SGLT2 inhibitors and left atrial function in heart failure with reduced or mildly reduced ejection fraction

Q: What does this research mean for the field?

SGLT2 inhibitor therapy is not independently associated with significant improvements in left atrial volume or functional parameters in patients with heart failure with reduced or mildly reduced ejection fraction. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Hakan Duman; Hüseyin Durak; Mustafa Çetın; Müjgan Ayşenur Şahin; Elif Ergül; Erhan Saraçoğlu; Barış Dindar; Nadir Emlek

doi:10.1186/s12872-025-05308-0

November 14, 2025BMC Cardiovascular DisordersOpen Access

SGLT2 inhibitors and left atrial function in heart failure with reduced or mildly reduced ejection fraction

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Why the study?

The effects of SGLT2 inhibitors on left atrial structure and function remain unclear, particularly in heart failure with reduced or mildly reduced ejection fraction.

Does SGLT2 inhibitor therapy improve left atrial volume index, left atrial emptying fraction, or left atrial functional index in patients with heart failure and reduced or mildly reduced ejection fraction?

Structured PICO

Does SGLT2 inhibitor therapy improve left atrial volume index, left atrial emptying fraction, or left atrial functional index in patients with heart failure and reduced or mildly reduced ejection fraction?

P

Population

134 patients with heart failure and reduced or mildly reduced ejection fraction (LVEF < 50%), mean age ~65, ~81-85% male, based in Türkiye. Key inclusion: HF diagnosis per 2021 ESC guidelines, LVEF < 50%, complete echocardiographic and laboratory records. Exclusion: ACS within 3 months, cardiac surgery within 6 months, coexisting structural heart diseases.

I

Intervention

SGLT2 inhibitors

C

Comparator

No SGLT2 inhibitors

O

Outcome

Left atrial volume index (LAVI), left atrial emptying fraction (LAEF), and left atrial functional index (LAFI) measured by echocardiographysurrogate

SGLT2 inhibitor use is not independently associated with improvements in left atrial volume or functional parameters in patients with HFrEF or HFmrEF, suggesting LA changes are primarily driven by underlying diastolic dysfunction and ventricular remodeling.

Limitations

Baseline imbalances between groups (higher DM, diuretic use, lower LVEF in SGLT2+ group) introducing residual confounding despite multivariable adjustment and PSM
Cross-sectional design

Implication

No independent link to LA indices in this HF cross-sectional analysis; hypothesis-generating and requires prospective trials.

Abstract

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce cardiovascular mortality and hospitalizations in heart failure (HF). However, their effects on left atrial (LA) structure and function remain unclear, particularly in patients with reduced or mildly reduced ejection fraction (EF). METHODS: This observational, cross-sectional study included 134 patients with HF and EF < 50%, divided into two groups: those receiving SGLT2 inhibitors (SGLT2+, n = 25) and those not receiving them (SGLT2-, n = 109). Echocardiographic measurements of LA volume index (LAVI), LA emptying fraction (LAEF), LA functional index (LAFI), and passive/active emptying fractions were obtained according to ASE/EACVI guidelines. Clinical, laboratory, and echocardiographic parameters were compared between groups, and correlations with LA indices were analyzed using multivariable linear regression. RESULTS: The prevalence of diabetes mellitus, spironolactone use, and furosemide use was significantly higher in the SGLT2 + group (all p < 0.05). LVEF was lower (32.9 ± 6.7 vs. 38.7 ± 8.6, p = 0.002), and left ventricular volumes were larger in the SGLT2 + group, while LAFI was significantly reduced (0.12 ± 0.08 vs. 0.18 ± 0.10, p = 0.008). However, there were no significant differences in LAVI or LAEF between groups. Multivariable regression identified E/A ratio, age, and LVEF as independent determinants of LAVI; posterior wall thickness and E/A ratio for LAEF; and E/A ratio, diabetes mellitus, posterior wall thickness, and interventricular septal thickness for LAFI. CONCLUSION: SGLT2 inhibitor use was not associated with significant improvement in LA volume or functional parameters in patients with HF and reduced or mildly reduced EF. The prognostic value of LA functions appears to be primarily influenced by diastolic dysfunction and ventricular remodeling rather than SGLT2 inhibitor therapy.