Long-term cardiotoxicity in germ cell cancer survivors after platinum-based chemotherapy: cardiac MR shows impaired systolic function and tissue alterations
Antonia Beitzen‐Heineke, Christina C. Rolling, Christoph Seidel, Jennifer Erley, Isabel Molwitz, Kai Muellerleile, Dennis Saering, Juliana Senftinger, Niklas Börschel, Nils W. Engel, Carsten Bokemeyer, Gerhard Adam, Enver Tahir, Hang Chen
Abstract
OBJECTIVES: Long-term toxicities of germ cell cancer (GCC) treatment are of particular importance in young men with a life expectancy of several decades after curative treatment. This study aimed to investigate the long-term effects of platinum-based chemotherapy on cardiac function and myocardial tissue in GCC survivors by cardiac magnetic resonance (CMR) imaging. METHODS: Asymptomatic GCC survivors ≥ 3 years after platinum-based chemotherapy and age-matched healthy controls underwent CMR assessment, including left ventricular (LV) and right ventricular (RV) ejection fraction (EF), strain analysis, late gadolinium enhancement (LGE) imaging, and T1/T2 mapping. RESULTS: Forty-four survivors (age 44 [interquartile range, IQR 37-52] years; follow-up time 10 [IQR 5-15] years after chemotherapy) and 21 controls were evaluated. LV- and RVEF were lower in GCC survivors compared to controls (LVEF 56 ± 5% vs. 59 ± 5%, p = 0.017; RVEF 50 ± 7% vs. 55 ± 7%, p = 0.008). Seven percent (3/44) of survivors showed reduced LVEF (< 50%), and 41% (18/44) showed borderline LVEF (50-54%). The strain analysis revealed significantly reduced deformation compared to controls (LV global longitudinal strain [GLS] -13 ± 2% vs. -15 ± 1%, p < 0.001; RV GLS -15 ± 4% vs. -19 ± 4%, p = 0.005). Tissue characterization revealed focal myocardial fibrosis in 9 survivors (20%) and lower myocardial native T1 times in survivors compared to controls (1202 ± 25 ms vs. 1226 ± 37 ms, p = 0.016). Attenuated LVEF was observed after two cycles of platinum-based chemotherapy (54 ± 5% vs. 62 ± 5%, p < 0.001). CONCLUSION: is associated with attenuated biventricular systolic function and myocardial tissue alterations in asymptomatic long-term GCC survivors. CLINICAL RELEVANCE STATEMENT: Platinum-based chemotherapy is associated with decreased systolic function, non-ischemic focal myocardial scar, and decreased T1 times in asymptomatic long-term germ cell cancer survivors. Clinicians should be particularly aware of the risk of cardiac toxicity after platinum-based chemotherapy. KEY POINTS: . • Cardiac MRI can help to identify chemotherapy-associated changes in cardiac function and tissue in asymptomatic long-term germ cell cancer survivors.