Multimodality Imaging to Detect Anthracycline-induced Cardiotoxicity in Breast Cancer Patients: A Mechanistic Pilot Study (The MIDAC Study)

Background: Anthracycline-induced cardiotoxicity remains highly prevalent among cancer patients undergoing chemotherapy and its pathophysiology remains poorly understood. Objective: In the Multimodality Imaging to Detect Anthracycline-induced Cardiotoxicity (MIDAC) study, the aim was to use hybrid cardiac PET/MRI to provide mechanistic insights into the pathophysiology of anthracycline-induced cardiotoxicity. Methods: Seventeen female breast cancer patients scheduled for doxorubicin chemotherapy were prospectively recruited to undergo serial cardiac imaging at baseline (PET/MRI), 3 months (PET/MRI) and 12 months post-chemotherapy (MRI only). Results: Compared to baseline, at 3 months there was: a reduction in left ventricular ejection fraction (57 ± 6% versus 62 ± 4%; p<0.001); a reduction in both global circumferential and longitudinal strain (global circumferential strain and global longitudinal strain); higher native myocardial T1 values (1,304 ± 35 versus 1,260 ± 51 ms; p=0.004); increased extracellular volume fraction (29 ± 3% versus 26 ± 3%; p=0.012); a reduction in intracellular mass (44 ± 7 versus 47 ± 8 g; p=0.03); and a reduction in standardised uptake values of fluorine-18 fluorodeoxyglucose uptake (4.2 ± 2.3 versus 6.2 ± 2.6; p=0.012). There was a positive correlation between relative standardised uptake values reductions and global longitudinal strain at 3 months (R 0.54, p=0.032). At 12 months, left ventricular ejection fraction remained lower than baseline (56 ± 6% versus 62 ± 4%; p<0.001) with an associated reduction in global circumferential strain and global longitudinal strain. Native myocardial T1 values remained higher than baseline but with no significant differences in T2, intracellular mass and extracellular volume fraction. Conclusion: Observations at 3 months post-doxorubicin chemotherapy were diffuse interstitial fibrosis, a reduction in intracellular mass, and a reduction in myocardial glucose metabolism; changes which were associated with a reduction in global longitudinal strain and left ventricular ejection fraction. Diffuse interstitial fibrosis persisted at 12 months and was associated with lower left ventricular ejection fraction and global longitudinal strain.