Role of the Epicardium in the Development of the Atrioventricular Valves and Its Relevance to the Pathogenesis of Myxomatous Valve Disease

This paper is dedicated to the memory of Dr. Adriana “Adri” Gittenberger-de Groot and in appreciation of her work in the field of developmental cardiovascular biology and the legacy that she has left behind. During her impressive career, Dr. Gittenberger-de Groot studied many aspects of heart development, including aspects of cardiac valve formation and disease and the role of the epicardium in the formation of the heart. In this contribution, we review some of the work on the role of epicardially-derived cells (EPDCs) in the development of the atrioventricular valves and their potential involvement in the pathogenesis of myxomatous valve disease (MVD). We provide an overview of critical events in the development of the atrioventricular junction, discuss the role of the epicardium in these events, and illustrate how interfering with molecular mechanisms that are involved in the epicardial-dependent formation of the atrioventricular junction leads to a number of abnormalities. These abnormalities include defects of the AV valves that resemble those observed in humans that suffer from MVD. The studies demonstrate the importance of the epicardium for the proper formation and maturation of the AV valves and show that the possibility of epicardial-associated developmental defects should be taken into consideration when determining the genetic origin and pathogenesis of MVD.

Prenatal evaluation of fetal atrioventricular valves by real-time 4D volume imaging with electronic matrix probe

Background The purpose of this study is to evaluate the feasibility using real-time four-dimensional (RT 4D) volume imaging with electronic matrix probe to observe the morphology of atrioventricular valves in normal and abnormal fetuses, measure the area and circumference of atrioventricular valves in normal fetuses and analyze the correlation with gestational age. Methods RT 4D volume imaging with electronic matrix probe was used to collect cardiac volume data of 162 normal fetuses with the gestational age from 22 to 32 weeks and 19 fetuses with atrioventricular valves abnormalities were also enrolled. All the volume data were analyzed and processed in real-time. The morphology of mitral and tricuspid valves was observed in surface mode. The area and circumference of valves were measured in a 4D render view at the end of diastole and analyzed the correlation with gestational age. Results In 148 of 162 fetuses (91%), the 4D rendered image could be successfully obtained, which clearly showed the morphology of the atrioventricular valves. The area and circumference of mitral and tricuspid valves were positively correlated with gestational age (P < 0.01). Furthermore, 4D rendered images were successfully obtained in 17 of 19 fetuses (89%) with atrioventricular valves abnormalities. Conclusions The reference range of the area and circumference of atrioventricular valves in normal fetuses at different gestational weeks could be determined by using the RT 4D volume imaging with electronic matrix probe, which can provide certain diagnostic information for the clinic. The RT 4D images could display the valves morphology vividly in both normal and abnormal fetuses, including some subtle lesions which are not identified by traditional two-dimensional (2D) echocardiography. It is feasible to use the RT 4D volume imaging with electronic matrix probe to perform the prenatal evaluation in the fetal atrioventricular valves.