Adult Congenital Heart Disease, Congenital Heart Disease, Systemic Right Ventricle, Transposition of the Great Arteries, Congenitally Corrected Transposition of the Great Arteries, Fontan, Single Ventricle, Tetralogy of Fallot (TOF)
Conditions
Keywords
adult congenital heart disease, ACHD, congenital heart disease, CHD, sodium-glucose cotransporter 2 inhibitors, SGLT2i, SGLT2, heart failure, HF, transposition of the great arteries, TGA, systemic right ventricle, sRV, Fontan, single ventricle, tetralogy of fallot, ToF
Brief summary
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.
Detailed description
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.
Interventions
DRUGSGLT2 inhibitors
Treatment with any type and dose of sodium-glucose cotransporter 2 inhibitor.
Sponsors
Leiden University Medical Center
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Congenital heart defect. * Age ≥ 18 years. * Initiated on treatment with an SGLT2i.
Exclusion criteria
\- No consent for data collection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prescription patterns | Baseline information. | The primary outcome of this registry is an overview of the prescription patterns of SGLT2i in the ACHD population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Side effects [Safety and Tolerability] | From enrollment through study completion, with an average follow-up duration of 1 year. | Incidence and specification of any experienced side effects. |
| SGLT2i-related complications [Safety and Tolerability] | From enrollment through study completion, with an average follow-up duration of 1 year. | Incidence and specification of any SGLT2i-related complications. |
| SGLT2i discontinuation [Safety and Tolerability] | From enrollment through study completion, with an average follow-up duration of 1 year. | Incidence of any discontinuation of SGLT2i (including reason for discontinuation). |
| Mortality [Safety and Tolerability] | From enrollment through study completion, with an average follow-up duration of 1 year. | Mortality and documentation of cause of death. |
| Admissions [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Documentation of number of hospitalizations, including number of heart failure-related hospitalizations and number of urgent heart failure visits. |
| Clinical parameters - weight [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on weight (kg) |
| Clinical parameters - systolic blood pressure [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on systolic blood pressure (mmHg) |
| Clinical parameters - diastolic blood pressure [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on diastolic blood pressure (mmHg) |
| Clinical parameters - heart rate [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on heart rate (beats per minute) |
| Clinical parameters - saturation [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on oxygen saturation (%) |
| Laboratory parameters - sodium [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on serum sodium (mmol/L) |
| Laboratory parameters - potassium [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on serum potassium (mmol/L) |
| Laboratory parameters - creatinine [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on serum creatinine (µmol/L) |
| Laboratory parameters - eGFR [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on estimated glomerular filtration rate (eGFR, ml/min/1.73m2) |
| Laboratory parameters - NT-proBNP [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on serum NT-proBNP (ng/L) |
| Laboratory parameters - glucose [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on serum glucose (mmol/L) |
| Laboratory parameters - HbA1c [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on serum HbA1c (mmol/mol Hb) |
| Transthoracic echocardiography - LV function [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on systolic left ventricular (LV) function (categorical: good, mildly reduced, moderately reduced, severely reduced function) |
| Transthoracic echocardiography - LV GLS [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on LV global longitudinal strain (GLS, %) assessed with transthoracic echocardiography |
| Transthoracic echocardiography - LV FAC [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on LV fractional area change (FAC, %) assessed with transthoracic echocardiography |
| Transthoracic echocardiography - RV GLS [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on RV GLS (%) assessed with transthoracic echocardiography |
| Transthoracic echocardiography - RV FAC [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on RV FAC (%) assessed with transthoracic echocardiography |
| Transthoracic echocardiography - RV S' [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on RV S' (cm/s) assessed with transthoracic echocardiography |
| Transthoracic echocardiography - TAPSE [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on tricuspid annular plane systolic excursion (TAPSE, mm) assessed with transthoracic echocardiography |
| Exercise parameters - 6MWT [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on exercise parameter 6-minute walk test (6MWT, meters) |
| Exercise parameters - maximum performance [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on maximum performance (Watt) with bicycle ergometry. |
| Exercise parameters - validity [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on validity (%-predicted of the maximum performance) with bicycle ergometry. |
| Exercise parameters - VO2 max [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on VO2 max (mL/kg/min) with bicycle ergometry. |
| Exercise parameters - %-predicted VO2 max [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the longitudinal effect of SGLT2i on %-predicted of VO2 max (% of the VO2 max) with bicycle ergometry. |
| Transthoracic echocardiography - RV function [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | 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 |
| Concomitant medication changes [Heart Failure-related Efficacy] | From enrollment through study completion, with an average follow-up duration of 1 year. | Evaluation of the concomitant changes in other heart failure pharmacotherapy. |
Countries
Germany, Netherlands, North Macedonia, United Kingdom, United States
Contacts
CONTACTRalph M.L. Neijenhuis, MD
CONTACTBjörn N. Westdorp, MD
PRINCIPAL_INVESTIGATORAnastasia D. Egorova, MD PhD
Leiden University Medical Center
Outcome results
None listed