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Recruiting NCT02691689

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

No phase Interventional Heart Defects, Congenital Pulmonary Arterial Hypertension Genetic Testing

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Genetic testing.
Who it may be relevant to
Registry conditions: Heart Defects, Congenital, Pulmonary Arterial Hypertension, Genetic Testing. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Belgium
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Interventions

  • Other Genetic testing
    Genetic testing by DNA sequencing on blood samples after DNA extraction

Primary outcome measures

  • Presence of pathogenic mutations in PAH or ASD genes [Time frame: 18 months]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Diagnostic

Study locations

Belgium · 1 center
  • University Hospitals Leuven — Leuven

Identifiers

NCT: NCT02691689 · S57936

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗