SGLT2 inhibitors and risk of new-onset left bundle branch block in heart failure with preserved ejection fraction
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Updated: Jan 26, 2026
Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
Marco Zuin1, Francesco Vitali2, Luca Canovi3
1Department of Translational Medicine, University of Ferrara, Ferrara 44121, Italy; Department of Cardio-Thoraco-Vascular Sciences and Public Health, University of Padova, Padua, Italy - PhD Program in Translational Specialist Medicine 'G.B. Morgagni', Curriculum Cardiovascular Sciences, University of Padua, Italy; Department of Cardiology, Madre Teresa di Calcutta Hospital, AULSS 6, South Padova Hospitals, Schiavonia 35043, Italy.
Insights
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) significantly reduced the risk of new-onset left bundle branch block (LBBB) in patients with heart failure with preserved ejection fraction (HFpEF). This finding suggests SGLT2i may help preserve conduction integrity and prevent electrical dyssynchrony.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Heart failure with preserved ejection fraction (HFpEF) is associated with increased risk of conduction abnormalities like left bundle branch block (LBBB).
- The potential benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in preventing new-onset LBBB in HFpEF patients is not well established.
Purpose of the Study:
- To investigate the association between SGLT2i use and the incidence of new-onset LBBB in patients diagnosed with HFpEF.
- To evaluate the efficacy of SGLT2i in mitigating conduction abnormalities within this patient population.
Main Methods:
- A cohort study utilizing a prospectively collected database of HFpEF patients.
- Propensity score matching was employed to compare patients receiving SGLT2i with historical controls not on SGLT2i (1:1 ratio).
- New-onset LBBB was the primary endpoint, assessed over a median 24-month follow-up using Cox proportional hazards and competing risk analyses.
Main Results:
- The study included 254 matched patients (127 SGLT2i, 127 controls), with a median follow-up of 24 months.
- New-onset LBBB occurred in 4.7% of SGLT2i users versus 11.8% of controls, yielding a hazard ratio of 0.41 (p < 0.001).
- This protective association remained significant in competing risk analysis (sHR 0.40, p = 0.01) and was consistent across most subgroups.
Conclusions:
- SGLT2i use was associated with a reduced risk of incident LBBB in HFpEF patients over a two-year period.
- These findings suggest SGLT2i may play a role in preserving cardiac conduction integrity and preventing the progression of electrical dyssynchrony in HFpEF.
- The results support further investigation into SGLT2i's role in managing conduction abnormalities in heart failure.
Background:
Whether sodium-glucose cotransporter 2 inhibitors (SGLT2i) may reduce the risk of developing new-onset left bundle branch block (LBBB) in patients with heart failure with preserved ejection fraction (HFpEF) remains unknown. We investigate the association between SGLT2i use and incident LBBB in patients with HFpEF.
Methods:
We conducted a cohort study using a prospectively database of patients with HFpEF. Patients receiving SGLT2i were propensity score-matched 1:1 with historical controls not receiving SGLT2i. The primary endpoint was new-onset LBBB, over a median 24-month follow-up. Cox proportional hazards models and Fine-Gray competing risk analyses were used to assess the association. Pre-specified subgroup analyses evaluated potential effect modification.
Results:
A total of 254 patients were included after matching (mean age 73 years, 62% female; 127 SGLT2i, 127 controls). Over a median follow-up of 24 month [interquartile range 22-26 months], new-onset LBBB occurred in 6 of 127 patients (4.7%) treated with SGLT2i versus 15 of 127 patients (11.8%) in the control group, corresponding to a hazard ratio (HR) of 0.41 (95% CI: 0.18-0.61, p < 0.001), which remained significant in competing risk analysis for all-cause of death (sHR 0.40; 95% CI 0.18-0.92; p = 0.01). The association was consistent across most subgroups, with no significant interactions. In patients with baseline QRS ≥110 ms and in those without diabetes, the effect did not reach statistical significance, although point estimates were directionally similar.
Conclusions:
In HFpEF, SGLT2i use reduced incident LBBB risk over two years, consistent across subgroups, suggesting a role in preserving conduction integrity and preventing electrical dyssynchrony progression.
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