Skip to main content
SpringerLink
Log in

Effects of SGLT2 inhibitors on cardiac structure and function

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

SGLT2 inhibitors reduce cardiovascular death or hospitalization for heart failure, regardless of the presence or absence of diabetes in patients at high cardiovascular risk and in those with heart failure and reduced ejection fraction (HFrEF). In patients with HF and preserved EF, empagliflozin also showed favorable effects mainly related to the reduction of hospitalization for heart failure. These favorable effects are beyond the reduction of glycemic levels and mainly related to beneficial hemodynamic and anti-inflammatory effects of these drugs and improved cardiac energy metabolism. In this review, we aimed to evaluate the effects of SGLT2 inhibitor on cardiac remodeling and function, which is still incompletely clear.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, Federici M, Filippatos G, Grobbee DE, Hansen TB, Huikuri HV, Johansson I, Jüni P, Lettino M, Marx N, Mellbin LG, Östgren CJ, Rocca B, Roffi M, Sattar N, Seferović PM, Sousa-Uva M, Valensi P, Wheeler DC, ESC Scientific Document Group (2020) 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 41(2):255–323. https://doi.org/10.1093/eurheartj/ehz486. Erratum in: Eur Heart J. 2020 Dec 1;41(45):4317. PMID: 31497854

  2. Seferović PM, Fragasso G, Petrie M, Mullens W, Ferrari R, Thum T, Bauersachs J, Anker SD, Ray R, Çavuşoğlu Y, Polovina M, Metra M, Ambrosio G, Prasad K, Seferović J, Jhund PS, Dattilo G, Čelutkiene J, Piepoli M, Moura B, Chioncel O, Ben Gal T, Heymans S, de Boer RA, Jaarsma T, Hill L, Lopatin Y, Lyon AR, Ponikowski P, Lainščak M, Jankowska E, Mueller C, Cosentino F, Lund L, Filippatos GS, Ruschitzka F, Coats AJS, Rosano GMC (2020) Sodium-glucose co-transporter 2 inhibitors in heart failure: beyond glycaemic control. A position paper of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 22(9):1495- 1503.: https://doi.org/10.1002/ejhf.1954. Epub 2020 Aug 5. PMID: 32618086

  3. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, Böhm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukát A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjöstrand M, Langkilde AM, DAPA-HF Trial Committees and Investigators (2019) Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 381(21):1995–2008. https://doi.org/10.1056/NEJMoa1911303. Epub 2019 Sep 19. PMID: 31535829

  4. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, Jamal W, Kimura K, Schnee J, Zeller C, Cotton D, Bocchi E, Böhm M, Choi DJ, Chopra V, Chuquiure E, Giannetti N, Janssens S, Zhang J, Gonzalez Juanatey JR, Kaul S, Brunner-La Rocca HP, Merkely B, Nicholls SJ, Perrone S, Pina I, Ponikowski P, Sattar N, Senni M, Seronde MF, Spinar J, Squire I, Taddei S, Wanner C, Zannad F, EMPEROR-Reduced Trial Investigators (2020) Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med 383(15):1413–1424. https://doi.org/10.1056/NEJMoa2022190. Epub 2020 Aug 28. PMID: 32865377

  5. Zannad F, Ferreira JP, Pocock SJ, Anker SD, Butler J, Filippatos G, Brueckmann M, Ofstad AP, Pfarr E, Jamal W, Packer M (2020) SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet 396(10254):819–829. https://doi.org/10.1016/S0140-6736(20)31824-9. Epub 2020 Aug 30 PMID: 32877652

    Article  PubMed  Google Scholar 

  6. Martinez FA, Serenelli M, Nicolau JC, Petrie MC, Chiang CE, Tereshchenko S, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Ponikowski P, Sabatine MS, DeMets DL, Dutkiewicz-Piasecka M, Bengtsson O, Sjöstrand M, Langkilde AM, Jhund PS, McMurray JJV (2020) Efficacy and safety of dapagliflozin in heart failure with reduced ejection fraction according to age: insights from DAPA-HF. Circulation 141(2):100–111. https://doi.org/10.1161/CIRCULATIONAHA.119.044133. Epub 2019 Nov 17 PMID: 31736328

    Article  CAS  PubMed  Google Scholar 

  7. Packer M, Anker SD, Butler J, Filippatos G, Ferreira JP, Pocock SJ, Rocca HB, Janssens S, Tsutsui H, Zhang J, Brueckmann M, Jamal W, Cotton D, Iwata T, Schnee J, Zannad F, EMPEROR-Reduced Trial Committees and Investigators (2021) Influence of neprilysin inhibition on the efficacy and safety of empagliflozin in patients with chronic heart failure and a reduced ejection fraction: the EMPEROR-Reduced trial. Eur Heart J 42(6):671–680. https://doi.org/10.1093/eurheartj/ehaa968. PMID: 33459776; PMCID: PMC7878011

  8. Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Voors AA, Metra M, Lund LH, Komajda M, Testani JM, Wilcox CS, Ponikowski P, Lopes RD, Verma S, Lapuerta P, Pitt B, SOLOIST-WHF Trial Investigators (2021) Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med 384(2):117–128. https://doi.org/10.1056/NEJMoa2030183. Epub 2020 Nov 16. PMID: 33200892

  9. Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaffey KW, CREDENCE Trial Investigators (2019) Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 380(24):2295–2306. doi: https://doi.org/10.1056/NEJMoa1811744. Epub 2019 Apr 14. PMID: 30990260

  10. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-Valenzuela E, Giannetti N, Gomez-Mesa JE, Janssens S, Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Piña IL, Ponikowski P, Senni M, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Carson P, Lam CSP, Marx N, Zeller C, Sattar N, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M, EMPEROR-Preserved Trial Investigators (2021) Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 385(16):1451–1461. https://doi.org/10.1056/NEJMoa2107038. Epub 2021 Aug 27. PMID: 34449189

  11. Abraham WT, Lindenfeld J, Ponikowski P, Agostoni P, Butler J, Desai AS, Filippatos G, Gniot J, Fu M, Gullestad L, Howlett JG, Nicholls SJ, Redon J, Schenkenberger I, Silva-Cardoso J, Störk S, Krzysztof Wranicz J, Savarese G, Brueckmann M, Jamal W, Nordaby M, Peil B, Ritter I, Ustyugova A, Zeller C, Salsali A, Anker SD (2021) Effect of empagliflozin on exercise ability and symptoms in heart failure patients with reduced and preserved ejection fraction, with and without type 2 diabetes. Eur Heart J 42(6):700–710. https://doi.org/10.1093/eurheartj/ehaa943. PMID: 33351892

    Article  CAS  PubMed  Google Scholar 

  12. Nassif ME, Windsor SL, Tang F, Khariton Y, Husain M, Inzucchi SE, McGuire DK, Pitt B, Scirica BM, Austin B, Drazner MH, Fong MW, Givertz MM, Gordon RA, Jermyn R, Katz SD, Lamba S, Lanfear DE, LaRue SJ, Lindenfeld J, Malone M, Margulies K, Mentz RJ, Mutharasan RK, Pursley M, Umpierrez G, Kosiborod M (2019) Dapagliflozin effects on biomarkers, symptoms, and functional status in patients with heart failure with reduced ejection fraction: the DEFINE-HF Trial. Circulation 140(18):1463–1476. https://doi.org/10.1161/CIRCULATIONAHA.119.042929. Epub 2019 Sep 16 PMID: 31524498

    Article  CAS  PubMed  Google Scholar 

  13. Zelniker TA, Braunwald E (2020) Mechanisms of cardiorenal effects of sodium-glucose cotransporter 2 inhibitors: JACC state-of-the-art review. J Am Coll Cardiol 75(4):422-434. https://doi.org/10.1016/j.jacc.2019.11.031. Erratum in: J Am Coll Cardiol. 2020 Sep 22;76(12):1505. PMID: 32000955] [Packer M, Anker SD, Butler J, Filippatos G, Zannad F (2017) Effects of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with heart failure: proposal of a novel mechanism of action. JAMA Cardiol 2(9):1025-1029. https://doi.org/10.1001/jamacardio.2017.2275. PMID: 28768320

  14. Verma S, McMurray JJV (2018) SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia 61(10):2108–2117. https://doi.org/10.1007/s00125-018-4670-7. Epub 2018 Aug 22 PMID: 30132036

    Article  CAS  PubMed  Google Scholar 

  15. Santos-Gallego CG, Vargas-Delgado AP, Requena-Ibanez JA, Garcia-Ropero A, Mancini D, Pinney S, Macaluso F, Sartori S, Roque M, Sabatel-Perez F, Rodriguez-Cordero A, Zafar MU, Fergus I, Atallah-Lajam F, Contreras JP, Varley C, Moreno PR, Abascal VM, Lala A, Tamler R, Sanz J, Fuster V, Badimon JJ, EMPA- TROPISM (ATRU-4) Investigators (2021) Randomized trial of empagliflozin in nondiabetic patients with heart failure and reduced ejection fraction. J Am Coll Cardiol 77(3):243–255. https://doi.org/10.1016/j.jacc.2020.11.008. Epub 2020 Nov 13. PMID: 33197559

  16. Gaasch WH, Zile MR (2011) Left ventricular structural remodeling in health and disease: with special emphasis on volume, mass, and geometry. J Am Coll Cardiol 58(17):1733–1740. https://doi.org/10.1016/j.jacc.2011.07.022. PMID: 21996383

    Article  PubMed  Google Scholar 

  17. Merlo M, Pyxaras SA, Pinamonti B, Barbati G, Di Lenarda A, Sinagra G (2011) Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment. J Am Coll Cardiol 57(13):1468–1476. https://doi.org/10.1016/j.jacc.2010.11.030. PMID: 21435516

    Article  PubMed  Google Scholar 

  18. Choi JO, Kim EY, Lee GY, Lee SC, Park SW, Kim DK, Oh JK, Jeon ES (2013) Predictors of left ventricular reverse remodeling and subsequent outcome in nonischemic dilated cardiomyopathy. Circ J 77(2):462–469. https://doi.org/10.1253/circj.cj-12-0507. Epub 2012 Oct 24 PMID: 23095684

    Article  PubMed  Google Scholar 

  19. Bozkurt B, Coats AJS, Tsutsui H, Abdelhamid CM, Adamopoulos S, Albert N, Anker SD, Atherton J, Böhm M, Butler J, Drazner MH, Felker GM, Filippatos G, Fiuzat M, Fonarow GC, Gomez-Mesa JE, Heidenreich P, Imamura T, Jankowska EA, Januzzi J, Khazanie P, Kinugawa K, Lam CSP, Matsue Y, Metra M, Ohtani T, Piepoli MF, Ponikowski P, Rosano GMC, Sakata Y, Seferović P, Starling RC, Teerlink JR, Vardeny O, Yamamoto K, Yancy C, Zhang J, Zieroth S (2021) Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by Canadian Heart Failure Society, Heart Failure Association of India, the Cardiac Society of Australia and New Zealand, and the Chinese Heart Failure Association. Eur J Heart Fail. https://doi.org/10.1002/ejhf.2115. Epub ahead of print. PMID: 33605000

  20. Wilcox JE, Fang JC, Margulies KB, Mann DL (2020) Heart failure with recovered left ventricular ejection fraction: JACC Scientific Expert Panel. J Am Coll Cardiol 76(6):719–734. https://doi.org/10.1016/j.jacc.2020.05.075. PMID: 32762907

    Article  PubMed  Google Scholar 

  21. Kubanek M, Sramko M, Maluskova J, Kautznerova D, Weichet J, Lupinek P, Vrbska J, Malek I, Kautzner J (2013) Novel predictors of left ventricular reverse remodeling in individuals with recent-onset dilated cardiomyopathy. J Am Coll Cardiol 61(1):54–63. https://doi.org/10.1016/j.jacc.2012.07.072. PMID: 23287372

    Article  PubMed  Google Scholar 

  22. Carluccio E, Biagioli P, Alunni G, Murrone A, Pantano P, Biscottini E, Zuchi C, Zingarini G, Cavallini C, Ambrosio G (2011) Presence of extensive LV remodeling limits the benefits of CRT in patients with intraventricular dyssynchrony. JACC Cardiovasc Imaging 4(10):1067–1076. https://doi.org/10.1016/j.jcmg.2011.07.006. PMID: 21999865

    Article  PubMed  Google Scholar 

  23. Merlo M, Stolfo D, Anzini M, Negri F, Pinamonti B, Barbati G, Ramani F, Lenarda AD, Sinagra G (2015) Persistentrecovery of normal left ventricular function and dimension in idiopathic dilated cardiomyopathy during long‐ term follow‐up: does real healing exist? J Am Heart Assoc 4(1):e001504. https://doi.org/10.1161/JAHA.114.000570. PMID: 25587018; PMCID: PMC4330074

  24. Lee MMY, Brooksbank KJM, Wetherall K, Mangion K, Roditi G, Campbell RT, Berry C, Chong V, Coyle L, Docherty KF, Dreisbach JG, Labinjoh C, Lang NN, Lennie V, McConnachie A, Murphy CL, Petrie CJ, Petrie JR, Speirits IA, Sourbron S, Welsh P, Woodward R, Radjenovic A, Mark PB, McMurray JJV, Jhund PS, Petrie MC, Sattar N (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. https://doi.org/10.1161/CIRCULATIONAHA.120.052186. Epub 2020 Nov 13. PMID: 33186500; PMCID: PMC7864599

  25. Konstam MA, Kramer DG, Patel AR, Maron MS, Udelson JE (2011) Left ventricular remodeling in heart failure: current concepts in clinical significance and assessment. JACC Cardiovasc Imaging 4(1):98–108. https://doi.org/10.1016/j.jcmg.2010.10.008. PMID: 21232712

    Article  PubMed  Google Scholar 

  26. Wende AR, Brahma MK, McGinnis GR, Young ME (2017) Metabolic origins of heart failure. JACC Basic Transl Sci 2(3):297–310. https://doi.org/10.1016/j.jacbts.2016.11.009. PMID: 28944310; PMCID: PMC5609457

    Article  PubMed  PubMed Central  Google Scholar 

  27. 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. https://doi.org/10.2337/dc16-0330. PMID: 27289126

    Article  PubMed  Google Scholar 

  28. Santos-Gallego CG, Requena-Ibanez JA, San Antonio R, Ishikawa K, Watanabe S, Picatoste B, Flores E, Garcia- Ropero A, Sanz J, Hajjar RJ, Fuster V, Badimon JJ (2019) Empagliflozin ameliorates adverse left ventricular remodeling in nondiabetic heart failure by enhancing myocardial energetics. J Am Coll Cardiol 73(15):1931–1944. https://doi.org/10.1016/j.jacc.2019.01.056. PMID: 30999996

    Article  CAS  PubMed  Google Scholar 

  29. Juni RP, Kuster DWD, Goebel M, Helmes M, Musters RJP, van der Velden J, Koolwijk P, Paulus WJ, van Hinsbergh VWM (2019) Cardiac microvascular endothelial enhancement of cardiomyocyte function is impaired by inflammation and restored by empagliflozin. JACC Basic Transl Sci 4(5):575–591. https://doi.org/10.1016/j.jacbts.2019.04.003. PMID: 31768475; PMCID: PMC6872802

    Article  PubMed  PubMed Central  Google Scholar 

  30. Cohen ND, Gutman SJ, Briganti EM, Taylor AJ (2019) Effects of empagliflozin treatment on cardiac function and structure in patients with type 2 diabetes: a cardiac magnetic resonance study. Intern Med J 49(8):1006–1010. https://doi.org/10.1111/imj.14260. PMID: 30784160

    Article  CAS  PubMed  Google Scholar 

  31. Matsutani D, Sakamoto M, Kayama Y, Takeda N, Horiuchi R, Utsunomiya K (2018) Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes. Cardiovasc Diabetol 17(1):73. https://doi.org/10.1186/s12933-018-0717-9. PMID: 29788955; PMCID: PMC5963148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Verma S, Mazer CD, Yan AT, Mason T, Garg V, Teoh H, Zuo F, Quan A, Farkouh ME, Fitchett DH, Goodman SG, Goldenberg RM, Al-Omran M, Gilbert RE, Bhatt DL, Leiter LA, Jüni P, Zinman B, Connelly KA (2019) Effect of empagliflozin on left ventricular mass in patients with type 2 diabetes mellitus and coronary artery disease: the EMPA-HEART CardioLink-6 Randomized Clinical Trial. Circulation 140(21):1693–1702. https://doi.org/10.1161/CIRCULATIONAHA.119.042375. Epub 2019 Aug 22 PMID: 31434508

    Article  PubMed  Google Scholar 

  33. Soga F, Tanaka H, Tatsumi K, Mochizuki Y, Sano H, Toki H, Matsumoto K, Shite J, Takaoka H, Doi T, Hirata KI (2018) Impact of dapagliflozin on left ventricular diastolic function of patients with type 2 diabetic mellitus with chronic heart failure. Cardiovasc Diabetol 17(1):132. https://doi.org/10.1186/s12933-018-0775-z. PMID: 30296931; PMCID: PMC6174555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Recommendations for Cardiac Chamber Quantification by Echocardiography in Adults: An Update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging (2016) Eur Heart J Cardiovasc Imaging 17(4):412. https://doi.org/10.1093/ehjci/jew041. Epub 2016 Mar 15. Erratum for: Eur Heart J Cardiovasc Imaging. 2015 Mar;16(3):233–70. PMID: 26983884

  35. Hammoudi N, Jeong D, Singh R, Farhat A, Komajda M, Mayoux E, Hajjar R, Lebeche D (2017) Empagliflozin improves left ventricular diastolic dysfunction in a genetic model of type 2 diabetes. Cardiovasc Drugs Ther 31(3):233–246. https://doi.org/10.1007/s10557-017-6734-1. PMID: 28643218; PMCID: PMC6681671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Joubert M, Jagu B, Montaigne D, Marechal X, Tesse A, Ayer A, Dollet L, Le May C, Toumaniantz G, Manrique A, Charpentier F, Staels B, Magré J, Cariou B, Prieur X (2017) The sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents cardiomyopathy in a diabetic lipodystrophic mouse model. Diabetes 66(4):1030–1040. https://doi.org/10.2337/db16-0733. Epub 2017 Jan 4 PMID: 28052965

    Article  CAS  PubMed  Google Scholar 

  37. Byrne NJ, Parajuli N, Levasseur JL, Boisvenue J, Beker DL, Masson G, Fedak PWM, Verma S, Dyck JRB (2017) Empagliflozin prevents worsening of cardiac function in an experimental model of pressure overload-induced heart failure. JACC Basic Transl Sci 2(4):347–354. https://doi.org/10.1016/j.jacbts.2017.07.003. PMID: 30062155; PMCID: PMC6034464

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lan NSR, Yeap BB, Fegan PG, Green G, Rankin JM, Dwivedi G (2021) Empagliflozin and left ventricular diastolic function following an acute coronary syndrome in patients with type 2 diabetes. Int J Cardiovasc Imaging 37(2):517–527. https://doi.org/10.1007/s10554-020-02034-w. Epub 2020 Sep 21 PMID: 32959096

    Article  PubMed  Google Scholar 

  39. Tanaka H, Soga F, Tatsumi K, Mochizuki Y, Sano H, Toki H, Matsumoto K, Shite J, Takaoka H, Doi T, Hirata KI (2020) Positive effect of dapagliflozin on left ventricular longitudinal function for type 2 diabetic mellitus patients with chronic heart failure. Cardiovasc Diabetol 19(1):6. https://doi.org/10.1186/s12933-019-0985-z. PMID: 31910853; PMCID: PMC6947966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hsu JC, Wang CY, Su MM, Lin LY, Yang WS (2019) Effect of empagliflozin on cardiac function, adiposity, and diffuse fibrosis in patients with type 2 diabetes mellitus. Sci Rep 9(1):15348. https://doi.org/10.1038/s41598-019-51949-5. PMID: 31653956; PMCID: PMC6814842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hwang IC, Cho GY, Yoon YE, Park JJ, Park JB, Lee SP, Kim HK, Kim YJ, Sohn DW (2020) Different effects of SGLT2 inhibitors according to the presence and types of heart failure in type 2 diabetic patients. Cardiovasc Diabetol 19(1):69. https://doi.org/10.1186/s12933-020-01042-3. PMID: 32466760; PMCID: PMC7254690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Otagaki M, Matsumura K, Kin H, Fujii K, Shibutani H, Matsumoto H, Takahashi H, Park H, Yamamoto Y, Sugiura T, Shiojima I (2019) Effect of tofogliflozin on systolic and diastolic cardiac function in type 2 diabetic patients. Cardiovasc Drugs Ther 33(4):435–442. https://doi.org/10.1007/s10557-019-06892-y. PMID: 31321581

    Article  CAS  PubMed  Google Scholar 

  43. Omar M, Jensen J, Ali M, Frederiksen PH, Kistorp C, Videbæk L, Poulsen MK, Tuxen CD, Möller S, Gustafsson F, Køber L, Schou M, Møller JE (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 Cardiol 6(7):836–840. https://doi.org/10.1001/jamacardio.2020.6827. PMID: 33404637; PMCID: PMC7788505

    Article  PubMed  Google Scholar 

  44. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 28(1):1-39.e14. https://doi.org/10.1016/j.echo.2014.10.003. PMID: 25559473

    Article  PubMed  Google Scholar 

  45. Ambrosio G, Carluccio E (2018) Prognostic role of left ventricular ejection fraction in heart failure: back to the future? Int J Cardiol 15(273):189–190. https://doi.org/10.1016/j.ijcard.2018.09.025. Epub 2018 Sep 8 PMID: 30219254

    Article  Google Scholar 

  46. Carluccio E, Pugliese NR, Biagioli P, Zuchi C, Lauciello R, Mengoni A, D’Agostino A, Galeotti GG, Dini FL, Ambrosio G (2021) Global longitudinal strain in heart failure with reduced ejection fraction: prognostic relevance across disease severity as assessed by automated cluster analysis. Int J Cardiol 1(332):91–98. https://doi.org/10.1016/j.ijcard.2021.02.072. Epub 2021 Mar 10 PMID: 33713708

    Article  Google Scholar 

  47. Bonow RO, Mann DL, Zipes DP, Libby P (2012) Braunwald’s heart disease: a textbook of cardiovascularmedicine, 9th ed., vol. I. Philadelphia: Elsevier Saunders

  48. Shah AM, Solomon SD (2012) Myocardial deformation imaging: current status and future directions. Circulation 125(2):e244–e248. https://doi.org/10.1161/CIRCULATIONAHA.111.086348.Erratum.In:Circulation.2013Mar5;127(9):e479. PMID: 22249531

    Article  PubMed  Google Scholar 

  49. Voigt JU, Pedrizzetti G, Lysyansky P, Marwick TH, Houle H, Baumann R, Pedri S, Ito Y, Abe Y, Metz S, Song JH, Hamilton J, Sengupta PP, Kolias TJ, d’Hooge J, Aurigemma GP, Thomas JD, Badano LP (2015) Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging. J Am Soc Echocardiogr 28(2):183–193. https://doi.org/10.1016/j.echo.2014.11.003. PMID: 25623220

    Article  PubMed  Google Scholar 

  50. Thirunavukarasu S, Jex N, Chowdhary A, Hassan IU, Straw S, Craven TP, Gorecka M, Broadbent D, Swoboda P, Witte KK, Cubbon RM, Xue H, Kellman P, Greenwood JP, Plein S, Levelt E (2021) Empagliflozin treatment is associated with improvements in cardiac energetics and function and reductions in myocardial cellular volume in patients with type 2 diabetes. Diabetes 70(12):2810–2822. https://doi.org/10.2337/db21-0270. Epub 2021 Oct 5. PMID: 34610982; PMCID: PMC8660983

  51. Gamaza-Chulián S, Díaz-Retamino E, González-Testón F, Gaitero JC, Castillo MJ, Alfaro R, Rodríguez E, González-Caballero E, Martín-Santana A (2021) Effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on left ventricular remodeling and longitudinal strain: a prospective observational study. BMC Cardiovasc Disord 21(1):456. https://doi.org/10.1186/s12872-021-02250-9. PMID: 34548011; PMCID: PMC8456580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Oka S, Kai T, Hoshino K, Watanabe K, Nakamura J, Abe M, Watanabe A (2021) Effects of empagliflozin in different phases of diabetes mellitus-related cardiomyopathy: a prospective observational study. BMC Cardiovasc Disord 21(1):217. https://doi.org/10.1186/s12872-021-02024-3. PMID: 33926386; PMCID: PMC8086321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bluemke DA, Kronmal RA, Lima JA, Liu K, Olson J, Burke GL, Folsom AR (2008) The relationship of left ventricular mass and geometry to incident cardiovascular events: the MESA (Multi-Ethnic Study of Atherosclerosis) study. J Am Coll Cardiol 52(25):2148–2155. https://doi.org/10.1016/j.jacc.2008.09.014. PMID: 19095132; PMCID: PMC2706368

    Article  PubMed  PubMed Central  Google Scholar 

  54. Mathew J, Sleight P, Lonn E, Johnstone D, Pogue J, Yi Q, Bosch J, Sussex B, Probstfield J, Yusuf S, Heart Outcomes Prevention Evaluation (HOPE) Investigators (2001) Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor ramipril. Circulation 104(14):1615–21. https://doi.org/10.1161/hc3901.096700. PMID: 11581138

  55. Brown AJM, Gandy S, McCrimmon R, Houston JG, Struthers AD, Lang CC (2020) A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: the DAPA-LVH trial. Eur Heart J 41(36):3421–3432. https://doi.org/10.1093/eurheartj/ehaa419. PMID: 32578850; PMCID: PMC8202417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, Flachskampf FA, Gillebert TC, Klein AL, Lancellotti P, Marino P, Oh JK, Popescu BA, Waggoner AD (2016) Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 29(4):277–314. https://doi.org/10.1016/j.echo.2016.01.011. PMID: 27037982

    Article  PubMed  Google Scholar 

  57. Bode D, Semmler L, Wakula P, Hegemann N, Primessnig U, Beindorff N, Powell D, Dahmen R, Ruetten H, Oeing C, Alogna A, Messroghli D, Pieske BM, Heinzel FR, Hohendanner F (2021) Dual SGLT-1 and SGLT-2 inhibition improves left atrial dysfunction in HFpEF. Cardiovasc Diabetol 20(1):7. https://doi.org/10.1186/s12933-020-01208-z. PMID: 33413413; PMCID: PMC7792219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Higashikawa T, Ito T, Mizuno T, Ishigami K, Kohori M, Mae K, Usuda D, Takagi S, Sangen R, Saito A, Iguchi M, Kasamaki Y, Fukuda A, Kanda T, Okuro M (2020) Effects of tofogliflozin on cardiac function in elderly patients with diabetes mellitus. J Clin Med Res 12(3):165–171. https://doi.org/10.14740/jocmr4098. Epub 2020 Mar 2. PMID: 32231752; PMCID: PMC7092764

  59. Cappetta D, De Angelis A, Ciuffreda LP, Coppini R, Cozzolino A, Miccichè A, Dell’Aversana C, D’Amario D, Cianflone E, Scavone C, Santini L, Palandri C, Naviglio S, Crea F, Rota M, Altucci L, Rossi F, Capuano A, Urbanek K, Berrino L (2020) Amelioration of diastolic dysfunction by dapagliflozin in a non-diabetic model involves coronary endothelium. Pharmacol Res 157:104781. https://doi.org/10.1016/j.phrs.2020.104781. Epub 2020 Apr 28 PMID: 32360273

    Article  CAS  PubMed  Google Scholar 

  60. Sezai A, Sekino H, Unosawa S, Taoka M, Osaka S, Tanaka M (2019) Canagliflozin for Japanese patients with chronic heart failure and type II diabetes. Cardiovasc Diabetol 18(1):76. https://doi.org/10.1186/s12933-019-0877-2. PMID: 31167663; PMCID: PMC6551875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Rau M, Thiele K, Hartmann NK, Schuh A, Altiok E, Möllmann J, Keszei AP, Böhm M, Marx N, Lehrke M (2021) Empagliflozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular filling pressure in patients with type 2 diabetes: a randomized controlled study. Cardiovasc Diabetol 20(1):6. https://doi.org/10.1186/s12933-020-01175-5. PMID: 33413355; PMCID: PMC7791833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kayano H, Koba S, Hirano T, Matsui T, Fukuoka H, Tsuijita H, Tsukamoto S, Hayashi T, Toshida T, Watanabe N, Hamazaki Y, Geshi E, Murakami M, Aihara K, Kaneko K, Yamada H, Kobayashi Y, Shinke T (2020) Dapagliflozin influences ventricular hemodynamics and exercise-induced pulmonary hypertension in type 2 diabetes patients - a randomized controlled trial. Circ J 84(10):1807–1817. https://doi.org/10.1253/circj.CJ-20-0341. Epub 2020 Sep 12 PMID: 32921680

    Article  PubMed  Google Scholar 

  63. Shim CY, Seo J, Cho I, Lee CJ, Cho IJ, Lhagvasuren P, Kang SM, Ha JW, Han G, Jang Y, Hong GR (2021) Randomized, controlled trial to evaluate the effect of dapagliflozin on left ventricular diastolic function in patients with type 2 diabetes mellitus: the IDDIA Trial. Circulation 143(5):510–512. https://doi.org/10.1161/CIRCULATIONAHA.120.051992. Epub 2020 Nov 13 PMID: 33186508

    Article  CAS  PubMed  Google Scholar 

  64. Chowdhury B, Luu AZ, Luu VZ, Kabir MG, Pan Y, Teoh H, Quan A, Sabongui S, Al-Omran M, Bhatt DL, Mazer CD, Connelly KA, Verma S, Hess DA (2020) The SGLT2 inhibitor empagliflozin reduces mortality and prevents progression in experimental pulmonary hypertension. Biochem Biophys Res Commun 524(1):50–56. https://doi.org/10.1016/j.bbrc.2020.01.015. Epub 2020 Jan 21 PMID: 31980166

    Article  CAS  PubMed  Google Scholar 

  65. Rosito GA, Massaro JM, Hoffmann U, Ruberg FL, Mahabadi AA, Vasan RS, O’Donnell CJ, Fox CS (2008) Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation 117(5):605–613. https://doi.org/10.1161/CIRCULATIONAHA.107.743062. Epub 2008 Jan 22 PMID: 18212276

    Article  PubMed  Google Scholar 

  66. Yagi S, Hirata Y, Ise T, Kusunose K, Yamada H, Fukuda D, Salim HM, Maimaituxun G, Nishio S, Takagawa Y, Hama S, Matsuura T, Yamaguchi K, Tobiume T, Soeki T, Wakatsuki T, Aihara KI, Akaike M, Shimabukuro M, Sata M (2017) Canagliflozin reduces epicardial fat in patients with type 2 diabetes mellitus. Diabetol Metab Syndr 4(9):78. https://doi.org/10.1186/s13098-017-0275-4. PMID: 29034006; PMCID: PMC5628447

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialities, University of Palermo, Cardiology Unit, University Hospital P. Giaccone, Palermo, Italy

    Giuseppina Novo, Tommaso Guarino & Daniela Di Lisi

  2. Cardiology and Cardiovascular Pathophysiology, S. Maria della Misericordia Hospital, University of Perugia, Perugia, Italy

    Paolo Biagioli & Erberto Carluccio

Authors
  1. Giuseppina Novo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tommaso Guarino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniela Di Lisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paolo Biagioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Erberto Carluccio
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Novo: conception of the study, design, and supervision. Guarino: literature review and writer especially concerning diastolic function. Di Lisi: literature review and writer especially concerning strain analysis and tables. Biagioli: literature review and writer especially concerning systolic function. Carluccio: supervision and critical review.

Corresponding author

Correspondence to Tommaso Guarino.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Novo, G., Guarino, T., Di Lisi, D. et al. Effects of SGLT2 inhibitors on cardiac structure and function. Heart Fail Rev 28, 697–707 (2023). https://doi.org/10.1007/s10741-022-10256-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-022-10256-4

Keywords

Search

Navigation