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Dapagliflozin Effects on Left Ventricular Remodeling and Filling Pressures in Heart Failure With Reduced Ejection
Mauro Acquaro1, Laura Scelsi1, Camilla Mascolo2
1Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Insights
Dapagliflozin improved cardiac structure and function in heart failure with reduced ejection fraction (HFrEF) patients. These changes correlated with fewer hospitalizations and reduced natriuretic peptides, suggesting a mechanism for clinical benefit.
Area of Science:
- Cardiology
- Pharmacology
- Medical Science
Background:
- Sodium glucose cotransporter 2 inhibitors (SGLT2i) show proven benefits in heart failure with reduced ejection fraction (HFrEF).
- The precise mechanisms underlying these benefits remain unclear.
- Understanding these mechanisms is crucial for optimizing HFrEF management.
Purpose of the Study:
- To evaluate cardiac morphofunctional changes after initiating dapagliflozin in stable HFrEF outpatients.
- To determine if these cardiac changes predict improved clinical outcomes.
Main Methods:
- A multicenter, prospective observational study enrolled 300 HFrEF patients on optimized therapy.
- Echocardiographic and laboratory assessments were conducted at baseline and 6 months post-dapagliflozin initiation.
- Patients were followed for 12 months to assess clinical outcomes.
Main Results:
- 47% of patients showed improvements in left ventricular volumes and/or ejection fraction at 6 months.
- Elevated left ventricular filling pressures decreased significantly, from 26% to 3% (P < .001).
- Combined improvements in cardiac remodeling and filling pressures were linked to no heart failure hospitalizations and reduced natriuretic peptides at 12 months.
Conclusions:
- Dapagliflozin induced significant left ventricular remodeling and improved filling pressures in HFrEF patients on optimal therapy.
- These echocardiographic improvements were associated with reduced heart failure hospitalizations and natriuretic peptide levels.
- The findings suggest a mechanistic link between dapagliflozin's cardiac effects and improved clinical outcomes in HFrEF.
Aims:
The benefits of sodium glucose cotransporter 2 inhibitors in patients with heart failure with reduced ejection fraction (HFrEF) have been clearly demonstrated in randomized clinical trials. However, the mechanisms of the observed beneficial effects remain incompletely understood. This study aimed to assess morphofunctional cardiac changes following dapagliflozin introduction in stable outpatients with HFrEF and to investigate whether these changes were determinants of the improved clinical outcome.
Methods:
In this multicenter, prospective observational study, 300 consecutive HFrEF patients ≥18 years old on optimized medical therapy and eligible for dapagliflozin therapy were enrolled between April 2022 and January 2023. Laboratory and echocardiographic assessments were performed at baseline and after a median of 6 months.
Results:
Following dapagliflozin initiation, 47% of patients achieved a target of improvement in left ventricular end-diastolic volume (Δ EDVi < -10%) and/or end-systolic volume (Δ ESVi < -15%) and/or ejection fraction (Δ EF% > 10%) at 6 months. The proportion of patients with elevated left ventricular filling pressures decreased from 26% to 3% at 6 months (P < .001). The combination of left ventricular remodeling and filling pressures improvements was associated with absence of heart failure-related hospitalizations and significant natriuretic peptide reduction at 12 months.
Conclusions:
Dapagliflozin determined left ventricular remodeling and improved left ventricular filling pressures in a high proportion of patients with stable HFrEF patients already on optimized medical therapy. These improvements were associated with absence of heart failure-related hospitalizations and a significant natriuretic peptide reduction at 12 months.
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