Genes Associated With Development of Pulmonary Arterial Hypertension in Patients With Congenital Shunt Lesions

NCT ID: NCT02691689

Last Updated: 2025-03-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2026-02-28

Brief Summary

Pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) is associated with considerable morbidity and even mortality.

Next to environmental risk factors, the investigators believe that there is an important role of genetic predisposition to develop PAH in CHD. There often is a discrepancy between the severity of PAH and the CHD, where it is useful to screen for PAH gene mutations. The investigators hypothesize that the genotype is partly responsible for the phenotypic variability in patients with congenital shunt lesions, where some develop PAH and others do not. If a genetic predisposition for PAH in CHD could be identified, then genetic screening could be a useful additional tool for early detection of patients at risk of pulmonary vascular disease and PAH development, with new opportunities for prevention or early treatment.

Detailed Description

Pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) usually develops secondary to chronic volume overload of the pulmonary circulation following left to right shunt. This overload leads to elevated pulmonary artery pressure (PAP) and later to increased pulmonary vascular resistance. This causes pressure overload in the right heart, and thereby right ventricular and right atrial dysfunction, which may implicate considerable morbidity and even mortality.

Since PAH nowadays is mostly detected when symptoms occur and PAP are elevated, the disease already evolved to an advanced (partially irreversible) stage and treatment is often initiated too late.

Next to environmental risk factors, the investigators believe that there is an important role of genetic predisposition to develop PAH in CHD. In the past, certain genes have been identified that play a role in the development of atrial septal defect (ASD). There are also a lot of genes identified that play a role in PAH. Until now, not many research groups have studied a genetic link between CHD and PAH development. But it becomes more and more clear that there often is a discrepancy between the severity of PAH and the CHD, where it is useful to screen for PAH gene mutations. The investigators hypothesize that mutations in some of these known PAH genes or in other, still unidentified, genes are partly responsible for the phenotypic variability in patients with congenital shunt lesions, where some develop PAH and others do not. If a genetic predisposition for PAH in CHD could be identified, then genetic screening could be a useful additional tool for early detection of patients at risk of pulmonary vascular disease and PAH development, with new opportunities for prevention or early treatment.

Conditions

Heart Defects, Congenital; Pulmonary Arterial Hypertension; Genetic Testing

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Patients with ASD or VSD and PAH

Group Type: OTHER

Genetic testing

Intervention Type: OTHER

Genetic testing by DNA sequencing on blood samples after DNA extraction

Interventions

Genetic testing

Genetic testing by DNA sequencing on blood samples after DNA extraction

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Previous diagnosis of secundum atrial septal defect (ASD) or ventricular septal defect (VSD), with or without repair
• Development of PAH, defined as mean PAP ≥ 25 mmHg by right heart catheterization, in combination with a pulmonary wedge pressure of ≤ 15 mmHg and a PVR (pulmonary vascular resistance) of > 3 Wood units
• Preferably, families with congenital shunt lesions (at least three family members affected with ASD or VSD) will be considered for inclusion

Exclusion Criteria

• Other congenital heart disease
• Mental retardation
• Dysmorphic characteristics
• Chronic lung disease or total lung capacity < 80% of predicted value
• History of pulmonary embolism

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

prof. dr. Werner Budts

Werner Budts, MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Werner Budts, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Universitaire Ziekenhuizen KU Leuven

Locations

University Hospitals Leuven

Leuven, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Werner Budts, MD, PhD

Role: CONTACT

werner.budts@uzleuven.be

+32 16 344369

Charlien Gabriels, MD

Role: CONTACT

charlien.gabriels@uzleuven.be

+32 16 341486

Facility Contacts

Werner Budts, MD, PhD

Role: primary

werner.budts@uzleuven.be

+32 16 344369

Charlien Gabriels, MD

Role: backup

charlien.gabriels@uzleuven.be

+32 16 341486

Other Identifiers

S57936

Identifier Type: -

Identifier Source: org_study_id