Improving Care for Children With Congenital Heart Disease.

Improving Care for Children With Congenital Heart Disease by Cardiovascular Biomarker Profiling and Advanced Non-invasive Cardiac Imaging Techniques.

Establish a cardiovascular biomarker profile to help screening for congenital heart disease in infants and children as well as use non-invasive cardiac imaging in combination with such profiling to better predict the need for future cardiac interventions such as open heart surgery or cardiac catheter intervention selected types of with congenital heart disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases; Atrial Septal Defect; Patent Ductus Arteriosus; Ventricular Septal Defect; Aortopulmonary Window; Heart Disease Congenital; Partial Anomalous Pulmonary Venous Connection
• Intervention / Treatment: Diagnostic test: Biomarker analysis at enrolment; Diagnostic test: Biomarker analyses throughout the study

Detailed Description

Analyzing circulating cardiovascular biomarkers using blood samples should improve identification of congenital heart disease in newborns, in particular for those needing future cardiac interventions.

Comparing such biomarker profiles and non-invasive cardiac imaging results over time in infants and children should lead to better understanding of the complex cardiovascular remodeling processes in common congenital heart lesions such as atrial or ventricular septal defects. This in turn should lead to an improved risk factor assessment model to guide treatment decisions in children with congenital heart disease in the foreseeable future.

To test our hypothesis, that cardiovascular biomarker profiling and non-invasive cardiac imaging findings in infants and children with congenital heart disease, differs from healthy controls, we will assess controls at enrolment and follow cases with predefined congenital heart disease lesions over a maximum of three years or up till one year after open heart surgery / cardiac catheter intervention to correct such lesions.

Infants and children resident in designated healthcare regions of Sweden will be invited to participate after study advertisement. Written informed consent will be obtained from legal guardians and assent will be sought from children who can communicate verbally with the dedicated paediatric research team.

Healthy subjects 0-17 years at enrolment will undergo standard electrocardiogram (ECG), echocardiography and blood sampling to evaluate the heart's anatomy and function and to obtain samples for subsequent biomarker analyses.

Additionally, saliva will be sampled and/or neonatal blood samples from national biobank storage will be retrieved for comparison with cardiovascular biomarker profiles in these controls if available.

To evaluate these cardiovascular assessments in predefined age groups, a subgroup of these participating subjects will be asked to complete additional cardiac magnetic resonance imaging based on study protocols.

Incidental findings will be followed up according to standard care protocols in designated paediatric cardiology clinics throughout the participating healthcare regions in Sweden.

Cases of congenital heart disease that lead to pulmonary over-circulation, such as atrial and ventricular septal defects, partial anomalous pulmonary venous drainage, aort-pulmonary windows and patent ductus arterious, will be asked to participate if the lesion has not been treated by open heart surgery or cardiac catheter interventions at enrolment.

Subjects with these predefined types of congenital heart disease aged 0-17 years at enrolment will undergo standard electrocardiograms (ECG), echocardiography and blood sampling to assess biomarkers at baseline and at 6-12 month follow-up intervals in dedicated paediatric cardiology clinics over a maximum period of three years.

Saliva samples and/or cardiovascular tissue obtained during open heart surgery may also be analysed for studied cardiovascular biomarkers. Additionally, neonatal blood samples from national biobank storage will be retrieved for comparison with current biomarker profiles if available.

For those congenital heart disease cases referred for open heart surgery or cardiac catheter intervention to correct the congenital heart lesion based on standard care assessment decisions during the study period, follow-up will end one year after such intervention.

To evaluate cardiovascular assessments in predefined age groups, a subgroup of participating cases will be asked to complete additional cardiac magnetic resonance imaging based on study protocols.

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Skania
    • Lund, Skania, Sweden, 221 85
      • Children's Heart Centre at Lund's University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• obtained written informed consent prior to enrolment
• resident within participating healthcare regions in Sweden during study
• age 0-17 years at enrolment
• Controls: No evidence of congenital heart disease and no history of cardiovascular disease
• Cases: one of the following congenital heart lesions prior to open heart surgery or cardiac catheter intervention: ventricular septal defect, atrial septal defect, patent ductus arteriosus, partial anomalous pulmonary venous drainage, aortopulmonary window.

Exclusion Criteria:

• inability to obtain written informed consent prior to study enrolment
• non-resident in participating healthcare regions of Sweden during study
• age more than 17 years at enrolment
• presence of congenital heart disease where one of the above lesions is part of a more complex lesion or where the lesion has been treated by open heart surgery or cardiac catheter intervention
• participation in other research study with conflicting aims / interests

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control subjects; Infants and Children with no evidence of congenital heart disease based on echocardiography and standard ECG assessment
Active Comparator: Congenital heart disease subjects; Infants and Children with evidence of predefined congenital heart disease lesions based on echocardiography and standard ECG assessment	Diagnostic test: Biomarker analysis at enrolment; Controls will be compared to cases using biomarker analyses and non-invasive cardiac imaging techniques to improve risk stratification of cases; Other Names: non-invasive cardiac imaging modalities at enrolment; Diagnostic test: Biomarker analyses throughout the study; Controls will be compared to cases using biomarker analyses and non-invasive cardiac imaging techniques to improve risk stratification of cases; Other Names: non-invasive cardiac imaging modalities throughout the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days from diagnosis to open-heart surgery or cardiac catheter intervention in predefined congenital heart disease lesions	Number of days from date of diagnosis of predefined congenital heart disease lesion until date of open-heart surgery or cardiac catheter intervention to treat lesion	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Screening for congenital heart disease in newborns using circulating biomarkers in blood samples	Results will be based on circulating biomarker analysis in infants using dried blood spot samples to improve detection of congenital heart disease. Results in normal controls will be compared to predefined congenital heart disease lesions and results expressed in ng/l using cardiovascular biomarkers such as NT-pro-BNP, ST2 and troponin T.	3 years
Circulating cardiovascular protein biomarker profiling in infants and children with predefined congenital heart disease lesions vs normal controls using blood samples.	Circulating biomarker profiling results will be expressed in 'NPX' units (Normalized Protein eXpression concentrations from proximity extension assay analyses of protein concentrations in blood samples using O-link's 'Target 96 cardiovascular III' panel, link: https://www.olink.com/products/cvd-iii-panel/)	3 years
Measurement of cardiac magnetic resonance 4-dimensional flows to estimate 'kinetic energy' supported by advanced echocardiography in normal controls vs predefined lesions of congenital heart disease	Results will be based on cardiac magnetic resonance 4D flow and supported by advanced echocardiographic assessments and expressed as kinetic energy (milli Joule) to assess for normal and abnormal patterns of cardiac function.	3 years

Collaborators and Investigators

• Sponsor: Lund University Hospital
• Collaborators: Göteborg University; Region Jönköping County
• Investigators: Principal Investigator: Henning Clausen, MD, Children's Heart Centre, University Hospital of Lund

Publications and helpful links

Helpful Links

• pilote phase publication (open access)

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2020
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: October 26, 2020
• First Submitted That Met QC Criteria: December 11, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: congenital heart disease
• Additional Relevant MeSH Terms: Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Cardiovascular Diseases; Heart Septal Defects; Heart Septal Defects, Atrial; Heart Defects, Congenital; Heart Septal Defects, Ventricular; Ductus Arteriosus, Patent
• Other Study ID Numbers: 2019-05490

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymised clinical data relevant to the publication process of peer-reviewed scientific journals may be made available on request.
• IPD Sharing Time Frame: December 2024
• IPD Sharing Access Criteria: After conclusion of the study, anonymised clinical data may be may available after reasonable request to medical researcher in recognised non-profit academic institutions
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No