Pulmonary Artery Hypertension


Pulmonary artery hypertension is a health condition characterized by abnormally high blood pressure in lung arteries of the making it for the wider right side of the heart to work. There are alternative names that are used to refer to the health condition including sporadic primary hypertension, secondary pulmonary hypertension, familial primary pulmonary hypertension and idiopathic pulmonary arterial hypertension among others. The health condition is usually fatal when not addressed in the shortest time possible although it is uncommon. As time goes by, the condition is said to get worse, for instance, shortness of breath which is a symptom of the disease starts slowly and gets worse over time. This research paper will be aimed at looking at the historical view of the illness, its diagnosis, its treatment together with its prognosis. This will make use of different peer-reviewed articles in order to acquire a wider content on the topic.

Pulmonary Hypertension Defined

Pulmonary hypertension is a rare progressive condition characterized by elevated pulmonary arterial pressure leading to right ventricular failure. The right ventricle receives blood from the right atrium and pumps it to the main pulmonary artery to receive oxygen. The blood is being pumped for a shorter distance; thus the pressures are usually lower when compared to the pressures in the systemic circulation. As a result, it is rare for the pressures in the pulmonary circulation to become abnormally elevated, but when they do this is usually termed as pulmonary hypertension. The American Pediatric Association describes pulmonary hypertension as the stress of the heart which leads to enlargement of the right side of the heart and eventually excess fluid can build up in other body organs such as liver and legs. This is a condition that exists in both adult and pediatric forms which have similar characteristics. This means that the right side of the heart is working harder than normal because of abnormal blood pressure in the arteries. The condition often leads to a number of symptoms with the most common one being shortness of breath. Shortness of breath starts slowly, but it is seen to get worse over time. This makes individuals become winded so they cannot perform an activity as they did before. There are also other symptoms that can be used to establish the condition such as chest pain, fatigue, swelling of the legs and lethargy.

When it comes to classification, pulmonary arterial hypertension is categorized into two main categories: primary and secondary pulmonary arterial hypertension. Primary pulmonary arterial hypertension is not caused by any other condition or disease while secondary pulmonary arterial hypertension is usually caused by another underlying condition. When it comes to commonness, secondary pulmonary arterial hypertension is more common than primary pulmonary arterial hypertension. Primary pulmonary arterial hypertension is believed to be more common in young people and more in females than males. It is also said to be more fatal and aggressive when it occurs. The main cause of primary pulmonary arterial hypertension is not yet known; however, there is some advancement on the same that identify it with a genetic cause. Some scientists claim that primary pulmonary arterial hypertension is caused by BMPR2 gene mutations. There are other medical practitioners who classify different types of pulmonary arterial hypertension according to their underlying causes.


This disease has many causative factors that are pathological. It can also be hereditary or idiopathic. With pulmonary hypertension, it is very important to understand the underlying cause and try to treat the patient from their homes. That leads to the hypothesis that there is a short lifespan with pulmonary hypertension due to many complications that ultimately lead to a decrease in a patient`s lifespan. There are different conditions that have been identified as possible causes of pulmonary hypertension. One of the common conditions that may cause the illness is congestive heart failure, which means an abnormal collection of blood in heart making the environment unfavorable for arteries to perform their duty effectively. Another condition that may be the cause of the illness is a venous thromboembolic disease which is characterized by clots of blood in lungs. The widely known and rapidly spreading human immunodeficiency virus infection may also result to the illness. There are different illegal drugs such as cocaine that may also cause pulmonary hypertension. Some medical practitioners have found cirrhosis of the liver to be a cause of pulmonary arterial hypertension. Some health professionals have claimed that when the cause is identified after testing, the condition is known as idiopathic pulmonary arterial hypertension.

Hypoxic pulmonary vasoconstriction is another cause of pulmonary arterial hypertension. This is defined as the process during which lung vessels narrow with an aim of diverting blood from poorly functioning segments of the whole organ (the lungs). As lung vessels try to divert blood from the poorly working areas and send it to the effectively working areas of the tissue, a problem normally develops when the oxygen level in blood is low, a condition termed as hypoxia. This results to constriction of the vessels on the pulmonary arterial side; hence the pressure in the right side of the heart is increased, causing pulmonary arterial hypertension. At times, remodeling of blood vessels takes place because of some diseases and results to the health condition. This is usually evident where the inner lining of the vessel becomes narrowed due to wrong growth of the tissue within and around the vessel. When the vessels are narrowed from the inner side, resistance is usually increased, and pressure hence rises.

Historical View and Research on Pulmonary Hypertension

Since the discovery of pulmonary hypertension over three decades ago, there have been extensive research done that can ultimately lead to the extension of life for a period but there is still no cure for the disease.

In 1984 pulmonary hypertension was not common, and it is still not common today. However researchers knew that they had researched what was to be some groundbreaking facts on pulmonary hypertension. Although the disease was first seen in the 1800's and again in the 1900s the first publication on pulmonary hypertension was done in 1951 by Drysdale et al. During this time, after being diagnosed an overall survival rate was 2.8 years. In the study conducted by Fuster et al, 120 patients have studied of which 21 patients were still alive 5 years later. This research was done to see if anticoagulant therapy was deemed helpful. It was deemed a success because it brought to light the fact that pulmonary arterial saturation (p. <.00001) and anticoagulant therapy (p. =.01) were actually helpful. This study also showed that there were two classifications of pulmonary hypertension in patients. It entailed thromboembolic pulmonary hypertension in 32 patients and plexogenic pulmonary arteriopathy in 18 patients.

There are five groups when it comes to classification of pulmonary hypertension based on the 2003 World Health Organization. Group 1 consists of idiopathic and familial pulmonary artery hypertension. Group 1 can be also associated with collagen vascular disease, congenital systemic-to-pulmonary shunt, portal hypertension, HIV infection and drugs and toxins. Factors that are found in group 2 are pulmonary hypertension with left heart disease, left-sided ventricular or arterial disease and left-sided valvular disease. Group 3 classifications are pulmonary hypertension associated with lung disease and or hypoxemia, chronic obstructive lung disease, interstitial lung disease, developmental disorders, chronic exposure to high altitudes and alveolar hypoventilation disorders. Group 4 classifications are pulmonary hypertension due to chronic thrombotic and embolic disease, thromboembolic obstruction of the proximal pulmonary artery and thromboembolic obstruction of distal pulmonary artery. Group 5 is miscellaneous reasons, for example, sarcoidosis, compression of pulmonary vessels (tumor, adenopathy) etc.

Evaluation and Diagnosis of Pulmonary Hypertension

The main and most fatal changes in persons with pulmonary hypertension are vasoconstriction, smooth muscle cell and endothelial cell proliferation and thrombosis. In a patient with pulmonary hypertension, it becomes very difficult for blood to circulate. This can lead to fatal outcomes where a person with pulmonary hypertension can either experience blood clots and artery blockage.

Populations that have been studied show that diagnosis of pulmonary artery hypertension takes an average of 2-2.9 years to make. This is because the initial symptoms are minimized and resemble other more common health conditions.

Initial Clinical Assessment


The first step in diagnosing pulmonary arterial hypertension is to suspect it. This can be done by looking at the signs and symptoms that a patient has or by evaluation of other diseases. Pulmonary hypertension should be considered in patients with progressive dyspnea or fatigue as these were the most common symptoms, according to the National Institutes of Health (NIH) registry on PPH from 1981 to 1987. There are other common symptoms that can be used including angina caused by right ventricular myocardial oxygen demand, syncope or lower extremity edema. Special attention should be given to men and women in their 30s and 40s together with patients whose families have a history of this health condition. Patients with connective tissue diseases, HIV, previous exposure to illegal drugs such as cocaine or anorexigens, chronic hypoxia and those with congenital heart defects should be also given more attention.

Physical Examination

Under physical examination, there are different conditions that may be suggestive of elevated right-side heart pressures including a loud P2, holosystolic murmur, right ventricular heave and increased jugular venous distention and probably elevated T waves. In thin patients, it is common to have a palpable pulmonary artery normally located along the left upper sternal border. In case of heart sounds, the patient should be given special attention. In patients with congenital heart defects, cyanosis may also be evident.

Diagnostic Testing


ECG testing is used to provide some evidence of pulmonary artery dysfunction through the presence of right axis deviation (seen in 79 percent of patients) and right ventricular hypertrophy (seen in 87 percent of patients). Right atrial enlargement is also associated with a 2.8-fold increased risk of mortality through a six-year observation in patients associated with the health condition. However, all the latter findings in suspected pulmonary arterial hypertension patients merit further testing.

Chest radiography

Medical practitioners claim that chest radiography only provides fewer specific clues to aid in the diagnosis of PAH. However, it plays a critical role in offering insight into the severity of the health condition through chronic thromboembolic disease, pulmonary edema due to left ventricular dysfunction. There are no associations so far that have been made regarding the use of radiographic changes to show the severity of the health condition; there are only classic changes such as pruning or enlarged main pulmonary arteries.


Patients suspected to have pulmonary arterial hypertension are required to undergo serological testing for connective tissue diseases such as mixed connective tissue disease, systemic sclerosis and systemic lupus erythematosus. All these diagnoses are crucial in the final therapy.


Transthoracic Doppler echocardiography is currently a widely used non-invasive tool for pulmonary hypertension evaluation. The sensitivity range of Transthoracic Doppler echocardiography is from 0.79 to 1.0 while the specificity range is from 0.6 to 0.98. This is mostly used for initial testing of pulmonary hypertension together with screening of patients whose families have a history of pulmonary hypertension. This is also a method of screening that is used for patients at high risks. It has many advantages over other methods since it can be used in demonstrating exercise-induced PAH. Quantification of maximal jet velocity and tricuspid regurgitation severity using the Bernoulli equation is used in the estimation of right ventricular systolic pressure. This method works effectively in 59-72% of patients screened; however, in some cases it is usually overestimated.

Perfusion scanning/ventilation

Perfusion scans are often used in ruling out other causes of dyspnea and in determining the clot burden involved. Under normal conditions, perfusion scans are also used in ruling out chronic thromboembolic disease.

Computed tomography

This is also termed as magnetic resonance imaging and is mainly used in the evaluation of the presence of pulmonary embolism and chronic thromboembolic pulmonary hypertension. This is usually crucial for characterization of the clot burden which becomes very significant in therapy.

Pulmonary function testing

Pulmonary function testing is aimed at ruling out obstructive lung disease as one of the main causes of the patient’s symptoms.

Disease monitoring

Exercise testing

Exercise testing is used to reveal early disease activity since victims of pulmonary hypertension have a limited capacity to increase their cardiac output. Exercise testing is crucial since it helps in revealing and monitoring early disease activity and the response of the patient to the disease. There are different changes that are associated with PAH patients; thus through exercise testing it becomes easy to reveal the changes such as those occurring in blood pressure, pulse, ventilator efficiency and anaerobic threshold.

Treatment of pulmonary hypertension

Currently, there is no known cure for pulmonary artery hypertension. The treatments that are employed are normally aimed at controlling the symptoms of the illness and preventing further damage of the lungs. In other cases, the conditions that caused the disease are the ones that are treated. By 2008, there were several advancements in the treatment of pulmonary hypertension, which started with the approval of epoprostenol in 2008. The discovery of epoprostenol in 1998 led to many clinical trials that were very helpful in moving treatment of these patients forward. One of which was the long-term intravenous infusion of epoprostenol to patients with primary pulmonary hypertension. In this study, insight into the long-term use of IV epoprostenol was very helpful in the patients that were studied in the functional class 3 and 4. Prior to this, the treatments were very limited. However, this study helped these patients live a longer life. This meant that the survival rate for these patients went up from 2.8 to 5 years. Epoprostenol (i.e., Prostaglandin I2 or Prostacyclin (PGI2)) is a potent, short-acting vasodilator and inhibitor or platelet aggregation that is produced by the vascular endothelin.

Another known treatment of pulmonary hypertension is Sitaxentan. Sitaxentan is an endothelin receptor blocker. Sitaxentan may benefit patients with pulmonary arterial hypertension by blocking the vasoconstrictor effects of endothelin-A while maintaining the vasodilator/clearance functions of endothelin-B receptors. This study was done for a 12 week period. Upon the entirety of the study, which is at 12 weeks, patients experienced improvement on both the 100mg and 300 mg dose of the medication. Both the 100-mg dose and the 300-mg dose, compared with placebo, increased 6-minute walk distance (100 mg: +35 m, p < 0.01; 300 mg: +33 m, p < 0.01); functional class, cardiac index, and pulmonary vascular resistance also improved (p < 0.02 for each parameter at both doses).

Later studies have shown different results in this area. In the past, endothelin receptor antagonists have been deemed very useful in the treatment of pulmonary artery hypertension.However, in light of new studies by the European society of cardiology, the endothelin receptor known as sitaxentan or Thelin was pulled from the market. The study found that the endothelin receptor antagonist caused fatal liver injury.After the study, the medication was told to be pulled from the market in Europe. Europeans were told to see their physician and seek medical advice to either start using different endothelin receptor or ambrisentan (Volibris).

There are also two other medications deemed helpful in controlling and stabilizing pulmonary hypertension. These are treprostinil and imatinib. In a study done on this medication in 2000, it was found that the exercise capacity improved when using this medication as opposed to being unchanged when using placebo medicine. There was also an improvement in exercise capacity. The findings showed that the exercise capacity dramatically improved in the sicker patients. With the use of Treprostinil, indices of dyspnea, signs and symptoms of pulmonary hypertension also improved. This article gave insight into the first experience with the use of a specific antagonist to the platelet-derived growth factor receptor for the treatment of pulmonary artery hypertension. Even though, this prior research was a single case study; this research was very helpful because this medication is still deemed very helpful in treating patients with pulmonary hypertension. The outcome of this study changed in 6-minute walk test (which improved), changes in hemodynamics, functional class, and serum levels of N-terminal brain natriuretic peptide. After 24 weeks, the mean placebo-corrected treatment-effect on 6MWD was 32 m (95% confidence interval [CI], 12, 52; P=0.002), an effect maintained in the extension study in patients remaining on imatinib. PVR decreased by 379 dynes•sec•cm-5 (95% CI: -502, -255; P<0.001; between-group difference). Functional class, TTCW and mortality did not differ between treatments.