Project details


Life-long myocardial and pulmonary adaptation to abnormal loading conditions in congenital heart disease.

pediatric cardiology congenital heart disease pulmonary hypertension

prof. dr. R.M.F. Berger

Nature of the research:
Within our translational research line, projects can either focus on clinical retrospective and prospective research or on experimental research using animal models of disease.

Fields of study:
cardiology and thoracic surgery pediatrics

Background / introduction
Congenital heart diseases are among the most common congenital malformations. In the Netherlands, 1500 children are born with congenital heart defects every year. The long term outcome of (corrected) congenital heart defects is not yet satisfying. Pulmonary vascular disease and right ventricular failure, due to abnormal loading conditions, remain major problems in the follow up of patients with congenital heart disease. Insight in the adaptation of the heart and vasculature to these abnormal loading conditions will help to improve treatment strategies and will help to prevent pulmonary vascular disease and heart failure. With that, we can enable the rapidly growing population of (corrected) congenital heart disease patients to age healthier.
Our research focuses on the pulmonary vascular and right ventricular mal-adaptation in congenital heart disease and the treatment of pulmonary arterial hypertension. It is a translational research line; we apply the knowledge obtained from our experimental studies to our patient population within clinical our studies.
Our experimental studies involve animal models mimicking pulmonary hypertension and right ventricular failure. In these models, we aim to identify the pathophysiological and molecular pathways involved in right ventricular adaptation and pulmonary vascular disease.
Our clinical research includes retrospective and prospective studies within our population of children with (corrected) congenital heart defects focusing on the types of corrective surgery, their outcome and long term follow-up. Furthermore, within our national cohort of children with pulmonary hypertension (for whom our department is the national referral center), several retrospective and prospective studies can be performed, investigating disease progression, genetics, treatment strategies, treatment effects and outcome of pediatric pulmonary hypertension.
Research question / problem definition
Within our translational research line, several studies are available for student research projects. For example a clinical research project to study the effects and outcome of different treatment strategies in children with pulmonary hypertension and an experimental study aiming to identify transcriptional profiles involved in right ventricular failure, by using microarray analysis to identify targets, which subsequently can be tested in in-vitro studies.
However, we welcome new ideas. Our students can write their own research proposals and new projects can be developed based on the interests and ideas of students.
The research protocols and planning are dependent on the chosen project. Our students have the opportunity to write their own research protocol and develop their own work plan. During this process they will be guided by our PhD-students and principal investigators.
1: Berger RM, Beghetti M, Humpl T, Raskob GE, Ivy DD, Jing ZC, Bonnet D, Schulze-Neick I, Barst RJ. Clinical features of paediatric pulmonary hypertension: a registry study. Lancet. 2012 Feb 11;379(9815):537-46. Epub 2012 Jan 11. PubMed PMID: 22240409.

2: Bartelds B, Borgdorff MA, Smit-van Oosten A, Takens J, Boersma B, Nederhoff MG, Elzenga NJ, van Gilst WH, De Windt LJ, Berger RM. Differential responses of the right ventricle to abnormal loading conditions in mice: pressure vs. volume load. Eur J Heart Fail. 2011 Dec;13(12):1275-82. Epub 2011 Oct 24. PubMed PMID:

3: van Loon RL, Roofthooft MT, Hillege HL, ten Harkel AD, van Osch-Gevers M, Delhaas T, Kapusta L, Strengers JL, Rammeloo L, Clur SA, Mulder BJ, Berger RM. Pediatric pulmonary hypertension in the Netherlands: epidemiology and characterization during the period 1991 to 2005. Circulation. 2011 Oct 18;124(16):1755-64. Epub 2011 Sep 26. PubMed PMID: 21947294.

4: Bartelds B, van Loon RL, Mohaupt S, Wijnberg H, Dickinson MG, Boersma B, Takens J, van Albada M, Berger RM. Mast cell inhibition improves pulmonary vascular remodeling in pulmonary hypertension. Chest. 2012 Mar;141(3):651-60. Epub 2011 Sep 22. PubMed PMID: 21940767.

5: Dickinson MG, Bartelds B, Molema G, Borgdorff MA, Boersma B, Takens J, Weij M, Wichers P, Sietsma H, Berger RM. Egr-1 expression during neointimal development in flow-associated pulmonary hypertension. Am J Pathol. 2011 Nov;179(5):2199-209.
Epub 2011 Sep 13. PubMed PMID: 21924231; PubMed Central PMCID: PMC3204093.

6: Douwes JM, van Loon RL, Hoendermis ES, Vonk-Noordegraaf A, Roofthooft MT, Talsma MD, Hillege HL, Berger RM. Acute pulmonary vasodilator response in paediatric and adult pulmonary arterial hypertension: occurrence and prognostic value when comparing three response criteria. Eur Heart J. 2011 Dec;32(24):3137-46. Epub 2011 Sep 4. PubMed PMID: 21893489.

7: van Loon RL, Roofthooft MT, Delhaas T, van Osch-Gevers M, ten Harkel AD, Strengers JL, Backx A, Hillege HL, Berger RM. Outcome of pediatric patients with pulmonary arterial hypertension in the era of new medical therapies. Am J Cardiol. 2010 Jul 1;106(1):117-24. PubMed PMID: 20609658.

8: van Albada ME, Bartelds B, Wijnberg H, Mohaupt S, Dickinson MG, Schoemaker RG, Kooi K, Gerbens F, Berger RM. Gene expression profile in flow-associated pulmonary arterial hypertension with neointimal lesions. Am J Physiol Lung Cell
Mol Physiol. 2010 Apr;298(4):L483-91. Epub 2009 Dec 18. PubMed PMID: 20023177.

9: van Loon RL, Roofthooft MT, van Osch-Gevers M, Delhaas T, Strengers JL, Blom NA, Backx A, Berger RM. Clinical characterization of pediatric pulmonary hypertension: complex presentation and diagnosis. J Pediatr. 2009 Aug;155(2):176-82.e1. Epub 2009 Jun 12. PubMed PMID: 19524254.
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