Aug 2026· JACC CardioOncology· Vol 8, pp. 364 - 375· 1 citation· 29 references
Medicine
TL;DR
A simplified risk score based on readily available clinical and echocardiographic variables for predicting anthracycline-related cardiotoxicity and the RE-ACT score provides additional post-treatment prognostic value is developed and validated and supports a practical 2-step strategy for personalized surveillance in cardio-oncology.
Abstract
Background Anthracycline-induced cardiotoxicity is a major limitation of cancer therapy, highlighting the need for accurate and practical risk stratification. Although current guidelines recommend the Heart Failure Association–International Cardio-Oncology Society (HFA-ICOS) score for baseline risk assessment, its complexity may limit routine clinical use. Objectives This study sought to develop and validate a simplified risk score based on readily available clinical and echocardiographic variables for predicting anthracycline-related cardiotoxicity, and to compare its performance with the HFA-ICOS model. Methods We retrospectively analyzed 2,612 adult cancer patients with baseline left ventricular ejection fraction (LVEF) of ≥50% treated with anthracyclines. Echocardiography was performed at baseline, during therapy, and up to 2 years after treatment. Cardiotoxicity was defined as a decrease in LVEF of >10 percentage points to a value <50% or the development of heart failure. The predictive performance of the HFA-ICOS score was assessed using the area under the receiver operating characteristic curve (AUC). A simplified model was derived using logistic regression with cross-validation and was further validated with machine learning techniques. External validation was conducted in an independent cohort of 819 patients. Results Over the first 2 years, the likelihood of cardiotoxicity was higher in the moderate (HR: 1.44, 95% CI: 1.02-2.06) and high (HR: 1.84, 95%:CI: 1.36-2.50) HFA-ICOS risk categories compared to the low-risk group. The cumulative incidence of cardiotoxicity was 8.3% (95% CI: 7.1%-9.1%) at 12 months, with only 5 additional events observed in patients still at risk through 2 years. The HFA-ICOS score showed good discrimination at 1 year (AUC: 0.76, 95% CI: 0.67-0.86). A simplified model including postchemotherapy LVEF and cumulative anthracycline dose (RE-ACT score) demonstrated higher accuracy at 1 year (AUC: 0.83, 95% CI: 0.74-0.93) though not statistically different. Combining both scores in the derivation cohort further improved predictive performance (AUC: 0.87, 95% CI: 0.80-0.95; P < 0.001 vs HFA-ICOS score). In the validation cohort, the RE-ACT score achieved an AUC of 0.88 (95% CI: 0.80-0.95) at 1 year. Conclusions HFA-ICOS score effectively stratifies baseline risk, while the RE-ACT score provides additional post-treatment prognostic value. Their integration supports a practical 2-step strategy for personalized surveillance in cardio-oncology.
Cardio-oncology patients face an increased risk of chemotherapy-related cardiotoxicity (CTRCD). The Heart Failure Association (HFA)/International Cardio-Oncology Society (ICOS) score is a validated tool for cardiovascular (CV) risk stratification. Although cardiac biomarkers play a key role in CTRCD risk assessment and diagnosis, their availability in routine clinical practice remains limited.
We aimed to compare the performance of the full HFA-ICOS model, incorporating cardiac biomarkers, with biomarker-free models, including a simplified clinical model and a modified model integrating baseline global longitudinal strain (GLS), in anthracycline-treated patients.
We retrospectively analyzed 316 patients treated with anthracyclines across three centers. Baseline CV risk was assessed using the HFA-ICOS score. Three models were evaluated: (1) the full HFA-ICOS model including cardiac biomarkers (troponin and NT-proBNP), (2) the mini-HFA-ICOS model excluding biomarkers, and (3) a modified biomarker-free HFA-ICOS model including baseline GLS. CTRCD was defined according to the 2022 ESC guidelines. Discriminative performance was assessed using recever operating characteristic (ROC) curves, and comparisons between models were performed using DeLong’s test. Risk reclassification analyses were also conducted.
Asymptomatic (27%, 39%, 46%, and 60%; p 0.017) and symptomatic CTRCD (1.3%, 4.6%, 13%, and 40%; p < 0.001) were more frequent in higher risk groups. For all CTRCD definitions, the full HFA-ICOS model showed higher discrimination than the mini model (AUC 0.640 vs 0.604; p = 0.004). When baseline GLS was incorporated into the biomarker-free model, discrimination was numerically improved compared with the mini model (AUC 0.643 vs 0.604; p = 0.0004) and was comparable to the full HFA-ICOS model (AUC 0.643 vs 0.640; p = 0.75), although differences in AUC did not reach statistical significance. When excluding mild asymptomatic CTRCD to minimize biomarker-related circularity, the modified biomarker-free HFA-ICOS model including GLS demonstrated discrimination comparable to the full and mini models (AUC 0.622 vs 0.617; p = 0.87; AUC 0.622 vs 0.605; p = 0.39). Compared with the full HFA-ICOS model, the mini model resulted in risk reclassification in 7.6% of patients, entirely driven by downgrading, whereas inclusion of GLS reduced discordance with the full model (5.1%) and reclassified 3.8% of patients compared with the mini model.
While integration of cardiac biomarkers improves CTRCD risk stratification within the HFA-ICOS framework, baseline GLS provides meaningful incremental value when biomarkers are unavailable or when biomarker-independent CTRCD definitions are applied. GLS may therefore represent a pragmatic alternative to biomarkers for refining cardiotoxicity risk assessment in routine cardio-oncology practice.
C. Madaudo, A. Cannatà, M. Camilli et al.· European Heart Journal, Supp...· 0 citations
In advanced stage breast cancer, conventional chemotherapy is one of the most commonly used therapeutic options; however, it is associated with a potential risk of cardiotoxicity. Although the cardiotoxic effects of anthracyclines on the left ventricular function have been well studied, alterations of the right ventricle continue to be controversial. The assessment of conventional echocardiographic parameters remains the first-line imaging approach for evaluating and monitoring longitudinal right ventricular function.
The purpose of this study was to evaluate the early effects of anthracycline-based chemotherapy on right ventricular function in newly diagnosed breast cancer patients at low risk for cardiotoxicity.
This prospective study included 31 newly diagnosed breast cancer patients at low risk for cardiotoxicity who were treated with anthracycline-based chemotherapy. Baseline cardiovascular risk assessment was conducted according to established evidence-based risk stratification proformas for anthracycline cardiotoxicity. All patients received four cycles of chemotherapy. Transthoracic echocardiography was performed prior to anthracycline initiation, after the fourth (last) cycle, and 12 months after treatment completion. Variables included right heart parameters such as right ventricular (RV) end-diastolic and outflow tract dimensions, tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (FAC%), Tissue Doppler systolic RV velocity (RVs’) and systolic pulmonary artery pressure.
Right ventricular (RV) outflow tract dimensions increased by the end of the treatment protocol and persisted up to one year; however, statistical significance was observed only at the end of follow-up (III) compared with both baseline (I) and end-of-treatment (II) values (27,97±4,48 vs. 30,42±2,27, III vs. I (>) p=0,005; III vs. II (>) p=0,0001). RV end-diastolic dimensions although increasing, showed no significant change during follow-up. TAPSE and RVs′ demonstrated a significant reduction, with statistical significance evident at the end of follow-up compared with both baseline and end-of-treatment values. (22,42±2,80 vs. 21,19±2,04, III vs. I (<) p=0,029, III vs. II (<) p=0,028 and 14,00±1,69 vs. 13,03±1,37, III vs. I (<) p=0,002; III vs. II (<) p=0,001 respectively). No significant changes were observed in RV FAC% or systolic pulmonary artery pressure during treatment or at one-year follow-up.
Although right ventricular dysfunction is not considered in the universal definition of cardiotoxicity, the right heart may undergo significant deteriorations. Our analysis demonstrated a significant decline in right ventricular function during anthracycline-based cardiotoxic therapy and persisting up to one year after treatment completion, even in patients with low cardiotoxic risk, despite changes being subclinical and largely within normal ranges.
I. Gigovska Dimova, G. Petkovska, I. Ismaili et al.· European Heart Journal, Supp...· 0 citations
Anthracycline chemotherapy is associated with cardiotoxicity, underscoring the importance of minimizing modifiable cardiac risk factors in affected individuals. This study evaluated cardiac function, prevalence of metabolic syndrome and smoking, and awareness of prior cardiotoxic treatment among adult survivors of childhood cancer treated with anthracyclines at the pediatric oncology service in Iceland between 1981 and 2011 (n=89). Data were collected from medical records, self-reported questionnaires, and clinical assessments conducted between 2016 and 2019. Of 76 eligible survivors, 60 participated (29 females, 31 males; aged 20 to 48 y). Two individuals were excluded before enrollment due to previously diagnosed heart failure. Left ventricular dilation was observed in 15 participants (25%), predominantly mild to moderate, with 1 severe case. The prevalence was lower after BSA indexing. Metabolic syndrome was present in 20% of participants, and 20% reported current smoking. Approximately half of the participants reported undergoing echocardiography within the past 10 years, while only 10% were aware that their cancer treatment could cause cardiotoxicity. These findings suggest that survivors treated with anthracyclines require systematic surveillance and targeted interventions to address modifiable cardiovascular risk factors. Increasing awareness of prior cardiotoxic cancer treatment among survivors and health care providers may facilitate cardiovascular risk reduction.
Vigdís H Viggósdóttir, H. Helgason, Helga Jónsdóttir et al.· Journal of pediatric hematol...· 0 citations
Background and Objectives: Although modern oncologic therapies have substantially improved cancer survival and overall prognosis, they have also led to an increasing burden of cardiovascular toxicity. Preventing severe complications such as heart failure and death remains a major priority, while maintaining the need for effective and potentially curative cancer therapy. Careful patient monitoring and early detection of cardiovascular complications may allow the timely implementation of cardioprotective strategies and treatments that could delay or prevent myocardial toxicity. Materials and Methods: A total of 92 women with breast cancer were enrolled in a prospective observational cohort study. All patients received an anthracycline-based chemotherapy regimen, cyclophosphamide, docetaxel and trastuzumab. Biomarker assessment, including NT-proBNP, high-sensitivity cardiac troponin I (hs-cTnI), Gal-3, and GDF-15, was performed at baseline and at the initiation of trastuzumab-based therapy. A comprehensive diastolic function assessment was performed, including transmitral Doppler flow parameters and tissue velocities. Patients were followed for 12 months, and all cardiovascular events occurring during the follow-up period were recorded. Results: Biological and ecocardiographic parameters were analyzed and multiple models of prediction were made. To identify predictors of estimated left ventricular filling pressure (eLVFP), stepwise multiple linear regression analyses were performed, and four significant predictors of left ventricular end-diastolic filling pressure were identified: one echocardiographic parameter (baseline LV filling pressure) and three biological variables (changes in Gal-3, GDF-15, and hs-cTnI levels after treatment). The overall regression model was highly significant (p < 0.001) and explained 77.07% of the variance in the dependent variable. Gal-3 was the strongest predictor of left ventricular filling pressure (p < 0.001). Conclusions: The regression analyses suggest that this phenotype is multifactorial, with echocardiographic indices capturing the functional component and circulating biomarkers reflecting complementary aspects of the underlying biological response. This multimodal approach may therefore help identify patients with early treatment-related cardiac changes and potentially those at increased risk of subsequent CTRCD, particularly during a period when conventional LVEF-based surveillance may still appear reassuring.
A. Farcaș, C. Goidescu, M. Stoia et al.· Medicina· 0 citations
Anthracyclines remain a cornerstone of breast cancer therapy but carry a significant risk of cancer therapy-related cardiac dysfunction (CTRCD). This study evaluates the incidence of CTRCD in an Indonesian setting using the latest 2022 ESC Cardio-Oncology guidelines, focusing on subclinical markers such as high-sensitivity Troponin I (hs-cTnI), Global Longitudinal Strain (GLS) and Mechanical Dispersion (MD).
This retrospective analytical cohort study involved 98 breast cancer patients treated with anthracyclines at a national referral hospital in Indonesia from July 2018 to February 2020. Clinical assessments, hs-cTnI, and echocardiography (LVEF, GLS, and MD) were performed at baseline, 1, 3, and 6 months. CTRCD was defined per the 2022 ESC criteria.
CTRCD occurred in 74.5% of patients, predominantly as asymptomatic mild cases (63.26%). While symptomatic CTRCD was relatively low (7.14%), asymptomatic dysfunction was detected as early as one-month post-chemotherapy. A significant progressive decline was observed in LVEF (68.2 ± 6.2% to 61.3 ± 8.8%,
p
< 0.001) and GLS (-19.7 ± 2.9% to -17.1 ± 3.5%,
p
< 0.001). Notably, mechanical dispersion significantly increased over time (
p
= 0.029), and median hs-cTnI surged from 1.6 ng/L to 82.2 ng/L (
p
< 0.001) by month 6.
The high incidence of asymptomatic CTRCD underscores the inadequacy of relying on clinical symptoms alone. Integration of hs-cTnI, GLS, and mechanical dispersion monitoring is may be essential for early detection and enables timely cardioprotective intervention.
Breast cancer is one of the most common malignancies worldwide. Despite advances in treatment, such as anthracycline-based chemotherapy and trastuzumab, which have contributed to increased survival of cancer patients, these therapies can increase the risk of cardiotoxicity, making cardiac monitoring crucial in this population. The Myocardial Work Index (MWI) has emerged as a tool to predict the risk of cardiotoxicity, especially in patients with significant blood pressure variations during treatment. Using the left ventricular pressure-strain loop technique, MWI evaluates myocardial work and calculates global work index (GWI), global wasted work (GWW), global constructive work (GCW), and global work efficiency (GWE).
To determine the added value of myocardial work indices compared with global longitudinal strain (GLS) assessed by transthoracic echocardiography (TTE) in the diagnosis of chemotherapy-associated cardiotoxicity in women with breast cancer.
This was a retrospective, observational, descriptive-correlational study. A total of 40 women with breast cancer were included through a non-probabilistic sampling method, all of whom underwent chemotherapy with anthracyclines and adjuvant therapy with trastuzumab. Serial echocardiographic monitoring of systolic and diastolic function parameters was performed, including the assessment of global longitudinal deformation and myocardial work index, at four time points: pre-treatment (baseline TTE), first evaluation during treatment (TTE 2), second evaluation during treatment (TTE 3), and post-treatment (final TTE). Cardiac dysfunction related to oncological therapy was defined as a decrease in LVEF to < 50% and/or a relative reduction in GLS of > 15%, according to the 2022 consensus document of the European Society of Cardiology (ESC). Study variables: systolic and diastolic blood pressure, left ventricular ejection fraction (LVEF), GLS, global work index, global wasted work, global constructive work, and global work efficiency - analysed using EchoPAC™ software (version 206).
The mean follow-up time between the first and last TTE was 17 months, with a standard deviation of 3.1 months. When analysed together and separately in two groups—women who developed cardiotoxicity and those who did not—the MWI indices showed patterns similar to GLS and LVEF, decreasing between TTE1 and TTE3 and partially recovering at final TTE, except for GWW, which behaved in the opposite manner. It was observed that in the group that developed cardiotoxicity, some women already had altered GWW and GWE before treatment. The most significant changes in all study variables occurred at TTE3.
This study highlighted the added value of MWI relative to GLS in diagnosing cardiotoxicity in women with breast cancer. The results showed that MWI behaves similarly to GLS, suggesting that combining the two methods—MWI and GLS—may enhance the detection of cardiotoxicity.Correlation between GLS and MWI
R. M. Figueiredo De Sousa, V. Fonseca, C. Azevedo et al.· European Heart Journal, Supp...· 0 citations