An increase in myocardial 18-fluorodeoxyglucose uptake is associated with left ventricular ejection fraction decline in Hodgkin lymphoma patients treated with anthracycline

Background: Doxorubicin (DOX)-based chemotherapy for Hodgkin lymphoma (HL) yields excellent disease-free survival, but poses a substantial risk of subsequent left ventricular (LV) dysfunction and heart failure, typically with delayed onset. At the cellular level, this cardiotoxicity includes deranged cardiac glucose metabolism. Methods: By reviewing the hospital records from January 2008 through December 2016, we selected HL patients meeting the following criteria: ≥ 18 year-old; first-line DOX-containing chemotherapy; no diabetes and apparent cardiovascular disease; 18-fluoro-deoxyglucose positron emission tomography (¹⁸FDG-PET) scans before treatment (PET^STAGING), after 2 cycles (PET^INTERIM) and at the end of treatment (PET^EOT); at least one echocardiography ≥ 6 months after chemotherapy completion (ECHO^POST). We then evaluated the changes in LV ¹⁸FDG standardized uptake values (SUV) during the course of DOX therapy, and the relationship between LV-SUV and LV ejection fraction (LVEF), as calculated from the LV diameters in the echocardiography reports with the Teicholz formula. Results: Forty-three patients (35 ± 13 year-old, 58% males) were included in the study, with 26 (60%) also having a baseline echocardiography available (ECHO^PRE). LV-SUV gradually increased from PET^STAGING (log-transformed mean 0.20 ± 0.27) to PET^INTERIM (0.27 ± 0.35) to PET^EOT (0.30 ± 0.41; P for trend < 0.001). ECHO^POST was performed 22 ± 17 months after DOX chemotherapy. Mean LVEF was normal (68.8 ± 10.3%) and only three subjects (7%) faced a drop below the upper normal limit of 53%. However, when patients were categorized by median LV-SUV, LVEF at ECHO^POST resulted significantly lower in those with LV-SUV above than below the median value at both PET^INTERIM (65.5 ± 11.8% vs. 71.9 ± 7.8%, P = 0.04) and PET^EOT (65.6 ± 12.2% vs. 72.2 ± 7.0%, P = 0.04). This was also the case when only patients with ECHO^PRE and ECHO^POST were considered (LVEF at ECHO^POST 64.7 ± 8.9% vs. 73.4 ± 7.6%, P = 0.01 and 64.6 ± 9.3% vs. 73.5 ± 7.0%, P = 0.01 for those with LV-SUV above vs. below the median at PET^INTERIM and PET^EOT, respectively). Furthermore, the difference between LVEF at ECHO^PRE and ECHO^POST was inversely correlated with LV-SUV at PET^EOT (P < 0.01, R² = - 0.30). Conclusions: DOX-containing chemotherapy causes an increase in cardiac ¹⁸FDG uptake, which is associated with a decline in LVEF. Future studies are warranted to understand the molecular basis and the potential clinical implications of this observation.