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Journal of Cardiovascular Translational Research

Erschienen in:

15.03.2022 | Review

Sodium-Glucose Cotransporter 2 Inhibitors and Cardiac Remodeling

verfasst von: Husam M. Salah, Subodh Verma, Carlos G. Santos-Gallego, Ankeet S. Bhatt, Muthiah Vaduganathan, Muhammad Shahzeb Khan, Renato D. Lopes, Subhi J. Al’Aref, Darren K. McGuire, Marat Fudim

Erschienen in: Journal of Cardiovascular Translational Research | Ausgabe 5/2022

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Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have evident cardiovascular benefits in patients with type 2 diabetes with or at high risk for atherosclerotic cardiovascular disease, heart failure with reduced ejection fraction, heart failure with preserved ejection fraction (only empagliflozin and dapagliflozin have been investigated in this group so far), and chronic kidney disease. Prevention and reversal of adverse cardiac remodeling is one of the mechanisms by which SGLT2 inhibitors may exert cardiovascular benefits, especially heart failure-related outcomes. Cardiac remodeling encompasses molecular, cellular, and interstitial changes that result in favorable changes in the mass, geometry, size, and function of the heart. The pathophysiological mechanisms of adverse cardiac remodeling are related to increased apoptosis and necrosis, decreased autophagy, impairments of myocardial oxygen supply and demand, and altered energy metabolism. Herein, the accumulating evidence from animal and human studies is reviewed investigating the effects of SGLT2 inhibitors on these mechanisms of cardiac remodeling.

Salah, H. M., Al’Aref, S. J., Khan, M. S., et al. (2021). Effect of sodium-glucose cotransporter 2 inhibitors on cardiovascular and kidney outcomes-Systematic review and meta-analysis of randomized placebo-controlled trials. American Heart Journal, 232, 10–22.PubMedCrossRef

Salah, H. M., Al’Aref, S. J., Khan, M. S., et al. (2021). Effects of sodium-glucose cotransporter 1 and 2 inhibitors on cardiovascular and kidney outcomes in type 2 diabetes: A meta-analysis update. American Heart Journal, 233, 86–91.PubMedCrossRef

McGuire, D. K., Shih, W. J., Cosentino, F., et al. (2021). Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: A meta-analysis. JAMA Cardiology., 6(2), 148–158.PubMedCrossRef

Zannad, F., Ferreira, J. P., Pocock, S. J., et al. (2020). SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: A meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. The Lancet., 396(10254), 819–829.CrossRef

Ghezzi, C., Loo, D. D. F., & Wright, E. M. (2018). Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2. Diabetologia, 61(10), 2087–2097.PubMedPubMedCentralCrossRef

Zhou, L., Cryan, E. V., D’Andrea, M. R., Belkowski, S., Conway, B. R., & Demarest, K. T. (2003). Human cardiomyocytes express high level of Na+/glucose cotransporter 1 (SGLT1). Journal of Cellular Biochemistry, 90(2), 339–346.PubMedCrossRef

Vrhovac, I., Balen Eror, D., Klessen, D., et al. (2015). Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart. Pflugers Archiv. European Journal of Physiology, 467(9), 1881–1898.PubMedCrossRef

Georgianos, P. I., & Agarwal, R. (2019). Ambulatory blood pressure reduction with SGLT-2 inhibitors: Dose-response meta-analysis and comparative evaluation with low-dose hydrochlorothiazide. Diabetes Care, 42(4), 693–700.PubMedPubMedCentralCrossRef

Kawasoe, S., Maruguchi, Y., Kajiya, S., et al. (2017). Mechanism of the blood pressure-lowering effect of sodium-glucose cotransporter 2 inhibitors in obese patients with type 2 diabetes. BMC Pharmacology and Toxicology, 18(1), 23.PubMedPubMedCentralCrossRef

10.

Lopaschuk, G. D., & Verma, S. (2020). Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors: A state-of-the-art review. JACC Basic to Translational Science, 5(6), 632–644.PubMedPubMedCentralCrossRef

11.

Pereira, M. J., & Eriksson, J. W. (2019). Emerging role of SGLT-2 inhibitors for the treatment of obesity. Drugs, 79(3), 219–230.PubMedPubMedCentralCrossRef

12.

Heerspink, H. J., Perkins, B. A., Fitchett, D. H., Husain, M., & Cherney, D. Z. (2016). Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: Cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation, 134(10), 752–772.PubMedCrossRef

13.

Vallon, V., & Verma, S. (2021). Effects of SGLT2 inhibitors on kidney and cardiovascular function. Annual Review of Physiology, 83, 503–528.PubMedCrossRef

14.

Packer, M., Anker, S. D., Butler, J., et al. (2020). Cardiovascular and renal outcomes with empagliflozin in heart failure. New England Journal of Medicine, 383(15), 1413–1424.PubMedCrossRef

15.

McMurray, J. J. V., Docherty, K. F., & Jhund, P. S. (2020). Dapagliflozin in patients with heart failure and reduced ejection fraction. Reply. New England Journal of Medicine, 382(10), 973.

16.

Verma, S., McGuire, D. K., & Kosiborod, M. N. (2020). Twotales: One story. Circulation, 142(23), 2201–2204.PubMedCrossRef

17.

Anker, S. D., Butler, J., Filippatos, G., et al. (2021). Empagliflozin in heart failure with a preserved ejection fraction. New England Journal of Medicine., 385(16), 1451–1461.PubMedCrossRef

18.

Butler, J., Packer, M., Filippatos, G., et al. (2021). Effect of empagliflozin in patients with heart failure across the spectrum of left ventricular ejection fraction. European Heart Journal

19.

Parizo, J. T., Goldhaber-Fiebert, J. D., Salomon, J. A., et al. (2021). Cost-effectiveness of Dapagliflozin for treatment of patients with heart failure with reduced ejection fraction. JAMA Cardiology

20.

Bhatt, D. L., Szarek, M., Steg, P. G., et al. (2020). Sotagliflozin in patients with diabetes and recent worsening heart failure. New England Journal of Medicine., 384(2), 117–128.PubMedCrossRef

21.

Bhatt, D. L., Szarek, M., Pitt, B., et al. (2020). Sotagliflozin in patients with diabetes and chronic kidney disease. New England Journal of Medicine., 384(2), 129–139.PubMedCrossRef

22.

Heerspink, H. J. L., Stefánsson, B. V., Correa-Rotter, R., et al. (2020). Dapagliflozin in patients with chronic kidney disease. New England Journal of Medicine., 383(15), 1436–1446.PubMedCrossRef

23.

Cannon, C. P., Pratley, R., Dagogo-Jack, S., et al. (2020). Cardiovascular outcomes with ertugliflozin in type 2 diabetes. New England Journal of Medicine., 383(15), 1425–1435.PubMedCrossRef

24.

Cohn, J. N., Ferrari, R., & Sharpe, N. (2000). Cardiac remodeling—concepts and clinical implications: A consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. Journal of the American College of Cardiology, 35(3), 569–582.PubMedCrossRef

25.

Azevedo, P. S., Polegato, B. F., Minicucci, M. F., Paiva, S. A. R., & Zornoff, L. A. M. (2016). Cardiac remodeling: Concepts, clinical impact, pathophysiological mechanisms and pharmacologic treatment. Arquivos Brasileiros de Cardiologia, 106(1), 62–69.PubMedPubMedCentral

26.

Konstam, M. A., Kramer, D. G., Patel, A. R., Maron, M. S., & Udelson, J. E. (2011). Left ventricular remodeling in heart failure: Current concepts in clinical significance and assessment. JACC: Cardiovascular Imaging, 4(1), 98–108.PubMed

27.

Azevedo, P. S., Polegato, B. F., Minicucci, M. F., Paiva, S. A., & Zornoff, L. A. (2016). Cardiac remodeling: Concepts, clinical impact, pathophysiological mechanisms and pharmacologic treatment. Arquivos Brasileiros de Cardiologia, 106(1), 62–69.PubMedPubMedCentral

28.

Kurosaki, E., & Ogasawara, H. (2013). Ipragliflozin and other sodium–glucose cotransporter-2 (SGLT2) inhibitors in the treatment of type 2 diabetes: Preclinical and clinical data. Pharmacology & Therapeutics., 139(1), 51–59.CrossRef

29.

Hammoudi, N., Jeong, D., Singh, R., et al. (2017). Empagliflozin improves left ventricular diastolic dysfunction in a genetic model of type 2 diabetes. Cardiovascular Drugs and Therapy, 31(3), 233–246.PubMedPubMedCentralCrossRef

30.

Shiojima, I., Sato, K., Izumiya, Y., et al. (2005). Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure. The Journal of Clinical Investigation, 115(8), 2108–2118.PubMedPubMedCentralCrossRef

31.

Younis, F., Leor, J., Abassi, Z., et al. (2018). Beneficial effect of the SGLT2 inhibitor empagliflozin on glucose homeostasis and cardiovascular parameters in the cohen rosenthal diabetic hypertensive (CRDH) rat. Journal of Cardiovascular Pharmacology and Therapeutics., 23(4), 358–371.PubMedCrossRef

32.

Park, S. H., Farooq, M. A., Gaertner, S., et al. (2020). Empagliflozin improved systolic blood pressure, endothelial dysfunction and heart remodeling in the metabolic syndrome ZSF1 rat. Cardiovascular Diabetology, 19(1), 19.PubMedPubMedCentralCrossRef

33.

Weir-McCall, J. R., Lambert, M., Gandy, S. J., et al. (2018). Systemic arteriosclerosis is associated with left ventricular remodeling but not atherosclerosis: A TASCFORCE study. Journal of Cardiovascular Magnetic Resonance, 20(1), 7.PubMedPubMedCentralCrossRef

34.

Santos-Gallego, C. G., Requena-Ibanez, J. A., San Antonio, R., et al. (2019). Empagliflozin ameliorates adverse left ventricular remodeling in nondiabetic heart failure by enhancing myocardial energetics. Journal of the American College of Cardiology, 73(15), 1931–1944.PubMedCrossRef

35.

Santos-Gallego, C. G., Requena-Ibanez, J. A., Antonio, R. S., et al. (2021). Empagliflozin ameliorates diastolic dysfunction and left ventricular fibrosis/stiffness in nondiabetic heart failure. JACC: Cardiovascular Imaging, 14(2), 393–407.PubMed

36.

Paulus, W. J., & Tschöpe, C. (2013). A novel paradigm for heart failure with preserved ejection fraction: Comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. Journal of the American College of Cardiology., 62(4), 263–271.PubMedCrossRef

37.

Yurista, S. R., Silljé, H. H. W., Oberdorf-Maass, S. U., et al. (2019). Sodium-glucose co-transporter 2 inhibition with empagliflozin improves cardiac function in non-diabetic rats with left ventricular dysfunction after myocardial infarction. European Journal of Heart Failure, 21(7), 862–873.PubMedCrossRef

38.

Connelly, K. A., Zhang, Y., Desjardins, J. F., et al. (2020). Load-independent effects of empagliflozin contribute to improved cardiac function in experimental heart failure with reduced ejection fraction. Cardiovascular Diabetology, 19(1), 13.PubMedPubMedCentralCrossRef

39.

Byrne, N. J., Parajuli, N., Levasseur, J. L., et al. (2017). Empagliflozin prevents worsening of cardiac function in an experimental model of pressure overload-induced heart failure. JACC Basic to Translational Science, 2(4), 347–354.PubMedPubMedCentralCrossRef

40.

Connelly, K. A., Zhang, Y., Visram, A., et al. (2019). Empagliflozin improves diastolic function in a nondiabetic rodent model of heart failure with preserved ejection fraction. JACC Basic to Translational Science, 4(1), 27–37.PubMedPubMedCentralCrossRef

41.

Bode, D., Semmler, L., Wakula, P., et al. (2021). Dual SGLT-1 and SGLT-2 inhibition improves left atrial dysfunction in HFpEF. Cardiovascular Diabetology, 20(1), 7.PubMedPubMedCentralCrossRef

42.

Zhang, N., Feng, B., Ma, X., Sun, K., Xu, G., & Zhou, Y. (2019). Dapagliflozin improves left ventricular remodeling and aorta sympathetic tone in a pig model of heart failure with preserved ejection fraction. Cardiovascular Diabetology, 18(1), 107.PubMedPubMedCentralCrossRef

43.

Connelly, K. A., Zhang, Y., Desjardins, J. F., Thai, K., & Gilbert, R. E. (2018). Dual inhibition of sodium-glucose linked cotransporters 1 and 2 exacerbates cardiac dysfunction following experimental myocardial infarction. Cardiovascular Diabetology, 17(1), 99.PubMedPubMedCentralCrossRef

44.

Kang, S., Verma, S., Hassanabad, A. F., et al. (2020). Direct effects of empagliflozin on extracellular matrix remodelling in human cardiac myofibroblasts: Novel translational clues to explain EMPA-REG OUTCOME results. Canadian Journal of Cardiology, 36(4), 543–553.PubMedCrossRef

45.

Verma, S., Mazer, C. D., Yan, A. T., et al. (2019). Effect of empagliflozin on left ventricular mass in patients with type 2 diabetes mellitus and coronary artery disease. Circulation, 140(21), 1693–1702.PubMedCrossRef

46.

Mason, T., Coelho-Filho, O. R., Verma, S., et al. (2021). Empagliflozin reduces myocardial extracellular volume in patients with type 2 diabetes and coronary artery disease. JACC Cardiovasc Imaging

47.

Shim, C. Y., Seo, J., Cho, I., et al. (2021). Randomized, Controlled trial to evaluate the effect of dapagliflozin on left ventricular diastolic function in patients with type 2 diabetes mellitus. Circulation, 143(5), 510–512.PubMedCrossRef

48.

Brown, A. J. M., Gandy, S., McCrimmon, R., Houston, J. G., Struthers, A. D., & Lang, C. C. (2020). A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: The DAPA-LVH trial. European Heart Journal., 41(36), 3421–3432.PubMedPubMedCentralCrossRef

49.

Nagai, T., Anzai, T., Kaneko, H., et al. (2011). C-reactive protein overexpression exacerbates pressure overload-induced cardiac remodeling through enhanced inflammatory response. Hypertension, 57(2), 208–215.PubMedCrossRef

50.

Santos-Gallego, C. G., Vargas-Delgado, A. P., Requena-Ibanez, J. A., et al. (2021). Randomized trial of empagliflozin in nondiabetic patients with heart failure and reduced ejection fraction. Journal of the American College of Cardiology., 77(3), 243–255.PubMedCrossRef

51.

Lee, M. M. Y., Brooksbank, K. J. M., Wetherall, K., et al. (2021). Effect of empagliflozin on left ventricular volumes in patients with type 2 diabetes, or prediabetes, and heart failure with reduced ejection fraction (SUGAR-DM-HF). Circulation, 143(6), 516–525.PubMedCrossRef

52.

Omar, M., Jensen, J., Ali, M., et al. (2021). Associations of empagliflozin with left ventricular volumes, mass, and function in patients with heart failure and reduced ejection fraction: A substudy of the empire HF randomized clinical trial. JAMA Cardiology

53.

Singh, J. S. S., Mordi, I. R., Vickneson, K., et al. (2020). Dapagliflozin versus placebo on left ventricular remodeling in patients with diabetes and heart failure: The REFORM trial. Diabetes Care, 43(6), 1356–1359.PubMedPubMedCentralCrossRef

54.

Nassif, M. E., Qintar, M., Windsor, S. L., et al. (2021). Empagliflozin effects on pulmonary artery pressure in patients with heart failure. Circulation, 143(17), 1673–1686.PubMedCrossRef

55.

Wang, C., & Wang, X. (2015). The interplay between autophagy and the ubiquitin-proteasome system in cardiac proteotoxicity. Biochimica et Biophysica Acta, 1852(2), 188–194.PubMedCrossRef

56.

Tarone, G., & Brancaccio, M. (2014). Keep your heart in shape: Molecular chaperone networks for treating heart disease. Cardiovascular Research, 102(3), 346–361.PubMedCrossRef

57.

Burchfield, J. S., Xie, M., & Hill, J. A. (2013). Pathological ventricular remodeling: Mechanisms: Part 1 of 2. Circulation, 128(4), 388–400.PubMedPubMedCentralCrossRef

58.

Shirakabe, A., Zhai, P., Ikeda, Y., et al. (2016). Drp1-dependent mitochondrial autophagy plays a protective role against pressure overload-induced mitochondrial dysfunction and heart failure. Circulation, 133(13), 1249–1263.PubMedPubMedCentralCrossRef

59.

Nakai, A., Yamaguchi, O., Takeda, T., et al. (2007). The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress. Nature Medicine, 13(5), 619–624.PubMedCrossRef

60.

Nishida, K., Kyoi, S., Yamaguchi, O., Sadoshima, J., & Otsu, K. (2009). The role of autophagy in the heart. Cell Death & Differentiation., 16(1), 31–38.CrossRef

61.

Mancini, S. J., Boyd, D., Katwan, O. J., et al. (2018). Canagliflozin inhibits interleukin-1beta-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms. Science and Reports, 8(1), 5276.CrossRef

62.

Hawley, S. A., Ford, R. J., Smith, B. K., et al. (2016). The Na+/glucose cotransporter inhibitor canagliflozin activates AMPK by inhibiting mitochondrial function and increasing cellular AMP levels. Diabetes, 65(9), 2784–2794.PubMedCrossRef

63.

Sayour, A. A., Korkmaz-Icoz, S., Loganathan, S., et al. (2019). Acute canagliflozin treatment protects against in vivo myocardial ischemia-reperfusion injury in non-diabetic male rats and enhances endothelium-dependent vasorelaxation. Journal of Translational Medicine, 17(1), 127.PubMedPubMedCentralCrossRef

64.

Inoue, M. K., Matsunaga, Y., Nakatsu, Y., et al. (2019). Possible involvement of normalized Pin1 expression level and AMPK activation in the molecular mechanisms underlying renal protective effects of SGLT2 inhibitors in mice. Diabetology and Metabolic Syndrome, 11, 57.PubMedPubMedCentralCrossRef

65.

Lu, Q., Liu, J., Li, X., et al. (2020). Empagliflozin attenuates ischemia and reperfusion injury through LKB1/AMPK signaling pathway. Molecular and Cellular Endocrinology, 501, 110642.PubMedCrossRef

66.

Kim, J. W., Lee, Y. J., You, Y. H., et al. (2018). Effect of sodium-glucose cotransporter 2 inhibitor, empagliflozin, and alpha-glucosidase inhibitor, voglibose, on hepatic steatosis in an animal model of type 2 diabetes. Journal of Cellular Biochemistry

67.

Ye, Y., Jia, X., Bajaj, M., & Birnbaum, Y. (2018). Dapagliflozin attenuates Na(+)/H(+) exchanger-1 in cardiofibroblasts via AMPK activation. Cardiovascular Drugs and Therapy, 32(6), 553–558.PubMedCrossRef

68.

Kim, S., Jo, C. H., & Kim, G. H. (2019). Effects of empagliflozin on nondiabetic salt-sensitive hypertension in uninephrectomized rats. Hypertension Research, 42(12), 1905–1915.PubMedPubMedCentralCrossRef

69.

Chang, Y. K., Choi, H., Jeong, J. Y., et al. (2016). Dapagliflozin, SGLT2 inhibitor, attenuates renal ischemia-reperfusion injury. PLoS One., 11(7), e0158810.PubMedPubMedCentralCrossRef

70.

Packer, M. (2020). Autophagy stimulation and intracellular sodium reduction as mediators of the cardioprotective effect of sodium–glucose cotransporter 2 inhibitors. European Journal of Heart Failure., 22(4), 618–628.PubMedCrossRef

71.

Packer, M. (2020). SGLT2 inhibitors produce cardiorenal benefits by promoting adaptive cellular reprogramming to induce a state of fasting mimicry: A paradigm shift in understanding their mechanism of action. Diabetes Care, 43(3), 508–511.PubMedCrossRef

72.

Takimoto, E., & Kass, D. A. (2007). Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension, 49(2), 241–248.PubMedCrossRef

73.

Sabri, A., Hughie, H. H., & Lucchesi, P. A. (2003). Regulation of hypertrophic and apoptotic signaling pathways by reactive oxygen species in cardiac myocytes. Antioxidants & Redox Signaling, 5(6), 731–740.CrossRef

74.

Rababa’h, A. M., Guillory, A. N., Mustafa, R., & Hijjawi, T. (2018). Oxidative stress and cardiac remodeling: An updated edge. Current Cardiology Reviews, 14(1), 53–59.PubMedPubMedCentralCrossRef

75.

Li, C., Zhang, J., Xue, M., et al. (2019). SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart. Cardiovascular Diabetology, 18(1), 15.PubMedPubMedCentralCrossRef

76.

Campos, D. H., Leopoldo, A. S., Lima-Leopoldo, A. P., et al. (2014). Obesity preserves myocardial function during blockade of the glycolytic pathway. Arquivos Brasileiros de Cardiologia, 103(4), 330–337.PubMedPubMedCentral

77.

Santos, P. P., Oliveira, F., Ferreira, V. C., et al. (2014). The role of lipotoxicity in smoke cardiomyopathy. PLoS One, 9(12), e113739.PubMedPubMedCentralCrossRef

78.

Ferrannini, E., Mark, M., & Mayoux, E. (2016). CV Protection in the EMPA-REG OUTCOME Trial: A “thrifty substrate” hypothesis. Diabetes Care, 39(7), 1108–1114.PubMedCrossRef

79.

Byrne, N. J., Soni, S., Takahara, S., et al. (2020). Chronically elevating circulating ketones can reduce cardiac inflammation and blunt the development of heart failure. Circulation: Heart Failure, 13(6), e006573.

80.

Maejima, Y. (2019). SGLT2 inhibitors play a salutary role in heart failure via modulation of the mitochondrial function. Frontiers in Cardiovascular Medicine, 6, 186.PubMedCrossRef

81.

Daniele, G., Xiong, J., Solis-Herrera, C., et al. (2016). Dapagliflozin enhances fat oxidation and ketone production in patients with type 2 diabetes. Diabetes Care, 39(11), 2036–2041.PubMedPubMedCentralCrossRef

82.

Cai, T., Ke, Q., Fang, Y., et al. (2020). Sodium-glucose cotransporter 2 inhibition suppresses HIF-1alpha-mediated metabolic switch from lipid oxidation to glycolysis in kidney tubule cells of diabetic mice. Cell Death & Disease, 11(5), 390.CrossRef

83.

Lauritsen, K. M., Nielsen, B. R. R., Tolbod, L. P., et al. (2021). SGLT2 inhibition does not affect myocardial fatty acid oxidation or uptake, but reduces myocardial glucose uptake and blood flow in individuals with type 2 diabetes: A randomized double-blind, placebo-controlled crossover trial. Diabetes, 70(3), 800–808.PubMedCrossRef

84.

Verma, S., Rawat, S., Ho, K. L., et al. (2018). Empagliflozin increases cardiac energy production in diabetes: Novel translational insights into the heart failure benefits of SGLT2 inhibitors. JACC Basic to Translational Science, 3(5), 575–587.PubMedPubMedCentralCrossRef

85.

Olgar, Y., Tuncay, E., Degirmenci, S., et al. (2020). Ageing-associated increase in SGLT2 disrupts mitochondrial/sarcoplasmic reticulum Ca(2+) homeostasis and promotes cardiac dysfunction. Journal of Cellular and Molecular Medicine, 24(15), 8567–8578.PubMedPubMedCentralCrossRef

86.

Takagi, S., Li, J., Takagaki, Y., et al. (2018). Ipragliflozin improves mitochondrial abnormalities in renal tubules induced by a high-fat diet. Journal of Diabetes Investigation, 9(5), 1025–1032.PubMedPubMedCentralCrossRef

87.

Sun, M., Chen, M., Dawood, F., et al. (2007). Tumor necrosis factor-alpha mediates cardiac remodeling and ventricular dysfunction after pressure overload state. Circulation, 115(11), 1398–1407.PubMedCrossRef

88.

Schirone, L., Forte, M., Palmerio, S., et al. (2017). A review of the molecular mechanisms underlying the development and progression of cardiac remodeling. Oxidative Medicine and Cellular Longevity, 2017, 3920195.PubMedPubMedCentralCrossRef

89.

Heerspink, H. J. L., Perco, P., Mulder, S., et al. (2019). Canagliflozin reduces inflammation and fibrosis biomarkers: A potential mechanism of action for beneficial effects of SGLT2 inhibitors in diabetic kidney disease. Diabetologia, 62(7), 1154–1166.PubMedPubMedCentralCrossRef

90.

Kim, S. R., Lee, S. G., Kim, S. H., et al. (2020). SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease. Nature Communications, 11(1), 2127.PubMedPubMedCentralCrossRef

91.

Sokolova, M., Sjaastad, I., Louwe, M. C., et al. (2019). NLRP3 inflammasome promotes myocardial remodeling during diet-induced obesity. Frontiers in Immunology, 10, 1621.PubMedPubMedCentralCrossRef

92.

Byrne, N. J., Matsumura, N., Maayah, Z. H., et al. (2020). Empagliflozin blunts worsening cardiac dysfunction associated with reduced NLRP3 (nucleotide-binding domain-like receptor protein 3) inflammasome activation in heart failure. Circulation: Heart Failure, 13(1), e006277.

93.

Yerra, V. G., Batchu, S. N., Kabir, G., et al. (2021). Empagliflozin disrupts a Tnfrsf12a-mediated feed forward loop that promotes left ventricular hypertrophy. Cardiovascular Drugs and Therapy

94.

Camici, P. G., & Lorenzoni, R. (1994). Microcirculation and remodelling. Cardiologia, 39(12 Suppl 1), 197–201.PubMed

95.

Miličić, D., Jakuš, N., & Fabijanović, D. (2018). Microcirculation and heart failure. Current Pharmaceutical Design, 24(25), 2954–2959.PubMedCrossRef

96.

Adingupu, D. D., Göpel, S. O., Grönros, J., et al. (2019). SGLT2 inhibition with empagliflozin improves coronary microvascular function and cardiac contractility in prediabetic ob/ob(-/-) mice. Cardiovascular Diabetology, 18(1), 16.PubMedPubMedCentralCrossRef

97.

Juni, R. P., Kuster, D. W. D., Goebel, M., et al. (2019). Cardiac microvascular endothelial enhancement of cardiomyocyte function is impaired by inflammation and restored by empagliflozin. JACC Basic to Translational Science., 4(5), 575–591.PubMedPubMedCentralCrossRef

98.

Ott, C., Jumar, A., Striepe, K., et al. (2017). A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation. Cardiovascular Diabetology, 16(1), 26.PubMedPubMedCentralCrossRef

99.

Herat, L. Y., Magno, A. L., Rudnicka, C., et al. (2020). SGLT2 inhibitor-induced sympathoinhibition: A novel mechanism for cardiorenal protection. JACC Basic to Translational Science, 5(2), 169–179.PubMedPubMedCentralCrossRef

100.

Verma, S. (2020). Are the cardiorenal benefits of SGLT2 inhibitors due to inhibition of the sympathetic nervous system? JACC Basic to Translational Science, 5(2), 180–182.PubMedPubMedCentralCrossRef

101.

Shimizu, W., Kubota, Y., Hoshika, Y., et al. (2020). Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: The EMBODY trial. Cardiovascular Diabetology., 19(1), 148.PubMedPubMedCentralCrossRef

102.

Spiegel, J. (2010). Diagnostic and pathophysiological impact of myocardial MIBG scintigraphy in Parkinson’s disease. Parkinson’s Disease, 2010, 295346.PubMed

103.

Garg, V., Verma, S., Connelly, K. A., et al. (2020). Does empagliflozin modulate the autonomic nervous system among individuals with type 2 diabetes and coronary artery disease? The EMPA-HEART CardioLink-6 Holter analysis. Metabology Open, 7, 100039.CrossRef

104.

Sag, C. M., Wagner, S., & Maier, L. S. (2013). Role of oxidants on calcium and sodium movement in healthy and diseased cardiac myocytes. Free Radical Biology & Medicine, 63, 338–349.CrossRef

105.

Makielski, J. C. (2016). Late sodium current: A mechanism for angina, heart failure, and arrhythmia. Trends in Cardiovascular Medicine, 26(2), 115–122.PubMedCrossRef

106.

Philippaert K, Kalyaanamoorthy S, Fatehi M, et al. The cardiac late sodium channel current is a molecular target for the sodium-glucose co-transporter 2 inhibitor empagliflozin. Circulation.0(0).

107.

Uthman, L., Baartscheer, A., Bleijlevens, B., et al. (2018). Class effects of SGLT2 inhibitors in mouse cardiomyocytes and hearts: Inhibition of Na(+)/H(+) exchanger, lowering of cytosolic Na(+) and vasodilation. Diabetologia, 61(3), 722–726.PubMedCrossRef

108.

Baartscheer, A., Schumacher, C. A., Wüst, R. C., et al. (2017). Empagliflozin decreases myocardial cytoplasmic Na(+) through inhibition of the cardiac Na(+)/H(+) exchanger in rats and rabbits. Diabetologia, 60(3), 568–573.PubMedCrossRef

109.

Chung, Y. J., Park, K. C., Tokar, S., et al. (2020). Off-target effects of sodium-glucose co-transporter 2 blockers: Empagliflozin does not inhibit Na+/H+ exchanger-1 or lower [Na+]i in the heart. Cardiovascular Research

110.

Tomek, J., & Bub, G. (2017). Hypertension-induced remodelling: On the interactions of cardiac risk factors. Journal of Physiology, 595(12), 4027–4036.PubMedPubMedCentralCrossRef

111.

González, A., Ravassa, S., López, B., et al. (2018). Myocardial remodeling in hypertension. Hypertension, 72(3), 549–558.PubMedCrossRef

112.

Tikkanen, I., Narko, K., Zeller, C., et al. (2015). Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care, 38(3), 420–428.PubMedCrossRef

113.

Majewski, C., & Bakris, G. L. (2015). Blood pressure reduction: An added benefit of sodium–glucose cotransporter 2 inhibitors in patients with type 2 diabetes. Diabetes Care, 38(3), 429–430.PubMedPubMedCentralCrossRef

114.

Oliva, R. V., & Bakris, G. L. (2014). Blood pressure effects of sodium-glucose co-transport 2 (SGLT2) inhibitors. Journal of the American Society of Hypertension, 8(5), 330–339.PubMedCrossRef

115.

Kario, K., Okada, K., Kato, M., et al. (2019). Twenty-four-hour blood pressure-lowering effect of a sodium-glucose cotransporter 2 inhibitor in patients with diabetes and uncontrolled nocturnal hypertension. Circulation, 139(18), 2089–2097.CrossRef

116.

Kaesler, N., Babler, A., Floege, J., & Kramann, R. (2020). Cardiac remodeling in chronic kidney disease. Toxins (Basel), 12(3).

117.

Rasić, S., Kulenović, I., Haracić, A., & Catović, A. (2004). Left ventricular hypertrophy and risk factors for its development in uraemic patients. Bosnian Journal of Basic Medical Sciences, 4(1), 34–40.PubMedPubMedCentralCrossRef

118.

Kramann, R., Erpenbeck, J., Schneider, R. K., et al. (2014). Speckle tracking echocardiography detects uremic cardiomyopathy early and predicts cardiovascular mortality in ESRD. Journal of the American Society of Nephrology, 25(10), 2351–2365.PubMedPubMedCentralCrossRef

119.

Heerspink, H. J. L., Stefansson, B. V., Correa-Rotter, R., et al. (2020). Dapagliflozin in patients with chronic kidney disease. New England Journal of Medicine, 383(15), 1436–1446.PubMedCrossRef

120.

Perkovic, V., Jardine, M. J., Neal, B., et al. (2019). Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. New England Journal of Medicine, 380(24), 2295–2306.PubMedCrossRef

121.

Simon, T. G., Bamira, D. G., Chung, R. T., Weiner, R. B., & Corey, K. E. (2017). Nonalcoholic steatohepatitis is associated with cardiac remodeling and dysfunction. Obesity (Silver Spring), 25(8), 1313–1316.CrossRef

122.

Salah, H. M., Pandey, A., Soloveva, A., et al. (2021). Relationship of nonalcoholic fatty liver disease and heart failure with preserved ejection fraction. JACC Basic to Translational Science, 6(11), 918–932.PubMedPubMedCentralCrossRef

123.

Xing, B., Zhao, Y., Dong, B., Zhou, Y., Lv, W., & Zhao, W. (2020). Effects of sodium-glucose cotransporter 2 inhibitors on non-alcoholic fatty liver disease in patients with type 2 diabetes: A meta-analysis of randomized controlled trials. Journal of Diabetes Investigation, 11(5), 1238–1247.PubMedPubMedCentralCrossRef

124.

Nishiya, D., Omura, T., Shimada, K., et al. (2006). Effects of erythropoietin on cardiac remodeling after myocardial infarction. Journal of Pharmacological Sciences, 101(1), 31–39.PubMedCrossRef

125.

Sano, M., & Goto, S. (2019). Possible mechanism of hematocrit elevation by sodium glucose cotransporter 2 inhibitors and associated beneficial renal and cardiovascular effects. Circulation, 139(17), 1985–1987.PubMedCrossRef

126.

Mazer, C. D., Hare, G. M. T., Connelly, P. W., et al. (2020). Effect of empagliflozin on erythropoietin levels, iron stores, and red blood cell morphology in patients with type 2 diabetes mellitus and coronary artery disease. Circulation, 141(8), 704–707.PubMedCrossRef

127.

Maruyama, T., Takashima, H., Oguma, H., et al. (2019). Canagliflozin improves erythropoiesis in diabetes patients with anemia of chronic kidney disease. Diabetes Technology & Therapeutics, 21(12), 713–720.CrossRef

Titel: Sodium-Glucose Cotransporter 2 Inhibitors and Cardiac Remodeling
verfasst von: Husam M. Salah
Subodh Verma
Carlos G. Santos-Gallego
Ankeet S. Bhatt
Muthiah Vaduganathan
Muhammad Shahzeb Khan
Renato D. Lopes
Subhi J. Al’Aref
Darren K. McGuire
Marat Fudim
Publikationsdatum: 15.03.2022
Verlag: Springer US
Erschienen in: Journal of Cardiovascular Translational Research / Ausgabe 5/2022
Print ISSN: 1937-5387
Elektronische ISSN: 1937-5395
DOI: https://doi.org/10.1007/s12265-022-10220-5

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Sodium-Glucose Cotransporter 2 Inhibitors and Cardiac Remodeling

Abstract

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