Overview of Pulmonary Arterial Hypertension


Pulmonary arterial hypertension (PAH) is a progressive, chronic disorder of the blood vessels that supply the lungs (the pulmonary arteries). It's a serious condition that can damage the heart.


The walls of the pulmonary arteries become thick and stiff, and can not expand as well to allow blood through. The reduced blood flow makes it harder for the right-hand side of the heart to pump blood leading to abnormally high blood pressure in the arteries in the lungs. When the right-hand side of the heart has to continually work harder, it can gradually become weaker. This can lead to heart failure.

PAH is a long-term, debilitating and life-threatening condition that shortens patients’ life expectancy. It can affect people of all ages, and it's more common in people who have another heart or lung condition. It also predominately affects young women with a female to male ratio of 70% to 30%, respectively.

Symptoms of PAH


Symptoms of PAH include:

  • tiredness

  • shortness of breath

  • fainting

  • dizziness

  • fast pulse

  • chest pain

  • heart palpitations

  • joint pain or swelling


Due to the nature of PAH disease development, symptoms may not appear until the condition is already quite advanced. The symptoms often get worse during exercise, which can severely limit the ability to take part in physical activities.

These symptoms often have considerable detrimental effects on a patient’s quality of life, ability to function in daily activities, and overall social and societal engagement.

The underlying pathological hallmarks of PAH include pulmonary arterial endothelial cell (EC) dysfunction, excessive vasoconstriction, pulmonary artery EC and smooth muscle cell (SMC) proliferation, fibrosis & inflammation, in situ thrombosis and RV hypertrophy.

PAH, Pulmonary Arterial Hypertension

Diagnosis of PAH

As PAH shares symptoms with many other diseases, it can be difficult to diagnose.


To confirm PAH diagnosis and rule out other conditions, healthcare providers will determine what tests are needed, but they typically involve:

  • Electrocardiogram (ECG)

  • Pulmonary Function Test (PFT)

  • Lung Scan (Pulmonary Angiography CT)

  • Right Heart Catheterization (RHC)

Right heart catheterization is required to provide a definitive diagnosis of PAH. This test involves passing a thin tube (catheter) into the right side of the heart in order to test heart function and measure blood pressure.

Causes of PAH

PAH can be classified into four different types, based on the guidelines set forth by the World Health Organization (WHO) at the Fifth World Symposium on pulmonary hypertension in Nice, France in 2013;

  • The vast majority of PAH cases are of unknown origin, and are termed idiopathic PAH.

  • A number of drugs and toxins have been identified as risk factors for the development of PAH. Specifically, the use of anorexigens (appetite suppressants), such as fenfluramine, and central nervous system stimulants, such as methamphetamine or cocaine, are associated with an increased risk of developing PAH.

  • Some cases of PAH are inherited in an autosomal-dominant manner. Of these, about 80% of cases of familial PAH, which is PAH that occurs in multiple family members, have been linked to mutations occurring in the bone morphogenic protein receptor type 2 (BMPR2) gene, while other mutations include those found in the activin-like receptor kinase-1 (ALK1) and caveolin-1 (CAV1) genes, and in a gene encoding potassium channel super family K member-3 (KCNK3).

  • Another form of PAH is referred to as associated PAH, which occurs as a complication of other associated diseases, such as connective tissue disease (CTD), human immunodeficiency virus (HIV) infection, portal hypertension, congenital heart disease, and schistosomiasis.



Treating PAH


PAH can not be cured without lung transplantation, but treatment can reduce the symptoms and help to manage the condition. 


Untreated, PAH has a mean survival of just under 3 years. Recent advances in diagnosis, management and treatment options have extended mean survival to about 4 years, with 1-, 3- and 5-year survival rates of 85%, 67% and 58%, respectively.


PAH usually gets worse over time. Left untreated, it may cause heart failure, which can be fatal, so it's critical that treatment is started as soon as possible.

The currently available treatments for PAH largely fall into four classes and mainly treat the excessive pulmonary vasoconstriction/reduced vasodilation to restore or improve basic pulmonary function, as typically assessed by the “6-Minute Walk Test”.


These four drug classes include;

  • Endothelin receptor (ET) antagonists (ERAs), that inhibit excessive ET-induced vasoconstriction by mainly targeting the ETA receptor.

  • Phosphodiesterase (PDE) type 5 inhibitors that inhibit breakdown of cGMP and cAMP, prolonging the action of NO and the prostanoid Prostacyclin, respectively.

  • Activators of soluble guanylyl cyclase (sGC), that aim to restore NO/cGMP-induced vasodilation.

  • Prostacyclin analogues, that aim to restore Prostacyclin/cAMP-induced vasodilation.

However, these current therapies mainly treat the reduced vasodilation to lower pulmonary vascular resistance and improve exercise capacity, but do little to treat the other major clinical features of the disease or to reduce disease progression and, thus, patient outcomes remain poor.


At the FDA public meeting on PAH in May 2014, (“Voice of the Patient”) several participants commented on the downsides of current therapies. They commented on fears of site infections and how living with an intravenous line impacts daily activities. Female participants noted the emotional burden of monthly pregnancy testing and counselling required by some PAH medications. Access to medications through specialty pharmacies only, an often high frequency of dosing and cumbersome route of administration are all noted to be major factors in poor compliance with existing treatment regimes.


Therefore, there is an urgent unmet medical need for new targets and therapeutic drugs that offer greater tolerability/compliance and overall efficacy.


The outlook for pulmonary hypertension varies, depending on factors such as:

  • what's causing it

  • how quickly it's diagnosed

  • how advanced your symptoms are

  • whether you have another underlying health condition


The patient advocacy groups listed below offer practical information and support for people living with pulmonary hypertension and their friends and families;