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

Prospective, Monocentric Pilot Study for the Identification of Known or Novel Genes Associated With Development of Pulmonary Arterial Hypertension in Patients With Congenital Shunt Lesions

Sponsors

Lead Sponsor: Universitaire Ziekenhuizen Leuven

Source Universitaire Ziekenhuizen Leuven
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.

Overall Status Unknown status
Start Date November 2015
Completion Date June 2017
Primary Completion Date June 2017
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Presence of pathogenic mutations in PAH or ASD genes 18 months
Enrollment 21
Condition
Intervention

Intervention Type: Other

Intervention Name: Genetic testing

Description: Genetic testing by DNA sequencing on blood samples after DNA extraction

Arm Group Label: Patients with ASD or VSD and PAH

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Werner Budts, MD, PhD Principal Investigator Universitaire Ziekenhuizen Leuven
Overall Contact

Last Name: Werner Budts, MD, PhD

Phone: +32 16 344369

Email: [email protected]

Location
Facility: Status: Contact: Contact Backup: Investigator: University Hospitals Leuven Werner Budts, MD, PhD +32 16 344369 [email protected] Charlien Gabriels, MD Sub-Investigator
Location Countries

Belgium

Verification Date

May 2017

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Universitaire Ziekenhuizen Leuven

Investigator Full Name: prof. dr. Werner Budts

Investigator Title: Werner Budts, MD, PhD

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Patients with ASD or VSD and PAH

Type: Other

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Diagnostic

Masking: None (Open Label)

Source: ClinicalTrials.gov