Left Atrial Mechanics and Integrated Calibrated Backscatter in Anthracycline-Treated Long-Term Survivors of Childhood Cancers

Abstract

We tested the hypothesis that left atrial (LA) mechanics and myocardial calibrated integrated backscatter (cIB) are altered in anthracycline-treated long-term survivors of childhood cancers. Forty-nine survivors and 25 controls were studied. Survivors had significantly smaller maximal (p = 0.009) and minimal (p = 0.017) LA volumes and lower peak negative LA strains (p = 0.011). For left ventricular (LV) indices, survivors had significantly lower shortening fraction (p < 0.001), ejection fraction (p < 0.001) and mitral annular late diastolic velocity (p = 0.003). Myocardial cIB of the LA posterior wall, ventricular septum and LV posterior wall was significantly greater in survivors than controls (all p values <0.05). Peak negative LA strain was related to late diastolic mitral annular velocity (r = 0.27, p = 0.018), whereas LA cIB was related to the average of septal and LV posterior wall cIB (r = 0.54, p < 0.001). In conclusion, LA remodeling as characterized by contractile dysfunction and increased cIB suggestive of fibrosis occurs in adult survivors of childhood cancers.

Introduction

Long-term cardiac sequelae of pediatric cancer survivors, including reduced ventricular mass (Lipshultz et al. 2005), increased afterload (Lipshultz et al. 2005) and impaired left ventricular (LV) global function and mechanics (Cheung et al., 2010, Ganame et al., 2007), are well-documented. Optimal performance of the heart requires normal functioning not only of the ventricles, but also of the atria. Physiologically, the atrium acts as a reservoir during ventricular systole, functions as a conduit during opening of the atrioventricular valve in early ventricular diastole and performs as a pump at late ventricular diastole (Todaro et al. 2012). Previous studies in anthracycline-treated long-term survivors of childhood cancers have, however, focused on functional assessment of the ventricles. Nonetheless, there is evidence to suggest potential involvement of the atria in anthracycline cardiotoxicity.

In an ovine model of anthracycline-induced cardiomyopathy, significant left atrial (LA) remodeling as characterized by atrial enlargement, dysfunction and increased fibrosis has been reported (Lau et al. 2011). With accumulation of collagen, as part of either the reactive fibrosis or reparative process to replace degenerating myocardial tissue (Silver et al. 1990), deformation of the atrial wall might be affected. Nevertheless, data on atrial function and its significance in long-term survivors of childhood cancer have hitherto not been reported. The absence of data on atrial function in anthracycline cardiotoxicity may in part be related to the laborious methods required previously for its assessment.

Recent advancements in speckle tracking echocardiography (STE) have enabled convenient and comprehensive evaluation of LA function (Todaro et al. 2012). Determination at different phases of the cardiac cycle of LA strain and strain rate, which represent respectively the magnitude and rate of atrial myocardial deformation, provides functional assessment of atrial reservoir, conduit and pump function. Additionally, there has also been increasing clinical application of 2-D echocardiography-derived calibrated integrated backscatter (cIB) analysis in the assessment of LA fibrosis (den Uijl et al., 2011, Kubota et al., 2012, Wang et al., 2009).

Given the aforementioned experimental data on possible alteration of atrial substrate and function in anthracycline-induced cardiomyopathy, we hypothesized that LA mechanics and myocardial cIB are altered in anthracycline-treated long-term survivors of childhood cancers. The aims of this study were to test the hypothesis by assessment of LA mechanics, in terms of global atrial strain and strain rates using STE, and LA myocardial cIB as a marker of fibrosis in long-term childhood cancer survivors and to explore their relationships with left ventricular (LV) function.