Aug 2026· European Heart Journal, Supplement· 0 citations
TL;DR
It is suggested that RV strain assessment provides information complementary to conventional LV–based cardiotoxicity criteria and may occur in the absence of concurrent changes in conventional LV cardiotoxicity parameters as currently defined.
Abstract
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
Cancer therapy–related cardiac dysfunction (CTRCD) remains a major limitation of anthracycline and anti-HER2 therapy, and most monitoring focuses on left ventricular (LV) function. Data on the role of right ventricular (RV) function as an early marker of CTRCD are limited.
To evaluate the association between echocardiographic RV parameters - TAPSE, tricuspid S’ velocity and RV free-wall longitudinal strain (RV-FWLS) - and the development of CTRCD in patients treated with anthracyclines and/or anti-HER2 therapy.
Retrospective, single-center observational study including patients treated with anthracyclines and/or anti-HER2 agents and followed in Cardio-oncology consultation in a district hospital. CTRCD was defined according to contemporary cardio-oncology criteria based on LV ejection fraction and global longitudinal strain. RV function was evaluated by TAPSE, tricuspid S’ and RV-FWLS.
We included 65 women, mean age 60±10 years. Chemotherapy regimens comprised anthracyclines only in 45%, anti-HER2 therapy only in 10% and combined anthracyclines plus anti-HER2 in 45%. According to the HFA-ICOS tool, 34% were at low, 37% at moderate, 17% at high and 12% at very high cardiovascular risk at baseline. Over a median follow-up of 36 months (IQR 23–70), CTRCD occurred in 15 patients (23%). 9 patients (14%) died, including 2 cardiovascular deaths.
At baseline, TAPSE and tricuspid S’ were similar in patients with and without CTRCD (TAPSE 22±2.7 vs 23±2.1mm, p=0.19; S’ 12.5±1.9 vs 12±1.8cm/s, p=0.30), whereas RV-FWLS was significantly less negative in those who subsequently developed CTRCD (−23.6±3.1% vs −26.1±2.8%, p=0.02).
During follow-up, patients with CTRCD showed a greater decline in RV function, with larger reductions in TAPSE (−2±1.9 vs −0.5±1.5mm, p=0.01) and RV-FWLS (+4.8±3.7 vs +2.9±3%, p=0.04). A relative reduction in RV-FWLS ≥15% occurred in 60% of patients with CTRCD versus 20% of those without (p=0.01).
In univariable logistic regression, baseline RV-FWLS was associated with higher odds of CTRCD (OR per 1% less negative strain 1.17, 95% CI [1.03–1.28], p=0.01).
In this cohort of women treated with anthracyclines and anti-HER2 therapy, RV-FWLS identified patients who developed CTRCD, supporting RV strain as a useful tool for early risk stratification and refinement of cardio-oncology surveillance strategies.
B. Andrade, N. Cotrim, C. Coelho et al.· European Heart Journal, Supp...· 0 citations
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 and may improve identification of subclinical cardiac dysfunction before a measurable decline in left ventricular ejection fraction occurs.
T. Mainka, Emil Sergejuk, W. Kotlarski et al.· International Journal of Inn...· 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
Cancer therapy can cause left and right ventricular (RV) cancer therapy-related cardiac dysfunction (CTRCD). How patients transition from having normal myocardial function to isolated left ventricular (LV), RV, or biventricular (BV) CTRCD, and the associations of these phenotypes with post-therapy prognostic measures remain unknown.
We aimed to define patterns of ventricular dysfunction during anthracycline and trastuzumab therapy.
This ancillary study of the EMBRACE-MRI study included women with early-stage HER2-positive breast cancer treated with sequential anthracycline and trastuzumab, prospectively enrolled between 2014 and 2021 at our Hospitals. LV and RV function were assessed by CMR pre-anthracyclines, post-anthracyclines, at 3 and 6 months during trastuzumab therapy, and early post-completion of trastuzumab. All CMR analyses were performed using CVI42. Cardiopulmonary exercise testing was performed early post-completion of trastuzumab. LV CTRCD was defined based on the CREC criteria while RV CTRCD was defined as a >10% reduction in RVEF from baseline to <49%. Patients were classified as having isolated LV CTRCD, isolated RV CTRCD, or biventricular (BV) CTRCD based on the first CTRCD event. Descriptive statistics were used to summarize baseline clinical characteristics, the timing of CTRCD, and CMR data. Between-group comparisons were evaluated using Wilcoxon rank-sum tests for continuous variables.
Among the 153 patients (median age 51.4, IQR: [43.5-57.5] years), the first CTRCD event included LV, RV, or BV CTRCD in 36 (24%), 4 (3%) and 6 (4%) patients respectively (Figure 1). The first instance of RV, LV, and BV CTRCD was 3 months, 3 to 6 months, and 12 months after trastuzumab initiation respectively. Patients also transitioned between phenotypes, with one patient with initial RV CTRCD developing BV CTRCD. Baseline demographics characteristics were similar between groups with no difference in cumulative anthracycline dose. However, patients with RV/BV CTRCD had a lower baseline RVEF (58 [55-59] % vs 61 [58-64]%, p=0.02) and more frequently received right-sided radiation (62% vs 35%) (Figure 2). Post-completion of trastuzumab, LV CTRCD patients had lower VO2 max (17.1 vs 19.2 mL/kg/min, p=0.059) and significantly reduced predicted VO2 max (73% vs 89%, p=0.014) compared to RV/BV CTRCD.
In this cohort of HER2-positive breast cancer patients treated with anthracycline and trastuzumab LV CTRCD was the commonest type of CTRCD, however RV/BV CTRCD occurred in 7% of patients with distinct temporal patterns. LV CTRCD was associated with lower post-treatment functional capacity and RV CTRCD may be more common in those receiving right-sided radiation. These findings underscore the importance of systematic BV monitoring throughout cancer therapy. The long-term prognostic implications of LV vs RV CTRCD is a focus on ongoing investigation.Flow chart, transition between states Baseline characteristics
T. Gonçalves, S. Cai, J. Weiss et al.· European Heart Journal, Supp...· 0 citations
Cancer therapy-induced left ventricular diastolic dysfunction (LVDD) is gaining research attention as a potential early marker of cardiotoxicity. Radiotherapy, chemotherapy, and targeted agents may cause cardiomyocyte energy depletion, cardiac fibrosis, and microvascular dysfunction—known mechanisms of diastolic dysfunction. Heart failure (HF) with preserved ejection fraction and LVDD remain understudied in oncological settings.
We aimed to assess the changes in LV diastolic function caused by cancer treatment.
We prospectively enrolled 60 adults planned for chemotherapy (CT) for breast (n = 50) or gastrointestinal (n = 10) cancers. Exclusion criteria were fewer than 3 visits, a poor acoustic window, or pre-existing cardiac or chronic pulmonary disease. We performed 2D echocardiography at baseline and 1, 3, 6, 9, 12, and 18 months after CT initiation. Left ventricular ejection fraction (LVEF) was considered abnormal if it dropped by over 10% to below 50%. Longitudinal LV systolic dysfunction was defined as a decrease of over 15% to below 7 cm/s in systolic tissue S′ velocity, averaged from septal and lateral S′. We assessed LVDD using the 2025 American Society of Echocardiography algorithm and the parameters: indexed left atrial volume (LAVi); early (E) and late (A) mitral inflow velocities; E/A ratio; isovolumic relaxation time (IVRT); pulmonary artery systolic pressure (PASP); early diastolic tissue e′ velocity (average of septal and lateral e′) (LVe′); and E/e′ ratio. The temporal parameters' changes were estimated using generalised estimating equations (GEE) regression. Correlations were examined using the Spearman and chi-squared tests and Goodman-Kruskal's gamma (γ) statistic.
The mean patient age was 53 years (SD 11.6), with 91.7% female. Half (n = 30) received anthracycline-based CT, either with or without trastuzumab; the remainder received non-anthracycline CT, with or without trastuzumab. The median CT duration was 98 days (IQR: 64, 112). Twenty-seven patients (45%) had radiotherapy. Over a median follow-up of 381 days (IQR: 187, 464), LVE/e' and LVe' declined significantly in the third month. Both parameters showed moderate correlation with LVS’ (Figure 1). Six patients had baseline LVDD; in one, it progressed from grade 1 to grade 2. New-onset LVDD occurred in 6 patients (10%), all grade 1 (Figure 2). Among them, two had transient LVDD; in two cases, LVDD advanced to grade 2, and one patient showed symptoms of HF (NYHA class II). There was a trend toward LVDD at the first and sixth months (Figure 2). No new-onset LVDD patient developed abnormal LVEF, although two had concurrent longitudinal systolic dysfunction. LVDD and longitudinal systolic dysfunction showed a positive association (ꭓ² = 5.2, p = 0.022; Kruskal’s γ = 0.64).
Cancer therapy-related LVDD may develop early and present as either a transient or persistent condition. Its clinical implications need further investigation.
S. Slavcheva, A. Angelov· European Heart Journal, Supp...· 0 citations
Subclinical cardiac dysfunction may develop early during anticancer treatment, preceding a decline in left ventricular ejection fraction (LVEF). While myocardial deformation imaging enables early detection of myocardial injury, the temporal evolution of diastolic dysfunction and left atrial (LA) remodeling during therapy remains incompletely characterized.
To evaluate the 12-month temporal evolution of myocardial deformation, diastolic function, and LA volumetric and functional parameters in patients with breast cancer receiving anticancer treatment.
This multicenter prospective study included 123 patients from four medical centers with HER2-positive breast cancer. All patients received standard-of-care anticancer therapy, including anthracycline-based chemotherapy followed by trastuzumab. Transthoracic echocardiography was performed at baseline and at 3, 6, 9, and 12 months of follow-up. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were assessed, along with tissue Doppler e′ velocities (septal, lateral), average E/e′. Left atrial remodeling and function were assessed using indexed maximal and minimal LA volumes (LAVmax, LAVmin) and total LA emptying function (LAEF).Data are presented as mean ± standard deviation. Changes over time were assessed using repeated-measures ANOVA; a two-sided p-value <0.05 was considered statistically significant.
LVEF remained within the normal range throughout follow-up (62 ± 4% at baseline; 59 ± 5% at 12 months). GLS progressively deteriorated from −20.2 ± 1.8% to −17.1 ± 2.0% at 6 months and −15.7 ± 2.3% at 12 months (relative reduction of 15% and 22%, respectively). Diastolic indices worsened with septal e′ decreasing from 8.1 ± 1.4 to 5.9 ± 1.2 cm/s and lateral e′ from 11.2 ± 1.8 to 8.1 ± 1.5 cm/s, while average E/e′ increased from 10.1 ± 2.1 to 15.6 ± 3.0 at 12 months, indicating progressively elevated left ventricular filling pressures. Of particular interest, significant involvement of the LA was observed. Indexed LAVmin increased from 10.4 ± 4.2 to 18.1 ± 6.3 ml/m², preceding enlargement of LAVmax from 28.3 ± 6 to 38 ± 8.1 ml/m². LAEF progressively declined from 62% at baseline to 46% at 12 months, reflecting progressive atrial functional impairment and remodeling.
Anticancer treatment is associated with a structured temporal continuum of subclinical cardiac dysfunction, in which early impairment of myocardial deformation is followed by progressive alterations in diastolic mechanics and left atrial structure and function, despite preserved left ventricular ejection fraction. Serial echocardiographic assessment enables early identification of cardiotoxicity and supports timely risk stratification before overt systolic dysfunction develops.
L. Hazarapetyan, H. Hayrapetyan, P. Zelveian et al.· European Heart Journal, Supp...· 0 citations