Diseases

The first step in diagnosis of pulmonary hypertension is to clinically suspect it. This may be done as part of an evaluation of another disease that can lead to pulmonary hypertension (such as scleroderma or chronic obstructive pulmonary disease), or based on patients and signs and symptoms as described above.Echocardiogram, Doppler, heart catheterization

• Many tests, such as echocardiogram, may be performed that may give clues to the possibility of pulmonary hypertension. It is important that a Doppler study be performed with the echocardiogram, which enables the doctor to approximate the pulmonary artery pressures. These values are calculated based on the sound quality of the wave approaching and leaving the echocardiogram machine sensor/probe. This is based on the principle that explains why the sound of an approaching and then passing train varies.
• But the gold standard (the best test available) is right heart catheterization. This test entails inserting a catheter through the groin into the femoral vein, a large vein in the lower body (or under the collar bone or in the upper arm or neck into a large vein in the upper body) and advancing it to the right side of the heart. The catheter is connected to a device that can monitor and measure blood pressure in the right side of the heart and pulmonary arteries.
  • During right heart catheterization, oxygen levels are measured during various positions of the catheter in the pulmonary circulation. This can help determine if a congenital or acquired hole has formed in the heart contributing to the elevated pulmonary pressures. Certain medications or activities can be administered or performed during the procedure to help with the assessment. Nitric oxide can be inhaled and in certain forms of PAH a dramatic improvement in pressures can occur suggesting specific treatment options such as the use of calcium channel blocker medication. Some patients have an exaggerated pulmonary pressure response to exercise and this too can be measured by utilizing arm exercise during the procedure. Titration of medications for pulmonary hypertension while the he catheter is in place can help monitor the response to treatment and assist in optimizing therapy. This can assist in providing individualized therapy for patients with this complex disease.

Pulmonary hypertension is defined as the mean pulmonary artery blood pressure greater than 25 millimeter of mercury (mmHg) measured by right heart catheterization. The pressures can be much higher than 25 mmHg in some people. Therefore, the pulmonary hypertension can be labeled as mild, moderate, or severe based on the pressures. Mean arterial pressure calculated by multiplying the diagnostic pressure two times, and adding the systolic pressure to that number, and then divide by three (systolic is the upper number and diastolic is the lower number in measuring blood pressure). Normally, the pulmonary blood pressure is much lower pressure system than the systemic blood pressure (which is usually measured with a blood pressure cuff).What tests may be used in diagnosing pulmonary hypertension?Other tests available for diagnosing pulmonary hypertension include electrocardiogram (ECG, EKG), chest X-ray, and echocardiogram. An ECG may show some abnormalities that may be suggestive of right heart failure. Chest x-ray may also show enlargement of the chambers of the right heart. And echocardiogram (ultrasound of the heart) shows ultrasound images of the heart and can detect evidence of right heart failure and with the use of Doppler (as described previously) can estimate pressures in the pulmonary artery. These tests, in the right clinical setting, are very useful in diagnosing and managing pulmonary hypertension.Other tests may be useful in evaluating the conditions leading to secondary pulmonary hypertension. For example, a ventilation-perfusion scan (V/Q scan) can suggest blood clots in the pulmonary arteries or sometimes a CT scan of the chest can be used. The chest CT scan can detect pulmonary arterial clots, but also can show abnormalities of the lung tissue and surrounding structures that can contribute to pulmonary hypertension.Pulmonary function testing can be useful in diagnosing chronic obstructive pulmonary disease (COPD), and other lung diseases, and monitor disease progression. This test can be used to detect many aspects of lung function including airflow and evidence of obstruction, lung volumes, and the capacity for the lung to extract oxygen from the air.Sleep studies can confirm the diagnosis of sleep apnea and its severity and management options such as CPAP therapy.

Despite advances in various treatments, there is no cure for pulmonary hypertension.

There are many causes of pulmonary hypertension. Often more than one mechanism is involved in a specific disease process. This can also change as the disease progresses.

1. Diseases that affect flow out of the heart to the rest of the body result in backflow of blood (stacking of blood) that raises pulmonary venous pressures leading to pulmonary hypertension.
2. Hypoxic pulmonary vasoconstriction is the process in which the lung vessels narrow in attempt to divert blood from poorly functioning segments of the lung. For instance, when pneumonia develops, a portion of lung becomes inflamed and works poorly in performing the functions of the lung (to add oxygen and remove carbon dioxide from the blood). This process diverts blood from these poorly working areas and sends it to better functioning lung tissue. However, a problem develops when all the blood has a low oxygen level (hypoxia). This causes constriction of the vessels on the pulmonary arterial side and hence raises the pressure.
3. Remodeling of blood vessels also occurs in some diseases whereby the inner lining (lumen) of the vessel becomes narrowed due to inappropriate growth of the tissue within and around the vessel. Masses and scarring from other diseases can compress and narrow vessels causing increased resistance to flow resulting in elevation of pressures.
4. In a fairly common parasitic infection in the Middle East (schistosomiasis), the blood vessels in the lung become blocked by the parasites causing pulmonary artery hypertension.
5. Some substances cause constriction of the blood vessels. Pulmonary hypertension has been rarely reported with the use of anti-obesity drugs, such as dexfenfluramine (Redux) and Fen/Phen. These medications have seen been removed from the market. Some street drugs such as, cocaine and methamphetamines can cause severe pulmonary hypertension.
6. Some diseases raise pulmonary pressures to cause pulmonary artery hypertension for unclear reasons. Perhaps an unknown toxin or chemical effects the blood vessels by causes constriction or inappropriate growth of the tissue within or around the vessel. For example, there is a condition known as portopulmonary hypertension that is result of liver failure. When these individuals receive a liver transplant, the pulmonary hypertension disappears suggesting that the failing liver is unable to clear some biochemical that leads to pulmonary artery hypertension.

What causes idiopathic pulmonary hypertension?Primary pulmonary hypertension has no identifiable underlying cause. This term is mainly a historical name and no longer used. The current term used to describe this condition is idiopathic pulmonary hypertension. Idiopathic pulmonary hypertension is more common in young people and more common in females than males.Idiopathic pulmonary hypertension unusually is an aggressive and often fatal form of pulmonary hypertension. Whereas it is known that the arterial obstruction is caused by a building up of the smooth muscle cells that line the arteries, the underlying cause of the disease has long been a mystery.A genetic cause of the familial form of idiopathic pulmonary hypertension, now referred to as Heritable PAH, has been discovered. It is caused by mutations in a gene called BMPR2. BMPR2 encodes a receptor (a transforming growth factor beta type II receptor) that sits on the surface of cells and binds molecules of the TGF-beta superfamily. Binding triggers conformational changes that are shunted down into the cell's interior where a series of biochemical reactions occur, ultimately affecting the cell's behavior. The mutations block this process. This discovery may provide a means of genetic diagnosis and a potential target for the therapy of people with familial (and possibly also sporadic) primary pulmonary hypertension.

Pulmonary hypertension occurs when the pressure in the pulmonary arteries increases abnormally. To help explain this condition further, here is how the pulmonary arteries work.What are pulmonary arteries?The human body has two major sets of blood vessels that distribute blood from the heart to the body. One set pumps blood from the right heart to the lungs, and the other from the left heart to the rest of the body (systemic circulation). When a doctor or a nurse measures the blood pressure on a person's arm, he/she is measuring the pressures in the systemic circulation. When these pressures are abnormally high, the person is diagnosed as having high blood pressure (systemic hypertension).The portion of the circulation that distributes the blood from the right side of the heart to the lungs and back to the left side of the heart is referred to as the pulmonary (lung) circulation.The right ventricle pumps blood returning from the body into the pulmonary arteries to the lungs to receive oxygen. The pressures in the lung arteries (pulmonary arteries) are normally significantly lower than the pressures in the systemic circulation. When pressure in the pulmonary circulation becomes abnormally elevated, it is referred to as pulmonary hypertension. This most commonly occurs when the pulmonary venous pressure is elevated, so called pulmonary venous hypertension (PVH). This pressure is transmitted back to the right side of the heart and the pulmonary arteries. The result is elevated pulmonary pressure throughout the pulmonary circulation. Some of this is a direct pressure transmission from the venous system backward and some can result from a reactive constriction of the pulmonary arteries.Less commonly, pulmonary hypertension results from constriction, or stiffening, of the pulmonary arteries that supply blood to the lungs, so called pulmonary arterial hypertension (PAH).Whether it is pulmonary venous or pulmonary arterial hypertension, it becomes more difficult for the heart to pump blood forward through the lungs. This stress on the heart leads to enlargement of the right heart and eventually fluid can build up in the liver and other tissues, such as the in the legs.What are normal pulmonary artery pressure ranges?When the heart pumps blood it is referred to as systole, and when the heart fills with blood it is referred to as diastole. Normal pulmonary artery pressures range from an upper pressure (systolic) of 15-30 mmHg and a lower pressure (diastolic) of 4-12 mmHg. These values can be obtained approximately by and ultrasound of the heart (echocardiogram), and more accurately using a catheter to measure the pressures in the pulmonary circulation (right heart catheterization).

Generally, the prognosis of pulmonary varies depending on the underlying condition that is causing it. For idiopathic or familial pulmonary hypertension, the overall prognosis depends on the severity and whether treatment was instituted. The statistics show a survival of about 3 years in idiopathic pulmonary hypertension without any therapy. Some of the other factors may indicate even poorer prognosis which include severe symptoms, age of onset greater than 45 years, evidence of right sided heart failure, and failure to respond to treatment. For patients with idiopathic pulmonary hypertension who get started on treatment and respond to it, the prognosis is better. Studies are underway to determine optimal treatment regimens.

The treatment for pulmonary hypertension depends on the underlying cause.

• If left sided heart failure is the primary problem, then adequate treatment of the left heart failure by a cardiologist is the mainstay of treatment.
• In cases where hypoxia (low oxygen levels) due to any chronic lung disease, such as COPD, is the cause, then providing oxygen and appropriately treating the underlying lung disease by a lung doctor (pulmonologist) is the first step in treatment.
• In some patients, the elevated pressure may be related to obstructive sleep apnea syndrome (OSAS), and can be reduced with the use of a CPAP, (a device that delivers positive airway pressure during sleep).
• In conditions, such as scleroderma, which often can cause pulmonary hypertension, a rheumatologist is involved in the treatment program.
• Anticoagulation (thinning the blood) may be a treatment option if the main underlying cause is thought to be recurrent blood clot (chronic thromboembolic pulmonary hypertension). As indicated in previous section, referral to a specialty center may be warranted for a possible surgical removal of blood clot (thromboendarterectomy).
• For patients with primary pulmonary hypertension (those with no underlying cause), more advanced therapy may be attempted. These drugs have complex mechanisms, but in general they work by dilating (opening up) the pulmonary arteries and, therefore, by reducing the pressure in these blood vessels and some help prevent the excessive overgrowth of tissue in the blood vessels (that decrease remodeling of the vessels, as described previously). Besides constriction, PAH can result in an actual structural change of the pulmonary arteries, whether it is due to chronically elevated pressures or the disease itself, or a combination of the two is not completely clear. These drugs also can delay and in some cases reduce the degree of remodeling of the pulmonary arteries.

There are no clear statistical data on the prevalence of pulmonary hypertension. Since pulmonary hypertension is seen in multiple different conditions, it is perhaps better to look at the prevalence in each condition. It is fairly common in patients with heart failure, COPD, and sleep apnea. It occurs in 7% to 12% of patients with collagen vascular disease, and in less than 5% of HIV patients.

Generally, pulmonary physicians (pulmonologists) and cardiologists treat pulmonary hypertension. Depending on the cause, other physicians also may be involved such as sleep medicine doctors, rheumatologists, and perhaps even infectious disease specialists. Today, more health-care professionals in the community are becoming adept at managing pulmonary hypertension. However, it is reasonable to get a second opinion regarding management at a tertiary, university setting because the field of management of pulmonary artery hypertension is evolving rapidly.