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/m² 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/m², p = 0.02) and indexed myocardial cell volume (30.5 ± 5.7 vs 34.8 ± 7.2 ml/m², 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 T₁: 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 T1, ECV, CMR-derived 2D and 3D GLS, compared to controls, with good to excellent levels of inter- and intra-observer reproducibility.