The Value Of Non-invasive Myocardial Work In The Follow-up Of Children And Young Adults With Cancer Following Anthracycline Chemotherapy

BackgroundLeft ventricular ejection fraction(LVEF)and global longitudinal strain(GLS)have conventionally been used for surveillance of cardiac function after cancer therapy,but indices of myocardial work(MW)are potentially superior for this purpose because they take into account both myocardial deformation and loading conditions.ObjectiveWe aimed to investigate the usefulness of MW in the follow-up of children and young adults following anthracycline chemotherapy.MethodsConventional markers of LV function(LV fractional shortening[LVFS],LVEF,GLS)and MW indices(global work index[GWI],global constructive work[GCW],global wasted work[GWW],and global work efficiency[GWE])were obtained from 2,342 echocardiographic examinations in 598 patients(59%male,12.2[4.7-17.3]years of age at initiation of chemotherapy).Results1.GWI,GCW,GLS,LVFS,and LVEF all deteriorated significantly during and after anthracycline chemotherapy,while GWW decreased and GWE was preserved.There were statistically significant differences in GWI and GCW before chemotherapy and during chemotherapy(GWI:1714.51mmHg%vs 1514.38mmHg%,p<0.001;GCW:2076.48mmHg%vs 1864.56mmHg%,p<0.001).Compared with during chemotherapy,no significant changes in GWI and GCW were observed after chemotherapy.Compared with before chemotherapy,GWW decreased after chemotherapy and the difference was statistically significant(88.35mmHg%vs 76.16mmHg%,p<0.001).However,there was no significant change in GWE before,during and after chemotherapy.2.In the correlation analysis,GWI and GCW were strongly positively correlated with each other(r=0.86,p<0.001),and both were moderately negatively correlated with GLS(GWI with GLS:r=-0.67,p<0.001;GCW with GLS:r=-0.64,p<0.001).GWI and GCW were only weakly correlated with LVEF and LVFS(GWI with LVFS:r=0.32,p<0.001;GWI with LVEF:r=0.34,p<0.001;GCW with LVFS and LVEF:r=0.30,p<0.001).There was a moderate positive correlation between GCW and SBP(r=0.52,p<0.001).GWW and GWE were strongly negatively correlated with each other(r=-0.89,p<0.001),and both were only weakly correlated with GLS,LVEF and LVFS(GWW with LVEF:r=-0.10,p<0.001;GWI with GLS:r=0.29,p<0.001;GWE with LVFS:r=0.12,p<0.001;GWE with LVEF:r=0.20,p<0.001;GWE with GLS:r=-0.50,p<0.001).On multivariable analysis,MW indices were correlated with conventional markers of LV function and with clinical information relating to underlying malignancy and chemotherapy(GWI:-78 mmHg%per%deterioration,p<0.001;GCW:-86 mmHg%per%deterioration,p<0.001;GWW:+6.2 mmHg%per%deterioration,p<0.001;GWE:-0.60%per%deterioration,p<0.001).3.Cox regression analysis revealed that similar levels of deterioration in GWW,GWI,and GCW preceded those in GLS,LVFS,and LVEF.15%deteriorations in GWW(hazard ratio[HR]1.50,95%confidence interval[CI]1.11-2.02)and GWI(HR 1.46,95%CI 1.09-1.97)preceded a similar level of deterioration of GLS(HR>1).Furthermore,there was a trend towards earlier detection with GCW(HR 1.24,95%CI 0.91-1.68).In contrast,LVEF deteriorated much later than GLS(HR 0.39,95%CI 0.26-0.57),while no events were observed for GWE.It is clear that GWW lagged behind GLS between 0%and 5%deterioration but preceded GLS at any level of deterioration from 13%onwards,while GWI preceded GLS between 13%and 46%and GCW preceded GLS between 20%and 26%.In contrast,LVFS and LVEF lagged behind GLS at levels of deterioration from 28%to 49%and 4%to 49%,respectively,while GWE lagged behind at any given level.ConclusionNon-invasive MW indices correlate well with conventional markers of LV function.Indices of MW appear to provide an earlier and more sensitive marker of progression towards chemotherapy-related cardiac dysfunction.Future studies are warranted to validate whether the incorporation of non-invasive MW into the routine clinical surveillance in patients after chemotherapy would improve outcomes.