Myocardial work, combined with arterial stiffness and biomarkers, are able to detect earlier and predict cardiotoxicity in non-Hodgkin lymphoma

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. CHOP (cyclophosphamide, doxorubicin, oncovin, prednisone) in non-Hodgkin lymphoma (NHL) is limited by risk of cardiotoxicity. Aim. To define new parameters of LV myocardial work, arterial stiffness, and biomarkers for early diagnosis and prediction of cardiotoxicity. Methods. 91 patients (34 men, 57 ± 11 years), with NHL, with LVEF >50%, scheduled for CHOP, were assessed at baseline, and after 4th and 8th cycle (doxorubicin total dose of 341 ± 52 mg). 3D echo was used for LVEF; 2D STE for longitudinal strain (LS) and myocardial work: global constructive work (GCW) as "the positive" work of the heart; global wasted work (GWW) as "the negative" work of the heart; global work efficiency (GWE) by formula GCW/(GCW + GWW), and global work index (GWI) as sum of GCW and GWW; echo-tracking for pulse wave velocity (PWV) and β index. Troponin I and NTproBNP were measured. Cardiotoxicity was defined as LVEF decrease <50%, with >10% from baseline. Results. After 8th cycle, 17 patients (18%) (group I) developed cardiotoxicity (3D LVEF: 63 ± 3 vs. 48 ± 1, p < 0.0001), whereas 74 patients (group II) did not (3D LVEF: 63 ± 2 vs. 57 ± 3, p < 0.0001). There was a significant reduction of LS, GCW and GWE, with an increase of GWW and arterial stiffness, starting with the 4th cycle; changes in group I were higher than in group II (p < 0.001) (table). Univariate analysis showed significant correlation between reduction of 3D LVEF and decrease of LS, GCW, GWE (r = 0.65; r = 0.74; r = 0.54), and increase of GWW, PWV, β index, and troponin level after 4th cycle (r=-0.44; r=-0.38; r=-0.39; r=-0.35; all p < 0.05). Reduction of GCW after the 4th cycle was the best independent predictor of decrease of 3D LVEF after the 8th cycle (R2 = 0.48, p = 0.001). By ROC analysis, decrease of GCW by more than 29% after the 4th cycle predicted development of cardiotoxicity after the 8th cycle of CHOP (Sb 82%, Sp 81%). Conclusion. Assessment of myocardial work, combined with arterial stiffness and biomarkers, are able to detect early chemotherapy-induced cardiotoxicity and to predict further decline of LVEF in non-Hodgkin lymphoma. Myocardial work and cardiotoxicity CHOP Group I Group II LS(-%) Baseline 4th cycle 8th cycle 22 ± 2 17 ± 1† 13 ± 2† 22 ± 2 19 ± 2† 17 ± 2±† GCW (mmHg%) Baseline 4th cycle 8th cycle 2256 ± 123 1902 ± 133† 1633 ± 167† 2278 ± 168 2104 ± 111† 1937 ± 102† GWW (mmHg%) Baseline 4th cycle 8th cycle 84 ± 4 124 ± 18† 198 ± 24† 85 ± 11 94 ± 21† 113 ± 19† GWE (%) Baseline 4th cycle 8th cycle 98 ± 1 92 ± 2† 86 ± 2† 98 ± 1 95 ± 2 94 ± 1† GWI (mmHg%) Baseline 4th cycle 8th cycle 1982 ± 155 1888 ± 136† 1723 ± 172† 2003 ± 189 1945 ± 111 1873†±102† GCW = global constructive work; GWE = global work efficiency; GWI = global work index; GWW = global waste work; LS = longitudinal strain; † p < 0.001