Advertisement

Efficacy of SGLT2 Inhibitors in Patients With Diabetes and Nonobstructive Hypertrophic Cardiomyopathy

Published:December 03, 2022DOI:https://doi.org/10.1016/j.amjcard.2022.10.054
      The objective of this study was to evaluate the effects of sodium glucose co-transporter 2 inhibitors (SGLT2i) on functional capacity and diastolic function in patients with diabetes with nonobstructive hypertrophic cardiomyopathy (nHCM) and preserved left ventricular (LV) function. From January 2019 to October 2020, a prospective open-label study was performed on patients with type 2 diabetes mellitus and nHCM with New York Heart Association class II-III symptoms. Patients with a LV ejection fraction <50% were excluded. Patients were recruited from January 2019 to November 2019 to the SGLT2i arm and from November 2019 to October 2020 to the control arm. The primary composite end point was defined as achieving an improvement of at least 1.5 in E/e′ and a reduction of ≥1 New York Heart Association functional class after 6 months of therapy. At baseline, there were no significant differences between the SGLT2i (n = 24) and control arms (n = 24). More patients in the SGLT2i arm achieved the primary end point than the patients in the control arm (70.8% vs 4.2%, p <0.001). After 6 months of therapy, patients in the SGLT2i arm showed a significant improvement in all diastolic function parameters (E/e′ 16.3 ± 1.9 vs 13.3 ± 1.6, p <0.001; E/A 2.8 ± 0.1 vs 2.4 ± 0.1, p <0.001; left atrial volume 45.6 ± 5.2 vs 40.8 ± 4.9 ml/m2, p = 0.003). There was also an improvement in the 6-minute walk distance (295.1 ± 31.5 vs 343.0 ± 31.1 m, p <0.001) and N-terminal pro-B-type natriuretic peptide (481.4 ± 52.6 vs 440.9 ± 43.9 pg/ml, p <0.001) in patients who received SGLT2i. There was no significant change in the LV mass in the SGLT2i or control arm (−0.1 ± 0.3 vs 0.1 ± 0.5 g/m2, p = 0.319) after 6 months of therapy. A patient in the SGLT2i arm discontinued therapy because of a urinary tract infection. In conclusion, the use of SGLT2i improved diastolic function and functional capacity in patients with diabetes with nHCM and a preserved LV function.

      Graphical Abstract

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Maron MS
        • Rowin EJ
        • Olivotto I
        • Casey SA
        • Arretini A
        • Tomberli B
        • Garberich RF
        • Link MS
        • Chan RHM
        • Lesser JR
        • Maron BJ.
        Contemporary natural history and management of nonobstructive hypertrophic cardiomyopathy.
        J Am Coll Cardiol. 2016; 67: 1399-1409
        • Maron BJ
        • Rowin EJ
        • Maron MS
        • Braunwald E.
        Nonobstructive hypertrophic cardiomyopathy out of the shadows: known from the beginning but largely ignored... until now.
        Am J Med. 2017; 130: 119-123
        • Lu DY
        • Pozios I
        • Haileselassie B
        • Ventoulis I
        • Liu H
        • Sorensen LL
        • Canepa M
        • Phillip S
        • Abraham MR
        • Abraham TP.
        Clinical outcomes in patients with nonobstructive, labile, and obstructive hypertrophic cardiomyopathy.
        J Am Heart Assoc. 2018; 7e006657
        • van der Velden J
        • Tocchetti CG
        • Varricchi G
        • Bianco A
        • Sequeira V
        • Hilfiker-Kleiner D
        • Hamdani N
        • Leite-Moreira AF
        • Mayr M
        • Falcão-Pires I
        • Thum T
        • Dawson DK
        • Balligand JL
        • Heymans S.
        Metabolic changes in hypertrophic cardiomyopathies: scientific update from the Working Group of Myocardial Function of the European Society of Cardiology.
        Cardiovasc Res. 2018; 114: 1273-1280
        • Olivotto I
        • Hellawell JL
        • Farzaneh-Far R
        • Blair C
        • Coppini R
        • Myers J
        • Belardinelli L
        • Maron MS.
        Novel approach targeting the complex pathophysiology of hypertrophic cardiomyopathy: the impact of late sodium current inhibition on exercise capacity in subjects with symptomatic hypertrophic cardiomyopathy (LIBERTY-HCM) trial.
        Circ Heart Fail. 2016; 9e002764
        • Olivotto I
        • Camici PG
        • Merlini PA
        • Rapezzi C
        • Patten M
        • Climent V
        • Sinagra G
        • Tomberli B
        • Marin F
        • Ehlermann P
        • Maier LS
        • Fornaro A
        • Jacobshagen C
        • Ganau A
        • Moretti L
        • Hernandez Madrid A
        • Coppini R
        • Reggiardo G
        • Poggesi C
        • Fattirolli F
        • Belardinelli L
        • Gensini G
        • Mugelli A
        Efficacy of ranolazine in patients with symptomatic hypertrophic cardiomyopathy: the RESTYLE-HCM randomized, double-blind, placebo-controlled study.
        Circ Heart Fail. 2018; 11e004124
        • Coats CJ
        • Pavlou M
        • Watkinson OT
        • Protonotarios A
        • Moss L
        • Hyland R
        • Rantell K
        • Pantazis AA
        • Tome M
        • McKenna WJ
        • Frenneaux MP
        • Omar R
        • Elliott PM.
        Effect of trimetazidine dihydrochloride therapy on exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy: a randomized clinical trial.
        JAMA Cardiol. 2019; 4: 230-235
        • 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. Dapagliflozin in patients with heart failure and reduced ejection fraction.
        N Engl J Med. 2019; 381: 1995-2008
        • Anker SD
        • Butler J
        • Filippatos G
        • Ferreira JP
        • Bocchi E
        • Bohm 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
        • Pina 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
        • Investigators EM-PT.
        Empagliflozin in heart failure with a preserved ejection fraction.
        N Engl J Med. 2021; 385: 1451-1461
        • Lopaschuk GD
        • Verma S.
        Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors: a state-of-the-art review.
        JACC Basic Transl Sci. 2020; 5: 632-644
        • 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.
        Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.
        Eur Heart J Cardiovasc Imaging. 2015; 16: 233-270
        • Nagueh SF
        • Smiseth OA
        • Appleton CP
        • Byrd 3rd, BF
        • Dokainish H
        • Edvardsen T
        • Flachskampf FA
        • Gillebert TC
        • Klein AL
        • Lancellotti P
        • Marino P
        • Oh JK
        • Alexandru Popescu B
        • Waggoner AD
        • Houston T
        • Oslo N
        • Phoenix A
        • Nashville T
        • Hamilton OC
        • Uppsala S
        • Ghent
        • Liege B
        • Cleveland O
        • Novara I
        • Rochester M
        • Bucharest R
        • St. Louis M
        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.
        Eur Heart J Cardiovasc Imaging. 2016; 17: 1321-1360
        • Devereux RB
        • Alonso DR
        • Lutas EM
        • Gottlieb GJ
        • Campo E
        • Sachs I
        • Reichek N.
        Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings.
        Am J Cardiol. 1986; 57: 450-458
        • Matsutani D
        • Sakamoto M
        • Kayama Y
        • Takeda N
        • Horiuchi R
        • Utsunomiya K.
        Effect of canagliflozin on left ventricular diastolic function in patients with type 2 diabetes.
        Cardiovasc Diabetol. 2018; 17: 73
        • Verma S
        • Garg A
        • Yan AT
        • Gupta AK
        • Al-Omran M
        • Sabongui A
        • Teoh H
        • Mazer CD
        • Connelly KA.
        Effect of empagliflozin on left ventricular mass and diastolic function in individuals With diabetes: an important clue to the EMPA-REG OUTCOME trial?.
        Diabetes Care. 2016; 39: e212-e213
        • Shim CY
        • Seo J
        • Cho I
        • Lee CJ
        • Cho IJ
        • Lhagvasuren P
        • Kang SM
        • Ha JW
        • Han G
        • Jang Y
        • Hong GR.
        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. 2021; 143: 510-512
        • Soga F
        • Tanaka H
        • Tatsumi K
        • Mochizuki Y
        • Sano H
        • Toki H
        • Matsumoto K
        • Shite J
        • Takaoka H
        • Doi T
        • Hirata KI.
        Impact of dapagliflozin on left ventricular diastolic function of patients with type 2 diabetic mellitus with chronic heart failure.
        Cardiovasc Diabetol. 2018; 17: 132
        • Brown AJM
        • Gandy S
        • McCrimmon R
        • Houston JG
        • Struthers AD
        • Lang CC.
        A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: the DAPA-LVH trial.
        Eur Heart J. 2020; 41: 3421-3432
        • Connelly KA
        • Zhang Y
        • Visram A
        • Advani A
        • Batchu SN
        • Desjardins JF
        • Thai K
        • Gilbert RE.
        Empagliflozin improves diastolic function in a nondiabetic rodent model of heart failure with preserved ejection fraction.
        JACC Basic Transl Sci. 2019; 4: 27-37
        • Anker SD
        • Butler J
        • Filippatos G
        • Shahzeb Khan M
        • Ferreira JP
        • Bocchi E
        • Böhm M
        • Brunner-La Rocca HP
        • Choi DJ
        • Chopra V
        • Chuquiure 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
        • Seronde MF
        • Sim D
        • Spinar J
        • Squire I
        • Taddei S
        • Tsutsui H
        • Verma S
        • Vinereanu D
        • Zhang J
        • Jamal W
        • Schnaidt S
        • Schnee JM
        • Brueckmann M
        • Pocock SJ
        • Zannad F
        • Packer M
        EMPEROR-Preserved Trial Committees and Investigators. Baseline characteristics of patients with heart failure with preserved ejection fraction in the EMPEROR-Preserved trial.
        Eur J Heart Fail. 2020; 22: 2383-2392
        • Scheffer M
        • Driessen-Waaijer A
        • Hamdani N
        • Landzaat JWD
        • Jonkman NH
        • Paulus WJ
        • van Heerebeek L.
        Stratified Treatment of Heart Failure with preserved Ejection Fraction: rationale and design of the STADIA-HFpEF trial.
        ESC Heart Fail. 2020; 7: 4478-4487
        • Vakrou S
        • Abraham MR.
        Hypertrophic cardiomyopathy: a heart in need of an energy bar?.
        Front Physiol. 2014; 5: 309
        • Verma S
        • Rawat S
        • Ho KL
        • Wagg CS
        • Zhang L
        • Teoh H
        • Dyck JE
        • Uddin GM
        • Oudit GY
        • Mayoux E
        • Lehrke M
        • Marx N
        • Lopaschuk GD.
        Empagliflozin increases cardiac energy production in diabetes: novel translational insights into the heart failure benefits of SGLT2 inhibitors.
        JACC Basic Transl Sci. 2018; 3: 575-587