TY - JOUR
T1 - The effect of empagliflozin on peripheral microvascular dysfunction in patients with heart failure with preserved ejection fraction
AU - Mourmans, Sanne G.J.
AU - Achten, Anouk
AU - Hermans, Raquel
AU - Scheepers, Marijne J.E.
AU - D’Alessandro, Elisa
AU - Swennen, Geertje
AU - Woudstra, Janneke
AU - Appelman, Yolande
AU - Goor, Harry van
AU - Schalkwijk, Casper
AU - Knackstedt, Christian
AU - Weerts, Jerremy
AU - Eringa, Etto C.
AU - van Empel, Vanessa P.M.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Background: Empagliflozin is an effective treatment for heart failure with preserved ejection fraction (HFpEF), but its definite mechanism of action is unclear. Systemic microvascular dysfunction strongly relates to HFpEF aetiology, and we hypothesised that empagliflozin improves microvascular function in HFpEF. Objective: To investigate the effect of the sodium–glucose cotransporter-2 inhibitor empagliflozin on peripheral microvascular function in HFpEF. Methods: This is a pre-post intervention study in patients diagnosed with HFpEF who are eligible for treatment with empagliflozin. Microvascular function assessment using laser speckle contrast analysis of the dorsal forearm during iontophoresis of vasoactive stimuli (acetylcholine, insulin sodium nitroprusside) was performed at baseline and after 3 months of empagliflozin treatment (10 mg daily). The primary outcome was the difference in blood flow measured in the forearm microvasculature between baseline and at follow-up (cutaneous vascular conductance, CVC). Secondarily we investigated quality-of-life based on the EQ-5D-5 L questionnaire at baseline and follow-up. Results: Twenty six patients finished the study according to protocol (mean age of 74 ± 7 years, 62% female). We observed a decreased blood flow response to acetylcholine after 3 months of empagliflozin (CVC: 0.77 ± 0.24 vs. 0.64 ± 0.20, p < 0.001). In contrast, the response to insulin improved (CVC: 0.61 ± 0.43 vs. 0.81 ± 0.32, p = 0.03), and the response to sodium nitroprusside remained stable after 3 months. No significant correlations were found between the changes in blood flow and quality of life. Conclusion: This study shows that three months treatment with empagliflozin changed peripheral microvascular function in patients with HFpEF. Empagliflozin may enhance microvascular blood flow specifically via vascular actions of insulin, rather than a general effect on endothelial vasoregulation or smooth muscle cell function. As such, systemic microvascular dysfunction can be a modifiable factor in patients with HFpEF, while the clinical implications thereof warrant further investigations. Trial registration: The trial was preregistered at clinicaltrials.gov (NCT06046612).
AB - Background: Empagliflozin is an effective treatment for heart failure with preserved ejection fraction (HFpEF), but its definite mechanism of action is unclear. Systemic microvascular dysfunction strongly relates to HFpEF aetiology, and we hypothesised that empagliflozin improves microvascular function in HFpEF. Objective: To investigate the effect of the sodium–glucose cotransporter-2 inhibitor empagliflozin on peripheral microvascular function in HFpEF. Methods: This is a pre-post intervention study in patients diagnosed with HFpEF who are eligible for treatment with empagliflozin. Microvascular function assessment using laser speckle contrast analysis of the dorsal forearm during iontophoresis of vasoactive stimuli (acetylcholine, insulin sodium nitroprusside) was performed at baseline and after 3 months of empagliflozin treatment (10 mg daily). The primary outcome was the difference in blood flow measured in the forearm microvasculature between baseline and at follow-up (cutaneous vascular conductance, CVC). Secondarily we investigated quality-of-life based on the EQ-5D-5 L questionnaire at baseline and follow-up. Results: Twenty six patients finished the study according to protocol (mean age of 74 ± 7 years, 62% female). We observed a decreased blood flow response to acetylcholine after 3 months of empagliflozin (CVC: 0.77 ± 0.24 vs. 0.64 ± 0.20, p < 0.001). In contrast, the response to insulin improved (CVC: 0.61 ± 0.43 vs. 0.81 ± 0.32, p = 0.03), and the response to sodium nitroprusside remained stable after 3 months. No significant correlations were found between the changes in blood flow and quality of life. Conclusion: This study shows that three months treatment with empagliflozin changed peripheral microvascular function in patients with HFpEF. Empagliflozin may enhance microvascular blood flow specifically via vascular actions of insulin, rather than a general effect on endothelial vasoregulation or smooth muscle cell function. As such, systemic microvascular dysfunction can be a modifiable factor in patients with HFpEF, while the clinical implications thereof warrant further investigations. Trial registration: The trial was preregistered at clinicaltrials.gov (NCT06046612).
KW - Acetylcholine
KW - Endothelial function
KW - Heart failure
KW - Insulin
KW - Laser speckle contrast analysis
KW - Microcirculation
KW - Nitroprusside
KW - SGLT-2 inhibitor
UR - https://www.scopus.com/pages/publications/105003743205
U2 - 10.1186/s12933-025-02679-8
DO - 10.1186/s12933-025-02679-8
M3 - Article
C2 - 40281528
AN - SCOPUS:105003743205
SN - 1475-2840
VL - 24
JO - Cardiovascular Diabetology
JF - Cardiovascular Diabetology
IS - 1
M1 - 182
ER -