In the previous chapter, we discussed the diagnosis and evaluation methods of precardiac disease combined with pulmonary arterial hypertension (hereinafter referred to as PAH). In this chapter, we talk about the treatment issues, which are the main concern of many patients. 1. The doctor said that my child can undergo corrective surgery for precardiac disease, but then said that his pulmonary artery pressure is a little high and somewhat dangerous, how do I decide? First of all, as an invasive operation, any surgery is subject to risks. We cannot live without the normal functioning of the heart all the time, and once the heart stops beating, or movement is significantly abnormal, it can mean the end of life; therefore, the risks of heart surgery are more prominent than those of other organs. The point is that surgery is necessary to treat heart disease, and heart disease cannot be cured without taking risks. Moreover, in the vast majority of cases, the risk of surgery is a low-probability event. While modern medicine cannot completely eliminate the possibility of surgical failure, it is clearly the most unwise choice to choke on it. It is self-evident that the more severe the PAH, the greater the probability of surgical failure. However, as long as there is still an indication for surgery, efforts should be made to try and give the patient a chance for long-term survival. In the previous two chapters, we have talked about the grasp of the indication for surgery in patients with different degrees of PAH. For patients with predominantly power PAH, the postoperative pulmonary artery pressure tends to drop significantly, but this does not mean that the pulmonary artery pressure will not rebound. Under the strong stimulation of surgery, a small number of patients may experience severe pulmonary artery spasm and rapid increase in pulmonary artery pressure during or after surgery (especially early), which may lead to uncontrollable heart failure and lower blood pressure. This phenomenon, which we call “pulmonary hypertensive crisis,” is a dangerous complication that is difficult to treat with conventional medications. If a patient with severe PAH develops a crisis, the consequences will be even more serious. Therefore, we will make efforts to prevent the occurrence of crisis, including the adjustment of ventilator and the routine application of anti-pulmonary hypertension drugs. The patient is 20 years old and has a ventricular septal defect. The doctor said that her pulmonary hypertension is already very severe and although the ventricular defect can be surgically repaired, a “hole” should be left to prevent postoperative rebound of pulmonary artery pressure. In Chapter 2, we have mentioned that for some patients with PAH in a critical state, there is still a chance of surgical correction of preexisting heart disease. However, in the early postoperative period, their pulmonary artery pressure will not decrease significantly, and they are also highly susceptible to pulmonary hypertension crisis, which requires us to make adjustments in the surgical design. In the case of ventricular septal defect, for example, the caliber of the ventricular defect is often large in patients with combined severe PAH, and patch repair is required. A hole is left in the patch and covered by another smaller patch, which is called a “one-way valve patch” and is equivalent to a “living door” or a smaller ventricular defect. If the pulmonary artery pressure continues to rise, the blood can be shunted from the right ventricle to the left ventricle via the one-way valve, so that the pressure in the right heart is reduced and does not develop into severe heart failure, thus ensuring that the patient can pass through the early postoperative instability more safely. After a period of time, as the patient’s condition becomes more stable, the pulmonary artery pressure gradually decreases, the blood shunted through the valve becomes increasingly reduced, the patch will adhere and the valve will gradually close. From the clinical results, the ventricular defect in the majority of patients can be completely closed within a few months, so that both the early postoperative safety and the long-term surgical results can be ensured to a certain extent. It should be noted that advances in surgical techniques may reduce the risk in the early postoperative period, but they cannot reverse the natural course of PAH. Patients who have developed Eissenmenger Syndrome (ESS), even if they are lucky enough to survive the early postoperative period, will not have an improved quality of life in the long term and their life expectancy may even be shortened. Therefore, patients who are otherwise inoperable do not have the opportunity to regain surgical correction (please see Chapter 1 of this article for details). 3. I have had all the tests and seen many doctors, and they all say that my pulmonary artery pressure is too high for surgery, is there any other way to completely eliminate PAH? As mentioned before, once PAH has reached an irreversible stage, it will continue to evolve according to its own laws and become the main cause of life-threatening disease; there is no point in correcting precordial disease at this point; eliminating pulmonary vasculopathy is the core of success or failure of treatment. Unfortunately, modern medicine has not yet found an effective means to reverse the pulmonary vasculopathy in patients with PAH; the only way to completely solve the problem is through lung transplantation or combined heart-lung transplantation. The vast majority of patients with combined PAH suffer from simple congenital heart disease (e.g., ventricular septal defect, patent ductus arteriosus, etc.), which is not very difficult to correct. A lung transplant can be done at the same time as the congenital heart disease, which can completely eliminate PAH and lower the pulmonary artery pressure to normal. In the case of complex congenital heart disease that is difficult to correct, or if the heart function has become unsustainable and the correction of the congenital heart disease + lung transplantation cannot be completed, the only option is to perform a combined heart-lung transplantation. The latter has inferior surgical risks and long-term survival than simple lung transplantation, so combined heart-lung transplantation should not be performed in patients who have the opportunity to receive simple lung transplantation. Lung transplantation also faces many problems, such as a severe shortage of donor organs, and many patients always have difficulty in obtaining a suitable donor. Long-term postoperative immunosuppressive drugs are required to control rejection; these drugs can also have adverse effects on patients. After lung transplantation, there is still a large gap in the long-term survival rate of patients compared to the norm. There are not many cases of lung transplantation in China yet, and fewer medical centers are capable and qualified to perform lung transplantation. Another important obstacle is that the surgery is expensive and the postoperative medication consumes a lot of money. Patients with PAH combined with precardiac disease, often from less developed areas, can hardly afford such high costs. However, in any case, lung transplantation has been widely recognized as the most efficacious standard of care for advanced PAH that is difficult to control. 4. If lung transplantation is not possible, are there other ways to control PAH? For patients who cannot undergo surgery, the only strategy is to adopt conservative treatment. The details are: ① Pay attention to rest and avoid exertion. Patients with severe pulmonary hypertension are most likely to have reduced activity tolerance. It is unwise to force oneself to maintain the original intensity of exercise at this time, even if one is forced to do so at the cost of serious damage to health. ② Exercise in moderation to maintain physical strength. The above two recommendations seem to contradict each other, but they are actually two sides of the same coin, just expressed in different ways. If rehabilitation is completely abandoned, the patient’s physical strength will also be severely reduced; therefore, for most patients who are still somewhat active, it is important to maintain a certain amount of exercise, but the bottom line should be that it does not cause significant clinical symptoms. If there is a good level of rehabilitation department in a nearby hospital, you can seek consultation with a rehabilitation doctor and carry out rehabilitation training in a planned manner. ③ Establish good habits to prevent and control pneumonia. Some patients have the habit of smoking, which is a vice that must be quit. Smoking can stimulate pulmonary vasospasm, which can exacerbate pulmonary hypertension. There are also some patients who are still participating in a work environment with more dust, which may also have adverse effects and should be transferred to another job if possible. Regular lifestyle habits are essential for good health. Overwork and late nights can accelerate the progression of the disease process, which is corroborated by the previous recommendations. Pneumonia is an important cause of rapid progression and even life-threatening disease in patients with PAH, and is the subject of our efforts to prevent it. Patients should pay attention to improving nutrition, strengthening immunity, adding clothing, and preventing colds (do not take colds lightly); if possible, get a flu vaccination. ④Oxygenation. Oxygen therapy is certainly beneficial in controlling pulmonary artery pressure, but long-term oxygen therapy may not slow down the progression of the disease. For patients with advanced PAH development, additional oxygenation equipment at home to ensure regular daily oxygen intake can effectively relieve symptoms and enhance the ability to move around on their own. Patients who have difficulty taking care of themselves can also receive oxygen continuously; the concentration of inhaled oxygen does not need to be too high, as long as the oxygen saturation is above 90%. The inevitable consequence of continued development of PAH is right heart failure; therefore, medications for heart failure, although not effective in controlling pulmonary artery pressure, can be beneficial in relieving symptoms. For example, classical cardiac (digoxin) and diuretic (furosemide, spironolactone, etc.) drugs are given orally, or catecholamines (dobutamine, dobutamine) are pumped intravenously. (vi) Anticoagulation therapy. Patients with severe PAH have a compensatory increase in hemoglobin due to low oxygen levels in the blood, leading to increased blood viscosity; reduced activity, prolonged bed rest, heart failure, and arrhythmias also increase the risk of thrombosis. Although anticoagulation is not necessary in all patients who develop the Eissenmenger syndrome stage, some of these patients with a high thrombotic risk (e.g., history of thrombosis, persistent atrial fibrillation, etc.) should still be anticoagulated with oral warfarin and have their coagulation monitored regularly under medical supervision. (7) Selective pulmonary vasodilators (PAH-targeted therapy). This part will be specifically addressed in the next question. 5. I have already had a right heart catheterization and a rapid pulmonary artery dilation test, and the results are not very good. My doctor recommended that I take a drug to lower my pulmonary artery pressure and come back for a review in three months. This medicine is expensive, does it really work? Is surgery still possible for me? As the name implies, the action of selective pulmonary vasodilators is characterized by lowering pulmonary artery pressure while having less effect on the pressure of the body circulation; therefore, we also call it targeted therapy for PAH. Currently, the commonly used drugs in China include iloprost (Vantave), bosentan (Quancoli), sildenafil (Viagra), vardenafil (Elidel), tadalafil, etc. In fact, breakthroughs in the development of these drugs have been achieved in the last decade or so. Clinical trials and medical practice at home and abroad have confirmed that they can all dilate the pulmonary arteries to varying degrees and reduce pulmonary artery resistance, thus achieving symptom relief, improving exercise tolerance and prolonging life. This also means that we really have the means to effectively control PAH. It is not the intention of this article to review each of the various drugs, but only to point out a few misconceptions. (1) The main role of targeted therapy is to induce pulmonary vasodilation, or, in other words, to maximize the removal of factors that drive PAH. However, the available studies have not confirmed that pulmonary vasodilators can reverse severe pulmonary vascular (organic) lesions. Therefore, we cannot yet expect that a true cure of PAH can be achieved with pharmacological treatment.② In patients with precordial disease that has progressed to the Eissenmenger syndrome stage, even with standardized targeted drug therapy, a significant reduction in pulmonary artery pressure may not be observed, but it is possible to confirm a slight decrease in pulmonary artery resistance, a possible increase in the patient’s quality of life, some expected improvement in mobility A slight decrease in pulmonary artery resistance may be confirmed, patients’ quality of life may be improved, mobility may be expected to be improved to some extent, and survival time may be prolonged; – however, it is still unrealistic to expect a return to normal life status. (iii) Currently, the recommended duration of treatment for most drugs is 6 months, but because pulmonary artery disease is difficult to reverse, pulmonary artery pressure may gradually increase after discontinuation of the drug. Therefore, long-term adherence to the medication may not make otherwise an option. Selective pulmonary vasodilators are often expensive, costing tens of thousands of dollars for a single course of treatment, which is a heavy burden for patients with PAH. However, in recent years, as drug patents expire, the cost of related drugs may be significantly reduced. In some patients, right heart catheterization and acute pulmonary artery dilatation tests confirm that PAH has reached a critical state, at this time, rash surgery is very dangerous in the perioperative period, and the long-term consequences are difficult to predict, then, we often recommend that patients first use medication (mostly for 3 months), if the pulmonary artery resistance can be significantly reduced after taking medication, surgery can be carried out with confidence; on the contrary, if there is no significant change, or even higher than If there is no significant change, or even if it continues to rise compared to the pre-drug period, the procedure will be abandoned. In a few patients, the results of the review are still borderline, and we recommend to continue taking the medication and review it again in a few months. This means that medication may recruit more patients for surgery, but it does not change the selection criteria for surgery. Medication is not a panacea, and although we do see patients who were thought to be completely lost to surgery, who eventually underwent successful corrective surgery for precordial disease after a significant reduction in pulmonary artery resistance following the application of medication, such cases are a rare occurrence. Finally, we often see primary care physicians recommending PAH patients to take general antihypertensive drugs (body circulation antihypertensive drugs), such as Kepone (which is a type of angiotensin-converting enzyme inhibitor [ACEI]), which is clearly wrong. Because these drugs have a significantly greater effect on lowering pressure in the body circulation than in the pulmonary circulation, overdosing may cause an increase in symptoms leading to sudden death. Some physicians may also prescribe calcium antagonists, thinking that they may have some benefit in lowering pulmonary artery pressure. It must be understood that calcium antagonists are only effective in patients with positive acute pulmonary artery dilation tests. In patients with severe PAH, the criteria for a positive acute pulmonary artery dilation test is very difficult to meet. 6.I am 22 years old, recently married, and now I have congenital heart disease and severe pulmonary arterial hypertension, can I still have sex? Can I have children? Patients with congenital heart disease combined with severe PAH, if they have reached the stage of Eissenmenger syndrome, their physical strength is likely to be affected to some extent, but this does not necessarily mean that they cannot have sex. The patient’s current exercise capacity is the decisive basis. If the physical strength is now only mildly impaired, it is still possible to enjoy sex without overexerting oneself; of course, overindulgence is not good for anyone. However, pregnancy and childbirth is a different matter. Especially in the middle and late stages of pregnancy, as the fetus grows, the burden on the pregnant woman increases significantly, which is very difficult for patients with severe PAH to tolerate. According to statistics, the morbidity and mortality rate of pregnant women with combined severe PAH can reach 30% to 50%, therefore, women of childbearing age must pay attention to contraception; if they are already pregnant, they should decisively terminate the pregnancy to prevent life-threatening consequences.