Anthracycline Cardiotoxicity In Patients Research Articles

Echocardiographic indicators of anthracycline cardiotoxicity in breast cancer patients with normal left ventricular ejection fraction: Experience of the first cardio-oncology unit in Morocco

Anthracycline is a mainstay in the treatment of many cancers, especially breast cancer. Anthracyclines are known for their significant cardiotoxic potential. Although the cardiotoxicity induced by anthracyclines is dose-dependent and often irreversible, it can occur very early at the start of treatment and sometimes even very late after several years from the end of treatment. The aim of this study was to assess whether echocardiographic measurements of LV function, in the case of normal LVEF, predict the development of anthracycline cardiotoxicity in patients followed for breast cancer. We conducted a longitudinal study of 2329 cancer patients including 2284 female breast cancer survivors, recruited from the cardio-oncology unit in Casablanca, who were diagnosed with primary invasive breast cancer between January 2017 and April 2022. All patients underwent pre-, per- and post-chemotherapy echocardiography. LV volumes, LVEF, MAPSE, S’LV, maximum longitudinal strain were measured. Of 2284 patients, 64% had normal resting LVEF. Mean LVEF was 56 ± 5%, global longitudinal strain (GLS) was −17.4 ± 2.2%, and LV end diastolic volume (LVEDV) was 108 ± 17 mL, MAPSE was 17 ± 5 mm and S’VG was 9+/4 cm/s. 12% percent presented with cardiotoxicity: heart failure with alteration of LVEF by more than 15% (CI) in 163 patients, 67% of whom had an altered S’LV < 8 cm/s) and an altered SGL (>−18%), arterial hypertension in 58 patients, 17 cases of pericardial effusions, 15 cases of arrhythmias, 6 cases of 3rd degree atrioventricular block and 3 cases of right ventricular dysfunction. Age, diabetes, obesity, GLS and LVEDV were all predictive of MACE (P = 0.028, 0.017, 0.041, 0.038 and 0.014 respectively). In patients treated with anthracyclines with normal pre-chemotherapy LVEF, longitudinal function (MAPSE AND S’LV) and baseline GLS predict the development of cardiotoxicity. This helps us to develop algorithms for close monitoring in this type of patient.

Myocardial extracellular volume derived from contrast-enhanced chest computed tomography for longitudinal evaluation of cardiotoxicity in patients with breast cancer treated with anthracyclines

ObjectivesTo assess the value of myocardial extracellular volume (ECV) derived from contrast-enhanced chest computed tomography (CT) for longitudinal evaluation of cardiotoxicity in patients with breast cancer (BC) treated with anthracycline (AC).Materials and methodsA total of 1151 patients with BC treated with anthracyclines, who underwent at least baseline, and first follow-up contrast-enhanced chest CT were evaluated. ECV and left ventricular ejection fraction (LVEF) were measured before (ECV0, LVEF0), during ((ECV1, LVEF1) and (ECV2, LVEF2)), and after (ECV3, LVEF3) AC treatment. ECV values were evaluated at the middle of left ventricular septum on venous phase images. Cancer therapy-related cardiac dysfunction (CTRCD) was recorded.ResultsMean baseline LVEF values were 65.85% ± 2.72% and 102 patients developed CTRCD. The mean ECV0 was 26.76% ± 3.03% (N0 = 1151). ECV1, ECV2, and ECV3 (median interval: 61 (IQR, 46–75), 180 (IQR, 170–190), 350 (IQR, 341–360) days from baseline) were 31.32% ± 3.10%, 29.60% ± 3.24%, and 32.05% ± 3.58% (N1 = 1151, N2 = 841, N3 = 511). ECV1, ECV2, and ECV3 were significantly higher than ECV0 (p < 0.001). ECV0 and ECV1 showed no difference between CTRCD (+) and CTRCD (−) group (p1 = 0.150; p2 = 0.216). However, ECV2 and ECV3 showed significant differences between the two groups (p3 < 0.001; p4 < 0.001).ConclusionCT-derived ECV is a potential biomarker for dynamic monitoring AC cardiotoxicity in patients with BC.

Sarcopenia and anthracycline cardiotoxicity in patients with cancer

BackgroundSeveral studies have suggested that sarcopenia is associated with an increased treatment toxicity in patients with cancer. The aim of this study is to evaluate the relationship between sarcopenia and...

Bioinformatic analysis of peripheral blood miRNA of breast cancer patients in relation with anthracycline cardiotoxicity

BackgroundThe current diagnostic methods and treatments still fail to lower the incidence of anthracycline-induced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy.MethodsCardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the Gene Expression Omnibus (GEO) database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the micro RNAs (miRNAs) regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the Gene Ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy.ResultThe data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and Target Scan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain seven cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273 g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. The signaling pathway is mainly concentrated in TGF-β signaling pathway and adhesion signaling pathway.ConclusionsChanges in expression of hsa-miR-4638-3p and hsa-miR-1273 g-3p may contribute to the detection of anthracyclines induced cardiac toxicity, and their potential function may be related to TGF-β signaling pathway and adhesion signaling pathway.

Changes in Citric Acid Cycle and Nucleoside Metabolism Are Associated with Anthracycline Cardiotoxicity in Patients with Breast Cancer.

Anthracyclines and HER2-targeted antibodies are very effective for the treatment of breast cancer, but their use is limited by cardiotoxicity. In this nested case-control study, we assessed the role of intermediary metabolism in 38 women with breast cancer treated with anthracyclines and trastuzumab. Using targeted mass spectrometry to measure 71 metabolites in the plasma, we identified changes in citric acid and aconitic acid that differentiated patients who developed cardiotoxicity from those who did not. In patients with cardiotoxicity, the magnitude of change in citric acid at threemonths correlated with the change in left ventricular ejection fraction (LVEF) and absolute LVEF at ninemonths. Patients with cardiotoxicity also demonstrated more pronounced changes in purine and pyrimidine metabolism. Early metabolic changes may therefore provide insight into the mechanisms associated with the development of chemotherapy-associated cardiotoxicity.

Speckle tracking echocardiography predicts early subclinical anthracycline cardiotoxicity in patients with breast cancer.

This study aimed to assess the early changes of left ventricular (LV) and right ventricular (RV) mechanics associated with anthracycline treatment for breast cancer and to determine whether two-dimensional speckle tracking echocardiography (2D-STE) analysis could predict chemotherapy-induced cardiotoxicity. Anthracycline generates progressive LV dysfunction associated with a poor prognosis. Early detection of minor change of myocardial mechanics is thus important. Pretreatment (T0), first (T1), and second (T2) on-treatment echocardiograms were available for analysis with 2D-STE. All patients had normal pretreatment left ventricular ejection fraction (LVEF). Cardiotoxicity was defined as a drop in LVEF to ≤53% or an absolute decrease of 10% on a follow-up echocardiogram. Analysis of variance receiver operating curve and area under the curve (AUC) analysis was performed. Eighty-six patients with breast cancer who received anthracycline treatment were included. Compared with T0, LV and RV global longitudinal strain (GLS), and LV global circumferential strain (GCS) at T1 and T2 were reduced significantly (p < 0.005 for all). There was a significant decrease in the LV GLS with increasing age at both T1 and T2 (p < 0.05 for all). GLS at T1 (AUC 0.83; cutoff -14.06; sensitivity 83%; specificity 84%; p = 0.0033) and at T2 (AUC 0.90; cutoff -13.84; sensitivity 93%; specificity 84%; p < 0.0001) was the strongest indicator of subsequent cardiotoxicity. Anthracycline treatment induces early deterioration of LV global longitudinal and circumferential strain, involving also the RV. Early change in the GLS seems to be a good predictor of the development of chemotherapy-induced cardiotoxicity. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:222-230, 2017.

Anthracycline induced cardiac toxicity in pediatric Ewing sarcoma: A longitudinal study

Reports on incidence and factors associated with anthracycline cardiotoxicity in patients with Ewing sarcoma vary and few studies evaluate effect over time. Longitudinal trends in cardiac function and prognostic value of % decline in ejection fraction (EF) during therapy have not been previously described in Ewing sarcoma. A retrospective review of patients age <17 years, diagnosed with Ewing sarcoma during 1978-2006, treated at British Columbia Children's Hospital with anthracycline chemotherapy was undertaken. Echocardiograms performed pre-treatment, worst function during treatment, on therapy completion; worst function during surveillance and the most recent echocardiogram were reviewed. Cardiac toxicity was graded using Common Terminology Criteria for Adverse Events v 3.0 and 4.0. Among 71 eligible patients, median age at diagnosis 11.1 years, median cumulative dose of anthracycline was 365 mg/m2 . There were 397 echocardiograms with 153 (39%) abnormal. There were 21/71 patients with EF < 50%, 11 with EF < 40% and five cardiac deaths including 2/3 patients post-cardiac transplant. The median time to worst cardiac function was 51 months. Post-therapy completion 16/71 patients with progressive decline in cardiac function were noted. No patient with 10-15% decline in EF during therapy developed cardiotoxicity. Younger age (P = 0.004) and low BMI (P = 0.034) as continuous variables with anthracycline administration by IV push (P = 0.03) were risk factors for cardiotoxicity on univariate analysis but not significant within logistic regression models. The high incidence of cardiotoxicity associated with higher administered anthracycline dose, young age, bolus infusion, and EF decline warrants evaluation in a larger cohort.

Subclinical Anthracycline Cardiotoxicity in Patients With Acute Promyelocytic Leukemia in Long‐Term Remission After the AIDA Protocol

Anthracycline chemotherapy remains a critical component of cancer treatment despite its established risk of cardiotoxicity. To investigate whether the AIDA protocol, which combines idarubicin, mitoxantrone, and all-trans retinoic acid (ATRA) for treatment of acute promyelocytic leukemia (APL) results in late cardiotoxicity, 34 APL patients in long-term remission were evaluated. The cumulative dose of idarubicin and mitoxantrone were 80 mg/m(2) and 50 mg/m(2), respectively. Median follow-up was 7 years. Segmental wall motion abnormalities (SWMAs) were detected in 11 AIDA patients who still presented with an ejection fraction (EF) within normal limits (EF 56% in the AIDA group vs 59% in the control group, P=.01). However, parameters of diastolic dysfunction were significantly impaired in the AIDA group (E/A ratio: 1.04 in the AIDA group vs 1.28 in the control group, P=.001; E/E' lateral ratio: 10.04 in the AIDA group vs 5.79 in the control group, P≤.001) as well as left atrial volume (52 mL in the AIDA group vs 35 mL in the control group, P<.001). Cardiac toxicity due to anthracycline therapy is often frequent. Changes in diastolic function are helpful in the detection of subclinical anthracycline cardiotoxicity in long-term cardiac follow-up despite a preserved systolic ventricular function.

Doxorubicin cardiac toxicity manifesting seven years after treatment. Case report and review

This report describes a patient treated for lymphoma who had development of doxorubicin (Adriamycin) cardiotoxicity proved by endomyocardial biopsy seven years after treatment. Doxorubicin cardiotoxicity is reviewed with emphasis on the implications of the long latency period for anthracycline cardiotoxicity in patients treated with this widely used antineoplastic agent.