Cardiovascular Diseases Unit, IRCCS Ospedale Policlinico San Martino, IRCCS Italian Cardiovascular Network, Genova, Italy.
Department of Internal Medicine, University of Genova, Genoa, Italy.
J Transl Med. 2018 Oct 25;16(1):295. doi: 10.1186/s12967-018-1670-9.
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 (FDG-PET) scans before treatment (PET), after 2 cycles (PET) and at the end of treatment (PET); at least one echocardiography ≥ 6 months after chemotherapy completion (ECHO). We then evaluated the changes in LV FDG 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). LV-SUV gradually increased from PET (log-transformed mean 0.20 ± 0.27) to PET (0.27 ± 0.35) to PET (0.30 ± 0.41; P for trend < 0.001). ECHO 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 resulted significantly lower in those with LV-SUV above than below the median value at both PET (65.5 ± 11.8% vs. 71.9 ± 7.8%, P = 0.04) and PET (65.6 ± 12.2% vs. 72.2 ± 7.0%, P = 0.04). This was also the case when only patients with ECHO and ECHO were considered (LVEF at ECHO 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 and PET, respectively). Furthermore, the difference between LVEF at ECHO and ECHO was inversely correlated with LV-SUV at PET (P < 0.01, R = - 0.30).
DOX-containing chemotherapy causes an increase in cardiac FDG 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.
多柔比星（DOX）为基础的霍奇金淋巴瘤（HL）化疗可获得极好的无病生存，但会导致随后发生左心室（LV）功能障碍和心力衰竭，通常是延迟发病。在细胞水平上，这种心脏毒性包括心脏葡萄糖代谢紊乱。
通过回顾 2008 年 1 月至 2016 年 12 月的医院记录，我们选择了符合以下标准的 HL 患者：≥18 岁；一线含 DOX 的化疗；无糖尿病和明显的心血管疾病；治疗前（PET）、2 个周期后（PET）和治疗结束时（PET）进行 18-氟-脱氧葡萄糖正电子发射断层扫描（FDG-PET）扫描；化疗完成后至少有一次心脏超声心动图检查（ECHO）≥6 个月。然后，我们评估了 DOX 治疗过程中 LV FDG 标准化摄取值（SUV）的变化，并通过 Teicholz 公式从超声心动图报告中的 LV 直径计算 LV-SUV 与 LV 射血分数（LVEF）之间的关系。
共有 43 名患者（35±13 岁，58%为男性）纳入研究，其中 26 名（60%）也有基线超声心动图（ECHO）。LV-SUV 从 PET（对数转换平均值 0.20±0.27）逐渐增加到 PET（0.27±0.35）和 PET（0.30±0.41；P 趋势<0.001）。ECHO 在 DOX 化疗后 22±17 个月进行。平均 LVEF 正常（68.8±10.3%），只有 3 名患者（7%）的 LVEF 低于 53%的正常上限。然而，当根据 LV-SUV 的中位数对患者进行分类时，在 PET（65.5±11.8%对 71.9±7.8%，P=0.04）和 PET（65.6±12.2%对 72.2±7.0%，P=0.04）时，ECHO 时的 LVEF 在 LV-SUV 高于和低于中位数的患者中明显较低。当仅考虑有 ECHO 和 ECHO 的患者时，这种情况也是如此（ECHO 时的 LVEF 为 64.7±8.9%对 73.4±7.6%，P=0.01 和 64.6±9.3%对 73.5±7.0%，P=0.01，LV-SUV 高于和低于 PET 和 PET 时的中位数）。此外，ECHO 时的 LVEF 与 ECHO 时的 LVEF 之间的差异与 PET 时的 LV-SUV 呈负相关（P<0.01，R=-0.30）。
含 DOX 的化疗会导致心脏 FDG 摄取增加，这与 LVEF 下降有关。需要进一步研究以了解这种观察结果的分子基础和潜在临床意义。
