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

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.

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.

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).

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.