Early detection and prediction of CHOP-induced cardiotoxicity in Non-Hodgkin Lymphoma by myocardial work, vascular ultrasound and cardiac biomarkers

Introduction: CHOP (cyclophosphamide, doxoru-bicin, oncovin, prednisone) use in patients with non-Hodgkin lymphoma (NHL) is limited by the risk of cardiotoxicity, increasing morbidity and mortality.

Objective: To define new parameters of LV myocardial work, arterial stiffness and biomarkers, for early dia-gnosis and prediction of cardiotoxicity.

Methods: 88 patients (32 men, 59 ± 13 years), with NHL, with LVEF >50%, scheduled to receive CHOP, were assessed at baseline, after 3rd and 6th cycle (doxo-rubicin cumulative dose 344 ± 49mg). During mecha-nical systole and isovolumetric relaxation, 2D STE was used to calculate longitudinal strain (LS) and myocar-dial work: global constructive work (GCW) as the „po-sitive” work of the heart; global wasted work (GWW) as the „negative” work of the heart; global work effi-ciency (GWE) by formula GCW/ (GCW+GWW) (%) and global work index (GWI), as the sum of GCW and GWW. By Echotracking Aloka we evaluated pulse wave velocity (PWV), augmentation index (AIX) and index; troponin I and NTproBNP were measured as markers of cardiac injury and high overload. Cardio-toxicity was defined as a decrease of LVEF<50%, with more than 10% from the baseline value.

Results: After the 6th cycle, 17 patients (19%) (group I) developed cardiotoxicity (3D LVEF=63 ± 2 vs. 48 ± 1, p<0.0001), while 71 patients (group II) did not (3D LVEF=63 ± 3 vs. 56 ± 2, p<0.0001). There was a signi-ficant reduction of LS, GCW and GWE, with increa-sed GWW and arterial stiffness starting with the 3rd cycle, but group I had greater changes than group II (p<0.001). There were no significant changes of systolic and diastolic blood pressure. Univariate analysis show-ed a significant correlation between the LVEF reducti-on and the decrease of LS, GCW, GWE and increased GWW, PWV, β index and troponin level after the 3rd cycle (r=0.54; r=0.63, r=0.42, r=-0.41, r=-0.39, r=-0.377, r=-0.341 respectively, all p<0.05). The reduction of the GCW after the 3rd cycle was the best independent predictor for the decrease of LVEF after the 6th cycle (R2=0.45, p=0.001). ROC analysis showed that a de-crease of GCW with more than 28% after the 3rd cycle predicted with a Sb of 87% and Sp of 83% development of cardiotoxicity after the 6th cycle of CHOP Conclusions: Assessment of myocardial work and ar-terial stiffness parameters and cardiac biomarkers are able to detect early chemotherapy-induced cardiotoxi-city and to predict further decline of LVEF in patients with non-Hodgkin lymphoma. Further studies are ne-eded to assess if these parameters can be used into rou-tine clinical practice.



ISSN – online: 2734 – 6382
ISSN-L 1220-658X
ISSN – print: 1220-658X
The Romanian Journal of Cardiology is indexed by:
ESC search engine
CODE: 379
CME Credits: 10 (Romanian College of Physicians)