Epirubicin-induced Cardiotoxicity Research Articles

Protective Effects of Hesperetin on Cardiomyocyte Integrity and Cytoskeletal Stability in a Murine Model of Epirubicin-Induced Cardiotoxicity: A Histopathological Study

Anthracyclines, including epirubicin (Epi), are effective chemotherapeutics but are known for their cardiotoxic side effects, primarily inducing cardiomyocyte apoptosis. This study investigates the protective role of hesperetin (HSP) against cardiomyopathy triggered by Epi in a murine model. Male CD1 mice were divided into four groups, with the Epi group receiving a cumulative dose of 12 mg/kg intraperitoneally, reflecting a clinically relevant dosage. The co-treatment group received 100 mg/kg of HSP daily for 13 days. After the treatment period, mice were euthanized, and heart tissues were collected for histopathological, immunofluorescence/immunohistochemistry, and transmission electron microscopy (TEM) analyses. Histologically, Epi treatment led to cytoplasmic vacuolization, myofibril loss, and fiber disarray, while co-treatment with HSP preserved cardiac structure. Immunofluorescent analysis of Bcl-2 family proteins revealed Epi-induced upregulation of the pro-apoptotic protein Bax and a decrease in anti-apoptotic Bcl-2, which HSP treatment reversed. TEM observations confirmed the preservation of mitochondrial ultrastructure with HSP treatment. Moreover, in situ detection of DNA fragmentation highlighted a decrease in apoptotic nuclei with HSP treatment. In conclusion, HSP demonstrates a protective effect against Epi-induced cardiac injury and apoptosis, suggesting its potential as an adjunctive therapy in anthracycline-induced cardiomyopathy. Further studies, including chronic cardiotoxicity models and clinical trials, are warranted to optimize its therapeutic application in Epi-related cardiac dysfunction.

Blocking Store-Operated Ca2+ Entry to Protect HL-1 Cardiomyocytes from Epirubicin-Induced Cardiotoxicity.

Epirubicin (EPI) is one of the most widely used anthracycline chemotherapy drugs, yet its cardiotoxicity severely limits its clinical application. Altered intracellular Ca2+ homeostasis has been shown to contribute to EPI-induced cell death and hypertrophy in the heart. While store-operated Ca2+ entry (SOCE) has recently been linked with cardiac hypertrophy and heart failure, its role in EPI-induced cardiotoxicity remains unknown. Using a publicly available RNA-seq dataset of human iPSC-derived cardiomyocytes, gene analysis showed that cells treated with 2 µM EPI for 48 h had significantly reduced expression of SOCE machinery genes, e.g., Orai1, Orai3, TRPC3, TRPC4, Stim1, and Stim2. Using HL-1, a cardiomyocyte cell line derived from adult mouse atria, and Fura-2, a ratiometric Ca2+ fluorescent dye, this study confirmed that SOCE was indeed significantly reduced in HL-1 cells treated with EPI for 6 h or longer. However, HL-1 cells presented increased SOCE as well as increased reactive oxygen species (ROS) production at 30 min after EPI treatment. EPI-induced apoptosis was evidenced by disruption of F-actin and increased cleavage of caspase-3 protein. The HL-1 cells that survived to 24 h after EPI treatment demonstrated enlarged cell sizes, up-regulated expression of brain natriuretic peptide (a hypertrophy marker), and increased NFAT4 nuclear translocation. Treatment by BTP2, a known SOCE blocker, decreased the initial EPI-enhanced SOCE, rescued HL-1 cells from EPI-induced apoptosis, and reduced NFAT4 nuclear translocation and hypertrophy. This study suggests that EPI may affect SOCE in two phases: the initial enhancement phase and the following cell compensatory reduction phase. Administration of a SOCE blocker at the initial enhancement phase may protect cardiomyocytes from EPI-induced toxicity and hypertrophy.

Protective effect of propolis from Tigzirt on epirubicin-induced cardiotoxicity and nephrotoxicity

Context: Epirubicin (EPI), belonging to the anthracycline family, is one of the most effective chemo-therapeutic agents used in the treatment of a variety of solid and hematologic malignant tumors but Its anti-tumor efficacy is dose-dependent, but its clinical use is limited by the development of cardiac, hepatic and nephrotic toxicities. Aims: To evaluate the protective effect of ethyl acetate extract of propolis (EAP) native to Tigzirt on selected antioxidant status parameters and biomarkers of epirubicin-induced cardiotoxicity and nephrotoxicity in rats. Methods: Thirty male Wistar albino rats were divided into five groups. It orally dosed with (EAP) or quercetin during 15 days before being subjected to toxicity by injection (i.v) of a cumulative dose of 9 mg/kg of epirubicin to repair cardiac and renal damage. Results: Injection of epirubicin to rats induced cardiac and renal dysfunction as evidenced by a significant increase (P<0.05) in serum levels of biochemical markers (CKmb, BNP, LDH, troponin, urea, creatinine and uric acid). This toxicity thus caused lesions, necrosis, and inflammatory infiltrate in the heart and kidneys. The administration of 250 mg/kg of EAP allowed restoring these functions by lowering the level of these parameters. Thus, a balance of oxidative stress was demonstrated with a decrease of +50% in the level of malondialdehyde and nitric oxide and an increase in superoxide dismutase, catalase and glutathione peroxidase. Therefore, significant restoration was observed on organ architecture. Conclusions: These results show that propolis is rich in phenolic substances, which gave the protective and curative effects against epirubicin-induced cardiotoxicity and nephrotoxicity in Wistar rats.

Use of strain rate imaging for early detection of epirubicin-induced cardiotoxicity in patients with breast cancer.

e12531 Background: Although epirubicin has improved outcome in breast cancer (BC) patients, its application is limited by its cardiotoxicity . Assessment of left ventricular (LV) ejection fraction (EF) is performed to demonstrate cardiac dysfunction. Changes in cardiac function induced by this therapy, however, are difficult to quantitate by conventional echocacardiography. Tissue Doppler myocardial imaging (TDI) derived wall motion velocity, and strain rate (SR) have been shown to sensitively quantify abnormalities in cardiac function. The aim of this study was to determine if sensitive indices of LV dysfunction, would be useful for addressing the early detection of cardiotoxic side effects of epirubicin. Methods: BC patients (N = 45 median age 60.2years) without cardiovascular risk factors were prospectively included. All patients received epirubicin. Twenty patients received further trastuzumab. Conventional and TDI echocardiography were obtained at baseline , every 2cycles of treatment and 3 months after chemotherapy. Segmental peak systolic longitudinal and radial velocity, SR and strain, were measured. Results: at baseline, median LV-EF was > 55 %. There was no overall change in LV dimensions, EF and peak systolic velocity. In contrast, a significant reduction in longitudinal and radial SR and strain was found after 3 cycles (longitudinal strain -10.2% +/- 1.3 % vs baseline 22 +/- 4.1 %, P = .001; radial strain 26.1% +/-4,2% vs baseline 47.3% +/- 9.2 %, P < .001). Changes in radial strain appeared earlier and were more pronounced than longitudinal strain. Conclusions: In this study we confirm the clinical use of TDI parameters for early detection of epirubicin mediated cardiac dysfunction. TDI detected subtle changes of LV function after 3 cycles of therapy. Use of Strain Rate Imaging detects subclinical LV dysfunction and can predict further changes in EF ,therefore can be used to monitor epirubicin-induced cardiotoxicity.

The Predictive Value of 2D Myocardial Strain for Epirubicin-Induced Cardiotoxicity.

Introduction Although epirubicin has significantly improved outcome in breast cancer (BC) patients, it is responsible for myocardial dysfunction that affects patients' quality of life. The use of 2D global longitudinal strain (GLS) has been reported to detect early myocardial dysfunction. The aim of this study was to evaluate how GLS changes can predict cardiotoxicity. Methods We conducted a prospective study from March 2018 to March 2020 on 66 patients with no cardiovascular risk factors, who presented with BC and received epirubicin. We measured left ventricular ejection fraction (LVEF) and GLS before chemotherapy, at three months (T3), and at 12 months (T12) from the last epirubicin infusion. Chemotherapy-Related-Cardiac-Dysfunction (CTRCD) was defined as a decrease of 10% in LVEF to a value below 53% according to ASE and EACI 2014 expert consensus. Results The mean age at diagnosis was 47 ± 9 years old. At baseline, median LVEF was 70% and median GLS was −21%. Shortly after chemotherapy completion, two patients presented with symptomatic heart failure while asymptomatic CTRCD was revealed in three other patients at T12. Three months after the last epirubicin infusion, median LVEF was 65%, median GLS was −19%, and median GLS variation was 5%. However, in patients who presented with subsequent CTRCD, median GLS at T3 was −16% and median GLS variation was 19% (p=0.002 and p < 0.001, respectively, when compared to patients who did not develop cardiotoxicity). Persistent GLS decrease at T3 was an independent predictor of CTRCD at T12. Age and left-sided thoracic irradiation did not increase the risk of cardiotoxicity in our study while the cumulative dose of epirubicin significantly affected cardiologic findings (p=0.001). Conclusion This was the first North African study that assesses the value of measuring GLS to early detect cardiotoxicity. Patients whose GLS remained decreased after 3 months from anthracyclines-base chemotherapy had an increased risk for developing subsequent CTRCD. Further studies with larger sample size are warranted to identify the best cardioprotective molecules to be initiated in these patients before LVEF declines.

1506P The predictive value of 2-D myocardial strain for epirubicin-induced cardiotoxicity

Although epirubicin-based regimens are highly effective in breast cancer care, their cardiotoxicity may be limiting for their prescriptions. The use of left ventricular ejection fraction (LVEF) for screening of epirubicin-induced cardiotoxicity (EIC) may be too late to allow intervention and preventive measures. The aim of our study was to investigate the predictive value of 2D- Global Longitudinal Strain (GLS) to early detect EIC.

197P Epirubicin-induced cardiotoxicity: Use of myocardial strain for early detection of left ventricular dysfunction before LVEF declines

Although epirubicin has improved outcome in breast cancer (BC) patients, it is associated to myocardial dysfunction that affects patients’ quality of life. The use of 2D-myocardial strain echocardiography for Global Longitudinal Strain (GLS) measurment allows to detect early myocardial dysfunction. The aim of this study was to evaluate early changes in GLS and their association with onset of later cardiotoxicity.

Application of a combination of echocardiographic techniques in an experimental model of epirubicin-induced cardiotoxicity.

This study compared the potential ability of multinomial echocardiographic parameters in early detection, prediction and combined diagnosis of antineoplastic-related cardiotoxicity. Male Balb/c mice were repeatedly administered with low doses of epirubicin (6 × 3mg/kg; n = 20) to induce cardiac injury or with placebo as control (n = 10). Conventional and strain parameters as well as myocardial performance index (MPI) were analyzed at baseline, 1day after the second, fourth and sixth cycle, and 12days after completion of chemotherapy (as follow-up) by a high-resolution rodent ultrasound machine. After the experiment, serum cTnI levels were measured, and myocardialinjury was evaluated by histological analyses. Thirteen mice developed cardiotoxicity after epirubicin exposure. Global longitudinal (GLS), radial strain (GRS) and longitudinal strain rate (LSR) were markedly decreased (all P ≤ 0.01) and MPI was increased (P ≤ 0.05) at the completion of treatment compared with baseline values. GLS expressed the best correlations with myocardial pathological injury, especially with collagen content (ρ = -0.68, P < 0.01). Additionally, GLS and MPI were associated with serum cTnI levels. A > 9.5% decrease in GLS from baseline to the fourth cycle of chemotherapy could predict future cardiotoxicity (odds ratio = 0.331, P < 0.05). GLS (cutoff value, -15.16%) combined with MPI (cutoff value, 0.64) could improve the accuracy of diagnosing cardiotoxicity (sensitivity, 92%; specificity, 87%). GLS was the only predictor of cardiotoxicity. GLS combined with MPI may provide a noninvasive and accurate method for the early detection of cardiotoxicity.

Identification of differential gene expression related to epirubicin-induced cardiomyopathy in breast cancer patients.

Epirubicin is a potent chemotherapeutic agent for the treatment of breast cancer. However, it may lead to cardiotoxicity and cardiomyopathy, and no reliable biomarker was available for the early prediction of epirubicin-induced cardiomyopathy. Global gene expression changes of peripheral blood cells were studied using high-throughput RNA sequencing in three pair-matched breast cancer patients (patients who developed symptomatic cardiomyopathy paired with patients who did not) before and after the full session of epirubicin-based chemotherapy. Functional analysis was conducted using gene ontology and pathway enrichment analysis. We identified 13 significantly differentially expressed genes between patients who developed symptomatic epirubicin-induced cardiomyopathy and their paired control who did not. Among them, the upregulated Bcl-associated X protein was related to "apoptosis," while the downregulated 5'-aminolevulinate synthase 2 (ALAS2) was related to both "glycine, serine, and threonine metabolism" and "porphyrin and chlorophyll metabolism" in pathway enrichment analysis. ALAS2 and the metabolic pathways which were involved may play an important role in the development of epirubicin-induced cardiomyopathy. ALAS2 may be useful as an early biomarker for epirubicin-induced cardiotoxicity detection.

Cardioprotective effect of paeonol against epirubicin-induced heart injury via regulating miR-1 and PI3K/AKT pathway

Cardiotoxicity is a dose-dependent side effect of epirubicin that restricts its clinical utility in cancer chemotherapy. Paeonol is an active constituent with various biological activities, including the protection of antineoplastic-induced toxicities. In the present study, we investigated the protective effect of paeonol on epirubicin-induced cardiotoxicity and explored the underlying mechanism. A series of methods were used including a MTT assay, flow cytometry, echocardiography, TUNEL staining, a dual-luciferase reporter assay, immunofluorescence, RT-PCR and Western blotting. The results indicate that paeonol improves cardiac dysfunction, relieves histopathological changes, alleviates inflammation, reduces myocardial apoptosis and increases autophagy. Further studies suggest that paeonol upregulates the decreased expression of miR-1 caused by epirubicin and thus inhibits the activation of PI3K/AKT/mTOR and NF-κB pathways. In conclusion, paeonol effectively ameliorates myocardial injury by increasing miR-1 expression to suppress the PI3K/AKT/mTOR and NF-kB signalling pathways.

Early assessment of the left ventricular function by epirubicin-induced cardiotoxicity in postoperative breast cancer patients.

Epirubicin (Epi) is a potent and effective drug for many malignant cancers with serious cardiotoxicity. Therefore, layer-specific two-dimensional speckle tracking echocardiography (2D-STE) was used to evaluate the longitudinal and circumferential systolic function of the left ventricular for the early detection of cardiotoxicity in this retrospective work. Overall, 130 female patients with postoperative breast cancer who did not receive radiotherapy were classified into three groups: Group A (control group, n=40) without any chemotherapy; Group B (n=44) administered Epi at 180~240mg/m2 ; and Group C (n=46) administered Epi at ≥360mg/m2 . Peak and global systolic longitudinal strains (GLS) in the total and endocardium, mid-myocardium, and epicardium were measured and calculated from apical four-chamber, apical two-chamber, and left ventricular long-axis views, respectively. Peak and global circumferential strains (GCS) in the total and endocardium, mid-myocardium, and epicardium were measured and calculated from mitral annulus, papillary muscle, and apical levels of the short-axis view, respectively. The total GLS and GLS of the endocardium in every view were significantly reduced in group C compared with both groups A and B (P<.05), but there was no significant difference between groups A and B (P>.05). The GLS of the epicardium and mid-myocardium in groups B and C were not significantly reduced (P>.05). There were no significant differences in the total GCS and layer-specific GCS of endocardium, mid-myocardium, and epicardium among the three groups (P>.05). Left ventricular longitudinal systolic dysfunction was detected. Moreover, an impaired endocardium was also detected in an early assessment by layer-specific 2DSTE.

The Early Predictive Value of Right Ventricular Strain in Epirubicin-Induced Cardiotoxicity in Patients with Breast Cancer.

As cancer therapies have improved, patient life spans have been extended but quality of life has been threatened by chemotherapy induced cardiotoxicity. Most cardiac complications remain unobserved until specific symptoms develop. Speckle-tracking echocardiography is a sensitive imaging modality in detecting early occult myocardial dysfunction. A total number of 35 patients newly diagnosed with breast cancer and preparing for epirubicin therapy were prospectively recruited. Echocardiography, including speckle-tracking echocardiography, was performed sequentially at baseline (T1), after the first cycle (T2) and after the third cycle (T3) of epirubicin. At each visit, the severity of dyspnea was evaluated by the assessment scale. Compared with the baseline, right ventricular longitudinal strain (RVLS_FW) at T2 significantly declined (-22.49 ± 4.97 vs. -18.48 ± 4.46, p = 0.001), which was also positively associated with the development of dyspnea (R2 = 0.8, p = 0.01). At T3, both the left ventricular global longitudinal strain and RVLS_FW were significantly impaired (-21.4 ± 4.12 vs. -16.94 ± 6.81%; -22.49 ± 4.97 vs. -16.86 ± 7.27%, p = 0.01; 0.001, respectively). Also, the accumulating dose of epirubicin positively correlated with the development of dyspnea (R2 = 0.38, p = 0.04) and the decline of RVLS_FW (R2 = 0.53, p = 0.02). Notably, compared with the other echocardiographic parameters only RVLS_FW at the early stage (T2) significantly correlated with the development of dyspnea (odds ratio: 1.84, 95% confidence interval: 1.22-2.78, p = 0.04). RVLS_FW sensitively predicts dyspnea development in breast cancer patients receiving epirubicin therapy. However, larger scale studies are required to validate its role in long-term patient survival.

Xinmailong mitigated epirubicin-induced cardiotoxicity via inhibiting autophagy

Ethnopharmacological relevanceUsing insects, such as the cockroach, for the treatment of disease has a long history in traditional Chinese medicine. Xinmailong (XML) Injection, a bioactive composite extracted from Periplaneta americana (a species of cockroach), shows reasonable protective effects against cardiovascular injury and was approved for the use in the treatment of cardiac dysfunction in 2006, yet its cardio protective mechanisms remain unclear. AimThe present study aims to examine the protective effects of XML against epirubicin-induced cardiotoxicity in vivo and determine its underlying mechanisms. Materials and methodsThe chemical characteristics of XML were identified using high performance liquid chromatography (HPLC). Rats were intraperitoneally injected with epirubicin and then treated with XML for 14 days. Survival rate, echocardiography, electrocardiographic recordings and Masson staining were used to evaluate the cardioprotective activity of XML. Western blot and quantitative real time reverse transcriptase polymerase chain reaction (RT-PCR) analyses were used to investigate the molecular mechanisms underlying the actions of XML. ResultsXML treatment significantly enhanced the survival rate of rats from epirubicin-induced heart failure. XML prevented left ventricle dilatation, improved cardiac function. Furthermore, treatment with XML also significantly inhibited the accumulation of collagen, reduced the levels of mRNA for matrix metalloproteinases-9 (Mmp9) and transforming growth factor-β 1(Tgfb1). This action of XML therefore might be responsible, at least in part, for the attenuation of cardiac fibrotic remodeling. XML inhibited autophagy as evidenced by the decreased accumulation of Beclin1 and autophagy related 7 (Atg7), which are necessary to form autophagosome structures. Protein kinase B (PKB/Akt), phosphatidylinositol 3 kinase (PI3K) and B cell lymphoma2 (Bcl2) levels were up-regulated, while significantly decreased protein levels for phosphorylated P38 and extracellular regulated protein kinases 1/2 (Erk1/2) were observed in the XML treated rats. The autophagy related results suggested that the increase in PI3K/Akt levels and inhibition of the phosphorylation of P38 MAPK and Erk1/2 contributed to the anti-autophagic activity of XML. ConclusionsOur data suggest that XML may be effective for mitigating epirubicin-induced cardiomyopathy and inhibits autophagy via activating the PI3K/Akt signaling pathway and inhibiting the Erk1/2 and P38 MAPK signaling pathways.

Alleviating Damage from Epirubicin-Induced Cardiotoxicity with an Increased Dosage of Cardioprotective Magnesium

Alleviating Damage from Epirubicin-Induced Cardiotoxicity with an Increased Dosage of Cardioprotective Magnesium

Enhanced antitumor activity and attenuated cardiotoxicity of Epirubicin combined with Paeonol against breast cancer.

Epirubicin is widely used for the therapy of various breast cancers. However, it has serious adverse side effects, particularly cardiotoxicity, which can cause irreversible damage in patients. Paeonol, an active component from Moutan Cortex, enhances antitumor activity of antineoplastics and reduces toxicities induced by chemotherapeutics. In this study, we investigated the anticancer activity of Paeonol in combination with Epirubicin against breast cancer and the alleviated effect of Paeonol on cardiotoxicity induced by Epirubicin. The apoptosis results and the coefficient of drug interaction values suggested significantly synergistic in combination of Paeonol and Epirubicin to 4T1 and MCF-7 cells. We further examined antitumor activities of Paeonol or/and Epirubicin in vivo in BALB/c mice and found that co-treatment of Paeonol and Epirubicin had a synergistic inhibitory effect on tumor growth and enhanced apoptosis in tumors in vivo compared with Epirubicin alone. Increased apoptosis was associated with the activation of apoptosis-related proteins including PARP, Bax, caspase 3, and inhibition of p38/JNK/ERK MAPKs. Moreover, Paeonol exhibited a mitigative effect on Epirubicin-induced cardiotoxicity through suppressing NF-kB pathway. In conclusion, Paeonol (a) enhanced the antitumor activity of Epirubicin in a synergistic manner against breast cancer cells via inhibiting p38/JNK/ERK MAPKs and (b) alleviated Epirubicin-induced cardiotoxicity by suppressing NF-kB pathway. These findings suggest that combination of Paeonol and Epirubicin is potentially applicable for breast cancer treatment.

Clinical Application of the Heart Rate Deceleration Capacity Test to Predict Epirubicin-induced Cardiotoxicity.

Objective:To investigate the clinical value of heart rate deceleration capacity (DC) in predicting the risk of epirubicin-induced cardiotoxicity.Methods:The CK-MB and cTnI levels and DC values of 86 patients were examined before chemotherapy and again after 2 and 4 cycles of chemotherapy. Patients were divided into low-risk group (LRG) (40 cases), medium-risk group (26 cases), and high-risk group (HRG) (20 cases) based on the calculated DC values.Results:After 4 cycles of chemotherapy, HRG showed a significantly greater increase in serum CK-MB (17.1 ± 4.9 vs. 14.6 ± 3.7) and cTnI (1.28 ± 0.38 vs. 1.0 ± 0.29) concentrations over the prechemotherapy levels when compared with LRG. After 2 and 4 cycles of chemotherapy, HRG exhibited a significantly greater increase in mean heart rate (2 cycles: 79.6 ± 6.0 vs. 77.6 ± 6.7; 4 cycles: 88.2 ± 10.2 vs. 82.4 ± 6.2) and the supraventricular (2 cycles: 68.9 ± 19.3 vs. 57.2 ± 17.6; 4 cycles: 131.1 ± 29.5 vs. 91.7 ± 16.5) and ventricular arrhythmia counts (2 cycles: 179.0 ± 20.5 vs. 162.3 ± 16.3; 4 cycles: 228.6 ± 44.8 vs. 187.4 ± 22.6) over the prechemotherapy values compared with LRG. When the supraventricular and ventricular arrhythmia counts measured after 4 cycles of chemotherapy were compared with those obtained before chemotherapy, HRG (131.1 ± 29.5 and 228.6 ± 44.8, respectively) showed the largest differences, followed by medium-risk group (107.4 ± 31.9 and 202.0 ± 29.8, respectively) and then LRG (91.7 ± 16.5 and 187.4 ± 22.6, respectively) (P < 0.01). After 4 cycles of chemotherapy, the incidence rates of ventricular arrhythmia greater than Lown's grade 3 (30% vs. 2.5%), QTc (20% vs. 0) elongation, and ST-T (40% vs. 5%) changes in HRG were significantly higher than those observed in LRG (P < 0.05).Conclusions:DC test was shown to be an effective predictor of the risk of epirubicin-induced cardiotoxicity.

Early Detection of Epirubicin-Induced Cardiotoxicity in Patients with Breast Cancer

Epirubicin is a cytotoxic drug, widely used in patients with breast cancer, but its application is limited by its cardiotoxicity. Assessment of left ventricular (LV) ejection fraction (EF) is performed to demonstrate cardiac dysfunction. Because normal EF can mask LV impairment, the aim of this study was to evaluate whether deformation and rotation assessed using speckle-tracking echocardiography represent better markers of early epirubicin-induced cardiotoxicity. Forty women with breast cancer (mean age, 51 ± 8 years), scheduled to be treated with epirubicin-based chemotherapy, were prospectively enrolled. All patients underwent conventional echocardiography, tissue velocity imaging, and speckle-tracking echocardiography to evaluate LV geometry and EF, S', deformation (longitudinal, circumferential, and radial strain and strain rate), and rotation. Patients were reevaluated after the third and sixth cycles of epirubicin (mean cumulative dose, 268 ± 22 g/m(2)). After the sixth cycle of treatment, 14 patients (35%) had developed epirubicin-induced cardiotoxicity (a decrease in EF of ≥10% to an EF of <55%; group I), and 26 patients (65%) did not fulfill the criteria for cardiotoxicity (group II). In the entire study population, after the third cycle of epirubicin, there were reductions in diastolic and longitudinal function, but patients in group I had significantly lower S', longitudinal strain, and longitudinal strain rate than those in group II. Although after the third cycle of treatment, radial and circumferential deformation and rotation remained unchanged, these parameters showed significant reductions after the sixth cycle of epirubicin. A decrease in longitudinal strain after the third cycle of epirubicin was the best independent and accurate predictor of cardiotoxicity after the completion of treatment. Assessment of myocardial longitudinal deformation detects subclinical LV dysfunction and can predict further changes in EF and therefore can be used to monitor epirubicin-induced cardiotoxicity.

EARLY DETECTION OF SUBCLINICAL EPIRUBICIN-INDUCED CARDIOTOXICITY USING TWO-DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY

ObjectivesTo assess the early subclinical epirubicin-induced cardiotoxicity during treatment of non-Hodgkin's lymphoma using two-dimensional (2D) speckle tracking echocardiography (STE).MethodsThirty-six patients (15 male/21 female) aged 56.88±9.76 with non-Hodgkin's lymphoma were included....

Protective Effects of Salidroside on Epirubicin-Induced Early Left Ventricular Regional Systolic Dysfunction in Patients with Breast Cancer

BackgroundSalidroside [2-(4-hydroxyphenyl)ethyl-β-D-glucopyranoside], one of the most potent ingredients extracted from the plant Rhodiola rosea L., has been shown to have a cardiovascular protective effect as an antioxidant, and early treatment of epirubicin-induced cardiotoxicity has been the focus of clinical chemotherapy in patients with breast cancer. However, the cardioprotective effects of salidroside on epirubicin-induced cardiotoxicity, especially early left ventricular regional systolic dysfunction, have to date been sparsely investigated.ObjectiveThe aim of this study was to investigate the protective effects of salidroside in preventing early left ventricular regional systolic dysfunction induced by epirubicin.MethodsSixty patients with histologically confirmed breast cancer were enrolled. Eligible patients were randomized to receive salidroside (600 mg/day; n= 30) or placebo (n = 30) starting 1 week before chemotherapy. Patients were investigated by means of echocardiography and strain rate (SR) imaging. We also measured plasma concentrations of reactive oxygen species (ROS). All parameters were assessed at baseline and 7 days after each new epirubicin dose of 100 mg/m2.ResultsA decline of the SR peak was observed at an epirubicin dose of 200 mg/m2, with no significant differences between salidroside and placebo (1.35 ± 0.36 vs 1.42 ± 0.49/second). At growing cumulative doses of epirubicin, the SR normalized only with salidroside, showing a significant difference in comparison with placebo at epirubicin doses of 300 mg/m2 (1.67 ± 0.43 vs 1.32 ± 0.53/second, p< 0.05) and 400 mg/m2 (1.68±0.29 vs 1.40 ± 0.23/second, p < 0.05). Moreover, a significant increase in plasma concentrations of ROS was found with placebo, but they remained unchanged with salidroside.ConclusionSalidroside can provide a protective effect on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.

Protective Effects of Salidroside on Epirubicin-Induced Early Left Ventricular Regional Systolic Dysfunction in Patients with Breast Cancer

BackgroundSalidroside [2-(4-hydroxyphenyl)ethyl-β-D-glucopyranoside], one of the most potent ingredients extracted from the plant Rhodiola rosea L., has been shown to have a cardiovascular protective effect as an antioxidant, and early treatment of epirubicin-induced cardiotoxicity has been the focus of clinical chemotherapy in patients with breast cancer. However, the cardioprotective effects of salidroside on epirubicin-induced cardiotoxicity, especially early left ventricular regional systolic dysfunction, have to date been sparsely investigated.ObjectiveThe aim of this study was to investigate the protective effects of salidroside in preventing early left ventricular regional systolic dysfunction induced by epirubicin.MethodsSixty patients with histologically confirmed breast cancer were enrolled. Eligible patients were randomized to receive salidroside (600 mg/day; n= 30) or placebo (n = 30) starting 1 week before chemotherapy. Patients were investigated by means of echocardiography and strain rate (SR) imaging. We also measured plasma concentrations of reactive oxygen species (ROS). All parameters were assessed at baseline and 7 days after each new epirubicin dose of 100 mg/m2.ResultsA decline of the SR peak was observed at an epirubicin dose of 200 mg/m2, with no significant differences between salidroside and placebo (1.35 ± 0.36 vs 1.42 ± 0.49/second). At growing cumulative doses of epirubicin, the SR normalized only with salidroside, showing a significant difference in comparison with placebo at epirubicin doses of 300 mg/m2 (1.67 ± 0.43 vs 1.32 ± 0.53/second, p< 0.05) and 400 mg/m2 (1.68±0.29 vs 1.40 ± 0.23/second, p < 0.05). Moreover, a significant increase in plasma concentrations of ROS was found with placebo, but they remained unchanged with salidroside.ConclusionSalidroside can provide a protective effect on epirubicin-induced early left ventricular regional systolic dysfunction in patients with breast cancer.