P43603D myocardial deformation, arterial stiffness, and cardiac biomarkers allows early diagnosis and prediction of CHOP-induced cardiotoxicity in non-Hodgkin lymphoma

Abstract

Standard CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristin, prednisone) in non‐Hodgkin lymphoma (NHL) has risk of cardiotoxicity, with increased morbidity and mortality. Aim. To define new parameters of 3D LV deformation, arterial stiffness and biomarkers, for early detection and prediction of cardiotoxicity. Methods: 75 NHL patients (33 men, 58+/‐15 years), with LVEF >50%, scheduled to receive CHOP, were assessed at baseline, after 3rd cycle, and after treatment completion (doxorubicin cumulative dose of 384+/‐66 mg). 3D echocardiography (3DE) was used to assess LVEF and systolic deformation: longitudinal, radial, circumferential, and area strain (LS, RS, CS, AS); Complior to measure pulse wave velocity (PWV); and troponin I and NT‐proBNP as markers of cardiac injury and high overload. Cardiotoxicity was defined as a decrease of LVEF<50%, with more than 10% from the baseline value. Results: At the end of CHOP therapy, 19 patients (group I) developed cardiotoxicity (LVEF=63+/‐2 vs. 49+/‐1, p<0.0001), whereas 56 patients (group II) did not (LVEF=63+/‐3 vs. 55+/‐3, p<0.0001). There was a significant reduction of all LV deformation parameters and a significant increase of arterial stiffness, starting with the 3rd cycle, but group I had greater changes than group II (p<0.001) (Table). Univariate analysis showed a significant correlation between changes of LVEF and changes of LS, CS, RS, AS, PWV, and troponin I after the 3rd cycle (r of 0.64; 0.41; 0.39; 0.43; ‐0.50; ‐0.31, all p<0.05). The reduction of LS after the 3rd cycle was the best independent predictor for the decrease of LVEF at the end of treatment (R2=0.387, p=0.001); decrease of LS with more than 21% after the 3rd cycle predicted the development of cardiotoxicity at the end of CHOP therapy (sensitivity 85%, specificity 72%). Conclusion: 3DE myocardial deformation, arterial stiffness, and cardiac biomarkers are very useful tools to detect early chemotherapy induced cardiotox‐ icity, and to predict further decline of LVEF in patients with non‐Hodgkin lymphoma.