Pathophysiology Prior to birth, the fetus receives oxygen from maternal blood in the placenta, rather than from

its own pulmonary circulation. In utero, the fetal heart's various passageways allow most blood to bypass the nonfunctioning lungs. Fetal blood pressure is higher in the pulmonary circulation due to the resistance to blood flow in the pulmonary vessels. At the time of birth and in the period shortly after birth, the fetal circulatory system is altered by the closure of the heart's bypass systems. At this point, the fetal circulatory system reverses and assumes a higher pressure in the systemic circulatory system. However, the fetal heart's vessels and passageways do not always close properly. When this happens, the HLHS infant's right ventricular output is split between the systemic and pulmonary circulations. These circulations are completely dependent upon the patency of the ductus arteriosus. Frequently, the ductus arteriosus closes a few days following birth. Prior to closure, signs of inadequate systemic perfusion are absent. In HLHS infants, the closure of the ductus arteriosus signals metabolic acidosis and low systemic perfusion. Without immediate surgical and medical intervention, the HLHS neonate will experience circulatory collapse, progressive metabolic acidosis, and death

Pathophysiology
After birth, 3 factors affect the hemodynamic status of infants with HLHS10: a decrease in pulmonary vascular resistance (PVR), the size of the interatrial communication, and involution and closure of the PDA. With parallel circulation, pulmonary and systemic blood flow is determined by the ratio of PVR to systemic vascular resistance (SVR). The ratio of pulmonary blood flow to systemic blood flow ( p/ s) describes how the cardiac output from the single ventricle is partitioned. After birth, the PVR gradually decreases during the first several days of life, resulting in increasing pulmonary blood flow. With this increase in pulmonary blood flow, the volume load on the right ventricle also increases. An infant may have increases in systemic oxygen saturation but be at risk for progressive congestive heart failure and decreased systemic perfusion because of the inadequate size and function of the left-sided cardiac structures, including the mitral valve, left ventricle, aortic valve, and ascending aorta. These multiple sites of left-sided obstruction cause diminished aortic blood flow and subsequent reduced coronary artery flow. In HLHS, coronary flow depends on retrograde flow during diastole from the PDA into the small ascending aorta. With the ductus arteriosus open, most infants with HLHS can maintain a balance between PVR and SVR, resulting in appropriate pulmonary and systemic perfusion.10,11 However, if a marked discrepancy occurs in blood flow to the pulmonary and systemic circulations, rapid onset of hemodynamic instability may occur. The most common scenario resulting in an increase in the p/ s ratio is excessive pulmonary flow at the expense of systemic flow. Conversely, low SVR or high PVR results in decreased pulmonary blood flow and a marked decrease in oxygen saturation. Without prompt attention, either of these conditions can result in rapid decompensation. The character of the interatrial communication is a major determinant of pulmonary blood flow.11 The left ventricle accepts little to no blood flow, so the interatrial communication provides the only route for the pulmonary venous blood to exit the left atrium. If an infant has a small, restrictive interatrial communication, the result is increased left atrial and pulmonary venous pressures. In extreme cases, the restrictive interatrial communication will result in profound hypoxemia and decreased pulmonary blood flow. In infants with an unobstructed, large interatrial communication, the blood flow from the left atrium to the right atrium increases as the PVR decreases, and volume overload of the right ventricle and systemic hypoperfusion may occur. The PDA is a normal fetal structure that typically constricts and closes shortly after birth. As the PDA begins to close, blood is diverted from the systemic circulation to the pulmonary circulation. Increased flow to the lungs results in pulmonary congestion and a corresponding increase in the PaO2 and oxygen saturation. Because the ductus arteriosus provides the source of blood flow to both the coronary arteries and the descending aorta, as it continues to constrict, progressive systemic and coronary hypoperfusion occurs, ultimately resulting in a profound shock state.

Pathophysiology of HLHS: Infants with HLHS have a complex cardiovascular physiology. These infants have fully saturated pulmonary venous blood returning to the left atrium (from the lungs) that cannot flow into the left ventricle and to the rest of the body due to atresia, hypoplasia or stenosis of the mitral valve. To compensate for this lack of oxygenated blood flow, blood must cross the atrial septum and mix with desaturated systemic venous blood which is in the right atrium. Mixed venous blood is then sent to the right ventricle which now has the job of moving blood both to the lungs as well as the systemic circulation (this is done by moving blood through the Ductus Arteriosus). The end result is that poorly oxygenated blood is sent through the systemic circulation causing a plethora of system conditions such as poor perfusion, metabolic acidosis and organ failure. Because coronary artery and cerebral perfusion are also dependent on systemic circulation through the Ductus Arteriosus; the infant is at risk for myocardial and/or cerebral ischemia as well.

Pathophysiology
Prenatal circulation The oxygenated blood from the placenta is returned to the inferior vena cava and is not shunted preferentially across the patent foramen ovale into the left atrium; instead, it mixes with the superior vena caval blood in the right atrium. The pulmonary veins drain into the left atrium, and the pulmonary venous blood gets shunted across the atrial septum into the right atrium because of mitral valve obstruction. The vena caval and pulmonary venous blood along with the coronary sinus flow enters the right ventricle and the pulmonary artery.13,14 Because of widely patent ductus arteriosus and high pulmonary vascular resistance in the fetus, a small portion of the blood from the right heart enters the lungs. Most of the blood is directed into the aorta via the ductus. Once in the aorta, the blood gets distributed into the brachiocephalic vessels, ascending aorta, and descending aorta. The quantitative distribution into these different vascular beds depends on their relative vascular resistances. The ascending aortic blood flows in a reverse direction and supplies the coronary arteries. The fetal hypoplastic left heart syndrome circulation differs from the normal fetus in the following manner: y Larger quantity of flow across the ductus with a higher PO2: Whether these factors influence the development of ductal musculature, which may, in turn, influence postnatal ductal closure, is unclear. Lower PO2 and questionably lower blood flow to the brain: The weight of the brain is generally normal, although no detailed studies on the cellular development of brain have been performed. However, whether the reported association between brain anomalies and hypoplastic left heart syndrome is related to abnormal flow and PO2 to the brain remains unknown. Higher PO2 to the lungs: The low PO2 in the pulmonary artery blood in the normal fetus is believed to be responsible for development of muscular pulmonary arterioles. Higher-than-normal PO2 in hypoplastic left heart syndrome may lead to lack of normal medial muscular hypertrophy, which may result in rapid decline of pulmonary vascular resistance after birth.

Retrograde coronary blood flow via a long channel with lower PO2: This abnormality is not believed to interfere with supply of normal quantities of oxygen and nutrients to the myocardium. However, whether myocardial reserve is adversely affected is unclear.

Postnatal circulation The newborn infant with hypoplastic left heart syndrome has a complex cardiovascular physiology. Fully saturated pulmonary venous blood returning to the left atrium cannot flow into the left ventricle because of atresia, hypoplasia, or stenosis of the mitral valve. Therefore, pulmonary venous blood must cross the atrial septum. In most babies, a patent foramen ovale is present and is small and partially obstructive.15 This blood mixes with desaturated systemic venous blood in the right atrium. The right ventricle then must pump this mixed blood to both the pulmonary and the systemic circulations that are connected in parallel, rather than in series, by the ductus arteriosus. Blood exiting the right ventricle may flow (1) to the lungs via the branch pulmonary arteries or (2) to the body via the ductus arteriosus. The amount of blood that flows into each circulation is based on the resistance in each circuit.6,13 Blood flow is inversely proportional to resistance (Ohm law); that is, when resistance in blood vessels decreases, blood flow through these vessels increases. Following birth, pulmonary vascular resistance decreases, which allows a higher percentage of the fixed right ventricular output to go to the lungs instead of the body. Although increased pulmonary blood flow results in higher oxygen saturation, systemic blood flow is decreased. Perfusion becomes poor, and metabolic acidosis and oliguria may develop. Coronary artery and cerebral perfusion also depend on blood flow through the ductus arteriosus and then retrograde flow via the aortic arch and ascending aorta. Therefore, increased pulmonary blood flow results in decreased flow to the coronary arteries and brain, with a risk of myocardial or cerebral ischemia. Alternatively, if pulmonary vascular resistance is significantly higher than systemic vascular resistance, systemic blood flow is increased at the expense of pulmonary blood flow. This may result in hypoxemia. A delicate balance between pulmonary and systemic vascular resistances should be maintained to ensure adequate oxygenation and tissue perfusion. Most patients with hypoplastic left heart syndrome also have coarctation of the aorta. This can be significant enough to interfere with retrograde flow to the proximal aorta. In summary, the postnatal circulation in hypoplastic left heart syndrome depends on 3 major factors: 1. Adequacy of interatrial communication 2. Patency of the ductus arteriosus 3. level of pulmonary vascular resistance