Congenital heart disease is one of the most common birth defects in humans and poses a serious threat to the health and life of patients. These diseases are caused by structural abnormalities of the heart and large blood vessels formed during embryonic development, resulting in a series of pathophysiological changes in the circulatory system, which produce various clinical symptoms. Pulmonary hypertension is one of the most common complications of congenital heart disease and is an important factor in determining the condition and prognosis of congenital heart disease. In this article, we will give a general and brief introduction to the formation mechanism, clinical manifestations, as well as the diagnosis and treatment process of congenital heart disease combined with pulmonary hypertension, so that you can have a fuller understanding of the disease. I. Structure and physiology of the cardiopulmonary vascular system The human circulatory system is mainly composed of the heart and blood vessels. The heart is like a pump, which keeps contracting and diaphrasing rhythmically to push the blood to flow in the blood vessels according to a certain path. The normal heart consists of four chambers: the left atrium, the left ventricle, the right atrium and the right ventricle. Oxygen-rich arterial blood leaves the left ventricle, enters the aorta, and then divides into small arteries at various levels to enter the capillaries of the body’s organs, supplying cells with oxygen and nutrients while receiving carbon dioxide produced by cellular metabolism. The oxygen-consumed blood becomes venous blood and returns to the right atrium of the heart in the body vein, completing a cycle. This circulation is called the body circulation. The venous blood from the right atrium flows into the right ventricle and is then pumped into the pulmonary arteries, where it enters the capillaries of the alveoli through the various branches of the pulmonary arteries. The body’s alveoli constantly exchange gases through respiratory movements, causing the oxygen in the air to dissolve into the flowing blood, while releasing the carbon dioxide in the blood into the air. The blood that carries abundant oxygen again becomes arterial blood, and then returns to the left atrium of the heart through the pulmonary veins, completing a cycle called the pulmonary circulation. The blood of human body enters the body circulation after passing through the pulmonary circulation, and then enters the body circulation again, and so on and so forth, to achieve the purpose of bringing the oxygen in the air to the cells of the whole body, and at the same time releasing the carbon dioxide produced by the cells out of the body. Second, pulmonary artery pressure and pulmonary hypertension When it comes to pulmonary hypertension, perhaps many people are unfamiliar with it; but when it comes to hypertension, everyone should be familiar with it. In fact, pulmonary hypertension is the high blood pressure of the pulmonary arteries. Blood flowing in blood vessels generates a certain pressure, and the pressure varies from one vessel to another. We call the pressure in the aorta the aortic pressure, which is what we usually call blood pressure, and when this pressure exceeds the normal value, it is hypertension. Similarly, we call the pressure in the pulmonary artery the pulmonary artery pressure, and when this pressure exceeds normal, it is called pulmonary hypertension. In general, we can simply think that hypertension is when the pressure in the body circulation is too high, and pulmonary hypertension is when the pressure in the pulmonary circulation is too high. Arterial blood pressure fluctuates with the heartbeat, so we usually use the three values of systolic, diastolic and mean pressure to express it. The normal pulmonary artery systolic pressure is 15~30mmHg, diastolic pressure is 5~10mmHg, and mean pressure is 10~20mmHg. When the mean pulmonary artery pressure is higher than 25mmHg, we call it pulmonary hypertension, where 26~35mmHg is mild, 36~45mmHg is moderate, and greater than 45mmHg is severe. Third, the mechanism of pulmonary hypertension caused by congenital heart disease According to the principle of fluid mechanics, the pressure of the pulmonary artery is equal to the blood flow through the pulmonary artery multiplied by the pulmonary vascular resistance. Therefore, when the pulmonary blood flow increases or the pulmonary vascular resistance increases due to various reasons, it will lead to an increase in pulmonary artery pressure. In normal people, there is no traffic between the body circulation and the pulmonary circulation, but a significant number of patients with congenital heart disease have defects or abnormal ducts in the heart that cause traffic between the body circulation and the pulmonary circulation, resulting in blood from one circulation entering the other, which is called a shunt. In general (when the pulmonary circulation is not obstructed), the body circulation is usually greater than the pressure in the corresponding part of the pulmonary circulation, thus causing some of the blood from the body circulation to enter the pulmonary circulation. Because the body circulation is supported by the left heart system and the pulmonary circulation is supported by the right heart system, this shunt is called a left-to-right shunt, and congenital heart disease that can produce this shunt is called left-to-right shunt congenital heart disease. A significant number of common congenital heart diseases are of this type. For example, ventricular septal defect is due to traffic between the left and right ventricles, resulting in the flow of blood from the left ventricle to the right ventricle; atrial septal defect is due to traffic between the left and right atria, resulting in the flow of blood from the left ventricle to the right ventricle; and patent ductus arteriosus is due to traffic between the aorta and the pulmonary artery, resulting in the flow of blood from the aorta to the pulmonary artery. The left-to-right shunt causes an increase in blood flow into the pulmonary circulation, which can lead to pulmonary hypertension if it exceeds the capacity of the pulmonary vasculature. This type of pulmonary hypertension due to increased pulmonary blood flow is what we call powered pulmonary hypertension. Most early pulmonary hypertension due to congenital heart disease is of this type. If congenital heart disease is not treated promptly and pulmonary hypertension persists, a series of changes occur in the pulmonary vessels (mainly the small pulmonary arteries). Initially, the small pulmonary arteries become constricted, and as the disease progresses, the walls of the pulmonary vessels become thickened and fibrotic, and in advanced stages, they may even become completely occluded. This series of changes causes the diameter of the pulmonary vessels to become smaller, thus increasing pulmonary vascular resistance and causing further increase in pulmonary hypertension. In the advanced stage, the increase in pulmonary artery pressure exceeds the aortic pressure, and the left-to-right shunt may become a right-to-left shunt, at which time the patient will clinically develop cyanosis, which is known as Eisenmenger syndrome. This kind of pulmonary hypertension caused by increased pulmonary vascular resistance is called obstructive pulmonary hypertension, and is a manifestation of pulmonary hypertension that has progressed to an advanced stage. In summary, pulmonary hypertension caused by congenital heart disease is a progressive process. Its early manifestation is power pulmonary hypertension, which can develop into resistance pulmonary hypertension at a later stage. The speed of this process varies from person to person, and it is related to the type of heart malformation, the size of the fractional flow, and the genetic quality. Clinical manifestations of pulmonary hypertension associated with congenital heart disease Early mild pulmonary hypertension can have no obvious symptoms, but as the disease worsens, patients can develop a series of non-specific symptoms. These include: 1. Decreased physical activity capacity. This is related to the decrease in cardiac function and the decrease in oxygen saturation due to pulmonary hypertension. Patients may experience shortness of breath, fatigue, bruising of the lips and chest pain when performing normal physical activity or even at rest. 2. Cyanosis. Generally, when the disease progresses to severe obstructive pulmonary hypertension, cyanosis of the lips and nail bed will appear, which is the result of excessive pressure in the pulmonary artery causing part of the venous blood to flow into the artery (right to left shunt). It is important to note that not all cyanosis is related to pulmonary hypertension. Some congenital heart diseases (e.g., tetralogy of Fallot) can cause cyanosis themselves, but the patient does not necessarily have pulmonary hypertension in combination. There are also some special types of congenital heart disease that show cyanosis in a certain part of the body, such as arteriovenous catheterization and severe pulmonary hypertension may only have cyanosis of the lower extremities. Other symptoms, such as hemoptysis and syncope. They are relatively rare, but often indicate severe disease. The World Health Organization (WHO) classifies pulmonary hypertension into four classes according to the severity of its clinical manifestations: Class I: Patients have pulmonary hypertension but no limitation of physical activity. General physical activity does not cause dyspnea, fatigue, chest pain or near syncope. Grade II: Patients have pulmonary hypertension with mild limitation of physical activity. There is no discomfort at rest, but general physical activity can cause dyspnea, fatigue, chest pain, or near syncope. Grade III: The patient has pulmonary hypertension with severe limitation of physical activity. No discomfort at rest, but below normal physical activity can cause dyspnea, fatigue, chest pain or near syncope. Grade IV: The patient has pulmonary hypertension and is unable to perform any physical activity. The patient shows signs of right heart failure and may exhibit dyspnea and/or fatigue even at rest. Any physical activity increases the patient’s discomfort. In addition to the clinical evaluation of patients with congenital heart disease and pulmonary hypertension, a series of tests are needed to determine the presence or absence of pulmonary hypertension, its degree and cause, to guide further treatment, and to determine the prognosis. These tests include: 1. Echocardiography. This is the test of choice to confirm the diagnosis of congenital heart disease and is the primary method for non-invasive diagnosis of pulmonary hypertension. This method allows estimation of pulmonary artery pressure by measurement of blood flow velocity. Its advantages are that it is noninvasive, simple, relatively accurate, and can provide some indicators related to cardiac function at the same time; its disadvantages are that there is a certain degree of error in the results, which may even lead to misdiagnosis, and the hemodynamic indicators that can be provided are relatively limited, so in many cases it needs to be combined with cardiac catheterization. 2. Cardiac catheterization and acute pulmonary vasodilatation test. Cardiac catheterization is performed by delivering a catheter through peripheral vessels (usually femoral arteries and veins) into various parts of the heart and great vessels to perform pressure and oxygen saturation testing, as well as the calculation of relevant hemodynamic indices. On the basis of the cardiac catheterization, the patient is given drugs that can dilate the pulmonary vessels (such as oxygen, iloprost, etc.) and the changes in the relevant hemodynamic indices are detected, which is known as the acute pulmonary vasodilation test. This test is a standard method for confirming the diagnosis of pulmonary hypertension, evaluating the degree and nature of pulmonary hypertension, detecting pulmonary vascular reactivity, judging the indication for surgery and evaluating prognosis, guiding drug therapy, and following up the effectiveness of treatment. In addition, pulmonary angiography can be performed at the same time as cardiac catheterization, which helps to visually determine the extent of pulmonary vascular disease. 3. 6 minute walk test and cardiopulmonary exercise test. Both of these tests can objectively evaluate the exercise capacity of patients with pulmonary hypertension. The 6-minute walk test is more widely used in clinical practice because it is simple, less expensive, can be repeatedly tested and has been well standardized, and the degree of improvement in the 6-minute walk distance is an important indicator of the effect of treatment. 4.Blood test. Serum uric acid, atrial natriuretic peptide and brain natriuretic peptide (BNP) are important indicators for assessing and monitoring right ventricular function in patients with pulmonary hypertension and are of great value in evaluating prognosis. Autoantibodies are also tested in patients with suspected autoimmune disease causing pulmonary hypertension. 5. Other tests, such as pulmonary function, pulmonary ventilation/perfusion scan, lung CT, MRI, etc. They are not usually performed as routine tests, but will be considered when other causes of pulmonary hypertension need to be ruled out. Treatment of congenital heart disease-associated pulmonary hypertension For congenital heart disease-associated pulmonary hypertension, early surgery is the key to treatment. However, in patients who have developed resistance pulmonary hypertension, surgery to correct the cardiac malformation does not reduce the pulmonary artery pressure, but even leads to worsening of the disease. The treatment of this group of patients has always been a difficult clinical problem. In recent years, with the application of a series of new drugs targeting the treatment of pulmonary hypertension in the clinic, promising progress has been made in the treatment of pulmonary hypertension, and some patients without surgical indications have even regained the opportunity of surgery through medical treatment. At present, the treatment of patients with combined severe pulmonary hypertension needs to follow a complete treatment strategy, including: evaluation of the severity of the patient’s disease, evaluation of vascular reactivity, evaluation of the indication for surgery, evaluation of the effectiveness of drugs and evaluation of the combination of different drugs, combination of general treatment, supportive treatment, drug therapy and surgical and interventional treatment. 1.General treatment. Prevent lung infection, avoid dehydration and being at altitude. Patients who are prone to severe dyspnea, dizziness and chest pain after activity should avoid strenuous exercise. Pregnancy is a high risk for both mother and fetus, and Eisenmenger syndrome is a contraindication to pregnancy. 2. Supportive therapy. Oxygen therapy is recommended if it results in a sustained increase in arterial oxygen saturation and a reduction in symptoms. Diuretics and digoxin can improve the patient’s symptoms of cardiac insufficiency. Oral anticoagulants can be used in patients with pulmonary artery thrombosis, heart failure and no hemoptysis. 3.Specific drug therapy. This class of drugs directly targets the formation mechanism of pulmonary hypertension, so it is called targeted therapy. Currently, there are three main classes of drugs: 1) endothelin receptor antagonists, such as bosentan, sitaxsartan, and ambesentan; 2) prostaglandin-like drugs, such as intravenously applied epoprostenol, inhaled iloprost (Vantavir), and orally administered beriberi; 3) phosphodiesterase-5 inhibitors, such as sildenafil (Viagra), vardenafil, and tadalafil. Patients can choose a targeted drug according to the responsiveness to drugs, side effects and economic situation, or a combination of drugs if necessary. 4. Heart-lung transplantation or lung transplantation with heart surgery. This is a treatment option for patients who do not respond to drug therapy, but due to the very limited supply of organs and the low survival rate after heart-lung transplantation, it is usually only considered when the patient is in very poor condition.