目的:钠-葡萄糖协同转运体-2抑制剂(SGLT-2i)是一类新的药物,可降低射血分数(HFrEF)降低的心力衰竭患者的血糖并降低死亡率。它们还具有抗氧化作用。SGLT-2i的确切机制未知。这项研究调查了SGLT-2i对asprosin,基质金属蛋白酶(MMP),以及MMP-1的组织抑制剂(TIMP-1)浓度和超声心动图测量左心室应变。
方法:这项前瞻性随访研究包括56名最初未接受SGLT-2抑制剂的HFrEF和糖尿病(DM)患者。对照组由30名健康个体组成。HFrEF患者除治疗外,还接受了依帕列净(n=28)或达格列净(n=28)。对患者组进行左心室整体纵向应变(LVGLS)评估,左心房(LA)拉伤,以及研究开始和第三个月的洛杉矶卷。对照组采血一次,而患者组有两次:在试验开始时,在超声心动图评估的同一天,在启动SGLT-2i后的第三个月底。血清水平,评估MMP-1和TIMP-1。
结果:与基线相比,在第三个月评估时,HFrEF患者的LVGLS显着增加(-8.6±2.3%vs.-9±2.5%,分别为;p<0.001),LVEF差异无统计学意义(p=0.593)。与基线值相比,左心房射血分数(LAEF)显着增加(36.3±9.4%vs.42.1±8.7%,分别为;p<0.001),由最小LA体积的减少驱动[32.5(19-96)ml与32(20-86)ml,分别为;p=0.018]。与基线评估相比,左油箱[13(6-25)vs.16.5(2-26),分别为;p<0.001]和收缩应变(7.7±4.3vs.分别为9.4±5.6;p=0.014)值在第三个月也得到了增强。在基线和第3个月之间,患者组的LA导管应变(p=0.122)和LA最大容积(p=0.716)保持不变.血清丙蛋白显着增加(11.7±5.1ng/mLvs.14±9.4ng/mL,分别;p=0.032);然而,MMP(p=0.278)和TIMP-1(p=0.401)水平无统计学意义的改变.
结论:SGLT-2i与LVGLS水平升高相关,LAEF,LA收缩应变,和洛杉矶储层应变。SGLT-2i药物可能会改善血浆中的asprosin水平,以促进能量代谢,减少氧化应激和活性氧自由基。
OBJECTIVE: Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are a new class of drugs that lower blood glucose and reduce mortality in heart failure patients with reduced ejection fraction (HFrEF). They also have antioxidant effects. The exact mechanism of SGLT-2i is unknown. This study investigated the effects of SGLT-2i on asprosin, matrix metalloproteinase (MMP), and tissue inhibitor of MMP (TIMP-1) concentrations and echocardiographic measurements of strain in the left heart chamber.
METHODS: This prospective follow-up study included 56 patients with HFrEF and diabetes mellitus (DM) who did not initially receive SGLT-2 inhibitors. The control group consisted of 30 healthy individuals. Patients with HFrEF were administered either empagliflozin (n=28) or dapagliflozin (n=28) in addition to their treatment. The patient group was evaluated for left ventricular global longitudinal strain (LVGLS), left atrial (LA) strain, and LA volumes at the beginning and third month of the study. The control group had blood collected once, while the patient group had it twice: at the start of the trial, on the same day as the echocardiographic evaluation, and at the end of the third month after starting an SGLT-2i. Serum levels of asprosin, MMP-1 and TIMP-1 were assessed.
RESULTS: LVGLS increased significantly in HFrEF patients at the third-month assessment compared to baseline (-8.6±2.3% vs. -9±2.5%, respectively; p<0.001), but there was no significant difference in LVEF (p=0.593). A substantial increase was observed in the left atrial ejection fraction (LAEF) compared to baseline values (36.3±9.4% vs. 42.1±8.7%, respectively; p<0.001), driven by a reduction in minimal LA volume [32.5 (19-96) ml vs. 32 (20-86) ml, respectively; p=0.018]. Compared to baseline evaluation, LA reservoir [13 (6-25) vs. 16.5 (2-26), respectively; p<0.001] and contraction strain (7.7±4.3 vs. 9.4±5.6, respectively; p=0.014) values were also enhanced at the third month. Between the baseline and the 3rd month, the patient group\'s LA conduit strain (p=0.122) and LA maximum volume (p=0.716) remained unchanged. Serum asprosin significantly increased (11.7±5.1 ng/mL vs. 14±9.4 ng/mL, respectively; p=0.032); however, no statistically significant alteration was detected in MMP (p=0.278) and TIMP-1 levels (p=0.401).
CONCLUSIONS: SGLT-2i are associated with elevated levels of LVGLS, LAEF, LA contraction strain, and LA reservoir strain. SGLT-2i medications may improve plasma asprosin levels to boost energy metabolism, reduce oxidative stress and reactive oxygen radicals.