Pediatric simple pulmonary artery ostium stenosis

　　First, the cause of the disease

　　During the first three months of embryogenesis, the fetus can develop pulmonary artery stenosis due to various reasons. Two important causes are worth mentioning: one is environmental factors, that is, rubella syndrome, and the other is familial genetic factors. If the mother is infected with rubella in the first three months of pregnancy, it can cause rubella syndrome in the fetus, manifested as cataracts, deafness, and cardiovascular malformations, among which the most common cardiovascular malformation is pulmonary artery stenosis, which can also be pulmonary valve stenosis. Recently, familial pulmonary valve stenosis has been found, with an incidence rate of 2.9% among brothers; in other syndromes, such as Noonan syndrome, there may also be pulmonary valve stenosis, but the etiology of most patients has not been confirmed. The aortic semilunar valve develops from the prominence and intercalated (intercalated) prominence of the aorta. The anterior leaflet of the pulmonary valve comes from the left intercalated prominence, and the left and right leaflets respectively come from the left and right subclavian artery prominences. The valve leaflets are fused by the separation between these embryonic tissues. The mechanism of pulmonary artery stenosis is still unclear. If there is no trace of valve leaflet fusion on the valve leaflets, it is speculated that there was no separation between the artery trunk or intercalated prominence in the early stage of embryonic development. If there are connective tissue bundles or suture marks on the valve leaflets, it may be caused by fusion between the valve leaflets in the late stage of embryonic development. Some believe that fetal endocarditis is related to the occurrence of valve stenosis.

　　2. Pathogenesis

　　Pulmonary artery orifice stenosis includes stenosis of the pulmonary valve, pulmonary artery infundibulum, pulmonary artery trunk, and its branches. The clinical incidence rate accounts for 4% to 10% of congenital heart disease, with a roughly equal male-to-female ratio. 'Simple pulmonary artery orifice stenosis' refers to cases with an intact ventricular septum, but may be accompanied by patent foramen ovale or atrial septal defect. According to Abbott's statistics, pulmonary artery orifice stenosis with patent foramen ovale accounts for about 2.5%.

　　1. Pathological anatomy

　　The orifice of the pulmonary artery at birth is about 0.5 cm2 in a normal fetus, which gradually increases with growth and development, reaching 2.0 cm2/m2 at maturity. Generally, an effective pulmonary artery orifice must decrease by about 60% to cause a significant hemodynamic change. Clinically, valve-type pulmonary artery stenosis is the most common, accounting for about 75%. It is often caused by valve fusion in the middle and late stages of embryogenesis, with the three-leaf valve of the pulmonary artery fusing into a conical shape and bulging into the pulmonary artery. A small hole remains in the center, with a diameter of 2-10 mm, the smallest being 1-3 mm. The valves in children are soft and thin, and the orifice is usually central. As age increases, the valves become thicker and the orifice is no longer central. In some cases, the valves are only bilobed. The stenosis of the infundibulum accounts for about 15%, and can be located in the upper, middle, or lower part of the outflow tract of the right ventricle. It can be muscular, that is, the entire infundibulum muscle thickens, forming a narrow and long channel; or it can be membranous, that is, a local fibrous septum is formed in one place of the infundibulum, presenting as a ring-like stenosis, separating the infundibulum or part of the infundibulum from the right ventricle, forming a two-chambered right ventricle. When the infundibular stenosis is combined with valve-type stenosis, it is called a mixed stenosis, accounting for about 10%. The main cause of pulmonary artery orifice stenosis is intrauterine infection during embryogenesis, especially rubella virus infection. Pulmonary artery orifice stenosis can affect part or all of the pulmonary trunk, or extend to the branches of the left and right pulmonary arteries, or multifocally affect peripheral pulmonary artery branches, or mixedly affect the main trunk and peripheral secondary arteries or small artery branches. The pulmonary artery wall after stenosis is often thinner and dilated, known as post-stenotic dilation, which is more common in valve-type stenosis and less common in infundibular stenosis. The cause of post-stenotic dilation may be a developmental defect of the pulmonary artery itself or blood flow impact on the pulmonary artery. In this disease, the right ventricle is thickened, and the right atrium is also large.

　　2. Pathophysiology

　　Due to pulmonary artery stenosis, the right ventricle is overloaded during systole, the systolic pressure of the right ventricle increases, part of the pressure is consumed to overcome the resistance of the stenosis, causing the pulmonary artery pressure to be lower than the right ventricular pressure, resulting in a pressure gradient between the right ventricle and the pulmonary artery. However, this disease is different from tetralogy of Fallot, and it can still maintain a certain cardiac output, and the patient also has a certain degree of activity. This compensation is achieved by increasing the pressure of the right ventricle. Generally, the maximum systolic transvalvular pressure difference is between 50-80 mmHg (6.7-10.6 kPa), or the maximum systolic pressure of the right ventricle is between 75-100 mmHg (10.0-13.3 kPa), indicating moderate stenosis; below or above this range, it is mild or severe stenosis, respectively. In severe cases, the systolic pressure of the right ventricle can reach 150 mmHg (33.3 kPa). In children with moderate or severe stenosis, the degree of stenosis becomes more obvious with age, the valve fibrosis thickens, the right ventricular outflow tract thickens progressively, leading to secondary stenosis of the infundibulum. If the right ventricular compensation is disordered, the diastolic pressure also increases, the right atrial pressure also increases, and even right-to-left shunting occurs at the atrial level, leading to cyanosis, it is called tricuspid atresia. In late cases, heart failure may occur.

　　It may lead to heart failure or arrhythmia, and may cause brain abscess, and is prone to pulmonary infections, and may develop infectious endocarditis. Infectious endocarditis is a microbial infection on the surface of the heart endocardium, accompanied by the formation of vegetation. Vegetations are clumps of platelets and fibrin of varying sizes and shapes, containing a large number of microorganisms and a small number of inflammatory cells. This is an infection, so the patient may have fever, and the patient may have chills before the fever. Generally, this kind of fever is very severe, and it takes a long time to treat it.

　　1. General symptoms

　　The severity of symptoms is related to the degree of pulmonary artery stenosis. Mild stenosis often has no symptoms, grows well, and is often discovered to have a heart murmur during physical examination, leading to further examination and diagnosis. Moderate stenosis may cause palpitations, dyspnea after exertion, and severe stenosis patients often have a patent foramen ovale, in addition to dyspnea, may have cyanosis, clubbing (of fingers or toes), and heart failure and other symptoms.

　　2. Cardiac examination

　　When the stenosis is mild, the size of the heart is often normal. In cases of moderate and severe stenosis, due to the enlargement of the right ventricle, a bulge in the anterior chest area may form. Patients with pulmonary valve stenosis have a systolic thrill at the second intercostal space on the left side of the sternum, and a rough and longer喷射性 systolic murmur can be heard. In patients with infundibular stenosis, the murmur is most pronounced between the third and fourth intercostal spaces, and on the phonocardiogram, the murmur appears in the shape of a rhombus. The intensity of the murmur increases with the degree of stenosis, and the maximum amplitude of the rhombus-shaped murmur gradually shifts from the early systole to the middle and late systole. The second heart sound of the pulmonary artery decreases and the degree of splitting also gradually becomes more obvious with mild, moderate, and severe stenosis. In addition, patients with mild, moderate, and severe valve stenosis often hear a systolic early ejection sound at the second and third intercostal spaces on the left side of the sternum. If it progresses to right heart failure, liver enlargement, ascites, and edema may be seen; however, due to the decrease in pulmonary blood flow, pulmonary congestion is not observed.

　　Inquiring about family history to understand genetic conditions, investigating the influence of environmental factors to explore the etiology of congenital heart disease. Shaw investigated the address to understand the potential environmental teratogenic factors that the pregnant mother may have been exposed to. The address where the mother gave birth was sometimes used to represent the address during early pregnancy to estimate environmental factors. The author investigated the addresses of the mothers during pregnancy and childbirth, and about 24.8% of the mothers moved between the beginning of pregnancy and childbirth. Therefore, observing the address of childbirth may reduce the positive results of the association between congenital malformations and the environmental exposure of the mother. It is necessary to investigate the environmental factors of the address during pregnancy. Schwanitz advocates that the detection of heart malformations before birth can be a sign of chromosomal examination. The author mentioned that chromosomal examinations were performed on 588 fetuses diagnosed with growth retardation and/or congenital malformations before birth, among whom 116 cases (19.7%) were found to have chromosomal abnormalities. Among these prenatally diagnosed malformed fetuses, 102 (17.3%) had heart malformations, making heart malformations the most common malformations. Among the fetuses diagnosed with heart malformations before birth in this group, 41 (40.2%) had syndromes with chromosomal abnormalities (the most common being trisomy 18 and 21). In addition to monitoring the fetus, the mother's disease should also be monitored. Breton reported that mothers with phenylketonuria had a continuous increase in phenylalanine in plasma during pregnancy, and the children born to them had heart malformations. Breton reported a child with coronary artery abnormalities originating from the right pulmonary artery, ventricular septal defect, fetal growth retardation, and facial malformation, with a continuous increase in phenylalanine in the mother's plasma during pregnancy. The heart malformation was diagnosed at 8 months after birth. The developmental delay was due to the mother's phenylketonuria, which could also lead to ventricular septal defect and coronary artery malformation. The author proposed that if dietary treatment for the mother began before pregnancy, it may prevent damage to the fetus. Therefore, if a deep understanding of the etiology is obtained, it is possible to monitor the mother's disease and fetal malformations from before pregnancy to during pregnancy, and make every effort to prevent the occurrence of fetal congenital malformations if possible. However, from the perspectives of genetics and environmental damage, the etiology of congenital heart disease is not completely clear, and most prevention efforts are ineffective. Therefore, explaining the etiology and fundamentally preventing the occurrence of congenital heart disease remains an extremely arduous task that requires the joint efforts of scholars in clinical and basic research.

　　1. X-ray examination

　　The size of the heart increases gradually with the worsening of stenosis. Generally, the heart does not increase in size in cases of mild stenosis. If it does increase, it is mainly the right ventricle that increases, and the right atrium may also slightly increase, but the left ventricle does not increase significantly. In addition, the main pulmonary artery and the left pulmonary artery, due to the expansion after stenosis, have a more obvious pulsation, while the pulmonary texture within the pulmonary field decreases. There should be a sharp contrast between the two, which is a characteristic of this disease. However, in cases of funnel stenosis, the main pulmonary artery may appear concave.

　　2. Electrocardiogram

　　It is very meaningful for the judgment of the degree of stenosis. In addition to the normal electrocardiogram in cases of mild stenosis, in general, it shows right ventricular hypertrophy, deviation of the electrical axis to the right, or incomplete right bundle branch block. The degree of right ventricular hypertrophy is often proportional to the severity of the stenosis. In cases of severe stenosis, the right ventricular pressure exceeds 100mmHg.

　　3. Echocardiography

　　Mildly narrowed pulmonary artery valves have normal activity. When moderate or severe stenosis is present, the use of two-dimensional echocardiography combined with continuous-wave Doppler can accurately assess the location and severity of the stenosis. The diameter of the right atrium and right ventricle widens, the free wall of the right ventricle and the interventricular septum thicken, the pulmonary valve thickens, and its opening is restricted, forming a rounded bulge. In severe stenosis, the pulmonary valve may open prematurely during systole. In cases of funnel stenosis, the outflow tract of the right ventricle is narrow, and the diameter of the main pulmonary artery and its left and right branches can also be measured. In addition, continuous Doppler examination can estimate the transvalvular pressure gradient based on the modified Bernoulli equation.

　　4. Cardiac catheterization

　　It is very helpful for diagnosis. The distal pressure of pulmonary artery stenosis is reduced, but the pressure in the right ventricle near the stenosis is significantly increased. When the catheter is withdrawn from the pulmonary artery to the right ventricle, the systolic pressure in the pressure curve suddenly increases, while the diastolic pressure remains unchanged, indicating stenosis of the pulmonary valve. If there is a third type of pressure waveform between the pulmonary artery and the right ventricle, with systolic pressure the same as the pulmonary artery and diastolic pressure equal to the right ventricle, it indicates infundibular stenosis. In severe stenosis, the pressure in the right atrium can also increase. The oxygen content of blood in the various atria, ventricles, and major blood vessels in the heart is within the normal range. If the foramen ovale is not closed, the catheter can pass through the patent foramen ovale into the left atrium.

　　5. CT and MRI

　　Simple pulmonary valve stenosis generally does not require CT or MRI scans, but if accompanied by peripheral pulmonary artery stenosis or right ventricular dysfunction, CT and MRI scans are very helpful. The spin-echo T1W MRI image can show thickening of the pulmonary valve, dilatation of the main pulmonary artery and the proximal left pulmonary artery, concentric hypertrophy of the right ventricle, and the gradient echo movie sequence can show abnormal blood flow束 towards the main pulmonary artery with low signal. The gradient echo movie sequence can also accurately measure the end-diastolic volume and ejection fraction of the right ventricle, and contrast-enhanced magnetic resonance angiography sequences and multi-slice spiral CT show the peripheral pulmonary artery stenosis well.

　　6. Cardiovascular angiography

　　The cardiovascular angiography of pulmonary valve stenosis mainly involves right ventricular angiography, which can show the location and severity of pulmonary artery stenosis. If it is valvular stenosis, the narrowed valve orifice presents a fish mouth shape, and there is dilatation after pulmonary artery stenosis. Sometimes, there is dilatation of the right pulmonary artery, and severe pulmonary valve stenosis is often accompanied by secondary right ventricular infundibular systolic stenosis.

　　1. Regular eating habits can help establish order in the digestive system.

　　2. Eating small, frequent meals. Eating too much at once can cause bloating and diarrhea.

　　3. Eating slowly. Swallowing food too quickly can lead to the intake of more air, causing intestinal and gastric bloating.

　　4. Chewing thoroughly, allowing the enzymes in saliva more time to digest food and stimulate the secretion of gastric juice.

　　5. Large amounts of water supplementation. Water combines with intestinal fiber to increase the volume of feces, making it easier to pass; it can also act as a fluid supplement during diarrhea.

　　1. Differentiation of pulmonary stenosis from other cardiovascular anomalies

　　1. Differentiation from primary pulmonary artery dilation

　　Primary pulmonary artery dilation is extremely difficult to differentiate from mild pulmonary valve stenosis. The former may have a mild early ejection systolic murmur, but it is not as rough as the latter and is rarely accompanied by a thrill. Electrocardiogram and vectorcardiogram are normal, and right ventricular hypertrophy suggests pulmonary valve stenosis. Echocardiography can be used for differentiation, and right heart catheterization and cardiovascular angiography may be necessary for diagnosis if required.

　　2. Distinguish from atrial septal defect

　　The systolic murmur at the left sternal border in patients with atrial septal defect is not as loud and rough as that in patients with pulmonary artery stenosis, and it is usually not accompanied by a thrill; the second sound of the pulmonary artery is fixed split, but the split is not as obvious as that in pulmonary artery stenosis, and there is often a diastolic mid-period murmur at the left sternal border.

　　3. Distinguish from ventricular septal defect

　　Patients with ventricular septal defect have a very loud systolic murmur with a thrill at the left sternal border, no systolic ejection sound, X-ray shows an enlarged left atrium and left ventricle, increased pulmonary blood flow, and an electrocardiogram shows double ventricular hypertrophy or only right ventricular hypertrophy; echocardiography can be used for differentiation.

　　4. Distinguish from pulmonary atresia with intact ventricular septum

　　Attention should be paid to differentiate between neonates or young infants. Both may have cyanosis, heart failure, and reduced pulmonary blood flow. The most common type of pulmonary atresia patients often have underdeveloped right ventricles, no obvious cardiac enlargement, an electrocardiogram showing left ventricular hypertrophy, and a two-dimensional echocardiogram can be used for initial differentiation. Only selective cine cardiovascular angiography can definitely differentiate between atresia and severe stenosis.

　　5. Distinguish from Ebstein's anomaly

　　Typical physical signs and electrocardiographic findings can be used for differentiation.

　　Second, differentiate between simple pulmonary artery stenosis and pulmonary artery stenosis with other malformations

　　1. Distinguish from pulmonary artery stenosis with small ventricular septal defect

　　This type is more common with funnel stenosis, and due to the small ventricular septal defect, the right ventricular pressure can be higher than the left ventricular pressure. Accurate differentiation requires cardiovascular angiography.

　　2. Distinguish from patent ductus arteriosus with pulmonary artery stenosis

　　These patients have clinical manifestations similar to patent ductus arteriosus, but there is a loud systolic murmur with a thrill and a喷射音 above the left sternal border, and an electrocardiogram suggesting right ventricular hypertrophy due to pulmonary artery stenosis. Echocardiography can be used for differentiation.

　　3. Distinguish from Noonan syndrome

　　Fifty percent of patients with this disease may have congenital heart disease, and the most common associated malformation is pulmonary artery stenosis, which is often due to maldevelopment of the pulmonary artery. In addition, atrial septal defect and left ventricular myocardial disease may also occur. Patients with this disease have a special facial appearance, short stature, winged neck, ptosis of the eyelids, and hypogonadism can be used to distinguish.