Effect of Sodium-glucose Co-transporter 2 Inhibitor on Ventricular Remodeling

doi:10.12114/j.issn.1007-9572.2020.00.638

Abstract

Abstract: Ventricular remodeling is a pathophysiological process associated with the progression of cardiovascular diseases，the more severe of ventricular remodeling，the worse of prognosis of cardiovascular diseases，and it will eventually lead to heart failure and death.However，there are limited available drugs to delay or reverse ventricular remodeling clinically.As a new type of oral hypoglycemic drug，sodium-glucose co-transporter 2（SGLT-2）inhibitor has been indicated a protective effect on cardiovascular system by many studies.This paper selectively analyzed the effect of SGLT-2 inhibitor on ventricular remodeling in acute myocardial infarction，diabetic cardiomyopathy，hypertensive heart disease and heart failure，so as to provide a reference for more scientific and reasonable application of SGLT-2 inhibitor.

Key words: Ventricular remodeling, Sodium-glucose transporter 2, Myocardial infarction, Diabetic cardiomyopathies, Hypertension, Heart failure

摘要： 心室重构是多种心血管疾病进展过程中伴随的病理生理反应，心室重构越严重则心血管疾病患者预后越差，并最终导致心力衰竭及死亡，但目前临床可用于延缓或逆转心室重构的药物有限。钠-葡萄糖共转运蛋白2（SGLT-2）抑制剂是一种新型口服降糖药，已有多项研究表明其具有心血管保护作用。本文重点分析了SGLT-2抑制剂对急性心肌梗死、糖尿病性心肌病、高血压心脏病及心力衰竭等疾病进展过程中心室重构的影响，以期为临床医师更科学、合理地应用SGLT-2抑制剂提供参考。

关键词: 心室重构, 钠-葡萄糖转运体2, 心肌梗死, 糖尿病心肌病, 高血压, 心力衰竭

LI Zhao,CHENG Gong. Effect of Sodium-glucose Co-transporter 2 Inhibitor on Ventricular Remodeling　[J]. Chinese General Practice, 2021, 24(3): 267-271. DOI: 10.12114/j.issn.1007-9572.2020.00.638.
李兆,程功. 钠-葡萄糖共转运蛋白2抑制剂对心室重构的影响[J]. 中国全科医学, 2021, 24(3): 267-271. DOI: 10.12114/j.issn.1007-9572.2020.00.638.

References

［1］YANG W，ZHANG F，TANG H，et al．Summed thickening score by myocardial perfusion imaging：a risk factor of left ventricular remodeling in patients with myocardial infarction［J］．J Nucl Cardiol，2018，25（3）：742-753．DOI：10.1007/s12350-018-1200-4.
［2］LI X，JIN F，JING C，et al．Predictive value of left ventricular remodeling by area strain based on three-dimensional wall-motion tracking after PCI in patients with recent NSTEMI［J］．Ultrasound Med Biol，2012，38（9）：1491-1501．DOI：10.1016/j.ultrasmedbio.2012.05.006.
［3］BERSELL K，ARAB S，HARING B，et al．Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury［J］．Cell，2009，138（2）：257-270．DOI：10.1016/j.cell.2009.04.060.
［4］BOSTR?M P，MANN N，WU J，et al．C/EBPβ controls exercise-induced cardiac growth and protects against pathological cardiac remodeling［J］．Cell，2010，143（7）：1072-1083．DOI：10.1016/j.cell.2010.11.036.
［5］TAKEDA N，MANABE L，UCHINO Y，et al．Cardiac fibroblasts are essential for the adaptive response of the murine heart to pressure overload［J］．J Clin Invest，2010，120（1）：254-265．DOI：10.1172/JCI40295.
［6］HEINEKE J，AUGER-MESSIER M，XU J，et al．Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the murine heart［J］．J Clin Invest，2007，117（11）：3198-3210.
［7］KOSIBOROD M，GAUSE-NILSSON I，XU J，et al．Efficacy and safety of dapagliflozin in patients with type 2 diabetes and concomitant heart failure［J］．J Diabetes Complications，2017，31（7）：1215-1221．DOI：10.1016/j.jdiacomp.2017.02.001.
［8］AKKOYUN D C，AKYüZ A，ALPSOY S，et al．Plasma urotensin Ⅱ and neurokinin B levels in acute myocardial infarction and stable coronary artery disease［J］．Anatol J Cardiol，2014，15（8）：628-633．DOI：10.5152/akd.2014.5596.
［9］仲伟智.急性心肌梗死合并糖尿病患者冠状动脉介入治疗后心室重构的变化［J］．中国医药指南，2020，18（18）：108-109.　
ZHONG W Z.Changes of ventricular remodeling after coronary intervention in patients with acute myocardial infarction and diabetes mellitus［J］．Guide of China Medicine，2020，18（18）：108-109.
［10］ULVENSTAM A，HENRIKSSON R，S?DERSTR?M L，et al．Ischemic stroke rates decrease with increased ticagrelor use after acute myocardial infarction in patients treated with percutaneous coronary intervention［J］．Eur J Prev Cardiol，2018，25（11）：1219-1230．DOI：10.1177/2047487318784082.
［11］BHATT D L，FOX K，HARRINGTON R A，et al．Rationale，design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients intervention study［J］．Clin Cardiol，2019，42（5）：498-505．DOI：10.1002/clc.23164.
［12］IANNANTUONI F，DE MARA?ON A M，DIAZ-MORALES N，et al．The SGLT2 inhibitor empagliflozin ameliorates the inflammatory profile in type 2 diabetic patients and promotes an antioxidant response in leukocytes［J］．J Clin Med，2019，8（11）：1814．DOI：10.3390/jcm8111814.
［13］HEERSPINK H，PERCO P，MULDER S，et al．Canagliflozin reduces inflammation and fibrosis biomarkers：a potential mechanism of action for beneficial effects of SGLT2 inhibitors in diabetic kidney disease［J］．Diabetologia，2019，62（7）：1154-1166．DOI：10.1007/s00125-019-4859-4.
［14］LENG W，WU M，PAN H，et al．The SGLT2 inhibitor dapagliflozin attenuates the activity of ROS-NLRP3 inflammasome axis in steatohepatitis with diabetes mellitus［J］．Ann Transl Med，2019，7（18）：429．DOI：10.21037/atm.2019.09.03.
［15］LEE T M，CHANG N C，LIN S Z，et al．Dapagliflozin，a selective SGLT2 inhibitor，attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts［J］．Free Radic Biol Med，2017，104：298-310．DOI：10.1016/j.freeradbiomed.2017.01.035.
［16］ANVERSA P，OLIVETTI G，CAPASSO J M.Cellular basis of ventricular remodeling after myocardial infarction［J］．Am J Cardiol，1991，68（14）：7D-16D．DOI：10.1016/0002-9149（91）90256-k.
［17］KANG S，VERMA S，HASSANABAD A，et al．Direct effects of empagliflozin on extracellular matrix remodelling in human cardiac myofibroblasts：novel translational clues to explain EMPA-REG OUTCOME results［J］．Can J Cardiol，2020，36（4）：543-553．DOI：10.1016/j.cjca.2019.08.033.
［18］SANTOS-GALLEGO C G，REQUENA-IBANEZ J A，ANTONIO R S，et al．Empagliflozin ameliorates adverse left ventricular remodeling in nondiabetic heart failure by enhancing myocardial energetics［J］．J Am Coll Cardiol，2019，73（15）：1931-1944．DOI：10.1016/j.jacc.2019.01.056.
［19］VERMA S，GARG A，YAN A T，et al．Effect of empagliflozin on left ventricular mass and diastolic function in individuals with diabetes：an important clue to the EMPA-REG OUTCOME Trial？［J］．Diabetes Care，2016，39（12）：e212-213．DOI：10.2337/dc16-1312.
［20］RUBLER S，DLUGASH J，YUCEOGLU Y Z，et al．New type of cardiomyopathy associated with diabetic glomerulosclerosis［J］．Am J Cardiol，1972，30（6）：595-602．DOI：10.1016/0002-9149（72）90595-4.
［21］SOLIMAN E，BYINGTON R P，BIGGER J T，et al．Effect of intensive blood pressure lowering on left ventricular hypertrophy in patients with diabetes mellitus：action to control cardiovascular risk in diabetes blood pressure trial［J］．Hypertension，2015，66（6）：1123-1129.
［22］TAEGTMEYER H，MCNULTY P，YOUNG M E J C.Adaptation and maladaptation of the heart in diabetes：PartⅠgeneral concepts［J］．Circulation，2002，105（14）：1727-1733．DOI：10.1161/01.cir.0000012466.50373.e8.
［23］JOUBERT M，JAGU B，MONTAIGNE D，et al．The sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents cardiomyopathy in a diabetic lipodystrophic mouse Model［J］．Diabetes，2017，66（4）：1030-1040．DOI：10.2337/db16-0733.
［24］YE Y，BAJAJ M，YANG H，et al．SGLT-2 inhibition with dapagliflozin reduces the activation of the Nlrp3/ASC inflammasome and attenuates the development of diabetic cardiomyopathy in mice with type 2 diabetes.Further augmentation of the effects with saxagliptin，a DPP4 inhibitor［J］．Cardiovasc Drugs Ther，2017，31（2）：119-132．DOI：10.1007/s10557-017-6725-2.
［25］LI C，ZHANG J，XUE M，et al．SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart［J］．Cardiovasc Diabetol，2019，18（1）：15．DOI：10.1186/s12933-019-0816-2.
［26］CAO X，BROUGHTON S T，WAITS G S，et al．Interrelations between hypertension and electrocardiographic left ventricular hypertrophy and their associations with cardiovascular mortality［J］．Am J Cardiol，2019，123（2）：274-283．DOI：10.1016/j.amjcard.2018.10.006.
［27］DAWSON A，MORRIS A D，STRUTHERS A D.The epidemiology of left ventricular hypertrophy in type 2 diabetes mellitus［J］．Diabetologia，2005，48（10）：1971-1979．DOI：10.1007/s00125-005-1896-y.
［28］COOPER R S，SIMMONS B E，CASTANER A，et al．Left ventricular hypertrophy is associated with worse survival independent of ventricular function and number of coronary arteries severely narrowed［J］．Am J Cardiol，1990，65（7）：441-445．DOI：10.1016/0002-9149（90）90807-d.
［29］LIAO Y，COOPER R S，MCGEE D L，et al．The relative effects of left ventricular hypertrophy，coronary artery disease，and ventricular dysfunction on survival among black adults［J］．JAMA，1995，273（20）：1592-1597.
［30］ARTHAM S M，LAVIE C J，MILANI R V，et al．Clinical impact of left ventricular hypertrophy and implications for regression［J］．Prog Cardiovasc Dis，2009，52（2）：153-167．DOI：10.1016/j.pcad.2009.05.002.
［31］DRAZNER M H，RAME J E，MARINO E K，et al．Increased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years：the Cardiovascular Health Study［J］．J Am Coll Cardiol，2004，43（12）：2207-2215．DOI：10.1016/j.jacc.2003.11.064.
［32］FERRANNINI E，BALDI S，FRASCERRA S，et al．Renal handling of ketones in response to sodium-glucose cotransporter 2 inhibition in patients with type 2 diabetes［J］．Diabetes Care，2017，40（6）：771-776．DOI：10.2337/dc16-2724.
［33］LEE H C，SHIOU Y L，JHUO S J，et al．The sodium-glucose co-transporter 2 inhibitor empagliflozin attenuates cardiac fibrosis and improves ventricular hemodynamics in hypertensive heart failure rats［J］．Cardiovasc Diabetol，2019，18（1）：45．DOI：10.1186/s12933-019-0849-6.
［34］ZHANG N，FENG B，MA X，et al．Dapagliflozin improves left ventricular remodeling and aorta sympathetic tone in a pig model of heart failure with preserved ejection fraction［J］．Cardiovasc Diabetol，2019，18（1）：107．DOI：10.1186/s12933-019-0914-1.
［35］MCMURRAY J J V，SOLOMON S D，INZUCCHI S，et al．Dapagliflozin in patients with heart failure and reduced ejection fraction［J］．N Engl J Med，2019，381（21）：1995-2008．DOI：10.1056/NEJMoa1911303.
［36］MAGGIONI A P，DAHLSTR?M U，FILIPPATOS G，et al．EURObservational Research Programme：regional differences and 1-year follow-up results of the Heart Failure Pilot Survey（ESC-HF Pilot）［J］．Eur J Heart Fail，2013，15（7）：808-817．DOI：10.1093/eurjhf/hft050.
［37］梁逸强，潘朝锌，何新兵，等．心室重构发病机制的研究进展［J］．河北医药，2013，35（24）：3781-3784.
［38］BYRNE N J，PARAJULI N，LEVASSEUR J，et al．Empagliflozin prevents worsening of cardiac function in an experimental model of pressure overload-induced heart failure［J］．JACC Basic Transl Sci，2017，2（4）：347-354．DOI：10.1016/j.jacbts.2017.07.003.
［39］SINGH J S S，MORDI I R，VICKNESON K，et al．Dapagliflozin versus placebo on left ventricular remodeling in patients with diabetes and heart failure：the REFORM trial［J］．Diabetes Care，2020，43（6）：1356-1359.
［40］SINGH J S S，FATHI A，VICKNESON K，et al．Research into the effect of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus（REFORM）trial rationale and design［J］．Cardiovasc Diabetol，2016，15：97．DOI：10.1186/s12933-016-0419-0.

[1]	ZHANG Jin, DING Zhiguo, QI Shuo, LI Ying, LI Weiqiang, ZHANG Yuanyuan, ZHOU Tong. Relationship between Serum Thyroid Hormone Levels and Prognosis during Hospitalization in Heart Failure Patients [J]. Chinese General Practice, 2023, 26(33): 4125-4129.
[2]	WANG Yu, CHEN Yan, HAN Yuanyuan, XU Qing, CHEN Shengyue, LYU Zhibo, LU Chuan, ZHENG Mingxin, ZHAO Xin. Platelet-lymphocyte Ratio Predicts In-hospital Mortality in Elderly Patients with Acute Myocardial Infarction [J]. Chinese General Practice, 2023, 26(33): 4137-4142.
[3]	ZHANG Shuai, LI Qin, LI Dongfeng, XIAO Jinping, LI Yunpeng. A Prospective Cohort Study of Solid Fuels Use and Risk of Hypertension in Chinese Older Adults [J]. Chinese General Practice, 2023, 26(32): 4001-4006.
[4]	MA Yanyan, REN Fuxian, WANG Yu, GAO Dengfeng. The Prediction Value of (Neutrophil+Monocyte) /Lymphocyte Ratio on In-hospital Mortality of Heart Failure Patients [J]. Chinese General Practice, 2023, 26(30): 3791-3796.
[5]	WANG Zhen, SHEN Guoqi, LI Yanan, ZHU Yinghua, QIU Hang, ZHENG Di, XU Tongda, LI Wenhua. Development and Validation of a Risk Prediction Model for Contrast-induced Acute Kidney Injury after Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction [J]. Chinese General Practice, 2023, 26(29): 3650-3656.
[6]	ZHANG Zhendong, CAI Bin, WANG Hongwei, QIAO Zengyong. Study on the Changes of Intestinal Flora and Its Metabolite Phenylacetylglutamine in Patients with Chronic Heart Failure [J]. Chinese General Practice, 2023, 26(29): 3665-3673.
[7]	XIAO Liqi, YANG Li, CUI Saixian, ZHANG Yayuan, WANG Yulu, HE Yan. Advances in the Association of High Salt-induced Gut Microbiota Disturbances with Salt-sensitive Blood Pressure [J]. Chinese General Practice, 2023, 26(29): 3704-3709.
[8]	CHENG Xiaoran, ZHANG Xiaotian, LI Mingyue, CHENG Haozhe, TANG Haoqing, ZHENG Huixian, ZHANG Baisong, LIU Xiaoyun. Impact of Chronic Diseases Follow-up on Health Behaviors and Blood Pressure/Glucose Control of Patients with Hypertension and Diabetes in the Context of Treatment-prevention Integration [J]. Chinese General Practice, 2023, 26(28): 3482-3488.
[9]	MIAO Guangrui, PANG Shuo, ZHOU Yuanhang, DUAN Mingxuan, BAI Linpeng, ZHANG Qingyang, ZHAO Xiaoyan, DONG Jianzeng. Short-term Prognostic Value of Early Fluid Balance and Lactate Clearance in Patients with Acute Myocardial Infarction Combined with Cardiogenic Shock Treated with Extracorporeal Membrane Oxygenation [J]. Chinese General Practice, 2023, 26(27): 3397-3402.
[10]	BIAN Lili, LI Xiaoxiao, DU Xueping, DAI Qinfang, WU Lin, SONG Beibei. Risk Stratification of Atherosclerotic Cardiovascular Disease and Lipid Goal Attainment in Hypertensive Patients Registered in Community [J]. Chinese General Practice, 2023, 26(27): 3388-3391.
[11]	FEI Sijie, ZHANG Qiang, LIU Fangfang, BAI Lu, SUN Caihong, XIN Caifeng. Correlation between Glycated Hemoglobin Variability and New-onset Atrial Fibrillation in Type 2 Diabetes Patients Combined with Heart Failure with Preserved Ejection Fraction [J]. Chinese General Practice, 2023, 26(26): 3246-3251.
[12]	ZHAO Wei, TANG Rongjie, YANG Shanshan, YANG Fang, SUN Feng, LIAN Qiufang. The Role and Molecules Mechanism of Klotho in Renal Injury in Salt-sensitive Hypertension [J]. Chinese General Practice, 2023, 26(24): 3042-3049.
[13]	ZUO Xu, HUANG Zhaolan, LU Biao. Differences between the First and Another 3-day Blood Pressure Levels and Associated Factors in a Self-reported Non-hypertensive Population Aged 35-64 Years [J]. Chinese General Practice, 2023, 26(22): 2771-2777.
[14]	FENG Jia, WANG Jie, YU Dan, LIU Yongheng, ZHAO Weidong, TIAN Hongyuan. Analysis of Research Hotspots of Multiple Chronic Conditions in the Elderly in 2010-2021 [J]. Chinese General Practice, 2023, 26(21): 2574-2580.
[15]	YU Tong, YANG Yi, DU Shihong, DING Zihao, HONG Xiuqin. Correlation of Shearing Force and Estradiol with Hypertension [J]. Chinese General Practice, 2023, 26(20): 2469-2475,2495.