Received Anthracycline Therapy Research Articles

SGLT2 Inhibitors, Malnutrition, Cachexia, and Survival in Heart Failure Patients with a History of Anthracycline Treatment.

Patients undergoing anthracycline-based cancer treatments have an increased risk of heart failure (HF) and adverse metabolic outcomes such as malnutrition and cachexia. This retrospective study explored the impact of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on these outcomes in HF patients previously treated with anthracyclines. Using the TriNetx research network, we identified 1,545 patients with a history of SGLT2i use and 17,681 without. We then performed 1:1 propensity score matching resulting in 1,323 patients within each cohort. Patients were analyzed over a 5-year period. SGLT2i use was associated with significantly reduced risks of cachexia (HR 0.453, 95% CI [0.286-0.718]), malnutrition (HR 0.702, 95% CI [0.547-0.900]), adult failure to thrive (HR 0.489, 95% CI [0.345-0.693]), and all-cause mortality (HR 0.490, 95% CI [0.423-0.568]). These findings call for additional research to determine whether SGLT2i may indeed improve nutritional status and survival in patients receiving anthracycline therapy.

Effect on cardiovascular outcome of sodium-glucose co-transporter-2 (SGLT2) inhibitors among patients with cancer treated with anthracycline: A systematic review and meta-analysis.

e24001 Background: Sodium-glucose-co-transporter-2 (SGLT2) inhibitors have shown benefit in reducing cardiovascular outcomes in diabetes patients. Anthracycline therapy is associated with a risk of cardiomyopathy. However, the impact of SGLT2 inhibitors in the prevention of cardiomyopathy and heart failure in cancer patients undergoing anthracycline treatment remains unclear. Thus, we conducted a systematic review and meta-analysis to explore the effect of the prevention of cardiovascular outcomes in patients with cancer and diabetes who had received anthracycline therapy. Methods: We systematically reviewed Medline and EMBASE databases from inception to January 2024 for studies focusing on cancer patients with a history of anthracycline therapy. Eligible studies had to report relative risk (RR) with 95% confidence intervals for the clinical endpoints of mortality outcomes and the risk of HF exacerbation, comparing cohorts with and without SGLT2 inhibitor use. Results: Our study included 4 retrospective cohort studies in the meta-analysis (n = 6,708, 24% received SGLT2). There was significantly lower all-cause mortality in the SGLT2 inhibitors group (pooled RR of 0.52, 95% CI 0.35-0.77, I2 64%). However, there were no differences in the risk of heart failure exacerbation (pooled RR of 0.67, 95% CI 0.39-1.14, I2 17%). Conclusions: Our study found that anthracycline-treated cancer patients using SGLT2 inhibitors experienced lower all-cause mortality compared to the control group. A randomized clinical trial is necessary to further elucidate these findings.

Cardioprotective Potential of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Cancer Treated With Anthracyclines: An Observational Study

Anthracyclines are pivotal in cancer treatment, yet their clinical utility is hindered by the risk of cardiotoxicity. Preclinical studies highlight the effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in mitigating anthracycline-induced cardiotoxicity. Nonetheless, the translation of these findings to clinical practice remains uncertain. This study aims to evaluate the safety and potential of SGLT2i for preventing cardiotoxicity in patients with cancer, without preexisting heart failure (HF), receiving anthracyclines therapy. Using the TriNetX Global Research Network, patients with cancer, without previous HF diagnosis, receiving anthracycline therapy were identified and classified into 2 groups based on SGLT2i usage. A 1:1 propensity score matching was used to control for baseline characteristics between the 2 groups. Patients were followed for 2 years. The primary end point was new-onset HF, and the secondary end points were HF exacerbation, new-onset arrhythmia, myocardial infarction, all-cause mortality, and all-cause hospitalization. Safety outcomes included acute renal failure and creatinine levels. A total of 79,074 patients were identified, and 1,412 were included post-matching (706 in each group). They comprised 53% females, 62% White, with a mean age of 62.5 ± 11.4 years. Over the 2-year follow-up period, patients on SGLT2i had lower rates of new-onset HF (hazard ratio 0.147, 95% confidence interval 0.073 to 0.294) and arrhythmia (hazard ratio 0.397, 95% confidence interval 0.227 to 0.692) compared with those not on SGLT2i. The incidence of all-cause mortality, myocardial infarction, all-cause hospitalization, and safety outcomes were similar between both groups. In conclusion, among patients with cancer receiving anthracycline therapy without preexisting HF, SGLT2i use demonstrates both safety and effectiveness in reducing anthracycline-induced cardiotoxicity, with a decreased incidence of new-onset HF, HF exacerbation, and arrhythmias.

Biomarkers and Strain Echocardiography for the Detection of Subclinical Cardiotoxicity in Breast Cancer Patients Receiving Anthracyclines.

The optimal surveillance and management strategies for breast cancer patients receiving anthracycline therapy are limited by our incomplete understanding of the role of biomarkers heralding the onset of cardiotoxicity. The purpose of this study was to determine whether there is a temporal correlation between cardiac biomarkers and subclinical left ventricular dysfunction in breast cancer patients receiving anthracycline chemotherapy. Thirty-one females between 46 and 55 years old with breast cancer treated with anthracycline chemotherapy were prospectively enrolled. Cardiac biomarkers were correlated with echocardiography with speckle tracking at baseline, post-anthracycline therapy, and 6 months post-anthracycline chemotherapy. Subclinical cardiotoxicity was defined as ≥ 10% reduction in global longitudinal strain (GLS). There was a relative reduction in left ventricular ejection fraction (LVEF) ≥ 10% in 5/30 (17%) and 7/27 (26%) patients post-anthracycline therapy and 6 months post-anthracycline therapy, respectively. Subclinical cardiotoxicity was noted in 8/30 (27%) and 10/26 (38%) patients post-anthracycline and 6 months post-anthracycline therapy, respectively. Baseline N-terminal pro B-type natriuretic peptide (NT-proBNP) was the strongest predictor of LVEF (ρ = -0.45; p = 0.019), with post-therapy NT-proBNP values illustrating similar predictive value (ρ = -0.40; p = 0.038). Interim changes in suppression of tumorigenicity 2 (ST2) and galectin-3 correlated with a 6-month change in LVEF (ρ = -0.48; p = 0.012 and ρ = -0.45; p = 0.018, for ST2 and galectin-3, respectively). Changes in galectin-3 from baseline to mid-therapy paralleled changes in GLS. NT-proBNP, ST2, and galectin-3 correlate with reduced LVEF among breast cancer patients receiving anthracycline therapy. Additional trials focusing on a cardiac biomarker approach may provide guidance in the early diagnosis and management of anthracycline-induced cardiotoxicity.

Abstract 15808: Sodium Glucose Co-Transporter-2 Inhibitors and Clinical Outcomes in Cancer Patients Treated With Anthracyclines

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been proven to improve clinical outcomes in heart failure (HF). However, there remains a paucity of data on the potential cardioprotective impact of SGLT2i in cancer patients receiving anthracyclines. Aim: To evaluate if SGLT2i use is associated with improved outcomes in anthracycline-treated cancer patients. Methods: Using TriNetX Global Research Network from 2013 to 2021, patients diagnosed with cancer and receiving anthracycline therapy were identified and categorized into those who were taking SGLT2i versus those who were not. A 1:1 propensity score matching was used to control for baseline characteristics between the two groups. Patients were followed for 2 years. The primary endpoint was all-cause mortality and secondary endpoints were new-onset HF, acute HF exacerbation, myocardial infarction, new-onset atrial fibrillation/flutter, and all-cause hospitalization. Results: A total of 82,369 anthracycline-treated cancer patients were identified. After propensity score matching application, 1,412 patients were included in our analysis (706 patients in each group). Patients on SGLT2i had lower rates of all-cause mortality (OR: 0.7 [95% CI: 0.56, 0.88]; P=0.002), acute HF exacerbation (OR: 0.64 [95% CI: 0.41-1]; P=0.048), and new-onset atrial fibrillation/flutter (OR: 0.52 [95% CI: 0.33, 0.8]; P=0.003) compared to those not on SGLT2i. The incidence of myocardial infarction, new-onset HF, and all-cause hospitalization were similar between the two groups (Figure). Conclusion: Among cancer patients receiving anthracyclines, SGLT2i were associated with lower rates of mortality, acute HF exacerbations, and new-onset atrial fibrillation/flutter and similar rates of myocardial infarction, new-onset HF, and hospitalization.

Influencing factors of anthracycline-induced subclinical cardiotoxicity in acute leukemia patients

BackgroundCurrent treatment of acute leukemia is based on anthracycline chemotherapy. Anthracyclines, despite improving patient survival, have serious cardiotoxicity and therefore cardiac monitoring should be a priority. The purpose of this study is to explore the possible early predictors of anthracycline-induced subclinical cardiotoxicity(AISC)in acute leukemia patients.MethodsWe conducted a prospective observational study involving 51 patients with acute leukemia treated with anthracycline. Demographic data, clinical variables, echocardiography variables and biochemical variables were collected at baseline and after 3 cycles of chemotherapy. Patients were divided into the AISC and No-AISC groups according to changes of global longitudinal peak systolic strain. Regression models and receiver operating characteristic curve analysis were used to explore the relationship between the variables and AISC.Result17 of the patients suffered subclinical cardiotoxicity after 3 cycles of anthracycline treatment. Multiple logistic regression analysis showed a significant association of DBil (OR 0.612, 95% CI 0.409–0.916, p = 0.017), TBil (OR 0.841, 95% CI 0.717–0.986, p = 0.033), PLT (OR 1.012, 95% CI 1.002–1.021, p = 0.016) and Glu (OR 1.873, 95% CI 1.009–3.475, p = 0.047) with the development of AISC. After 3 cycles of chemotherapy, there was a significant difference in PLT between the AISC and NO-AISC groups. Moreover, the dynamic changes in PLT from baseline to after 3 cycles of chemotherapy were each statistically significant in the AISC and NO-AISC groups. The combination of PLT and N-terminal pro–B-type natriuretic peptide (NT-proBNP) had the highest area under curves (AUC) for the diagnosis of AISC than PLT and NT-proBNP alone (AUC = 0.713, 95%CI: 0.56–0.87, P = 0.017).ConclusionTotal bilirubin (TBil), direct bilirubin (DBil), platelets (PLT) and blood glucose (Glu) are independent influencing factors for AISC in acute leukemia patients receiving anthracycline therapy. Bilirubin may be a protective factor and PLT may be a contributing factor for AISC. The combination of baseline PLT and baseline NT-proBNP shows satisfactory predictive ability for AISC in acute leukemia cases treated with 3 cycles of chemotherapy.

Abstract P5-08-17: Monitoring for cardiotoxicity in early breast cancer: an Australian experience

Abstract Background Breast cancer is the most commonly diagnosed cancer in Australia. Patient outcomes continue to improve with current 10 year survival of 86%. Given this, greater focus is needed to minimise potential long term toxicities of prescribed therapies. Anthracyclines and HER2 targeted therapies are commonly prescribed agents for high risk early breast cancers and are associated with acute and long term cardiotoxicity. Despite this, screening of cardiotoxicity in Australian patients receiving these therapies remains variable due to a lack of endorsed national screening guidelines. We conducted a retrospective review of screening procedures for cardiotoxicity in 2 major oncology centres in metropolitan Sydney and compared the findings to current international recommendations from ASCO/ESMO guidelines. Methods Patients were included if they received doxorubicin, epirubicin or trastuzumab with neoadjuvant or adjuvant intent during 2021. Baseline patient and tumour characteristics including cardiovascular risk factors were reviewed. Baseline ECG, transthoracic echocardiogram (TTE) or cardiac biomarkers (cardiac troponin or brain natriuretic peptide) were recorded, as well as frequency of serial monitoring and incidence of cardiotoxicity and cardiology referrals. Results 111 patients receiving initial curative therapy were included of which 45 received anthracycline therapy without trastuzumab. 66 received trastuzumab of which 34 also received anthracycline. 38 patients were aged greater than 60 and 31 had 2 or more cardiovascular risk factors. Of the patients receiving anthracycline only, 96% had a baseline TTE. All patients receiving trastuzumab only had a baseline TTE and of the 34 patients who received anthracycline and trastuzumab 3 did not undergo baseline TTE but underwent one prior to commencing trastuzumab. 3 patients total had a baseline ECG. No patients had baseline biomarkers measured. Only 5 patients had biomarkers measured at 1 year and all 5 had developed grade 1 heart failure on treatment. These 5 patients were referred for cardiology review and 2 required an interruption of trastuzumab. All patients receiving trastuzumab underwent 3 monthly TTEs on treatment. Of the 35 patients now more than 1 year post treatment completion, only 3 patients had a TTE at 12 months. No patients referred to cardiology have reached 12 months post treatment. Discussion International guidelines recommend screening to identify and treat early cardiotoxicity and prevent long term morbidity. ASCO and ESMO guidelines both recommend patients receiving anthracycline undertake a TTE at baseline and at 6-12 months after completing therapy. Both recommend 3 monthly TTEs for patients receiving trastuzumab. The ESMO guidelines recommend a baseline ECG and consideration of further TTE at 2 years post therapy. For high risk patients the ASCO guidelines discuss offering routine TTEs during treatment. The ESMO guidelines recommend measurement of cardiac biomarkers for patients receiving anthracycline prior to each cycle and routine monitoring can be considered for patients receiving anti HER2 therapy. The ASCO guidelines reserve use of cardiac biomarkers for patients who develop signs or symptoms of cardiac dysfunction. Our study demonstrates that while baseline cardiac assessment is well performed a personalised approach to cardiac monitoring during curative therapy is not. These were unexpected findings given both treatment units are located in well resourced areas of Sydney. An outcome of this study has been the development of a cardio-oncology group within our oncology and cardiology departments. This has led to the development of new clinical guidelines to screen and manage high risk breast cancer patients receiving cardiotoxic therapies. This has empowered patients, care coordinators and physicians to proactively manage cardiac risks from therapy and we hope these institutional guidelines will be adopted nationally. Citation Format: Brendan Kirwin, Lina Pugliano, Sally Baron Hay. Monitoring for cardiotoxicity in early breast cancer: an Australian experience [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-17.

New advances in medical imaging technology for the evaluation of anthracycline-induced cardiotoxicity.

New advances in medical imaging technology for the evaluation of anthracycline-induced cardiotoxicity.

An artificial intelligence approach for predicting cardiotoxicity in breast cancer patients receiving anthracycline.

Although anti-cancer therapy-induced cardiotoxicity is known, until now it lacks a reliable risk predictive model of the subsequent cardiotoxicity in breast cancer patients receiving anthracycline therapy. An artificial intelligence (AI) with a machine learning approach has yet to be applied in cardio-oncology. Herein, we aimed to establish a predictive model for differentiating patients at a high risk of developing cardiotoxicity, including cancer therapy-related cardiac dysfunction (CTRCD) and symptomatic heart failure with reduced ejection fraction. This prospective single-center study enrolled patients with newly diagnosed breast cancer who were preparing for anthracycline therapy from 2014 to 2018. We randomized the patients into a 70%/30% split group for ML model training and testing. We used 15 variables, including clinical, chemotherapy, and echocardiographic parameters, to construct a random forest model to predict CTRCD and heart failure with a reduced ejection fraction (HFrEF) during the 3-year follow-up period (median, 30months). Comparisons of the predictive accuracies among the random forest, logistic regression, support-vector clustering (SVC), LightGBM, K-nearest neighbor (KNN), and multilayer perceptron (MLP) models were also performed. Notably, predicting CTRCD using the MLP model showed the best accuracy compared with the logistic regression, random forest, SVC, LightGBM, and KNN models. The areas under the curves (AUC) of MLP achieved 0.66 with the sensitivity and specificity as 0.86 and 0.53, respectively. Notably, among the features, the use of trastuzumab, hypertension, and anthracycline dose were the major determinants for the development of CTRCD in the logistic regression. Similarly, MLP, logistic regression, and SVM also showed higher AUCs for predicting the development of HFrEF. We also validated the AI prediction model with an additional set of patients developing HFrEF, and MLP presented an AUC of 0.81. Collectively, an AI prediction model is promising for facilitating physicians to predict CTRCD and HFrEF in breast cancer patients receiving anthracycline therapy. Further studies are warranted to evaluate its impact in clinical practice.

Treatment of patients with hematological malignancies and left-ventricular assisted device (LVAD) managed cardiomyopathy.

e19581 Background: An estimated 2-3% of individuals who undergo advanced heart failure therapies, such as left ventricular assist devices (LVAD) or orthotopic heart transplantation (OHT), have an antineoplastic-related cardiomyopathy. We investigated the incidence and clinical outcomes of non-ischemic or dilated cardiomyopathies on LVAD patients who have been diagnosed with lymphomas or leukemias in our institution between years 2015 - 2022. Methods: We found four cases of patients with newly diagnosed hematological malignancy who had existing underlying LVAD-dependent cardiomyopathy in our center. One patient was excluded due to loss to follow up. The other three patients were treated in the heart failure unit while concurrently managed by LVAD specialists. One patient required administration of continuous 72hr-infusion of doxorubicin to minimize the risk of right-sided ventricular failure. The response to treatment was assessed with use of PET-CT scans, bone marrow biopsies and serological markers per standard of care guidelines. Results: The median age was 54.6 years. Two were African Americans, one Caucasian and one Hispanic (lost to follow up). All patients were males. Of these four individuals, two were diagnosed with Non-Hodgkin Lymphomas (one Peripheral T-cell lymphoma, one Diffuse Large B-cell lymphoma), one with Chronic Lymphocytic Leukemia (CLL) and one with Acute Promyelocytic Leukemia (APL). Three patients completed or have ongoing chemotherapeutic treatment. All have achieved complete remission (CR 3/3) of their diseases. Conclusions: To date, there is no significant volume of data showing the administration of chemotherapy on patients with concurrent LVAD-dependent cardiomyopathies. The Peripheral T-cell lymphoma patient received anthracycline therapy via a continuous 72-hour infusion with close LVAD monitoring at the heart failure unit. After completion of total 6 cycles in 2021, he still is in complete remission. Our CLL patient, has also completed 5 cycles of rituximab and venetoclax while also maintaining disease remission. The APL patient has completed 5 cycles of arsenic trioxide and ATRA with also a complete remission of his leukemia. LVAD-dependent cardiomyopathy patients concurrently diagnosed with malignant hematological diseases, can be considered for treatment with antineoplastic therapies. Durable remission rates can be achieved while undergoing aggressive cardiovascular care.

Characterization of Pericarditis following Allogeneic Hematopoietic Cell Transplantation

Pericarditis is an uncommon cardiac complication following allogeneic hematopoietic cell transplantation (alloHCT), with limited data characterizing its incidence, presentation, and management. The etiology of pericarditis in this setting is poorly understood and may include conditioning-related toxicity, infection, or graft-versus-host disease (GVHD). The objective of the present study was to characterize the clinical presentation, management, and outcomes of post-alloHCT pericarditis observed at a single center. This retrospective case-control study of consecutive adults undergoing alloHCT over 5 years was conducted to identify patients who developed pericarditis. Pericarditis was diagnosed using clinical, electrocardiography, and echocardiography findings. Identified cases were compared with a cohort of patients who underwent alloHCT during the same period but did not develop pericarditis. A total of 620 patients underwent alloHCT over the 5-year period, 20 of whom developed pericarditis (3.2% incidence). One patient had a pre-alloHCT history of pericarditis. All but 3 patients had received anthracycline therapy and 1 patient had received chest irradiation before undergoing alloHCT. Patients with pericarditis were more likely than patients without pericarditis to have received total body irradiation (odds ratio [OR], 4.57; P=.003) or cyclophosphamide (OR, 2.35; P=.07) as conditioning or GVHD prophylaxis. Fourteen patients experienced their initial episode of pericarditis before day +100 post-alloHCT, with a median time to onset at day +7. Six patients had their initial episode on day +100 or later, with a median time to onset at day +268. Only 1 patient had active, previously diagnosed GVHD, and 3 patients were on systemic steroid therapy at the time of pericarditis diagnosis. Pericarditis was treated primarily with colchicine (median duration 91 days). Seven episodes of recurrence occurred in 5 patients. Two patients experienced cardiac tamponade following their initial diagnosis, and 3 developed tamponade at recurrence. Recurrence was more common in patients who received no or <90 days of colchicine compared with those who received ≥90 days (45.5% vs 0%; P=.02). No cardiac-related deaths occurred. Overall survival was 85% at a median follow-up of 30 months post-alloHCT. Pericarditis occurred in 3.2% of patients in this single-center study, with cases observed both before and after day +100 and some cases occurring ≥1 year after alloHCT. Colchicine was an effective intervention, with ≥90 days of treatment associated with reduced recurrence. Pericarditis should be considered in patients presenting with chest pain following alloHCT.

Cardiac Surveillance for Early Detection of Late Subclinical Cardiac Dysfunction in Childhood Cancer Survivors After Anthracycline Therapy.

BackgroundIn childhood cancer survivors (CCSs) anthracycline-related cardiotoxicity is an important cause of morbidity and late mortality, but the optimal modality of cardiac surveillance still remains to be defined. The aim of this study was to assess whether non-invasive echocardiography-based functional cardiac measures can detect early subclinical myocardial changes in long-term pediatric cancer survivors who received anthracycline therapy.MethodsTwenty anthracycline-treated long-term CCSs and 20 age, sex, and body surface area matched healthy controls were enrolled in this study. Among cancer survivors, mean age at diagnosis was 6.5 ± 4.4 years, and the mean cumulative anthracycline dose was 234.5 ± 87.4 mg/m2. All subjects underwent a comprehensive functional echocardiographic protocol study including two-dimensional echocardiography (2D Echo), tissue Doppler imaging (TDI), speckle tracking (STE) and three-dimensional echocardiography (3D Echo). Patients were studied at a mean follow-up time of 6.5 ± 2.8 years from the end of therapy.ResultsNo significant differences in two-dimensional left ventricle ejection fraction (LVEF), diastolic parameters and speckle tracking (STE)-derived myocardial strain were observed between patients treated with anthracyclines and controls. Myocardial performance index was significantly prolonged (p = 0.005) and three-dimensional LVEF was significantly reduced (p = 0.002) in CCSs compared to controls, even though most values were within the normal range. There were no significant correlations between 2D, STE, and 3D echocardiographic parameters and age at diagnosis or duration of follow-up. No significant differences in echocardiographic parameters were found when stratifying cancer patients according to established risk factors for anthracycline cardiomyopathy.ConclusionsThis study found significantly reduced three-dimensional LVEF in CCSs compared with controls, despite no significant differences in two-dimensional LVEF and longitudinal strain values. These findings suggest that long-term CCSs who had received anthracycline therapy may be found to have subclinical features of myocardial dysfunction. However, further studies are needed to demonstrate the validity of new imaging techniques, including STE and 3D Echo, to identify patients at risk for cardiomyopathy in the long-term follow-up of CCSs.

Characterization of subclinical diastolic dysfunction by cardiac magnetic resonance feature-tracking in adult survivors of non-Hodgkin lymphoma treated with anthracyclines

BackgroundThe use of anthracycline-based chemotherapy is associated with the development of heart failure, even years after the end of treatment. Early detection of cardiac dysfunction could identify a high-risk subset of survivors who would eventually benefit from early intervention. Cardiac magnetic resonance feature-tracking (CMR-FT) analysis offers a practical and rapid method to calculate systolic and diastolic strains from routinely acquired cine images. While early changes in systolic function have been described, less data are available about late effects of chemotherapy in diastolic parameters by CMR-FT. The main goal of this study was to determine whether left ventricular (LV) early diastolic strain rates (GDSR-E) by CMR-FT are impaired in long-term adult survivors of non-Hodgkin lymphoma (NHL). Our secondary objective was to analyze associations between GDSR-E with cumulative anthracycline dose, systolic function parameters and myocardial tissue characteristics.MethodsThis is a single center cross-sectional observational study of asymptomatic patients in remission of NHL who previously received anthracycline therapy. All participants underwent their CMR examination on a 3.0-T scanner, including cines, T2 mapping, T1 mapping and late gadolinium enhancement imaging. Derived myocardial extracellular volume fraction was obtained from pre- and post-contrast T1 maps. CMR-FT analysis was performed using Trufi Strain software. The data obtained were compared between anthracycline group and volunteers without cardiovascular disease or neoplasia.ResultsA total of 18 adult survivors of NHL, 14 (77.8%) males, at mean age of 57.6 (± 14.7) years-old, were studied 88.2 (± 52.1) months after exposure to anthracycline therapy (median 400 mg/m2). Compared with controls, anthracycline group showed impaired LV global early diastolic circumferential strain rate (GCSR-E) [53.5%/s ± 19.3 vs 72.2%/s ± 26.7, p = 0.022], early diastolic longitudinal strain rate (GLSR-E) [40.4%/s ± 13.0 vs 55.9%/s ± 17.8, p = 0.006] and early diastolic radial strain rate (GRSR-E) [− 114.4%/s ± 37.1 vs − 170.5%/s ± 48.0, p < 0.001]. Impaired LV GCSR-E, GLSR-E and GRSR-E correlated with increased anthracycline dose and decreased systolic function. There were no correlations between GDSR-E and myocardial tissue characteristics.ConclusionsLeft ventricular early diastolic strain rates by CMR-FT are impaired late after anthracycline chemotherapy in adult survivors of non-Hodgkin lymphoma.

Subclinical anthracycline therapy-related cardiac Dysfunction: an ignored stage B heart failure in an African population.

Anthracyclines are potent antineoplastic agents with a proven efficacy in the treatment of many paediatric and adult haematological and solid-organ cancers. Anthracycline therapy-related cardiac dysfunction (ATRCD) is the commonest and most well-studied chemotherapy-induced cardiovascular toxicity. Therefore patients who received anthracycline therapy are considered in stage A heart failure. Recent study findings suggest that anthracycline cardiotoxicity represents a continuum that begins with subclinical myocardial cell injury, followed by an early asymptomatic decline in left ventricular ejection fraction that can progress to symptomatic heart failure if left untreated. In Western countries, ATRCD has been reported in 57% of anthracyclines-treated patients. However, data on incidence and spectrum of ATRCD in Africa are not available. This literature review aimed to highlight the concept of subclinical ATRCD as a stage B heart failure in the spectrum of ATRCD, and the importance of early detection. We emphasise the potential burden and risk of subclinical ATRCD in the African population, with the ultimate aim of drawing the attention of health workers in Africa to improve care of the relevant population.

The role of proinflammatory cytokines in the development of anthracycline-induced heart failure

Objective. To study the pathogenetic and prognostic role of cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)) in the development of anthracycline-induced chronic heart failure (CHF).Material and Methods. A total of 176 women with breast cancer who received anthracycline antibiotics as a part of polychemotherapy regimens were examined. Upon examination, the patients in remission were divided into two groups within 12 months after the completion of chemotherapy: patients with the development of cardiotoxic remodeling (group 1, n = 52) and women with preserved cardiac function (group 2, n = 124). All patients received echocardiography study before, during, and after chemotherapy. Biochemical blood tests were done to determine the levels of TNF-α and IL-1β before chemotherapy, immediately after it, and 12 months after chemotherapy completion. Determination of polymorphisms of the TNF-α (–308G/A, rs1800629) and IL-1β genes (+3953, rs1143634) was carried out by polymerization chain reaction.Results. A higher level of TNF-α and IL-1β in group 1 was associated with the development of heart failure 12 months after the end of chemotherapy. The level of TNF-α over 7.5 pg/mL after the completion of chemotherapy allowed to predict the development of cardiovascular complications in women receiving anthracycline therapy with sensitivity of 44.2% and specificity of 75.8% (AUS = 0.600; 95% CI = 0.524–0.673; p = 0.035). The study did not reveal any significant differences in the frequency distribution for genotypes of 308G/A polymorphism (rs1800629) of the TNF-α gene and +3953 (rs1143634) polymorphism of the IL-1β gene in the studied groups.Conclusion. Patients with breast cancer who developed anthracycline-induced heart failure 12 months after the end of chemotherapy had the increased levels of TNF-α and IL-1β suggesting the pathogenetic role of proinflammatory cytokines in the development of cardiac injury during anthracycline therapy.

N-terminal pro-brain natriuretic peptide levels after receipt of anthracycline for breast cancer.

e24103 Background: Many of the 200,000 patients diagnosed with breast cancer (BC) annually in the United States receive anthracycline-based therapy, increasing their risk of future congestive heart failure. N-terminal brain natriuretic peptide (NT-proBNP) has been used as a biomarker of asymptomatic cardiac dysfunction in the general population and is of interest to identify patients who might benefit from echocardiography during survivorship. This study aimed to assess how age, baseline comorbidities, and time since BC diagnosis impact NT-proBNP levels after anthracycline-based chemotherapy. Methods: This retrospective study, using samples collected in our ongoing prospective Mayo Clinic Breast Disease Registry, included 20 survivors of non-metastatic BC patients per year for each of the first 5 years after anthracycline-based chemotherapy (n=100 total). NT-pro-BNP levels were assessed using a Roche immunoassay. Cardiac risk factors were obtained by chart review. Multivariable linear regression models assessed associations between NT-proBNP values and these independent variables: baseline cardiac risk factors (including hypertension, hyperlipidemia, obesity, diabetes mellitus, and smoking), tumor ER status (surrogate for possible endocrine therapy), time between diagnosis and serum collection, T and N status, use of trastuzumab, and age. Results: The mean age at the time of BC diagnosis was 52.2 (SD 9.8). 13% of tumors were human epidermal growth factor receptor (HER2)-positive and 71% were estrogen receptor (ER) positive. NT-proBNP was elevated in 34%. Mean NT-BNP level was higher (p=0.047) for those in years 4-5 (158 pg/mL) compared to those in years 1-3 (106 pg/mL) (See Table.) Models revealed years from diagnosis to serum draw (p=0.026), older age (p=0.006), more cardiac risk factors (p=0.064), and N2-3 (p=0.001) were associated with elevated NT-pro-BNP level. Use of trastuzumab, ER status, and tumor size were not associated with NT-proBNP. Conclusions: NT-proBNP is elevated in 1/3 of survivors who received anthracycline therapy for BC. As expected, cardiac risk factors and advancing age are associated with higher NT-proBNP. NT-proBNP values &gt;300 were only found in patients who were 4-5 years after diagnosis. Additional research will be needed to further define the diagnostic and prognostic merit of NT-proBNP in survivors after receipt of anthracycline therapy. [Table: see text]

Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer-a meta-analysis.

AimsChildhood cancer therapy is associated with a significant risk of therapy‐related cardiotoxicity. This meta‐analysis aims to evaluate cardiac biomarkers for the detection of cancer therapy‐related left ventricular (LV) dysfunction in childhood cancer patients.Methods and resultsPubMed, Cochrane Library, Wiley Library, and Web of Science were screened for studies investigating brain natriuretic peptide (BNP)/N‐terminal proBNP (NT‐proBNP) or cardiac troponin in childhood cancer patients. The odds ratios (OR) for elevation of cardiac biomarkers and association with LV dysfunction were calculated using a random‐effects model. Data from 27 studies with 1651 subjects were included. BNP/NT‐proBNP levels were higher post‐treatment compared with controls or pre‐treatment values [standardized mean difference = 1.0; 95% confidence interval (CI) = 0.6–1.4; n = 320; P < 0.001]. LV dysfunction was present in 11.76% of included patients, and risk for LV dysfunction was increased in patients with elevated BNP/NT‐proBNP (OR = 7.1; 95% CI = 2.0–25.5; n = 350; P = 0.003). The sensitivity of BNP/NT‐proBNP for the detection of LV dysfunction was 33.3%, and the specificity was 91.5%. Sensitivity increased when selecting for studies that assessed patients < 5 years after anthracycline exposure and for studies including high cumulative anthracycline doses. Anthracycline chemotherapy was associated with an increased frequency of elevated troponin (OR = 3.7; 95% CI = 2.1–6.5; n = 348; P < 0.001). The available evidence on the association between elevated troponin and LV dysfunction was insufficient for an adequate analysis. In five included studies, the frequency of LV dysfunction was not increased in patients with elevated troponin (OR = 2.5; 95% CI = 0.5–13.2; n = 179; P = 0.53).ConclusionsBNP/NT‐proBNP is associated with cardiotoxicity in paediatric cancer patients receiving anthracycline therapy, but owing to low sensitivity, BNP/NT‐proBNP has to be evaluated in the context of further parameters including clinical assessment and echocardiography. Future studies are needed to determine whether troponin serves as a marker for cardiotoxicity in children. Standardized recommendations for the application of cardiac biomarkers in children undergoing cardiotoxic cancer therapy may benefit management and clinical outcome.

P693Cardiac biomarkers for the detection of anthracycline cardiotoxicity in childhood cancer - a meta-analysis

Abstract Introduction Heart failure is the most concerning cardiovascular side effect of anthracycline chemotherapy. Pediatric cancer patients and survivors of childhood cancer are particularly vulnerable to cancer therapy-related cardiotoxicity. Cardiac biomarkers may be beneficial for screening and diagnosis of anthracycline-related heart failure in pediatric cancer patients and survivors of childhood cancer but systematic data is not yet available. Purpose To evaluate (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP) and cardiac troponin for screening and prediction of cancer therapy-related cardiotoxicity in pediatric cancer patients and survivors of childhood cancer. Methods Cochrane, PubMed, Web of Science, and Wiley Library were screened for studies investigating cardiac troponin or BNP/NT-proBNP in pediatric cancer patients receiving anthracycline therapy or survivors of childhood cancer. The primary endpoint was left ventricular (LV) dysfunction as defined by decreased ejection fraction (EF) or fractional shortening (FS). The study was registered at the International prospective register of systematic reviews (PROSPERO) (CRD42018106616). Results A total of 1643 subjects from 27 studies were included. BNP/NT-proBNP levels were higher in patients post-treatment compared to control subjects or pre-treatment values (standardized mean difference = 1.0; 95% CI: 0.6–1.4; n=239). The risk for left ventricular (LV) dysfunction was increased in patients with elevated BNP/NT-proBNP (OR=5.5; 95% CI: 2.0–15.2; n=357). This was demonstrated for acute cardiotoxicity (OR=22.3; 95% CI: 3.3–151.1; n=88) and in survivors of childhood cancer (OR=3.2; 95% CI: 1.0–10.0; n=269). Sensitivity for the prediction of acute or subacute LV dysfunction was 28.9% and specificity was at 91.7%. The frequency of troponin elevations was increased after anthracycline therapy (OR=3.6; 95% CI: 2.0–6.5; n=305) but troponin was not associated with LV dysfunction (OR=0.2; 95% CI: −0.2 to 0.5; n=273). Conclusion BNP/NT-proBNP is elevated in pediatric patients receiving anthracycline chemotherapy and serves as a marker for the prediction of cardiotoxicity and screening for late cardiotoxicity in survivors of childhood cancer. So far, there is no systematic evidence on a benefit of cardiac troponin for the detection of anthracycline cardiotoxicity in children. Standardized recommendations on the role of cardiac biomarkers are needed for the optimal detection of anthracycline cardiotoxicity in childhood cancer patients. Acknowledgement/Funding IFORES research grant of the Medical Faculty, University Duisburg-Essen, Essen, Germany

BNP as a marker for early prediction of anthracycline-induced cardiotoxicity in patients with breast cancer.

Anthracycline chemotherapy serves an important role in treating patients with breast cancer but is associated with cardiotoxicity. Although brain natriuretic peptide (BNP) is not the ideal marker for detecting the presence of diseases of the heart, several studies have demonstrated the predictive utility of BNP in the diagnosis of anthracycline-induced cardiotoxicity (AIC). The aim of the present study was to evaluate the role of BNP as a marker for the early prediction of AIC in patients with breast cancer. In the present study, a total of 149 patients with breast cancer who received anthracycline therapy were evaluated. The levels of BNP and echocardiography were detected during the anthracycline-based chemotherapy and patients were followed up after chemotherapy to determine the cardiotoxicity-free survival times. In the patients who received chemotherapy, an increase in the levels of BNP was observed. The concentration of BNP was significantly higher in the cardiotoxicity group during anthracycline chemotherapy (P=0.022) compared with the non-cardiotoxicity group and it was an independent predictor of cardiotoxicity (P=0.028). The optimal diagnostic threshold of BNP after the last anthracycline chemotherapy treatment was 107.9 pg/ml, the diagnostic sensitivity was 0.538, the specificity was 0.794, the Youden index was 0.332, the positive predictive value was 0.583 and the negative predictive value was 0.762. Based on the BNP threshold, a log-rank test was performed and it was determined that the cardiotoxicity-free survival rate of the group with higher levels of BNP was always lower compared with the group with lower levels of BNP. BNP elevation was associated with cardiotoxicity during the anthracycline chemotherapy. Detecting BNP after the final treatment of anthracycline chemotherapy may contribute to the early detection of cardiotoxicity.

Abstract P4-16-09: Effect of simvastatin on cardiac strain in breast cancer patients receiving anthracycline therapy

Abstract Background: Cardiac toxicity (CT) is a rare late effect of anthracycline therapy for breast cancer (BC). Statins may attenuate the CT of anthracyclines. Myocardial strain can detect subclinical CT before ejection fraction (EF) declines. Global longitudinal strain (GLS) ≥-19% and relative change (RelΔ) in GLS≥11% predict future decline in EF. We conducted a pilot study to evaluate the effect of simvastatin on GLS in BC patients receiving anthracyclines. Methods: We enrolled women with stage I-III BC planning doxorubicin/cyclophosphamide (AC) x 4. Women with heart disease or taking a statin were excluded. Participants were randomized 1:1 to simvastatin 40 mg daily x 24 weeks (wk) + AC or to AC alone. We performed echo with strain 5 times: baseline (BL), pre-AC#2, 1-3 wk after AC#4, 24 wk after AC #1 and 52 wk after AC#1. The primary endpoint was the mean absolute change (|Δ|) in GLS from BL to 1-3 wk after AC#4. Secondary endpoints included RelΔ in GLS, feasibility and safety. We used two-sample t-tests to compare mean changes in GLS and Fisher's exact test to compare dichotomized GLS values. The study closed early due to loss of staff. Results: Of 31 patients, 15 (48%) received simvastatin+AC. Mean age was 46 years; 71% pre-menopausal, 61% white and 32% black. There were no significant differences in BL cardiovascular risk factors between the arms. After AC, 3 HER2+ patients received trastuzumab. There were no grade 3-4 AEs with simvastatin. Common grade 1-2 AEs included myalgia (20%), elevated AST (27%) and elevated ALT (53%). One patient in the AC arm died from heart failure with low EF 2 months after having a normal echo 1-3 wk after AC#4. The rate of missing echos was 14%. Of 133 completed echos, 124 (93%) were evaluable for GLS. Mean GLS was &amp;lt;-19% at all times in the simvastatin+AC arm. Mean GLS was &amp;lt;-19% at BL and pre-AC#2 in the AC arm, but ≥-19% at post-AC times in the AC arm. Mean EF was &amp;gt;60% at all times in both arms. Among 27 patients evaluable for the primary endpoint, there was no significant difference in mean |Δ| in GLS from BL to 1-3 wk after AC#4 between the arms (Simvastatin+AC: 0.42%; AC: 1.11%, p=0.57). In addition, there were no differences in the mean|Δ| in GLS from BL to any other time between the arms (all p&amp;gt;0.1). The proportion of patients with GLS&amp;lt;-19% was higher in the simvastatin+AC arm than in the AC arm pre-AC#2 (73% vs 44%), 1-3 wk after AC#4 (67% vs 38%), 24 wk after AC #1 (53% vs 25%) and 52 wk after AC#1 (53% vs 25%) (all p&amp;gt;0.05). The proportion of patients with RelΔ in GLS≥11% from BL was lower in the simvastatin+AC arm than in the AC arm pre-AC#2 (13% vs 19%), 1-3 wk after AC#4 (20% vs 44%) and 24 wk after AC#1(27% vs 31%) (all p&amp;gt;0.05). Conclusion: Simvastatin did not result in a statistically significant difference in the mean |Δ| in GLS from BL to 1-3 wk after AC#4. However, the study was underpowered due to small sample size and there was a suggestion of reduced CT with simvastatin. Co-administration of simvastatin and AC was safe and serial echocardiographic strain monitoring was feasible. Further studies are needed to evaluate the cardioprotective effect of statins on strain in BC patients receiving anthracyclines. Citation Format: Smith KL, Griffin JM, Tsai H-L, Leathers M, Hays A, Lu D-Y, Zhang Z, Rosner GL, Russell SD, Connolly RM, Jelovac D, Visvanathan K, Wolff AC, Stearns V, Abraham T. Effect of simvastatin on cardiac strain in breast cancer patients receiving anthracycline therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-09.