ABC | Volume 110, Nº3, March 2018

Original Article Kang et al Multi-layer strain analysis in lymphoma survivors Arq Bras Cardiol. 2018; 110(3):219-228 accurate distinction between segments with non-transmural infarction vs those with no infarction and between segments with transmural vs non-transmural infarction as defined by late gadolinium enhancement cardiovascular magnetic resonance. In the present study, we adopted a multi‑layer strain approach in analyzing layer-specific ventricular deformation and observed the decrease of subendocardial circumferential strain values and transmural circumferential gradient in long-term survivors exposed to anthracycline. It has been proved in animal models of anthracycline cardiotoxicity that severe myocytolysis mainly involved the subendocardium of the ventricle. 20 Moreover, Perel et al. 21 observed a regional and diffuse pattern of subendocardial enhancement using cardiac magnetic resonance imaging in patients with anthracycline‑induced cardiomyopathy. Hence, the findings in our study of reduction of subendocardial circumferential strain values and transmural circumferential gradient but preserved subepicardial circumferential strain was consistent with the same hypothesis of subendocardial injury induced by anthracycline. Moreover, it has been proved 22 that in patients with chronic ischemic cardiomyopathy, subendocardial circumferential strain was a powerful predictor of cardiac events and appeared to be a better parameter than LVEF and other strain variables analyzed by echocardiography. Therefore, we believed that further importance may need to be attached to the changes of subendocardial circumferential strains. We observed that after anthracycline exposure, longitudinal strains of all the three layers decreased significantly. However, transmural longitudinal strain gradient did not show any difference compared to normal group. It is reported that the subendocardium is predominantly composed of longitudinal myocardial fiber. The subendocardial deformation is greatest in the longitudinal direction and verifies the endo-epicardial gradient in normal left ventricles on magnetic resonance imaging. 23,24 Hence, the longitudinal left ventricular mechanics are predominantly governed by the subendocardial region of the myocardium, which probably accounts for our findings of the reduction of all three layers of longitudinal strain values and the absence of difference in longitudinal transmural gradient. The lack of difference in radial strain between two groups in our study was perhaps not surprising, which was concordance with some previous studies. 25,26 It was recently published that peak radial strain differed largely between different software and algorithms, and small changes in width can change large RS differences. 27 In the present study, the interobserver variation did not show satisfactory reproducibility of RS measurement. Hence, it may suggest that indices of radial deformation are not as sensitive as circumferential and longitudinal strains in detecting subclinical left ventricular dysfunction. The absence of associations between strain parameters and cumulative anthracycline indicated lack of a safe dose that was free of cardiotoxicity. It has been proved that even children who have received a cumulative doxorubicin dose as low as 45mg/m 2 have reduced left ventricular mass 28 and anthracycline damage to all cardiac structures may begin with the first anthracycline dose. 29 Limitation Several limitations to this study warranted comment. This was a cross-sectional study of a relatively small patient cohort, which did not provide information on the value of myocardial deformation parameters in prognostication. Further out-come studies with hard clinical endpoints will be required to determine the clinical significance of our findings. Secondly, although speckle tracking echocardiography allows interrogation of global strain, these parameters are not entirely load dependent and need to be interpreted with caution when an alteration of cardiac status with acute changes in load is anticipated. Conclusion Despite normal left ventricular ejection fraction, subtle abnormalities in myocardial systolic function were present in long-term survivors after anthracycline exposure. It provided the evidence of preferential impairment of subendocardial deformation in long-term survivors after exposure to anthracycline. Multi-layer speckle tracking echocardiography, a potential non-invasive tool for the detection of subclinical anthracycline-induced myocardial abnormalities, might facilitate the longitudinal follow-up of this at-risk patient cohort. Author contributions Conception and design of the research: Kang Y, Shen X; Acquisition of data: Kang Y, Xiao F Xiao F, Chen H, Wang W, Zhao H; Analysis and interpretation of the data: Kang Y, Chen H, Wang W; Statistical analysis: Kang Y, Xiao F, Chen H, Shen L, Zhao H; Obtaining financing: Chen F, He B; Writing of the manuscript: Kang Y, Chen H, Shen L; Critical revision of the manuscript for intellectual content: Chen F, He B. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding This work was supported by grants from the National Nature Science Foundation of China (81401411) and Nature Science Foundation of Shanghai (14ZR1425200, 16ZR1420600). Study Association This study is not associatedwith any thesis or dissertationwork. Ethics approval and consent to participate This study was approved by the Ethics Committee of the Renji Hospital under the protocol number 2014(N012). All the procedures in this study were in accordancewith the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study. 226