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Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
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Empagliflozin Improves Diastolic Function in a Nondiabetic Rodent Model of Heart Failure With

Kim A Connelly1, Yanling Zhang1, Aylin Visram1

  • 1Keenan Research Centre, Li Ka Shying Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada.

JACC. Basic to Translational Science
|March 9, 2019
PubMed

Insights

Sodium-glucose-linked co-transporter-2 (SGLT2) inhibitors like empagliflozin reduce heart failure hospitalizations. This study shows empagliflozin improves heart function in a rodent model by reducing cardiac mass and improving hemodynamics.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Sodium-glucose-linked co-transporter-2 inhibitors (SGLT2i) are proven to prevent heart failure hospitalization in type 2 diabetes patients.
  • The precise mechanisms underlying the cardioprotective effects of SGLT2i remain incompletely understood.

Purpose of the Study:

  • To investigate the mechanistic effects of SGLT2 inhibition on heart failure with preserved ejection fraction (HFpEF) using a rodent model.
  • To elucidate how empagliflozin impacts cardiac structure and function in HFpEF.

Main Methods:

  • Utilized a rodent model of heart failure with preserved ejection fraction (HFpEF).
  • Administered the SGLT2 inhibitor empagliflozin to the rodent model.
  • Assessed changes in left ventricular mass, wall stress, and diastolic function.

Main Results:

  • Empagliflozin treatment significantly reduced left ventricular mass in the HFpEF rodent model.
  • Improved cardiac wall stress and diastolic function were observed following empagliflozin administration.
  • Findings suggest improved hemodynamics, including reduced preload and afterload, as a key mechanism.

Conclusions:

  • Empagliflozin demonstrates beneficial effects on cardiac structure and function in a preclinical model of HFpEF.
  • The cardioprotective effects are associated with improved hemodynamic parameters.
  • These results support further investigation of SGLT2 inhibitors in HFpEF patients, regardless of glycemic status.
Keywords:
ANP, atrial natriuretic peptideDOCA, deoxycorticosterone acetateGADPH, glyceraldehyde 3-phosphate dehydrogenaseHF, heart failureHFpEF, heart failure with preserved ejection fractionHFrEF, heart failure with reduced ejection fractionLV, left ventricularSGLT2i, sodium-glucose−linked co-transporter-2 inhibitorUNX, uninephrectomydiastoleheart failure with preserved ejection fractionsodium-glucose−linked co-transporter-2 inhibitorsystole

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