[Anthracycline-induced Heart Failure: Treatment and Recovery Prospects].

The article presents a clinical case of heart failure associated with the anthracycline-containing antitumor therapy in a breast cancer patient with an initially low risk of developing cardiovascular complications.

Anthracycline-induced arrhythmias in breast cancer therapy: A meta-analysis of single-arm trials.

INTRODUCTION: As of 2020, breast cancer has emerged as the predominant cause of cancer incidence globally. Anthracycline-based chemotherapy serves as a crucial element in the treatment regimen for breast cancer. However, these anthracycline-based drugs are associated with cardiac toxicity. This study represents the first clinical quantitative analysis aimed at accurately determining the incidences of arrhythmia and abnormal electrocardiogram (ECG) changes, thereby providing valuable data to bolster clinical drug usage and monitoring. METHODS: A systematic search was conducted across multiple databases including CNKI, VIP, Wanfang, PubMed, Embase, Web of Science, and the Cochrane Library. The incidence of combined arrhythmias in breast cancer patients and the associated heterogeneity were calculated using either a random effect model or a fixed effect model. Statistical analysis was performed using STATA16. RESULTS: The study encompassed a total of 37 articles, which included 5705 breast cancer patients undergoing anthracycline treatment. Among these patients, 2257 developed arrhythmias. The meta-analysis revealed that the incidence of anthracycline-associated arrhythmias and abnormal ECG changes in breast cancer patients was 0.41 (0.37, 0.44). Subgroup analysis indicated that the incidence of ST-T segment change was 0.19 (0.15, 0.23), the incidence of conduction block was 0.04 (0.02, 0.05), the incidence of premature beats was 0.09 (0.07, 0.11), and the incidence of atrial fibrillation was 0.04 (0.00, 0.12). Additional results are presented in Table 3. CONCLUSION: This pioneering study accurately assesses the incidence of arrhythmias in breast cancer patients treated with anthracyclines. The findings provide clinicians with valuable insights into understanding and managing the cardiac toxicity associated with such treatment. Moreover, this study lays the foundation for future research exploring the mechanisms underlying these arrhythmias and potential preventative strategies.

Cardiovascular magnetic resonance parametric techniques to characterize myocardial effects of anthracycline therapy in adults with normal left ventricular ejection fraction: a systematic review and meta-analysis.

BACKGROUND: The cardiotoxic effects of anthracyclines therapy are well recognized, both in the short and long term. Echocardiography allows monitoring of cancer patients treated with this class of drugs by serial assessment of left ventricle ejection fraction (LVEF) as a surrogate of systolic function. However, changes in myocardial function may occur late in the process when cardiac damage is already established. Novel cardiac magnetic resonance (CMR) parametric techniques, like native T1 mapping and extra-cellular volume (ECV), may detect subclinical myocardial damage in these patients, recognizing early signs of cardiotoxicity before development of overt cancer therapy-related cardiac dysfunction (CTRCD) and prompting tailored therapeutic and follow-up strategies to improve outcome. METHODS AND RESULTS: We conducted a systematic review and a meta-analysis to investigate the difference in CMR derived native T1 relaxation time and ECV values, respectively, in anthracyclines-treated cancer patients with preserved EF versus healthy controls. PubMed, Embase, Web of Science and Cochrane Central were searched for relevant studies. A total of 6 studies were retrieved from 1057 publications, of which, four studies with 547 patients were included in the systematic review on T1 mapping and five studies with 481 patients were included in the meta-analysis on ECV. Three out of the four included studies in the systematic review showed higher T1 mapping values in anthracyclines treated patients compared to healthy controls. The meta-analysis demonstrated no statistically significant difference in ECV values between the two groups in the main analysis (Hedges´s g =3.20, 95% CI -0.72-7.12, p =0.11, I2 =99%), while ECV was significantly higher in the anthracyclines-treated group when sensitivity analysis was performed. CONCLUSIONS: Higher T1 mapping and ECV values in patients exposed to anthracyclines could represent early biomarkers of CTRCD, able to detect subclinical myocardial changes present before the development of overt myocardial dysfunction. Our results highlight the need for further studies to investigate the correlation between anthracyclines-based chemotherapy and changes in CMR mapping parameters that may guide future tailored follow-up strategies in this group of patients.

Predictive Factors of Therapy-Related Cardiovascular Events in Patients with Lymphoma Receiving Anthracyclines.

BACKGROUND: Cancer-therapy-related cardiac dysfunction (CTRCD) is a growing concern for public health, with a growing incidence due to improved survival rates of patients with hematological malignancies due to diagnostic and therapeutic advances. The identification of patients at risk for CTRCD is vital to developing preventive strategies. METHODS: A single-center retrospective cohort study was conducted between 1 January 2017 and 15 February 2023. Medical records of patients with lymphoma treated with first-line anthracyclines were reviewed. Demographic data, cardiovascular risk factors, biomarkers of myocardial damage, and echocardiographic information were collected. RESULTS: A total of 200 patients were included. The incidence of CTRCD was 17.4% (35/200). Patients with CTRCD were older than those without CTRCD, with a mean age of 65.17 years vs. 56.77 (p = 0.008). Dyslipidemia (DL) (31.4% vs. 13.4% p = 0.017) and previous cardiovascular disease (40% vs. 13.3%; p < 0.001) were more frequent in the group who developed an event. Mean baseline NT-proBNP levels in the subgroup with cardiovascular events were 388.73 kg/L ± 101.02, and they were 251.518 kg/L ± 26.22 in those who did not (p = 0.004). Differences in Troponin I levels were identified during and after treatment without exceeding the laboratory's upper reference limit. Patients were followed for a median of 51.83 months (0.76-73.49). The presence of a CTCRD event had a negative impact on overall mortality from any cause (HR = 2.23 (95% CI: 1.08-2.93); p = 0.031). CONCLUSIONS: Early identification of risk factors is crucial to manage patients at risk for CTRCD.

Assessment of Native Myocardial T1 Mapping for Early Detection of Anthracycline-Induced Cardiotoxicity in Patients with Cancer: a Systematic Review and Meta-analysis.

Anthracycline antibiotic is one of the most effective anti-tumor drugs used to manage certain types of breast cancers, lymphomas, and leukemias. However, anthracyclines induce a dose-dependent cardiotoxicity that may progress to heart failure. Thus, using a sensitive predictor of early cardiac dysfunction in patients treated with anthracyclines can help detect subclinical cardiac dysfunction early and help initiate interventions to protect these patients. Among parameters of myocardial measure, cardiac magnetic resonance (CMR)-measured native myocardial T1 mapping is considered a sensitive and accurate quantitative measure of early subclinical cardiac changes, particularly cardiac inflammation and fibrosis. However, to understand the quality and the validity of the current evidence supporting the use of these measures in patients treated with anthracyclines, we aimed to conduct a systematic review of clinical studies of this measure to detect early myocardial changes in cancer patients treated with anthracyclines. The primary outcome was the level of native T1 mapping. We performed fixed-effects meta-analyses and assessed certainty in effect estimates. Of the 1780 publications reviewed (till 2022), 23 were retrieved, and 9 articles met the inclusion criteria. Our study showed that exposure to anthracycline was associated with a significant elevation of native myocardial T1 mapping from baseline (95% CI 0.1121 to 0.5802; p = 0.0037) as well as compared to healthy control patients (95% CI 0.2925 to 0.7448; p < 0.0001). No significant publication bias was noted on the assessment of the funnel plot and Egger's test. According to the Q test, there was no significant heterogeneity in the included studies (I2 = 0.0000% versus healthy controls and I2 = 14.0666% versus baseline). Overall, our study suggests that native myocardial T1 mapping is useful for detecting anthracycline-induced cardiotoxicity in patients with cancer.

Left atrial reservoir longitudinal strain and its incremental value to the left ventricular global longitudinal strain in predicting anthracycline-induced cardiotoxicity.

BACKGROUND: Left ventricular global longitudinal strain (LVGLS) has been recommended by current guidelines for diagnosing anthracycline-induced cardiotoxicity. However, little is known about the early changes in left atrial (LA) morphology and function in this population. Our study aimed to evaluate the potential usefulness of LA indices and their incremental value to LVGLS with three-dimensional echocardiography (3DE) in the early detection of subclinical cardiotoxicity in patients with lymphoma receiving anthracycline. METHODS: A total of 80 patients with diffuse large B-cell lymphoma who received six cycles of anthracycline-based treatment were enrolled. Echocardiography was performed at baseline (T0), after four cycles (T1), and after the completion of six cycles of chemotherapy (T2). Left ventricular ejection fraction (LVEF), LVGLS, LA volumes, LA emptying fraction (LAEF), LA active emptying fraction (LAAEF), and LA reservoir longitudinal strain (LASr) were quantified with 3DE. Left atrioventricular global longitudinal strain (LAVGLS) was calculated as the sum of peak LASr and the absolute value of peak LVGLS (LAVGLS = LASr+|LVGLS|). LV cardiotoxicity was defined as a new LVEF reduction by ≥10 percentage points to an LVEF of ≤50%. RESULTS: Fourteen (17.5%) patients developed LV cardiotoxicity at T2. LA volumes, LAEF, and LAAEF remained stable over time. Impairment of LASr (28.35 ± 5.03 vs. 25.04 ± 4.10, p < .001), LVGLS (-22.77 ± 2.45 vs. -20.44 ± 2.62, p < .001), and LAVGLS (51.12 ± 5.63 vs. 45.61 ± 5.22, p < .001) was observed by the end of the fourth cycle of chemotherapy (T1). Statistically significant declines in LVEF (61.30 ± 4.73 vs. 57.08 ± 5.83, p < .001) were only observed at T2. The relative decrease in LASr (ΔLASr), LVGLS (ΔLVGLS), and LAVGLS (ΔLAVGLS) from T0 to T1 were predictors of LV cardiotoxicity. A ΔLASr of >19.75% (sensitivity, 71.4%; specificity, 87.9%; area under the curve (AUC), .842; p < .001), a ΔLVGLS of >13.19% (sensitivity, 78.6%; specificity, 74.2%; AUC, .763; p < .001), and a ΔLAVGLS of >16.80% (sensitivity, 78.6%; specificity, 93.9%; AUC, .905; p < .001) predicted subsequent LV cardiotoxicity at T2, with the AUC of ΔLAVGLS significantly larger than that of ΔLVGLS (.905 vs. .763, p = .027). Compared to ΔLVGLS, ΔLAVGLS showed improved specificity (93.9% vs. 74.2%, p = .002) and maintained sensitivity in predicting LV cardiotoxicity. CONCLUSIONS: LASr could predict anthracycline-induced LV cardiotoxicity with excellent diagnostic performance. Incorporating LASr into LVGLS (LAVGLS) led to a significantly improved specificity and maintained sensitivity in predicting LV cardiotoxicity.

Thoracic aorta injury detected by 4D flow MRI predicts subsequent main adverse cardiovascular events in breast cancer patients receiving anthracyclines: A longitudinal study.

PURPOSE: To investigate longitudinal thoracic aorta injury using 3-dimensional phase-contrast magnetic resonance imaging (4D flow MRI) parameters and to evaluate their value for predicting the subsequent main adverse cardiovascular events (MACEs) in breast cancer patients receiving anthracyclines. METHODS: Between July 2020 and July 2021, eighty-eight female participants with breast cancer scheduled to receive anthracyclines with or without trastuzumab prospectively enrolled. Each subjects underwent 4D flow MRI at baseline, 3 and 6 months in relation to baseline. The diameter, peak velocity (Vpeak), wall shear stress (WSS), pulse wave velocity (PWV), energy loss (EL) and pressure gradient (PG) of thoracic aorta were measured. The association between these parameters and subsequent MACEs was performed by Cox proportional hazard models. RESULTS: Ten participants had subsequently MACEs. The Vpeak and PG gradually decreased and the WSS, PWV and EL progressively increased at 3 and 6 months compared with baseline. Adjusted multivariable analysis showed that the WSS of the proximal, mid- and distal ascending aorta [HR, 1.314 (95% confidence interval (CI): 1.003, 1.898)], [HR, 1.320 (95% CI: 1.002, 1.801)] and [HR, 1.322 (95% CI: 1.001, 1.805)] and PWV of ascending aorta [HR, 2.223 (95% CI: 1.010, 4.653)] at 3 months were associated with subsequent MACEs. Combined WSS and PWV of ascending aorta at 3 months yielded the highest AUC (0.912) for predicting subsequent MACEs. CONCLUSION: Combined WSS and PWV of ascending aorta at 3 months is helpful for predicting the subsequent MACEs in breast cancer patients treated by anthracyclines.

Heart failure related to contemporary breast cancer treatment.

ABSTRACT: This article addresses cardiotoxicity in patients with breast cancer who are treated with anthracyclines and/or anti-human epidermal growth factor 2 (HER2) therapy, namely doxorubicin and trastuzumab. Development of concise clinical guidelines for chemotherapy-induced heart failure is ongoing. Through identification of specific risk factors and clinical predictors of cardiotoxicity, clinicians are able to better understand and define effective monitoring strategies and optimize patient care. Close cardiac monitoring is recommended for patients throughout treatment with anthracyclines and anti-HER2 therapy. Pretreatment risk assessment with echocardiography and evaluation of cardiovascular risk factors aid in predicting the development of left ventricular (LV) dysfunction. Further clinical trials are needed to increase understanding and optimize treatment guidelines for LV dysfunction in patients taking anthracyclines or anti-HER2 therapy.

A review regarding the article 'The cardioprotective potential of sodium-glucose cotransporter 2-inhibitors in breast cancer therapy-related cardiac dysfunction-A systematic review'.

Breast cancer is one of the most common types of cancer, representing 15 % of all new cancer cases in the United States. Approximately 12.4 % of all women will be diagnosed with breast cancer during their lifetime. In the past decades, a decrease in cancer-related mortality is evident as a result of early screening and improved therapeutic options. Nonetheless, breast cancer survivors face long-term treatment side effects, with cardiotoxicity being the most significant one, which lead to increased morbidity and mortality. Breast cancer patients are particularly susceptible to cancer therapeutics-related cardiac dysfunction (CTRCD) as treatment regimens include cardiotoxic drugs, primarily anthracyclines and anti-human epidermal growth factor receptor 2 (anti-HER2) agents (recombinant humanized monoclonal antibodies directed against HER2 such as trastuzumab and pertuzumab). Cardiotoxicity is the most common dose-limiting toxicity associated with trastuzumab. Discontinuation of trastuzumab however, can lead to worse cancer outcomes. There have been case reports, registry-based, retrospective cohort-based and mechanistic studies suggesting the cardioprotective potential of SGLT2i in CTRCD. It is not known whether SGLT2i can prevent the development of incident HF or reduce the risk of HF in patients receiving trastuzumab with or without other concurrent anti-HER2 agent or sequential anthracycline for treatment of HER2 positive breast cancer. Based on these, there is now a call for randomized controlled trials to be performed in this patient cohort to advise guideline-directed therapy for CTRCD, which will in turn also provide detailed safety information and improve cancer and cardiovascular outcomes.

Superiority of anthracycline-free treatment in standard-risk acute promyelocytic leukemia: A systematic review and comparative epidemiological analysis.

BACKGROUND: Recent advances in the treatment of acute promyelocytic leukemia (APML) have seen unprecedented improvements in patient outcomes. However, such rapid growth in understanding often leads to uncertainty regarding superiority among candidate treatment regimens, especially when further scrutinized from an epidemiological perspective. AIMS: The aim of this systematic review with epidemiological analysis was to identify and compare commonly utilized protocols for standard-risk APML with a particular focus on complete remission (CR), overall/disease-free survival (DFS), and reported adverse events. METHODS AND RESULTS: Medline, Scopus, and CINAHL were interrogated to identify studies utilizing all-trans retinoic acid (ATRA) in addition to arsenic trioxide (ATO) and/or anthracyclines such as idarubicin (IDA) in the treatment of de-novo APML. After collation of studies, an epidemiological analysis was subsequently performed to compare protocols with regards to outcomes of interest using number needed to benefit (NNB) and number needed to harm (NNH) measures. Seventeen articles, describing 12 distinct trials, were included in the analysis. These trials made use of three unique protocols; CR rates were 94%-100% for ATO/ATRA regimens, 95%-96% for ATO/ATRA/anthracycline regimens, and 89%-94% for ATRA/anthracycline regimens. Epidemiological analysis demonstrated NNB for CR was 9.09 (ATO/ATRA vs. ATRA/IDA) and 20.00 (ATO/ATRA vs. ATO/ATRA/IDA), NNH for neutropenia was -3.45 (ATO/ATRA vs. ATRA/IDA), and NNH for infection was -3.13 (ATO/ATRA vs. ATRA/IDA) and -1.89 (ATO/ATRA vs. ATO/ATRA/IDA). CONCLUSION: The ATO/ATRA regimen is superior to chemotherapy-containing protocols at inducing remission and promoting survival in patients with APML. The regimen is better tolerated than the proposed alternatives with fewer adverse events. Future research opportunities include quantifying APML epidemiology and pursuing oral arsenic as an option for simplification of therapeutic protocols.

TXB-001, a newly-developed polymer-conjugated anthracycline: Significantly lower adverse effects in animal models of alopecia and hand-foot syndrome.

Anthracycline anti-cancer drugs have been widely used in the treatment of several cancers; however, their use is limited by adverse effects (AEs). Alopecia is a common AE that is minimally invasive, but adversely affects mental health and reduces quality of life (QoL). Hand-foot syndrome (HFS) is a dose-limiting AE of DOXIL, a liposomal formulation of doxorubicin (DOX). Although it is not a life-threatening condition, HFS affects function and reduces QoL. TXB-001 is a new candidate polymer-conjugated anthracycline anti-cancer drug, and modified and optimized polymerized pirarubicin (THP), known as P-THP, is expected to have low toxicity and high efficacy. The anti-cancer effects of TXB-001 were examined using the 4T1 mouse model. An alopecia mouse model and HFS rat model were used to evaluate the alopecia- and HFS-inducing effects of TXB-001 and compare their severity with existing anthracycline anti-cancer drugs. A pharmacokinetic analysis of plasma as well as chest, palmar, and plantar skin samples after the single intravenous administration of DOXIL and TXB-001 to rats was also performed. The results obtained revealed that TXB-001 exerted similar anti-cancer effects to those of DOXIL in mice, weaker alopecia-inducing effects than DOX, DOXIL, and THP in mice, and no or markedly weaker HFS-like changes than DOXIL, which induced significant histopathological changes. The results of the pharmacokinetic analysis showed the accumulation of DOXIL, but not TXB-001, in skin, particularly palmar and plantar skin samples, and these differences were considered to contribute to their HFS-inducing effects.

Early Detection and Prediction of Anthracycline-Induced Cardiotoxicity　- A Prospective Cohort Study.

BACKGROUND: In the present study, we aimed to investigate whether early cardiac biomarker alterations and echocardiographic parameters, including left atrial (LA) strain, can predict anthracycline-induced cardiotoxicity (AIC) and thus develop a predictive risk score.Methods and Results: The AIC registry is a prospective, observational cohort study designed to gather serial echocardiographic and biomarker data before and after anthracycline chemotherapy. Cardiotoxicity was defined as a reduction in left ventricular ejection fraction (LVEF) ≥10 percentage points from baseline and <55%. In total, 383 patients (93% women; median age, 57 [46-66] years) completed the 2-year follow-up; 42 (11.0%) patients developed cardiotoxicity (median time to onset, 292 [175-440] days). Increases in cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) and relative reductions in the left ventricular global longitudinal strain (LV GLS) and LA reservoir strain [LASr] at 3 months after anthracycline administration were independently associated with subsequent cardiotoxicity. A risk score containing 2 clinical variables (smoking and prior cardiovascular disease), 2 cardiac biomarkers at 3 months (TnT ≥0.019 ng/mL and BNP ≥31.1 pg/mL), 2 echocardiographic variables at 3 months (relative declines in LV GLS [≥6.5%], and LASr [≥7.5%]) was generated. CONCLUSIONS: Early decline in LASr was independently associated with subsequent cardiotoxicity. The AIC risk score may provide useful prognostication in patients receiving anthracyclines.

Artificial intelligence-enabled prediction of chemotherapy-induced cardiotoxicity from baseline electrocardiograms.

Anthracyclines can cause cancer therapy-related cardiac dysfunction (CTRCD) that adversely affects prognosis. Despite guideline recommendations, only half of the patients undergo surveillance echocardiograms. An AI model detecting reduced left ventricular ejection fraction from 12-lead electrocardiograms (ECG) (AI-EF model) suggests ECG features reflect left ventricular pathophysiology. We hypothesized that AI could predict CTRCD from baseline ECG, leveraging the AI-EF model's insights, and developed the AI-CTRCD model using transfer learning on the AI-EF model. In 1011 anthracycline-treated patients, 8.7% experienced CTRCD. High AI-CTRCD scores indicated elevated CTRCD risk (hazard ratio (HR), 2.66; 95% CI 1.73-4.10; log-rank p < 0.001). This remained consistent after adjusting for risk factors (adjusted HR, 2.57; 95% CI 1.62-4.10; p < 0.001). AI-CTRCD score enhanced prediction beyond known factors (time-dependent AUC for 2 years: 0.78 with AI-CTRCD score vs. 0.74 without; p = 0.005). In conclusion, the AI model robustly stratified CTRCD risk from baseline ECG.