Sagacity to Decode Cardiogenesis Mystries: Etiological Perspective of Cardiovascular Malformations

The Birth of etiological studies in the current era: Quarter-Century of our life has been passed while we are still diving in the science of human cardiogenesis and Cardiovascular Malformations. The far away, great dream in the horizon is establishment of cardiogenesis knowledge capable of leading us to intervene and abort the developmental derangement leading to congenital cardiovascular malformation in human species. Knowledge of the epidemiology of congenital heart disease is the basis on which investigative efforts will emerge to identify the causes of cardiac dysmorphogenesis and afford opportunities to prevent them. Anatomical and pathophysiological classification of congenital heart disease was found to be useful in clinical practice but useless or even misleading for investigating etiological factors of congenital heart diseases. We adopted an etiological perspective of congenital heart diseases which in many directions pose no relation to the current anatomical and pathophysiological classification. For example, bicuspid aortic valve which prove to be very common in all races with incidence of 3-5% of world populations, carries no clinical significance until hemodynamically significant gradient developed with aging to yield left ventricular outflow tract obstruction at valvular origin. On the other hand, in our new etiological perspective bicuspid aortic valve is strong developmental land mark for spectrum of congenital malformations of the heart ranging from simple aortic valve disease to the extreme Shones complex with sever hypoplasia of the left ventricle, mitral valve, aortic valve and the aortic arch and branches hypoplasia. Presence of simple spectrum of Shones disease in one family member may point to sever diseases in other family members with mutations in the gene encoding myosin and other shared mutations. On the other hand, clinical diseases with exactly same pharmaceutical treatment plans like muscular ventricular septal defect and supracristal ventricular septal defect, carries two different developmental pathways in our new etiological perspective. We in the current era need to base our approach to investigate cardiogenesis secrets, on embryologic terms but not the pathophysiological grouping which was established for clinical and therapeutic puposes. Viewing cardiac defects from mechanistic rather than strictly anatomical perspective is the true call for wisdom if we are targeting prevention of cardiac dysmorphogenesis in human.