Primary pulmonary hypertension is a hereditary pathology characterized by increased pressure inside the pulmonary artery and increased general pulmonary vascular resistance. It is manifested by shortness of breath, increased heart rate, unproductive cough, loss of consciousness, chest pains, intolerance to physical exertion, edema, hemoptysis. Instrumental methods of examination of the heart and blood vessels are prescribed, the diagnosis is confirmed by the data of pressure measurement in the pulmonary trunk. Treatment includes taking vasodilating drugs, correction of daily loads.
ICD 10
I27.0 Primary pulmonary hypertension
General information
Primary pulmonary hypertension (PPH) has a number of synonymous names: idiopathic pulmonary hypertension, Aerza-Arilago syndrome, Aerza disease, Escudero disease. The prevalence of this pathology is low, within a year the diagnosis is made to 1-2 people out of 1 million. The greatest susceptibility to the disease is determined in women from 20 to 30 years and in men from 30 to 40 years. Children, adolescents and senile people (after 60 years) rarely get sick, their share among all patients is no more than 7-9%. Sexual and racial predisposition to pathology was not revealed. The average time from the debut to the confirmation of the diagnosis is 2 years, the average survival of patients is from 3 to 5 years.
Causes
The etiology of the disease has not been studied enough. It is assumed that PLG refers to hereditary pathologies. Patients have mutations of genes that determine the production of vasodilating compounds – NO-synthase, carbimyl-phosphate synthase, serotonin transporters, as well as the activity of the receptor type of the second bone morphogenetic protein. The mechanism of genetic transmission is autosomal dominant, accompanied by incomplete penetration. This means that the onset of the disease is possible if there are one or two defective genes in the allele, but sometimes the disease remains unmanifested. Mutation transmission occurs with a tendency to manifest pathology at an earlier age and with a more severe course in subsequent generations. The carriage of a mutational gene or genes does not always lead to the development of symptoms, but only when exposed to triggering factors, which include:
- Drug, narcotic intoxication. PPH is potentiated by taking amphetamines, L-tryptophan, aminorex, fenfluramine. The negative impact of meta-amphetamines, cocaine, and chemotherapy drugs is assumed.
- Physiological conditions. Childbirth and gestation can provoke the onset of the disease. Pregnant women with diseases of the cardiovascular system and complications in childbirth are at high risk.
- Concomitant diseases. It has been established that systemic or portal hypertension, HIV infection, liver diseases, congenital shunts between the pulmonary and systemic vessels predispose to the development of PPH. Probably, thyropathies, hematological diseases, genetic metabolic pathologies can become triggers.
Pathogenesis
The development of primary pulmonary hypertension takes place in several stages. At first, dysfunction increases or vascular endothelial damage appears, there is an imbalance in the production and secretion of vasodilating and vasoconstrictor compounds. The production of thromboxane and endothelin-1 – peptide with mitogenic effect on smooth muscle cells increases. There is a shortage of vasodilating compounds, the main of which are nitric oxide and prostacyclin. The vessels of the lungs narrow.
At the second stage, irreversible changes in the structure of the pulmonary vessels are formed. Chemokines are released from endothelial cells, which cause smooth muscle cells to move into the inner lining of the pulmonary arterioles. The process of pathological growth of the vessel walls inside and increased production of mediators with a pronounced vasoconstrictive effect is started, thrombosis develops. The lesion of endothelial tissues deepens, vascular obstruction progresses. Pathological processes spread to all layers of vascular walls and different types of cells. The resistance to blood flow increases, the pressure increases.
Symptoms
The first and most common manifestation of PPH is inspiratory dyspnea. At first, it is noted only with moderate physical activity, later it begins to accompany daily motor activity. With a severe or prolonged course of the disease, respiratory rhythm disturbances occur suddenly at rest. Another common symptom is chest pain. By nature, it can be aching, burning, compressing, pressing, stabbing. The duration varies from a minute to several days. As a rule, the pain increases gradually, noticeably worsens during sports, physical labor.
About half of the patients experience dizziness and fainting during exercise. Externally, this is manifested by a sharp paling of the skin, and then the appearance of a bluish coloration of the face, hands and feet, clouding and sometimes loss of consciousness. The duration of such symptoms ranges from 1 to 20-25 minutes. In 60% of patients, palpitations and cardiac arrhythmias are detected, in 30% – an unproductive cough. Every tenth patient develops a single or several days of hemoptysis. Over time, the shape of the fingers changes – the end phalanges thicken, the nails are rounded.
Complications
Primary pulmonary hypertension is often complicated by thromboembolism of the subsegmental branches of the pulmonary artery, atrial fibrillation, acute heart failure. The most characteristic is right ventricular insufficiency, which is manifested by edema spreading from the lower extremities upwards, ascites, liver enlargement, swelling of the cervical veins, loss of body weight. With a prolonged course of the disease, decompensation occurs in a large circle of blood circulation. An acute condition is associated with a risk of death, about 27% of patients die due to sudden cardiac arrest.
Diagnostics
The diagnosis of primary pulmonary hypertension is difficult because the symptoms are nonspecific and the prevalence of the disease is insignificant. The examination is carried out by a cardiologist, a therapist. Patients complain of weakness, shortness of breath, chest pains. When collecting anamnesis, the presence of a provoking factor (viral infection, pregnancy, childbirth) and family burden is often determined. In order to clarify the diagnosis, exclude heart defects, recurrent PE, COPD and myocardial diseases,:
- Physical examination. During the examination, acrocyanosis (cyanosis of the skin) is detected. Right ventricular heart failure is manifested by swelling of the neck veins, swelling of the extremities, accumulation of fluid in the peritoneal organs. Auscultation of the heart reveals the accent of the second tone over the pulmonary artery, pansystolic noise, Stillness noise.
- Laboratory test. A clinical and biochemical blood test, a test for thyroid hormones, anticardiolipin antibodies, D-dimer, antithrombin III and protein C are prescribed. The results make it possible to differentiate cardiovascular diseases, for example, to exclude thrombophilia. With PLG, it is possible to determine the low titer of anticardiolipin antibodies.
- Instrumental diagnostics. According to the ECG results, the EOS deviates to the right, the right cardiac ventricle and atrium are hypertrophied, dilated. Phonocardiography diagnoses hypertension, hypervolemia of the pulmonary circulation. During chest x-ray, the left branch and trunk of the pulmonary artery bulge, the roots of the lungs are expanded, the right structures of the heart are enlarged. By catheterization of the heart, the blood pressure inside the artery of the lungs is measured, the minute volume of blood, the total pulmonary vascular resistance is estimated. The diagnosis of PPH is confirmed with a length of 25 mmHg. at rest or below 30 mmHg. with a load, the DLA is not higher than 15 mmHg. art., the OLSS is not less than 3 mmHg. art. / l / minute.
Treatment
Therapy is aimed at normalizing blood pressure in the arteries and pulmonary trunk, slowing the progression of the disease, preventing and eliminating complications. Patients are hospitalized with the initial appearance of symptoms, the detection of signs of accelerated development of the disease, the formation of decompensation in the systemic circle and pulmonary embolism. Treatment is carried out in three directions:
1. Drug therapy. Medicines can quickly improve the condition of patients, fully or partially achieve compensation for impaired cardiovascular functions. Drugs of the following groups are used:
- Anticoagulants, disaggregants. Oral anticoagulants are prescribed – warfarin, heparin, low molecular weight heparins. Among the disaggregants, the most common use of acetylsalicylic acid. Regular medication reduces the risk of thromboembolism.
- Diuretics. Diuretics (loop diuretics) reduce the volume of circulating blood, reduce systemic pressure. During therapy, the level of electrolytes in the blood and the functionality of the kidneys are carefully monitored.
- Cardiac glycosides, cardiotonics. Prevent the development and progression of heart failure, correct atrial fibrillation. Often drugs are administered intravenously.
- Calcium channel blockers. They cause relaxation of smooth muscle fibers in the walls of blood vessels, increasing their lumen. Treatment is advisable for people with a positive reaction to vasodilators who have one or more of the following indicators: a cardiovascular index of more than 2.1 l / min / m2, saturation of the veins with hemoglobin of more than 63%, pressure in the right atrium less than 10 mmHg.
- Prostaglandins. They have vasodilating, antiplatelet and antiproliferative effects. The use of prostaglandin E1 is widespread.
- Antagonists of endothelin receptors. According to studies of the lung tissue of patients, endothelin-1 is involved in the pathogenesis of PPH, exerting a vasoconstrictor effect. Activation of the endothelin system confirms the need for the use of receptor antagonists to this compound.
- Nitric oxide. This compound is a potent endogenous vasodilator. Patients are shown courses of inhalation for 2-3 weeks.
- FDE-5. Drugs of this group reduce the OLSS and the load on the right ventricle. Their intake improves blood flow through the vessels, increases tolerance to physical activity.
2. Lifestyle correction. Patients are recommended to exercise, which is not accompanied by severe shortness of breath and chest pain. Since hypoxia aggravates the course of the disease, it is contraindicated to stay in high-altitude regions. Air travel should be accompanied by the possibility of oxygen therapy. It is necessary to prevent colds, especially severe viral infections that can worsen the course of PPH. Women are recommended to use barrier contraceptives. Pregnancy and childbirth are associated with a high risk of maternal death.
3. Surgical treatment. The procedure of atrial septostomy is aimed at the artificial formation of perforation of the atrial septum – an additional discharge of blood reduces the pressure inside the atria, improves the functionality of the heart. The operation is accompanied by a risk of arterial hypoxemia and death, the mortality rate is 5-15%. Another option for surgical treatment is lung transplantation or a heart-lung complex. The survival rate of patients after 3 years reaches 55%.
Prognosis and prevention
The average life expectancy of patients is 3-5 years. The search for effective treatment methods continues. Currently, doctors manage to reduce the risk of death through lung transplantation operations, but mortality rates remain high. The system of preventive measures has not been established, geneticists and cardiologists are developing methods of screening examinations that will identify families with a burdened history and people from risk groups. The latter are recommended to solve the issue of pregnancy and childbirth safety together with a doctor, treat hypertension, liver pathology, endocrine diseases in a timely manner, avoid HIV infection and taking substances that can provoke PPH.
