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This real-world, international registry aims to evaluate the current experience with sodium-glucose cotransporter 2 inhibitors (SGLT2i) in adult congenital heart disease (ACHD) patients by investigating the prescription patterns, safety, tolerability, and potential beneficial effects on heart failure-related outcomes.
In the adult congenital heart disease (ACHD) population, heart failure currently represents the main cause of morbidity and mortality. The etiology of ACHD-related heart failure is heterogenous, and there is limited evidence for pharmacological treatment options for this population.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel pillar in the treatment of conventional LV heart failure. SGLT2i have been shown to reduce the risk of worsening heart failure and cardiovascular-related death in patients with LV heart failure.
While the exact mechanisms of action are still to be elucidated, SGLT2i seem to address heart failure by targeting several pathways. These include but are not limited to; a decrease in renin-angiotensin and sympathetic nervous system activation, a decrease in pressure overload-induced myocardial fibrosis, reverse cardiac remodeling, and improvement in myocardial energetics.
Given the compelling evidence on the effectiveness of SGLT2i over a broad range of cardiac dysfunction and initial promising reports of its utilization in the field of ACHD, SGLT2i deserve further exploration in the group of ACHD patients.
This real-world, international registry aims to evaluate the current experience with SGLT2i in ACHD patients by investigating the prescription patterns, safety, tolerability, and potential beneficial effects on heart failure-related outcomes.
Project design:
Data of all ACHD patients who were started on an SGLT2i will be collected in a real-world, international registry. Only data resulting from routine clinical care will be collected from the electronic health records at the participating centers, and participants will not undergo any interventions for this project. Data will be collected from 1 year before starting with the SGLT2i to most recent follow-up after starting with the SGLT2i, to evaluate if SGLT2i therapy halts the progression of clinical deterioration in ACHD patients with heart failure and can improve heart failure-related outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ACHD patients treated with SGLT2i | All participants included in the registry have to have a congenital heart defect, be ≥ 18 years old, and receive (or have received) treatment with SGLT2i. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SGLT2 inhibitors | Drug | Treatment with any type and dose of sodium-glucose cotransporter 2 inhibitor. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Prescription patterns | The primary outcome of this registry is an overview of the prescription patterns of SGLT2i in the ACHD population. | Baseline information. |
| Measure | Description | Time Frame |
|---|---|---|
| Side effects [Safety and Tolerability] | Incidence and specification of any experienced side effects. | From enrollment through study completion, with an average follow-up duration of 1 year. |
| SGLT2i-related complications [Safety and Tolerability] |
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Inclusion Criteria:
Exclusion Criteria:
- No consent for data collection.
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All adult patients (≥ 18 years) with congenital heart disease who have been treated with an SGLT2i are eligible for inclusion in the registry.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ralph M.L. Neijenhuis, MD | Contact | +31 71 5262020 | r.m.l.neijenhuis@lumc.nl | |
| Björn N. Westdorp, MD | Contact | +31 71 5262020 | b.n.westdorp@lumc.nl |
| Name | Affiliation | Role |
|---|---|---|
| Anastasia D. Egorova, MD PhD | Leiden University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins University | Recruiting | Baltimore | Maryland | 21205 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40695536 | Result | Neijenhuis RM, Regeer MV, Walker NL, Mertens BJ, Hunter A, Kies P, Swan L, Vliegen HW, MacDonald ST, Zemrak F, Zaidi AN, Cedars AM, Jongbloed MR, Jukema JW, Veldtman GR, Egorova AD. Effect of sodium-glucose cotransporter 2 inhibitors on ventricular function in systemic right ventricular failure. Open Heart. 2025 Jul 21;12(2):e003445. doi: 10.1136/openhrt-2025-003445. | |
| 40689152 |
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Incidence and specification of any SGLT2i-related complications.
| From enrollment through study completion, with an average follow-up duration of 1 year. |
| SGLT2i discontinuation [Safety and Tolerability] | Incidence of any discontinuation of SGLT2i (including reason for discontinuation). | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Mortality [Safety and Tolerability] | Mortality and documentation of cause of death. | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Admissions [Heart Failure-related Efficacy] | Documentation of number of hospitalizations, including number of heart failure-related hospitalizations and number of urgent heart failure visits. | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Clinical parameters - weight [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on weight (kg) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Clinical parameters - systolic blood pressure [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on systolic blood pressure (mmHg) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Clinical parameters - diastolic blood pressure [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on diastolic blood pressure (mmHg) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Clinical parameters - heart rate [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on heart rate (beats per minute) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Clinical parameters - saturation [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on oxygen saturation (%) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Laboratory parameters - sodium [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on serum sodium (mmol/L) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Laboratory parameters - potassium [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on serum potassium (mmol/L) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Laboratory parameters - creatinine [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on serum creatinine (µmol/L) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Laboratory parameters - eGFR [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on estimated glomerular filtration rate (eGFR, ml/min/1.73m2) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Laboratory parameters - NT-proBNP [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on serum NT-proBNP (ng/L) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Laboratory parameters - glucose [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on serum glucose (mmol/L) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Laboratory parameters - HbA1c [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on serum HbA1c (mmol/mol Hb) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Transthoracic echocardiography - LV function [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on systolic left ventricular (LV) function (categorical: good, mildly reduced, moderately reduced, severely reduced function) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Transthoracic echocardiography - LV GLS [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on LV global longitudinal strain (GLS, %) assessed with transthoracic echocardiography | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Transthoracic echocardiography - LV FAC [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on LV fractional area change (FAC, %) assessed with transthoracic echocardiography | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Transthoracic echocardiography - RV function [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on systolic right ventricular (RV) function (categorical: good, mildly reduced, moderately reduced, severely reduced function) assessed with transthoracic echocardiography | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Transthoracic echocardiography - RV GLS [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on RV GLS (%) assessed with transthoracic echocardiography | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Transthoracic echocardiography - RV FAC [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on RV FAC (%) assessed with transthoracic echocardiography | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Transthoracic echocardiography - RV S' [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on RV S' (cm/s) assessed with transthoracic echocardiography | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Transthoracic echocardiography - TAPSE [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on tricuspid annular plane systolic excursion (TAPSE, mm) assessed with transthoracic echocardiography | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Exercise parameters - 6MWT [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on exercise parameter 6-minute walk test (6MWT, meters) | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Exercise parameters - maximum performance [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on maximum performance (Watt) with bicycle ergometry. | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Exercise parameters - validity [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on validity (%-predicted of the maximum performance) with bicycle ergometry. | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Exercise parameters - VO2 max [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on VO2 max (mL/kg/min) with bicycle ergometry. | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Exercise parameters - %-predicted VO2 max [Heart Failure-related Efficacy] | Evaluation of the longitudinal effect of SGLT2i on %-predicted of VO2 max (% of the VO2 max) with bicycle ergometry. | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Concomitant medication changes [Heart Failure-related Efficacy] | Evaluation of the concomitant changes in other heart failure pharmacotherapy. | From enrollment through study completion, with an average follow-up duration of 1 year. |
| Helen DeVos Children's Hospital | Recruiting | Grand Rapids | Michigan | 49503 | United States |
|
| Mount Sinai Fuster Heart Hospital | Recruiting | New York | New York | 10029 | United States |
|
| Heart Center Duisburg (Evangelical Hospital Niederrhein) | Recruiting | Duisburg | Germany |
|
| Leiden University Medical Center (LUMC) | Recruiting | Leiden | South Holland | 2333ZA | Netherlands |
|
| Amsterdam University Medical Center | Recruiting | Amsterdam | Netherlands |
|
| University Medical Center Utrecht | Recruiting | Utrecht | Netherlands |
|
| Zan Mitrev Clinic | Recruiting | Skopje | North Macedonia |
|
| University Hospital of Wales | Recruiting | Cardiff | United Kingdom |
|
| Golden Jubilee University National Hospital | Recruiting | Glasgow | United Kingdom |
|
| Barts Heart Centre | Recruiting | London | United Kingdom |
|
| Neijenhuis RML, Regeer MV, Walker NL, Hunter A, Kies P, Holman ER, Jukema JW, Jongbloed MRM, Veldtman GR, Egorova AD. Echocardiographic effects of sodium-glucose cotransporter 2 inhibitors in single ventricle circulatory failure. Int J Cardiol Congenit Heart Dis. 2025 Jun 21;21:100603. doi: 10.1016/j.ijcchd.2025.100603. eCollection 2025 Sep. |
| 38530688 | Result | Neijenhuis RML, MacDonald ST, Zemrak F, Mertens BJA, Dinsdale A, Hunter A, Walker NL, Swan L, Reddy S, Rotmans JI, Jukema JW, Jongbloed MRM, Veldtman GR, Egorova AD. Effect of Sodium-Glucose Cotransporter 2 Inhibitors in Adults With Congenital Heart Disease. J Am Coll Cardiol. 2024 Apr 16;83(15):1403-1414. doi: 10.1016/j.jacc.2024.02.017. Epub 2024 Mar 25. |
| 37435053 | Result | Neijenhuis RML, Nederend M, Jongbloed MRM, Kies P, Rotmans JI, Vliegen HW, Jukema JW, Egorova AD. The potential of sodium-glucose cotransporter 2 inhibitors for the treatment of systemic right ventricular failure in adults with congenital heart disease. Front Cardiovasc Med. 2023 Jun 26;10:1093201. doi: 10.3389/fcvm.2023.1093201. eCollection 2023. |
| 35355435 | Result | Egorova AD, Nederend M, Tops LF, Vliegen HW, Jongbloed MRM, Kies P. The first experience with sodium-glucose cotransporter 2 inhibitor for the treatment of systemic right ventricular failure. ESC Heart Fail. 2022 Jun;9(3):2007-2012. doi: 10.1002/ehf2.13871. Epub 2022 Mar 30. |
| 42181636 | Derived | Neijenhuis RML, Cedars AM, Zaidi A, Torres-Viera G, Mazurek R, Walker NL, Zemrak F, MacDonald ST, Hunter A, Kies P, Bosch L, Swan L, van der Zwaan HB, Jukema JW, Jongbloed MRM, Veldtman GR, Egorova AD. Real-world experience with sodium-glucose cotransporter 2 inhibitors in adults with Fontan circulatory failure. Front Cardiovasc Med. 2026 May 8;13:1771868. doi: 10.3389/fcvm.2026.1771868. eCollection 2026. |
| ID | Term |
|---|---|
| D006330 | Heart Defects, Congenital |
| D014188 | Transposition of Great Vessels |
| D000080041 | Congenitally Corrected Transposition of the Great Arteries |
| D000080039 | Univentricular Heart |
| D013771 | Tetralogy of Fallot |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| D000077203 | Sodium-Glucose Transporter 2 Inhibitors |
| ID | Term |
|---|---|
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D007004 | Hypoglycemic Agents |
| D045505 | Physiological Effects of Drugs |
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