Pulmonary hypertension is an elevated pressure in the pulmonary circulation. It has many secondary causes. Some cases are idiopathic. In pulmonary hypertension, the pulmonary vessels are constricted. Severe pulmonary hypertension leads to an increased load on the right ventricle and ultimately failure. The symptoms consist of exhaustion, exertional dyspnea, and occasionally mild chest pain and syncope. The diagnosis is made by finding an elevated pulmonary artery pressure (suspected by echocardiography and by right heart catheterization confirmed). Treatment is with pulmonary vasodilators and diuretics. In some advanced cases, lung transplantation is an option. If no treatable secondary cause is found, the overall prognosis is poor.
Pulmonary hypertension is defined as a mean pulmonary arterial pressure ? 25 mm Hg at rest and a normal (? 15 mmHg) pulmonary artery wedge pressure (pulmonary capillary wedge pressure) measured by right heart catheterization.
Pulmonary hypertension is an elevated pressure in the pulmonary circulation. It has many secondary causes. Some cases are idiopathic. In pulmonary hypertension, the pulmonary vessels are constricted. Severe pulmonary hypertension leads to an increased load on the right ventricle and ultimately failure. The symptoms consist of exhaustion, exertional dyspnea, and occasionally mild chest pain and syncope. The diagnosis is made by finding an elevated pulmonary artery pressure (suspected by echocardiography and by right heart catheterization confirmed). Treatment is with pulmonary vasodilators and diuretics. In some advanced cases, lung transplantation is an option. If no treatable secondary cause is found, the overall prognosis is poor. Pulmonary hypertension is defined as a mean pulmonary arterial pressure ? 25 mm Hg at rest and a normal (? 15 mmHg) pulmonary artery wedge pressure (pulmonary capillary wedge pressure) measured by right heart catheterization. Etiology Many diseases and drugs cause pulmonary hypertension. The total common causes of pulmonary hypertension are Left-sided heart failure, including diastolic dysfunction parenchymal hypoxia Other: sleep apnea, connective tissue disorders and recurrent pulmonary embolism Pulmonary hypertension is currently divided into 5 groups (see table: classification of pulmonary hypertension), based on a series of pathological, physiological and clinical factors. In the first group (pulmonary arterial hypertension), the primary disease affects the small Lungenarteriolen. A small number of cases of pulmonary arterial hypertension occurs sporadically and is not associated with any detectable disease. These cases are called idiopathic pulmonary arterial hypertension. Hereditary forms of pulmonary arterial hypertension (autosomal dominant with incomplete penetrance) were determined; 75% of cases are due to mutations jn bone morphogenetic protein receptor type 2 causes (BMPR2). Other mutations identified are activin-like kinase type 1 receptor (ALK-1), caveolin 1 (CAV1), endoglin (ENG), potassium channel subfamily K member 3 (KCNK3) and mothers against decapentaplegic homologue 9 (SMAD9), but are much less common and occur in ~ 1% of cases. In about 20% of cases of hereditary pulmonary arterial hypertension, the causative mutations are not detected. Patients with hereditary causes of hemolytic anemia, such as sickle cell anemia, have a high risk of developing pulmonary hypertension (10% of cases based on the basis of right heart catheterization criteria). The mechanism is related to intravascular hemolysis and release of cell-free hemoglobin in the plasma nitric oxide cleans, generates reactive oxygen species and the hemostatic system activated. As with other risk factors for pulmonary hypertension in red blood cells include iron overload, liver dysfunction, thrombotic diseases and chronic kidney disease. Classification of pulmonary hypertension group type Specific disorders 1 Pulmonary arterial hypertension (PAH) Idiopathic PAH Inherited PAH: BMPR2 ALK-1, ENG, SMAD9, CAV1, KCN K3 Unknown drug and toxin-induced PAH associated with PAH: connective tissue diseases HIV infection portals hypertension Congenital heart disorders schistosomiasis 1 ‘Pulmonary Ve nenverschlusskrankheit and / or pulmonary capillary hemangiomatosis – 1 “Persistent pulmonary hypertension of the newborn (PPHN) – 2 Pulmonary hypertension with left-sided heart disease Left ventricular systolic dysfunction Left ventricular diastolic dysfunction, including left heart failure with preserved ejection fraction, heart valve disease, congenital or acquired left ventricular influencing or outflow tract obstruction and congenital cardiomyopathy 3 Pulmonary Hyperto never associated with lung diseases and / or hypoxemia Alveolar Hypoventilatiosstörungen COPD Chronic exposure to high altitude developmental disorders interstitial lung disease sleep disordered breathing Other pulmonary diseases with mixed restrictive and obstructive pattern. 4 Pulmonary hypertension due to chronic thrombotic or embolic diseases non-thrombotic pulmonary embolism (e.g., due to tumors, parasites, or foreign objects.) Thromboembolic obstruction of distal or proximal pulmonary arteries 5 Miscellaneous (unclear or multifactorial mechanisms) Haematological diseases: chronic hemolytic anemia Myeloproliferative diseases splenectomy systemic diseases: sarcoidosis Pulmonary Langerhans cell histiocytosis lymphangioleiomyomatosis metabolic disorders: glycogen storage disease Gaucher disease Schilddrüsenfunktionsstörun gen Other diseases: fibrosing mediastinitis tumor, can cause intestinal obstruction. Chronic kidney disease Segmental pulmonary hypertension Adapted from Fifth World Symposium on PAH, Nice, 2013; Simonneau G, Galié N, Rubin LJ, et al: Clinical classification of pulmonary hypertension. Journal of the American College of Cardiology 62 (supplement 1): D34-D41, 2013. Pathophysiology The pathophysiological mechanisms that cause pulmonary hypertension include Increased pulmonary vascular resistance Increased pulmonary venous pressure Increased pulmonary vascular resistance by the obliteration of the pulmonary vasculature and / or pathological vasoconstriction. Pulmonary hypertension is characterized by a variable and sometimes pathological vasoconstriction and by endothelial and smooth muscle proliferation, obesity and chronic inflammation which leads to remodeling of the vascular walls. The vasoconstriction is to be partly due to an increased activity of thromboxane and endothelin-1 (both vasoconstrictors), and a decreased activity of prostacyclin and nitric oxide (both vasodilators). The increased pulmonary vascular pressure resulting from vasoconstriction, damage beyond the endothelium. This blood clotting on the intimal surface is activated, which can degrade the high pressure. Further, a platelet coagulation disorder can contribute due to an increased activity of plasminogen activator type 1 and fibrinopeptide A and a reduced activity of tissue-specific plasminogen activators to the high pressure due to platelet dysfunction. Platelets can, when stimulated, also play a key role in the release of substances that enhance the proliferation of fibroblasts and smooth muscle cells, such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor-? ( TGF -?). A local clotting at the endothelial surface should not be confused with chronic thromboembolic pulmonary hypertension, wherein the pulmonary high pressure caused by organized pulmonary embolism. Elevated pulmonary venous pressure is typically caused by disorders affecting the left side of the heart and lift the left chamber pressures, which ultimately leads to increased pressure in the pulmonary veins. An elevated pulmonary venous pressure can cause acute damage to the jaw-capillary wall and subsequent edema. Sustained high pressures can eventually lead to irreversible thickening of the walls of pine-capillary membrane and reducing lung diffusion capacity. The most common manifestation of pulmonary venous hypertension is left heart failure with preserved ejection fraction (HF-PEF), usually in older women, the hypertension and the metabolic syndrome have. If the transpulmonary gradient (mean pulmonary artery pressure pulmonary artery occlusion gradient) is> 12 mm Hg or the diastolic pulmonary artery pressure on the pulmonary Arteriendruckgradienten is> 6 mm Hg, the prognosis is poor. In most patients, pulmonary hypertension leads over time to a right ventricular hypertrophy with subsequent dilatation and right ventricular failure. Right ventricular failure limits the cardiac ejection fraction during exercise. Symptoms and complaints Increasing exertional dyspnea and fatigue occur ei almost all patients. Atypical slight chest pain and dizziness during exercise or syncope may accompany the dyspnea and be signs of a more serious disease. These symptoms come about primarily by the insufficient cardiac output. Raynaud’s disease occurs in about 10% of patients with idiopathic pulmonary arterial hypertension, the majority are women. Hemoptysis is rare but can be fatal. Hoarseness of the recurrent laryngeal nerve by an enlarged pulmonary artery (Ortner’s syndrome) by the compression occurs rarely. In advanced cases, symptoms of right heart failure in the physical examination a shifted to the right lifting heart’s apex may distinct cleavage of the second heart sound (S2), accented Pulmonalissegment (P2) of the S2, ejection click the pulmonary artery, a right ventricular 3. heart sound (S3), “tricuspid murmur” and include distended neck veins. Liver congestion and peripheral edema are common late manifestations. Pulmonary auscultation is normal in general. The patients may also have manifestations of causative or associated disorders. Diagnosis exertional First Confirmation: X-ray chest radiograph, spirometry, ECG, echocardiography and complete blood count identification of the underlying disease: ventilation-perfusion scan or CT angiography, high-resolution CT (HRCT) of the chest, pulmonary function tests, polysomnography, HIV tests, liver function testing and auto-antibody assay determination of severity: 6-minute distance on foot, plasma levels of N-terminal brain natriuretic peptides (BNP) or pro-BNP and right heart catheter Pulmonary hypertension is suspected in patients with significant exertional, which are otherwise relatively healthy and where no anamnestic indications or symptoms of another disorder exist that could cause pulmonary symptoms. Patients initially receive a chest x-ray absorption, spirometry and ECG to diagnose frequent causes of dyspnea, followed by transthoracic Doppler echocardiography to determine the right ventricular function and pulmonary artery systolic pressures and to identify structural links heart disease that could cause pulmonary hypertension. A complete blood count is taken to document the presence or absence of erythrocytosis, anemia and thrombocytopenia. The most common x-ray findings in pulmonary hypertension are enlarged hilar vessels, the fast “prune” in the periphery, and a right ventricle, which fills the air space in front of the side view and the diffusing capacity for carbon monoxide (DLco) is generally reduced. Spirometry and lung volume can be normal or reveal slight restriction and diffusion capacity for carbon monoxide (DLCO) is usually reduced. Common signs in the ECG include displacement of the axis of the heart to the right, R> S in V1, S1Q3T3 (reference to right ventricular hypertrophy) type and increased P-waves (indicating right arterial dilation). Additional tests depending on the indication to determine secondary causes that are not clinically obvious performed. These tests may include ventilation / perfusion scan or CT angiography to detect thromboembolic disease HRCT for detailed information on parenchymal lung disease pulmonary function tests for the identification of obstructive or restrictive lung disease serum autoantibody tests (z. B. antinuclear antibodies [ANA] rheumatoid factor [RF ], Scl-70 [topoisomerase I], anti-ro (anti-SSA), Antiribonucleoprotein [anti-RNP] and anti-centromere antibodies) to provide evidence for or against associated autoimmune diseases. Chronic thromboembolic pulmonary hypertension is suspected on CT or lung scan and confirmed by angiography. CT angiography is useful to evaluate proximal clot and a fibrotic advance of the vascular lumen. Other tests such as HIV test, liver function tests, and polysomnography are performed in the appropriate clinical context. When the input studies allows the diagnosis of pulmonary hypertension is a pulmonary artery catheter (Monitoring and analysis of intensive care patients: monitoring with pulmonary artery catheter) for measuring occlusion pressures of the right atrium, right ventricle, the Lungenarterier and Pulmonalkapillaren; Heart means outputs and the diastolic pressure necessary. For the avoidance of atrial septal defects O2 saturation should be determined in the right heart. Although finding a mean pulmonary arterial pressure of> 25 mmHgund and pulmonary arterial occlusion in the absence of an underlying condition identify pulmonary hypertension, most patients present with pulmonary arterial hypertension a significantly higher pressure (eg. As an average of 60 mmHg) on. Vasodilating agents such as inhaled nitric oxide, i.v. Epoprostenol or adenosine are often administered during catheterization. A decreasing right-sided printing in response to these drugs can help in the selection of drugs used for treatment. A lung biopsy, whose taking was prevalent earlier, is neither required nor recommended because of its associated high morbidity and mortality. Echocardiography knowledge of right ventricular systolic dysfunction (z. B. “tricuspid annular design plane systolic excursion”) and certain right heart catheterization results (z. B. low cardiac output, high mean pulmonary arterial pressures and high pressure in the right atrium) show that pulmonary hypertension is severe. Other indicators of the severity of pulmonary hypertension are evaluated to assess the prognosis and to help monitor the therapy. They include a low 6-min walk distance, and high plasma levels of N-terminal pro-brain natriuretic peptide (NT-pro-BNP), or Brain Naturetic Peptide (BNP). Once pulmonary hypertension is diagnosed, family history is illuminated again to elicit a possible inheritance (z. B. premature death in otherwise healthy family members). In familial pulmonary hypertension, genetic counseling is needed to elucidate the mutation carriers on the risk of disease (about 20%) and to recommend echocardiographic screening tests. Tests for mutations in BMPR2 gene in idiopathic pulmonary arterial hypertension can help family members at risk to detect. Prognosis The 5-year survival rate for patients treated is about 50%. Recent findings, however in some patients registers suggest a lower mortality close (eg., 20 to 30% at 3 to 5 years in the French register and 10 to 30% for 1 to 3 years in the REVEAL registry), presumably because currently available therapies are superior. Among the indicators of a poor prognosis include lack of response to vasodilators, hypoxemia, reduced overall physical function, low 6-minute walk distance, high plasma levels of NT-pro-BNP or BNP, echocardiographic indicators of right ventricular systolic dysfunction (z. B. “Annular ricuspid plane systolic excursion”) and right heart catheterization showing low cardiac output, pulmonary artery pressures and high average high right arterial pressures. Patients with systemic sclerosis, sickle cell anemia, or HIV infection with pulmonary arterial hypertension have a worse prognosis than patients without pulmonary arterial hypertension. Patients with sickle cell disease and pulmonary hypertension have a 40% 4-year mortality rate. Treatment avoidance of activities that may worsen the condition idiopathic and familial pulmonary arterial hypertension (such as smoking, high altitude, pregnancy, use of sympathomimetic.): Iv Epoprostenol, inhaled, oral, or s.c. Prostacyclin analogs, oral endothelin receptor antagonists; oral phosphodiesterase-5 inhibitors and / or guanylatlösliche Zyklasestimulatoren Secondary Pulmonary Arterial Hypertension: Treatment of the underlying disease rare lung transplant adjunctive therapy: supplementary O2, diuretics and / or anticoagulants Pulmonary arterial hypertension, Group 1 Treatment rapidly evolving. Epoprostenol i.v., a prostacyclin analogue, improves the function and prolong survival even in patients who do not respond to a vasodilator as the catheter examination. Epoprostenol is currently the most effective therapy for pulmonary arterial hypertension. The disadvantages are the need for continuous infusion through a central venous catheter and frequent, problematic side effects, including flushing symptoms, diarrhea, and which is associated with the underlying central venous catheter bacteremia. Prostacyclin analogs that inhaled (Iloprost and Treprostinil) or s.c. or iv are added (Treprostinil), are available. Three oral endothelin receptor antagonist bosentan, ambrisentan and macitentan, are now available. Sildenafil and Tadalafil, oral phosphodiesterase 5 inhibitors, can also be used. Riociguat is the first available soluble guanylate cyclase stimulator. Drugs to improve exercise capacity and reduce combined endpoints in clinical deterioration, are often determined by a hospitalization for right heart failure. There were compared, no studies of oral medications. Most patients prefer to begin treatment with an oral medication if to add required a second oral drug based on clinical response. The physical performance is improved if the second drug from another class (endothelin receptor antagonist or phosphodiesterase 5 inhibitor) is selected. However, phosphodiesterase 5 inhibitors may not be combined with Riociguat because both groups of active ingredients cyclic guanosine monophosphate (cGMP) levels increase, and can result in the combination to dangerous blood pressure. Patients with severe right heart failure and high risk of sudden death can benefit from early treatment with an intravenous or subcutaneous prostacyclin. A lung transplant is the only hope for a cure, however, is accompanied by a high morbidity due to rejection (bronchiolitis obliterans-syndrome) and infection associated. The 5-year survival rate is 50%. Lung transplantation is patients with NYHA IV disease (defined as dyspnea in facilitated tester load, which the patient to bed or chair ties) or complex congenital heart disease subject in which all treatments have failed and meet the other health criteria to be transplant candidates. Many patients require adjuvant therapies for the treatment of heart failure, incl. Diuretics, and most should receive warfarin unless Kontrakindikation vorliegt.Pulmonale hypertension, Groups 2-5 The primary treatment is to treat the underlying condition. Patients with left-sided heart disease may need surgery for a heart valve disease. Patients with lung diseases and hypoxia benefit from additional O2 and treatment of the primary disease. Therapies for patients with severe pulmonary hypertension due to thromboembolic disease include Riociguat and operative pulmonary thromboendarterectomy. During a cardiopulmonary bypass, an organized thrombus endothelialisierter along the pulmonary vessels is dissected, which is a more expensive procedure than the acute surgical embolectomy. With this method, pulmonary hypertension can be cured in a significant number of patients and the cardiopulmonary function will be restored. The perioperative mortality is <10% in patients who are treated in centers with extensive experience. Patients with sickle cell disease suffering from pulmonary hypertension are treated aggressively as indicated by hydroxyurea, iron chelation and supplementary O2. In patients with pulmonary arterial hypertension and increased pulmonary vascular resistance by right heart catheter, a selective pulmonary vasodilator therapy can be considered (with epoprostenol or an endothelin receptor antagonist). Sildenafil increases the incidence of painful sickle cell crises in patients with sickle cell disease and should be used only when patients have limited vaso-occlusive sickle cell crises and are treated with hydroxyurea or transfusion therapy. Key points Pulmonary hypertension is divided into 5 groups. Pulmonary hypertension should be suspected in patients who have dyspnea, which can not be explained by any other clinically manifest heart or lung disease. At the beginning of the diagnosis are chest X-ray, spirometry, ECG and transthoracic Doppler echocardiography. The diagnosis is confirmed by right heart catheterization. Group 1 should be treated with pulmonary vasodilators and if these are ineffective pulled a lung transplant into consideration. Group 2 to 5, should be treated by therapy of the underlying disease, the treatment of symptoms and sometimes other measures.