Empagliflozin-Pirfenidone Dual Therapy Improves Cardiac Function and Structure in a Preclinical Two-Hits HFpEF Model
Abstract
Background: : : Heart failure with preserved ejection fraction (HFpEF) affects over half of heart failure patients and is life-threatening. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown potential in reducing cardiovascular death and heart failure hospitalization in HFpEF. This study examines if the effects of antifibrosis of EMPA can be synergized by coadministration of Pirfenidone, augmenting its benefit in restoring heart function.
Aims: : : We hypothesized that co-administration of the antifibrotic agent pirfenidone (PFD) with SGLT2i could enhance therapeutic outcomes.
Methods: : : HFpEF was induced in Sprague-Dawley rats (n=16 per group) using L-NAME and a high-fat diet over 5 weeks. Subsequently, rats received daily oral treatment of supratherapeutic dose of EMPA (0.35 g/kg/d), PFD (0.3 g/kg/d), or both (EMPA+PFD) for 4 weeks; untreated HFpEF rats served as controls. Cardiac function was evaluated by echocardiography, histopathology, and exercise tolerance tests. RNA sequencing was performed to elucidate transcriptional changes.
Results: : : Co-treatment with EMPA+PFD significantly enhanced diastolic indices in addition to left ventricular ejection fraction, fractional shortening, and cardiac output, compared with controls and monotherapy groups (p<0.05). Histological analysis revealed reduced cardiomyocyte hypertrophy and lower collagen deposition, particularly in the endocardium. RNA sequencing showed pronounced transcriptional shifts related to…
Read the paper
Related studies
- Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol
- Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance
- SGLT2 Inhibitors in Heart Failure: Targeted Metabolomics and Energetic Metabolism
- Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors
- Sodium-glucose cotransporter inhibitors: beyond glycaemic control
- Decoding the effects of SGLT2 inhibitors on cardiac arrhythmias in heart failure
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.