Pulmonary hypertension is a hemodynamic and pathophysiological state in which the pressure of the pulmonary arteries rises beyond a certain threshold, and can be an independent disease, a complication, or a syndrome, and in severe cases can cause right heart failure. The hemodynamic diagnostic criteria are: at rest at sea level, the right heart catheter detects the mean pressure of the pulmonary artery ≥25 mmHg. Pulmonary hypertension is a common disease, multiple diseases, and the disability rate and case fatality rate are very high, which has attracted great attention.
Pulmonary hypertension-related diseases is a rapidly developing medical field, in recent years, due to the deepening of its understanding of its pathogenesis, the continuous development of new targeted therapy drugs, a large number of evidence-based medical research continues to carry out, as well as the diagnosis and treatment guidelines and recommendations continue to be introduced, providing a good diagnostic basis for clinical practice.
On July 17, 2020, at the China International Heart Failure Conference (CIHFC), Professor Huang Lan, director of the Institute of Cardiovascular Medicine of the Third Military Medical University, gave a wonderful report on Pulmonary Hypertension (PH) at the meeting, summarizing and sharing the new progress and global perspectives in the diagnosis and treatment of pulmonary hypertension.
Clinical symptoms and diagnosis of pulmonary hypertension
First of all, Professor Huang Lan shared the latest clinical classification of PH and its basic concept, PH is a disease or pathophysiological syndrome caused by abnormal increase in pressure in the pulmonary artery caused by known or unknown causes, resulting in pulmonary circulation disorders and high load on the right heart, which can cause heart failure and even death in severe cases. Professor Huang Lan stressed that pulmonary hypertension is very common in clinical practice and is a serious health care problem that endangers people's health.
Figure 1: The latest clinical classification of PH
The clinical manifestations of PH lack specificity, and the common symptoms are dyspnea (the most common symptom, exertion), chest pain, syncope, fatigue, hemoptysis, hoarseness; etiological symptoms can be divided into congenital heart disease - heart murmur since childhood, susceptibility to colds, differential cyanosis, squatting phenomenon, etc.; connective tissue disease - skin, mucous membrane, joint, bone and other abnormalities; embolic disease - venous thrombosis related manifestations; respiratory diseases - occupational history, chronic cough, phlegm, asthma history, etc.
The main signs of PH are:
(1) Increased respiratory rate, pulse frequency, small;
(2) Jugular vein filling can be seen in right heart failure;
(3) There is a lifting beat on the left lower border of the sternum, reflecting the enlargement of the right ventricle;
(4) Hyperpsis, splitting, left second intercostal heard and systolic jet sound and jet murmur;
(5) The tricuspid valve total systolic regurgitation murmur can be heard between the 4th to 5th ribs of the left sternal margin
Professor Huang Lan said that clinicians should pay attention to the examination of the cause and signs of pulmonary hypertension, which is very likely to be related to the occurrence and development of other diseases, and for the diagnosis of PH, it is necessary to complete according to the following steps: screening of pulmonary hypertension, screening of etiology, hemodynamic diagnosis, and severity assessment. Esc guidelines suggest that patients with suspected PH need to perform some non-invasive tests to determine the presence of Type II and III pulmonary hypertension. If no evidence of these two types of disorders is found, or if the increase in PH is disproportionate to the severity of the patient's condition, a relatively uncommon cause of PH should be sought, and further diagnostic strategies include right heart catheterization (RHC) and acute vascular response testing.
Figure 2: Diagnostic strategies for pulmonary hypertension
Imaging and laboratory manifestations of pulmonary hypertension
1. Cardiac ultrasound
Manifested by enlargement of the right atrium and right ventricle, widening of the inner diameter of the pulmonary artery and decreased compliance, tricuspid regurgitation, flat or abnormal movement of the ventricular septum, pericardial effusion, re-opening of the foramen ovale, etc. Cardiac acoustic contrast has diagnostic value for congenital heart disease and the reopening of the ovary hole.
2. Tricuspid valve reflux and differential pressure
Ph is excluded if the tricuspid regurgitation velocity < 2.8m/s or sPAP < 36 mmHg, the tricuspid valve reflux velocity > 3.4 m/s or sPAP >50 mmHg is diagnostic, and right heart catheterization is indicated when the tricuspid valve reflux velocity is 2.8-3.4 m/s or the SPAP is between 36 and 50 mmHg.
3. Lung perfusion/ventilation imaging
A pulmonary segmental-distributed perfusion defect does not match ventilation imaging, suggesting chronic thromboembolic pulmonary hypertension (CTEPH), with the exception of CTEPH if completely normal; subsectional distribution or "patchy" perfusion defects or completely normal consider arterial pulmonary hypertension (PAH). False positive manifestations should also be noted, such as pulmonary artery sarcoma, aortic arteritis (lung type), pulmonary venous occlusion and external vascular pressure, etc. - similarly, pulmonary perfusion and ventilation mismatch can be seen, which needs to be further differentiated.
4. The diagnostic value of high-resolution CT for lung diseases
Interstitial lung disease, emphysema, lymph node disease, pleural shadow, pleural effusion on tumors, cellulose mediastinitis, etc. caused by PH also have high diagnostic value; CT vascular imaging for pulmonary hypertension can observe the embolus in the pulmonary artery and the degree of lesions, which can indicate the presence of PH.
5. Hemodynamic examination of PAH
Definitive diagnosis and quantification of PH, evaluation of patient severity, consideration of PAH-targeted drug therapy or evaluation of drug effects; preoperative examination and evaluation of congenital heart disease; acute vascular drug response testing.
Clinical diagnostic tests and prognostic indicators of pulmonary hypertension
Professor Huang Lan first explained the severity assessment of PH, put forward the importance of clinical diagnostic tests for the judgment of PAH conditions, and called on major hospitals in China to carry out clinical diagnostic tests on PH. Among them, he proposed that the 6-minute walk test (6MWT) is a simple and easy test method, which has important diagnostic value for the mobility of PAH patients and the evaluation of drug treatment.
Figure 3: Clinical diagnostic tests and prognostic indicators of pulmonary hypertension
Professor Huang Lan concluded that clinicians should improve their awareness of PH diagnosis and strengthen differential diagnosis. This is because screening for phH causes is multidisciplinary, making a definitive diagnosis is sometimes difficult, and there is a high rate of missed and misdiagnosed diagnoses. Screening for phH causes requires multidisciplinary knowledge or a multidisciplinary team of experts. It is necessary to follow clinical guidelines, identify high-risk patients, screen for etiology, and pay attention to clinical practice, accumulate clinical experience, and improve the level of diagnosis.
Treatment of arterial pulmonary hypertension
Professor Huang Lan introduced that the treatment of PAH can be divided into three parts, general treatment and basic treatment, drug therapy for the pathogenesis of PAH, and interventional and surgical treatment.
1. General treatment and basic treatment
Includes treatment of primary and pathogenic factors, health education, oxygen therapy (oxygen saturation at rest and exercise is guaranteed>90%), anticoagulation, diuresis, and digoxin use (for patients with increased ventricular rate of PAH with atrial fibrillation)
2. Targeted drug therapy for the pathogenesis of PAH
(1) Calcium channel blocker: strictly grasp the indications according to the acute vascular reaction test; start from a small dose, gradually increase the dose, until the tolerated dose is reached; after 1 year, it needs to be re-examined, and the continuous sensitivity can be used for a long time. The main side effects of calcium channel blockers include hypotension, ventilation-perfusion mismatch, redness, palpitations, etc.
(2) Prostacyclin and its analogues: Prostacyclin is a metabolite of arachidonic acid, a strong inhibitor of pulmonary vasodilators and platelet aggregation, and also has endothelial cell protection and antiproliferative properties. Prostacyclins and their analogues that have been shown to be effective in the treatment of PAH include: epoprost (Epoprostenol), treprost (Treprostinil), berapost, and iloprost (Hoprost). The prostacprost analogues that have been approved for marketing in China include inhaled preparations of inoprost and oral bepost.
(3) Selexipag: oral prostacyclin receptor agonist, highly selective to prostacyclin IP receptor, low adverse reactions, patients may tolerate larger doses. Selexipag significantly improves hemodynamic parameters including pulmonary vascular resistance and cardiac index in patients with PAH, and is well tolerated by the drug.
(4) Endothelin receptor resistance: bosentan (Bosentan), sitaxsentan (Sitaxsentan), ambrisentan (Ambr isentan), bosentan (bosentan, quancoride) has been listed in China, for oral preparations, the starting amount of 62.5mg bid, after 4 weeks of treatment, increase the dose to 125mg bid maintenance treatment, the main side effect is abnormal liver function, need to detect liver function once a month. Bosentan can be used in patients with PAH who have functional levels 3 and 4.
(5) Macitentan: a dual endothelin receptor antagonist with high efficiency, strong tissue penetration, lipophilicity, and strong affinity with the receptor. Studies have shown that macitentan acts 10 times stronger than bosentan, has a twice as long duration of action, and does not inhibit the bile salt output pump, has little effect on liver function, and has less effect with food and drugs.
(6) Phosphodiesterase-5 inhibitors: sildenafil, valdenafil and tadaranafe. At present, there are no indications for the treatment of pulmonary hypertension in China, nor is there a special dosage form, dosage and method for the treatment of pulmonary hypertension, and the dose of sildenafil recommended by foreign countries is 20mg tid.
(7) Rho kinase inhibitors: intravenous injection of fasudil can reduce pulmonary vascular resistance in patients with pulmonary hypertension, increase cardiac output, and have good safety, which is similar to the effect of inhaling iloprostaglandin.
(8) Riociguat: A stimulator of soluble guanylate cyclase (sGC) that activates guanylate cyclase to function through the nitric oxide pathway. On October 8, 2013, the drug for the treatment of PAH was approved by the FDA.
Professor Huang Lan said that the combination of drugs can improve the efficacy and significantly reduce side effects. The combination of two drugs at the beginning of treatment is a new perspective on current clinical use.
Figure 4: Drug-targeted therapy strategies
Pulmonary hypertension is a more dangerous disease in the history of modern medicine, and patients with pulmonary hypertension have only a survival rate of 40-55% if they are not treated effectively. Therefore, Professor Huang Lan stressed that for patients with pulmonary hypertension, they must follow the doctor's instructions and receive treatment in time to avoid further deterioration of the condition.