ABC | Volume 110, Nº3, March 2018

Original Article Subclinical Anthracycline-Induced Cardiotoxicity in the Long‑ Term Follow‑Up of Lymphoma Survivors: A Multi-Layer Speckle Tracking Analysis Yu Kang, 1* Fei Xiao, 2* Haiyan Chen, 3* Wei Wang, 1 Lijing Shen, 2 Hang Zhao, 1 Xuedong Shen, 1 Fangyuan Chen, 2 Ben He 1 Department of Cardiology - Renji Hospital - School of Medicine - Shanghai Jiaotong University, Shanghai - China 1 Department of Hemotology - Renji Hospital - School of Medicine - Shanghai Jiaotong University, Shanghai - China 2 Department of Echocardiography - Zhongshan Hospital of Fudan University, Shanghai - China 3 * Yu Kang, Fei Xiao and Haiyan Chen contribute equally to the work. Mailing Address: Fangyuan Chen and Ben He • Department of Hemotology - Renji Hospital - School of Medicine - Shanghai Jiaotong University. No. 1630 Dongfang Rd, 200126, Shanghai - China E-mail: chenfangyuan1027@163.com; heben1027@163.com Manuscript received July 11, 2017, revised manuscript September 05, 2017, accepted October 06, 2017 DOI: 10.5935/abc.20180042 Abstract Background: Anthracycline generates progressive left ventricular dysfunction associated with a poor prognosis. Objectives: The purpose of this study was to evaluate whether layer-specific strain analysis could assess the subclinical left ventricular dysfunction after exposure to anthracycline. Methods: Forty-two anthracycline-treated survivors of large B-cell non-Hodgkin lymphoma, aged 55.83 ± 17.92 years (chemotherapy group) and 27 healthy volunteers, aged 51.39 ± 13.40 years (control group) were enrolled. The cumulative dose of epirubicin in chemotherapy group was 319.67 ± 71.71mg/m 2 . The time from last dose of epirubicin to the echocardiographic examination was 52.92 ± 22.32 months. Global longitudinal (GLS), circumferential (GCS) and radial strain (GRS), subendocardial, mid and subepicardial layer of longitudinal (LS-ENDO, LS-MID, LS-EPI) and circumferential strain (CS-ENDO, CS-MID, CS-EPI) values were analyzed. Transmural strain gradient was calculated as differences in peak systolic strain between the subendocardial and subepicardial layers. A value of p < 0.05 was considered significant. Results: Conventional parameters of systolic and diastolic function showed no significant difference between two groups. Compared with controls, patients had significantly lower GCS and GLS. Multi-layer speckle tracking analysis showed significant reduction of circumferential strain of subendocardial layer, transmural CS gradient and longitudinal strain of all three layers. In contrast, the two groups did not differ in transmural longitudinal strain gradient and radial strains. Conclusions: It proved the preferential impairment of subendocardial deformation in long-term survivors after exposure to anthracycline. Multi-layer speckle tracking echocardiography might facilitate the longitudinal follow-up of this at-risk patient cohort. (Arq Bras Cardiol. 2018; 110(3):219-228) Keywords: Cardiotoxicity;Anthracyclines;Lymphoma,Non-Hodgkin;HematologicNeoplasias/drugtherapy;Echocardiography. Introduction Anthracycline, a commonly used chemotherapeutic agent in the treatment of a wide spectrum of hematologic malignancies and solid tumors, is undermined by potential life-threatening cardiotoxicity. 1,2 Anthracycline-induced left ventricular dysfunction is believed to be refractory to conventional pharmacological therapy and to be associated with a poor prognosis. Therefore, detection of subclinical myocardial dysfunction is of vital importance to balance between the cardiac risk and the potential cancer treatment. Two-dimensional speckle tracking echocardiography, based on tracking local image details from frame to frame throughout the cardiac cycle, 3-6 has allowed more accurate measurements of regional myocardial systolic performance. It has been proved that patients treated with epirubicin‑based chemotherapy experienced significant decrease in strain values while LVEF remained stable and within normal limits. 7,8 Based on the 2D speckle tracking technology, a novel offline tool is recently introduced which has a potential of measuring strains in subendocardial and subepicardial layers comparatively. Therefore, the objectives of this study were to evaluate whether layer-specified systolic strain analysis could differentiate the subclinical left ventricular function changes in patients after exposure to anthracycline-based chemotherapy. Methods Study population A total of 45 anthracycline-treated survivors of histopathologically confirmed large B-cell non-Hodgkin lymphoma who have been off treatment for at least one year were enrolled in this study between March 2014 and Dec 2015 (chemotherapy group). Exclusion criteria were uncontrolled hypertension, significant valvular disease, congenital disease, a widened QRS complex on surface 219