TY - JOUR
T1 - Real-world experience with sodium-glucose cotransporter 2 inhibitors in adults with Fontan circulatory failure
AU - Neijenhuis, Ralph M L
AU - Cedars, Ari M
AU - Zaidi, Ali
AU - Torres-Viera, Guillermo
AU - Mazurek, Renata
AU - Walker, Niki L
AU - Zemrak, Filip
AU - MacDonald, Simon T
AU - Hunter, Amanda
AU - Kiès, Philippine
AU - Bosch, Lena
AU - Swan, Lorna
AU - van der Zwaan, Heleen B
AU - Jukema, J Wouter
AU - Jongbloed, Monique R M
AU - Veldtman, Gruschen R
AU - Egorova, Anastasia D
N1 - © 2026 Neijenhuis, Cedars, Zaidi, Torres-Viera, Mazurek, Walker, Zemrak, MacDonald, Hunter, Kiès, Bosch, Swan, van der Zwaan, Jukema, Jongbloed, Veldtman and Egorova.
PY - 2026/5/8
Y1 - 2026/5/8
N2 - BACKGROUND: Patients with Fontan physiology frequently develop Fontan circulatory failure (FCF), but there are no evidence-based pharmacological treatment options.OBJECTIVES: This study evaluated the safety and efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in FCF.METHODS: A real-world, multicenter study of all adult FCF patients included in the international ACHIEVE-SGLT2i registry (NCT06932081) was conducted. Data on side effects, treatment discontinuation, and clinical outcomes were collected. Longitudinal changes in serum biomarkers and clinical parameters from one year before to one year after SGLT2i initiation were evaluated using linear mixed models. Responses between patients with reduced (FCFrEF) vs. preserved ventricular function (FCFpEF) were compared.RESULTS: Thirty-three FCF patients were started on SGLT2i between January 2017 and October 2024. The median age was 32 [20.5-42] years, 17 (51.5%) were female, 11 (33.3%) had FCFrEF, and 22 (66.7%) FCFpEF. Over a median follow-up of 8.0 [3.2-12.2] months, 5 (15.2%) patients reported side effects, of whom 3 (9.1%) permanently discontinued SGLT2i. There were 11 FCF-related hospitalizations in the year before SGLT2i and 7 during follow-up in 9 patients. Blood pressure and renal function remained stable. NT-proBNP increased from 186.3 [116.8-297.1] to 272.6 [180.7-411.3] ng/L in the year before treatment (+46.4%, p = 0.022). In the year after starting SGLT2i, NT-proBNP levels decreased significantly to 200.4 [126.5-317.4] ng/L (-26.5%, p = 0.010), in both FCFrEF and FCFpEF patients.CONCLUSIONS: SGLT2i were safe and well-tolerated in adult patients with FCF. SGLT2i treatment was associated with a reduction in NT-proBNP, regardless of FCF phenotype.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT06932081.
AB - BACKGROUND: Patients with Fontan physiology frequently develop Fontan circulatory failure (FCF), but there are no evidence-based pharmacological treatment options.OBJECTIVES: This study evaluated the safety and efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in FCF.METHODS: A real-world, multicenter study of all adult FCF patients included in the international ACHIEVE-SGLT2i registry (NCT06932081) was conducted. Data on side effects, treatment discontinuation, and clinical outcomes were collected. Longitudinal changes in serum biomarkers and clinical parameters from one year before to one year after SGLT2i initiation were evaluated using linear mixed models. Responses between patients with reduced (FCFrEF) vs. preserved ventricular function (FCFpEF) were compared.RESULTS: Thirty-three FCF patients were started on SGLT2i between January 2017 and October 2024. The median age was 32 [20.5-42] years, 17 (51.5%) were female, 11 (33.3%) had FCFrEF, and 22 (66.7%) FCFpEF. Over a median follow-up of 8.0 [3.2-12.2] months, 5 (15.2%) patients reported side effects, of whom 3 (9.1%) permanently discontinued SGLT2i. There were 11 FCF-related hospitalizations in the year before SGLT2i and 7 during follow-up in 9 patients. Blood pressure and renal function remained stable. NT-proBNP increased from 186.3 [116.8-297.1] to 272.6 [180.7-411.3] ng/L in the year before treatment (+46.4%, p = 0.022). In the year after starting SGLT2i, NT-proBNP levels decreased significantly to 200.4 [126.5-317.4] ng/L (-26.5%, p = 0.010), in both FCFrEF and FCFpEF patients.CONCLUSIONS: SGLT2i were safe and well-tolerated in adult patients with FCF. SGLT2i treatment was associated with a reduction in NT-proBNP, regardless of FCF phenotype.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT06932081.
U2 - 10.3389/fcvm.2026.1771868
DO - 10.3389/fcvm.2026.1771868
M3 - Article
C2 - 42181636
SN - 2297-055X
VL - 13
JO - Frontiers in Cardiovascular Medicine
JF - Frontiers in Cardiovascular Medicine
M1 - 1771868
ER -