No detectable early subclinical cardiotoxicity within 12 weeks of thoracic radiotherapy under predominantly low cardiac dose exposure: a prospective cohort study

Dosimetric associations between high-dose cardiac exposure and global longitudinal strain deterioration after definitive radiotherapy for lung cancer

Radiation-induced cardiac injury is an important late effect of definitive radiotherapy for lung cancer (1). Global longitudinal strain (GLS) is a sensitive marker of subclinical myocardial dysfunction; however, its relationship with detailed cardiac dosimetry remains incompletely defined (2). To evaluate associations between cardiac dose–volume parameters and GLS deterioration after definitive radiotherapy for non-metastatic lung cancer, and to assess effect modification by hypertension. Patients with non-metastatic lung cancer treated with definitive radiotherapy or concurrent chemoradiotherapy were identified from a prospective registry with protocol-driven echocardiographic follow-up. Cardiac dose–volume parameters for the whole heart and cardiac substructures were derived using a standardized cardiac atlas. GLS change from baseline to follow-up was analyzed using multivariable linear regression adjusted for baseline GLS and established cardiovascular risk factors, with interaction analyses for hypertension. Ninety-eight patients with paired baseline and follow-up echocardiography were included. Median GLS significantly deteriorated from −16.17 at baseline to −14.11 at follow-up, corresponding to a median increase of 1.82% (95% CI, 1.40–2.25; p < 0.001) (Figure 1). In adjusted analyses, higher total prescribed dose was significantly associated with GLS deterioration (β = 0.009 per 10 Gy increase, 95% CI 0.001–0.017, p = 0.032). Among cardiac substructures, ventricular high-dose exposure demonstrated the strongest associations with GLS change. Specifically, both left ventricular (LV) and right ventricular (RV) V45 (percentage volume receiving ≥45 Gy) were significantly associated with GLS deterioration (LV V45: β = 0.351 per 10% increase, 95% CI 0.044–0.658, p = 0.026; RV V45: β = 0.840, 95% CI 0.240–1.439, p = 0.007). In contrast, atrial dose parameters were not associated with GLS change. Hypertension significantly modified the association between LV V45 and GLS deterioration. GLS change per 10% increase in LV V45 was modest among patients without hypertension but markedly greater among patients with hypertension, with a significant interaction (p for interaction = 0.027) (Figure 2). During follow-up, 8 patients (8.2%) experienced CVD events, including arrhythmia, heart failure, and pulmonary thromboembolism. High-dose ventricular cardiac exposure during definitive radiotherapy for lung cancer is associated with subclinical myocardial dysfunction as measured by GLS, with a disproportionately greater impact among patients with hypertension. These findings support ventricular dose optimization and hypertension-informed cardiac surveillance strategies in lung cancer radiotherapy.Paired change in GLS  Association between V45 and GLS

Temporal dynamics of cardiac biomarkers in therapy‑related cardiotoxicity: a prospective cardio‑oncology cohort study

Cardiotoxicity associated with antineoplastic therapies remains an important clinical challenge in modern oncology. Early identification of subclinical cardiac injury may improve cardiovascular surveillance and long-term outcomes in cancer patients. This prospective observational cohort study included 90 adult patients with breast cancer, lymphoma, or lung cancer receiving potentially cardiotoxic therapy. Patients with clinically manifest heart failure, severe arrhythmias, advanced renal disease, recent acute myocardial infarction, untreated severe valvular disease, or other major cardiovascular comorbidities were excluded. High-sensitivity cardiac troponin T (hs-cTnT), NT-proBNP, and soluble ST2 (sST2) were measured at baseline, during treatment, at therapy completion, and at late follow-up. Non-parametric tests were used for repeated-measures and subgroup comparisons. Significant temporal variations were observed for all biomarkers. hs-cTnT increased from 5 [3–8] ng/L at baseline to 15 [10–25] ng/L at T2, while NT-proBNP increased from 120 [80–190] pg/mL to 210 [150–320] pg/mL. sST2 demonstrated a delayed elevation and remained increased at follow-up. Distinct biomarker patterns were observed across malignancy subgroups, with higher hs-cTnT increases in breast cancer, more prominent NT-proBNP elevation in lymphoma, and higher sST2 values in lung cancer. Serial biomarker assessment may provide complementary information on myocardial injury, ventricular stress, and fibrotic remodeling during cancer therapy. The observed biomarker trajectories are suggestive of different biological processes involved in therapy-related cardiotoxicity, but they should be interpreted in conjunction with imaging findings and clinical outcomes.

Layer-specific myocardial strain for early detection of anthracycline-induced cardiotoxicity: the CARDIAC-STRAIN prospective diagnostic study protocol

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.

Baseline and early changes in cardiac biomarkers as predictors of global longitudinal strain deterioration during breast cancer therapy: a PRADAII substudy

Cardiac biomarkers are recommended for risk stratification before and during potentially cardiotoxic cancer therapy, but the prognostic value of baseline levels and early changes for subsequent left ventricular (LV) dysfunction remains unclear. To evaluate wheter baseline and early changes in high-sensitivity cardiac troponins (hs-cTnI, hs-cTnT) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) predict changes in global longitudinal strain (GLS) over 18 months. In the randomized PRADAII, 138 women treated with anthracyclines (±trastuzumab) received sacubitril/valsartan or placebo and underwent serial biomarker sampling and cardiac imaging at baseline, post-anthracycline, and 18 months. Longitudinal changes in GLS and left ventricular ejection fraction (LVEF) were analyzed using adjusted linear mixed models, including exploratory analyses of combined, persistent, and peak biomarker elevations. Mean age was 54.0±9.4 years. At baseline, no patients had hs-cTnI values above the sex-specific 99th percentile, 6 (4%) had hs-cTnT >99th percentile, and 16 (12%) had NT-proBNP >125 ng/L. Mean baseline GLS was −19.5±2.1% and CMR- and echocardiography-derived LVEF was 60.3±4.8% and 58.3±6.2%, respectively. GLS declined modestly over follow-up, with less deterioration in the sacubitril/valsartan group than in the placebo group (ΔΔ −1.26, 95% CI −2.19 to −0.33). Both hs-cTnI and hs-cTnT increased markedly after anthracycline therapy, with 16.7% and 71.7% exceeding the sex-specific 99th percentile at peak, whereas NT-proBNP showed modest changes with wide inter-individual variability. Transient and persistent troponin elevation occurred in 60.1% and 11.6%, respectively; corresponding NT-proBNP elevations in 5.1% and 7.3%, and combined troponin and NT-proBNP elevation in 9.4%. Baseline biomarker levels were not associated with GLS deterioration, and no biomarker–treatment interactions were observed (all p for interaction >0.27). Early post-anthracycline changes in hs-cTnI, hs-cTnT, or NT-proBNP were not predictive of subsequent GLS decline, nor were peak or persistent elevations (Table 1, Figure 1). No significant associations were observed between baseline or early biomarker levels and changes in LVEF assessed by echocardiography or CMR. In our breast cancer cohort with preserved baseline LV function, baseline levels and early changes in hs-cTnI, hs-cTnT, and NT-proBNP were not associated with subsequent deterioration in GLS over 18 months. Larger studies including higher-risk patients and clinical endpoints are needed to clarify the role of cardiac biomarkers in individualized cardiotoxicity risk stratification.  

Late cardiac effects of anthracycline-based therapy in childhood cancer survivors: a CMR study of cardiac strain and function.

Cardiac monitoring and incidence of cardiotoxicity cardiomyopathy among breast cancer patients undergoing anthracycline regimen chemotherapy: insight from a single centre study

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.