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Editor's note
The field of pulmonary hypertension has been developing rapidly in recent years. First, a number of genes that are clearly related to pulmonary arterial hypertension (PAH) have been newly discovered. Secondly, targeted therapies have been on the market one after another. Third, a major breakthrough has been made in the treatment of chronic thromboembolic pulmonary hypertension (CTPEH). In addition, the concept of risk stratification and the recognition of initial combined treatment strategies have injected new vitality into the diagnosis and treatment of pulmonary hypertension. At the 15th Qianjiang International Cardiovascular Conference (QICC 2021), Professor Huang Lan from the Second Affiliated Hospital of the Army Military Medical University made a special analysis on the status and evaluation of the diagnosis and treatment of pulmonary hypertension.
The latest research implications
The latest research suggests that pulmonary hypertension may be an immune and inflammatory process triggered by cancer cells, and the use of targeted drugs tyrosine kinase inhibitors (TKIs) may increase The risk of pulmonary hypertension in clinical pulmonary hypertension, and the older the patient, the longer the medication time, the more significant the above risk increases. Therefore, in the process of tumor treatment, especially during targeted drug treatment, we must be alert to the occurrence of pulmonary hypertension.
Relevant data show that the incidence of pulmonary hypertension in high-dose dasatinib is as high as 0.45%. Although pulmonary hypertension can be partially or even completely reversed after stopping the drug, more than one-third of patients will still have persistent pulmonary hypertension. Other studies have shown that the activation of the TGF-β signaling pathway can lead to the occurrence of PAH, which is expected to become a new target for the treatment of pulmonary hypertension.
concept analysis
Pulmonary hypertension and Pulmonary hypertension is not a concept. pulmonary hypertension is a hemodynamic concept , which refers to the mean pulmonary artery pressure (mPAP) ≥25 mm Hg measured by the right heart catheter. PAH is a type of malignant pulmonary vascular disease characterized by progressively increased pulmonary vascular resistance, which can lead to right heart failure or even death; the diagnostic criteria is sea level, and the right heart catheter is at rest to check the mean pulmonary artery pressure ≥25 mm Hg, while pulmonary capillary wedge pressure (PAWP) ≤15 mm Hg, pulmonary vascular resistance> 3 WU. It should be noted that in order to advance the prevention and treatment front, the diagnostic criteria for mPAP for pulmonary hypertension has a tendency to be reduced to 20 mm Hg.
The causes of pulmonary hypertension are complex and diverse, and the hemodynamic classification is shown in Figure 1. Among them, postcapillary pulmonary hypertension (pulmonary hypertension caused by left heart disease) is the most common. There are five major clinical categories (Figure 2), namely PAH, pulmonary hypertension caused by left heart disease, pulmonary hypertension caused by respiratory system disease and/or hypoxia, pulmonary hypertension caused by pulmonary artery obstructive disease, and unknown factors. Caused by pulmonary hypertension. Among them, PAH can be further divided into idiopathic PAH, acute pulmonary vasodilation test positive PAH, hereditary PAH, drug and toxicant-related PAH, related factors (connective tissue disease, HIV infection, portal hypertension, congenital diseases, Schistosomiasis) caused by PAH, pulmonary venous occlusive disease/pulmonary capillary hemangioma, persistent pulmonary hypertension in newborns. In the future, with the deepening of understanding, the classification of pulmonary hypertension is expected to be more refined.
Figure 1 Hemodynamic classification of pulmonary hypertension
Figure 2 Clinical classification of pulmonary hypertension
Precautions for diagnosis and treatment of various types of pulmonary hypertension The dose of calcium channel blocker is sensitive, the prognosis is good, and there is a specific treatment plan.
Pulmonary venous occlusive disease/pulmonary capillary hemangioma-related PAH is mainly related to EIF2AK4 biallelic mutations, and is associated with signs of pulmonary vein and pulmonary capillary involvement.It should be noted that pulmonary edema may occur after this type of PAH targeted therapy.
Epidemiological data overview
Epidemiological studies in western countries have shown that the prevalence of pulmonary hypertension in the general population is about 1%, and as high as 10% in people over 65 years old. Pulmonary hypertension caused by systemic diseases and/or hypoxia is the most common. The incidence and prevalence of PAH in the general population are 5-10 per million person-years and 15-60 per million, respectively, and about half of them are idiopathic PAH and hereditary PAH or drug-related PAH. The most common factor for PAH is connective tissue disease , of which systemic sclerosis accounts for about two-thirds. It should be noted that the average age at diagnosis of idiopathic PAH has been increasing in recent years, but the reason is unknown.
my country currently lacks epidemiological data on pulmonary hypertension and PAH in the general population. In general, the most common PAH disease in my country is congenital heart disease, followed by idiopathic PAH and connective tissue disease-related PAH. Among them, the most common PAHs associated with connective tissue diseases are systemic lupus erythematosus and Sjogren’s syndrome . Idiopathic PAH is dominated by young and middle-aged women, and elderly patients are relatively rare.
Fortunately, the 5-year survival rate of patients with pulmonary hypertension is higher, exceeding 50%.
PAH pathogenesis, genetics and pathology
The occurrence and development of PAH are closely related to pulmonary vascular remodeling and the tension changes involved in a variety of vasoactive molecules and ion channels. Genetic research has now found nine pathogenic genes (BMPR2, BMP9, ACVRL1, ENG, SMAD9, BMPR18, TBX4, CAV1 and KCNK3),It can explain 50%~80% of hereditary PAH and 20%~50% of idiopathic PAH. Among them, BMP9 is the newly discovered PAH pathogenic gene, which can increase the risk of PAH by 22 times. It can explain the genetic cause of 6.7% of Chinese idiopathic PAH patients. It is the second only to BMPR2.
PAH mainly involves small pulmonary arteries with a diameter of <500> fibrosis , adventitia thickening and fibrosis, etc. Severe lesions include plexiform lesions, dilated lesions And other compound lesions. It should be noted that in addition to pulmonary artery remodeling, pulmonary veins and even pulmonary capillaries can also undergo remodeling or proliferative changes in all types of pulmonary hypertension.
Diagnosis points and precautions of pulmonary hypertension
First of all, we must strengthen the awareness of the diagnosis of pulmonary hypertension . Suspected patients should be asked in detail about related symptoms and predisposing factors, and past medical history, family history, reproductive history, The history of exposure to weight loss drugs or poisons and the history of living in plateaus, etc., and perfect physical examination. Secondly, for patients with clinically suspected pulmonary hypertension, laboratory tests should be perfected (blood routine, electrolytes, transaminase, bilirubin, creatinine, uric acid, DD dimer, BNP or NT-proBNP, thyroid function and arterial blood gas analysis, etc.), comprehensively evaluate the condition. In addition, for patients with clinically suspected pulmonary hypertension, routine electrocardiogram, chest X-ray film, echocardiography, respiratory function, CT pulmonary angiography, pulmonary ventilation perfusion imaging, cardiopulmonary exercise test and other examinations should also be routinely performed to improve the right as soon as possible. Cardiac catheterization for accurate diagnosis and classification.
BNP, NT-proBNP
can reflect the severity of the disease, curative effect and estimate the prognosis,It plays an important role in PAH screening and diagnosis. Therefore, patients with PAH should routinely check BNP and NT-proBNP, and try to keep them in the normal or close to normal range during treatment.
Echocardiography
In addition to judging pulmonary hypertension, it also helps to find abnormalities in heart structure, function, or vascular malformations , and evaluate right heart function. It should be emphasized that tricuspid regurgitation velocity is of great value in judging the possibility of pulmonary hypertension (Figure 3)
Figure 3 The diagnostic value of tricuspid regurgitation velocity for pulmonary hypertension
right Cardiac catheterization
is not only the gold standard for diagnosing PAH, but also an indispensable means to guide the development of scientific treatment plans. In clinical practice, some common mistakes should be avoided (cardiac output, PAWP, oxygen saturation are not measured; ventricular mean pressure is measured instead of ventricular end diastolic pressure), and attention should be paid to the selection of puncture route, guide wire, etc. (use Swan-Ganz catheter to avoid femoral vein approach) to improve the success rate of the operation.
Echocardiography is the first-line non-invasive diagnosis method for suspected pulmonary hypertension. For unexplained pulmonary hypertension and need to exclude CTEPH, it is recommended to perform lung perfusion or pulmonary ventilation perfusion imaging. CT pulmonary angiography should also be recommended when CTEPH is suspected. It is particularly emphasized that all patients with pulmonary hypertension should undergo routine blood tests, blood biochemistry, autoimmune antibodies, HIV antibodies, and thyroid function tests.
In addition, for patients with pulmonary hypertension, cardiac function classification and motor function evaluation should also be done . Six major indicators of WHO cardiac function classification, 6-minute walking distance, NT-proBNP, right atrial pressure, cardiac index , and mixed venous blood oxygen saturation were used for risk stratification.It helps to make the treatment more targeted.
Follow-up of pulmonary hypertension
The guidelines recommend that during follow-up, cardiac function, exercise tolerance, serum biochemical markers, echocardiography and hemodynamic indicators should be used to evaluate the severity of PAH patients. If the patient's condition is stable, follow-up can be done every 3 to 6 months. In addition, during the follow-up period, adequate targeted drug therapy is recommended to achieve or maintain a low-risk condition. If the patient has been treated with targeted drugs and the disease is still progressing or maintains an intermediate-risk state, then the targeted drug treatment should be considered insufficient.
PAH treatment
General treatment and supportive treatment recommendations are shown in Figure 4. In terms of drug therapy, the main drugs include calcium channel blockers and targeted drugs. Patients with idiopathic PAH, hereditary PAH, and drug-related PAH can be treated with high-dose calcium channel blockers if the acute pulmonary vasodilation test is positive. Close follow-up should be followed after treatment, and a full re-evaluation should be performed after 3 to 4 months of treatment. As far as targeted drug therapy is concerned, the current initial combination therapy is an important trend and strategy, and the sequential combination therapy plan should be selected according to the specific conditions of the patient.
Figure 4 Recommendations for general treatment and supportive treatment
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