Table of Contents

  1. Introduction to Pulmonary Hypertension
  2. Causes and Prevalence of Pulmonary Hypertension
  3. Pathophysiology of Pulmonary Hypertension
  4. Classification of Pulmonary Hypertension
  5. Diagnosis of Pulmonary Hypertension
  6. Tests to Determine Severity of Pulmonary Hypertension
  7. Treatment of Pulmonary Hypertension


Pulmonary hypertension is defined as the mean pulmonary artery pressure ≥25 mm Hg at rest as determined by right heart catheterization. The upper level of normal for mean pulmonary artery pressure is 20 mm Hg.

In simple terms it is elevated blood pressure in the pulmonary circulation, that affects the arteries in the lungs and the right side of the heart. Pulmonary hypertension probably affects around 1% of the global population even then it is not uncommon. For people above 65 years of age, the prevalence of pulmonary hypertension is around 10%. However, the various forms of pulmonary hypertension differ considerably in incidence and prevalence. Although some forms of pulmonary hypertension aren’t curable, treatment can help lessen symptoms and improve the quality of life.

According to European guidelines on pulmonary hypertension published in 2015 and the second Cologne Consensus Conference held on 16–18 June 2016, Pulmonary hypertension is not in itself a diagnosis, but solely a hemodynamic state characterized by resting mean pulmonary artery pressure (PAPm) of ≥ 25 mm Hg.

In the lungs, the blood releases carbon dioxide and picks up oxygen. The oxygen-rich blood then flows through blood vessels in the lungs (pulmonary arteries, capillaries and, veins) to the left side of the heart. Ordinarily, the blood flows easily through the vessels in the lungs, so blood pressure is usually much lower in the lungs. With pulmonary hypertension, the rise in blood pressure is caused by changes in the cells that line the pulmonary arteries. These changes can cause the walls of the arteries to become stiff and thick, and extra tissue may form. The blood vessels may also become inflamed and tight. These changes in the pulmonary arteries can reduce or block blood flow through the blood vessels. This makes it harder for blood to flow, raising the blood pressure in the pulmonary arteries. Eisenmenger syndrome, a type of congenital heart disease, causes pulmonary hypertension. It’s most commonly caused by a large hole in the heart between the two lower heart chambers (ventricles), called a ventricular septal defect. This hole in the heart causes blood to circulate abnormally in the heart. Oxygen-carrying blood (red blood) mixes with oxygen-poor blood (blue blood). The blood then returns to the lungs instead of going to the rest of the body, increasing the pressure in the pulmonary arteries and causing pulmonary hypertension.

Clinically, pulmonary hypertension is divided into 5 broad categories as shown in Table. For group1 patients, all 3 layers of the pulmonary arteriolar wall intima, media, and adventitia get affected. An increase in the number and size of smooth muscle cells in the media of the vessel wall leads to medial hypertrophy. Migration of smooth muscle cells from the media to the layer of endothelial cells that normally lines the lumen of the vessel leads to intimal proliferation. Plexiform lesions in the vessel lumen consist of a proliferation of endothelial cells and an interstitial layer of myogenic cells. Expansion of cells surrounding the media fibroblasts, progenitor cells, macrophages, and other immune cells leads to thickening of the adventitia. Adventitia is a layer that serves as a resource for the repair of vessel injury.  In addition, Group 2 pulmonary hypertension caused by left heart disease features enlarged pulmonary veins and capillaries. In Group 4 chronic thromboembolic pulmonary hypertension (CTEPH), organized thrombi replace the intima of proximal or distal elastic pulmonary arteries and attach to the medial layer, causing variable degrees of stenosis or complete occlusion of the lumen.

Chronic hypoxia is also recognized to be an important cause of pulmonary hypertension. It influences diverse cellular and metabolic processes. Also, Pulmonary hypertension affects ∼10% of adult patients with sickle cell disease (SCD). More affected are those with the homozygous genotype. Nevertheless, relatively little attention has been given to upregulation of the hypoxic response as a potential factor in Sickle cell disease pulmonary hypertension.

Pulmonary hypertension is hard to diagnose early because it’s not often detected in a routine physical examination. Even when the condition is more advanced, its signs and symptoms are similar to those of other heart and lung conditions. To diagnose pulmonary hypertension, and determine the severity few tests are performed – Echocardiogram, where sound waves create moving images of the beating heart. An echocardiogram helps to check the size and functioning of the right ventricle, and the thickness of the right ventricle’s wall. It is also used to measure the pressure in pulmonary arteries. Chest X-ray, which can show enlargement of the right ventricle of the heart or the pulmonary arteries.

Electrocardiogram (ECG), a noninvasive test shows heart’s electrical patterns and can detect abnormal rhythms and signs of right ventricle enlargement or strain. Right heart catheterization might follow Echocardiogram depending on the status of the disease. This test is performed to confirm pulmonary hypertension and to determine the severity of the condition. In the procedure, a thin, flexible tube (catheter) is placed into a vein in the neck or groin. The catheter is then threaded into the right ventricle and pulmonary artery. This procedure allows direct measure of the pressure in the main pulmonary arteries and right ventricle. Blood tests are also performed to check for certain substances that might be indicative of pulmonary hypertension or its complications. Computerized tomography(CT) scan is performed to look at the heart’s size and function and to check for blood clots in the lungs’ arteries. Magnetic resonance imaging (MRI) helps to check the right ventricle’s function and the blood flow in the lung’s arteries. An MRI uses a magnetic field and pulses of radio wave energy to make pictures of the body. Pulmonary function test, a noninvasive test measures air holding capacity of the lungs. Polysomnogram, it detects brain activity, heart rate, blood pressure, oxygen levels and other factors in sleeping condition. It can help diagnose a sleep disorder such as obstructive sleep apnea. Ventilation/perfusion (V/Q) scan, where a tracer is injected into a vein in the arm. The tracer maps blood flow and air to the lungs and helps to determine whether blood clots are causing symptoms of pulmonary hypertension. In rare cases, Open-lung biopsy is performed which a small sample of tissue is removed from the lungs by surgery under general anesthesia to check for a possible secondary cause of pulmonary hypertension.

Pulmonary hypertension can’t be cured but can be managed with the treatment. It often takes some time to find the most appropriate treatment for pulmonary hypertension. The treatments are often complex and require extensive follow-up care. The general treatment of pulmonary hypertension is predominantly symptomatic and depends on the type and severity of the disease and the patient’s requirements. In current times ten drugs from five different substance classes are licensed for the treatment of pulmonary arterial hypertension and are used singly or in combination. The severity of the pulmonary arterial hypertension decides the choice of medication. According to current guidelines recommended classification for  the disease is low-, intermediate-, and high-risk. Newly diagnosed patients and low or intermediate risk receive initial or early combination treatment. This comprises an endothelin receptor antagonist (ERA) with a phosphodiesterase-5 (PDE5) inhibitor or a soluble guanylate cyclase (sGC) stimulator. For high-risk patients, the recommended initial treatment is a triple combination of an ERA, a PDE5 inhibitor or an sGC stimulator, and an intravenously administered prostacyclin analog. Treatment result is usually verified after 4 to 12 weeks and then at intervals of 3 to 6 months. If the response is not better, PDE5 inhibitor is switched to riociguat. It is currently being evaluated (RESPITE; identifier NCT02007629). Further inadequate patient response leads to evaluation for lung transplantation without delay. It is indispensable only for those patients where medication fails to relieve patients successfully. Combined heart and lung transplantation is necessary only in exceptional cases because right heart function is almost always restored to normal after lung transplantation.

The goal of treatment for Pulmonary hypertension is the containment of the disease. Stabilization of the patient at a satisfactory clinical level without signs of right heart failure and ideally without disease progression. The best treatment for Pulmonary hypertension patients has to be determined on an individual basis. Similar to any serious, life-threatening rare disease, pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and other severe forms of pulmonary hypertension should be diagnosed and treated at specialized centers.


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