# The Impact of SGLT2 Inhibitors on Anatomic and Metabolic Cardiac Remodeling in Heart Failure with Preserved Ejection Fraction

> **NIH NIH F32** · STANFORD UNIVERSITY · 2023 · $30,739

## Abstract

PROJECT SUMMARY/ABSTRACT
Though implicated in half of all incident heart failure presentations, heart failure with preserved ejection fraction
(HFpEF) is a poorly understood disease process with limited available therapies. Indeed, no medications were
definitively shown to improve clinical outcomes in HFpEF until the recent serendipitous discovery of the benefit
of sodium-glucose cotrasporter-2 inhibitors (SGLT2i) in heart failure. Unfortunately, the mechanisms of SGLT2i
in HFpEF remain largely undefined. Elucidating these mechanisms will facilitate expansion of the HFpEF
therapeutic armamentarium. While prior studies have suggested a positive anatomic cardiac remodeling
benefit of SGLT2i in HFpEF, the molecular mechanisms driving this process are not understood. Recent
animal data linking the anatomic remodeling benefits of SGTL2i in systolic heart failure to favorable shifts in
cardiac energy metabolism have motivated strong speculation that SGLT2i afford benefit in HFpEF via similar
mechanistic pathways. This study will investigate if SGLT2i therapy is associated with both positive anatomic
and metabolic cardiac remodeling benefits in HFpEF. To achieve this, multiple novel cardiac imaging methods
will be employed in service of two specific aims: (1) Evaluate the impact of SGLT2i therapy on cardiac
remodeling in patients with HFpEF via retrospective analysis of serial echocardiograms and (2) explore the
impact of SGLT2i therapy on metabolic cardiac remodeling in patients with HFpEF via Cr-CEST MRI.
Application of novel echocardiographic artificial intelligence platforms will facilitate a standardized, high
throughput retrospective analysis of select echocardiographic parameters derived from a large clinical cohort to
detect changes in anatomic cardiac remodeling following initiation of SGLT2i. Additionally, creatine chemical
exchange saturation transfer magnetic resonance imaging (Cr-CEST MRI) will be utilized to detect relative
levels of intracellular creatine, a surrogate marker for cardiac metabolic activity, following SGLT2i therapy in
HFpEF. Beyond facilitating these specific aims, the application of emerging advanced cardiac imaging
techniques as outlined above will (1) demonstrate the utility of AI platforms in standardizing retrospective
echocardiographic data and (2) outline the feasibility of Cr-CEST MRI in detecting shifts in HFpEF cardiac
metabolism. This work will advance the field’s collective understanding of novel HFpEF therapeutics,
operationalize innovative cardiac imaging techniques, and provide training in cardiac imaging research
methodologies central to the applicant’s long-term goal of becoming a physician-scientist with expertise in
heart failure and advanced cardiac imaging.

## Key facts

- **NIH application ID:** 10751587
- **Project number:** 1F32HL170695-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** SHIRE BEACH
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $30,739
- **Award type:** 1
- **Project period:** 2024-02-12 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10751587

## Citation

> US National Institutes of Health, RePORTER application 10751587, The Impact of SGLT2 Inhibitors on Anatomic and Metabolic Cardiac Remodeling in Heart Failure with Preserved Ejection Fraction (1F32HL170695-01). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10751587. Licensed CC0.

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