Definition

Pulmonary hypertension is a type of high blood pressure that affects the arteries in your lungs and the right side of your heart. In one form of pulmonary hypertension, tiny arteries in your lungs, called pulmonary arterioles, and capillaries become narrowed, blocked or destroyed. This makes it harder for blood to flow through your lungs, and raises pressure within your lungs’ arteries. As the pressure builds, your heart’s lower right chamber (right ventricle) must work harder to pump blood through your lungs, eventually causing your heart muscle to weaken and fail. Some forms of pulmonary hypertension are serious conditions that become progressively worse and are sometimes fatal. *1

Clinical features *2

The signs and symptoms of pulmonary hypertension in its early stages might not be noticeable for months or even years. As the disease progresses, symptoms become worse.

Pulmonary hypertension symptoms include:

• Shortness of breath (dyspnea), initially while exercising and eventually while at rest
• Fatigue
• Dizziness or fainting spells (syncope)
• Chest pressure or pain
• Swelling (edema) in your ankles, legs and eventually in your abdomen (ascites)
• Bluish color to your lips and skin (cyanosis)
• Racing pulse or heart palpitations

Causes

Your heart has two upper chambers (atria) and two lower chambers (ventricles). Each time blood passes through your heart, the lower right chamber (right ventricle) pumps blood to your lungs through a large blood vessel (pulmonary artery).In your lungs, the blood releases carbon dioxide and picks up oxygen. The oxygen-rich blood then flows through blood vessels in your lungs (pulmonary arteries, capillaries and veins) to the left side of your heart. Ordinarily, the blood flows easily through the vessels in your lungs, so blood pressure is usually much lower in your lungs.With pulmonary hypertension, the rise in blood pressure is caused by changes in the cells that line your 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. *3-*4

Pulmonary hypertension is classified into five groups, depending on the cause:

Group 1: Pulmonary arterial hypertension. Cause unknown, known as idiopathic pulmonary arterial hypertension. A specific gene mutation that can cause pulmonary hypertension to develop in families, also called heritable pulmonary arterial hypertension. Certain drugs — such as certain prescription diet drugs or illegal drugs such as methamphetamines — or certain toxins. Heart abnormalities present at birth (congenital heart disease). Other conditions, such as connective tissue disorders (scleroderma, lupus, others), HIV infection or chronic liver disease (cirrhosis).

Group 2: Pulmonary hypertension caused by left-sided heart disease. Left-sided valvular heart disease, such as mitral valve or aortic valve disease. Failure of the lower left heart chamber (left ventricle).

Group 3: Pulmonary hypertension caused by lung disease. Chronic obstructive pulmonary disease, such as emphysema. Lung disease such as pulmonary fibrosis, a condition that causes scarring in the tissue between the lungs’ air sacs (interstitium). Sleep apnea and other sleep disorders. Long-term exposure to high altitudes in people who may be at higher risk of pulmonary hypertension.

Group 4: Pulmonary hypertension caused by chronic blood clots. Chronic blood clots in the lungs (pulmonary emboli).

Group 5: Pulmonary hypertension associated with other conditions that have unclear reasons why the pulmonary hypertension occurs:

-Blood disorders
-Disorders that affect several organs in the body, such as sarcoidosis
-Metabolic disorders, such as glycogen storage disease
-Tumors pressing against pulmonary arteries
-Eisenmenger syndrome and pulmonary hypertension. Eisenmenger syndrome, a type of congenital heart disease, causes pulmonary hypertension. It’s most commonly caused by a large hole in your heart between the two lower heart chambers (ventricles), called a ventricular septal defect. This hole in your heart causes blood to circulate abnormally in your heart. Oxygen-carrying blood (red blood) mixes with oxygen-poor blood (blue blood). The blood then returns to your lungs instead of going to the rest of your body, increasing the pressure in the pulmonary arteries and causing pulmonary hypertension.*5

Figure 1: The five groups of pulmonary hypertension

Risk factors *6

Your risk of developing pulmonary hypertension may be greater if:

• You’re a young adult, as idiopathic pulmonary arterial hypertension is more common in younger adults.
• You’re overweight
• You have a family history of the disease
• You have one of various conditions that can increase your risk of developing pulmonary hypertension
• You use illegal drugs, such as cocaine
• You take certain appetite-suppressant medications
• You have an existing risk of developing pulmonary hypertension, such as a family history of the condition, and you live at a high altitude .

Figure 2: Risk factors for pulmonary hypertension

6-Minute Walking Test

Figure 3: description, instructions and indications for the 6-minute walking test

Complications *7

Pulmonary hypertension can lead to a number of complications, including:

• Right-sided heart enlargement and heart failure (cor pulmonale). In cor pulmonale, your heart’s right ventricle becomes enlarged and has to pump harder than usual to move blood through narrowed or blocked pulmonary arteries. At first, the heart tries to compensate by thickening its walls and expanding the chamber of the right ventricle to increase the amount of blood it can hold. But this thickening and enlarging works only temporarily, and eventually the right ventricle fails from the extra strain.
• Blood clots. Clots help stop bleeding after you’ve been injured. But sometimes clots form where they’re not needed. A number of small clots or just a few large ones dislodge from these veins and travel to the lungs, leading to a form of pulmonary hypertension that can generally be reversible with time and treatment.
•  Having pulmonary hypertension makes it more likely you’ll develop clots in the small arteries in your lungs, which is dangerous if you already have narrowed or blocked blood vessels.
• Arrhythmia. Irregular heartbeats (arrhythmias) from the upper or lower chambers of the heart are complications of pulmonary hypertension. These can lead to palpitations, dizziness or fainting and can be fatal.
• Bleeding. Pulmonary hypertension can lead to bleeding into the lungs and coughing up blood (hemoptysis). This is another potentially fatal complication.

Bosentan for Pulmonary artery hypertension:

Oral: <40 kg: Initial and maintenance: 62.5 mg twice daily ≥40 kg: Initial: 62.5 mg twice daily for 4 weeks; increase to maintenance dose of 125 mg twice daily. Doses >125 mg twice daily do not appear to confer additional clinical benefit but may increase risk of hepatotoxicity.
Note: When discontinuing treatment, consider a reduction in dosage to 62.5 mg twice daily for 3 to 7 days (to avoid clinical deterioration).

Diagnosis *8

Pulmonary hypertension is hard to diagnose early because it’s not often detected in a routine physical exam. Even when the condition is more advanced, its signs and symptoms are similar to those of other heart and lung conditions. Doctors may order several tests to diagnose pulmonary hypertension, determine the severity of your condition and find out the cause of your condition. Tests may include:

Echocardiogram. Sound waves can create moving images of the beating heart. An echocardiogram can help your doctor to check the size and functioning of the right ventricle, and the thickness of the right ventricle’s wall. An echocardiogram can also show how well your heart chambers and valves are working. Doctors may also use this to measure the pressure in your pulmonary arteries. Other exercise tests may also be done. These tests can help determine the severity and cause of your condition.

Chest X-ray. A chest X-ray can show images of your heart, lungs and chest. This test can show enlargement of the right ventricle of the heart or the pulmonary arteries, which can occur in pulmonary hypertension.

Electrocardiogram (ECG). This noninvasive test shows your heart’s electrical patterns and can detect abnormal rhythms. Doctors may also be able to see signs of right ventricle enlargement or strain.

Right heart catheterization. After you’ve had an echocardiogram, if your doctor thinks you have pulmonary hypertension, you’ll likely have a right heart catheterization. During the procedure, a cardiologist places a thin, flexible tube (catheter) into a vein in your neck or groin. The catheter is then threaded into your right ventricle and pulmonary artery. Right heart catheterization allows your doctor to directly measure the pressure in the main pulmonary arteries and right ventricle. It’s also used to see what effect different medications may have on your pulmonary hypertension.

Blood tests. Your doctor might order blood tests to check for certain substances in your blood that might show you have pulmonary hypertension or its complications. Blood tests can also test for certain conditions that may be causing your condition.

Additional tests

Computerized tomography (CT) scan. During a CT scan, you lie on a table inside a doughnut-shaped machine. CT scanning generates X-rays to produce cross-sectional images of your body. Doctors may inject a dye into your blood vessels that helps your arteries to be more visible on the CT pictures (CT angiography). Doctors may use this test to look at the heart’s size and function and to check for blood clots in the lungs’ arteries.

Magnetic resonance imaging (MRI). This test may be used to check the right ventricle’s function and the blood flow in the lung’s arteries. In this test, you lie on a movable table that slides into the tunnel. An MRI uses a magnetic field and pulses of radio wave energy to make pictures of the body.

Pulmonary function test. This noninvasive test measures how much air your lungs can hold, and the airflow in and out of your lungs. During the test, you’ll blow into a simple instrument called a spirometer.

Polysomnogram. This test detects your brain activity, heart rate, blood pressure, oxygen levels and other factors while you sleep. It can help diagnose a sleep disorder such as obstructive sleep apnea.

Ventilation/perfusion (V/Q) scan. In this test, a tracer is injected into a vein in your arm. The tracer maps blood flow and air to your lungs. This test can be used to determine whether blood clots are causing symptoms of pulmonary hypertension.

Open-lung biopsy. Rarely, a doctor might recommend an open-lung biopsy. An open-lung biopsy is a type of surgery in which a small sample of tissue is removed from your lungs under general anesthesia to check for a possible secondary cause of pulmonary hypertension.

Medications *9-*10

Oxygen Therapy: Some patients with pulmonary hypertension may need to breathe pure oxygen through an oxygen mask or though tubes that fit into the nose. Breathing pure oxygen can help relieve shortness of breath and can reduce blood pressure in the pulmonary arteries.

Vasodilators open narrowed blood vessels. One of the most commonly prescribed vasodilators for pulmonary hypertension is epoprostenol (Flolan, Veletri). The drawback to epoprostenol is that its effects last only a few minutes. This drug is continuously injected through an intravenous (IV) catheter via a small pump that you wear in a pack on your belt or shoulder. Potential side effects of epoprostenol include jaw pain, nausea, diarrhea and leg cramps, as well as pain and infection at the IV site. Another form of the drug, iloprost (Ventavis), can be inhaled six to nine times a day through a nebulizer, a machine that vaporizes your medication. Because it’s inhaled, it goes directly to the lungs. Side effects associated with iloprost include chest pain — often accompanied by a headache and nausea — and breathlessness. Treprostinil (Tyvaso, Remodulin, Orenitram), another form of the drug, can be given four times a day. It can be inhaled, taken as oral medication or administered by injection. It can cause side effects such as a headache, nausea and diarrhea.

Endothelin receptor antagonists. These medications reverse the effect of endothelin, a substance in the walls of blood vessels that causes them to narrow. These drugs may improve your energy level and symptoms. These medications include bosentan (Tracleer), macitentan (Opsumit), and ambrisentan (Letairis).

Sildenafil and tadalafil. Sildenafil (Revatio, Viagra) and tadalafil (Cialis, Adcirca) are sometimes used to treat pulmonary hypertension. These drugs work by opening the blood vessels in the lungs to allow blood to flow through more easily. Side effects can include an upset stomach, headache and vision problems.

High-dose calcium channel blockers. These drugs help relax the muscles in the walls of your blood vessels. They include medications such as amlodipine (Norvasc), diltiazem (Cardizem, Tiazac, others) and nifedipine (Procardia, others). Although calcium channel blockers can be effective, only a small number of people with pulmonary hypertension respond to them.

Soluble guanylate cyclase (SGC) stimulator. Soluble guanylate cyclase (SGC) stimulators (Adempas) interact with nitric oxide and help relax the pulmonary arteries and lower the pressure within the arteries. These medications should not be taken if you’re pregnant. They can sometimes cause dizziness or nausea.

Anticoagulants: Take warfarin exactly as prescribed, because warfarin can cause severe side effects if taken incorrectly.

Digoxin. Digoxin (Lanoxin) can help the heart beat stronger and pump more blood. It can help control the heart rate if you experience arrhythmias.

Diuretics. Commonly known as water pills, these medications help eliminate excess fluid from your body. This reduces the amount of work your heart has to do. They may also be used to limit fluid buildup in your lungs.

Oxygen. Your doctor might suggest that you sometimes breathe pure oxygen, a treatment known as oxygen therapy, to help treat pulmonary hypertension, especially if you live at a high altitude or have sleep apnea. Some people who have pulmonary hypertension eventually require continuous oxygen therapy.

Figure 4: Therapeutic approach to arterial pulmonary hypertension in ICU

Surgeries

Atrial septostomy. If medications don’t control your pulmonary hypertension, this open-heart surgery might be an option. In an atrial septostomy, a surgeon will create an opening between the upper left and right chambers of your heart (atria) to relieve the pressure on the right side of your heart. Atrial septostomy can have serious complications, including heart rhythm abnormalities (arrhythmias).

Transplantation. In some cases, a lung or heart-lung transplant might be an option, especially for younger people who have idiopathic pulmonary arterial hypertension. Major risks of any type of transplantation include rejection of the transplanted organ and serious infection, and you must take immunosuppressant drugs for life to help reduce the chance of rejection.

Conclusion

General treatment measures include optimal weight, physical activity, and pulmonary rehabilitation, avoidance of pregnancy and combination birth control for prevention of pregnancy in women on PAH-specific treatment, psychosocial support, seasonal flu and pneumonia vaccine, oral anticoagulants for idiopathic and heritable PAH, diuretics, oxygen as determined in the 6MW and nocturnal monitoring, and digoxin (no clear evidence). Iron deficiency and associated anemia are common and should be treated when present. Consultation from PH experts should be obtained in conjunction with other specialists for care during pregnancy; elective, urgent, and emergency surgery; and PAH treatment perioperatively. Patients suspected to have PAH should be referred to an expert center for confirmation and treatment including acute vasoreactivity testing (idiopathic PAH/heritable PAH/drug-induced PAH only); risk stratification and selection, and institution of the most appropriate treatment(s). Patients on PAH-specific drugs should be followed by the expert center for clinical response and subsequent therapeutic decisions including various combination therapies, end-of-life decisions, and consideration of referral for lung transplantation.

 

 

References:

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