Cardiac Monitoring and Incidence of Cardiotoxicity Cardiomyopathy Among Breast Cancer Patients Undergoing Anthracycline Regimen Chemotherapy: Insight From a Single Centre Study

Cardiac Monitoring and Incidence of Cardiotoxicity Cardiomyopathy Among Breast Cancer Patients Undergoing Anthracycline Regimen Chemotherapy: Insight From a Single Centre Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cardiac Monitoring and Incidence of Cardiotoxicity Cardiomyopathy Among Breast Cancer Patients Undergoing Anthracycline Regimen Chemotherapy: Insight From a Single Centre Study Astri Astuti, Adila Aafiyah, Aurora Adila Arderia, Melawati Hasan, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9465827/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 16 You are reading this latest preprint version Abstract Background Anthracyclines remain a cornerstone of breast cancer therapy but carry a significant risk of cancer therapy-related cardiac dysfunction (CTRCD). This study evaluates the incidence of CTRCD in an Indonesian setting using the latest 2022 ESC Cardio-Oncology guidelines, focusing on subclinical markers such as hs-Troponin I, Global Longitudinal Strain (GLS) and Mechanical Dispersion (MD). Methods This retrospective analytical study involved 98 breast cancer patients treated with anthracyclines at a top-tier referral hospital in Indonesia from July 2018 to February 2020. Clinical assessments, hs-Troponin I, and echocardiography (LVEF, GLS, and MD) were performed at baseline, 1, 3, and 6 months. CTRCD was defined per the 2022 ESC criteria. Results CTRCD occurred in 74.5% of patients, predominantly as asymptomatic mild cases (63.26%). While symptomatic CTRCD was relatively low (7.14%), asymptomatic dysfunction was detected as early as one month post-chemotherapy. A significant progressive decline was observed in LVEF (68.2 ± 6.2% to 61.3 ± 8.8%, p < 0.001) and GLS (-19.7 ± 2.9% to -17.1 ± 3.5%, p < 0.001). Notably, mechanical dispersion significantly increased over time (p = 0.029), and median hs-Troponin I surged from 1.6 ng/L to 82.2 ng/L (p < 0.001) by month 6. Conclusion The high incidence of asymptomatic CTRCD underscores the inadequacy of relying on clinical symptoms alone. Integration of hs-troponin, GLS, and mechanical dispersion monitoring is essential for early detection, enabling timely cardioprotective intervention. Anthracycline Breast Cancer Cardiotoxicity Chemotherapy Figures Figure 1 Figure 2 Figure 3 Introduction Breast cancer is one of the most common types of cancer in the world. In 2020, approximately 2.3 million women were diagnosed with breast cancer, and the mortality rate was 635000 [ 1 ]. In Indonesia, breast cancer is the type of cancer with the highest number of patients and one of the leading causes of death. According to data from Global Cancer Statistics in 2020, the number of new cases of breast cancer in Indonesia reached 68,858, or 16.6% of the total 396,914 new cases, and the number of deaths reached more than 22,000 [ 2 ]. Chemotherapy is an important breakthrough in the treatment of cancer, but it is also associated with major adverse effects, especially cardiotoxicity [ 3 ]. The incidence rate of cancer therapeutic-related cardiac dysfunction (CTRCD) during or shortly after the completion of cancer therapy ranges from 9–26% after treatment with doxorubicin, 13–17% with trastuzumab, and 27–34% with combination therapy [ 4 ]. Anthracyclines are among the most commonly used chemotherapeutic drugs and have shown efficacy against several kinds of malignancies, particularly lymphoma and breast cancer. On the other hand, anthracyclines may cause progressive and irreversible cardiac damage[ 5 , 6 ]. Cardiotoxicity due to anthracycline begins with damage to myocardial cells, followed by a decrease in left ventricular function, which ultimately, if not treated, can cause heart failure [ 6 ]. Cardiotoxicity can be detected early and avoided by monitoring disease progression, including declines in left ventricular function, or by identifying subclinical myocardial injury through biomarker assessment, such as troponin measurement [ 7 – 9 ]. The recovery rate of cancer patients who are increasing in life expectancy afterwards also needs to be considered, and a focus on cardiac health has to be our priority. On the other hand, there is still much uncertainty in assessing cardiovascular risk in patients undergoing chemotherapy, especially in detecting subclinical changes [ 3 ]. There are several different definitions of cardiotoxicity, making it difficult to compare results across trials to determine the true incidence of various types of cardiovascular cardiotoxicity and CTRCD. Therefore, we aimed to assess the incidence of CTRCD in Indonesia, especially West Java, on the basis of the latest consensus definition of cardiovascular toxicity adopted in the 2022 European Society of Cardiology (ESC) cardio-oncology guidelines [ 10 ]. Methods This study was a retrospective descriptive study involving medical records of 98 breast cancer patients receiving chemotherapy with an anthracycline regimen at Dr. Hasan Sadikin General Hospital Bandung. This research was conducted after ethical approval was obtained from the Research Ethics Committee (number 204/UN6). KEP/EC/2024 and research permission from the Director of Human Resources, Education and Research at Dr. Hasan Sadikin General Hospital Bandung with number DP.04.03/D.XIV.4.4/599/2024. The inclusion criteria of this study included all breast cancer patients over the age of 18 years who were indicated to receive anthracycline regimens by an oncologist at Dr. Hasan Sadikin General Hospital Bandung from July 2018 to February 2020. The data that were assessed included clinical assessment and biomarker and echocardiography examination results at baseline and at 1, 3, and 6 months after the initiation of chemotherapy. The exclusion criterion in this study was patients with breast cancer whose medical records were illegible. The definition of CTRCD was using the ESC Cardio-oncology guideline 2022. Symptomatic CTRCD was defined as the presence of cardiac dysfunction with symptoms of heart failure resulting from cancer treatment and was grouped into very severe (heart failure requiring inotropic support, mechanical circulatory support, or consideration of transplantation), severe (heart failure hospitalization), moderate (requiring intensification of diuretic therapy and outpatient heart failure) and mild (mild symptoms of heart failure, no need for intensification of therapy). Asymptomatic CTRCD was defined as the absence of symptoms of heart failure resulting from cancer treatment. Asymptomatic CTRCD was grouped into severe (new decrease in Left ventricular Ejection Fraction (LVEF) to < 40%), moderate (new LVEF reduction by ≥ 10 percentage points to an LVEF of 40–49% or new LVEF reduction by 15% or a new increase in cardiac biomarkers) and mild (LVEF ≥ 50% and a decrease in GLS by > 15% from baseline and/or new increases in cardiac biomarkers) [ 11 ]. High-sensitivity troponin I (hs-cTnI) was evaluated via the Vidas BioMérieux assay, which combines a one-step sandwich enzyme immunoassay with fluorescence detection (ELFA). The global 99th percentile URL for high-sensitivity troponin I is 19 ng/L on the platforms used in this study. The data that were obtained were processed via Microsoft Excel and IBM SPSS Statistics version 27 applications. The data analysis began by performing the Kolmogorov‒Smirnov and Shapiro‒Wilk normality tests to determine whether the data that were collected were normally distributed. Then, the data are presented as a frequency distribution or cross-tabulation. If the data are normally distributed, the variables are presented using the mean value (𝑥̅) and standard deviation (σ). Moreover, for data that are not normally distributed, variables are presented using median (Me) values ​​as well as minimum (Min) and maximum (Max) values. Results Ninety-eight breast cancer patients underwent chemotherapy with an anthracycline regimen at Dr. Hasan Sadikin General Hospital, Bandung, who fulfilled the inclusion criteria. The average age of the patients was 47 ± 8 years, with no difference in asymptomatic and symptomatic CTRCD. Most of the patients (62.2%) were under 50 years old. The mean dose of anthracycline was 570 mg/m 2 of body surface area, with no significant difference between the groups (p = 0.298). A total of 73 patients developed CTRCD (74.48%), 7 (7.14%) of whom were symptomatic, and the rest were asymptomatic. A total of 41.8% of patients were classified as obese, and 30.6% were overweight based on body mass index (BMI) category. There was no significant variation in the distribution of BMI categories between the groups (p = 0.978). Among all patients, 20.4% had hypertension, with a greater prevalence in the asymptomatic CTRCD group (22.7%) than in the other groups; this difference was not statistically significant (p = 0.712). There was also no significant difference in diabetes mellitus between the groups (p = 0.161), with a higher rate of diabetes mellitus in patients with asymptomatic CTRCD (10.6%) than in those with normal and symptomatic CTRCD. Among all patients, 2% received mediastinal radiotherapy, with a greater proportion in the symptomatic CTRCD group (14.3%) than in the other groups. Table 1 Baseline characteristics of breast cancer patients receiving chemotherapy Characteristic Total (n = 98) Normal (n = 25) Asymptomatic CTRCD (n = 66) Symptomatic CTRCD (n = 7) p value Age (years) 47 ± 8 49 ± 9 47 ± 7 46 ± 9 0.533 Age Category (n, %) 0.855 < 50 61 (62.2) 15 (60.0) 42 (63.6) 4 (57.1) 0.911 ≥ 50 37 (37.8) 10 (40.0) 24 (36.4) 3 (42.9) BMI (kg/m 2 ) 25.6 ± 4.1 25.7 ± 4.8 25.6 ± 3.9 25.8 ± 4.4 0.974 BMI Category (n, %) 0.978 Underweight 2 (2.0) 1 (4.0) 1 (1.5) 0 (0.0) 0.880 Normal 26 (26.6) 6 (24.0) 18 (27.3) 2 (28.6) Overweight 30 (30.6) 10 (40.0) 18 (27.3) 2 (28.6) Obesity 40 (41.8) 8 (32.0) 29 (43.9) 3 (42.9) Risk Factor (n, %) Hypertension 20 (20.4) 4 (16.0) 15 (22.7) 1 (14.3) 0.712 Diabetes Mellitus 7 (7.1) 0 (0.0) 7 (10.6) 0 (0.0) 0.161 Concomitant Diseases 1 (1.1) 0 (0.0) 1 (1.5) 0 (0.0) 0.783 History of Mediastinal Radiotherapy 2 (2.0) 0 (0.0) 1 (1.5) 1 (14.3) 0.053 Anthracycline Cumulative Dose (mg/m 2 ), n = 51 570 ± 60 599 ± 100 570 ± 52 540 ± 76 0.298 *Categorical data are presented as counts, and percentages were analyzed via the chi-square test. Continuous data are presented as the means ± SDs and were analyzed via one-way ANOVA. The mean LVEF values are shown in Table 2 was similar across all groups, with a mean LVEF of 68.2%, with minor variations between groups (67.2% in the normal group, 68.4% in the asymptomatic CTRCD group, and 69.5% in the symptomatic CTRCD group). There were no significant differences between the groups (p = 0.709). The global longitudinal strain (GLS) values ranged from − 18.4 ± 2.5% to -20.2 ± 2.9%, indicating decreased longitudinal function in the asymptomatic CTRCD group. However, this difference did not reach statistical significance (p = 0.051). The other echocardiography parameters shown in Table 2 were not significantly different between the groups. The median troponin level was normal at 1.6 (1.4–6.5) ng/L, with no difference between the groups (p = 0.345). However, there was a significant difference in myocardial contraction (p = 0.016). Overall, these results indicate no significant differences in most baseline echocardiographic characteristics or troponin levels among the groups. In addition, there was decreased myocardial contraction in the asymptomatic group. Table 2 Baseline Echocardiographic Characteristics and Troponin Levels of Breast Cancer Patients Undergoing Chemotherapy Variable Total (n = 98) Normal (n = 25) Asymptomatic CTRCD (n = 66) Symptomatic CTRCD (n = 7) p value LVEF 68.2 ± 6.2 67.2 ± 6.2 68.4 ± 6.1 69.5 ± 9.3 0.709 GLS -19.7 ± 2.9 -18.4 ± 2.5 -20.2 ± 2.9 -18.5 ± 1.7 0.051 LVEDV 83.7 ± 22.8 82.3 ± 23.6 84.3 ± 23.3 81.5 ± 14.5 0.929 LVESV 24.0 (20.0–32.0) 25.0 (20.3–32.8) 24.0 (19.0–32.0) 20.5 (18.5–25.5) 0.540 LVSV 57.0 ± 15.6 54.9 ± 18.8 57.6 ± 14.8 57.3 ± 14.8 0.801 TAPSE 21.3 (20.0–23.3) 21.3 (19.2–23.3) 21.1 (20.0–23.3) 22.5 (21.0–23.3) 0.706 E/A 1.09 ± 0.38 1.03 ± 0.39 1.13 ± 0.38 0.87 ± 0.15 0.279 E/e’ 8.65 ± 2.25 8.96 ± 2.32 8.53 ± 2.26 9.24 ± 2.04 0.702 Myocardial Contraction 398.8 ± 39.5 420.1 ± 43.2 391.0 ± 36.4 417.5 ± 33.1 0.016* Mechanical Dispersion 43.2 (36.5–48.0) 43.0 (34.4–56.6) 42.6 (36.3–46.7) 52.8 (46.6–54.9) 0.085 Hs Troponin I 1.6 (1.4–6.5) 1.4 (1.4–4.8) 2.7 (1.4–7.2) 1.8 (1.4–3.5) 0.345 LVEF: Left Ventricular Ejection Fraction, GLS: Global Longitudinal Strain, LVEDV: Left Ventricular End-Diastolic Volume, LVESV: Left Ventricular End-Systolic Volume, LVSV: Left Ventricular Stroke Volume, TAPSE: Tricuspid Annular Plane Systolic Excursion *Continuous data with a normal distribution are presented as the means ± SDs and were analyzed via one-way ANOVA. Continuous data without a normal distribution are presented as medians and interquartile ranges and were analyzed via the Kruskal‒Wallis test. At 6 months of follow-up, a significant decrease was observed in LVEF among all patients who underwent chemotherapy, from 68.2% at baseline to 61.3% (p < 0.001), and in GLS values, from − 19.7 at baseline to − 17.1 at the 6th month ( p < 0.001). The decrease became significant at the third month of follow-up compared with baseline, and it was even more pronounced at month 6. This finding indicates a progressive decline during therapy, especially after 3 months of follow-up. The left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) increased significantly after the baseline measurement and remained elevated throughout the 6-month follow-up, with a significant increase starting from the third month of follow-up (LVEDV: 83.7–90.0 mL; LVESV: 24.0–31.0 mL, p < 0.001). However, there were no significant differences between month-1, month-3, and month-6. This may indicate progressive cardiac remodelling along with a reduction in systolic function during chemotherapy. In terms of the echocardiography parameters, the E/e’ ratio significantly increased at the 6th month of follow-up (p = 0.020), indicating an increase in left ventricular diastolic filling pressure. Moreover, the E/A ratio did not significantly change (p = 0.345). There was a significant increase in myocardial contraction from the first month of follow-up to month 6 (p = 0.017). Similarly, the mechanical dispersion value significantly increased over time (p = 0.029). Overall, these findings demonstrate that chemotherapy is associated with a progressive decline in systolic function, accompanied by structural remodelling, altered diastolic filling pressures, and increased mechanical dispersion, which may contribute to subclinical cardiotoxicity within six months. Table 3 Echocardiographic characteristics of breast cancer patients receiving chemotherapy Variable Baseline Month-1 Month-3 Month-6 p value LVEF 68.2 ± 6.2 66.3 ± 6.6 64.5 ± 6.7 61.3 ± 8.8 < 0.001* GLS -19.7 ± 2.9 -19.2 ± 2.7 -18.6 ± 2.3 -17.1 ± 3.5 < 0.001* LVEDV 83.7 ± 22.8 86.2 ± 21.8 90.0 ± 21.9 94.4 ± 21.2 < 0.001* LVESV 24.0 (20.0–32.0) 27.0 (20.8–32.3) 31.0 (25.0–38.0) 34.0 (27.0–44.0) < 0.001* LVSV 57.0 ± 15.6 58.4 ± 16.4 58.0 ± 16.3 56.9 ± 12.5 0.759 TAPSE 21.3 (20.0–23.3) 21.3 (19.1–23.8) 21.1 (19.0–23.0) 21.0 (20.0–22.2) 0.729 E/A 1.09 ± 0.38 1.11 ± 0.61 1.07 ± 0.38 1.15 ± 0.49 0.345 E/e’ 8.65 ± 2.25 8.24 ± 2.44 8.47 ± 2.39 9.49 ± 3.49 0.020* Myocardial Contraction 398.8 ± 39.5 399.5 ± 36.2 400.5 ± 34.5 413.5 ± 38.9 0.017* Mechanical Dispersion 43.2 (36.5–48.0) 42.3 (36.3–47.7) 43.6 (38.9–50.4) 46.3 (41.7–51.7) 0.029* LVEF: Left Ventricular Ejection Fraction, GLS: Global Longitudinal Strain, LVEDV: Left Ventricular End-Diastolic Volume, LVESV: Left Ventricular End-Systolic Volume, LVSV: Left Ventricular Stroke Volume, TAPSE: Tricuspid Annular Plane Systolic Excursion Troponin levels increased significantly and progressively, from a median of 1.6 ng/L at baseline to 82.2 ng/L at six months of follow-up (p < 0.001). By the third month, the median score was already above the 99th percentile, suggesting that a significant proportion of patients experienced cardiac injury or stress after chemotherapy. During the follow-up, 62 patients (63%) had hs-cTnI values > 19 ng/L. Table 4 Troponin levels in patients with breast cancer receiving chemotherapy Variabel Baseline Month-1 Month-3 Month-6 p value hs Troponin I 1.6 (1.4–6.5) 4.6 (1.6–11.2) 29.7 (20.0-60.9) 82.2 (38.5-151.2) < 0.001* Table 5 Number of CTRCD cases among breast cancer patients receiving chemotherapy Characteristics Baseline Month-1 Month-3 Month-6 n % n % n % n % All CTRCD 0 0% 7/98 7.1% 33/91 36.3% 33/58 56.9% Mild asymptomatic 0 0% 7/98 7.1% 30/91 32.9% 25/58 43.1% Moderate asymptomatic 0 0% 0 0.00% 0 0.00% 2/58 3.4% Severe asymptomatic 0 0.00% 0 0.00% 0 0.00% 2/58 3.44% Mild symptomatic 0 0.00% 0 0.00% 3/91 3.29% 4/58 6.89% CTRCD: Cancer Therapy-Related Cardiac Dysfunction As shown in Table 5 , 7 cases of CTRCD were found in the first month of the 6-month follow-up period (7.14% of all patients), all of which were mildly asymptomatic. This number increased significantly to 33 out of 91 undermonitored patients (36.26%) at the third month, with 30 patients categorized as mildly asymptomatic (32.97%) and 3 patients categorised as mildly symptomatic (3.30%). Among the 7 mild symptomatic patients, 1 high-risk patient had cardiotoxicity due to a history of radiotherapy in the mediastinum and obesity, and 1 moderate-risk patient had a history of hypertension and obesity based on the HFA-ICOS (Heart Failure Association – International Cardio-Oncology Society) score. Four symptomatic patients were initially diagnosed as asymptomatic CTRCD at month 3. The number of cases continued to increase until the sixth month, when more than half of the undermonitor patients (33 out of 58 patients; 56.9%) experienced CTRCD. Four patients (6.9%) experienced mild symptomatic CTRCD, 25 patients (43.1%) experienced mild asymptomatic CTRCD, 2 patients experienced moderate asymptomatic CTRCD (3.4%), and 2 patients experienced severe asymptomatic CTRCD (3.4%). Although there was an increase in the number of symptomatic CTRCD patients, its incidence remains lower than that of asymptomatic CTRCD patients, indicating that most patients are asymptomatic. Table 6 Incidence Rate of Cardiotoxicity Cardiomyopathy in Breast Cancer Patients Undergoing Chemotherapy Outcome Total Event Time at Risk Rate (95% CI) Rate in 100 person-month All CTRD 98 73 454 0.161 (0.128–0.202) 16.1 (12.8–20.2) Symptomatic CTRCD 98 7 454 0.015 (0.007–0.032) 1.5 (0.7–3.2) Asymptomatic CTRCD 98 66 454 0.145 (0.114–0.185) 14.5 (11.4–18.5) With respect to the incidence rate of CTRCD in breast cancer patients who underwent chemotherapy, among 98 patients, 73 (74.48%) experienced CTRCD during chemotherapy, with a cumulative risk time of 6 months. Sixty-six patients were asymptomatic, and 7 patients had symptomatic CTRCD. The incidence rate of CTRCD is 0.16 per person-month (95% CI: 0.128–0.202), equivalent to 16.1 events per 100 person-months (95% CI: 3.1–6.7), with a total monitoring time of 454 person-months. The incidence of symptomatic CTRCD is relatively low; there were 7 cases with an incidence rate of 0.015 per person-month (95% CI: 0.007–0.032) or 1.5 cases per 100 person-months. However, the incidence of asymptomatic CTRCD is quite high, with 66 cases and an incidence rate of 0.145 per person-month (95% CI: 0.114–0.185), or 14.5 cases per 100 person-months. Figure 3 shows that the incidence of CTRCD increased significantly during therapy, peaking at month 3. Most cases are mild and asymptomatic, whereas severe or symptomatic cases are less common. Discussion This study revealed that the incidence rate of CTRCD in breast cancer patients who underwent chemotherapy was 73 out of 98 patients (74.5%) during chemotherapy, with a cumulative risk time of 6 months. Sixty-six (67.34%) patients were asymptomatic, most of whom were classified as mildly asymptomatic (62 of 98 [63.26%]), and 7 (7.14%) patients had symptomatic CTRCD. The incidence rate of CTRCD is 0.161 per person-month (95% CI: 0.128–0.202), which is equivalent to 16.1 events per 100 person-months. The results of the present study are consistent with previous findings reported by Oristrell et al. that, over an average follow-up of 13.6 months, no cases of symptomatic CTRCD were observed. However, asymptomatic CTRCD occurred in 60% of patients, with 53 (55.8%) classified as mild, 3 (3.2%) as moderate, and 1 (1.1%) as severe [ 11 ] Similarly, Mecinaj et al. reported that most CTRCD cases were mildly asymptomatic (58 of 118 [49.2%]), with the highest incidence observed after anthracycline therapy, when 55 of 115 patients (47.8%) were identified with mild asymptomatic CTRCD [ 12 ]. The CARDIOTOX registry defines cardiotoxicity as the presence of new or worsening myocardial damage/dysfunction and classifies it as mild (abnormal biomarkers and/or LV dysfunction (LVD) with an LV ejection fraction (LVEF) ≥ 50%), moderate (LVD with LVEF 40–49%), or severe (LVD with LVEF < 40% or symptomatic heart failure). Cardiotoxicity was identified in 37.5% of patients during follow-up [95% confidence interval (CI) 34.22–40.8%]: 31.6% with mild, 2.8% with moderate, and 3.1% with severe myocardial damage/dysfunction [ 13 ]. This research revealed that the incidence of CTRCD was 7.14% in the first month of therapy. In a previous study by Astuti et al., there was subclinical left ventricular dysfunction after the first chemotherapy cycle, which indicates a possible incidence of mild CTRCD [ 14 ]. A previous study by Mecinaj et al. revealed that out of 115 patients, only 1 (0.9%) experienced CTRCD after the first cycle of anthracycline (approximately 21 days), and the CTRCD was mild when sex-specific cardiac troponin T 99th percentile (9.0 ng/L) was used. There was a significant increase in the CTRCD incidence to 56.89% in the sixth month of chemotherapy. The results of our study are inconsistent with those of several other previous studies, which reported a cardiotoxicity incidence of 16.5%, mostly occurring after 1 year of follow-up. This is because the different definitions of cardiotoxicity used in the study (new-onset heart failure, according to the Framingham criteria; reduction in LVEF ≥ 10 percentage points from baseline to LVEF less than 55%; sustained ventricular arrhythmias; or sudden cardiac death) may explain the differences in incidence [ 15 ]. Moreover, other studies have reported that the incidence rate of CTRCD during or shortly after the completion of cancer therapy ranges from 9 to 26% after treatment with doxorubicin [ 4 ] The incidence of asymptomatic CTRCD is relatively high. Asymptomatic cases were found earlier than symptomatic cases, in which mild cases can be found earlier in the first month after chemotherapy, and the number of symptomatic cases increased in the following month. This finding is in line with research conducted by Daniela et al., who reported that most cardiotoxicity patients in their research population did not present any clinical symptoms but already presented a decrease in LVEF, which was detected via scheduled echocardiography assessment [ 6 ]. In this study, the incidence rate of each CTRCD category increased over time, with the highest rate occurring in the third month after chemotherapy. Moreover, other research by Narayan et al. was conducted on 277 breast cancer patients, where the median time for a significant decrease in LVEF was seven months after chemotherapy [ 16 ]. In our study, some of the asymptomatic patients developed heart failure symptoms. Anthracycline causes cardiotoxicity primarily through free radical formation during mitochondrial metabolism. The reduction of doxorubicin by NADH dehydrogenase results in the formation of semiquinone radicals, which react with molecular oxygen to produce superoxide radicals. The hydroxyl radical and hydrogen peroxide are then produced as a result of redox cycling. Furthermore, the formation of doxorubicin-iron complexes may catalyze the Fenton reaction (Fe-catalyzed conversion of hydrogen peroxide to hydroxyl radicals), resulting in the generation of reactive oxygen species (ROS). Owing to their high mitochondrial content and reliance on oxidative metabolism, cardiomyocytes are more vulnerable to this oxidative stress than are tumor cells, which are more glycolytic. ROS accumulation leads to apoptotic cell death, and doxorubicin disrupts mitochondrial function by binding to cardiolipin, a phospholipid in the inner mitochondrial membrane, facilitating cytochrome c release, which increases apoptosis. Myocardial cell damage can cause a decrease in left ventricular function, which, if not treated, can cause heart failure [ 17 ]. Heart failure itself may be preceded by asymptomatic subclinical left ventricular dysfunction, such as a decrease in GLS, or an increase in cardiac biomarkers that is characterized by early onset with a slow and progressive deterioration that may continue several times after the end of chemotherapy, before LVEF reduction [ 6 ]. Most of the subjects were < 50 years old, and CTRCD cases also occurred more frequently in those aged < 50 years. These results are in line with other research conducted by Lu et al., who reported that the incidence of cardiotoxicity within three years after the administration of anthracyclines is greater in women aged ≤ 50 years than in women aged > 50 years [ 18 ]. Previous research revealed that the incidence of cardiotoxicity due to anthracyclines is associated with increasing age [ 19 ]. Most studies have shown that patients with advanced age (≥ 65 years) are at greater risk of cardiotoxicity than younger patients due to the age-related loss of cardiomyocytes. This subsequently leads to a decrease in myocardial volume, which is correlated with increased cardiovascular events. It has also been shown that the pharmacokinetics of anthracyclines change during aging, resulting in significantly increased doxorubicin concentrations, which is particularly evident in the heart. Furthermore, doxorubicin induces cellular senescence and telomere dysfunction, leading to increased proinflammatory cytokine expression. Telomere dysfunction results in the activation of the tumor suppressor gene p 53, which represses PGC-1α and PGC-1β transcription, thereby inhibiting downstream protein targets and impairing mitochondrial biogenesis. This results in mitochondrial dysfunction, increased ROS, reduced ATP production, and enhanced senescence [ 10 , 19 – 22 ]. However, this was not observed in this study because the number of elderly people was too small. The body mass index revealed that the majority of asymptomatic CTRCDs were obese (50%), and the other 5.56% were overweight. Among symptomatic patients, 40% were obese. These findings are supported by the statement that a BMI ≥ 25 (overweight) is considered a cardiotoxicity risk factor, and a BMI ≥ 27 (obesity) has been correlated with an increased incidence of cardiac dysfunction in patients receiving anthracycline-based chemotherapy compared with those with a BMI < 27 [ 20 ]. Another study by Kaboré et al. revealed that, compared with patients with a BMI ≥ 25, those with a BMI ≥ 25 were independently associated with higher rates of cardiotoxicity [ 23 ]. The epidemiological association between obesity and heart failure was explained by Kenchaiah et al., who reported that every 1 kg/m2 increase in BMI was associated with an 11% increase in the risk of heart failure [ 24 ]. The incidence of hypertension in the asymptomatic group (22.7%) was greater than that in the symptomatic (14.3%) and normal groups (16.0%). Similarly, a history of diabetes mellitus was more common in the asymptomatic group (10.6%) than in the normal group (0%). These results are in line with previous studies that have shown that there may be a decrease in LVEF in diabetic patients who undergo anthracycline or trastuzumab therapy, which might not be accompanied by clinical symptoms and can be detected only through subclinical examinations, such as echocardiograms [ 25 ]. Oxidative stress in diabetic patients can lead to gradual heart damage, which may not be severe enough to cause clinical symptoms in the early stages. This can also be influenced by decreased cardiovascular sensitivity in diabetic patients, which is related to endothelial dysfunction, myocardial energy metabolism disorders, and decreased sensory perception due to autonomic nerve dysfunction [ 26 , 27 ]. Other previous studies also reported that certain preexisting comorbidities, including hypertension and diabetes mellitus, can increase the risk for cardiotoxicity in cancer patients undergoing chemotherapy [ 10 , 19 – 21 ]. The percentage of patients with a history of mediastinal radiotherapy was greater in the symptomatic group (14.3%) than in the normal group (2%). A history of mediastinal radiation is a risk factor for cardiotoxicity. Mediastinal radiation can cause inflammation and fibrosis, leading to progressive diastolic dysfunction and restrictive hemodynamics, thereby affecting disease progression and recovery from cardiotoxicity. [ 6 ] Several previous studies have shown a relationship between the cumulative dose of anthracyclines and the incidence rate of cardiotoxicity among breast cancer patients, indicating that higher cumulative doses are associated with an increased risk of cardiotoxicity [ 20 , 28 ]. The highest incidence of cardiotoxicity was observed in the third month, at an average cumulative dose of 260 mg/m². This finding is consistent with the ESC cardio-oncology guidelines, which indicate that a cumulative dose of ≥ 250 mg/m² is associated with an increased risk of CTRCD [ 10 ]. Echocardiography is still the first-line diagnostic tool for the clinical evaluation of cardiac function in patients undergoing chemotherapy, and the LVEF is the most commonly used evaluation index [ 3 ]. Compared to baseline, the average LVEF value is lower in the first months after chemotherapy. A reduction in LVEF provides an early warning for detecting cardiotoxicity, even without heart failure symptoms. Our study revealed a significant decrease in LVEF over 6 months of chemotherapy, with a baseline LVEF of 68.2 ± 6.2, which decreased to 61.3 ± 8.8 by the 6th month (p value < 0.001). Up to 10% of cancer patients who are treated with anthracyclines will develop LVEF reduction after the completion of chemotherapy [ 29 ]. Similar to our study, a study by Avila et al. revealed that 27 (14%) out of 192 patients had a decrease in LVEF of at least 10% at 6 months after the initiation of chemotherapy [ 15 , 30 ] A decrease in the GLS value was also observed, even within the first month after chemotherapy. There was a significant decrease in GLS values over 6 months, with a baseline GLS value of -19.7 ± 2.9, which decreased to -17.1 ± 3.5 at the 6th month (p value < 0.001). This finding is consistent with another prospective cohort study by Astuti et al., who reported a GLS reduction in breast cancer patients three weeks after receiving the first cycle of fluorouracil, adriamycin, and cyclophosphamide chemotherapy. The GLS was reduced from − 20.7 ± 2.4% at baseline to -19.1 ± 2.8%, with an average reduction of -1.63 ± 2.83% (P < 0.05) [ 14 ]. Similarly, in a study of breast cancer patients receiving treatment with anthracyclines, with or without adjuvant trastuzumab. A reduction in GLS was noted during follow-up, indicating impaired cardiac deformation (GLS ≥ 18%) [ 31 ]. Another study revealed that 22% of patients had subclinical LV dysfunction according to GLS, but no cardiotoxicity was measured by LVEF. This finding shows that GLS is a better way to detect subclinical LV systolic dysfunction immediately after anthracycline therapy [ 32 ]. This finding is also in line with previous research conducted by Gripp et al., which confirmed that the GLS assessment is a very good predictor of cardiotoxicity, which also shows that changes in the GLS value could be detected earlier than changes in the LVEF value [ 33 ]. Several previous studies also reported that a change in GLS on echocardiography has greater potential as a better predictor of cardiotoxicity than does LVEF [ 34 ]. GLS measurements are better because of their ability to measure the longitudinal function of the entire ventricle than the basal segment alone. Clinical studies in breast cancer patients have shown that the specificity of GLS for assessing cardiac toxicity reaches 93%, and the negative predictive value is 91% [ 35 ] The mechanical dispersion increased from the first month to the sixth month. GLS and E/e′ are significantly related to mechanical dispersion. Mechanical dispersion itself has been proven and recommended for detecting arrhythmias and sudden cardiac death in populations with existing heart disease, such as myocardial infarction, cardiomyopathy and heart failure. The increased prevalence of coronary heart disease and hypertension is associated with increased mechanical dispersion, which likely indicates an increased risk of fatal arrhythmias and sudden cardiac death [ 36 ]. Chemotherapy has direct cytotoxic effects on the myocardium through excessive ROS generation during anthracycline drug metabolism, leading to cardiomyocyte injury. In addition, oxidative stress also targets ion channels and affects ion membrane currents. This results in abnormal action potential propagation and arrhythmia. Anthracyclines can also form iron complexes that further generate ROS. The interaction between mitochondrial damage and impaired iron metabolism prolongs the action potential and increases cell membrane instability, which may reflect the irregularity of ventricular contractions that develop during chemotherapy [ 37 ]. The myocardial contraction value increased from 398.8 ± 39.5 at baseline to 413.5 ± 38.9 at the 6th month (p = 0.017). This finding is in line with previous studies that showed that chemotherapy with anthracyclines can decrease cardiac systolic function in some patients. Nevertheless, the long-term effects on myocardial contraction are not always adverse. This increase may reflect the heart's adaptation to the increased workload due to impaired diastolic relaxation, as seen in the increased E/e' [ 38 ]. There was also remodelling of left ventricular dimensions in this study, with an increase in the LVEDV and LVESV during follow-up. Research by Esteban-Fernández et al. also revealed an increase in the LVEDV and LVESV from baseline ​​to the time at which CTRCD was diagnosed (the median time from the start of chemotherapy to the diagnosis of cardiotoxicity was eight months) [ 39 ]. This increase in the LVESV was possibly related to changes in the LVEF, and an increase in the LVESV could cause a decrease in the LVEF as a reflection of reduced myocardial contractility. The CTRCD-induced increase in LVESV is later on partially compensated for by an increase in LVEDV as part of cardiac remodeling to maintain LVEF and cardiac output [ 40 ]. The assessment of LVSV revealed an increase in the first month and then a decrease in the third and sixth months. Another study conducted by Ferreira et al. revealed an increase in the LVSV at four to six months after chemotherapy, and then a decrease from the 12th to the 14th month after chemotherapy [ 41 ]. Repeated exposure to anthracyclines during chemotherapy leads to mitochondrial damage, which disrupts cardiac metabolism. Normally, the heart relies on fatty acid oxidation as its main energy source. Anthracyclines inhibit this process and shift metabolism toward the utilization of glucose, lactate, and pyruvate. This metabolic remodelling, together with mitochondrial injury, promotes apoptotic signalling, ultimately driving cardiac remodelling and functional decline [ 17 ]. In parallel, anthracyclines activate the MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinase) pathway through oxidative stress, which plays a role in regulating cell survival. However, they may also impair the ability of cardiomyocytes to sustain prosurvival pathways such as the PI3K/Akt pathway, which normally protects against apoptosis. In the injured heart, the activity of these protective pathways is further reduced, increasing the vulnerability of cardiomyocytes to subsequent anthracycline exposure. This mechanism may explain persistent ventricular remodelling and the increased susceptibility of the heart to cumulative anthracycline toxicity [ 42 ]. Assessment of left ventricular diastolic function can be performed from the E/e' ratio. In this study, there was an increase in the E/e' value in the third month after chemotherapy compared with the baseline value, and an increase was also observed in the sixth month compared with the previous month. These results are similar to those of previous studies reporting a significant increase in E/e' in breast cancer patients after undergoing chemotherapy with anthracycline. These findings suggest that chemotherapy induces myocardial stress and causes increased myocardial fibrosis and impaired left ventricular relaxation [ 43 ]. Another study by Serrano et al. and Ferreira et al. also revealed a rapid increase in the ratio of E/e' [ 44 , 41 ]. However, the use of E/e' as a parameter to predict CTRCD is still a matter of debate because fluctuations in the E and e' values in these patients can be caused by changes in loading conditions as a result of the side effects of chemotherapy (nausea, vomiting and diarrhea) [ 45 ] The right ventricular function evaluated by TAPSE was also decreased, beginning in the first months after chemotherapy. A previous study by Ferreira et al. revealed an increase, but not a significant increase, at two and fourteenth months after chemotherapy [ 41 ]. However, another previous study by El Sherbeny et al. reported a decrease in TAPSE values. Nevertheless, it was not significant in the cardiotoxic and noncardiotoxic groups of breast cancer patients who received an anthracycline regimen [ 46 ]. In this study, troponin levels increased significantly and progressively, from a median of 1.6 ng/L at baseline to 82.2 ng/L at six months of follow-up. In a previous cohort study of 204 patients, including 133 breast cancer survivors, Cardinale et al. measured these parameters before the start of chemotherapy and at 12, 24, 36 and 72 hours afterwards. In 53% of the patients, an increase in TnI occurred within 72 hours after chemotherapy. At the end of chemotherapy, a decrease in LVEF was observed in the TnI + and TnI− groups, but the decrease in LVEF was significantly lower in the TnI− group. At ten months, the LVEF was still impaired in the TnI+ group, whereas in the TnI− group, it remained at baseline levels [ 7 ]. This finding indicates that the incidence of mild asymptomatic CTRCD increased in accordance with the increase in troponin observed over the follow-up period. Previous research conducted by Shafi et al. revealed that the evaluation of troponin I provides a significant opportunity to identify patients who are more susceptible to cardiotoxicity [ 47 ]. Another study by Ky et al. confirmed that an increase in troponin I is associated with cardiac dysfunction and heart failure in breast cancer patients undergoing chemotherapy [ 48 ]. Troponins are essential proteins that help regulate muscle contraction; they interact with calcium ions to facilitate the binding of actin and myosin filaments, a crucial component of the sliding filament mechanism that enables muscle contraction. Anthracyclines disrupt the expression and activity of several molecules involved in intracellular Ca²⁺ regulation in myocardial cells. One of these proteins is sarcoplasmic reticulum ATPase (SERCA), a protein that regulates Ca²⁺ uptake in the sarcoplasmic reticulum (SR). resulting in impaired cardiac muscle. This may result in troponin release, and troponin levels have been shown to correlate with both systolic function and anthracycline dose. High-sensitivity troponin assays enable earlier and more accurate detection, supporting their use as biomarkers for anthracycline-induced cardiotoxicity [ 49 ]. There were several limitations of this study. This study did not classify the subject population into low-, medium-, and high-risk categories, so the results cannot reveal the relationship between the values of patient risk factors before chemotherapy and the incidence rate of CTRCD. The absence of NT-proBNP assessment, which is a key marker for hemodynamic stress, might limit the comprehensive evaluation of symptomatic heart failure, especially in mild cases. We did not conduct further follow-up because some patients were lost to follow-up. We did not evaluate the outcome, such as mortality or acute decompensated heart failure in mild asymptomatic CTRCD patients, since only the symptomatic patients that was related to mortality in the Cardio-TOX study. Conclusion Asymptomatic CTRCD could occur as early as the first month after the initiation of chemotherapy, whereas symptomatic CTRCD cases were discovered as early as the third month after chemotherapy. Our findings underscore that mild asymptomatic CTRCD is the most prevalent form of cardiac dysfunction, significantly outnumbering symptomatic cases. They experience several significant changes in symptoms, left ventricular remodelling, systolic and diastolic function, also myocardial contraction and dispersion. Therefore, they need special attention. It is also necessary to assess risk factors at the beginning of treatment, followed by monitoring of cardiac function, to enable early detection and initiation of therapy for cardiotoxicity in patients at risk. Abbreviations BMI Body mass index CTRCD Cancer therapy-related cardiac dysfunction ESC European Society of Cardiology ELFA Enzyme immunoassay with fluorescence detection GLS Global Longitudinal Strain HFA-ICOS Heart Failure Association – International Cardio-Oncology Society Hs-cTnI High-sensitivity troponin I LVEDV Left Ventricular End-Diastolic Volume LVEF Left ventricular Ejection Fraction LVESV Left Ventricular End-Systolic Volume LVSV Left Ventricular Stroke Volume MD Mechanical dispersion TAPSE Tricuspid Annular Plane Systolic Excursion ROS Reactive oxygen species Declarations Ethics Approval and Consent to Participate All experimental procedures were conducted in alignment with the Declaration of Helsinki and relevant ethical guidelines. The study received clearance from the Research Ethics Committee of Universitas Padjadjaran (No. 204/UN6.KEP/EC/2024) and Dr. Hasan Sadikin General Hospital (No. DP.04.03/D.XIV.4.4/599/2024). Due to the retrospective nature of the research, the ethics committee waived the necessity for patient-informed consent. Consent for publication Not applicable. Competing Interests The authors have no competing interests to declare. Fundings This research was partially supported by an internal grant from Universitas Padjadjaran, spanning the 2018–2019 funding cycle. Author Contribution This study was conducted by Astri Astuti, Adila Aafiyah, Aurora Adila Arderia , Melawati Hasan, Syarief Hidayat, Erwan Martanto, Mohammad R. Akbar. Astri astuti contributed to conceptualization, design of the study, planned the methodology, selected articles based on inclusion and exclusion criteria, oversaw the project, contributed to data acquisition and interpretation, prepared figures and tables, drafted and critically revised the manuscript, and took responsibility for the final decision to submit the manuscript. Adila Aafiyah conducted data analysis and interpretation, performed database searches, screened and selected studies, processed data, prepared figures and tables, drafted the manuscript, and contributed to technical editing. Aurora Adila Arderia contributed to investigation, data collection, and literature review. Melawati Hasan contributed to methodology, echocardiographic analysis, and provided expertise in summarizing and interpreting findings. Syarief Hidayat contributed to formal and statistical analysis and data interpretation. Erwan Martanto contributed to investigation, clinical data acquisition. Mohammad R. Akbar contributed to conceptualization, supervision, validation, and critically revised the manuscript for accuracy. All authors read and approved the final manuscript and agree to be accountable for all aspects of the work. Acknowledgement The authors would like to acknowledge Universitas Padjadjaran for supporting this research through an institutional research grant. The authors also thank to the staff of the Department of Cardiology and Vascular Medicine and Dr. Hasan Sadikin General Hospital, Bandung, for their assistance in data collection and patient management. Data Availability The authors commit to sharing all manuscript materials and underlying raw data with the scientific community for non-commercial research, provided such requests maintain the strict anonymity and confidentiality of study participants. References Ben-Dror J, Shalamov M, Sonnenblick A. The History of Early Breast Cancer Treatment. Genes (Basel). 2022;13. https://doi.org/10.3390/genes13060960 . 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Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9465827","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":637881066,"identity":"f31138b7-69f0-4a1c-93a4-b5811eff6c25","order_by":0,"name":"Astri Astuti","email":"data:image/png;base64,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","orcid":"","institution":"Universitas Padjadjaran, Dr. Hasan Sadikin General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Astri","middleName":"","lastName":"Astuti","suffix":""},{"id":637881067,"identity":"823d31bb-9aea-4b3a-b57f-08ea9687c177","order_by":1,"name":"Adila Aafiyah","email":"","orcid":"","institution":"Universitas Padjadjaran, Dr. Hasan Sadikin General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Adila","middleName":"","lastName":"Aafiyah","suffix":""},{"id":637881068,"identity":"29f493ae-62cd-492c-ab4a-19c3c9aef06a","order_by":2,"name":"Aurora Adila Arderia","email":"","orcid":"","institution":"Universitas Padjadjaran","correspondingAuthor":false,"prefix":"","firstName":"Aurora","middleName":"Adila","lastName":"Arderia","suffix":""},{"id":637881069,"identity":"b723c9aa-78f1-4947-9a49-0cbd77d8c9b7","order_by":3,"name":"Melawati Hasan","email":"","orcid":"","institution":"Universitas Padjadjaran, Dr. Hasan Sadikin General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Melawati","middleName":"","lastName":"Hasan","suffix":""},{"id":637881070,"identity":"821c4342-db9b-43c4-8bbf-536d6945c9b4","order_by":4,"name":"Syarief Hidayat","email":"","orcid":"","institution":"Universitas Padjadjaran, Dr. Hasan Sadikin General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Syarief","middleName":"","lastName":"Hidayat","suffix":""},{"id":637881071,"identity":"def28c7b-70d6-4e3c-ac83-df1b60184f01","order_by":5,"name":"Erwan Martanto","email":"","orcid":"","institution":"Universitas Padjadjaran, Dr. Hasan Sadikin General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Erwan","middleName":"","lastName":"Martanto","suffix":""},{"id":637881072,"identity":"ca268904-1fc2-4bd6-b602-45625064e355","order_by":6,"name":"Mohammad R. Akbar","email":"","orcid":"","institution":"Universitas Padjadjaran, Dr. Hasan Sadikin General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"R.","lastName":"Akbar","suffix":""}],"badges":[],"createdAt":"2026-04-20 02:38:35","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9465827/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9465827/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109153428,"identity":"c8447616-ddb1-4dbc-861f-a1993bd096b7","added_by":"auto","created_at":"2026-05-13 06:17:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":190990,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eChanges in the mean echocardiographic characteristics of breast cancer patients receiving chemotherapy at baseline, month 1, month 3, and month 6 of follow-up. \u003c/strong\u003e(A) There were significant LVEF changes from baseline to month 3, from baseline to month 6, from month 1 to month 6, and from month 3 to month 6. (B) GLS significantly decreased from baseline to month 3 and from month 6, while no significant differences were observed in the first month. (C) The LVEDV increased significantly from baseline to month 3 and month 6, with no significant differences among the postbaseline measurements. (D) The LVESV was significantly greater at month 3 and month 6 than at baseline and from month 1 to month 6. (E) No significant differences in the LVSV were observed across the time points. (F) No significant differences in the TAPSE were observed among the time points. (G) A significant increase in myocardial contraction was observed from month 1 to month 6. (H) A significant increase in mechanical dispersion was observed from month 1 to month 6.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9465827/v1/6a9eaba4c75ee31223f95ad3.png"},{"id":109153430,"identity":"7dc34088-2b02-4e1e-bac1-1f2640725041","added_by":"auto","created_at":"2026-05-13 06:17:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":75440,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTroponin changes at months 1, 3, and 6 during chemotherapy\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-9465827/v1/ced229f75a8a13a5e12a14aa.png"},{"id":109205396,"identity":"8a27a995-cf08-46b4-865b-ccc3f46726a0","added_by":"auto","created_at":"2026-05-13 15:04:34","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":165031,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCTRCD incidence in breast cancer patients receiving chemotherapy at 1, 3, and 6 months\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-9465827/v1/f4b412a5d9473cf5057ba3b1.png"},{"id":109296402,"identity":"3b1468e4-6e18-4b6e-8ba1-b90073ce0ea8","added_by":"auto","created_at":"2026-05-15 08:46:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":847626,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9465827/v1/3b791ec0-dc93-4e65-8c02-a64ef41cd71c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eCardiac Monitoring and Incidence of Cardiotoxicity Cardiomyopathy Among Breast Cancer Patients Undergoing Anthracycline Regimen Chemotherapy: Insight From a Single Centre Study\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBreast cancer is one of the most common types of cancer in the world. In 2020, approximately 2.3\u0026nbsp;million women were diagnosed with breast cancer, and the mortality rate was 635000 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In Indonesia, breast cancer is the type of cancer with the highest number of patients and one of the leading causes of death. According to data from Global Cancer Statistics in 2020, the number of new cases of breast cancer in Indonesia reached 68,858, or 16.6% of the total 396,914 new cases, and the number of deaths reached more than 22,000 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eChemotherapy is an important breakthrough in the treatment of cancer, but it is also associated with major adverse effects, especially cardiotoxicity [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The incidence rate of cancer therapeutic-related cardiac dysfunction (CTRCD) during or shortly after the completion of cancer therapy ranges from 9\u0026ndash;26% after treatment with doxorubicin, 13\u0026ndash;17% with trastuzumab, and 27\u0026ndash;34% with combination therapy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Anthracyclines are among the most commonly used chemotherapeutic drugs and have shown efficacy against several kinds of malignancies, particularly lymphoma and breast cancer. On the other hand, anthracyclines may cause progressive and irreversible cardiac damage[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Cardiotoxicity due to anthracycline begins with damage to myocardial cells, followed by a decrease in left ventricular function, which ultimately, if not treated, can cause heart failure [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Cardiotoxicity can be detected early and avoided by monitoring disease progression, including declines in left ventricular function, or by identifying subclinical myocardial injury through biomarker assessment, such as troponin measurement [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The recovery rate of cancer patients who are increasing in life expectancy afterwards also needs to be considered, and a focus on cardiac health has to be our priority. On the other hand, there is still much uncertainty in assessing cardiovascular risk in patients undergoing chemotherapy, especially in detecting subclinical changes [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. There are several different definitions of cardiotoxicity, making it difficult to compare results across trials to determine the true incidence of various types of cardiovascular cardiotoxicity and CTRCD. Therefore, we aimed to assess the incidence of CTRCD in Indonesia, especially West Java, on the basis of the latest consensus definition of cardiovascular toxicity adopted in the 2022 European Society of Cardiology (ESC) cardio-oncology guidelines [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study was a retrospective descriptive study involving medical records of 98 breast cancer patients receiving chemotherapy with an anthracycline regimen at Dr. Hasan Sadikin General Hospital Bandung. This research was conducted after ethical approval was obtained from the Research Ethics Committee (number 204/UN6). KEP/EC/2024 and research permission from the Director of Human Resources, Education and Research at Dr. Hasan Sadikin General Hospital Bandung with number DP.04.03/D.XIV.4.4/599/2024.\u003c/p\u003e \u003cp\u003e The inclusion criteria of this study included all breast cancer patients over the age of 18 years who were indicated to receive anthracycline regimens by an oncologist at Dr. Hasan Sadikin General Hospital Bandung from July 2018 to February 2020. The data that were assessed included clinical assessment and biomarker and echocardiography examination results at baseline and at 1, 3, and 6 months after the initiation of chemotherapy. The exclusion criterion in this study was patients with breast cancer whose medical records were illegible.\u003c/p\u003e \u003cp\u003e The definition of CTRCD was using the ESC Cardio-oncology guideline 2022. Symptomatic CTRCD was defined as the presence of cardiac dysfunction with symptoms of heart failure resulting from cancer treatment and was grouped into very severe (heart failure requiring inotropic support, mechanical circulatory support, or consideration of transplantation), severe (heart failure hospitalization), moderate (requiring intensification of diuretic therapy and outpatient heart failure) and mild (mild symptoms of heart failure, no need for intensification of therapy). Asymptomatic CTRCD was defined as the absence of symptoms of heart failure resulting from cancer treatment. Asymptomatic CTRCD was grouped into severe (new decrease in Left ventricular Ejection Fraction (LVEF) to \u0026lt;\u0026thinsp;40%), moderate (new LVEF reduction by \u0026ge;\u0026thinsp;10 percentage points to an LVEF of 40\u0026ndash;49% or new LVEF reduction by \u0026lt;\u0026thinsp;10 percentage points to an LVEF of 40\u0026ndash;49% accompanied by a decrease in Global Longitudinal Strain (GLS) of \u0026gt;\u0026thinsp;15% or a new increase in cardiac biomarkers) and mild (LVEF\u0026thinsp;\u0026ge;\u0026thinsp;50% and a decrease in GLS by \u0026gt;\u0026thinsp;15% from baseline and/or new increases in cardiac biomarkers) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. High-sensitivity troponin I (hs-cTnI) was evaluated via the Vidas BioM\u0026eacute;rieux assay, which combines a one-step sandwich enzyme immunoassay with fluorescence detection (ELFA). The global 99th percentile URL for high-sensitivity troponin I is 19 ng/L on the platforms used in this study.\u003c/p\u003e \u003cp\u003eThe data that were obtained were processed via Microsoft Excel and IBM SPSS Statistics version 27 applications. The data analysis began by performing the Kolmogorov‒Smirnov and Shapiro‒Wilk normality tests to determine whether the data that were collected were normally distributed. Then, the data are presented as a frequency distribution or cross-tabulation. If the data are normally distributed, the variables are presented using the mean value (\u0026#119909;̅) and standard deviation (σ). Moreover, for data that are not normally distributed, variables are presented using median (Me) values ​​as well as minimum (Min) and maximum (Max) values.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e Ninety-eight breast cancer patients underwent chemotherapy with an anthracycline regimen at Dr. Hasan Sadikin General Hospital, Bandung, who fulfilled the inclusion criteria. The average age of the patients was 47\u0026thinsp;\u0026plusmn;\u0026thinsp;8 years, with no difference in asymptomatic and symptomatic CTRCD. Most of the patients (62.2%) were under 50 years old. The mean dose of anthracycline was 570 mg/m\u003csup\u003e2\u003c/sup\u003e of body surface area, with no significant difference between the groups (p\u0026thinsp;=\u0026thinsp;0.298). A total of 73 patients developed CTRCD (74.48%), 7 (7.14%) of whom were symptomatic, and the rest were asymptomatic.\u003c/p\u003e \u003cp\u003eA total of 41.8% of patients were classified as obese, and 30.6% were overweight based on body mass index (BMI) category. There was no significant variation in the distribution of BMI categories between the groups (p\u0026thinsp;=\u0026thinsp;0.978). Among all patients, 20.4% had hypertension, with a greater prevalence in the asymptomatic CTRCD group (22.7%) than in the other groups; this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.712). There was also no significant difference in diabetes mellitus between the groups (p\u0026thinsp;=\u0026thinsp;0.161), with a higher rate of diabetes mellitus in patients with asymptomatic CTRCD (10.6%) than in those with normal and symptomatic CTRCD. Among all patients, 2% received mediastinal radiotherapy, with a greater proportion in the symptomatic CTRCD group (14.3%) than in the other groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of breast cancer patients receiving chemotherapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAsymptomatic CTRCD\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSymptomatic CTRCD\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.533\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge Category (n, %)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.855\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (62.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.911\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (37.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (36.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI (kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.974\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI Category (n, %)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.978\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnderweight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.880\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (26.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (24.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverweight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (30.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObesity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (43.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRisk Factor (n, %)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (20.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (22.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.712\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes Mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (10.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.161\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConcomitant Diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.783\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of Mediastinal Radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnthracycline Cumulative Dose (mg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e), n\u0026thinsp;=\u0026thinsp;51\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e570\u0026thinsp;\u0026plusmn;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e599\u0026thinsp;\u0026plusmn;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e570\u0026thinsp;\u0026plusmn;\u0026thinsp;52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e540\u0026thinsp;\u0026plusmn;\u0026thinsp;76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.298\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*Categorical data are presented as counts, and percentages were analyzed via the chi-square test. Continuous data are presented as the means\u0026thinsp;\u0026plusmn;\u0026thinsp;SDs and were analyzed via one-way ANOVA.\u003c/p\u003e \u003cp\u003eThe mean LVEF values are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e was similar across all groups, with a mean LVEF of 68.2%, with minor variations between groups (67.2% in the normal group, 68.4% in the asymptomatic CTRCD group, and 69.5% in the symptomatic CTRCD group). There were no significant differences between the groups (p\u0026thinsp;=\u0026thinsp;0.709).\u003c/p\u003e \u003cp\u003eThe global longitudinal strain (GLS) values ranged from \u0026minus;\u0026thinsp;18.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5% to -20.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9%, indicating decreased longitudinal function in the asymptomatic CTRCD group. However, this difference did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.051). The other echocardiography parameters shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e were not significantly different between the groups. The median troponin level was normal at 1.6 (1.4\u0026ndash;6.5) ng/L, with no difference between the groups (p\u0026thinsp;=\u0026thinsp;0.345). However, there was a significant difference in myocardial contraction (p\u0026thinsp;=\u0026thinsp;0.016).\u003c/p\u003e \u003cp\u003eOverall, these results indicate no significant differences in most baseline echocardiographic characteristics or troponin levels among the groups. In addition, there was decreased myocardial contraction in the asymptomatic group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline Echocardiographic Characteristics and Troponin Levels of Breast Cancer Patients Undergoing Chemotherapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAsymptomatic CTRCD\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSymptomatic CTRCD\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLVEF\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e69.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.709\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGLS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-19.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-18.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-20.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-18.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLVEDV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83.7\u0026thinsp;\u0026plusmn;\u0026thinsp;22.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82.3\u0026thinsp;\u0026plusmn;\u0026thinsp;23.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84.3\u0026thinsp;\u0026plusmn;\u0026thinsp;23.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e81.5\u0026thinsp;\u0026plusmn;\u0026thinsp;14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.929\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLVESV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.0 (20.0\u0026ndash;32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.0 (20.3\u0026ndash;32.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.0 (19.0\u0026ndash;32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.5 (18.5\u0026ndash;25.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.540\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLVSV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.9\u0026thinsp;\u0026plusmn;\u0026thinsp;18.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57.6\u0026thinsp;\u0026plusmn;\u0026thinsp;14.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e57.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.801\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTAPSE\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.3 (20.0\u0026ndash;23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.3 (19.2\u0026ndash;23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.1 (20.0\u0026ndash;23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22.5 (21.0\u0026ndash;23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.706\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eE/A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.279\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eE/e\u0026rsquo;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.65\u0026thinsp;\u0026plusmn;\u0026thinsp;2.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.96\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.53\u0026thinsp;\u0026plusmn;\u0026thinsp;2.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.24\u0026thinsp;\u0026plusmn;\u0026thinsp;2.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.702\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMyocardial Contraction\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e398.8\u0026thinsp;\u0026plusmn;\u0026thinsp;39.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e420.1\u0026thinsp;\u0026plusmn;\u0026thinsp;43.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e391.0\u0026thinsp;\u0026plusmn;\u0026thinsp;36.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e417.5\u0026thinsp;\u0026plusmn;\u0026thinsp;33.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.016*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMechanical Dispersion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.2 (36.5\u0026ndash;48.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.0 (34.4\u0026ndash;56.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42.6 (36.3\u0026ndash;46.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52.8 (46.6\u0026ndash;54.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.085\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHs Troponin I\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.6 (1.4\u0026ndash;6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4 (1.4\u0026ndash;4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.7 (1.4\u0026ndash;7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.8 (1.4\u0026ndash;3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eLVEF: Left Ventricular Ejection Fraction, GLS: Global Longitudinal Strain, LVEDV: Left Ventricular End-Diastolic Volume, LVESV: Left Ventricular End-Systolic Volume, LVSV: Left Ventricular Stroke Volume, TAPSE: Tricuspid Annular Plane Systolic Excursion\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*Continuous data with a normal distribution are presented as the means\u0026thinsp;\u0026plusmn;\u0026thinsp;SDs and were analyzed via one-way ANOVA. Continuous data without a normal distribution are presented as medians and interquartile ranges and were analyzed via the Kruskal‒Wallis test.\u003c/p\u003e \u003cp\u003eAt 6 months of follow-up, a significant decrease was observed in LVEF among all patients who underwent chemotherapy, from 68.2% at baseline to 61.3% (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and in GLS values, from \u0026minus;\u0026thinsp;19.7 at baseline to \u0026minus;\u0026thinsp;17.1 at the 6th month (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The decrease became significant at the third month of follow-up compared with baseline, and it was even more pronounced at month 6. This finding indicates a progressive decline during therapy, especially after 3 months of follow-up. The left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) increased significantly after the baseline measurement and remained elevated throughout the 6-month follow-up, with a significant increase starting from the third month of follow-up (LVEDV: 83.7\u0026ndash;90.0 mL; LVESV: 24.0\u0026ndash;31.0 mL, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, there were no significant differences between month-1, month-3, and month-6. This may indicate progressive cardiac remodelling along with a reduction in systolic function during chemotherapy.\u003c/p\u003e \u003cp\u003eIn terms of the echocardiography parameters, the E/e\u0026rsquo; ratio significantly increased at the 6th month of follow-up (p\u0026thinsp;=\u0026thinsp;0.020), indicating an increase in left ventricular diastolic filling pressure. Moreover, the E/A ratio did not significantly change (p\u0026thinsp;=\u0026thinsp;0.345). There was a significant increase in myocardial contraction from the first month of follow-up to month 6 (p\u0026thinsp;=\u0026thinsp;0.017). Similarly, the mechanical dispersion value significantly increased over time (p\u0026thinsp;=\u0026thinsp;0.029).\u003c/p\u003e \u003cp\u003eOverall, these findings demonstrate that chemotherapy is associated with a progressive decline in systolic function, accompanied by structural remodelling, altered diastolic filling pressures, and increased mechanical dispersion, which may contribute to subclinical cardiotoxicity within six months.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEchocardiographic characteristics of breast cancer patients receiving chemotherapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMonth-1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMonth-3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMonth-6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLVEF\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e61.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGLS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-19.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-19.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-18.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-17.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLVEDV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83.7\u0026thinsp;\u0026plusmn;\u0026thinsp;22.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86.2\u0026thinsp;\u0026plusmn;\u0026thinsp;21.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90.0\u0026thinsp;\u0026plusmn;\u0026thinsp;21.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94.4\u0026thinsp;\u0026plusmn;\u0026thinsp;21.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLVESV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.0 (20.0\u0026ndash;32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.0 (20.8\u0026ndash;32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31.0 (25.0\u0026ndash;38.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e34.0 (27.0\u0026ndash;44.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLVSV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.4\u0026thinsp;\u0026plusmn;\u0026thinsp;16.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58.0\u0026thinsp;\u0026plusmn;\u0026thinsp;16.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e56.9\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.759\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTAPSE\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.3 (20.0\u0026ndash;23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.3 (19.1\u0026ndash;23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.1 (19.0\u0026ndash;23.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.0 (20.0\u0026ndash;22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.729\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eE/A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.09\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eE/e\u0026rsquo;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.65\u0026thinsp;\u0026plusmn;\u0026thinsp;2.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.24\u0026thinsp;\u0026plusmn;\u0026thinsp;2.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.49\u0026thinsp;\u0026plusmn;\u0026thinsp;3.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.020*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMyocardial Contraction\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e398.8\u0026thinsp;\u0026plusmn;\u0026thinsp;39.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e399.5\u0026thinsp;\u0026plusmn;\u0026thinsp;36.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e400.5\u0026thinsp;\u0026plusmn;\u0026thinsp;34.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e413.5\u0026thinsp;\u0026plusmn;\u0026thinsp;38.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.017*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMechanical Dispersion\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.2 (36.5\u0026ndash;48.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.3 (36.3\u0026ndash;47.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43.6 (38.9\u0026ndash;50.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46.3 (41.7\u0026ndash;51.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.029*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eLVEF: Left Ventricular Ejection Fraction, GLS: Global Longitudinal Strain, LVEDV: Left Ventricular End-Diastolic Volume, LVESV: Left Ventricular End-Systolic Volume, LVSV: Left Ventricular Stroke Volume, TAPSE: Tricuspid Annular Plane Systolic Excursion\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTroponin levels increased significantly and progressively, from a median of 1.6 ng/L at baseline to 82.2 ng/L at six months of follow-up (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). By the third month, the median score was already above the 99th percentile, suggesting that a significant proportion of patients experienced cardiac injury or stress after chemotherapy. During the follow-up, 62 patients (63%) had hs-cTnI values\u0026thinsp;\u0026gt;\u0026thinsp;19 ng/L.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTroponin levels in patients with breast cancer receiving chemotherapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariabel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMonth-1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMonth-3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMonth-6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ehs Troponin I\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.6 (1.4\u0026ndash;6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.6 (1.6\u0026ndash;11.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.7 (20.0-60.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e82.2 (38.5-151.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNumber of CTRCD cases among breast cancer patients receiving chemotherapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMonth-1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMonth-3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eMonth-6\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAll CTRCD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7/98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33/91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e36.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e33/58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e56.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild asymptomatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7/98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30/91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e32.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25/58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e43.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate asymptomatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2/58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e3.4%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere asymptomatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2/58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e3.44%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild symptomatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.00%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3/91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.29%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4/58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e6.89%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eCTRCD: Cancer Therapy-Related Cardiac Dysfunction\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, 7 cases of CTRCD were found in the first month of the 6-month follow-up period (7.14% of all patients), all of which were mildly asymptomatic. This number increased significantly to 33 out of 91 undermonitored patients (36.26%) at the third month, with 30 patients categorized as mildly asymptomatic (32.97%) and 3 patients categorised as mildly symptomatic (3.30%). Among the 7 mild symptomatic patients, 1 high-risk patient had cardiotoxicity due to a history of radiotherapy in the mediastinum and obesity, and 1 moderate-risk patient had a history of hypertension and obesity based on the HFA-ICOS (Heart Failure Association \u0026ndash; International Cardio-Oncology Society) score. Four symptomatic patients were initially diagnosed as asymptomatic CTRCD at month 3.\u003c/p\u003e \u003cp\u003eThe number of cases continued to increase until the sixth month, when more than half of the undermonitor patients (33 out of 58 patients; 56.9%) experienced CTRCD. Four patients (6.9%) experienced mild symptomatic CTRCD, 25 patients (43.1%) experienced mild asymptomatic CTRCD, 2 patients experienced moderate asymptomatic CTRCD (3.4%), and 2 patients experienced severe asymptomatic CTRCD (3.4%). Although there was an increase in the number of symptomatic CTRCD patients, its incidence remains lower than that of asymptomatic CTRCD patients, indicating that most patients are asymptomatic.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIncidence Rate of Cardiotoxicity Cardiomyopathy in Breast Cancer Patients Undergoing Chemotherapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEvent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTime at Risk\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRate (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRate in 100 person-month\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAll CTRD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e454\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.161 (0.128\u0026ndash;0.202)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e16.1 (12.8\u0026ndash;20.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptomatic CTRCD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e454\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.015 (0.007\u0026ndash;0.032)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.5 (0.7\u0026ndash;3.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsymptomatic CTRCD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e454\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.145 (0.114\u0026ndash;0.185)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e14.5 (11.4\u0026ndash;18.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWith respect to the incidence rate of CTRCD in breast cancer patients who underwent chemotherapy, among 98 patients, 73 (74.48%) experienced CTRCD during chemotherapy, with a cumulative risk time of 6 months. Sixty-six patients were asymptomatic, and 7 patients had symptomatic CTRCD. The incidence rate of CTRCD is 0.16 per person-month (95% CI: 0.128\u0026ndash;0.202), equivalent to 16.1 events per 100 person-months (95% CI: 3.1\u0026ndash;6.7), with a total monitoring time of 454 person-months. The incidence of symptomatic CTRCD is relatively low; there were 7 cases with an incidence rate of 0.015 per person-month (95% CI: 0.007\u0026ndash;0.032) or 1.5 cases per 100 person-months. However, the incidence of asymptomatic CTRCD is quite high, with 66 cases and an incidence rate of 0.145 per person-month (95% CI: 0.114\u0026ndash;0.185), or 14.5 cases per 100 person-months.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows that the incidence of CTRCD increased significantly during therapy, peaking at month 3. Most cases are mild and asymptomatic, whereas severe or symptomatic cases are less common.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study revealed that the incidence rate of CTRCD in breast cancer patients who underwent chemotherapy was 73 out of 98 patients (74.5%) during chemotherapy, with a cumulative risk time of 6 months. Sixty-six (67.34%) patients were asymptomatic, most of whom were classified as mildly asymptomatic (62 of 98 [63.26%]), and 7 (7.14%) patients had symptomatic CTRCD. The incidence rate of CTRCD is 0.161 per person-month (95% CI: 0.128\u0026ndash;0.202), which is equivalent to 16.1 events per 100 person-months. The results of the present study are consistent with previous findings reported by Oristrell et al. that, over an average follow-up of 13.6 months, no cases of symptomatic CTRCD were observed. However, asymptomatic CTRCD occurred in 60% of patients, with 53 (55.8%) classified as mild, 3 (3.2%) as moderate, and 1 (1.1%) as severe [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Similarly, Mecinaj et al. reported that most CTRCD cases were mildly asymptomatic (58 of 118 [49.2%]), with the highest incidence observed after anthracycline therapy, when 55 of 115 patients (47.8%) were identified with mild asymptomatic CTRCD [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The CARDIOTOX registry defines cardiotoxicity as the presence of new or worsening myocardial damage/dysfunction and classifies it as mild (abnormal biomarkers and/or LV dysfunction (LVD) with an LV ejection fraction (LVEF)\u0026thinsp;\u0026ge;\u0026thinsp;50%), moderate (LVD with LVEF 40\u0026ndash;49%), or severe (LVD with LVEF\u0026thinsp;\u0026lt;\u0026thinsp;40% or symptomatic heart failure). Cardiotoxicity was identified in 37.5% of patients during follow-up [95% confidence interval (CI) 34.22\u0026ndash;40.8%]: 31.6% with mild, 2.8% with moderate, and 3.1% with severe myocardial damage/dysfunction [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis research revealed that the incidence of CTRCD was 7.14% in the first month of therapy. In a previous study by Astuti et al., there was subclinical left ventricular dysfunction after the first chemotherapy cycle, which indicates a possible incidence of mild CTRCD [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. A previous study by Mecinaj et al. revealed that out of 115 patients, only 1 (0.9%) experienced CTRCD after the first cycle of anthracycline (approximately 21 days), and the CTRCD was mild when sex-specific cardiac troponin T 99th percentile (9.0 ng/L) was used. There was a significant increase in the CTRCD incidence to 56.89% in the sixth month of chemotherapy. The results of our study are inconsistent with those of several other previous studies, which reported a cardiotoxicity incidence of 16.5%, mostly occurring after 1 year of follow-up. This is because the different definitions of cardiotoxicity used in the study (new-onset heart failure, according to the Framingham criteria; reduction in LVEF\u0026thinsp;\u0026ge;\u0026thinsp;10 percentage points from baseline to LVEF less than 55%; sustained ventricular arrhythmias; or sudden cardiac death) may explain the differences in incidence [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Moreover, other studies have reported that the incidence rate of CTRCD during or shortly after the completion of cancer therapy ranges from 9 to 26% after treatment with doxorubicin [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe incidence of asymptomatic CTRCD is relatively high. Asymptomatic cases were found earlier than symptomatic cases, in which mild cases can be found earlier in the first month after chemotherapy, and the number of symptomatic cases increased in the following month. This finding is in line with research conducted by Daniela et al., who reported that most cardiotoxicity patients in their research population did not present any clinical symptoms but already presented a decrease in LVEF, which was detected via scheduled echocardiography assessment [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In this study, the incidence rate of each CTRCD category increased over time, with the highest rate occurring in the third month after chemotherapy. Moreover, other research by Narayan et al. was conducted on 277 breast cancer patients, where the median time for a significant decrease in LVEF was seven months after chemotherapy [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, some of the asymptomatic patients developed heart failure symptoms. Anthracycline causes cardiotoxicity primarily through free radical formation during mitochondrial metabolism. The reduction of doxorubicin by NADH dehydrogenase results in the formation of semiquinone radicals, which react with molecular oxygen to produce superoxide radicals. The hydroxyl radical and hydrogen peroxide are then produced as a result of redox cycling. Furthermore, the formation of doxorubicin-iron complexes may catalyze the Fenton reaction (Fe-catalyzed conversion of hydrogen peroxide to hydroxyl radicals), resulting in the generation of reactive oxygen species (ROS). Owing to their high mitochondrial content and reliance on oxidative metabolism, cardiomyocytes are more vulnerable to this oxidative stress than are tumor cells, which are more glycolytic.\u003c/p\u003e \u003cp\u003eROS accumulation leads to apoptotic cell death, and doxorubicin disrupts mitochondrial function by binding to cardiolipin, a phospholipid in the inner mitochondrial membrane, facilitating cytochrome c release, which increases apoptosis. Myocardial cell damage can cause a decrease in left ventricular function, which, if not treated, can cause heart failure [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Heart failure itself may be preceded by asymptomatic subclinical left ventricular dysfunction, such as a decrease in GLS, or an increase in cardiac biomarkers that is characterized by early onset with a slow and progressive deterioration that may continue several times after the end of chemotherapy, before LVEF reduction [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMost of the subjects were \u0026lt;\u0026thinsp;50 years old, and CTRCD cases also occurred more frequently in those aged\u0026thinsp;\u0026lt;\u0026thinsp;50 years. These results are in line with other research conducted by Lu et al., who reported that the incidence of cardiotoxicity within three years after the administration of anthracyclines is greater in women aged\u0026thinsp;\u0026le;\u0026thinsp;50 years than in women aged\u0026thinsp;\u0026gt;\u0026thinsp;50 years [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Previous research revealed that the incidence of cardiotoxicity due to anthracyclines is associated with increasing age [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Most studies have shown that patients with advanced age (\u0026ge;\u0026thinsp;65 years) are at greater risk of cardiotoxicity than younger patients due to the age-related loss of cardiomyocytes. This subsequently leads to a decrease in myocardial volume, which is correlated with increased cardiovascular events. It has also been shown that the pharmacokinetics of anthracyclines change during aging, resulting in significantly increased doxorubicin concentrations, which is particularly evident in the heart. Furthermore, doxorubicin induces cellular senescence and telomere dysfunction, leading to increased proinflammatory cytokine expression. Telomere dysfunction results in the activation of the tumor suppressor gene \u003cem\u003ep\u003c/em\u003e53, which represses \u003cem\u003ePGC-1α\u003c/em\u003e and \u003cem\u003ePGC-1β\u003c/em\u003e transcription, thereby inhibiting downstream protein targets and impairing mitochondrial biogenesis. This results in mitochondrial dysfunction, increased ROS, reduced ATP production, and enhanced senescence [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, this was not observed in this study because the number of elderly people was too small.\u003c/p\u003e \u003cp\u003eThe body mass index revealed that the majority of asymptomatic CTRCDs were obese (50%), and the other 5.56% were overweight. Among symptomatic patients, 40% were obese. These findings are supported by the statement that a BMI\u0026thinsp;\u0026ge;\u0026thinsp;25 (overweight) is considered a cardiotoxicity risk factor, and a BMI\u0026thinsp;\u0026ge;\u0026thinsp;27 (obesity) has been correlated with an increased incidence of cardiac dysfunction in patients receiving anthracycline-based chemotherapy compared with those with a BMI\u0026thinsp;\u0026lt;\u0026thinsp;27 [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Another study by Kabor\u0026eacute; et al. revealed that, compared with patients with a BMI\u0026thinsp;\u0026ge;\u0026thinsp;25, those with a BMI\u0026thinsp;\u0026ge;\u0026thinsp;25 were independently associated with higher rates of cardiotoxicity [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. The epidemiological association between obesity and heart failure was explained by Kenchaiah et al., who reported that every 1 kg/m2 increase in BMI was associated with an 11% increase in the risk of heart failure [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe incidence of hypertension in the asymptomatic group (22.7%) was greater than that in the symptomatic (14.3%) and normal groups (16.0%). Similarly, a history of diabetes mellitus was more common in the asymptomatic group (10.6%) than in the normal group (0%). These results are in line with previous studies that have shown that there may be a decrease in LVEF in diabetic patients who undergo anthracycline or trastuzumab therapy, which might not be accompanied by clinical symptoms and can be detected only through subclinical examinations, such as echocardiograms [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Oxidative stress in diabetic patients can lead to gradual heart damage, which may not be severe enough to cause clinical symptoms in the early stages. This can also be influenced by decreased cardiovascular sensitivity in diabetic patients, which is related to endothelial dysfunction, myocardial energy metabolism disorders, and decreased sensory perception due to autonomic nerve dysfunction [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Other previous studies also reported that certain preexisting comorbidities, including hypertension and diabetes mellitus, can increase the risk for cardiotoxicity in cancer patients undergoing chemotherapy [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe percentage of patients with a history of mediastinal radiotherapy was greater in the symptomatic group (14.3%) than in the normal group (2%). A history of mediastinal radiation is a risk factor for cardiotoxicity. Mediastinal radiation can cause inflammation and fibrosis, leading to progressive diastolic dysfunction and restrictive hemodynamics, thereby affecting disease progression and recovery from cardiotoxicity. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eSeveral previous studies have shown a relationship between the cumulative dose of anthracyclines and the incidence rate of cardiotoxicity among breast cancer patients, indicating that higher cumulative doses are associated with an increased risk of cardiotoxicity [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The highest incidence of cardiotoxicity was observed in the third month, at an average cumulative dose of 260 mg/m\u0026sup2;. This finding is consistent with the ESC cardio-oncology guidelines, which indicate that a cumulative dose of \u0026ge;\u0026thinsp;250 mg/m\u0026sup2; is associated with an increased risk of CTRCD [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEchocardiography is still the first-line diagnostic tool for the clinical evaluation of cardiac function in patients undergoing chemotherapy, and the LVEF is the most commonly used evaluation index [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Compared to baseline, the average LVEF value is lower in the first months after chemotherapy. A reduction in LVEF provides an early warning for detecting cardiotoxicity, even without heart failure symptoms. Our study revealed a significant decrease in LVEF over 6 months of chemotherapy, with a baseline LVEF of 68.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2, which decreased to 61.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8 by the 6th month (p value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Up to 10% of cancer patients who are treated with anthracyclines will develop LVEF reduction after the completion of chemotherapy [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Similar to our study, a study by Avila et al. revealed that 27 (14%) out of 192 patients had a decrease in LVEF of at least 10% at 6 months after the initiation of chemotherapy [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eA decrease in the GLS value was also observed, even within the first month after chemotherapy. There was a significant decrease in GLS values over 6 months, with a baseline GLS value of -19.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9, which decreased to -17.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5 at the 6th month (p value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This finding is consistent with another prospective cohort study by Astuti et al., who reported a GLS reduction in breast cancer patients three weeks after receiving the first cycle of fluorouracil, adriamycin, and cyclophosphamide chemotherapy. The GLS was reduced from \u0026minus;\u0026thinsp;20.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4% at baseline to -19.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8%, with an average reduction of -1.63\u0026thinsp;\u0026plusmn;\u0026thinsp;2.83% (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Similarly, in a study of breast cancer patients receiving treatment with anthracyclines, with or without adjuvant trastuzumab. A reduction in GLS was noted during follow-up, indicating impaired cardiac deformation (GLS\u0026thinsp;\u0026ge;\u0026thinsp;18%) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Another study revealed that 22% of patients had subclinical LV dysfunction according to GLS, but no cardiotoxicity was measured by LVEF. This finding shows that GLS is a better way to detect subclinical LV systolic dysfunction immediately after anthracycline therapy [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. This finding is also in line with previous research conducted by Gripp et al., which confirmed that the GLS assessment is a very good predictor of cardiotoxicity, which also shows that changes in the GLS value could be detected earlier than changes in the LVEF value [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Several previous studies also reported that a change in GLS on echocardiography has greater potential as a better predictor of cardiotoxicity than does LVEF [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. GLS measurements are better because of their ability to measure the longitudinal function of the entire ventricle than the basal segment alone. Clinical studies in breast cancer patients have shown that the specificity of GLS for assessing cardiac toxicity reaches 93%, and the negative predictive value is 91% [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe mechanical dispersion increased from the first month to the sixth month. GLS and E/e\u0026prime; are significantly related to mechanical dispersion. Mechanical dispersion itself has been proven and recommended for detecting arrhythmias and sudden cardiac death in populations with existing heart disease, such as myocardial infarction, cardiomyopathy and heart failure. The increased prevalence of coronary heart disease and hypertension is associated with increased mechanical dispersion, which likely indicates an increased risk of fatal arrhythmias and sudden cardiac death [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Chemotherapy has direct cytotoxic effects on the myocardium through excessive ROS generation during anthracycline drug metabolism, leading to cardiomyocyte injury. In addition, oxidative stress also targets ion channels and affects ion membrane currents. This results in abnormal action potential propagation and arrhythmia. Anthracyclines can also form iron complexes that further generate ROS. The interaction between mitochondrial damage and impaired iron metabolism prolongs the action potential and increases cell membrane instability, which may reflect the irregularity of ventricular contractions that develop during chemotherapy [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe myocardial contraction value increased from 398.8\u0026thinsp;\u0026plusmn;\u0026thinsp;39.5 at baseline to 413.5\u0026thinsp;\u0026plusmn;\u0026thinsp;38.9 at the 6th month (p\u0026thinsp;=\u0026thinsp;0.017). This finding is in line with previous studies that showed that chemotherapy with anthracyclines can decrease cardiac systolic function in some patients. Nevertheless, the long-term effects on myocardial contraction are not always adverse. This increase may reflect the heart's adaptation to the increased workload due to impaired diastolic relaxation, as seen in the increased E/e' [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere was also remodelling of left ventricular dimensions in this study, with an increase in the LVEDV and LVESV during follow-up. Research by Esteban-Fern\u0026aacute;ndez et al. also revealed an increase in the LVEDV and LVESV from baseline ​​to the time at which CTRCD was diagnosed (the median time from the start of chemotherapy to the diagnosis of cardiotoxicity was eight months) [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. This increase in the LVESV was possibly related to changes in the LVEF, and an increase in the LVESV could cause a decrease in the LVEF as a reflection of reduced myocardial contractility. The CTRCD-induced increase in LVESV is later on partially compensated for by an increase in LVEDV as part of cardiac remodeling to maintain LVEF and cardiac output [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe assessment of LVSV revealed an increase in the first month and then a decrease in the third and sixth months. Another study conducted by Ferreira et al. revealed an increase in the LVSV at four to six months after chemotherapy, and then a decrease from the 12th to the 14th month after chemotherapy [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRepeated exposure to anthracyclines during chemotherapy leads to mitochondrial damage, which disrupts cardiac metabolism. Normally, the heart relies on fatty acid oxidation as its main energy source. Anthracyclines inhibit this process and shift metabolism toward the utilization of glucose, lactate, and pyruvate. This metabolic remodelling, together with mitochondrial injury, promotes apoptotic signalling, ultimately driving cardiac remodelling and functional decline [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In parallel, anthracyclines activate the MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinase) pathway through oxidative stress, which plays a role in regulating cell survival. However, they may also impair the ability of cardiomyocytes to sustain prosurvival pathways such as the PI3K/Akt pathway, which normally protects against apoptosis. In the injured heart, the activity of these protective pathways is further reduced, increasing the vulnerability of cardiomyocytes to subsequent anthracycline exposure. This mechanism may explain persistent ventricular remodelling and the increased susceptibility of the heart to cumulative anthracycline toxicity [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAssessment of left ventricular diastolic function can be performed from the E/e' ratio. In this study, there was an increase in the E/e' value in the third month after chemotherapy compared with the baseline value, and an increase was also observed in the sixth month compared with the previous month. These results are similar to those of previous studies reporting a significant increase in E/e' in breast cancer patients after undergoing chemotherapy with anthracycline. These findings suggest that chemotherapy induces myocardial stress and causes increased myocardial fibrosis and impaired left ventricular relaxation [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Another study by Serrano et al. and Ferreira et al. also revealed a rapid increase in the ratio of E/e' [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. However, the use of E/e' as a parameter to predict CTRCD is still a matter of debate because fluctuations in the E and e' values in these patients can be caused by changes in loading conditions as a result of the side effects of chemotherapy (nausea, vomiting and diarrhea) [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe right ventricular function evaluated by TAPSE was also decreased, beginning in the first months after chemotherapy. A previous study by Ferreira et al. revealed an increase, but not a significant increase, at two and fourteenth months after chemotherapy [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. However, another previous study by El Sherbeny et al. reported a decrease in TAPSE values. Nevertheless, it was not significant in the cardiotoxic and noncardiotoxic groups of breast cancer patients who received an anthracycline regimen [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, troponin levels increased significantly and progressively, from a median of 1.6 ng/L at baseline to 82.2 ng/L at six months of follow-up. In a previous cohort study of 204 patients, including 133 breast cancer survivors, Cardinale et al. measured these parameters before the start of chemotherapy and at 12, 24, 36 and 72 hours afterwards. In 53% of the patients, an increase in TnI occurred within 72 hours after chemotherapy. At the end of chemotherapy, a decrease in LVEF was observed in the TnI\u0026thinsp;+\u0026thinsp;and TnI\u0026minus; groups, but the decrease in LVEF was significantly lower in the TnI\u0026minus; group. At ten months, the LVEF was still impaired in the TnI+ group, whereas in the TnI\u0026minus; group, it remained at baseline levels [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This finding indicates that the incidence of mild asymptomatic CTRCD increased in accordance with the increase in troponin observed over the follow-up period.\u003c/p\u003e \u003cp\u003ePrevious research conducted by Shafi et al. revealed that the evaluation of troponin I provides a significant opportunity to identify patients who are more susceptible to cardiotoxicity [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. Another study by Ky et al. confirmed that an increase in troponin I is associated with cardiac dysfunction and heart failure in breast cancer patients undergoing chemotherapy [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. Troponins are essential proteins that help regulate muscle contraction; they interact with calcium ions to facilitate the binding of actin and myosin filaments, a crucial component of the sliding filament mechanism that enables muscle contraction. Anthracyclines disrupt the expression and activity of several molecules involved in intracellular Ca\u0026sup2;⁺ regulation in myocardial cells. One of these proteins is sarcoplasmic reticulum ATPase (SERCA), a protein that regulates Ca\u0026sup2;⁺ uptake in the sarcoplasmic reticulum (SR). resulting in impaired cardiac muscle. This may result in troponin release, and troponin levels have been shown to correlate with both systolic function and anthracycline dose. High-sensitivity troponin assays enable earlier and more accurate detection, supporting their use as biomarkers for anthracycline-induced cardiotoxicity [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere were several limitations of this study. This study did not classify the subject population into low-, medium-, and high-risk categories, so the results cannot reveal the relationship between the values of patient risk factors before chemotherapy and the incidence rate of CTRCD. The absence of NT-proBNP assessment, which is a key marker for hemodynamic stress, might limit the comprehensive evaluation of symptomatic heart failure, especially in mild cases. We did not conduct further follow-up because some patients were lost to follow-up. We did not evaluate the outcome, such as mortality or acute decompensated heart failure in mild asymptomatic CTRCD patients, since only the symptomatic patients that was related to mortality in the Cardio-TOX study.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAsymptomatic CTRCD could occur as early as the first month after the initiation of chemotherapy, whereas symptomatic CTRCD cases were discovered as early as the third month after chemotherapy. Our findings underscore that mild asymptomatic CTRCD is the most prevalent form of cardiac dysfunction, significantly outnumbering symptomatic cases. They experience several significant changes in symptoms, left ventricular remodelling, systolic and diastolic function, also myocardial contraction and dispersion. Therefore, they need special attention. It is also necessary to assess risk factors at the beginning of treatment, followed by monitoring of cardiac function, to enable early detection and initiation of therapy for cardiotoxicity in patients at risk.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCTRCD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCancer therapy-related cardiac dysfunction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eESC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Society of Cardiology\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eELFA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEnzyme immunoassay with fluorescence detection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGLS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlobal Longitudinal Strain\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHFA-ICOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHeart Failure Association \u0026ndash; International Cardio-Oncology Society\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHs-cTnI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHigh-sensitivity troponin I\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLVEDV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLeft Ventricular End-Diastolic Volume\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLVEF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLeft ventricular Ejection Fraction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLVESV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLeft Ventricular End-Systolic Volume\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLVSV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLeft Ventricular Stroke Volume\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMechanical dispersion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTAPSE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTricuspid Annular Plane Systolic Excursion\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eROS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eReactive oxygen species\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics Approval and Consent to Participate\u003c/h2\u003e \u003cp\u003e All experimental procedures were conducted in alignment with the Declaration of Helsinki and relevant ethical guidelines. The study received clearance from the Research Ethics Committee of Universitas Padjadjaran (No. 204/UN6.KEP/EC/2024) and Dr. Hasan Sadikin General Hospital (No. DP.04.03/D.XIV.4.4/599/2024). Due to the retrospective nature of the research, the ethics committee waived the necessity for patient-informed consent.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors have no competing interests to declare.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFundings\u003c/h2\u003e \u003cp\u003eThis research was partially supported by an internal grant from Universitas Padjadjaran, spanning the 2018\u0026ndash;2019 funding cycle.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eThis study was conducted by Astri Astuti, Adila Aafiyah, Aurora Adila Arderia , Melawati Hasan, Syarief Hidayat, Erwan Martanto, Mohammad R. Akbar. Astri astuti contributed to conceptualization, design of the study, planned the methodology, selected articles based on inclusion and exclusion criteria, oversaw the project, contributed to data acquisition and interpretation, prepared figures and tables, drafted and critically revised the manuscript, and took responsibility for the final decision to submit the manuscript. Adila Aafiyah conducted data analysis and interpretation, performed database searches, screened and selected studies, processed data, prepared figures and tables, drafted the manuscript, and contributed to technical editing. Aurora Adila Arderia contributed to investigation, data collection, and literature review. Melawati Hasan contributed to methodology, echocardiographic analysis, and provided expertise in summarizing and interpreting findings. Syarief Hidayat contributed to formal and statistical analysis and data interpretation. Erwan Martanto contributed to investigation, clinical data acquisition. Mohammad R. Akbar contributed to conceptualization, supervision, validation, and critically revised the manuscript for accuracy. All authors read and approved the final manuscript and agree to be accountable for all aspects of the work.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors would like to acknowledge Universitas Padjadjaran for supporting this research through an institutional research grant. The authors also thank to the staff of the Department of Cardiology and Vascular Medicine and Dr. Hasan Sadikin General Hospital, Bandung, for their assistance in data collection and patient management.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe authors commit to sharing all manuscript materials and underlying raw data with the scientific community for non-commercial research, provided such requests maintain the strict anonymity and confidentiality of study participants.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBen-Dror J, Shalamov M, Sonnenblick A. The History of Early Breast Cancer Treatment. 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Clin Chim Acta. 2025;565:120000. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.cca.2024.120000\u003c/span\u003e\u003cspan address=\"10.1016/j.cca.2024.120000\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\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":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Anthracycline, Breast Cancer, Cardiotoxicity, Chemotherapy","lastPublishedDoi":"10.21203/rs.3.rs-9465827/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9465827/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAnthracyclines remain a cornerstone of breast cancer therapy but carry a significant risk of cancer therapy-related cardiac dysfunction (CTRCD). This study evaluates the incidence of CTRCD in an Indonesian setting using the latest 2022 ESC Cardio-Oncology guidelines, focusing on subclinical markers such as hs-Troponin I, Global Longitudinal Strain (GLS) and Mechanical Dispersion (MD).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective analytical study involved 98 breast cancer patients treated with anthracyclines at a top-tier referral hospital in Indonesia from July 2018 to February 2020. Clinical assessments, hs-Troponin I, and echocardiography (LVEF, GLS, and MD) were performed at baseline, 1, 3, and 6 months. CTRCD was defined per the 2022 ESC criteria.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCTRCD occurred in 74.5% of patients, predominantly as asymptomatic mild cases (63.26%). While symptomatic CTRCD was relatively low (7.14%), asymptomatic dysfunction was detected as early as one month post-chemotherapy. A significant progressive decline was observed in LVEF (68.2 ± 6.2% to 61.3 ± 8.8%, p \u0026lt; 0.001) and GLS (-19.7 ± 2.9% to -17.1 ± 3.5%, p \u0026lt; 0.001). Notably, mechanical dispersion significantly increased over time (p = 0.029), and median hs-Troponin I surged from 1.6 ng/L to 82.2 ng/L (p \u0026lt; 0.001) by month 6.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe high incidence of asymptomatic CTRCD underscores the inadequacy of relying on clinical symptoms alone. Integration of hs-troponin, GLS, and mechanical dispersion monitoring is essential for early detection, enabling timely cardioprotective intervention.\u003c/p\u003e","manuscriptTitle":"Cardiac Monitoring and Incidence of Cardiotoxicity Cardiomyopathy Among Breast Cancer Patients Undergoing Anthracycline Regimen Chemotherapy: Insight From a Single Centre Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-13 06:17:41","doi":"10.21203/rs.3.rs-9465827/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision 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