Assessing cancer therapy-related cardiac dysfunction risk in non-Hodgkin lymphoma patients, the role of comprehensive echocardiographic monitoring

Abstract Background Cardiovascular disease is the second leading cause of mortality in cancer patients, with the highest risk observed during the first year after diagnosis [1, 2]. This is also seen in the treatment of non-Hodgkin lymphomas (NHL), where early detection of cardiotoxicity remains a major challenge [3]. Purpose To investigate the potential role of comprehensive echocardiography in the early detection of cancer therapy–related cardiac dysfunction (CTRCD) risk in patients with NHL. Methods A prospective cohort study included 127 patients with NHL, excluding those with other malignancies, prior chemotherapy or radiotherapy, coronary artery disease, significant valvular heart disease or in NYHA III-IV. Patients were evaluated using a comprehensive echo protocol before the initiation of antitumor treatment and at a 6-months. Parameters measured were LV-Tei index, RV-Tei index, lateral S' velocity of the LV, S' velocity at the RV free wall, TAPSE, LA volume/BSA, E/A ratio, E/e' ratio, and E/Vp ratio. CTRCD was diagnosed according to the 2022 ESC guidelines on Cardio-Oncology. Numerical variables were compared using the Mann–Whitney–Wilcoxon. SHAP analysis and permutation methods were used to validate the contribution of each variable to the prediction of CTRCD. Results CTRCD was confirmed in 18 patients (14.2%) at 6 months. The cohort was divided into Group I (CTRCD) and Group II (no CTRCD), and baseline echo parameters were analyzed. Initial LVEF did not show any statistically significant differences. LV -Tei index and lateral S' velocity of the LV free wall were significantly different in Group I compared to Group II. Specifically, the LV Tei index was 0.3 (IQR=0.2) in Group I vs. 0.1 (IQR=0.1) in Group II (p=0.017), and the LV S’ lateral velocity was 10.0 cm/s (IQR=1.8) in Group I vs. 12.0 cm/s (IQR=3.0) in Group II (p<0.001). TAPSE and RV free wall S’ velocity did not show significant differences. However, the RV-Tei index was significantly higher in Group I, indicating a stronger association with CTRCD. The RV-Tei index was 0.3 (IQR = 0.2) in Group I vs. 0.2 (IQR=0.1) in Group II (p=0.014). The E/e’ ratio was significantly higher in Group I (Fig.1), with a median value of 8.6 (IQR=6.1) vs. 5.5 (IQR = 3.6) in Group II (p=0.004). Similarly, the E/Vp ratio was also elevated in Group I (Fig.2): 1.0 (IQR = 0.3) vs. 0.7 (IQR=0.4) in Group II (p<0.001). Using SHAP analysis, the most influential echo predictors of CTRCD were LA volume/BSA and the E/e' ratio. The E/A ratio also contributed to the risk prediction, though to a lesser extent. Conclusion The initial LVEF did not differ and was not a predictor. The LV and RV-Tei indices, lateral S’ velocity, E/e’ and E/Vp ration were significantly associated with CTRCD development. However, SHAP analysis further identified LA volume/BSA and the E/e’ ratio as key predictors, underscoring the importance of comprehensive echocardiographic assessment for early detection of patients at risk of CTRCD.E/e’ ratio in the study groups E/Vp ratio in the study groups