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. 2024 Apr 16;83(15):1403-1414.
doi: 10.1016/j.jacc.2024.02.017. Epub 2024 Mar 25.

Effect of Sodium-Glucose Cotransporter 2 Inhibitors in Adults With Congenital Heart Disease

Ralph M L Neijenhuis  1 , Simon T MacDonald  2 , Filip Zemrak  3 , Bart J A Mertens  4 , Anna Dinsdale  5 , Amanda Hunter  6 , Niki L Walker  6 , Lorna Swan  6 , Sushma Reddy  7 , Joris I Rotmans  8 , J Wouter Jukema  9 , Monique R M Jongbloed  10 , Gruschen R Veldtman  6 , Anastasia D Egorova  11
Affiliations

Effect of Sodium-Glucose Cotransporter 2 Inhibitors in Adults With Congenital Heart Disease

Ralph M L Neijenhuis et al. J Am Coll Cardiol. .

Abstract

Background: Heart failure (HF) is the principal cause of morbidity and mortality in adults with congenital heart disease (ACHD). Robust evidence-based treatment options are lacking.

Objectives: This study aims to evaluate the safety, tolerability, and short-term HF-related effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in a real-world ACHD population.

Methods: All patients with ACHD treated with SGLT2i in 4 European ACHD centers were included in this retrospective study. Data were collected from 1 year before starting SGLT2i to the most recent follow-up. Data on side effects, discontinuation, mortality, and hospitalizations were collected.

Results: In total, 174 patients with ACHD were treated with SGLT2i from April 2016 to July 2023. The mean age was 48.7 ± 15.3 years, 72 (41.4%) were female, and 29 (16.7%) had type 2 diabetes mellitus. Ten (5.7%) patients had mild, 75 (43.1%) moderate, and 89 (51.1%) severe congenital heart disease. HF was the most frequent starting indication (n = 162, 93.1%), followed by type 2 diabetes (n = 11, 6.3%) and chronic kidney disease (n = 1, 0.6%). At median follow-up of 7.7 months (Q1-Q3: 3.9-13.2 months), 18 patients (10.3%) reported side effects, 12 (6.9%) permanently discontinued SGLT2i, and 4 (2.3%) died of SGLT2i-unrelated causes. A significant reduction in the HF hospitalization rate was observed from 6 months before to 6 months after starting SGLT2i (relative rate = 0.30; 95% CI: 0.14-0.62; P = 0.001).

Conclusions: SGLT2i generally seem safe, well-tolerated, and potentially beneficial in patients with ACHD. SGLT2i was associated with a 3-fold reduction in the 6-month HF hospitalization rate. These results warrant prospective randomized investigation of the potential benefits of SGLT2i for patients with ACHD.

Keywords: congenital heart disease; heart failure; pharmacotherapy; sodium-glucose cotransporter 2 inhibitors.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Neijenhuis has received support from the Foundation “De Drie Lichten” (Hilversum, the Netherlands), AstraZeneca, and the Leiden University Medical Center research council Cardio-Vascular cluster Themes for Innovation funding. Dr Zemrak has received speaker fees from Abbott Laboratories. Dr Rotmans has received an unrestricted research grant from AstraZeneca. Dr Jongbloed has received support from the Leiden University Medical Center research council Cardio-Vascular cluster Themes for Innovation funding; and has received a personal grant from the NWO/ZonMw (The Hague, the Netherlands), the Bontius Foundation (Leiden, the Netherlands), and the Rembrandt Institute (Leiden, the Netherlands). Dr Egorova has received support from the Leiden University Medical Center research council Cardio-Vascular cluster Themes for Innovation funding; and has received consultancy and speaker fees from Boston Scientific Corporation and Medtronic Inc. The Department of Cardiology of the Leiden University Medical Center has received unrestricted research and educational grants from Boston Scientific Corporation, Medtronic, and Biotronik. The funders were not involved in study design, collection, analysis, interpretation of data, the writing of this paper, or the decision to submit it for publication. No artificial intelligence programs contributed to the compilation of the submitted manuscript. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

FIGURE 1
FIGURE 1. Increasing Prescription of SGLT2i in the ACHD Population
Cumulative number of patients who started a Sodium-glucose cotransporter 2 inhibitor (SGLT2i) throughout the years, showing a sharp increase in SGLT2i prescription in the adults congenital heart disease (ACHD) population from 2021 onwards. The horizontal red line indicates the total number of patients included in the study (n = 174).
FIGURE 2
FIGURE 2. HF Pharmacotherapy at Baseline
Details on heart failure (HF) pharmacotherapy at baseline in patients who were started on SGLT2i due to HF. Data were available for 160 of 162 patients (98.8%). (A) The number of HF drugs used at baseline. Most patients were on ≥3 HF drugs (68.8%), consisting of the following categories: 1) beta-blockers (BB); 2) angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI); 3) mineralocorticoid receptor antagonist (MRA); and 4) diuretics. (B) Percentage (%) of patients using specific classes of HF drugs at baseline. (C) The most frequently encountered combinations of HF drugs at baseline, excluding diuretics use.
FIGURE 3
FIGURE 3. Freedom From HF Hospitalization
Kaplan-Meier curves show freedom from HF hospitalization in the year after starting SGLT2i in the HF cohort (n = 162). The 2 Kaplan-Meier curves represent patients with an HF hospitalization in the 12 months before starting SGLT2i (yes, blue) and the patients without (no, red). Patients with an HF hospitalization in the year before SGLT2i initiation had a higher risk of (re-)hospitalization (log-rank P = 0.0024). Abbreviations as in Figures 1 and 2.
CENTRAL ILLUSTRATION
CENTRAL ILLUSTRATION. Sodium-Glucose Cotransporter 2 Inhibitors in Adults With Congenital Heart Disease
In this multicenter retrospective cohort study, SGLT2i were safe, well-tolerated and potentially beneficial in 174 ACHD patients. Side effects were observed in 18 patients (10.3%), 9 of whom discontinued SGLT2i therapy. Overall, SGLT2i was permanently discontinued in 12 patients (6.9%). In a subset of 162 ACHD patients with heart failure, a 3-fold reduction in heart failure-hospitalization rate from the 6 months before to the 6 months after starting SGLT2i was observed (P = 0.001). There was no significant reduction in arrhythmia admission rate (P = 0.289). ACHD = adult congenital heart disease; SGLT2i = sodium-glucose cotransporter 2 inhibitor.
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References

    1. Brida M, Lovrić D, Griselli M, Riesgo Gil F, Gatzoulis MA. Heart failure in adults with congenital heart disease. Int J Cardiol. 2022;357: 39–45. - PubMed
    1. Arnaert S, De Meester P, Troost E, et al. Heart failure related to adult congenital heart disease: prevalence, outcome and risk factors. ESC Heart Fail. 2021;8:2940–2950. - PMC - PubMed
    1. Ladouceur M, Valdeolmillos E, Karsenty C, Hascoet S, Moceri P, Le Gloan L. Cardiac drugs in ACHD cardiovascular medicine. J Cardiovasc Dev Dis. 2023;10:190. - PMC - PubMed
    1. Baumgartner H, De Backer J, Babu-Narayan SV, et al. 2020 ESC guidelines for the management of adult congenital heart disease. Eur Heart J. 2021;42:563–645. - PubMed
    1. Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC guideline for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol. 2019;73(12):e81–e192. - PubMed