Abstract: Background　With advances in cancer diagnosis and treatment technologies，as well as the rapid development of anti-cancer drugs，the survival of cancer survivors has significantly improved. Cardiovascular diseases，particularly heart failure，resulting from cancer treatment have become a significant concern. Dapagliflozin，a novel sodium-glucose cotransporter 2（SGLT2）inhibitor，has demonstrated significant clinical benefits in the treatment of type 2 diabetes and heart failure（HF）. However，studies on its prognostic impact in elderly breast cancer survivors with heart failure with preserved ejection fraction（HFpEF）and type 2 diabetes remain scarce. Objective　To investigate the prognostic impact of dapagliflozin in elderly breast cancer survivors with HFpEF and type 2 diabetes. Methods　Ninety-three elderly female breast cancer survivors with HFpEF and type 2 diabetes admitted to the Affiliated Hospital of Qingdao University from January 2018 to August 2023 were enrolled. Based on the medication regimen，patients were divided into the dapagliflozin group（47 patients） and the control group（46 patients）. Baseline data were collected，and patients were followed up for 6 months，with the follow-up period ending in April 2024. The primary endpoint was the occurrence of rehospitalization due to heart failure during the follow-up. Adverse reactions during the follow-up were also recorded. The Kaplan-Meier method was used to plot survival curves，and the Log-rank test was used for comparisons between groups. A multivariate Cox proportional hazards model was employed to analyze the factors influencing rehospitalization events. Results　The average age of the patients was（70.1±3.8）years. There were no statistically significant differences in baseline characteristics between the two groups（P>0.05）. After 6 months of treatment，both the dapagliflozin group and the control group showed decreased levels of fasting plasma glucose（FPG） and glycated hemoglobin（HbA1c），and increased estimated glomerular filtration rate（eGFR）（P<0.05）. At 6 months post-treatment，the dapagliflozin group had lower FPG and HbA1c levels and higher eGFR levels compared to the control group （P<0.05）. Additionally，the left ventricular end-diastolic diameter（LVEDD），interventricular septal thickness（IVST），left ventricular posterior wall thickness（LVPWT），early diastolic mitral valve flow velocity（E）/early diastolic mitral annular peak velocity（e'），left atrial volume index（LAVI），and left ventricular mass index（LVMI）decreased in both groups，while the left ventricular ejection fraction（LVEF）increased compared to pre-treatment levels（P<0.05）. At 6 months post-treatment，the dapagliflozin group had lower LVEDD，IVST，LVPWT，LVMI，LAVI，and E/e'，and higher LVEF compared to the control group（P<0.05）. Levels of high-sensitivity cardiac troponin I（hs-cTnI）and N-terminal pro-B-type natriuretic peptide（NT-proBNP）decreased in both groups after 6 months of treatment（P<0.05）. At 6 months post-treatment，the dapagliflozin group had lower hs-cTnI and NT-proBNP levels compared to the control group（P<0.05）. During the 6-month follow-up，5 patients（10.6%）in the dapagliflozin group and 13 patients（28.3%）in the control group were rehospitalized due to heart failure. Kaplan-Meier survival analysis showed a statistically significant difference in cumulative rehospitalization-free survival rates between the two groups（P=0.032 6）. Multivariate Cox regression analysis results indicated that the use of dapagliflozin（HR=0.325，95%CI=0.116-0.912，P=0.033），angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitors（HR=0.562，95%CI=0.236-0.949，P=0.035），and spironolactone（HR=0.836，95%CI=0.710-0.985，P=0.037）were protective factors against rehospitalization events，while increasing age（HR=1.343，95%CI=1.198-1.506，P<0.001），higher BMI（HR=1.305，95%CI=1.111-1.532，P=0.001），and the use of anthracyclines （HR=1.197，95%CI=1.035-1.384，P=0.023）were risk factors for increased rehospitalization events. Conclusion　In elderly breast cancer survivors with HFpEF and type 2 diabetes，dapagliflozin not only effectively controls blood glucose and improves renal function but also significantly improves cardiac function，enhancing long-term prognosis.

Key words: Heart failure, Heart failure with reduced ejection fraction, Breast cancer, Breast cancer survivors, Type 2 diabetes mellitus, Dapagliflozin, Aged, Prognosis

摘要： 背景　随着肿瘤诊疗技术的进步以及抗肿瘤药物的快速发展，肿瘤幸存者的生存期显著延长。肿瘤治疗引发的心血管疾病，特别是心力衰竭，已成为一个重要的关注点。达格列净是一种新型钠-葡萄糖协同转运蛋白2抑制剂，已被证实在治疗2型糖尿病和心力衰竭方面具有显著的临床益处。然而，其在老年乳腺癌幸存者中射血分数保留的心力衰竭（HFpEF）合并2型糖尿病患者预后影响的研究仍然缺乏。目的　探讨达格列净对老年乳腺癌幸存者中HFpEF合并2型糖尿病患者预后的影响。方法　选取2018年1月—2023年8月在青岛大学附属医院收治的老年女性乳腺癌幸存者HFpEF合并2型糖尿病患者93例为研究对象，根据用药方案，患者被分为达格列净组（47例）和对照组（46例），收集入选患者基线资料，对患者进行为期6个月的随访，随访截止时间为2024年4月。研究的主要终点事件为随访期间因心力衰竭再入院的发生。同时记录患者在随访过程中出现的不良反应。应用Kaplan-Meier法绘制生存函数曲线，各组间比较采用Log-rank检验。采用多因素Cox比例风险模型分析再入院事件的影响因素。结果　患者平均年龄（70.1±3.8）岁，两组患者一般资料比较，差异无统计学意义（P>0.05）。治疗6个月后，达格列净组和对照组的空腹血糖（FPG）和糖化血红蛋白（HbA1c）水平降低，估算的肾小球滤过率（eGFR）水平升高（P<0.05）。治疗6个月后，达格列净组患者FPG、HbA1c水平低于对照组，eGFR水平高于对照组（P<0.05）；治疗6个月后，达格列净组和对照组的左室舒张末期内径（LVEDD）、室间隔厚度（IVST）、左心室后壁厚度（LVPWT）、左心室舒张早期二尖瓣血流最大速度（E）/舒张早期二尖瓣环峰值速度（e'）、左心房容积指数（LAVI）和左心室质量指数（LVMI）较治疗前降低，左心室射血分数（LVEF）较治疗前升高（P<0.05）。治疗6个月后，达格列净组患者LVEDD、IVST、LVPWT、LVMI、LAVI、E/e'低于对照组，LVEF高于对照组（P<0.05）；治疗6个月后，达格列净组和对照组的高敏心肌肌钙蛋白I（hs-cTnI）和N末端B型钠尿肽前体（NT-proBNP）水平降低（P<0.05）。治疗6个月后，达格列净组患者hs-cTnI和NT-proBNP水平低于对照组（P<0.05）。随访6个月，达格列净组和对照组因心力衰竭再入院的患者分别为5例（10.6%）和13例（28.3%）。Kaplan-Meier生存分析显示，两组累积无再入院生存率比较，差异有统计学意义（P=0.032 6）。多因素Cox回归分析结果显示，使用达格列净（HR=0.325，95%CI=0.116~0.912，P=0.033）、血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂/血管紧张素受体脑啡肽酶抑制剂（HR=0.562，95%CI=0.236~0.949，P=0.035）、螺内酯（HR=0.836，95%CI=0.710~0.985，P=0.037）为导致再入院事件降低的保护因素，年龄增大（HR=1.343，95%CI=1.198~1.506，P<0.001）、BMI升高（HR=1.305，95%CI=1.111~1.532，P=0.001）、使用蒽环类（HR=1.197，95%CI=1.035~1.384，P=0.023）为导致再入院事件升高的危险因素。结论　在老年乳腺癌幸存者中，对于HFpEF合并2型糖尿病患者，达格列净不仅能有效控制血糖、改善肾功能，还能显著改善心脏功能，提高患者的远期预后。

关键词: 心力衰竭, 射血分数保留的心力衰竭, 乳腺癌, 乳腺癌幸存者, 2 型糖尿病, 达格列净, 老年人, 预后