Pulmonary atresia with intact ventricular septum: Second heart field derived myocardial and epicardial developmental clues

Abstract

Pulmonary atresia with intact ventricular septum is a severe cardiac malformation that is ductus dependent and needs immediate postnatal care. The phenotype is characterized by three levels of pathology that are considered important for diagnosis and the choice of cardiac surgery. The pathology concerns an hypoplasia and hypertrophy of the right ventricle in which there is a variation in the involvement of the inlet, trabecular and outflow part of the right ventricle. There is also a variable degree of tricuspid valve pathology including hypoplasia and stenosis. The pulmonary valve is atretic which may have been preceded, in the fetal stage, by pulmonary stenosis. This latter phenomenon may be triggered by the severe coronary anomalies that are found in about 30% of the patients. This coronary anomaly is characterized by ventriculo-coronary arterial communications which is accompanied by sometimes severe main coronary artery pathology including interruptions of the main branches. In the latter situation the coronary myocardial perfusion becomes right ventricular dependent. Current cardiac developmental data show that the right ventricular myocardium is derived from the second heart field. Its anterior part contributes this myocardium to the outflow tract and is also employed by the neural crest cells to enter the heart. The posterior second heart field provides the epicardium derived cells (EPDC) that are important for myocardial wall compaction and formation of the coronary vasculature. We hypothesize that pulmonary atresia with intact ventricular septum without ventriculo-coronary arterial communications is primarily based on anterior SHF directed outflow tract septation anomalies, while pulmonary atresia with intact ventricular septum with ventriculo-coronary arterial communications has an additional major problem related to epicardium derived contribution. Developmentally they can therefore be considered as two different diseases that might need separate treatment protocols.