Abnormal, asynchronous electrical activation of the ventricles originate from intrinsic conduction abnormalities, such as left bundle branch block, and from ventricular pacing. Such electrical abnormalities lead to a variety of derangements: local differences in myofiber shortening and workload, reduced pump function, local and global remodeling.
The research in this program pays attention to scientific applications and clinical problems and opportunities of these consequences of asynchrony:
1. Improve cardiac resynchronization therapy (CRT) for patients with reduced pump function
2. Search pacing site(s) that are best for adult and pediatric patients requiring pacemaker therapy for antibradicardic therapy
3. Electrical remodeling due to mechano-electrical feedback in normal and failing hearts
4. Intermittent ventricular pacing for cardioprotection: mechanisms and applications
Ad 1. Currently CRT is indicated for all patients with severe heart failure and a wide QRS complex. Yet, improvements provided by CRT vary strongly between patients. Potential points of improvements are: optimization of atrioventricular and interventricular delays, better pacing sites and better selection of patients that receive CRT. To this purpose we investigate the use of various biomarkers (mechanical, electrophysiological and molecular). Usefulness of electrical and mechanical biomarkers and optimal choice of pacing sites may further be improved by combining biomarker data with mathematical models of the heart. Recent studies have shown that such “patient-specific modeling” can unveil myocardial properties that are not readily recognizable from the electrocardiogram and or echocardiogram. These studies are largely part of the CTMM grant “Biomarkers to predict cardiac failure, arrhythmias, and success of treatment”, acollaborative effort of five Dutch academic centers. Research on mathematical modelling is also supported by a Portfolio grant from the board of the Maastricht University. Recent animal studies in our laboratory show that major improvement of electrophysiological and hemodynamic effects of CRT can be achieved by choosing a better left ventricular (LV) pacing site (endocardial in stead of conventional LV epicardial (coronary sinus), strategic positioning with respect to a scar or infarction. These concepts and ideas are being translated to the clinical setting.
Ad 2. Conventional right ventricular pacing has adverse effects on cardiac pump function in adults and, even more, in children with pacemakers. In a combination of preclinical and clinical work we are investigating what pacing sites are best. For many patients the LV endocardium of the interventricular septum and the LV apex appear to provide the best conditions. We are developing new approaches toget at these sites and will investigate the benefits of pacing at these sites in patients.
Ad 3. In a combination of animal experimental, clinical and computer simulation studies we investigate the idea that local action potential duration is regulated by local stretch or workload. Such a regulation by “mechano-electrical feedback” (MEF) could explain phenomena like the T-wave being concordant with the QRS complex and the “T-wavememory” after stopping ventricular pacing. Implications for the presence or absence of MEF for cardiac function and arrhythmia are investigated.
Ad 4. In previous animal experiments we discovered “pacing pre and post conditioning”. Data from the recently completed clinical PROTECT trial in patients with acute myocardial infarction support the idea that brief periods of ventricular pacing can be used to reduce infarct size. Mechanistic studies indicate that mechanical stimuli rather than G-protein receptors trigger this kind of protection. Further studies will focus on further elucidation of the cellular mechanism and on further clinical application.
Main research topic: regional cardiac mechanics and long-term structural and functional adaptations to various conditions, with emphasis on asynchronousÂ electrical activation and cardiac resynchronization. Primarily animal experimental work, but with important links to Biomedical Engineering (computer models of cardiac electrophysiology and mechanics) and Cardiology (patients with pacemakers, bundle branch block, heart failure)., With this background Prof. Prinzen is a world expert on pacing therapies, both for bradycardia and for heart failure (cardiac resynchronization therapy, CRT).,