Congenital and Structural Cardiovascular Diseases

Congenital heart defects are the most common congenital defects in newborns with an incidence of 1 in 100 newborns. Mortality of patients with congenital heart disease has significantly decreased over the last decades due to improvements in (prenatal) diagnosis, immediate care after birth, as well as improved surgical, percutaneous and pharmacological treatment modalities.

Although is it still the main cause of death under the age of 15, about 90% of the children with a congenital heart defect reaches adulthood nowadays. The increase in life-expectancy of these patients, as well as the complexity of the abnormalities, lead to a spectrum of long-term complications, such as neurodevelopmental impairment,  arrhythmias, and heart failure. 

The LUMC as part of the Center for Congenital Heart Disease Amsterdam-Leiden (CAHAL), is an expertise center for congenital heart disease and part of the European Reference Network for rare cardiac diseases GuardHeart. Congenital heart disease research in the LUMC focuses on innovation of pre- and postnatal diagnostic tools and imaging, pathophysiology and treatment of heart failure, pulmonary hypertension, and arrhythmias from fetal life until adulthood, involving collaborating research groups from the departments of Anatomy and Embryology, Cardiology, Cardiothoracic Surgery, Pediatric Cardiology,  Obstetrics and Radiology.

During intra-uterine life research is focused on optimization of screening and diagnosis, exploration of innovative imaging techniques, including the use of artificial intelligence, and fetal surgery for valve stenoses (Prof. Haak, Prof. Lamb). The prenatal cases are systematically, prospectively registered in the largest fetal registry globally (PRECOR), at which a biobank is added (fetal/maternal/paternal blood and tissue). To goal of this biobank is to enable research on the origin of congenital heart defects and pathophysiological pathways leading to impairment of fetal growth and (neuro)development of these fetuses.

In children as well as in adults clinical studies focus on development, evaluation and continuous optimization of treatment strategies in complex congenital disease patients using advanced echocardiographic techniques, CT based 3D printing, and MRI techniques such as 4D flow (Dr. Holman, Dr. Kies, Dr. Regeer , Dr. Ten Harkel, Dr. Roest, Dr. van der Palen, Dr. Westenberg, Prof. Lamb, Dr. Kroft, Prof. Hazekamp).

Special focus is directed towards understanding of failure of the Fontan circulation in the palliative approach of single ventricle heart defects (Dr. Roest, Prof. Hazekamp). Collaboration with the computational fluid dynamics groups within the Medical Delta allows to take steps towards a virtual intervention platform to predict the hemodynamic effects of changes in the cardiovascular system. Furthermore, study of the effects of complex flow patterns within the cardiovascular system and more specific the Fontan circulation circulation on a molecular level is currently initiated. Subsequently, research is directed towards the construction of  tissue engineered solutions for Fontan failure (Dr. Jongbloed, Dr. Roest, Prof. Goumans, Prof Hazekamp).

The research of the ACHD team (Dr. Jongbloed, Dr. Vliegen, Dr. Kies, Dr. Egorova) focusses on treatment strategies in adult patients with a failing (systemic) right ventricle and Fontan circulation, anomalous coronary arteries, ECG related parameters in congenital heart disease and pulmonary hypertension, as well as on the introduction of new techniques to improve quality of life and 3D printing for educational and procedural planning purposes. The LUMC is a national referral center for advanced systemic right ventricular heart failure and ventricular assist device implantation as ‘destination therapy’ in this patient group. The ACHD group also has the leading role in the national MuSCAT trial (Multicenter Study on Coronary Anomalies in The Netherlands).

Basic research focusses on the development of new prosthetic heart valves (supported by external organizations, Prof. Hazekamp), as well on (patho)morphological developmental aspects of congenital cardiovascular diseases.

Within this theme the studies on primary and secondary pulmonary hypertension are incorporated as well. Pulmonary hypertension and the role of the TGFβ/BMPR2 are also addressed in collaboration with Prof. Goumans’ group, while the specific form of pulmonary hypertension. CTEPH is also addressed from a clinical point is relation with coagulation disorders (Prof. Klok).

Arrythmias are another aspect of acquired heart diseases. Clinical and basic research activities involving pathophysiology and treatment of atrial and ventricular arrhythmias are concentrated in this theme supervised by Prof. Zeppenfeld. Sequelae of cardiac damage in terms of arrhythmias related to pathological fibrosis and innervation patterns, are also studied in (transgenic) animal models as well as in human tissues in collaboration with the Department of Anatomy and Embryology (Prof. de Ruiter, Dr. Jongbloed). The basic and translational research within the Laboratory of Experimental Cardiology led by Prof. Pijnappels, involves the development of the so-called “Bio-ICD”: here biologists, physicians, engineers, and mathematicians investigate how to enable the heart to correct arrhythmias itself by genetic modification of basic cellular electrophysiological characteristics, which is currently explored by means of optogenetics. For this and other purposes, under the guidance of Dr. de Vries advanced lentivirus, adenovirus and adeno-associated virus vectors are produced and utilized. 

Valvular heart disease (VHD) is a pillar of the Department of Cardiology for both clinical care and basic and clinical research. The Departments of Cardiology (Prof. J.J. Bax, Dr. N. Ajmone Marsan, Dr. F .van der Kley) and Cardiothoracic surgery (Prof. R.J. Klautz, Dr. M. Palmen, Dr. J. Hjortnaes) are world recognized experts in the field and offer the most advanced diagnostic approaches and a large spectrum of the most modern treatment options for the different VHD. Particularly, LUMC is an heart valve center which receives specific referrals for surgical valve repair (both for aortic and mitral valve, and also using robotic techniques) and for transcatheter valvular interventions (including aortic, mitral  and tricuspid valve disease). Extensive clinical research is therefore conducted on the optimization of patient diagnosis, risk stratification and selection and outcome of the different surgical and transcatheter interventions, with >30 PhD students dedicated so far and >500 publications in peer-reviewed journals, including national and international guidelines and expert consensus documents on the topic. The group has also international collaborations with other heart valve centers, participates in large international randomized trials and in international training activities (also within the European society of Cardiology-ESC and Cardiothoracic surgery-EACTS).

Basic research program in the field of VHD is also highly developed. The genetical and developmental aspects of mitral valve prolapse (and specifically  Barlow’s disease) combined with the clinical characteristics are the topic of a large translational research project (Dr. N. Ajmone Marsan, Dr. D. Barge-Schaapveld, Dr. B. Kruithof) which has led already to important discoveries on the pathophysiology of this disease and in advances in diagnostic and therapeutic treatment, and for which LUMC has become a national referral center also for family screening. Also two new unique ex-vivo mouse and human models have been developed to study the pathophysiological mechanisms behind aortic valve stenosis, which have won the Clinical Established Investigator Dekkersbeurs (Dr. Nina Ajmone Marsan) for the development of new medical therapy for aortic stenosis. In addition, aortic pathology in patients with bicuspid aortic valve disease and connective tissue disorders is the topic of another ongoing study (led by Dr. Grewal).  

The non-invasive cardio-vascular imaging unit of the LUMC (Prof. J.J. Bax and N. Ajmone Marsan) is well renown internationally for the all-round expertise in multi-modalities imaging. The expertise includes advanced echocardiographic techniques (strain imaging, 3d Echocardiography, fusion imaging, guidance of interventional procedures), but also (in collaboration with the Radiology Department) multi-detector row computed tomography (also ultrafast volumetric CT imaging), magnetic resonance imaging (also realtime flow imaging and 4D flow imaging) and nuclear imaging. Their extensive use is not only in VHD but also in cardiomyopathies, heart failure, systemic disease, cardiac arrhythmias, coronary artery disease and congenital heart disease. Extensive research is performed on the clinical applications of these imaging modalities, also supporting all other research activities within the CV theme. Prof J.J. Bax and Dr.N. Ajmone Marsan host therefore regularly  international fellows for training and research in cardiovascular imaging and are highly involved within ESC and the board of the European Association of Cardiovascular Imaging for Education and Training activities.