CARDIAC DEVELOPMENT AND CONGENITAL HEART DEFECTS

Congenital heart defects are structural and/or functional abnormalities of the heart present at birth, resulting from an alteration in normal cardiac development during embryonic life. They represent the most common group of congenital malformations, with an incidence of approximately 8-10 cases per 1,000 live births. ---

Cardiac Ontogenesis and Septation

Heart development begins in the third week of embryonic life with the formation of the primitive cardiac tube, which subsequently undergoes folding and subdivision, giving rise to the cardiac chambers.

Role of Neural Crest Cells

Neural crest cells are essential for the formation of the conotruncal region and the separation of the truncus arteriosus into the aorta and pulmonary artery. Defects in their migration are associated with congenital heart defects such as Tetralogy of Fallot and Persistent Truncus Arteriosus.

Molecular Factors in Heart Development

Heart development is regulated by several transcription factors and molecular signals:

NKX2.5, GATA4, TBX5: fundamental for the formation of the cardiac tube and septation.
Notch, BMP, Wnt: involved in the formation of cardiac valves and separation of the great arteries.
Shh (Sonic Hedgehog): influences the arrangement of cardiac chambers and the formation of the interventricular septum.

Atrial Septum

Atrial separation begins in the fourth week with the growth of the septum primum, which extends from the roof of the primitive atrium downward. Initially, there is an opening, the ostium primum, which progressively closes with the fusion of the endocardial cushions. Before complete closure, a second opening, the ostium secundum, forms to maintain interatrial communication.
From the right atrium, the septum secundum subsequently develops, leaving the foramen ovale open, allowing fetal blood flow between the atria. After birth, the foramen ovale closes due to changes in pressure gradients.

Interventricular Septum

In the fourth week, the interventricular septum develops with:

Muscular component, originating from the cardiac apex and growing toward the center of the heart.
Membranous component, derived from the fusion of the endocardial cushions with the conotruncal region.

Fetal Circulation and Transition to Postnatal Life

During fetal life, blood circulation differs significantly from postnatal circulation, as the placenta serves as the organ responsible for gas exchange, replacing pulmonary function.

Adaptations at Birth

With the first breath, the lungs expand, pulmonary vascular resistance drops dramatically, and pulmonary blood flow increases. This results in:

Increased pulmonary venous return, leading to increased left atrial pressure.
Functional closure of the foramen ovale, due to pressure from the septum primum against the septum secundum.
Progressive closure of the ductus arteriosus, due to increased partial oxygen pressure and reduced circulating prostaglandins, leading to anatomical obliteration in the following weeks.
Closure of the ductus venosus, diverting portal flow through the liver.

Prenatal Diagnosis and Neonatal Screening

Fetal echocardiography, performed between the 18th and 22nd weeks of gestation, is the primary tool for prenatal diagnosis of congenital heart defects. After birth, neonatal screening using pulse oximetry is recommended to identify critical congenital heart defects requiring early intervention.

Classification of Congenital Heart Defects

Cyanotic vs. Acyanotic: Cyanotic heart defects cause reduced oxygenation of systemic blood, leading to cyanosis, whereas acyanotic defects do not significantly affect oxygen saturation.
With shunt vs. Without shunt: Some defects involve abnormal blood flow between cardiac chambers (shunt), altering normal circulation. Defects without shunts primarily involve stenosis or valvular anomalies.
Increased or Decreased Pulmonary Blood Flow: Depending on the nature of the malformation, blood flow to the lungs may be increased (leading to pulmonary overload) or reduced (causing systemic hypoxia).

References

Baumgartner H., De Backer J., Babu-Narayan S.V., et al. 2020 ESC Guidelines for the management of adult congenital heart disease. European Heart Journal. 2021;42(6):563-645. doi:10.1093/eurheartj/ehaa554.
Hoffman J.I., Kaplan S. The incidence of congenital heart disease. Journal of the American College of Cardiology. 2002;39(12):1890-1900. doi:10.1016/S0735-1097(02)01886-7.
Reller M.D., Strickland M.J., Riehle-Colarusso T., Mahle W.T., Correa A. Prevalence of congenital heart defects in metropolitan Atlanta, 1998-2005. The Journal of Pediatrics. 2008;153(6):807-813. doi:10.1016/j.jpeds.2008.05.059.
Van der Linde D., Konings E.E.M., Slager M.A., et al. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. Journal of the American College of Cardiology. 2011;58(21):2241-2247. doi:10.1016/j.jacc.2011.08.025.
Geva T., Martins J.D., Wald R.M. Atrial Septal Defects. The Lancet. 2014;383(9932):1921-1932. doi:10.1016/S0140-6736(13)62145-5.