provide a grade and detailed feedback for the following text: "Congenital heart disease (CHD) are structural abnormalities of the heart or great vessels which occur during fetal development and commonly create intracardiac shunts with abnormal blood pathways and flow. The incidence of live births with a congenital heart anomaly is approximately 1% worldwide (Shahjehan & Abraham, 2023). The management of patients may vary depending on the type of CHD and severity and ranges from clinical observation to surgical repair facilitated with cardiopulmonary bypass (CPB)(Sun et al., 2015). The following literature review will differentiate several cyanotic and acyanotic congenital heart lesions, aiming to provide a more in-depth look at some of the more common and clinically significant congenital heart defects (CHD) relevant to cardiovascular perfusion practice, including atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA), Tetralogy of Fallot (TOF), and transposition of the great arteries (TGA). Pathophysiology, etiology, clinical manifestations, diagnostics and treatments of each included CHD will also be reviewed. Furthermore, considerations for CPB management and circuit design, the effects of CPB support, and the role of the perfusionist will be examined. 
Background & Etiology
The etiology of CHD is not fully understood; however, it is widely believed that a combination of genetic predisposition and environmental factors contribute to many cases (Sun et al., 2015). CHD often presents in isolation but may also be associated with certain genetic syndromes, such as trisomy 21 (Shahjehan & Abraham, 2023). CHD pathologies can be classified into two types of lesions based on the presence or absence of cyanosis: cyanotic and acyanotic CHDs. Cyanosis occurs with low blood oxygen saturation, resulting in a bluish discoloration of the skin and mucous membranes (Shahjehan & Abraham, 2023). Acyanotic CHD is characterized by a left-to-right intracardiac shunt, resulting in increased pulmonary blood flow, congestion, and pulmonary arterial hypertension (PAH) in severe cases. The most prevalent types of acyanotic CHD include atrial septal defect (ASD), ventricular septal defect (VSD), and patent ductus arteriosus (PDA)(Shahjehan & Abraham, 2023). In contrast, cyanotic CHD involves a right-to-left intracardiac shunt, causing hypoxemia and cyanosis. Some of the most frequent cyanotic CHDs include Tetralogy of Fallot (TOF) and transposition of the great arteries (TGA)(Ossa et al., 2023). Treatment options will vary on a case-by-case basis and may include medical management, cardiac catheterization, or surgical intervention (Sun et al., 2015).
Acyanotic Disorders
Atrial Septal Defect
ASD is among the most common CHD, affecting nearly 1.6 per 1000 live births (Menillo et al., 2023). ASD is a defect of the interatrial septum, the myocardium (septum primum and septum secundum) located between the left and right atria, which fails to close during atrial septation of fetal heart development. The secundum ASD is the most common, accounting for nearly 70% of ASD pathologies (Menillo et al., 2023).
There are four different types of ASD (see Appendix, Table 1.), which vary primarily by anatomical location. Notably, a patent foramen ovale (PFO) is not considered a true ASD as it is a normal in-utero interatrial communication; however, it may fail to close after birth (Lilly et al., 2021). The clinical presentation of ASD is also variable due to the several possible anatomical locations and presenting lesion size and severity. Most ASDs will cause a left-to-right intracardiac shunting of blood, resulting in increased right-heart and pulmonary pressures; severe cases may result in PAH and right heart failure. Minor defects often remain asymptomatic and may evade clinical detection until well into adulthood. In contrast, larger ASDs create more significant intracardiac shunts, which may result in hemodynamic alterations due to the volume overload experienced by the right heart and pulmonary circulation (Menillo et al., 2023). 
Symptomatic ASD may present with fatigue, shortness of breath (SOB), palpitations, and arrhythmias. A diagnosis of ASD is established through physical exam findings, electrocardiogram (ECG), chest x-ray (CXR), transthoracic echocardiography (TTE)(or transesophageal [TEE]), computed tomography (CT), and magnetic resonance imaging (MRI). In addition, patients may require medications for rate control of dysrhythmias and anticoagulation to reduce the risk of thromboembolic events. Individuals with ASD <5 mm frequently experience spontaneous closure within the first year of life. Defects larger than 1 cm will typically require medical or surgical management. Closure options for ASD include percutaneous transcatheter ASD closure and open-heart surgery with CPB (Menillo et al., 2023).
Ventricular Septal Defect
VSD is the most common CHD in children (~37%) and the second most frequent cardiac anomaly in adults (Dakkak & Oliver, 2023). The incidence of VSD is approximately 1.5-3.5 per 1000 live births (Lilly et al., 2021). A VSD diagnosis describes a ventricular septation defect in which interventricular septal tissue fusion fails, resulting in interventricular communication between the left ventricle (LV) and right ventricle (RV)(left-to-right shunt). VSDs are frequently isolated defects; however, they may also occur in association with other CHD (ASD, PDA)(Dakkak & Oliver, 2023).
Similar to ASD, VSD also has four clinical subtypes and are categorized by their anatomical interventricular septal location (See Appendix, Table 2.); the membranous (type II) VSD accounts for nearly 80% of all VSD pathologies (Dakkak & Oliver, 2023). The development of a left-to-right shunt is the primary pathological mechanism of VSD. The hemodynamic significance of the VSD will depend on the anatomical location and size of the defect. Small VSDs have minimal shunting and are frequently asymptomatic. In contrast, those with moderate to large VSD may present with LV volume overload, PAH, and congestive heart failure (CHF); reversal of shunt direction (Eisenmenger syndrome) is possible with severe pulmonary vascular disease, resulting in signs and symptoms of heart failure such as fatigue, dyspnea, shortness of breath, and cyanosis (Lilly et al., 2021).
Diagnosing VSD is achieved through physical assessment findings, ECG, CXR, TTE or TEE with colour-doppler visualization, cardiac catheterization, CT, or MRI. Asymptomatic patients without PAH have an excellent prognosis with medical management alone (Dakkak & Oliver, 2023). However, for patients that have developed PAH and Eisenmenger syndrome, an interventional repair is often indicated due to hemodynamic significant shunting and development of heart failure; VSD repair may be accomplished with percutaneous VSD closure or with CPB-facilitated surgical repair (Dakkak & Oliver, 2023).
Patent Ductus Arteriosus
The ductus arteriosus is a fetal shunt that allows oxygenated blood from the placenta to bypass the lungs in-utero: the pulmonary artery and the ascending aorta are connected by the ductus arteriosus during fetal development. Following birth, the first fetal breaths cause pulmonary vascular resistance to drop and blood to flow into pulmonary circulation for oxygenation resulting in constriction and closure of the ductus arteriosus. Reduced levels of circulating prostaglandins aid in the closure of the PDA following birth (Gillam-Krakauer & Mahajan, 2023). PDA occurs in approximately 1/2500-5000 live births (Lilley et al., 2021). The pathophysiology of PDA involves the smooth muscle of the ductus arteriosus, which fails to close following birth, and results in a persistent left-to-right shunt between the descending aorta and the left pulmonary artery. PDA can lead the LV dilation and left-sided heart failure, resulting in symptoms of CHF (dyspnea, SOB, fatigue), tachycardia, and arrhythmias, such as atrial fibrillation. Eisenmenger syndrome may develop with shunt reversal (right-to-left) due to CHF from severe PDA, resulting in peripheral cyanosis due to the shunting of blood with reduced oxygen tension into the descending aorta. Small PDAs generally remain asymptomatic (Gillam-Krakauer & Mahajan, 2023).
Clinical presentation will depend on the size of the PDA shunt and may include signs of CHF and lower extremity cyanosis if Eisenmenger syndrome is present. Diagnosis of PDA is established based on physical assessments, CXR, ECG, echocardiography, and cardiac catheterization. Patients with small PDA are commonly referred for closure via surgical ligation or transcatheter approach with occluding device placement following a trial of prostaglandin synthesis inhibitors to constrict the PDA (Lilley et al., 2021).
Cyanotic Disorders
Tetralogy of Fallot
Tetralogy of Fallot (TOF) is the most common form of cyanotic CHD (5 per 10,000 live births)(Lilley et al., 2021). TOF results from an abnormal anterior and cephalad displacement of the interventricular septum's infundibular (outflow tract) portion. Four intracardiac anomalies comprise TOF resulting in systemic hypoxemia and cyanosis: VSD, pulmonic stenosis, an overriding aorta that receives blood from both ventricles and right ventricular hypertrophy (Lilley et al., 2021). TOF causes deoxygenated blood to be shunted (right-to-left) from the RV through the VSD, the LV, and into systemic circulation; increased sub-valvular pulmonic stenosis causes deoxygenated blood to be diverted toward the VSD. In addition, TOF is associated with microdeletion of chromosome 22 and is frequently observed with other abnormalities such as ASD and right-sided aortic arch (Diaz-Frias & Guillaume, 2023). 
Clinical manifestations of TOF often present in the form of “Tet Spells,” which commonly occur with dyspnea on exertion (irritability, crying) and result in cyanosis (digits, lips, mucous membranes), hyperventilation, and potential syncope. Children often alleviate these symptoms by squatting down – this is postulated to increase systemic vascular resistance and decrease the effects of the right-to-left shunt, improving pulmonary and cerebral oxygenation (Diaz-Frias & Guillaume, 2023). 
The diagnosis of TOF is established with conventional investigation techniques, such as physical assessment, ECG, CXR, and echocardiography. TOF often presents with RV hypertrophy and is readily identified. Within the first year of life, treatment of TOF requires definitive surgical repair with CPB support to facilitate closure of the VSD and enlargement of the sub-pulmonary infundibulum (Lilley et al., 2021).
Transposition of the Great Arteries 
TGA is a lethal, severe cyanotic CHD and medical emergency requiring prompt intervention. TGA involves inappropriate great vessel origin of the aorta and pulmonary artery trunk and occurs in approximately 7% of all CHD (Lilley et al., 2021). In-utero, TGA is compatible with life due to systemic oxygenation that occurs via the umbilical vein, which passes across the PDA and PFO to provide oxygenated blood to the body; closure of the ductus arteriosus and foramen ovale after birth will result in the child’s death unless prostaglandin therapy is initiated to promote shunt patency or surgical intervention to current transposition is undertaken (Szymanski et al., 2023). Patients with TGA often appear blue due to cyanosis; however, the intensity of cyanosis will depend on the variability of the mixing of the two parallel circulatory circuits. Generally, cyanosis worsens from the first day of life onward as primordial cardiac shunts begin to close (Lilley et al., 2021). 
Worsening cyanosis is an indicator for diagnostic evaluation. Diagnosis of TGA is facilitated with physical assessment, ECG, CXR, echocardiogram, and advanced imaging such as CT and MRI. Signs of RV hypertrophy may be apparent as the heart attempts to compensate for hypoxemia from blood with reduced oxygen content (Szymanski et al., 2023). Initial treatment of TGA may utilize prostaglandin therapy to promote shunt patency of additional CHD commonly found with TGA or the creation of an interatrial shunt with a percutaneous catheter (Rashkind procedure) to facilitate improved arterial oxygenation (Lilley et al., 2021). The definitive repair for TGA is an “arterial switch” procedure utilizing CPB, which involves transposing the great vessels to establish conventional cardiopulmonary circulation (Lilley et al., 2021).
Perfusion Considerations
Surgical repair of CHD requiring CPB necessitates several cardiovascular perfusion considerations to optimize patient safety and positive outcomes; additionally, a perfusionist should be in the room for all standby off-pump cardiac surgery if urgent CPB is required. Patient size has several consequences on the management of CPB. Utilizing the perspective of pediatric CHD surgery, the perfusionist must make several considerations for circuit adaptations, such as smaller diameter tubing to reduce hemodilution and the use of roller pumps for their precise operation at low RPM (Boettcher et al., 2020). Furthermore, many considerations are made by the perfusionist concerning the prime of the circuit, which is often comprised of PlasmaLyte-A (crystalloid), blood products (red blood cells, albumin), and several medications such as heparin, mannitol, sodium bicarbonate, calcium, and magnesium (Boettcher et al., 2020; Gravlee, 2018). All blood products and medications are weight-based in pediatric perfusion because small patients have small blood volumes. Pediatric CPB repairs also require special considerations for cannulation, and venting of the heart, due to their smaller anatomy and the presence of CHD (Whiting et al., 2015). Additional pediatric strategies for CPB include the use of offline modified ultrafiltration (MUF), a therapy employed at the end of a CPB run to predominantly remove activated inflammatory mediators and reduce hemodilution; MUF has been shown to reduce postoperative transfusion requirements and ICU length of stay (Gravlee, 2018). Moreover, pediatric procedures requiring deep hypothermic arrest may utilize a combination of alpha-stat and pH-stat blood gas management strategies (Gravlee, 2018).
Conclusion
Congenital heart disease (CHD) is a structural abnormality of the heart or great vessels which occurs during fetal development and can create intracardiac shunts with abnormal blood pathways and flow. CHD pathologies can be classified into two types of lesions based on the presence or absence of cyanosis: cyanotic and acyanotic CHD. Acyanotic CHD is characterized by a left-to-right intracardiac shunt, resulting in increased pulmonary blood flow. In contrast, cyanotic CHD involves a right-to-left intracardiac shunt, causing hypoxemia and cyanosis. Management of patients with CHD may vary depending on the type and severity of CHD and may include clinical observation, cardiac catheterization, or surgical repair facilitated with CPB. This review differentiated several cyanotic and acyanotic congenital heart lesions, providing an in-depth look at some of the more common and clinically significant CHDs relevant to cardiovascular perfusion practice, including pathophysiology, etiology, clinical manifestations, diagnostics, treatments, CPB management, circuit design, the effects of CPB support, and the role of the perfusionist. Proper identification, diagnosis, and timely management of CHD are crucial for achieving better outcomes and improving the quality of life for patients with CHD."