.303 – – – – Based on the Receiver Operating Characteristic (ROC) curve figure (8), low values of LV GLS, RV GLS, and RV FWLS at the baseline were predictors of CTRCD development with combining them together was the strongest baseline predictor (AUC = 0.751, sensitivity = 83.33%, specificity = 60%) as shown in table (6). Table (6) ROC curve for GLS%, RV-GLS% and RV-FWLS% at baseline to detect CTCRD Variables Cut off point AUC Sensitivity Specificity +PV -PV GLS % baseline <= -18 0.740 87.50 57.14 41.2 93.0 RVGLS % baseline <= -22.6 0.654 54.17 72.86 40.6 82.3 RV FWLS % baseline <= -24 0.652 41.67 80.00 41.7 80.0 Combined 0.751 83.33 60.00 41.7 91.3 After 3 months combining LV GLS, RV GLS, and RV FWLS together was the strongest predictor of the development of CTRCD as shown in Figure (9) and Table (7) (AUC = 0.947, sensitivity = 91.67%, specificity = 90%). Table (7) ROC curve for LV GLS, RV GLS, RV FWLS after 3 months to detect CTCRD Variables Cut off point AUC Sensitivity Specificity +PV -PV GLS % after 3 m <= -15 0.938 91.67 88.57 73.3 96.9 RV GLS% after 3 m <= -18 0.915 95.83 88.57 74.2 98.4 RV FWLS % after 3 m <= -19 0.909 95.83 90.00 76.7 98.4 Combined 0.947 91.67 90.00 75.9 96.9 Discussion Early detection of CTRCD is the main concern of the cardio-oncology team during chemotherapy to be able to start cardio-protective strategies as early as possible. The role of 2D speckle tracking echocardiography in early detection of CTRCD was previously tested in many studies. Alterations in strain parameters of 2D STE have been shown to precede a decrease in EF ( 15 ) . In this present study, we assessed the deformation mechanics in both LV and RV throughout a 6-month chemotherapy regimen. First of all, in our study RV dysfunction was more common than LV dysfunction at the end of the follow-up period. RV dysfunction occurred in 37 patients representing 39.4% of the study population with almost half of them occurring as early as the first follow-up visit after 3 months (T1). On the contrary, LV dysfunction was less prevalent and more delayed occurring in 25.5% of the cases with 45% of them at (T1). These results were consistent with the results shown by Zhao et al., 2020 in which the drop in RV function preceded LVEF decrease ( 16 ) . The underlying suggested reason was the fact that the RV wall is thinner, having less reserve for compensation compared to the LV, and thus more prone to cardiotoxicity. This is also confirmed by other imaging modalities, as evidenced by a study from Ylanen et al., 2013 which evaluated the late effects of Anthracycline-induced cardiotoxicity in childhood cancer survivors, using cardiac MRI. This study showed a 27% prevalence of abnormal RV function and only an 18% prevalence of abnormal LV function ( 17 ) . On the other side one study from Keramida et al., 2019 showed that LV GLS was significantly reduced after 3 months of chemotherapy earlier than RV GLS ( 18 ) . Although there was no postulated hypothesis justifying this earlier LV affection, it can be assumed to differences in the inclusion criteria of the study population in this study from our study. At Keramida et al., 2019 , 54.5% of the study population received previous radiotherapy treatment, unlike our study in which no patient received previous radiotherapy treatment. This controversy necessitates more studying of the change in RV mechanics during chemotherapy & comparing it to LV changes although the hypothesis of the thinner RV wall seems reasonable, but more evidence is still required. Regarding the changes in LV strain parameters, our study showed that LV GLS is the most sensitive strain parameter to predict later CTRCD. At baseline, people with lower LV GLS values –even may be still in the normal range- were associated with a higher risk for developing later CTRCD. In this study, a Baseline LV GLS value less than − 18% was associated with an increased possibility of CTRCD development than higher values (AUC = 0.740, sensitivity = 87.5%, specificity = 57.14%). The suggested explanation was that cancer itself is considered as an inflammatory process releasing various reactive oxidative species and combined with neuro-hormonal changes. This has a significant effect on myocardium which is usually aggravated by chemotherapy ( 18 ) . At the 3-month follow-up visit (T1), changes in LV GLS value were stronger predictors than LV GCS and GRS as evidenced by univariate and multivariate regression analysis models (using LV GLS cut-off value of -15% or a decrease from the baseline value by 12.5%). This result was consistent with the previous studies and with ASE/EACVI consensus guidelines which recommended measurement of GLS for follow-up of cancer patients receiving chemotherapy ( 8 ) . The postulated hypothesis behind this is that cardiotoxicity results from regional deformational changes of the myocardium which also explains why LV strain changes precede LV EF changes because some segments are affected usually earlier than others which on the contrary plays a compensatory role and thus LV EF remains stable. The long-axis function of the left ventricle is governed by subendocardial, longitudinally-arranged myocardial fibers, which are more susceptible to early hypoxia and myocardial injury ( 4 ) . That`s why in the case of early myocardial injury, longitudinal strain is usually affected first while circumferential strain may compensate for left ventricular function. With the progression of the disease, circumferential strain will be affected which might indicate transmural involvement ( 19 ) . In this study, our primary endpoint was trying to detect the earliest strain parameter that precedes EF changes and thus can predict CTRCD later on. In our study and based on the ROC curve, combining LV GLS with RV GLS and RVFWLS was the best predictor of subsequent CTRCD. Although there is a paucity of data in the literature studying the role of RV strain parameters in predicting LV EF drop, our study results are consistent with the results of Arciniegas Calle et al published in 2018 ( 20 ) . At Arciniegas Calle et al., 2018 , it was concluded that Combining both RV GLS at T1 and LV GLS was the strongest predictor of cardiotoxicity (area under the curve[AUC], 0.91; sensitivity, 100%; specificity, 73%; P < .001). LV GLS at T1 (AUC, 0.85; cutoff, − 14.06; sensitivity, 91%; specificity, 83%; P = .003) was also a strong indicator of subsequent cardiotoxicity. This can be explained because it is known that usually, longitudinal deformational changes are always the earliest to happen and thus measuring longitudinal RV strain would increase the ability to predict the future drop in EF because more muscle fibers are studied and the wall of the RV is even thinner than LV and thus it would be more affected. We aimed to highlight the importance of studying the changes in RV mechanics during the period of chemotherapy as combining some of these data with LV strain variables gives us the best chance to predict CTRCD and detect it as early as possible, so we can modify the chemotherapy regimen and start cardio-protective measures early and to detect patients based on their baseline data who are at risk of later development of CTRCD. Study Limitations Our study limitations were that it was a single-center study and the duration of follow-up was 6 months only. Also, we didn`t study whether these early cardiotoxic changes are reversible in a longer follow-up duration or not. Conclusion Anthracycline ± Trastuzumab treatment leads to changes in LV & RV mechanics with more prevalent deterioration in RV values. The presence of lower LV & RV strain values at the base line together with reduction of these values after chemotherapy treatment can predict the later development of CTRCD. Combining LV GLS with RV GLS & FWLS values at (T1) is the strongest predictor of subsequent CTRCD. Declarations Ethical Approval All patients were informed about the study and informed consent was obtained. This study was approved by Ain-shams University's ethical committee & complied with the ethical guidelines of the 1975 declaration of Helsinki as revised in 2008. Funding No funding has been received for this study from any institution or committee. Availability of data and materials The data of the studied patients are available with the authors upon request. 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Early detection and prediction of anthracycline-induced right ventricular cardiotoxicity by 3-dimensional echocardiography. Cardio Oncol. 2020;2(1):13–22. Ylänen K, Poutanen T, Savikurki-Heikkilä P, Rinta-Kiikka I, Eerola A, Vettenranta K. Cardiac magnetic resonance imaging in the evaluation of the late effects of anthracyclines among long-term survivors of childhood cancer. J Am Coll Cardiol. 2013;61(14):1539–47. Keramida K, Farmakis D, Bingcang J, Sulemane S, Sutherland S, Bingcang RA, et al. Longitudinal changes of right ventricular deformation mechanics during trastuzumab therapy in breast cancer patients. Eur J Heart Fail. 2019;21(4):529–35. Bansal M, Sengupta PP. Longitudinal and circumferential strain in patients with regional LV dysfunction. Curr Cardiol Rep. 2013;15:1–4. Arciniegas Calle MC, Sandhu NP, Xia H, Cha SS, Pellikka PA, Ye Z, et al. Two-dimensional speckle tracking echocardiography predicts early subclinical cardiotoxicity associated with anthracycline-trastuzumab chemotherapy in patients with breast cancer. BMC Cancer. 2018;18(1):1–8. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 01 Mar, 2024 Read the published version in Cardio-Oncology → Version 1 posted Editorial decision: Revision requested 05 Jan, 2024 Reviews received at journal 26 Dec, 2023 Reviewers agreed at journal 16 Dec, 2023 Reviewers invited by journal 13 Nov, 2023 Editor assigned by journal 26 Oct, 2023 Submission checks completed at journal 25 Oct, 2023 First submitted to journal 23 Oct, 2023 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3484121","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":242953527,"identity":"d39fce78-e816-4d39-84d1-29c797c2db9e","order_by":0,"name":"Ahmed A Fawzy","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"A","lastName":"Fawzy","suffix":""},{"id":242953528,"identity":"df5e4089-6d21-444d-9505-a34ec0fcb719","order_by":1,"name":"Khaled A El-Menyawi","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Khaled","middleName":"A","lastName":"El-Menyawi","suffix":""},{"id":242953529,"identity":"188bfc66-c71c-4b84-98c9-7a4f7b95fd40","order_by":2,"name":"Walid M Sallam","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Walid","middleName":"M","lastName":"Sallam","suffix":""},{"id":242953530,"identity":"ed559b01-6c2b-446a-a0cf-9075be3d5793","order_by":3,"name":"Mohamed E Zahran","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYFACHhBhA8QJUIEDxGlJI13LYRK0yLefPfbh547z0fzsCYwff7YxyPHdSGB8+AWPFsaevOSZvWdu587secAszdvGYCx5I4HZWAaPFmaGHGMG3rbbuRtuJDBIM7YxJAIZbNISeLSw8b8xZvzbdi53P9Dwn0CH1QO1sP/Gp4VHIseYmbftQO4GiQQ2CaDDEgyAtjB+wKNFQuKNMbNsW3LujDMP26x5zkkYzjzzsFkajw4G+f4cY8a3bXa5/e3Jh2/+KLOR5zuefPDjD3x6EICxAWQrmMHMQ5wWZN1E2jIKRsEoGAUjAwAAWyZM4OhcsX0AAAAASUVORK5CYII=","orcid":"","institution":"Ain Shams University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"E","lastName":"Zahran","suffix":""}],"badges":[],"createdAt":"2023-10-24 03:29:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3484121/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3484121/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s40959-024-00209-1","type":"published","date":"2024-03-01T15:02:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":45389166,"identity":"01711f4d-4042-4f2a-bac0-f9bdbc523137","added_by":"auto","created_at":"2023-10-29 02:12:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":29645,"visible":true,"origin":"","legend":"\u003cp\u003eEF by Simpson`s method changes in\u003cstrong\u003e \u003c/strong\u003eCTRCD and non-CTRCD cases at baseline, after 3 months and after 6 months\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3484121/v1/4811e2618840c5e8f0556761.png"},{"id":45390213,"identity":"ace6de32-90e3-439c-9074-54f7545a4fa1","added_by":"auto","created_at":"2023-10-29 02:20:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":24624,"visible":true,"origin":"","legend":"\u003cp\u003eRV S` changes in\u003cstrong\u003e \u003c/strong\u003eCTRCD and non-CTRCD cases at baseline, after 3 months and after 6 months\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3484121/v1/7b7ac358c363e2e2464afe5a.png"},{"id":45389162,"identity":"5b8e7bef-6199-4b34-aec3-d8a37dc19088","added_by":"auto","created_at":"2023-10-29 02:12:45","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":27720,"visible":true,"origin":"","legend":"\u003cp\u003eLV GLS% changes in\u003cstrong\u003e \u003c/strong\u003eCTRCD and non-CTRCD cases at baseline, after 3 months and after 6 months\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3484121/v1/10e4cc95f3561565cca2930a.png"},{"id":45389165,"identity":"4082a47b-7cd0-4a6a-81a0-50998b2489b7","added_by":"auto","created_at":"2023-10-29 02:12:45","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":25804,"visible":true,"origin":"","legend":"\u003cp\u003eLV GCS% changes in\u003cstrong\u003e \u003c/strong\u003eCTRCD and non-CTRCD cases at baseline, after 3 months and after 6 months\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-3484121/v1/d8278b54c4d4c0a96862bc9a.png"},{"id":45389163,"identity":"f90fe06c-28a0-4c86-a017-e75a2cc3fc04","added_by":"auto","created_at":"2023-10-29 02:12:45","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":28698,"visible":true,"origin":"","legend":"\u003cp\u003eLV GRS% changes in CTRCD and non-CTRCD cases at baseline, after 3 months and after 6 months\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-3484121/v1/75e9a59e2211b61c91b5d8e1.png"},{"id":45389167,"identity":"d47ea72d-b8c2-443a-ae8b-ab1030a32825","added_by":"auto","created_at":"2023-10-29 02:12:45","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":26554,"visible":true,"origin":"","legend":"\u003cp\u003eRV GLS% changes in\u003cstrong\u003e \u003c/strong\u003eCTRCD and non-CTRCD cases at baseline, after 3 months and after 6 months\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-3484121/v1/1df4b97e8e5d73208eebb630.png"},{"id":45389169,"identity":"975a1ea4-4439-4e21-ab45-dbc4cccb2226","added_by":"auto","created_at":"2023-10-29 02:12:45","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":26927,"visible":true,"origin":"","legend":"\u003cp\u003eRV FWLS% changes in CTRCD and non-CTRCD cases at baseline, after 3 months and after 6 months\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-3484121/v1/60a638b9f0eeb1654ed9103e.png"},{"id":45389170,"identity":"258a9a62-79ec-4b7f-a10d-0565e6575392","added_by":"auto","created_at":"2023-10-29 02:12:45","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":78742,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for GLS%, RV-GLS% and RV-FWLS% at baseline to detect CTCRD\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-3484121/v1/cef5b59926c403399c3a6fe6.png"},{"id":45389168,"identity":"a2c09446-3b29-4a7e-84d7-33d95a507e8f","added_by":"auto","created_at":"2023-10-29 02:12:45","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":83727,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for LV GLS, RV GLS, RV FWLS after 3 months to detect CTCRD\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-3484121/v1/9a5c6cf378a471d2d58a61df.png"},{"id":51958381,"identity":"e110c812-0718-462b-bb0a-8a9ce358282f","added_by":"auto","created_at":"2024-03-04 15:15:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1289334,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3484121/v1/1df57854-a159-4082-8b23-92d66cf2eeb1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Two-dimensional Speckle Tracking Echocardiography in Chemotherapy-Induced Cardiotoxicity in Females with Breast Cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast cancer is the most common cancer among females worldwide, and it is ranked as the fifth leading cause of cancer death \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. Anthracyclines and HER-2 inhibitor (Trastuzumab) are the mainstays of chemotherapy for breast cancer and although they prolonged survival in patients, they led to cardiac toxicity which ranges from mild asymptomatic decrease in EF to clinically overt form of heart failure.\u003c/p\u003e \u003cp\u003eAnthracyclines lead to cardiotoxicity in a dose-dependent manner with a 5% incidence of heart failure with an average cumulative dose of 400 mg/m\u003csup\u003e2\u003c/sup\u003e, but it can reach up to 48% with an average cumulative dose of 700 mg/m\u003csup\u003e2 \u003cb\u003e(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. Conversely, Trastuzumab-induced cardiotoxicity is not dose-dependent and is thought to be due to changing the expression of genes responsible for DNA repair and mitochondrial function leading to impaired systolic function \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTraditional follow-up of chemotherapy patients was done by LV EF measurement together with clinical surveillance of heart failure symptoms. Despite the prognostic value of EF measurement, it lacks sensitivity to detect early changes in myocardial function \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. This is due to pitfalls including inadequate LV apex visualization, the need for geometrical assumption for calculations, and the variability of measurements \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eBecause of the aforementioned causes, LVEF reduction is often detected late with failure to recover in 58% of the cases \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. Hence, there is a growing interest in identifying the earliest markers of myocardial impairment that can predict subsequent drops in EF. LV strain parameters measurement was used for early assessment of myocardial changes \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e and LV GLS was adopted by ASE/EACVI expert consensus to be used for follow-up during the chemotherapy treatment \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThere is a lack of literature about the effect of chemotherapy on RV function and strain parameters, whether LV changes precede RV changes or the opposite. Also, it`s questionable if changes in GLS values for the RV could predict LV EF drop or not. In this study, we aimed to study changes in LV \u0026amp; RV mechanics during the chemotherapy treatment and detect the strongest predictor of subsequent cardiotoxicity.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cp\u003eThis is an observational prospective study that included 101 asymptomatic female patients who were scheduled to receive chemotherapy for breast cancer during the period from April 2021 to December 2022.\u003c/p\u003e \u003cp\u003eExclusion criteria included history of previous chemotherapy or radiotherapy, reduced LV EF\u0026thinsp;\u0026lt;\u0026thinsp;50%, a history of coronary artery disease, patients with severe valvular disease or primary cardiomyopathy, history of medical diseases affecting right ventricular function, and patients with Atrial Fibrillation or with permanent pacemakers.\u003c/p\u003e \u003cp\u003eAll patients received anthracycline (doxorubicin or epirubicin) in 3-week cycles for an average of 3\u0026ndash;4 cycles. HER-2 (Human Epidermal growth factor Receptor-2) inhibitor (Trastuzumab) was administered in some patients and none of the study population received concurrent anthracyclines and Trastuzumab. Traditional cardiovascular risk factors such as hypertension, diabetes, chronic kidney disease, smoking, hypothyroidism, and obesity (BMI) were recorded in our study population.\u003c/p\u003e \u003cp\u003e All patients were informed about the study and informed consent was obtained. This study was approved by Ain-shams University's ethical committee \u0026amp; complied with the ethical guidelines of the 1975 declaration of Helsinki as revised in 2008.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e* The baseline visits\u003c/h2\u003e \u003cp\u003eAll patients underwent thorough history-taking regarding demographic data, previous oncological therapy, and cardiovascular risk factors. Hypertension was defined as patients taking antihypertensive treatment or patients with Systolic BP\u0026thinsp;\u0026ge;\u0026thinsp;140 mmHg or Diastolic BP\u0026thinsp;\u0026ge;\u0026thinsp;90 mmHg based on the mean of two or more properly measured seated blood pressure readings on two or more occasions \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. Patients with HbA1C\u0026thinsp;\u003cb\u003e\u0026ge;\u003c/b\u003e\u0026thinsp;6.5% or at least two fasting glucose levels\u0026thinsp;\u003cb\u003e\u0026ge;\u003c/b\u003e\u0026thinsp;126 mg/dL or in use of oral hypoglycemic drugs and/or insulin were classified as diabetics \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. Chronic kidney disease was defined as kidney damage or glomerular filtration rate\u0026thinsp;\u0026lt;\u0026thinsp;60 ml/min/1.73 m2 for 3 months or more \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. Data regarding the chemotherapy regimen and received doses were obtained from patients` files.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e* Two dimensional transthoracic Echocardiography (TTE)\u003c/h2\u003e \u003cp\u003eResting ECG-gated transthoracic echocardiography was performed for all patients. Patients were imaged in the left lateral decubitus position using a General Electric (GE) Vingmed Ultrasound Vivid 5 or Vivid 7 system. Full 2D, M-mode, and Doppler images in standard precordial apical and parasternal views were stored and digitally recorded for subsequent analysis. Each measurement was taken from the average of 3 continuous cardiac cycles. Left atrial (LA) diameter, LV end-systolic dimension (LVESD), LV end-diastolic dimension (LVEDD), and LV wall thickness were measured in the parasternal long-axis view. LV diastolic function was assessed by Mitral inflow pattern (E/A ratio), E velocity deceleration time, annular tissue Doppler curves (e`/a`), and E/e` ratio. LVEF was calculated using modified Simpson`s method and cardiotoxicity was defined as a decrease in EF\u0026thinsp;\u0026gt;\u0026thinsp;10% from baseline value to EF\u0026thinsp;\u0026lt;\u0026thinsp;55% in asymptomatic patients or \u0026gt;\u0026thinsp;5% in symptomatic patients \u0026ldquo;as defined by the cardiac review and evaluation committee (CREC)\u0026rdquo; \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. RV systolic function was assessed using systolic TV annular excursion velocity (S`). The lower reference value of S\u0026rsquo; was set as 10 cm/s. All the measurements were performed and reported according to the recommendations of the American Society of Echocardiography \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e* Measurement of myocardial strain\u003c/h2\u003e \u003cp\u003eThe standard three apical views together with the parasternal short axis view at the level of insertion of the papillary muscles were used to obtain LV strain values (LV longitudinal (GLS), circumferential (GCS), and radial (GRS)) and the focused RV apical four-chamber view for global longitudinal peak RV systolic strain (RV GLS) and longitudinal peak systolic strain of the RV free wall (RV FWLS) \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThree consecutive heart cycles were recorded and averaged. The frame rate was set between 60 and 80 frames per second; these settings were recommended to combine temporal resolution with adequate spatial definition and to enhance the feasibility of the frame-to-frame tracking technique. Offline analysis was performed using the commercially available software \u003cb\u003e(EchoPAC; GE Medical Systems).\u003c/b\u003e Segments of the LV with inadequate image quality were excluded from the analysis due to the presence of acoustic shadows, image artifacts, reverberations, or poor quality in the trace of the points by manual evaluation.\u003c/p\u003e \u003cp\u003eThe RV peak systolic global longitudinal strain (RVGLS) was measured from all 6 RV myocardial segments from an apical 4-chamber view (3 segments of the free wall plus 3 segments of the interventricular septum) while the RV free wall peak systolic longitudinal strain (RVFWLS) was obtained from the 3 RV free wall segments only. Both were measured because in RVGLS the interventricular septum is measured taking into consideration that it might partially reflect changes in the left ventricle as the septum is shared by both ventricles. While measuring RVFWLS focus is only on the RV-free wall and does not include the contribution of the septum; however, it doesn`t consider potential changes that may occur in the RV septum.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e* The follow-up visits\u003c/h2\u003e \u003cp\u003ePatients were asked to follow up after 3 and 6 months from the start of the chemotherapy. In every follow-up visit, revision of the chemotherapy regimen and proper clinical assessment for symptoms and signs of heart failure were done. Echocardiographic imaging (conventional and 2D-STE) was repeated, and the same study parameters were recorded. Patients in the 3-month follow-up visits who met the definition of CTRCD received the proper anti-failure treatment according to the latest ESC guidelines in 2021.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e* Statistical analysis\u003c/h2\u003e \u003cp\u003eAll data were plotted into tables and statistically studied. All statistical analyses were performed with SPSS software (version 12.0, SPSS Inc., Chicago, Illinois). Quantitative variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and compared by Student's \u003cem\u003et-test\u003c/em\u003e, whereas qualitative variables were expressed by their frequencies and percentages, and compared by the chi-square test. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Univariate and multivariate linear regression analysis were used with demographic and echocardiographic data introduced into the regression model to identify the independent predictors of cardiotoxicity. A receiver operator characteristic (ROC) analysis was used to detect the best cut-off values in strain values with the highest sensitivity and specificity for the prediction of future cardiotoxicity.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn the current study, 101 female patients diagnosed with non-metastatic breast cancer were initially recruited. Six patients were lost to follow-up, and 1 patient died before the first follow-up visit after 3 months, so finally we have 94 patients included in the statistical analysis at the follow-up visits.\u003c/p\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003e* Patient Characteristics and Chemotherapy regimens\u003c/h2\u003e\n\u003cp\u003eThe baseline demographic and clinical data of the study population are summarized in Table\u0026nbsp;(1). The mean age of the study population was 48.75\u0026thinsp;\u0026plusmn;\u0026thinsp;10.07 years old. Diabetes Mellitus was the most prevalent CV risk factor in our population, present in 34 patients representing 33.7% of the total population. None of the patients was an active smoker. The mean BSA of the study population was 1.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18 Kg/m2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(1)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDemographic data and characteristics of the studied patients\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Taba\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotal no. = 101\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGender\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e101 (100.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48.75\u0026thinsp;\u0026plusmn;\u0026thinsp;10.07\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20\u0026ndash;70\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eBSA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.5\u0026ndash;2.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eDiabetes Mellitus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e67 (66.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34 (33.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHypertension\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e73 (72.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28 (27.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eChronic Kidney Disease\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e100 (99.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (1.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eThyroid Disorders\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNormal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e97 (96.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHypothyroid\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (4.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAll patients received an anthracycline-based chemotherapy regimen (doxorubicin \u0026ldquo;Adriamycin\u0026rdquo; or epirubicin) in addition to cyclophosphamide. Forty-nine patients received Trastuzumab as shown in Table\u0026nbsp;(2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(2)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChemotherapy regimen details among the studied patients\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tabb\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTotal no. = 101\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"1\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eChemotherapy Regimen\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e46 (45.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55 (54.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCumulative Dose of Doxorubicin (mg/m2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e435.40\u0026thinsp;\u0026plusmn;\u0026thinsp;45.13\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e370\u0026ndash;552\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCumulative Dose of Epirubicin (mg/m2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e731.85\u0026thinsp;\u0026plusmn;\u0026thinsp;73.04\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e600\u0026ndash;896\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTrastuzumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52 (51.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eYes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49 (48.5%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\"\u003eAC regimen: Adriamycin (doxorubicin)\u0026thinsp;+\u0026thinsp;cyclophosphamide, EC regimen: Epirubicin\u0026thinsp;+\u0026thinsp;cyclophosphamide\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n\u003ch2\u003e* Incidence of Cancer Therapy Related Cardiac Dysfunction (CTRCD), Right ventricular dysfunction\u003c/h2\u003e\n\u003cp\u003eAt the end of the follow-up period, CTRCD occurred in 24 patients, 11 patients (45.8%) after 3 months (T1) and 13 (54.2%) after 6 months (T2). In these patients, none showed cardiac-related symptoms. Interestingly, Right ventricular dysfunction (defined as RV S`\u0026lt;10 cm/s) was more common occurring in 37 patients representing 39.4% of the study population. 18 patients had Right ventricular dysfunction at T1 and 19 patients at T2.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003e* CTRCD vs non-CTRCD cases at baseline echocardiography\u003c/h2\u003e\n\u003cp\u003eThe baseline parameters present in Table\u0026nbsp;(3) showed that CTRCD cases had lower mean EF at baseline, but this was not statistically significant when assessed by Simpson`s method. The mean LV GLS was \u0026minus;\u0026thinsp;18.85\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56% in non-CTRCD cases and \u0026minus;\u0026thinsp;17.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.28% in CTRCD cases which was statistically significant. LV GCS was also statistically different while LV GRS didn`t achieve statistical significance. RV S`, RV GLS, and RV FWLS were lower in CTRCD cases and this was statistically significant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(3)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eComparison between cases with and without CTRCD regarding ECHO parameters at baseline\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tabc\" border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eBaseline\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWithout CTRCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWith CTRCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTest value\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eP-value\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSig.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo. = 70\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo. = 24\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLVEDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e47.14\u0026thinsp;\u0026plusmn;\u0026thinsp;4.12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e48.42\u0026thinsp;\u0026plusmn;\u0026thinsp;3.59\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-1.348\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.181\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39\u0026ndash;55\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e44\u0026ndash;56\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLVESD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30.73\u0026thinsp;\u0026plusmn;\u0026thinsp;3.25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-2.527\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.013\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23\u0026ndash;37\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28\u0026ndash;40\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLA AP diameter\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35.59\u0026thinsp;\u0026plusmn;\u0026thinsp;4.11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35.96\u0026thinsp;\u0026plusmn;\u0026thinsp;2.77\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-0.412\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.681\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u0026ndash;45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30\u0026ndash;42\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eDiastolic function\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNormal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (22.9%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (4.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e4.214*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e0.040\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGrade I\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e54 (77.1%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23 (95.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGrade II\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGrade III\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eEF by M-mode\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.94\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e61.29\u0026thinsp;\u0026plusmn;\u0026thinsp;3.28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e2.660\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.009\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e58\u0026ndash;74\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e54\u0026ndash;68\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eEF by Simpson`s method\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60.21\u0026thinsp;\u0026plusmn;\u0026thinsp;2.80\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59.29\u0026thinsp;\u0026plusmn;\u0026thinsp;3.50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1.304\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.195\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52\u0026ndash;68\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53\u0026ndash;68\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRV S`\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.86\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e2.325\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.022\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u0026ndash;15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11\u0026ndash;14\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGLS %\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-18.85\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-17.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-3.603\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-22 \u0026ndash; -16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-21 \u0026ndash; -16\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGCS %\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-24.34\u0026thinsp;\u0026plusmn;\u0026thinsp;1.77\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-23.21\u0026thinsp;\u0026plusmn;\u0026thinsp;1.86\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-2.647\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.010\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-27.6 \u0026ndash; -21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-26.6 \u0026ndash; -20.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGRS %\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45.91\u0026thinsp;\u0026plusmn;\u0026thinsp;6.55\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43.76\u0026thinsp;\u0026plusmn;\u0026thinsp;6.83\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1.370\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.174\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33.8\u0026ndash;58.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37.2\u0026ndash;55.2\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRVGLS %\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-23.20\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-22.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.92\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-2.170\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.033\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-27 \u0026ndash; -21.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-25 \u0026ndash; -21.6\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRV FWLS %\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-25.47\u0026thinsp;\u0026plusmn;\u0026thinsp;1.20\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-24.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-2.354\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.021\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-30 \u0026ndash; -23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-27 \u0026ndash; -23\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"7\"\u003e*: Chi-square test; \u0026bull;: Independent t-test\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n\u003ch2\u003e* CTRCD vs non-CTRCD cases at 3-month follow-up echocardiography\u003c/h2\u003e\n\u003cp\u003eTable\u0026nbsp;(4) shows the difference regarding baseline echocardiography parameters between CTRCD cases and non-CTRCD cases. LV EF, LV GLS, and LV GCS were lower in CTRCD cases in a statistically significant value. LV GRS was also lower in CTRCD cases, but not statistically significant. RV S`, RV GLS \u0026amp; RV FWLS were lower with a statistical significance in CTRCD cases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(4)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eComparison between cases with and without CTRCD regarding ECHO parameters after 3 months\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tabd\" border=\"1\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eAfter 3 months\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWithout CTRCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWith CTRCD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTest value\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eP-value\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSig.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo. = 70\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNo. = 24\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLVEDD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e47.84\u0026thinsp;\u0026plusmn;\u0026thinsp;3.87\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50.88\u0026thinsp;\u0026plusmn;\u0026thinsp;4.50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-3.173\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40\u0026ndash;56\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43\u0026ndash;58\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLVESD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31.79\u0026thinsp;\u0026plusmn;\u0026thinsp;3.43\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37.42\u0026thinsp;\u0026plusmn;\u0026thinsp;4.36\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-6.464\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25\u0026ndash;39\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e29\u0026ndash;46\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eLA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36.53\u0026thinsp;\u0026plusmn;\u0026thinsp;3.45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2.87\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-1.664\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.099\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28\u0026ndash;45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32\u0026ndash;45\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eDiastolic degree\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNormal\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (15.7%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (4.2%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e2.140*\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003e0.143\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGrade I\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59 (84.3%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23 (95.8%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGrade II\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGrade III\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0.0%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eEF M mode\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e62.07\u0026thinsp;\u0026plusmn;\u0026thinsp;4.06\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52.50\u0026thinsp;\u0026plusmn;\u0026thinsp;5.65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e8.974\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55\u0026ndash;74\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35\u0026ndash;60\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eEF Simpson`s method\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59.13\u0026thinsp;\u0026plusmn;\u0026thinsp;2.53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49.54\u0026thinsp;\u0026plusmn;\u0026thinsp;5.63\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e11.356\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e54\u0026ndash;65\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35\u0026ndash;59\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRV S`\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e11.515\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9\u0026ndash;15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8\u0026ndash;11\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGLS %\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-17.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.88\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-13.54\u0026thinsp;\u0026plusmn;\u0026thinsp;1.91\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-9.539\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-22 \u0026ndash; -13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-19 \u0026ndash; -9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGCS %\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-24.37\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-21.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2.51\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-5.488\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-28 \u0026ndash; -21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-26 \u0026ndash; -15\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGRS %\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45.00\u0026thinsp;\u0026plusmn;\u0026thinsp;6.28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42.08\u0026thinsp;\u0026plusmn;\u0026thinsp;8.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e1.825\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.071\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32\u0026ndash;58\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26\u0026ndash;57\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRV GLS%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-22.14\u0026thinsp;\u0026plusmn;\u0026thinsp;2.92\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-15.38\u0026thinsp;\u0026plusmn;\u0026thinsp;2.57\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-10.101\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-26 \u0026ndash; -13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-24 \u0026ndash; -12\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eRV FWLS %\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-24.36\u0026thinsp;\u0026plusmn;\u0026thinsp;3.18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-17.13\u0026thinsp;\u0026plusmn;\u0026thinsp;2.42\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e-10.163\u0026bull;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e0.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eHS\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRange\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-28 \u0026ndash; -15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-26 \u0026ndash; -14\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"7\"\u003e*: Chi-square test; \u0026bull;: Independent t-test\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n\u003ch2\u003e* Changes in LV and RV echocardiographic parameters at T0, T1 and T2\u003c/h2\u003e\n\u003cp\u003eThe following figures show the temporal changes in LV and RV mechanics in both CTRCD and non-CTRCD cases.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e* Predicting a subsequent CTRCD development\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n\u003cp\u003eOn the univariate logistic regression analysis model, baseline LV GLS (\u0026lt;-18%), LV GCS (\u0026lt;-23.9%), RV GLS (\u0026lt;-22.6%), and RV FWLS (\u0026lt;-24%) were predictors of CTRCD occurrence as shown in table \u003cstrong\u003e(5)\u003c/strong\u003e. At the 3-month follow-up visit, LV GLS (\u0026lt;-15% with a relative reduction of 12.5% from the baseline) together with RV GLS (\u0026lt;-18%) and RV FWLS (\u0026lt;-19%) were predictors of later CTRCD development. A multivariate regression model showed that the relative reduction of LV GLS of 12.5% at 3 months from baseline was an independent predictor for the development of CTRCD as shown in Table\u0026nbsp;(5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(5)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUnivariate and multivariate logistic regression analysis for factors associated with CTCRD after 6 months\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tabe\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"3\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eUnivariate\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eMultivariate\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eP-value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eOdds ratio\u003c/p\u003e\n\u003cp\u003e(OR)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e95% C.I. for OR\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eP-value\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eOdds ratio\u003c/p\u003e\n\u003cp\u003e(OR)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e95% C.I. for OR\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLower\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eUpper\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLower\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eUpper\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDiabetes Mellitus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6.750\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.445\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e18.637\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTrastazumab\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.006\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4.241\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.500\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e11.989\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLVESD\u0026thinsp;\u0026gt;\u0026thinsp;33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.040\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.857\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.050\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7.772\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDiastolic function grade I\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.070\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6.815\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.853\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e54.461\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEF by M-mode\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;60\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.010\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.710\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.360\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10.123\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRV S` \u0026lt;=13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.073\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e4.098\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.878\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e19.123\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGLS % \u0026lt;= -18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e9.333\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.546\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e34.214\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGCS % \u0026lt;= -23.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.014\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.385\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.274\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8.995\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRVGLS % \u0026lt;= -22.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.018\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.172\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.214\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8.288\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRV FWLS % \u0026lt;= -24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.040\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e2.857\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.050\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7.772\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAfter 3 months\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLVESD\u0026thinsp;\u0026gt;\u0026thinsp;33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e10.217\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e3.128\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33.375\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEF M mode\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;58\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33.889\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e9.408\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e122.069\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEF Simpson`s method\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;55\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e82.500\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e18.904\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e360.046\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGLS % \u0026lt;= -15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e85.250\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e16.803\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e432.517\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRVGLS % \u0026lt;= -18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e178.250\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e21.115\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1504.785\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRV FWLS % \u0026lt;= -19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e207.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e24.136\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1775.303\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGLS change\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;12.5%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e207.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e24.136\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1775.303\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e198.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.046\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1701.117\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRVGLS change\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;21.74%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e198.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e23.046\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1701.117\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRVFWLS change\u0026thinsp;\u0026lt;\u0026thinsp;=\u0026thinsp;24%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e207.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e24.136\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1775.303\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026ndash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eBased on the Receiver Operating Characteristic (ROC) curve figure (8), low values of LV GLS, RV GLS, and RV FWLS at the baseline were predictors of CTRCD development with combining them together was the strongest baseline predictor (AUC\u0026thinsp;=\u0026thinsp;0.751, sensitivity\u0026thinsp;=\u0026thinsp;83.33%, specificity\u0026thinsp;=\u0026thinsp;60%) as shown in table (6).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(6) \u003c/strong\u003eROC curve for GLS%, RV-GLS% and RV-FWLS% at baseline to detect CTCRD\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tabf\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariables\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCut off point\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAUC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSensitivity\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSpecificity\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e+PV\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e-PV\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGLS % baseline\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;= -18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.740\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e87.50\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e57.14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e41.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e93.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRVGLS % baseline\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;= -22.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.654\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e54.17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e72.86\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e40.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e82.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRV FWLS % baseline\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;= -24\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.652\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e41.67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e80.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e41.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e80.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCombined\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.751\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e83.33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e60.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e41.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e91.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter 3 months combining LV GLS, RV GLS, and RV FWLS together was the strongest predictor of the development of CTRCD as shown in Figure (9) and Table\u0026nbsp;(7) (AUC\u0026thinsp;=\u0026thinsp;0.947, sensitivity\u0026thinsp;=\u0026thinsp;91.67%, specificity\u0026thinsp;=\u0026thinsp;90%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;(7) \u003c/strong\u003eROC curve for LV GLS, RV GLS, RV FWLS after 3 months to detect CTCRD\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"char\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tabg\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eVariables\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCut off point\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAUC\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSensitivity\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSpecificity\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e+PV\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e-PV\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGLS % after 3 m\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;= -15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.938\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e91.67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e88.57\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e73.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e96.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRV GLS% after 3 m\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;= -18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.915\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e95.83\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e88.57\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e74.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e98.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRV FWLS % after 3 m\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;= -19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.909\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e95.83\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e90.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e76.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e98.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCombined\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.947\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e91.67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e90.00\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e75.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e96.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eEarly detection of CTRCD is the main concern of the cardio-oncology team during chemotherapy to be able to start cardio-protective strategies as early as possible. The role of 2D speckle tracking echocardiography in early detection of CTRCD was previously tested in many studies. Alterations in strain parameters of 2D STE have been shown to precede a decrease in EF \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. In this present study, we assessed the deformation mechanics in both LV and RV throughout a 6-month chemotherapy regimen. First of all, in our study RV dysfunction was more common than LV dysfunction at the end of the follow-up period. RV dysfunction occurred in 37 patients representing 39.4% of the study population with almost half of them occurring as early as the first follow-up visit after 3 months (T1). On the contrary, LV dysfunction was less prevalent and more delayed occurring in 25.5% of the cases with 45% of them at (T1). These results were consistent with the results shown by \u003cb\u003eZhao et al., 2020\u003c/b\u003e in which the drop in RV function preceded LVEF decrease \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. The underlying suggested reason was the fact that the RV wall is thinner, having less reserve for compensation compared to the LV, and thus more prone to cardiotoxicity. This is also confirmed by other imaging modalities, as evidenced by a study from \u003cb\u003eYlanen et al., 2013\u003c/b\u003e which evaluated the late effects of Anthracycline-induced cardiotoxicity in childhood cancer survivors, using cardiac MRI. This study showed a 27% prevalence of abnormal RV function and only an 18% prevalence of abnormal LV function \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. On the other side one study from \u003cb\u003eKeramida et al., 2019\u003c/b\u003e showed that LV GLS was significantly reduced after 3 months of chemotherapy earlier than RV GLS \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. Although there was no postulated hypothesis justifying this earlier LV affection, it can be assumed to differences in the inclusion criteria of the study population in this study from our study. At \u003cb\u003eKeramida et al., 2019\u003c/b\u003e, 54.5% of the study population received previous radiotherapy treatment, unlike our study in which no patient received previous radiotherapy treatment. This controversy necessitates more studying of the change in RV mechanics during chemotherapy \u0026amp; comparing it to LV changes although the hypothesis of the thinner RV wall seems reasonable, but more evidence is still required.\u003c/p\u003e \u003cp\u003eRegarding the changes in LV strain parameters, our study showed that LV GLS is the most sensitive strain parameter to predict later CTRCD. At baseline, people with lower LV GLS values \u0026ndash;even may be still in the normal range- were associated with a higher risk for developing later CTRCD. In this study, a Baseline LV GLS value less than \u0026minus;\u0026thinsp;18% was associated with an increased possibility of CTRCD development than higher values (AUC\u0026thinsp;=\u0026thinsp;0.740, sensitivity\u0026thinsp;=\u0026thinsp;87.5%, specificity\u0026thinsp;=\u0026thinsp;57.14%). The suggested explanation was that cancer itself is considered as an inflammatory process releasing various reactive oxidative species and combined with neuro-hormonal changes. This has a significant effect on myocardium which is usually aggravated by chemotherapy \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAt the 3-month follow-up visit (T1), changes in LV GLS value were stronger predictors than LV GCS and GRS as evidenced by univariate and multivariate regression analysis models (using LV GLS cut-off value of -15% or a decrease from the baseline value by 12.5%). This result was consistent with the previous studies and with ASE/EACVI consensus guidelines which recommended measurement of GLS for follow-up of cancer patients receiving chemotherapy \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. The postulated hypothesis behind this is that cardiotoxicity results from regional deformational changes of the myocardium which also explains why LV strain changes precede LV EF changes because some segments are affected usually earlier than others which on the contrary plays a compensatory role and thus LV EF remains stable. The long-axis function of the left ventricle is governed by subendocardial, longitudinally-arranged myocardial fibers, which are more susceptible to early hypoxia and myocardial injury \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. That`s why in the case of early myocardial injury, longitudinal strain is usually affected first while circumferential strain may compensate for left ventricular function. With the progression of the disease, circumferential strain will be affected which might indicate transmural involvement \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this study, our primary endpoint was trying to detect the earliest strain parameter that precedes EF changes and thus can predict CTRCD later on. In our study and based on the ROC curve, combining LV GLS with RV GLS and RVFWLS was the best predictor of subsequent CTRCD. Although there is a paucity of data in the literature studying the role of RV strain parameters in predicting LV EF drop, our study results are consistent with the results of \u003cb\u003eArciniegas Calle et al\u003c/b\u003e published in 2018 \u003csup\u003e\u003cb\u003e(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/b\u003e\u003c/sup\u003e. At \u003cb\u003eArciniegas Calle et al., 2018\u003c/b\u003e, it was concluded that Combining both RV GLS at T1 and LV GLS was the strongest predictor of cardiotoxicity (area under the curve[AUC], 0.91; sensitivity, 100%; specificity, 73%; P\u0026thinsp;\u0026lt;\u0026thinsp;.001). LV GLS at T1 (AUC, 0.85; cutoff, \u0026minus; 14.06; sensitivity, 91%; specificity, 83%; P\u0026thinsp;=\u0026thinsp;.003) was also a strong indicator of subsequent cardiotoxicity. This can be explained because it is known that usually, longitudinal deformational changes are always the earliest to happen and thus measuring longitudinal RV strain would increase the ability to predict the future drop in EF because more muscle fibers are studied and the wall of the RV is even thinner than LV and thus it would be more affected.\u003c/p\u003e \u003cp\u003eWe aimed to highlight the importance of studying the changes in RV mechanics during the period of chemotherapy as combining some of these data with LV strain variables gives us the best chance to predict CTRCD and detect it as early as possible, so we can modify the chemotherapy regimen and start cardio-protective measures early and to detect patients based on their baseline data who are at risk of later development of CTRCD.\u003c/p\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eStudy Limitations\u003c/h2\u003e \u003cp\u003eOur study limitations were that it was a single-center study and the duration of follow-up was 6 months only. Also, we didn`t study whether these early cardiotoxic changes are reversible in a longer follow-up duration or not.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAnthracycline\u0026thinsp;\u0026plusmn;\u0026thinsp;Trastuzumab treatment leads to changes in LV \u0026amp; RV mechanics with more prevalent deterioration in RV values. The presence of lower LV \u0026amp; RV strain values at the base line together with reduction of these values after chemotherapy treatment can predict the later development of CTRCD. Combining LV GLS with RV GLS \u0026amp; FWLS values at (T1) is the strongest predictor of subsequent CTRCD.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;All patients were informed about the study and informed consent was obtained. This study was approved by Ain-shams University\u0026apos;s ethical committee \u0026amp; complied with the ethical guidelines of the 1975 declaration of Helsinki as revised in 2008.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding has been received for this study from any institution or committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe data of the studied patients are available with the authors upon request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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Circulation: Cardiovascular Imaging. 2012;5(5):596\u0026ndash;603.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\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. Eur Heart Journal\u0026ndash;Cardiovascular Imaging. 2014;15(10):1063\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilliams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). 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Curr Cardiol Rep. 2013;15:1\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArciniegas Calle MC, Sandhu NP, Xia H, Cha SS, Pellikka PA, Ye Z, et al. Two-dimensional speckle tracking echocardiography predicts early subclinical cardiotoxicity associated with anthracycline-trastuzumab chemotherapy in patients with breast cancer. BMC Cancer. 2018;18(1):1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cardio-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"caon","sideBox":"Learn more about [Cardio-Oncology](http://cardiooncologyjournal.biomedcentral.com)","snPcode":"40959","submissionUrl":"https://submission.nature.com/new-submission/40959/3","title":"Cardio-Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3484121/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3484121/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCancer and cardiovascular diseases are the main causes of mortality worldwide. Although the incidence of cancer is rising, modern comprehensive management including surgery, chemotherapy, and radiotherapy led to decreased mortality, but also different cardiovascular complications. Conventional EF measurement fails to detect subtle changes in LV function, so a more sensitive tool is needed.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe study included 101 asymptomatic female patients with newly diagnosed breast cancer who received anthracycline\u0026thinsp;\u0026plusmn;\u0026thinsp;trastuzumab-based chemotherapy regimen. A comprehensive echocardiographic examination was performed before receiving the chemotherapy (T0), at 3 months (T1), and at 6 months after (T2). All patients had pre-treatment normal LV EF. Cardiotoxicity was defined as a decrease in EF\u0026thinsp;\u0026gt;\u0026thinsp;10% from baseline value to EF\u0026thinsp;\u0026lt;\u0026thinsp;55% in asymptomatic patients or \u0026gt;\u0026thinsp;5% in symptomatic patients \u0026ldquo;according to the cardiac review and evaluation committee (CREC)\u0026rdquo;.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eCTRCD occurred in 24 patients (25.5%) while RV systolic dysfunction was more common occurring in 37 patients (39.4%). LV GLS at (T1) (cut-off value \u0026lt;-15% with relative 12.5% reduction from the baseline value) was a strong predictor of CTRCD, but combining LV GLS with RV GLS \u0026amp; RV FWLS was the strongest (AUC\u0026thinsp;=\u0026thinsp;0.947, sensitivity\u0026thinsp;=\u0026thinsp;91.67%, specificity\u0026thinsp;=\u0026thinsp;90%).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eChemotherapy induces biventricular changes with more prevalent deterioration in RV values. Low LV \u0026amp; RV strain values at baseline together with reduction of these values after chemotherapy treatment can predict later CTRCD development. Combining LV GLS with RV GLS \u0026amp; FWLS values at (T1) is the strongest predictor of subsequent CTRCD.\u003c/p\u003e","manuscriptTitle":"Two-dimensional Speckle Tracking Echocardiography in Chemotherapy-Induced Cardiotoxicity in Females with Breast Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-10-29 02:12:40","doi":"10.21203/rs.3.rs-3484121/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-01-05T14:08:34+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-12-26T15:22:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"256a7f23-472e-4470-ac64-fc7db5c0f8a8","date":"2023-12-16T08:11:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-11-13T15:46:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-10-26T16:04:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-10-26T03:41:55+00:00","index":"","fulltext":""},{"type":"submitted","content":"Cardio-Oncology","date":"2023-10-24T03:25:09+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"cardio-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"caon","sideBox":"Learn more about [Cardio-Oncology](http://cardiooncologyjournal.biomedcentral.com)","snPcode":"40959","submissionUrl":"https://submission.nature.com/new-submission/40959/3","title":"Cardio-Oncology","twitterHandle":"@OncoBioMed","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"67eae933-660e-4b58-a06c-b6edeff1e74d","owner":[],"postedDate":"October 29th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-03-04T15:09:19+00:00","versionOfRecord":{"articleIdentity":"rs-3484121","link":"https://doi.org/10.1186/s40959-024-00209-1","journal":{"identity":"cardio-oncology","isVorOnly":false,"title":"Cardio-Oncology"},"publishedOn":"2024-03-01 15:02:00","publishedOnDateReadable":"March 1st, 2024"},"versionCreatedAt":"2023-10-29 02:12:40","video":"","vorDoi":"10.1186/s40959-024-00209-1","vorDoiUrl":"https://doi.org/10.1186/s40959-024-00209-1","workflowStages":[]},"version":"v1","identity":"rs-3484121","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3484121","identity":"rs-3484121","version":["v1"]},"buildId":"wLkW0s4AflPzk-lpfg-fK","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}