Real-World Experience with Sodium-Glucose Cotransporter 2 Inhibitors in Adults with Fontan Circulatory Failure.

Authors

• Ralph M L Neijenhuis
• Ari M. Cedars
• Ali Zaidi
• Guillermo Torres-Viera
• Renata Mazurek
• Niki L. Walker
• Filip Zemrak
• Simon T. MacDonald
• Amanda Hunter
• Gruschen R Veldtman

Document Type

Article

Publication Date

5-2026

Publication Title

Frontiers in Cardiovascular Medicine

Abstract

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%,

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.

Volume

13

First Page

1771868

Last Page

1771868

Recommended Citation

Neijenhuis RML, Cedars AM, Zaidi A, Torres-Viera G, Mazurek R, Walker NL, et al. [Veldtman GR]. Real-world experience with sodium-glucose cotransporter 2 inhibitors in adults with Fontan circulatory failure. Front Cardiovasc Med. 2026;13:1771868. doi: 10.3389/fcvm.2026.1771868. PMID: 42181636.

Comments

Helen DeVos Children’s Hospital

DOI

10.3389/fcvm.2026.1771868

ISSN

2297-055X

PubMed ID

42181636