Endothelin-1 as a diagnostic and prognostic biomarker of subclinical anthracycline-induced vascular toxicity in lymphoproliferative diseases patients with low and intermediate cardiotoxic risk

Abstract

Anthracyclines remain a cornerstone of therapy for lymphoproliferative diseases eratie(LPD) but are associated with cardiovascular toxicity (CVT). While myocardial injury is well studied, anthracycline-induced vascular toxicity and endothelial dysfunction as early manifestations of cardiovascular damage remain insufficiently explored, particularly in patients with low or intermediate baseline CVT-risk, who do not meet criteria for cardioprotective therapy according to current guidelines. Identification of early biomarkers of subclinical vascular injury is, therefore, of major importance in cardio-oncology. To assess the diagnostic and prognostic value of endothelin-1 (ET-1) for detection and progression of endothelial dysfunction in lymphoma patients with low and intermediate CVT-risk receiving anthracycline-based chemotherapy. This prospective study included 37 patients with newly diagnosed LPDs (median age 46 [34–62] years) treated with anthracycline-containing chemotherapy. Baseline CVT-risk was assessed using HFA-ICOS scores; all patients were classified as low or intermediate risk and did not require cardioprotective therapy. Serum ET-1 levels were measured by ELISA before treatment initiation and after 3 chemotherapy cycles (cumulative anthracycline dose 270 mg/m²). Endothelial function was evaluated using digital photoplethysmography (ANGIOSCAN-01), assessing phase shift (PS) and occlusion index (OI). ROC analysis was performed to evaluate prognostic performance. Baseline ET-1 levels were elevated and increased significantly after 3 cycles of chemotherapy (5.39 [4.6–7.21] vs 7.19 [5.9–11.6] pg/mL; p = 0.003). This was accompanied by a significant decline in endothelial function parameters: PS (normal >10 ms) decreased from 8.6 [7.2–10.2] to 6.3 [5.2–9.8] ms (p = 0.014), and OI (normal >1.8) decreased from 1.7 [1.4–1.9] to 1.5 [1.2–1.9] (p = 0.004). ROC analysis demonstrated good prognostic performance of ET-1 for endothelial dysfunction: AUC 0.772 for PS (95% CI: 0.582-0.962, p=0.031) and 0.743 for OI (95% CI: 0.532-0.954, p=0.048). Endothelin-1 is a promising early diagnostic and prognostic biomarker of subclinical anthracycline-induced vascular toxicity in lymphoma patients with low and intermediate CVT-risk. ET-1 assessment may facilitate early risk reclassification and optimization of cardio-oncology surveillance strategies.