Cardiovascular magnetic resonance characterisation of anthracycline cardiotoxicity in adults with normal left ventricular ejection fraction

Background: Anthracycline therapy may lead to changes in cardiac structure and function not detectable by solely evaluating left ventricular ejection fraction (LVEF). Objectives: We hypothesized that cardiovascular magnetic resonance (CMR) would identify structural and functional myocardial abnormalities in anthracycline-treated cancer survivors with normal LVEF, compared to a matched control population. Methods: Forty-five cancer survivors (56 +/- 16 yrs., 60% female) with normal LVEF (59.5 +/- 4.1%) were studied a median of 11 months (range 3-36) following administration of 237 +/- 83 mg/m(2) anthracycline, and compared with forty-five healthy control subjects of similar age and sex (53 +/- 16 yrs., 60% female) with normal LVEF (60.8 +/- 2.4%) using 1.5 T CMR. Results: Significantly smaller indexed left ventricular mass (45.6 +/- 8.7 vs 50.3 +/- 10.1 g/m(2), p = 0.02) and indexed myocardial cell volume (30.5 +/- 5.7 vs 34.8 +/- 7.2 ml/m 2 , p = 0.002) were evident in cancer survivors and the latter was inversely associated with cumulative anthracycline dose (r = -0.31, p = 0.02). Surrogate CMR markers of myocardial fibrosis were significantly increased in cancer survivors (native myocardial Tj: 1021 +/- 40 vs 996 +/- 35 ms, p = 0.002; extracellular volume: 29.5 +/- 4.5 vs 27.4 +/- 2.3%, p = 0.006). CMR-derived feature-tracking global longitudinal strain (GLS) was significantly impaired in cancer survivors (2D GLS -18.3 +/- 2.6 vs -20.0 +/- 2.0%, p < 0.001; 3D GLS -14.5 +/- 2.3 vs -16.4 +/- 2.6%, p < 0.001). Parameters exhibited good to excellent (ICC = 0.86-0.98) inter- and intra-observer reproducibility. Conclusions: Anthracycline-treated cancer survivors with normal LVEF have significant perturbations of LV mass, myocardial cell volume, native myocardial Tl, ECV, CMR-derived 2D and 3D GLS, compared to controls, with good to excellent levels of inter- and intra-observer reproducibility.

Automated summary

Cancer survivors treated with anthracyclines exhibit significant abnormalities in cardiac structure and function, including smaller left ventricular mass, myocardial cell volume, and signs of myocardial fibrosis, despite having normal left ventricular ejection fraction. This study suggests that cardiovascular magnetic resonance imaging can help identify these abnormalities in cancer survivors with normal LVEF.