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达格列净对风湿性心脏病二尖瓣狭窄患者的影响。

Effect of Dapagliflozin on Patients with Rheumatic Heart Disease Mitral Stenosis.

作者信息

Asrial An Aldia, Reviono Reviono, Soetrisno Soetrisno, Setianto Budi Yuli, Widyaningsih Vitri, Nurwati Ida, Wasita Brian, Pudjiastuti Anggit

机构信息

Doctoral Program of Medical Sciences Department, Faculty of Medicine, Universitas Sebelas Maret, Surakarta 57126, Indonesia.

Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Sebelas Maret-Universitas Sebelas Maret Hospital, Surakarta 57126, Indonesia.

出版信息

J Clin Med. 2023 Sep 11;12(18):5898. doi: 10.3390/jcm12185898.

Abstract

(1) Background: Mitral stenosis is the most common rheumatic heart disease (RHD). Inflammation and fibrosis are the primary pathophysiology, resulting in left atrial stress and dysfunction. Dapagliflozin is a new heart failure treatment with anti-inflammation and anti-fibrosis effects from previous studies. However, the specific role of dapagliflozin in RHD mitral stenosis is unknown. This study aims to investigate (i) the effect of dapagliflozin on biomarkers of fibrosis, NT-pro BNP levels and left atrial function; (ii) the relationship between the changes in fibrosis biomarkers with left atrial function and NT-pro BNP levels. (2) Methods: An open-label randomized study was conducted on 33 RHD mitral stenosis patients divided into a dapagliflozin group which received 10 mg dapagliflozin and standard therapy, and a control group which only received standard therapy. All patients were examined for levels of PICP, MMP-1/TIMP-1 ratio, TGF-β1, NT-proBNP, mitral valve mean pressure gradient (MPG), and net atrioventricular compliance (Cn) pre- and post-intervention. (3) Results: This study found a significant increase in PICP and TGF-β1 and a reduction in the MMP-1/TIMP-1 ratio in the dapagliflozin group and the control group ( < 0.05). In the dapagliflozin group, the levels of NT-pro BNP decreased significantly ( = 0.000), with a delta of decreased NT-pro BNP levels also significantly greater in the dapagliflozin group compared to the control ( = 0.034). There was a significant increase in Cn values in the dapagliflozin group ( = 0.017), whereas there was a decrease in the control group ( = 0.379). Delta of changes in Cn values between the dapagliflozin and control groups also showed a significant value ( = 0.049). The decreased MPG values of the mitral valve were found in both the dapagliflozin and control groups, with the decrease in MPG significantly greater in the dapagliflozin group ( = 0.031). There was no significant correlation between changes in the value of fibrosis biomarkers with Cn and NT-pro BNP ( > 0.05). (4) Conclusions: This study implies that the addition of dapagliflozin to standard therapy for RHD mitral stenosis patients provides benefits, as evidenced by an increase in net atrioventricular compliance and decreases in the MPG value of the mitral valve and NT-pro BNP levels ( < 0.05). This improvement was not directly related to changes in fibrosis biomarkers, as these biomarkers showed ongoing fibrosis even with dapagliflozin administration.

摘要

(1)背景:二尖瓣狭窄是最常见的风湿性心脏病(RHD)。炎症和纤维化是主要的病理生理学过程,会导致左心房压力和功能障碍。达格列净是一种新型心力衰竭治疗药物,先前研究表明其具有抗炎和抗纤维化作用。然而,达格列净在风湿性心脏病二尖瓣狭窄中的具体作用尚不清楚。本研究旨在探讨:(i)达格列净对纤维化生物标志物、N末端B型利钠肽原(NT-pro BNP)水平和左心房功能的影响;(ii)纤维化生物标志物变化与左心房功能和NT-pro BNP水平之间的关系。(2)方法:对33例风湿性心脏病二尖瓣狭窄患者进行了一项开放标签随机研究,分为达格列净组(接受10mg达格列净和标准治疗)和对照组(仅接受标准治疗)。所有患者在干预前后均检测了I型前胶原羧基端前肽(PICP)、基质金属蛋白酶-1/金属蛋白酶组织抑制因子-1(MMP-1/TIMP-1)比值、转化生长因子-β1(TGF-β1)、NT-pro BNP、二尖瓣平均压力阶差(MPG)和房室净顺应性(Cn)水平。(3)结果:本研究发现,达格列净组和对照组的PICP和TGF-β1显著升高,MMP-1/TIMP-1比值降低(P<0.05)。在达格列净组中,NT-pro BNP水平显著降低(P = 0.000),与对照组相比,达格列净组NT-pro BNP水平降低的差值也显著更大(P = 0.034)。达格列净组的Cn值显著升高(P = 0.017),而对照组则降低(P = 0.379)。达格列净组和对照组之间Cn值变化的差值也显示出显著差异(P = 0.049)。达格列净组和对照组的二尖瓣MPG值均降低,达格列净组MPG的降低更为显著(P = 0.031)。纤维化生物标志物值的变化与Cn和NT-pro BNP之间无显著相关性(P>0.05)。(4)结论:本研究表明,在风湿性心脏病二尖瓣狭窄患者的标准治疗中加用达格列净有益,房室净顺应性增加、二尖瓣MPG值和NT-pro BNP水平降低证明了这一点(P<0.05)。这种改善与纤维化生物标志物的变化没有直接关系,因为即使使用达格列净,这些生物标志物仍显示存在纤维化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fb6/10532082/4e34e073812a/jcm-12-05898-g001.jpg

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