Aug 2026· European Heart Journal, Supplement· 0 citations
Abstract
Anthracyclines remain cornerstone agents in oncology, yet their cardiotoxic potential poses a substantial clinical challenge. Up to 30% of treated patients develop some degree of cardiac dysfunction, with overt heart failure occurring in 2–5% of cases. Current surveillance relies on serial ejection fraction measurements, which detect damage only after significant myocardial injury has occurred. Histopathological evidence consistently shows that the subendocardial layer suffers earliest and most severely from anthracycline exposure—often weeks before any decline in global ventricular function becomes apparent. This temporal gap represents a missed opportunity for timely cardioprotective intervention.
We designed the CARDIAC-STRAIN study to determine whether layer-specific strain analysis by cardiac magnetic resonance can identify subclinical cardiotoxicity substantially earlier than conventional echocardiographic surveillance, potentially enabling earlier initiation of cardioprotective treatment.
This prospective single-centre diagnostic cohort study will recruit 120 consecutive patients scheduled for anthracycline-based chemotherapy (sample size calculated to detect 20% sensitivity difference, power 80%, α=0.05). Eligible participants are aged 18–75 years with preserved baseline ejection fraction (≥50%) and no prior anthracycline exposure or known cardiomyopathy. Each patient undergoes blinded comprehensive cardiac evaluation at four timepoints: baseline, after the fourth chemotherapy cycle, four weeks post-treatment, and at six months' follow-up. The protocol includes 1.5T cardiac MRI with cine sequences, native and post-contrast T1 mapping, T2 mapping, and late gadolinium enhancement. Layer-specific strain is quantified at subendocardial, midmyocardial, and subepicardial levels using dedicated feature-tracking software. Parallel assessments include three-dimensional echocardiography and cardiac biomarkers (troponin, NT-proBNP). Primary endpoints: ejection fraction decline >10% to below 50%, decline >15% with preserved function, or layer-specific strain deterioration >15% from baseline.
Study hypothesis: We hypothesize that layer-specific strain analysis will detect subclinical myocardial injury approximately 2–4 weeks earlier than conventional ejection fraction monitoring, with significantly improved diagnostic sensitivity compared to standard surveillance protocols.
Expected outcomes: If layer-specific strain analysis proves capable of reliably identifying subclinical cardiotoxicity before irreversible damage occurs, this approach may help shift clinical practice from heart failure treatment to early prevention in cardio-oncology. The study received ethics committee approval in November 2025, and patient recruitment is underway.
Introduction: Anthracycline-based chemotherapy remains an important component of breast cancer treatment, but its use is limited by the risk of cardiotoxicity, including subclinical left ventricular dysfunction and cancer therapy-related cardiac dysfunction. Conventional monitoring based on left ventricular ejection fraction may detect myocardial injury relatively late. Left ventricular global longitudinal strain (LV GLS), assessed by speckle-tracking echocardiography, has emerged as a more sensitive parameter for identifying early myocardial impairment. This systematic review summarizes current evidence on the role of LV GLS in the early detection of anthracycline-induced cardiotoxicity in adult breast cancer patients.
Methods: A systematic literature review was performed using PubMed/MEDLINE. The search strategy combined terms related to breast cancer, anthracyclines, global longitudinal strain, speckle-tracking echocardiography, and cardiotoxicity. Original English-language studies focused on adult breast cancer patients receiving anthracycline-based chemotherapy and undergoing strain echocardiographic assessment were considered eligible. After title, abstract, and full-text screening, seven studies were included in the qualitative synthesis.
Results: The included studies consistently suggested that LV GLS detects subclinical myocardial dysfunction earlier than conventional left ventricular ejection fraction assessment in breast cancer patients treated with anthracyclines. Several studies reported early impairment in myocardial deformation parameters during or shortly after chemotherapy, even in the presence of preserved ejection fraction. The reviewed evidence also indicated that changes in GLS may have diagnostic and prognostic relevance for subsequent cardiotoxicity and later decline in cardiac function. More recent studies additionally supported the value of integrating GLS with other echocardiographic parameters in the assessment of cancer therapy-related cardiac dysfunction.
Conclusions: LV GLS appears to be a sensitive and clinically useful echocardiographic marker for the early detection of anthracycline-induced cardiotoxicity in adult breast cancer patients. Its use may improve identification of subclinical cardiac dysfunction before a measurable decline in left ventricular ejection fraction occurs. Further studies are needed to clarify optimal cutoff values, monitoring intervals, and the role of GLS within standardized cardio-oncology surveillance protocols.
T. Mainka, Emil Sergejuk, W. Kotlarski et al.· International Journal of Inn...· 0 citations
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.
D. Cardinale, Nicola Cosentino, Chiara Morocutti et al.· JACC CardioOncology· 1 citation
Early radiation-induced cardiac injury in patients receiving thoracic radiotherapy (RT) remains insufficiently characterized. Global longitudinal strain (GLS) and circulating biomarkers such as high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) may detect subclinical myocardialdamage. This prospective single-center cohort study enrolled 47 adults with thoracic malignancies treated with curative-intent RT. Cardiac assessments were performed at baseline, 1 week, and 12 weeks post-RT. GLS was measured by two-dimensional speckle-tracking echocardiography, and hs-cTnT and NT-proBNP were quantified using high-sensitivity immunoassays. Mean heart dose (MHD) was categorized as < 10 Gy or ≥ 10 Gy to explore dose-stratified differences within this predominantly low-dose exposure cohort. Temporal changes and dose-stratified differences were analyzed using non-parametric tests. GLS remained stable across timepoints (median − 18.06% at baseline, − 18.72% at week 1, and − 18.59% at week 12; p = 0.650). Similarly, hs-cTnT showed no significant variation (7.30, 7.50, and 6.60 ng/L, respectively; p = 0.842), and NT-proBNP demonstrated modest, non-significant increases (43.0, 48.5, and 55.5 pg/mL; p = 0.797). Stratification by MHD revealed no significant differences in GLS or biomarker levels at any timepoint. No dose-dependent associations were observed These findings were consistent across subgroups and in sensitivity analyses restricted to completers, in a cohort with a median MHD of 5.1 Gy. Contemporary thoracic RT was not associated with detectable early subclinical cardiotoxicity within the first 12 weeks under predominantly low cardiac dose exposure. Early cardiac alterations may depend on higher radiation exposure or longer follow-up, supporting longitudinal surveillance strategies.
Iván Valdés – Orrego, Francisco Acevedo, T. Merino· Cardio-Oncology· 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.
Cancer-therapy-related cardiac dysfunction (CTRCD) is traditionally assessed using left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (LV GLS). However, despite the recognized prognostic role of right ventricular (RV) function in other cardiovascular setting, RV deformation parameters are not included in current CTRCD definitions, are not routinely assessed in cardio-oncology, and remain incompletely characterized.
To evaluate changes in RV strain parameters during anthracycline-based chemotherapy in breast cancer (BC) patients stratified by baseline cardiotoxicity risk, and to explore whether RV strain changes occur independently of conventional LV cardiotoxicity criteria.
This prospective, single-center observational study included 71 consecutive women with BC (mean age 55.4 ± 11.2 years). Baseline cardiovascular risk was stratified using the HFA-ICOS score. All patients underwent cardiovascular monitoring and preventive management in accordance with the 2022 ESC Cardio-Oncology Guidelines. Comprehensive transthoracic echocardiography was performed at baseline (T0), during treatment (T1), and after completion of chemotherapy (T2). In addition to LVEF and LV GLS, right ventricular global longitudinal strain (RV GLS) and right ventricular free wall longitudinal strain (RV FWLS) were assessed. Subclinical RV dysfunction was operationally defined as a relative reduction of ≥15% in RV GLS from baseline. Patients were categorized into a low-risk group (group 1) and a combined moderate/high/very high-risk group (group 2). All patients received anthracycline-containing chemotherapy regimens with a mean cumulative anthracycline dose of 236.4 mg/m². Longitudinal changes across the three time points were analyzed using repeated-measures analysis with pairwise comparisons.
Across the entire cohort, a significant overall time effect was observed for LV GLS, RV GLS and RV FWLS across T0, T1 and T2 (Table 1). Subclinical CTRCD defined by a relative reduction in LV GLS, was identified in 19 (26.7%) patients, while subclinical RV cardiotoxicity occurred in 16 (22.5%) patients. Notably, subclinical RV dysfunction was not accompanied by parallel changes in LVEF or LV GLS at the same time points.
Anthracycline therapy is associated with progressive impairment of RV deformation parameters, which may occur in the absence of concurrent changes in conventional LV cardiotoxicity parameters as currently defined. These findings suggest that RV strain assessment provides information complementary to conventional LV–based cardiotoxicity criteria.Table 1
Z. Tlegenova, A. Amanova, S. Balmagambetova et al.· European Heart Journal, Supp...· 0 citations
Breast cancer is one of the most prevalent malignant neoplasms and cardiotoxicity induced by treatment with anthracyclines and trastuzumab is a major complication. Transthoracic echocardiography (TTE) is considered the gold-standard method for assessing cardiac function, with left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) being the main parameters used for early detection of cardiotoxicity. Left atrial (LA) strain represents the myocardial deformation of this structure and is assessed based on three main parameters, among which peak atrial longitudinal strain (PALS) stands out for best reflecting global LA function.
To evaluate left atrial strain by TTE as a predictor of cardiotoxicity at different stages of treatment with anthracyclines and trastuzumab in women with breast cancer.
This was a retrospective, quantitative, descriptive, and correlational study. A total of 51 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 two-dimensional left atrial deformation, 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: peak E-wave velocity, peak A-wave velocity, E/A ratio, septal e′ velocity, lateral e′ velocity, average E/e′ ratio, LA volume index, peak tricuspid regurgitation velocity, GLS, LVEF, and PALS - analysed using EchoPAC™ software (version 206).
The mean follow-up time between baseline TTE and final TTE was 17 months, with a standard deviation of ± 4.61 months. Cardiotoxicity was identified in 9 women, in whom early functional changes were observed, with significant reductions in septal and lateral e′ velocities at all analysed time points. Systolic function showed significant differences between groups at all time points, both in LVEF and GLS (p < 0.001), demonstrating progressive contractile dysfunction, whereas PALS showed significant changes only at TTE 2 (p < 0.001), suggesting early but non-sustained atrial dysfunction.
GLS and LVEF were the most sensitive echocardiographic parameters for differentiating between groups with and without cardiotoxicity, showing consistent changes throughout the study. Septal and lateral e′ velocities allowed identification of diastolic function alterations from intermediate stages onward, while PALS demonstrated discriminative capacity at an early point.Tabel 1Group without cardiotoxicity Tabel 2Group with cardiotoxicity
R. M. Figueiredo De Sousa, V. Fonseca, M. Henriques et al.· European Heart Journal, Supp...· 0 citations