Correlation between myocardial strain and adverse remodeling in a non-diabetic model of heart failure following empagliflozin therapy

ABSTRACT

Objectives

The sodium-glucose cotransporter type 2 inhibitors reduce mortality and heart failure (HF) hospitalizations. The underlying mechanisms remain unclear but seem to be irrespective of glucose-lowering properties. This study aims to evaluate the impact of empagliflozin on myocardial biomechanics and correlation with markers of adverse remodeling.

Methods

Following myocardial infarct induction to create a model of HF, 14 pigs were randomly assigned in a 1:1 ratio to receive either empagliflozin 10 mg daily or placebo for 2 months. Speckle-tracking echocardiography (STE) and feature-tracking cardiac magnetic resonance (FTCMR) were performed at baseline and at the end of the study to analyze myocardial deformation. The results were correlated with markers of adverse cardiac remodeling.

Results

Empagliflozin significantly improved STE indices. These parameters significantly correlated with adverse cardiac remodeling. In contrast, FTCMR indices showed only a trend toward improved myocardial deformation and without significant correlation with adverse cardiac remodeling. The correlation between both techniques to assess myocardial deformation was low.

Conclusion

Empagliflozin enhances myocardial deformation, assessed by STE techniques, in a non-diabetic porcine model of ischemic HF. This may be related to a mitigation of adverse cardiac remodeling following ischemia reperfusion injury. In contrast, FTCMR technique needs further development and validation.

KEYWORDS:

• Empagliflozin
• heart failure
• adverse remodeling
• myocardial strain
• cardiac fibrosis
• diabetes mellitus
• independent grant

Author contributions

• Alvaro Garcia-Ropero: involved in the conception, design, analysis and interpretation of the date as well as drafting of the paper and final approval of the version to be published.

• Carlos G. Santos-Gallego: involved in the conception, design and final approval of the version to be published.

• Ariana P. Vargas-Delgado: involved in the conception, design and final approval of the version to be published.

• Juan Antonio Requena-Ibanez: involved in the conception, design and final approval of the version to be published.

• Belen Picatoste: involved in the analysis of the date and final approval of the version to be published.

• Kiyotake Ishikawa: involved in the conception, design and final approval of the version to be published.

• Javier Sanz: involved in the conception, design and final approval of the version to be published.

• Jose Tunon: involved in the conception, design and final approval of the version to be published.

• Juan J. Badimon: involved in the conception, design and final approval of the version to be published.

• All the authors agree to be accountable for all aspects of this work.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. 

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This paper was funded by an independent grant from Boehringer Ingelheim Pharmaceuticals, which provided both drug and financial support for the study. The authors report that they have no relationships relevant to the contents of this paper to disclose.The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.