Cardiology 2

Cardiac Dysfunction and Arrhythmias

Principal investigator

Prof.Dr M.J. Schalij, Prof.Dr J.J. Bax

Aim and focus

To investigate the interrelationship between cardiac dysfunction and arrhythmias. This programme consists of cardiovascular diseases due to diminished right and/or left ventricular dysfunction and due to arrhythmias.   

Content / highlights / achievements

In this programme novel therapies for patients with heart failure are studied. Determination of interventricular and intraventricular dyssynchrony of segmental contraction has resulted in improvement of criteria for cardiac resynchronization therapy. New techniques to diagnose and quantify asynchronous contraction by speckle tracking analysis and evaluation of apical and basal twist have extended the methodology to select patients for cardiac resynchronization therapy, as well as assess efficacy of this therapy. Surgical therapy to treat mitral regurgitation and to reshape left ventricular geometry is assessed in close collaboration with the Department of Cardiothoracic Surgery. In laboratory studies it is investigated in what ways bone marrow-derived mesenchymal stem cells (MSCs) could be used to regenerate damaged myocardium. In a multi-electrode array system it has been found that MSCs are able to resynchronize two asynchronously contracting fields of neonatal rat cardiomyocytes by formation of gap junctions between cardiomyocytes and MSCs and between individual MSCs. In collaboration with the Department of Molecular Cell Biology, section Gene Therapy, MSCs are transfected with viral constructs containing transcription factor genes that are supposed to cause differentiation of MSCs into cardiomyocytes.

The programme “Cardiac Dysfunction and Arrhythmias” includes research of atrial and ventricular arrhythmias. For complex catheter ablation procedures several imaging modalities are integrated with 3-dimensional electrical mapping systems to pinpoint the anatomic structures and areas to be treated, and to improve the success of the intervention. Treatment of complex arrhythmias now also involves therapy of children with serious rhythm disturbances (in cooperation with the Department of Pediatrics) and therapy of patients with genetically determined arrhythmias (in cooperation with the Department of Clinical Genetics). Genetic factors implicated in the development of specialized conduction tissue in the heart are studied in fetal chicken heart operated upon in ovo and in hearts of transgenic mice in collaboration with the Department of Anatomy and Embryology.

Recently, the Department of Cardiology has started aortic valve replacements by using percutaneously introduced catheters carrying the folded valve to be deployed in the aortic root. Another approach of aortic valve implantation using a minimally invasive surgical procedure through the apex of the left ventricle is developed in cooperation with the Department of Cardiothoracic Surgery.   

In the research cluster entitled “Adult Congenital Heart Disease” the Department of Cardiology has joined the nation-wide registry called CONCOR. Research is focused on optimal care for patients with tetralogy of Fallot, in whom replacement of the pulmonary valve should be timed dependent on the severity of right ventricular dilatation.  

Future themes

By improving integration of several imaging modalities (intravascular echocardiography, nuclear cardiology, MRI, multislice CT, and NOGA) we aim to optimize diagnosis and interventions in patients with complicated atrial and ventricular dysrhythmias, as well as in patients with heart failure. More programmes will be developed to implement current guidelines for specific patient groups, thereby improving patient care with respect to diagnosis and therapy.   

Cohesion within the LUMC

In this programme the Department of Cardiology cooperates intensively with the Departments of Cardiothoracic Surgery, Anatomy and Embryology, Molecular Cell Biology, Hematology, Radiology and Nuclear Medicine.

Key publications

Borleffs CJW, van Erven L, Kies P, van der Burg AEB, van der Wall EE, Schalij MJ, Bax JJ.
Incidence of ventricular arrhythmias in ischemic secondary prevention ICD recipients: Long-term follow-up of the Leiden out-of-hospital cardiac arrest study. J Am Coll Cardiol 2008; 51: 16-26.
IF 11.054

Delgado V, Ypenburg C, van Bommel RJ, Tops LF, Mollema SA, Marsan NA, Bleeker GB, Schalij MJ, Bax JJ. Assessment of left ventricular dyssynchrony by speckle tracking strain imaging - Comparison between longitudinal, circumferential, and radial strain in cardiac resynchronization therapy. J Am Coll Cardiol 2008; 51: 1944-52.
IF 11.054

GademanMGJ, van Bommel RJ, Ypenburg C, Haest JCW, Schalij MJ, van der Wall EE, Bax JJ, Swenne CA. Biventricular pacing in chronic heart failure acutely facilitates the arterial baroreflex. Am J Physiol Heart Circ Physiol 2008; 295: H755-H760.
IF 3.973

Henkens IR, Mouchaers KTB, Vonk-Noordegraaf A, Boonstra A, Swenne CA, Maan AC, Man SC, Twisk JWR, van der Wall EE, Schalij MJ, Vliegen HW. Improved ECG detection of presence and severity of right ventricular pressure load validated with cardiac magnetic resonance imaging. Am J Physiol Heart Circ Physiol 2008; 294: 2150-H2157.
IF 3.973

Kolditz DP, Wijffels MCEF, Blom NA, van der Laarse A, Hahurij ND, Lie-Venema H, Markwald RR, Poelmann RE, Schalij MJ, Gittenberger-de Groot AC. Epicardium-derived cells in development of annulus fibrosis and persistence of accessory pathways. Circulation 2008; 117: 1508-17.
IF 12.755

Pijnappels DA, Schalij MJ, Ramkisoensing AA, van Tuyn J, de Vries AAF, van der Laarse A, Ypey DL, Atsma DE. Forced alignment of mesenchymal stem cells undergoing cardiomyogenic differentiation affects functional integration with cardiomyocyte cultures. Circ Res 2008; 103: 167-76.
IF 9.721

Tops LF, Wood DA, Delgado V, Schuijt JD, van der Wall EE, Schalij MJ, Webb JG, Bax JJ. Noninvasive evaluation of the aortic root with multislice computed tomography: Implications for transcatheter aortic valve replacement. J Am Coll Cardiol 2008; 51: 151-61.
IF 11.054

Tops LF, Delgado V, Schuijf JD, Brugada J, Schalij MJ, Thomas JD, Bax JJ. Assessment of mitral valve anatomy and geometry with multislice computed tomography. J Am Coll Cardiol 2008; 51: 151-61.
IF 11.054

Ypenburg C, van Bommel RJ, Delgado V, Mollema SA, Bleeker GB, Boersma E, Schalij MJ, Bax JJ. Optimal left ventricular lead position predicts reverse remodeling and survival after cardiac resynchronization therapy. J Am Coll Cardiol 2008; 52: 1402-9.
IF 11.054

Ypenburg C, Lancellotti P, Tops LF, Boersma E, Bleeker GB, Holman ER, Thomas JD, Schalij MJ, Pierard LA, Bax JJ. Acute versus late reduction in mitral regurgitation after cardiac resynchronization therapy. J Am Coll Cardiol 2008; 51: 13-23.
IF 11.054