3D echocardiography and biomarkers for early diagnosis and prediction of chemotherapy induced right ventricular dysfunction in non-Hodgkin lymphoma patients

Abstract Background RCHOP (rituximab, cyclophosphamide, doxorubicin, oncovin, prednisone) use in non-Hodgkin's lymphoma (NHL) is limited by the risk of cardiotoxicity. Although the prognostic value of right ventricular (RV) function in mortality and morbidity has been well established, its involvement in chemotherapy-induced cardiotoxicity remains unclear. Aim To define new parameters able to detect early RV cardiotoxicity. Methods 51 patients (22 men, 61±14 years) with NHL scheduled for RCHOP, with three dimensional (3D) left ventricular (LV) ejection fraction (EF) >50%, were assessed at baseline, after 3rd and 6th cycle for right ventricular (RV) parameters: 3D EF, two dimensional (2D) global longitudinal strain (GLS) and free wall LS (FWLS), peak systolic annular velocity (S’), tricuspid annulus systolic excursion (TAPSE) and fractional area change (FAC). Biomarkers (troponin I, NT-pro-BNP) were measured. Cardiotoxicity was defined as LVEF reduction below 50% or preserved LVEF with LV LS decrease more than 15% from baseline. Results 15 (29%) of patients developed LV cardiotoxicity (group 1) while 36 did not fulfill this criteria (group 2). There was a significant reduction of RVEF, GLS, and FWLS, but not of RV S’, FAC, and TAPSE, starting with the 3rd cycle, with greater changes in group 1 vs. group 2 (see Table). RVEF reduction correlated with changes of FWLS, GLS, RV S’, and troponin (r=0.612, r=0.513, r=0.362, r=-0.358, respectively; all p<0.05). Reduction of FWLS after the 3rd cycle was the best independent predictor for RVEF decrease after the 6th cycle (R²=0.433, p<0.0001). FWLS decrease with more than 26% predicted cardiotoxicity after the 6th cycle (sensitivity of 81%; specificity of 78%). Conclusion 3D EF, 2D systolic deformation, and troponin I are able to detect early chemotherapy-induced right ventricular cardiotoxicity, and to predict further decline of RVEF in NHL patients. Thus, routine follow-up of RV function, along with the LV function, should be assessed during and after chemotherapy.RV parameters and troponin during RCHOP