Early blood pressure, cardiac biomarker, and strain changes for risk stratification of cardiovascular toxicity during VEGFR-TKI therapy: a cardio-oncology cohort study

Background Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) have become integral to the treatment of several solid tumors but are associated with a distinctive spectrum of cardiovascular toxicity, particularly hypertension and myocardial dysfunction. Because vascular and myocardial abnormalities may emerge soon after treatment initiation, we evaluated whether early changes in blood pressure, cardiac biomarkers, and echocardiographic strain could provide complementary information for cardio-oncology risk stratification. Methods We analyzed a retrospective cohort of 640 adults initiating axitinib, sunitinib, pazopanib, sorafenib, or lenvatinib. Baseline cardiovascular risk factors, prior cardiotoxic therapy, blood pressure, high-sensitivity cardiac troponin I (hs-cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS) were assessed, with repeat evaluation at 4 weeks. The primary outcome was the first clinically significant cancer therapy-related cardiovascular toxicity (CTR-CVT) within 12 months, encompassing treatment-emergent or worsening hypertension requiring treatment escalation, cancer therapy-related cardiac dysfunction (CTRCD), heart failure, clinically significant arrhythmia, or arterial thromboembolism. Cox regression and fixed-horizon discrimination analyses were performed. Results The cohort had a mean age of 60.5 ± 11.4 years; 360 (56.2%) were men and 255 (39.8%) had baseline hypertension. Mean systolic blood pressure increased from 129.8 to 143.2 mmHg, while mean GLS changed from −19.0% to −17.7% at week 4. During 12 months, 155 patients (24.2%) experienced the composite outcome. In a multivariable Cox model, age (HR 1.023 per year, 95% CI 1.008–1.038), week-4 systolic blood pressure (HR 1.018 per mmHg, 95% CI 1.008–1.029), and relative GLS decline (HR 1.042 per percentage point, 95% CI 1.000–1.085) were associated with the outcome. Adding week-4 blood pressure, GLS, hs-cTnI, and NT-proBNP changes to baseline variables increased the 12-month AUC from 0.638 to 0.693. The AUC estimates describe apparent performance within the analyzed cohort, without internal or external validation. Conclusions Early vascular and myocardial changes after VEGFR-TKI initiation provided complementary information beyond baseline clinical risk. Week-4 systolic blood pressure and relative GLS decline were the strongest independent dynamic markers, while biomarker changes added more limited incremental information after mutual adjustment. These findings support multimodal early surveillance during VEGFR-TKI therapy and warrant prospective external validation before use for treatment decisions.