Left atrial contractile dysfunction and fibrosis occur in anthracyline-treated long-term survivors of childhood cancers

Abstract

Background: An animal model of anthracyclineinduced cardiotoxicity has revealed significant left atrial (LA) remodeling. Objective: We tested the hypothesis that LA mechanics and myocardial calibrated integrated backscatter (cIB), a marker of myocardial fibrosis, are altered in anthracylinetreated longterm survivors of childhood cancers and explored their associations with left ventricular (LV) functional indices and fibrosis. Method: Fortynine patients (26 males) aged 22.9±5.8 years at 14.2±5.4 years after anthracycline therapy and 25 controls (13 males) were studied. Left atrial volumes were measured using biplane Simpson's method, while LA positive, negative, and total strain and strain rate at ventricular systole, early diastole, and atrial contraction were interrogated using speckle tracking echocardiography. Calibrated integrated backscatter of the LA posterior wall, ventricular septum and LV posterior wall were determined. Doppler and threedimensional echocardiography was used to determine LV systolic and diastolic function. Results: Compared with controls, patients had significantly smaller maximal (p=0.009) and minimal (p=0.017) LA volumes, lower peak negative LA stain (p=0.011), but similar LA positive and total strain and strain rates (all p>0.05). For LV indices, patients had significantly lower shortening fraction (p<0.001), ejection fraction (p<0.001), and mitral annular late diastolic velocity (p=0.003). Of the 49 patients, 32 (65%) had LV ejection fraction less than 50%. The myocardial cIB of LA posterior wall (−21.3±3.1 dB vs −26.3±4.1 dB, p<0.001), ventricular septum (−25.5±5.8 dB vs −30.4±4.5 dB, p<0.001) and LV posterior wall (−22.5±4.8 dB vs −25.3±3.9 dB, p=0.012) were significantly greater in patients than controls. For the entire cohort, peak negative LA strain correlated positively with early diastolic mitral annular velocity (r=0.27, p=0.018), while LA cIB correlated positively with the average of septal and LV posterior wall cIB (r=0.54, p<0.001), but not indices of atrial deformation. There were no significantly relationships between cumulative dose of anthracycline and indices of LA deformation and cIB. Conclusion: Left atrial remodelling as characterised by LA contractile dysfunction and fibrosis occurs in adult survivors of childhood cancers, and is related to LV diastolic function and fibrosis.