Pediatric pulmonary hypertension

　　First, the causes of disease

　　Pulmonary hypertension is common in congenital heart disease, persistent pulmonary hypertension of newborns, hypoxic diseases (such as bronchial asthma, infantile pneumonia, high-altitude heart disease, and maldevelopment of bronchi, etc.), and primary pulmonary hypertension.

　　1. Classification

　　(1) According to etiology:

　　①Primary pulmonary hypertension: Refers to the cause of pulmonary hypertension is unknown.

　　②Secondary pulmonary hypertension: Refers to pulmonary hypertension with identifiable causes. The most common cause in children is congenital heart disease, especially large ventricular septal defects, patent ductus arteriosus, and other conditions in the left-to-right shunt group.

　　(2) Divided by degree: The generally accepted method by most scholars is:

　　①Pulmonary artery systolic pressure: When 4-5.3 kPa (30-40 mmHg) is mild; 5.3-9.3 kPa (40-70 mmHg) is moderate; >9.3 kPa (>70 mmHg) and above is severe.

　　②Divided by the ratio of pulmonary artery systolic pressure to systemic artery systolic pressure (Pp/Ps): Pp/Ps 0.75 is severe.

　　(3) Divided according to hemodynamic characteristics:

　　①Passive pulmonary hypertension: Due to increased left atrial pressure and pulmonary venous pressure, affecting the pulmonary artery through pulmonary capillaries to cause pulmonary hypertension, such as left heart failure, mitral valve disease, trilocular heart, pulmonary venous obstruction disease.

　　②Dynamic pulmonary hypertension: Due to high pulmonary artery blood flow causing increased pulmonary artery pressure, such as left-to-right shunt congenital heart disease.

　　③Reactive pulmonary hypertension: Increased pulmonary vascular resistance caused by pulmonary arteriolar spasm, muscular hypertrophy, or contraction of the arterial wall, such as pulmonary heart disease, primary pulmonary hypertension.

　　④Obstructive pulmonary hypertension: Mainly due to pulmonary artery embolism. Different degrees of pulmonary artery occlusion and reduction of pulmonary vascular bed, pulmonary artery endothelial hyperplasia, smooth muscle hypertrophy, collagen accumulation, lumen narrowing are common pathological manifestations in the late stage of various types of pulmonary hypertension.

　　2. Etiology of secondary pulmonary hypertension

　　According to the principles of fluid mechanics, pulmonary artery pressure, pulmonary venous pressure, pulmonary vascular resistance, and pulmonary blood flow are related, which can be expressed by the formula: pa = pv + RpQp. Where pa refers to pulmonary artery pressure, pv is pulmonary venous pressure, Rp is pulmonary vascular resistance, and Qp is pulmonary blood flow. Any factor that causes an increase in pa, Rp, and Qp can lead to pulmonary hypertension.

　　(1) Increased pulmonary blood flow: Congenital heart diseases with left-to-right shunts, such as atrial septal defect, ventricular septal defect, patent ductus arteriosus, atrioventricular canal, persistent truncus arteriosus, and single ventricle, where the pulmonary hypertension caused by these diseases is due to increased Qp.

　　(2) Pulmonary vascular disease: Mainly caused by increased pulmonary vascular resistance (Rp).

　　①Diffuse pulmonary embolism disease: such as thrombus, pus plug, amniotic fluid embolism, primary pulmonary artery thrombosis in sickle cell anemia with hemoglobin S.

　　②Pulmonary arteritis: Caused by large artery arteritis, Raynaud's syndrome, systemic sclerosis, systemic lupus erythematosus, polymyositis, dermatomyositis, eosinophilia syndrome,结节性动脉炎, etc., affecting the pulmonary artery.

　　(3) Pulmonary diseases:

　　①Chronic Obstructive Pulmonary Disease (COPD): Seen in bronchial asthma, emphysema, chronic bronchitis.

　　②Diffuse interstitial or alveolar diseases: such as idiopathic pulmonary hemosiderosis, sarcoidosis, granulomatosis, pulmonary interstitial fibrosis, alveolar proteinosis, alveolar microlithiasis.

　　③Insufficient alveolar ventilation: Primary and neuromuscular alveolar ventilation insufficiency.

　　(4) High-altitude pulmonary hypertension.

　　(5) Pulmonary venous hypertension: As mentioned earlier, when pv increases, pa also necessarily increases. Diseases that cause pulmonary venous hypertension include trilocular heart, mitral stenosis, complete pulmonary venous drainage with pulmonary venous obstruction, etc.

　　3, Etiology of primary pulmonary hypertension

　　The etiology of the disease is unclear, and it may be the result of the combined action of various congenital factors:

　　(1) Similar to primary hypertension, it belongs to a neuro-humoral disease.

　　(2) Secondary vascular lesions due to pulmonary arteritis.

　　(3) Pulmonary vascular changes in collagenous (connective tissue) diseases.

　　(4) The result of chronic microembolism.

　　(5) Familial inheritance. The literature reports that 63 cases of pulmonary hypertension were found in 25 family members. One thing is certain, primary pulmonary hypertension has no congenital cardiovascular disease.

　　2, Pathogenesis

　　1, Structure and blood flow of pulmonary artery

　　(1) Structure of pulmonary artery: The pulmonary artery is divided into 3 segments from a histological perspective:

　　① Elastic artery segment: The outer diameter is greater than 1mm, runs parallel to the bronchus, rich in annular elastic fibers, and has less muscle tissue.

　　② Muscular artery segment: This segment runs parallel to the bronchioles, respiratory bronchioles, and alveolar ducts. The wall has more muscle tissue, the wall is thin, the lumen is large, and although the wall has contraction and relaxation functions, the resistance is not great. When the outer diameter PA is vascularized, the capillaries are passively expanded, allowing blood flow. In the diastolic phase of the heart, Pa decreases, PaPv>PA, the transmural pressure is positive, the alveolar vessels are mostly expanded, which is caused by the gravitational effect of the hydrostatic pressure of blood fluid.

　　(4) The effect of changes in cardiac output on pulmonary circulation: Alveolar vessels have a high degree of compliance, and a slight increase in pulmonary artery pressure can cause obvious passive expansion; a part of the alveolar vessels do not open when cardiac output and pulmonary artery pressure are normal, but they open under high cardiac output with a slight increase in pulmonary artery pressure, which is enough to open these vessels and increase a new blood flow path. According to Poiseuille's formula R=△P/Q, the pulmonary vascular resistance (R) is inversely proportional to the pulmonary blood flow (Q). When pulmonary artery pressure (P) remains unchanged or slightly increases, and pulmonary blood flow increases, the reduction or change in pulmonary vascular resistance is not significant. In the early stage of congenital heart disease with left-to-right shunts, the pulmonary blood flow increases significantly, but the pulmonary vascular resistance is not high and the pulmonary artery pressure is normal or slightly increased, which is related to the compliance of alveolar vessels and the opening of vessels. This change is not unrelated to the compliance of alveolar vessels and the opening of vessels.

　　(2) Active regulation of pulmonary circulation: The basis of active regulation of pulmonary circulation is that the smooth muscle of pulmonary vessels produces a contraction and relaxation response under the action of neural, humoral, and chemical factors as well as the self-regulation of the vessels, resulting in changes in vascular resistance and pulmonary artery pressure.

　　① Nervous regulation of pulmonary circulation:

　　A, Nervous innervation of pulmonary vessels: The pulmonary vessels are mainly innervated by sympathetic and vagus nerves, with most nerve fibers located within 5 to 10μm of the outer edge of the muscular layer of the vascular smooth muscle. In larger elastic arteries, the nerve distribution is more than in muscular pulmonary arteries; pulmonary arteries with an outer diameter less than 30μm do not have nerve distribution, so the possibility of affecting vascular resistance and blood flow through neural regulation at the level of small pulmonary arteries is relatively small.

　　B. Regulatory role of the autonomic nervous system:

　　The central nervous system regulates the pulmonary circulation through the autonomic nervous system. Stimulation of the chest vagus nerve, cervical sympathetic ganglion, and stellate ganglion can cause an increase in pulmonary artery pressure, and it has been confirmed that this increase is due to vasoconstriction of the pulmonary vessels.

　　C. Reflex mechanism of peripheral chemoreceptors and pressure receptors: Cutting off the reflex arc of the carotid body chemoreceptor from any link of the central efferent and afferent nerves can significantly enhance the pulmonary artery pressure response caused by hypoxia, thus suggesting that this reflex participates in the regulation of the pulmonary circulation during hypoxia and has the effect of increasing cardiac output, compensating for hypoxia, and delaying the progression of hypoxic pulmonary hypertension to some extent.

　　② Humoral regulation of the pulmonary circulation: Many bioactive substances are activated, inactivated, synthesized, or released in the lung, among which many bioactive substances play an important role in pulmonary vascular contraction and relaxation. In the regulation of the pulmonary circulation, especially in the regional distribution of pulmonary blood flow, humoral regulation plays an important role and does not require neural participation. Histamine release; angiotensin II; prostaglandins, especially PGF2a, PGD2, PGE2, and TXA2; leukotrienes, especially LTC4, LTD4, etc., all have a vasoconstrictive effect on pulmonary vessels. The newly discovered endothelium-dependent relaxing factor (EDRF) produced and released by endothelial cells can directly act on smooth muscle cells, activate the soluble and cyclic nucleotide phosphodiesterase in the cytoplasm of smooth muscle cells, increase cGMP, and promote protein phosphorylation, thus relaxing and dilating the vascular smooth muscle. Endothelial cells can also release some growth factors that directly stimulate the hypertrophy and proliferation of vascular smooth muscle cells.

　　2. Basic mechanism of pulmonary hypertension

　　The basic mechanism of pulmonary hypertension can be simply explained by Ohm's law, Rp = (pa - pv) / Qp. Rp represents pulmonary circulation resistance; Qp represents pulmonary blood flow; pa represents the mean pulmonary artery pressure, and pv represents the mean pulmonary venous pressure. The formula can be rearranged as: pa = pv + Rp × Qp. From the formula, it can be seen that when the pulmonary venous pressure, pulmonary vascular resistance, or pulmonary blood flow increases, the pulmonary artery pressure can also increase.

　　(1) Increase in pulmonary venous pressure: Prolonged hypertension of the pulmonary veins due to various reasons can reversely cause an increase in pulmonary capillary pressure and pulmonary artery pressure. When the pulmonary capillary pressure exceeds the colloidal osmotic pressure of the blood, the liquid in the blood vessels渗出 to the tissue spaces increases, leading to a decrease in pulmonary compliance, causing hypoxia in the alveoli and vasoconstriction of the pulmonary vessels, which aggravates pulmonary hypertension.

　　(2) Increase in pulmonary vascular resistance: The resistance, pressure, and flow relationship when fluid flows through a cylindrical pipe can be determined by Poiseuille's modified formula: R = (8π)(l/kr^4)(η). Here, R is the resistance, l is the length of the pipe, r is the radius of the pipe, and η is the viscosity of the fluid. The length of the blood vessels does not change significantly before and after the disease, and the main factors affecting pulmonary vascular resistance are the changing viscosity η, lumen radius, and the number of blood vessels.

　　① Changes in viscosity: Changes in viscosity are often caused by polycythemia, where an increased hematocrit leads to increased viscosity, affecting pulmonary vascular resistance. The resistance of pulmonary vessels is approximately logarithmically related to the hematocrit.

　　② Changes in the number of vessels: A. Pulmonary vascular bed reserve: When the number of pulmonary vessels decreases, other pulmonary vessels compensate by dilating and opening. Research shows that when the number of pulmonary vessels decreases by more than 75%, the resting pulmonary artery pressure may rise, indicating a large capacity of the pulmonary vascular bed reserve. However, in newborns and infants, the pulmonary vascular bed reserve is limited due to the fewer number of pulmonary vessels, limited re-opening of the vessels, and muscular thickening of the vascular wall, which restricts vessel dilation, leading to increased pulmonary vascular resistance and pulmonary hypertension. B. Reduction in the number of alveolar arteries: The alveolar arteries that accompany alveolar growth are not fully developed until 8 to 10 years old. Alveolar arteries are the key vascular segments controlling pulmonary circulation and gas exchange. Normally, the ratio of alveolar arteries to alveoli is 1:10, and they grow simultaneously, maintaining a fixed ratio. However, in patients with increased pulmonary vascular resistance, the ratio of alveolar arteries to alveoli decreases to 1:30, meaning that about two-thirds of the alveoli do not develop, resulting in a significant reduction in the pulmonary vascular bed and accelerating the increase in pulmonary vascular resistance and pulmonary hypertension.

　　③ Reduction in luminal diameter: Whether the reduction in luminal diameter causes an increase in pulmonary artery pressure mainly depends on the number and extent of the affected vessels. The causes of luminal reduction include:

　　A. External compression or constriction of the vessels: During pulmonary edema, the enlarged left atrium compresses the airways, causing alveolar hypoxia and pulmonary vasoconstriction.

　　B. Thickening of the pulmonary vascular wall: The thickening of the pulmonary vascular wall will narrow the vascular lumen. The thickened muscular layer or thrombus organization can cause eccentric intimal thickening, which is an important cause of pulmonary hypertension in congenital heart disease and increased pulmonary vascular resistance.

　　C. Increase in pulmonary blood flow: When the shunt in congenital heart disease is greater than twice the normal cardiac output, the pulmonary artery pressure may remain unchanged, which is due to the compensatory dilation of the pulmonary vessels. When the shunt further increases and exceeds the limit of pulmonary vessel dilation, dynamic pulmonary hypertension will occur. It should be noted that an increase in pulmonary blood flow itself does not necessarily lead to pulmonary hypertension. It is often the result of increased resistance due to pulmonary arteriolar obstruction or stenosis, as the resistance of pulmonary arterioles is inversely proportional to the fourth power of their radius. Some scholars have observed that large ventricular septal defects often show significant muscular thickening of the pulmonary arterioles and luminal narrowing within 2 months after birth.

　　3. Pathological changes of pulmonary hypertension

　　(1)The basic pathological changes of dynamic pulmonary hypertension: Dynamic pulmonary hypertension can cause plexogenic pulmonary arteriopathy, which is characterized by muscular thickening of the middle layer of pulmonary arteries, muscularization of capillaries, cellular intimal hyperplasia, and luminal narrowing in the early stage. As the disease progresses, an increase in collagen and elastic fibers leads to laminar intimal fibrosis, which can cause complete occlusion of the lumen in severe cases. In the later stage, changes such as dilatation,纤维素样坏死, arteritis, and plexogenic lesions may occur.

　　(2) Pathological change grading: High-output pulmonary hypertension, Heath et al. first proposed a 6-level classification method: Grade I shows thickening of the pulmonary artery middle layer; Grade II is thickening of the pulmonary artery middle layer and endocardial cellular hyperplasia; Grade III shows obstructive endocardial fibrosis; Grade IV is plexiform lesions; Grade V appears pulmonary artery dilatation on the basis of the first four grades; Grade VI has necrotizing pulmonary arteritis. The Department of Pathology of Fuwai Hospital proposed a 4-level classification method: Grade I (mild) is the first and second grades described by Heath; Grade II is Heath's third grade (moderate); Grade III is the fourth and fifth grades in Heath's classification (severe); Grade IV is Heath's sixth grade (extremely severe). It is proposed that Grades I and II are reversible; Grade III is a critical lesion, where patients may have persistent pulmonary hypertension after surgery, but some may almost return to normal. Grades IV, V, and VI have highly fixed pulmonary vascular resistance, widespread and irreversible obstructive pulmonary vascular lesions.

　　(3) The relationship between lesion grading and pulmonary artery mean pressure and total resistance: According to research by Ruan Yingmiao: the mean pressure of the main pulmonary artery is above 6.7 kPa (50 mmHg), and the total resistance is greater than 1000 cm-5, it belongs to grade III, IV lesions. Most die of complications of pulmonary hypertension. When the mean pressure of the main pulmonary artery is less than 6.7 kPa (50 mmHg), and the total resistance is 600-800 dynscm-5, with moderate elevation, they die of causes other than pulmonary hypertension. It is proposed that left-to-right shunting congenital heart diseases with bidirectional flow belong to grade III, IV lesions, indicating that most patients with multishunting have late pulmonary vascular lesions.

　　It often complicates with respiratory tract infections, pneumonia, and heart failure. In the late stage, Eisenmenger syndrome may occur, and children often have delayed growth and development and malnutrition. Eisenmenger syndrome is a consequence of the development of congenital heart disease. Congenital heart diseases such as atrial and ventricular septal defects, patent ductus arteriosus, etc., can change from left-to-right shunting to right-to-left shunting due to progressive pulmonary hypertension and the development of organic pulmonary obstructive lesions. When the skin and mucous membranes turn from cyanosis-free to cyanotic, it is called Eisenmenger syndrome.

　　1. Secondary pulmonary hypertension

　　1. Symptoms:

　　In addition to the clinical symptoms of the existing underlying diseases, the symptoms of pulmonary hypertension itself are non-specific. The early symptoms of pulmonary hypertension are generally not obvious. Once clinical symptoms appear, it indicates that the disease has reached a late stage. Patients with severe pulmonary hypertension are prone to fatigue and weakness due to decreased cardiac output, limited oxygen transport, and tissue hypoxia. Since the compliance of pulmonary vessels decreases, cardiac output cannot increase with exercise, and patients present with exertional dyspnea. A sudden decrease in oxygen supply to the brain tissue can cause syncope, and arrhythmias may also occur, especially bradycardia. Due to the hypertrophy of the right ventricle and insufficient myocardial perfusion, patients may experience angina pectoris. If pulmonary dilation compresses the recurrent laryngeal nerve, hoarseness may occur.

　　2. Physical examination:

　　With the increase of pulmonary artery pressure, it can lead to the enlargement and functional failure of the right atrium and ventricle. Common signs include the lifting pulse of the right ventricle and the pulse in the pulmonary artery area. Palpation can find the vibration and impact sensation of the pulmonary valve area, and auscultation can find P2 hyperactivity, systolic ejection sound in the pulmonary valve area, and diastolic murmur caused by relative pulmonary valve insufficiency. Right heart failure signs such as jugular vein distension, liver enlargement, hepatic jugular vein reflux, and lower limb edema may also be found.

　　Secondly, primary pulmonary hypertension

　　The clinical symptoms of pulmonary hypertension often occur during childhood, and more than 5 years after birth, and some occur during infancy,表现为difficulty in feeding, delayed growth and development, rapid breathing, fatigue, and exercise-induced dyspnea are the main symptoms during childhood. Syncope may occur during exercise, chest pain, and a decrease in cardiac output may cause these symptoms. In the neonatal period, due to pulmonary hypertension, venous blood can flow through the foramen ovale from the right atrium to the left atrium, causing a decrease in arterial blood oxygen saturation, clinical cyanosis, known as persistent fetal circulation (PFC). The auscultation of the heart mainly shows P2 hyperactivity, most of which have no murmur, and occasionally there may be systolic murmur, which may be caused by tricuspid valve insufficiency. Due to the increased ejection resistance of the right ventricle, the systolic load is excessive, and signs of right heart failure such as liver enlargement and jugular vein distension may occur. The clinical manifestations of left-to-right shunt congenital heart disease depend on the nature of the lesion and the size of the shunt. A small shunt generally does not cause significant hemodynamic abnormalities, normal pulmonary vascular resistance, and is not prone to pulmonary hypertension. Therefore, clinical symptoms may be asymptomatic or mild for a long time. In infants with a large left-to-right shunt congenital heart disease, especially those with posterior tricuspid valve shunt, respiratory tract infections, pneumonia, and chronic heart failure are common. After 1 to 2 years, due to the increase in pulmonary artery pressure, the left-to-right shunt decreases, and the symptoms gradually improve. In the following years, there may be no obvious symptoms. In childhood, the symptoms of Eisenmenger syndrome appear slowly, manifested as shortness of breath after exercise, decreased activity, delayed growth and development, cyanosis, mild clubbing of fingers and toes. At this time, the arterial blood oxygen saturation has decreased, and during physical examination, the original murmur is reduced, P2 is significantly hyperactive with a closing sensation, and II to III grade ejection systolic murmur is often heard at the second intercostal space on the left side of the sternum.

　　Secondary pulmonary hypertension is often associated with congenital heart disease, while the etiology of primary pulmonary hypertension is not yet clear. The occurrence of congenital heart disease is a comprehensive result of various factors. To prevent the occurrence of congenital heart disease, it is necessary to carry out popular science publicity and education, focus on monitoring the population of appropriate age, and give full play to the role of medical personnel, pregnant women, and their families.

　　1. Abolish bad living habits, including those of the pregnant woman herself and her spouse, such as smoking and excessive drinking.

　　2. Before pregnancy, actively treat diseases that affect fetal development, such as diabetes, lupus erythematosus, anemia, etc.

　　3. Actively carry out prenatal examinations, prevent colds, and try to avoid using drugs confirmed to have teratogenic effects, as well as avoiding contact with toxic and harmful substances.

　　4. For elderly pregnant women, those with a family history of congenital heart disease, or couples where one has a serious illness or defect, close monitoring should be emphasized.

　　The diagnosis is based on medical history, physical examination, X-ray examination, and laboratory data. Even with 100% oxygen supply by positive pressure, the child may still have hypoxemia. If the child has primary pulmonary hypertension, chest X-ray shows the lungs to be completely normal, but can show pulmonary parenchymal lesions (such as meconium aspiration syndrome or neonatal pneumonia) or congenital diaphragmatic hernia. Echocardiography is used to evaluate the heart condition to exclude congenital heart disease and determine that there is pressure in the pulmonary artery exceeding that of the systemic circulation.

　　Increased pulmonary vascular resistance can lead to pulmonary hypertension and right-to-left shunting, exacerbating hypoxemia and acidosis. By increasing oxygen partial pressure and pH, these symptoms can be improved. Therefore, for any near-term newborn with neonatal hypoxemia, suspicion of persistent pulmonary hypertension of the newborn should be raised, and early treatment should be provided as soon as possible to prevent further progression.

　　Because such patients have a large amount of right-to-left shunting through the open ductus arteriosus, the oxygen partial pressure in the right brachial artery is higher than that in the descending aorta. If a pulse oximeter is placed simultaneously on the right hand and lower limb, showing low oxygen saturation in the foot, it proves that the level of right-to-left shunting is in the ductus arteriosus.

　　Ultrasound Doppler examination:

　　Indirect signs of pulmonary hypertension

　　1. The ratio of pre-ejection period (PEP) to right ventricular ejection time (RVET) can be measured using M-mode or Doppler methods, the normal value is generally around 0.35, and when it is greater than 0.5, the chance of pulmonary hypertension is extremely high.

　　2. Doppler method to measure the pulmonary artery blood flow acceleration time (AT) and the ratio of acceleration time to right ventricular ejection time (AT/RVET), a decrease in these values suggests pulmonary hypertension.

　　3. Using Doppler to measure the average blood flow velocity in the left or right pulmonary artery, a decrease in flow velocity suggests increased pulmonary vascular resistance and pulmonary hypertension. The normal value variation of these indicators is large, but serial dynamic observation has a certain significance for evaluating the therapeutic effect of PPHN.

　　Direct signs of pulmonary hypertension

　　1. Using two-dimensional color Doppler ultrasound to display an open ductus arteriosus in the high left sternum parasternal section, the direction of blood flow at the level of the duct can determine right-to-left shunting, bidirectional shunting, or left-to-right shunting. Doppler sampling points can also be placed inside the ductus arteriosus, according to the flow velocity, referring to systemic arterial pressure, and using Bernoulli's equation (pressure difference = 4 x velocity^2) to calculate pulmonary artery pressure.

　　2. Utilizing tricuspid regurgitation in children with pulmonary hypertension, continuous Doppler measurement of regurgitant flow velocity is used to simplify Bernoulli's equation and calculate pulmonary artery pressure: pulmonary artery systolic pressure = 4 x regurgitant blood flow velocity^2 + CVP (assuming CVP to be 5 mmHg). When pulmonary artery systolic pressure ≥ 75% of systemic arterial systolic pressure, pulmonary hypertension can be diagnosed.

　　3, Directly observe the right-to-left shunt at the atrial level through the foramen ovale with color Doppler. If it cannot be displayed, 2-3ml of normal saline can be rapidly infused through the upper limb or scalp vein (central vein is better). If 'snowflake-like' shadows are seen from the right atrium to the left atrium at the same time, the right-to-left shunt can be confirmed.

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　　Secondary pulmonary hypertension:

　　Etiological treatment:Secondary pulmonary hypertension due to congenital heart disease has an important impact on surgery and its effects. Some surgeries may be very successful, but due to pulmonary hypertension that cannot be relieved, death may occur. Adequate estimation of pulmonary hypertension before surgery should be made for these patients. The treatment of PAH patients cannot be limited to simple drug therapy but should be a comprehensive treatment strategy, including evaluation of the severity of the patient's condition, supportive treatment, evaluation of vascular reactivity, evaluation of drug efficacy, and evaluation of combination therapy with different drugs. Individualized treatment plans should be formulated according to the different clinical types of PAH; according to the functional classification of PAH, choose to reduce PAH drugs; for patients who are ineffective after standardized medical treatment, interventional or surgical treatment of heart-lung transplantation can be considered.