Results:

Weekly CMR examinations revealed no changes in left ventricular ejection fraction (LVEF) until week 9 (1 week after the fifth and final doxorubicin injection). From week 9 onwards, LVEF declined progressively, the decline becoming significant at week 12 (55 ± 4% at baseline vs. 33 ± 6% at week 12; p < 0.01). The lowest LVEF value was recorded at the 16-week time point (30 ± 8%; p = 0.01 vs. baseline).

The study authors found that the earliest doxorubicin-cardiotoxicity CMR parameter was T2 relaxation-time prolongation at week 6 (2 weeks after the third dose). T2 relaxation times were significantly longer than at baseline (45.2 ± 0.5 ms and 52.0 ± 1.4 ms at baseline and week 6, respectively; p = 0.007). T2 relaxation times subsequently increased, reaching a maximum at end follow-up (73.0 ± 4.6 ms and 72.8 ± 4.6 ms on weeks 12 and 16; p = 0.003 and p = 0.001 vs. baseline, respectively). T1 mapping, ECV, and LV motion were unaffected. At this early time point, isolated T2 prolongation correlated with intracardiomyocyte edema secondary to vacuolization without extracellular space expansion. Subsequent development of T1 mapping and ECV abnormalities coincided with LV motion defects: LVEF declined from week 10 (2 weeks after the fifth and final doxorubicin dose). A nonsignificant increase in T1 mapping was noted at week 10, followed by a progressive increase to end follow-up at week 16. Native T1 values were significantly longer than at baseline only from week 12 onwards (1,087 ± 101 ms and 1,220 ± 59 ms at baseline and week 12, respectively; p = 0.02). Stopping doxorubicin therapy upon detection of T2 prolongation halted progression to LV motion deterioration and resolved intracardiomyocyte vacuolization, demonstrating that early T2 prolongation occurs at a reversible disease stage.