Development of the cardiac conduction system and cardiac anatomy in relation to genesis and treatment of arrhythmias

Abstract

Clinical mapping studies demonstrate that cardiac arrhythmias are often encountered at specific anatomical sites. The anatomical development of the heart and the cardiac conduction system are narrowly related. The thesis starts with a Chapter 1 that provides a general overview of the basics of cardiac development, development of the cardiac conduction system, markers for the developing cardiac conduction system and anatomical predilection sites for the occurrence of clinical arrhythmias. Next, attention is focused on clinical arrhythmias in adults in relation to cardiac anatomy, the treatment of these arrhythmias and imaging techniques used to visualise the substrate. Subsequently, in part I (Chapter 2-4) of the thesis, a developmental origin of clinical arrhythmias is hypothesized. The developing cardiac conduction system is studied and a developmental origin of clinical arrhythmias is hypothesized based on the spatial expression pattern of the conduction system marker CCS-lacZ in murine embryos. Furthermore, incorporation of the primitive pulmonary vein in the left atrium is studied in sequential developmental stages in humans. In part II (Chapter 5-10), the treatment of clinical arrhythmias that are initiated and/or perpetuated at specific anatomical locations in the heart (particularly the pulmonary veins) guided by imaging techniques for visualisation of the substrate, is described.