Five things to know about pulmonary arterial hypertension

Pulmonary hypertension is a pathological condition that can be life-threatening for the patient. As the disease develops, a gradual closure of the lumen of the pulmonary vessels is observed, as a result of which the pressure increases and the functioning of the right ventricle and atrium is disrupted. The Yusupov Hospital diagnoses and treats patients with pulmonary hypertension. Cardiologists at the Yusupov Hospital use modern methods of instrumental and laboratory research to detect hypertension at the initial stage. Timely diagnosis of pulmonary hypertension increases the likelihood of a favorable treatment outcome.

Experts consider pulmonary hypertension to be one of the most common diseases of the cardiovascular system. Women between the ages of 30 and 40 get sick more often than men. A patient with pulmonary hypertension may not see a doctor at the initial stages of the pathological process, since the clinical picture is quite blurred. This disease is characterized by an increase in blood pressure in the pulmonary artery at rest by 25 mmHg. Art., and during physical activity - by 50 mm Hg. Art. And.

Pulmonary hypertension, if left untreated, leads to right ventricular failure, which can be fatal. If you notice signs of pulmonary hypertension, contact Yusupov Hospital immediately.

Kinds

Doctors distinguish several main types of pulmonary hypertension:

• Primary – a disease of unknown origin, which can be either congenital or acquired. The disease is called “idiopathic pulmonary hypertension.” It is characterized by changes in the pulmonary artery and enlargement of the right ventricle. Primary pulmonary hypertension causes disability for the patient, and if left untreated, leads to death;
• Secondary - develops as a complication of other diseases: congenital and acquired heart defects, HIV infection, connective tissue diseases, bronchial asthma, pathology of the respiratory system. The disease can develop due to blockage of blood vessels by blood clots. In this case, chronic pulmonary hypertension is diagnosed.

Pathogenesis

Primary PH is characterized by smooth muscle hypertrophy, variable vasoconstriction, and vessel wall remodeling. Vasoconstriction is caused by an increase in the activity of thromboxane and endothelin 1, as well as a decrease in the activity of nitric oxide and prostacyclin. Increased pulmonary vascular pressure is caused by vascular obstruction. It affects endothelial damage.

As a result, coagulation on the intimal surface is activated, which can aggravate arterial hypertension. This is also facilitated by thrombotic coagulopathy, which is a consequence of an increase in the content of plasmogen activator inhibitor type 1 and fibrinopeptide A and a decrease in the activity of tissue plasmogen activator. Focal coagulation on the surface of the endothelium must be distinguished from chronic thromboembolic pulmonary arterial hypertension, which is provoked by organized pulmonary thromboembolism.

As a result, in most patients, primary pulmonary hypertension becomes a provoking factor of right ventricular hypertrophy with dilatation and right ventricular failure.

Degrees of pulmonary hypertension by pressure

Doctors at the Yusupov Hospital use echocardiography or cardiac catheterization to determine the severity of the disease. There are three degrees of severity of pulmonary hypertension:

• Increase in pressure in the pulmonary artery by 25 - 45 mmHg. Art. Indicates stage I of the disease;
• Increase in pressure by 45-65 mmHg. Art. – pulmonary hypertension II degree;
• An increase in pressure of more than 65 mm Hg. Art. – pulmonary hypertension stage III.

Pulmonary hypertension syndrome is also classified depending on the observed clinical picture. In this case, 4 classes are distinguished:

• Class I: patients do not experience a decrease in physical activity. Habitual loads do not cause shortness of breath, dizziness, weakness and pain;
• Class II: patients experience a decrease in physical activity. During normal exercise, the patient experiences dizziness, shortness of breath, chest pain, and weakness. At rest, these symptoms disappear;
• Class III: the physical activity of patients is significantly impaired. With a slight load, symptoms characteristic of this disease appear;
• Class IV: significant decrease in activity. Stage 4 pulmonary hypertension is characterized by severe symptoms both at rest and with minimal physical activity.

Symptoms

Pulmonary hypertension does not have pronounced symptoms, so treatment begins in the later stages of the disease. At the onset of the disease, the following symptoms can be detected:

• The appearance of slight shortness of breath at rest or with little physical activity;
• Hoarse voice or dry cough;
• Loss of body weight for no apparent reason;
• Rapid heartbeat, as the disease progresses, pulsation of the jugular vein is clearly noticeable in the patient’s neck;
• Depressed mood and constant feeling of fatigue and weakness;
• Fainting and dizziness, which are a consequence of hypoxia - lack of oxygen.
• In later stages, pulmonary hypertension is manifested by the following symptoms:
• Heart rhythm disturbances - arrhythmia;
• Symptoms of myocardial ischemia and angina attacks, in which the patient is overcome by a feeling of fear, cold sweat appears and pain appears in the chest;
• Hemoptysis and the appearance of blood streaks in the sputum.

At the terminal stage, tissue death occurs due to the formation of blood clots in the arterioles. Hypertensive crises in patients occur at night. Acute heart failure or blockage of the pulmonary artery by a thrombus can be the main causes of death.

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Interview and examination of the patient

It is necessary to find out whether the patient has had episodes of deep vein thrombosis, sudden swelling of the legs, or thrombophlebitis. Many patients have a family history of sudden death, cardiovascular disease, and an increased tendency to thrombus formation.

Objective evidence of a history of pulmonary embolism (PE) is the coincidence in time of the clinical presentation of thrombosis of the veins of the lower extremities and the appearance of shortness of breath. In the coming months after PE, a period can be identified in patients when the condition remains stable and asymptomatic. This is due to the fact that the right ventricle copes with the load and allows maintaining good exercise tolerance until progressive pulmonary vascular remodeling develops. Almost the only reliable evidence of previous PE can be data from perfusion scintigraphy or computed tomography of the lungs performed during an acute episode of PE.

During a general examination of patients with CTEPH, blueness (cyanosis) may be detected. With the development of right ventricular heart failure, swollen neck veins, enlarged liver, peripheral edema, and abdominal dropsy are noted.

Causes of the disease

The causes of pulmonary hypertension vary. Scientists have not yet established why idiopathic pulmonary hypertension occurs. The likelihood of its development is high in people with autoimmune diseases who take oral contraceptives or have close relatives with this disease. Secondary pulmonary hypertension occurs due to complications of vascular diseases, lungs, and heart defects.

A gradual narrowing of arterioles and capillaries belonging to the pulmonary artery system precedes the development of the disease. In the later stages of arterial damage, inflammatory destruction of the vessel wall may occur. As a result of these changes in the blood vessels, a progressive increase in pressure or pulmonary arterial hypertension occurs.

Pulmonary hypertension is closely associated with disorders of the cardiovascular system and lungs:

• Chronic obstructive pulmonary disease;
• Insufficient ventilation of the lungs;
• Stopping breathing during sleep (apnea);
• Anomalies in the development of the respiratory system;
• Congenital and acquired heart defects (mitral valve stenosis, non-closure of the septum between the ventricles, pathology of the left ventricle);
• Coronary heart disease;
• Inflammation of the myocardium – myocarditis;
• Chronic heart failure.

Risk factors for the development of pulmonary hypertension include family history, use of narcotic substances, certain medications (Fenfluramine, Aminorex, Dexfenfluramine) and chemotherapy drugs. Pulmonary hypertension is often diagnosed in patients with autoimmune diseases. A strong increase in pressure in the pulmonary artery can be caused by hemolytic anemia, sarcoidosis and damage to the thyroid gland.

Prevention

Every person can significantly reduce their risk of developing this lung disease. To do this, patients with varying degrees of pulmonary hypertension need to follow several rules:

• give up bad habits (smoking, excessive alcohol consumption), adhere to healthy eating rules;
• perform light exercise every morning;
• undergo regular preventive examinations with a pulmonologist;
• if a person has chronic diseases of the respiratory system, it is necessary to strictly monitor their course;
• there should be regular physical activity in a moderate mode;
• It is also necessary to exclude situations that can expose a person to severe and prolonged stress (conflicts in the family, at work).

But the most important thing that any patient should remember is that the causes of pulmonary hypertension are very diverse, and at the very first “bells” of this insidious disease, you need to urgently contact a qualified specialist to undergo a detailed examination. After all, only when the disease is diagnosed in the early stages there is a high chance of successful recovery; when the disease is detected in the later stages, in 50% of cases it leads to death within 5 years after the onset of this type of hypertension. And in no case do not self-medicate; only a doctor can select competent comprehensive treatment; the dosage of certain medications depends on the severity of the disease and the type of concomitant pathologies.

Diagnostics

Normal pulmonary artery pressure at rest is about 15 mmHg. Art. If it exceeds 25 mmHg. Art., then this is already a pathology. More than 65 mm Hg. Art. considered the most severe degree of pulmonary hypertension.

At the Yusupov Hospital, blood pressure is measured using a probe. A puncture is made in the jugular vein and a probe is inserted; the attached catheter reaches the artery itself. This is a very complex procedure, but today it is considered the best way to diagnose pulmonary hypertension. Research at the Yusupov Hospital is carried out by a highly qualified cardiologist. He prescribes studies that allow you to assess the condition of the lungs and heart and establish the cause of high blood pressure:

• Registration of an electrocardiogram – allows to identify hypertrophy of the right ventricle and atrium;
• Computed tomography – provides information about enlarged arteries and the presence of concomitant diseases;
• Echocardiography – is carried out to determine the speed of blood movement and examine the cavities of the heart and blood vessels;
• Chest X-ray – necessary to establish the size of the heart and confirm the diagnosis;
• Pulmonary angiography is a method in which a contrast agent is injected to establish the vascular pattern in the pulmonary artery system.

Pulmonary hypertension in newborns is extremely rare. The overwhelming majority of these diagnoses are made in the first days of a baby’s life. This helps reduce the number of deaths.

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Treatment

Standards for the treatment of pulmonary hypertension require a combination of adequate therapy with the use of drugs, implementation of recommendations to reduce symptoms, and surgical methods. Non-drug methods of treating pulmonary hypertension syndrome involve maintaining a water-salt balance, moderate physical activity and oxygen therapy. Doctors at the Yusupov Hospital recommend that patients diagnosed with pulmonary hypertension observe the following restrictions:

• Reduce fluid intake - no more than 1.5 liters per day. Also reduce salt intake;
• Avoid climbing to heights (no more than 1000 meters);
• Avoid fainting, shortness of breath and chest pain, which can be achieved through dosed physical activity.

To treat pulmonary hypertension, drugs are used whose action is aimed at restoring the function of the respiratory and cardiovascular systems. Using medication, specialists are able to reduce the load on the heart, dilate blood vessels and lower blood pressure.

At the Yusupov Hospital, cardiologists prescribe the following pharmacological drugs to patients with pulmonary hypertension:

• Calcium antagonists. They change the heart rate, relax the muscles of the bronchi, reduce spasm of pulmonary vessels, reduce platelet aggregation, increase the stability of the heart muscle;
• Diuretics. Remove excess water from the body, reduce blood pressure;
• ACE inhibitors. Dilate blood vessels, reduce the load on the heart, reduce blood pressure;
• Nitrates;
• Antiplatelet agents. Reduce the ability of red blood cells and platelets to stick together. Prevents them from sticking to the inner lining of blood vessels;
• Direct acting anticoagulants. These drugs prevent the formation of fibrin (a substance in the blood that forms the basis of a blood clot) and also prevent the formation of blood clots (thrombi);
• Indirect anticoagulants. Drugs belonging to this group affect blood clotting and also reduce blood clotting;
• Endothelin receptor antagonists;
• Bronchodilators. These drugs improve ventilation;
• Nitric oxide NO in the form of inhalations - for vasodilation;
• Antibiotics - if there is a bronchopulmonary infection;
• Prostaglandins. Powerful vasodilators that have a whole range of additional effects, such as preventing the adhesion of platelets and red blood cells, slowing down the formation of connective tissue, and reducing damage to endothelial cells.

Severe pulmonary hypertension in adults requires surgical treatment:

• Thromboendarterectomy – removal of blood clots from blood vessels;
• Atrial saptostomy - creating an opening between the atria to reduce pressure;
• Transplantation of the lung and heart complex or just the lung is used in the later stages of the disease and in the presence of other diseases.

To stop the progression and prevent complications of the disease, contact specialists at the Yusupov Hospital in a timely manner.

Primary pulmonary hypertension

Oksana Mikhailovna Drapkina , professor, doctor of medical sciences:

– Alexey Nikolaevich, thank you very much. I know that in the program that you are presenting, being the face of your institution, we have Sergei Nikolaevich Ivanov. Despite the fact that we still have questions, we are following the regulations. And I want to tell you about Professor Sergei Nikolaevich Ivanov. This is a doctor of medical sciences, professor, leading researcher in the laboratory of congenital heart defects of the Center for Pediatric Cardiac Surgery and Surgery of Newborns, Novosibirsk Research Institute of Circulatory Pathology named after Meshalkin. Pediatric cardiologist, Sergei Nikolaevich is fluent in functional and ultrasound diagnostic methods and is engaged in a comprehensive program of clinical and functional assessment of hemodynamics of the pulmonary circulation and pathogenetic methods of treating secondary pulmonary hypertension.

And therefore, dear colleagues, you have a unique opportunity to ask questions to Sergei Nikolaevich live and get answers about primary pulmonary hypertension. Hello, Sergey Nikolaevich. And please, you have the floor.

Sergey Nikolaevich Ivanov , professor, doctor of medical sciences:

- Good afternoon. We have already met. I am very pleased to take part in this form of communication with Russia, with our cardiologists, with our doctors, with patients. Indeed, this is a unique opportunity, very simple and accessible, to discuss some topical issues.

I don’t know how much time I have left, but today and last time we discussed that we will continue the topic of pulmonary hypertension, because this is really a very interesting problem. And if you allow me, I will begin.

Pulmonary hypertension. It includes a group of diseases that are characterized by a progressive increase in pulmonary vascular resistance, which leads to the development of right ventricular heart failure and premature death of patients.

If we talk about the criteria - this is always a very pressing question - then, according to European recommendations from 2009, the pressure in the pulmonary artery, and the average pressure in the pulmonary artery, and not the peak pressure, should exceed 25 millimeters of mercury. But it is very important to emphasize that it must be measured according to right heart catheterization, that is, according to invasive examination. Ultrasound data is not entirely accurate data today.

Epidemiology of pulmonary hypertension. If we look at our usual monographs, it is believed that this is a rather rare pathology. But with a closer look at this problem, it is believed that there are about 15 cases of such patients with high blood pressure in the small circle per one million population. If we take today's topic - idiopathic pulmonary hypertension - or, as they used to say, primary pulmonary hypertension or Aerz's disease - this is about six cases per one million population. That is, this is not a rare pathology.

If we take, say, the pediatric category of patients, which is what I am primarily concerned with, according to the European TOPP registry, in which 22 countries participated, there are about 500 patients from 3 months to 18 years with pulmonary hypertension.

It is very important to note that the past 2012 was the year of orphan pathology in Russia. And a number of landmark federal laws were adopted, which were included in our federal law “On the Fundamentals of Protecting the Health of Citizens of the Russian Federation.” And in February 2012, by order of the Ministry of Health and Social Development, a draft list of rare, so-called orphan diseases was prepared, which included more than 250-260 diseases. This is a very large number. And it is pleasant to note that those seven rare nosologies have today been expanded by order of the President of Russia to 24.

In April 2012, Government Decree No. 403 of the Russian Federation stated that all constituent entities of the Federation must maintain a so-called register of rare orphan life-threatening diseases, which includes pulmonary hypertension.

Here is a slide of the list of rare orphan diseases. And I would like to draw attention to paragraph 24, which includes pulmonary arterial hypertension, in particular idiopathic primary pulmonary hypertension. This is a serious legal, legal and legislative achievement, which included this group of patients.

As for pulmonary hypertension, it is a rapidly progressing disease. I would like to draw your attention to this slide: the earlier treatment is started at the first symptomatic manifestations, at the first complaints, the effect and life expectancy in this category of patients is higher. That is, there is no need to wait for the terminal stage - there the effect of treatment is already much lower.

If we look at the survival curves of patients with the most common pathologies, then survival is better, of course, with high pressure in the pulmonary circle in patients with congenital heart defects. But the survival rate is significantly lower, but still high, in patients with idiopathic pulmonary hypertension. The lowest survival rate is in patients with high pulmonary blood pressure based on HIV infections.

There are accepted classifications. Here is one of the generally accepted classifications of pulmonary hypertension, adopted in Venice. It differs little from the latest classification of 2009, which distinguishes five groups of diseases that are accompanied by pulmonary arterial hypertension.

This is a large list of diseases. And one of the first is idiopathic, the so-called primary, of unknown nature. This is part of the diseases associated with high pulmonary hypertension, these are systemic diseases, these are congenital heart defects, these are HIV infection, persistent pulmonary hypertension of newborns, and so on.

The second group is diseases in which the pressure in the small circle also increases. These are all pathologies of the left parts of the heart, and in particular, what the first report was about now, this is decompensation, this is severe heart failure, severe decompensation of the left parts. It is always accompanied by secondary signs of increased pressure in the pulmonary circulation.

The third, large well-known group is associated with pulmonary hypertension caused by pathology of the respiratory systems and hypoxemia. This is COPD, this is bronchial asthma, this is hypoxemia, and so on.

The fourth group, well known to cardiologists and therapists, is pulmonary hypertension due to chronic thromboembolic and embolic lesions, the so-called CTEPH - chronic thromboembolic pulmonary hypertension.

Well, the so-called fifth – mixed conditions – are already rare diseases. Sarcoidosis, histiocytosis and other pathologies that also cause increased pressure in the pulmonary circulation.

Thus, I would like to draw your attention to the fact that this is a fairly large group of pathologies that are accompanied by an increase in pressure in the pulmonary circulation.

The development of pulmonary hypertension is probably based on a now generally accepted mechanism - endothelial dysfunction, dysfunction of vascular smooth muscle fibers, which causes inflammation, remodeling, which is accompanied by a compensatory increase in pulmonary resistance. Of course, there are predisposing factors for this: genetic, risk factors, and all sorts of other reasons that lead primarily to endothelial vascular dysfunction.

Methods for examining patients with indiopathic pulmonary hypertension are standard and well-known. Of course, in the first place is a well-collected anamnesis and clinical examination of patients. Laboratory tests and standard cardiac examination methods are required. These are ECG, X-ray, computed tomography, echocardiography and right heart catheterization.

First of all, if you have a patient at risk, or a patient who is suspected of having high pressure in the pulmonary circulation, we must first exclude a large category of patients in whom pulmonary hypertension may be caused by lung damage . All these patients are usually referred to pulmonologists, and there it may be associated, for example, with obstructive pulmonary disease.

The second category is a huge category of patients where pulmonary hypertension is caused by damage to the left ventricle. If we exclude these two large categories, then we have to think that perhaps the pressure in the pulmonary circle is due to pulmonary embolism. And if this is not the case, we must send these patients for catheterization to confirm or exclude our diagnosis, in particular idiopathic pulmonary hypertension.

What are the main complaints in patients with primary pulmonary hypertension? The main, nonspecific complaint is shortness of breath, decreased tolerance to physical activity, increased fatigue, and palpitations. They may very often experience fainting and chest pain. In advanced cases - hemoptysis, edema, liver enlargement, ascites. That is, the so-called all signs associated with damage to the lungs, heart and decompensation. But if you look at the list of these complaints, you will notice that they are not of such a specific nature, they are of a non-specific nature.

If we examine a patient, then, of course, we need to pay attention to auscultatory data. Pay attention to the emphasis of the second tone over the pulmonary artery. Cyanosis is possible, especially central/peripheral. It is necessary to pay attention to signs of right ventricular heart failure, to dilatation of the neck veins; possible liver enlargement, peripheral edema, hepatojugular reflux.

The simplest thing to do in these cases is to conduct electrocardiography in these patients. And you can immediately notice that you will have signs of so-called right atrial hypertrophy, right ventricular hypertrophy. Functionalists will pay attention to this. That is, you may already have some kind of thought. Then, from a routine, standard examination, you need to take a chest x-ray. And you will clearly see that there are extensions of the shadow of the pulmonary artery, the so-called second arch.

If we further consider our specific material, we see about 50 such patients today; their ages range from 11 to 56 years. Of course, women of the second functional class, with load tolerance, predominate mainly. But I would like to draw attention to this slide that almost 80% of this category of patients received calcium antagonists for treatment, although we will talk about this now that these are still not first-line drugs.

As for the clinical data on our patients, almost all patients with primary pulmonary hypertension had shortness of breath, fatigue, malaise in 92%, two had fainting; cough, hemoptysis in three patients; palpitations, swelling in the legs.

As for echocardiography, of course, for all these patients this is the main diagnostic method from routine examinations. And they pay attention to pronounced dilatation of the right ventricle, dilatation of the pulmonary artery and high pressure in the right ventricle (both systolic and diastolic calculated pressure); severe tricuspid valve insufficiency and decreased right ventricular ejection fraction.

If we consider the frequency in various types of pulmonary hypertension, which can be determined using echocardiography, we would like to note that this method has a significant advantage in diagnosing hypertension in diseases of the left ventricle. A significantly lower percentage in patients with idiopathic pulmonary hypertension.

Correspondence of the calculated systolic pressure in the pulmonary artery according to the literature. I would like to point out that only 48% have a match between echocardiography data, that is, the calculated pressure using ultrasound, and the true pressure that was measured according to catheterization in the right side of the heart. This suggests that only every second person has a correspondence to this pressure. This suggests that all these patients should be catheterized.

When will we consider that pulmonary hypertension exists? Now, if we take the level of evidence, then the calculated pressure in the pulmonary artery according to echocardiography is determined by the transtricuspid pressure gradient. It must exceed 3.5 meters per second. That is, the calculated systolic pressure should be more than 50 millimeters of mercury. This figure suggests that this category should first be paid attention to and should be referred for catheterization of the right heart, that is, sent to specialized cardiac surgery clinics, where the diagnosis should be verified and confirmed using catheterization of the right heart.

Right heart catheterization is an invasive technique. It should, I emphasize, be carried out in special clinics that have the appropriate equipment, experience and specialists. It is indicated for all patients with pulmonary arterial hypertension. Firstly, to confirm the diagnosis, assess the severity, and most importantly, select the therapy that is indicated in the individual case for each patient.

During catheterization, new clinicians must understand that measuring blood pressure alone is not enough. Measurement of pulmonary artery wedge pressure is always included in the examination complex. This is a very important indicator, because it allows us to imagine what kind of patient is in front of us: with precapillary, so-called arterial hypertension, or with postcapillary, venous pulmonary hypertension. Because approaches to therapy are completely different, and this is very important.

If the pressure with pulmonary artery wedging is less than 15 millimeters of mercury, then these are patients, in particular with idiopathic pulmonary hypertension, with congenital defects, their arterioles suffer. If the wedging pressure of the pulmonary artery is more than 15 millimeters of mercury, that is, the pressure in the left atrium is more than 15 millimeters of mercury, then this is a category associated with pathologies of the left heart. This is the so-called venous pulmonary hypertension, and there are completely different approaches to the treatment of this category of patients.

Here is our data. We catheterized all of our patients with idiopathic pulmonary hypertension. And our pulmonary artery pressure was very high. The average pressure was about 45 millimeters of mercury. Their average wedge pressure was no more than 10, and their total pulmonary resistance was very high and exceeded 35 Wood units. Normally, it should fluctuate 2-3 Wood units.

What are the diagnostic criteria? The so-called “25-15-3” rule. This is very important, and you must remember and imagine it well. That is, the average pulmonary artery pressure must exceed 25 millimeters of mercury, the wedge pressure must be less than 15, and the total pulmonary resistance must exceed 3 Wood units. Here is the basic rule of pulmonary arterial hypertension.

Well, catheterization is only the beginning of a long diagnostic journey. And all patients with pulmonary arterial hypertension should undergo so-called acute pharmacological tests at the time of catheterization to assess so-called vasoreactivity. Today, in leading clinics it is generally accepted to carry them out with the main vasodilators. But in our clinic we settled on three main vasodilators: oxygen, nitric oxide and one of the prostaglandin drugs - Ventavis.

The sequential use of these drugs allows us to answer the main questions: is there significant vasoreactivity or not? As for positive vasoreactivity - that is, whether a patient with idiopathic pulmonary hypertension responds to some basic vasodilator or not - these three principles must coincide. That is, the mean pulmonary artery pressure should decrease by more than 10 millimeters of mercury in the pulmonary artery and should reach a level of less than 40 millimeters of mercury. In this case, cardiac output should increase, or at least not change.

Well, we've done about 28 of these vasoreactive tests in patients with idiopathic pulmonary hypertension. Please note that only two out of 28 - that's 7% - had positive vascular vasoreactivity. Quite rarely, according to the literature, it ranges from 10% to 15%.

As for therapy. Therapy is a very complex process for this category of patients. And we do not strive to completely cure this patient. Drug therapy is primarily aimed at slowing the progression of the disease and increasing survival in this category of patients.

Here is an algorithm for treating patients with pulmonary arterial hypertension, a very complex table. But I would like to point out that there are generally accepted recommendations that we will talk about. Naturally, if patients are young women, pregnancy is contraindicated for them. They must be vaccinated, avoid hypothermia, avoid acute diseases, prevent influenza, and receive standard therapy, which I will talk about later. They should definitely consult with expert centers where they have experience in consultations and examinations with this complex pathology. And everyone is shown the so-called acute pharmacological tests that I just mentioned.

If the reaction is positive, then calcium antagonist drugs are indicated. If the vasoreactive test is negative, depending on the functional class, medications are prescribed, which I will talk about below.

Basic therapy is generally accepted and known. And before, without special pathophysiological or pathogenetic drugs, we treated all patients this way. Anticoagulants, diuretics, cardiac glycosides, oxygen therapy, and calcium antagonists must be prescribed.

As for calcium antagonists. This group of drugs is not indicated for all patients. And it is indicated only if we have a positive response to an acute test. Well, even according to our data, I repeat, we only had two patients who gave a positive vasoreactive test. In this case, the systolic index should exceed 2 liters per minute square meter. Venous blood saturation should be greater than 63% and right atrial pressure should be less than 10 millimeters of mercury. That is, in general, quite strict criteria for therapy with calcium antagonists.

It’s just that sometimes patients come to our clinic who all receive calcium antagonists, to whom therapists and cardiologists prescribe them a priori, without performing a vasoreactive test, without assessing the main hemodynamic parameters. That's why we don't get the corresponding effect.

The dose of calcium antagonists, of course, primarily depends on the degree of pulmonary hypertension. Calcium antagonists can be prescribed any known, from Felodipine, Amlodipine, Nifedipine, prolonged forms. The doses are clear: the higher the blood pressure, the higher the dose of calcium antagonists should be.

If we consider the main lines of pathogenesis, regulation of pressure in the pulmonary artery, then today three main mechanisms are known. This is the influence of Endothelin, Prostacyclin and nitric oxide. Depending on this, a drug that blocks these mechanisms causes dilation of the pulmonary vessels, helps reduce pressure in the pulmonary vessels, and reduces the symptoms of pulmonary hypertension.

In this regard, today there are three main groups of so-called specific progressive therapy, which include prostanoids, phosphodiesterase type 5 inhibitors and endothelin receptor antagonists. Three groups – three treatment mechanisms.

Prostanoids. Prostacyclin is by far the most powerful vasodilator, and therefore it is the main drug in the pathogenesis of pulmonary hypertension. This group of drugs includes today three well-known ones: Epoprostenol (Floran), Iloprost (Ventavis) and Vazaprostan.

Of the prostaglandins E, Alprostan, Vazaprostan, and Prostin are well known to us. They are available in Russia today. But I would like to draw your attention to the fact that they all must be administered intravenously. Yes, they reduce general pulmonary resistance well, but at the same time they also reduce general peripheral resistance. But the longer we use intravenous administration of Vazaprostan, Prostin, side effects very often develop in the form of a decrease in blood pressure. Apnea and thrombocytopenia may develop. Therefore, this drug can be used, but in some kind of crisis, in intensive care conditions.

But we now have another stable inhaled analogue of Prostacyclin, which has a good advantage. It is injected directly into the lungs, and therefore we do not have the main disadvantages that are inherent in Epoprostenol: there is no headache, leg pain, diarrhea, and so on. It is injected directly into the pulmonary artery using a nebulizer. The half-life of this drug is 20-25 minutes. However, there are other problems. It should be prescribed almost every two hours, and the frequency of administration is 6-9 inhalations per day through a special device - through a nebulizer.

The effects of Iloprost inhalation, due to the fact that it enters directly into the lungs, through a nebulizer using inhalation, we observe immediately: a decrease in pressure in the pulmonary artery, an increase in hemodynamics and saturation of capillary blood with oxygen.

Inhaled Iloprost or so-called Ventavis. Multicenter clinical studies AER study, AER-2 study, STEP study were conducted, which showed the effectiveness of this drug in patients with idiopathic pulmonary hypertension, systemic diseases, pulmonary hypertension, which is based on congenital heart defects, chronic thromboembolism.

Since 2010, this drug has been approved in Russia for patients with idiopathic pulmonary, familial forms, systemic diseases and pulmonary embolism.

The second group of drugs that are used to treat pulmonary hypertension are phosphodiesterase inhibitors. The mechanism is very similar and is primarily associated with inhibition of cyclic GMP phosphodiesterase, this is the so-called dependent pathway where nitric oxide is produced. Nitric oxide is a known potent vasodilator that inhibits platelet activation and is widely used to reduce pulmonary pressure.

Of the tablet forms, Sildenafil (Revacio) and Tadalafil are well known today. The SUPER-1 study showed that Sildenafil, in particular the drug Revatio, has proven itself very well, it is effective and safe. When given three times over 12 weeks for pulmonary hypertension, it significantly improves exercise capacity, reduces pulmonary artery pressure, lowers functional class, and is safe and well tolerated. It has been approved since last year in our country, but only in patients over 18 years of age, and is indicated in patients with idiopathic pulmonary hypertension, with systemic diseases and with residual pulmonary hypertension after surgical correction of defects.

The third group of drugs are endothelin receptor antagonists. Endothelin is today the main vasoconstrictor and is considered the leading substance in the pathogenesis of the development of pulmonary arterial hypertension. There are two types of receptors. And in this regard, there is Bosentan (Trakleer) with an effect on both receptors; it is a non-selective drug. And Ambrisentan, which is a highly selective antagonist that acts on endothelin A receptors.

But nevertheless, if we compare these two drugs, today Bosentan has a good evidence base, it has been used all over the world since 2001. To date, about 70-80 thousand patients have been treated. And in front of you on this slide you can clearly see the dynamics of use for various diseases that are accompanied by pulmonary hypertension: these are systemic diseases of pulmonary hypertension, HIV infection, congenital defects, idiopathic pulmonary hypertension. With a good evidence base.

To date, the EARLY study has significantly demonstrated that the use of bosentan significantly reduces pulmonary vascular resistance in patients with idiopathic pulmonary hypertension. Quality of life indicators improve, which persist for a long time after three months of use of this drug; it persists as its prolonged effect.

The safety profile of Tracleer has been well studied and proven long ago. In this TRAX study, which evaluated five thousand patients, only 7.6% of cases showed an increase in liver transaminases while taking this drug. Today, this is the only drug that is approved in Russia. And here you have the indications for which Bosentan is used in the treatment of patients with pulmonary arterial hypertension. These are adults, and I would like to emphasize that children can also be treated with this drug from the age of three. One of the indications, in particular, is idiopathic pulmonary hypertension, pulmonary hypertension against the background of systemic scleroderma. And very important indications are pulmonary hypertension due to congenital heart defects of the Eisenmenger complex type. This is the only drug with these indications. Unfortunately, other drugs do not have these indications for use in Russia yet.

If for a long time, at least three months, six months, we do not see any improvement in the clinical status of patients, if we see that exercise tolerance, in particular the six-minute walk test, decreases and will be less than 350 meters; if we see that our systolic function indicators according to ECHO data are decreasing; if we note that natriuretic peptide decreases by at least 20%, this indicates that we do not have a significant clinical and functional effect from the use of a particular drug.

Therefore, we will have every reason to switch to so-called combination therapy, where we can use two or even three drugs from the main ones that we currently have. These are the three groups I mentioned. These are endothelin receptor antagonists, phosphodiesterase inhibitors and prostanoids. Depending on the drugs we have, we can combine two or three drugs.

We conducted a clinical evaluation of the long-term use of three to six months of treatment, particularly bosentan, in patients with idiopathic pulmonary hypertension. According to the table, I would like to point out that over the course of three to six months of therapy, there is an increase in oxygen saturation. The six-minute walk test significantly improves from 250 to almost 450 meters. There is a tendency to reduce pressure in the pulmonary artery and reduce pulmonary resistance. At the same time, the systolic index, an indicator of contractile function, improves significantly.

Indicators of quality of life - this is very important in patients with idiopathic pulmonary hypertension - with treatment, of course, improves. It is very important.

And in conclusion, I would like to say that the earlier we identify patients with idiopathic pulmonary hypertension, a comprehensive assessment of hemodynamic parameters, including catheterization, individual selection of drug therapy, significantly improves the quality and life expectancy of this complex category of patients. Thank you.

Forecast

The prognosis for life and recovery with pulmonary hypertension depends on the form and stage of the disease, the timeliness and adequacy of the therapy. When using modern treatment methods, the mortality rate of patients with chronic forms of the disease is 10%. The five-year survival rate of patients with primary pulmonary hypertension varies from 20 to 35%.

The overall prognosis is influenced by the following factors:

• The degree of pulmonary hypertension by pressure - with a decrease in pressure in the pulmonary artery, the prognosis will be favorable, with an increase in pressure by more than 50 mm Hg. Art. – unfavorable. A patient diagnosed with secondary pulmonary hypertension may be more likely to have a favorable prognosis;
• An increase in symptoms of the disease or a decrease in their severity;
• Improvement or deterioration of the patient's condition during therapeutic treatment.

When pulmonary hypertension develops in newborns, the prognosis depends on how long the doctor identifies the problem. In most cases, it takes up to three days to make a diagnosis, after which doctors begin to implement a set of therapeutic measures.

Disease in children

There are cases when pulmonary hypertension is diagnosed in newborns; its manifestation is caused by congenital heart defects; the hereditary factor also plays a significant role in the development of this disease in a child.

Often, pulmonary hypertension in children occurs against the background of previous diseases of the respiratory system: pneumonia, bronchitis, complications after influenza or ARVI.

The first symptom of pulmonary hypertension in newborns is the occurrence of shortness of breath; less commonly, the disease begins with fainting.

The rest of the course of the disease in a newborn is similar to the clinical picture of an adult patient.