In optimally treated HFrEF patients, LV size and systolic and diastolic function significantly improved during the 6 months after dapagliflozin initiation, with no significant differences in the magnitude of LV reverse remodeling by eGFR or LGE burden.
Key Findings
Results
Six months after starting dapagliflozin 10 mg daily, 2D echocardiography showed lower LV volumes and higher LVEF in patients with HFrEF on guideline-directed therapy.
Seventy-five patients with LVEF ≤40% on guideline-directed therapy were prospectively enrolled, with assessments at baseline and at 6-month follow-up (6MFU).
2D LV end-diastolic volume: 88[72-122] vs. 92[79-122] mL/m2. 2D LV end-systolic volume: 58[42-80] vs. 57[48-88] mL/m2. 2D LVEF: 36.6±8.8 vs. 34.5±7.7%; p < 0.001.
The abstract reports that volumes decreased and LVEF increased. The value pairs appear to be listed as follow-up vs. baseline, though the order is not stated explicitly.
Results
3D echocardiography gave results consistent with 2D, with reduced LV volumes and increased LVEF after dapagliflozin.
3D LV end-diastolic volume: 100[79-140] vs. 108[90-136] mL/m2. 3D LV end-systolic volume: 64[46-82] vs. 69[55-93] mL/m2.
3D LVEF: 37.4±8.7 vs. 34.4±7.9%; p < 0.001.
The paper states that both 2D and 3D echocardiography consistently demonstrated LV reverse remodeling.
Results
LV diastolic function improved, with fewer patients having grade ≥2 diastolic dysfunction at 6 months.
Grade ≥2 diastolic dysfunction was present in 4.7% vs. 18.7% of patients (p = 0.015). The lower figure appears to be the 6MFU value, in keeping with the reported improvement.
Results
Systolic pulmonary artery pressure was lower at 6-month follow-up.
Systolic pulmonary artery pressure was 25[23-29] vs. 27[24-29] mmHg (p = 0.037).
The lower value appears to be the follow-up value, in keeping with the reported improvement.
Results
No significant association was detected between baseline eGFR and the magnitude of LV reverse remodeling.
Sub-analyses compared patients with eGFR <45 vs. ≥45 mL/min/1.73 m2.
The authors describe these as exploratory analyses that did not detect a statistically significant association between baseline renal function and reverse remodeling.
Results
In the CMR subgroup, a greater LGE burden was possibly inversely correlated with improvement in 2D LVEF, although overall reverse remodeling did not differ significantly by LGE burden.
Myocardial fibrosis was assessed as late gadolinium enhancement (LGE) extent on cardiac magnetic resonance.
The authors call this a preliminary finding, with CMR analyses suggesting a possible inverse correlation.
The abstract also states that no significant differences in the magnitude of LV reverse remodeling were detected according to LGE burden.
Discussion
Some patients with baseline LVEF ≤35% crossed the 35% threshold by 6-month follow-up.
The authors describe this as hypothesis-generating.
They suggest it may warrant investigation of how reverse remodeling affects subsequent device-therapy assessment.
What This Means
This study followed 75 people with heart failure and reduced pumping function (LVEF 40% or lower) who were already on well-optimized standard medications. Researchers measured heart size and function with 2D and 3D ultrasound before and 6 months after dapagliflozin 10 mg daily was added. Both ultrasound methods showed that the main pumping chamber (the left ventricle) became smaller and pumped more efficiently, a pattern called reverse remodeling. Filling function of the heart improved, with fewer patients having moderate or worse diastolic dysfunction, and estimated pressure in the lung arteries was slightly lower.
The researchers also asked whether kidney function or heart scarring (seen on cardiac MRI) affected how much the heart improved. They found no statistically significant link between starting kidney function and the degree of improvement. In the MRI subgroup, more scarring seemed possibly linked to less improvement in 2D pumping function. However, no significant difference in overall remodeling by scar burden was detected, and the authors describe this finding as preliminary.
Some patients whose pumping function was at or below 35% at the start rose above that level at 6 months. This could matter when doctors decide about implanted devices, but the authors present it only as a hypothesis for further study. This research suggests dapagliflozin is associated with measurable heart improvements even in patients who are already well treated. The study had no comparison group, and the findings come from a relatively small group.
Amelotti N, Mantegazza V, Garlaschè A, Salvioni E, Mapelli M, Baggiano A, et al.. (2026). DAPAgliflozin-Related Cardiac REverse Remodeling by 2D and 3D Echocardiography in OptiMally Treated HFrEF Patients: The DAPA-REM Study.. Echocardiography (Mount Kisco, N.Y.). https://doi.org/10.1111/echo.70654