Abstract
Introduction
Sodium Glucose Cotransporter inhibitor (SGLTi) has revolutionized the medical management of heart failure in the last decade. This molecule was initially described as a glucose-lowering agent but now it has been recommended in patients with chronic heart failure irrespective of ejection fraction and diabetic status. SGLT2 inhibitor reduces preload by natriuresis and diuresis, reduces afterload, decreases pulmonary artery pressure, improves myocardial energetics, and decreases myocardial fibrosis. It also reduces NT-pro BNP levels in heart failure patients, decreases serum uric acid, and promotes weight loss. It has also been proposed that this molecule has a favorable effect on vascular remodeling. SGLT-2i improves cardiac output and attenuates maladaptive cardiac remodeling, chronic inflammation, oxidative stress, and endothelial dysfunction (ED) by restoring the activity of nitric oxide (NO) within the vascular endothelium. As was foreseeable this molecule became one of the foundation pillars in the management of heart failure with reduced as well as preserved ejection fraction. SGLT2i also has a reno-protective effect, particularly in patients with heart failure and diabetes.
References
- Solomon SD, de Boer RA, DeMets D, et al. Dapagliflozin in heart failure with preserved and mildly reduced ejection fraction: rationale and design of the DELIVER trial. Eur J Heart Fail. 2021 Jul;23(7):1217-1225. doi: 10.1002/ejhf.2249. Epub 2021 Jun 9. PMID: 34051124; PMCID: PMC8361994.
- Anker SD, Butler J, Filippatos G, Ferreira JP, et al; EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021 Oct 14;385(16):1451-1461. doi: 10.1056/NEJMoa2107038. Epub 2021 Aug 27. PMID: 34449189.
- Packer M, Anker SD, Butler J, Filippatos G et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020; 383:1413–1424.
- McMurray JJV, Solomon SD, Inzucchi SE, Køber L, et al; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303. Epub 2019 Sep 19. PMID: 31535829.
- Voors, A.A., Angermann, C.E., Teerlink, J.R. et al.The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med 28, 568–574 (2022). https://doi.org/10.1038/s41591-021-01659-1.
- Dirk von Lewinski, Ewald Kolesnik, Norbert J Tripolt, et al, on behalf of the EMMY Investigators, Empagliflozin in acute myocardial infarction: the EMMY trial, European Heart Journal, Volume 43, Issue 41, 1 November 2022, Pages 4421–4432, https://doi.org/10.1093/eurheartj/ehac494.
- Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016; 375:323-334.
- Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019; 380:2295-2306.
- Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17. PMID: 26378978.
- Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24. PMID: 32970396.
- Hernandez, M.; Sullivan, R.D.; McCune, D. et al. Sodium-Glucose Cotransporter-2 Inhibitors Improve Heart Failure with Reduced Ejection Fraction Outcomes by Reducing Edema and Congestion. Diagnostics2022, 12, 989.
- Hammon M, Grossmann S, Linz P, et al. (2015) 23Na magnetic resonance imaging of the lower leg of acute heart failure patients during diuretic treatment. PLoS One 10(10): e0141336.
- 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145: e895–e1032. DOI: 10.1161/CIR.0000000000001063.
- 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal (2021) 42, 3599-3726. doi:10.1093/eurheartj/ehab368.
- 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal (2023) 00, 1–13 https://doi.org/10.1093/eurheartj/ehad195.
Corresponding Author
Dr Sandipta Ray
Consultant Interventional Cardiologist, Department of Cardiology, AMRI Hospital, Saltlake, Kolkata