Pulmonary Hypertension & PAH

Pulmonary Hypertension

Pulmonary hypertension means high blood pressure in the lungs. This is a rare chronic lung disease where the blood pressure in the pulmonary arteries increase, making it harder for the heart to pump blood through the lungs. The pulmonary arteries are blood vessels in the lungs that carry deoxygenated blood pumped by the lower right chamber of the heart (right ventricle) to pick up oxygen and shed carbon dioxide at the lungs and return to the upper left chamber (left atrium) of the heart to be pumped to supply oxygen to the rest of the body by the lower left chamber (left ventricle). When the pressure in the pulmonary arteries continues to build-up, the right side of the heart needs to work harder and harder to pump blood through the lungs to maintain adequate oxygen supply to the body. Without proper intervention, the muscles of the right side of the heart will overtire and weaken overtime and eventually fail leading to serious complications and often fatal.


Pulmonary hypertension is said to be present when the blood pressure of the lungs becomes greater than 25 mm Hg at rest and 30 mm Hg when exercising. (Normal pulmonary artery pressure is between 8 to 20 mm Hg when a person is resting.) Most people will not notice symptoms during the early stages of pulmonary hypertension as the heart can still maintain an adequate oxygen supply to the body by working harder. Some people with pulmonary hypertension may not notice any discomfort for years. However, as the disease progresses, the heart will eventually lose the battle and symptoms begin to arise and become worse overtime.

The common symptoms of pulmonary hypertension include:

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


The World Health Organization (WHO) has categorized pulmonary hypertension into five groups based on the cause. Understanding the cause of your pulmonary hypertension is the most important factor for determining the right prevention and treatment course.

Group 1: Pulmonary arterial hypertension (PAH)
The tiny arteries in the lungs, called pulmonary arterioles, become narrowed, damaged, blocked, and destroyed. The continuous narrowing and destruction of pulmonary arterioles cause the pulmonary artery pressure to rise.

  • Unknown cause – referred to as idiopathic pulmonary arterial hypertension
  • Caused by a specific gene mutation – referred to as heritable pulmonary arterial hypertension. This often runs within families.
  • Caused by certain drugs and toxins— such as certain prescription diet drugs or illegal drugs such as methamphetamine
  • Caused by heart abnormalities present at birth (congenital heart disease)
  • Caused by connective tissue disorders (scleroderma, lupus, others)
  • Caused by viral infections such as HIV infection
  • Caused by chronic liver disease (cirrhosis)

Group 2: Pulmonary hypertension caused by left-sided heart disease
This is also known as pulmonary venous hypertension. This happens when the left-side of the heart can not effectively carry away blood from the lungs, resulting in a back-up of fluid in the lungs (pulmonary edema) causing the pulmonary pressure to increase. This is most often a result of diseases to the left side of the heart:

  • Left-sided valvular heart disease, such as mitral valve or aortic valve disease
  • Left-sided heart failure – failure of the lower left heart chamber (left ventricle)

Group 3: Pulmonary hypertension caused by lung disease
This is also known as pulmonary hypoxic hypertension. The small arteries of the lungs are programmed to restrict themselves under low oxygen environments. This mechanism is suppose to help redistribute blood to other regions of the lung to find richer oxygen environments. However, when the overall environment the lung is in has poor oxygen level, all the arteries in the lung become restricted. If this happens for a prolonged period of time, pulmonary hypertension starts to develop. Causes include:

  • Chronic obstructive pulmonary disease (COPD), such as emphysema
  • Lung disease such as pulmonary fibrosis (IPF)
  • Sleep apnea and other sleep disorders
  • Long-term exposure to high altitudes and low oxygen environments

Group 4: Pulmonary hypertension caused by chronic blood clots
This is self-explanatory – chronic blood clots in the lungs (pulmonary emboli) blocks blood vessels in the lungs causing increased pulmonary pressure.

Group 5: Miscellaneous Pulmonary Hypertension Causes
This catagory includes all causes associated with other conditions that have unclear reasons why the pulmonary hypertension occurs. These include:

  • 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


As you can see from the previous section on cause, Group 2 to 5 of pulmonary hypertension are secondary to other diseases or conditions. If your pulmonary hypertension is determined to be secondary to another condition, your doctor will also treat the underlying condition whenever possible. For instance, if your pulmonary hypertension is caused by chronic blood clots in your lungs, by dissolving your blood clots and preventing them from forming in the future, you may be free from pulmonary hypertension. Unfortunately, certain types of pulmonary hypertension, such as pulmonary artery hypertension (PAH) can not be cured,  but treatments can help manage your condition by improving symptoms and your quality of life and also slow down disease progression and preventing right-sided heart failure.


  • Blood vessel dilators (vasodilators). Vasodilators help to open up your 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. As a result, epoprostenol often needs to be continuously injected through an intravenous (IV) catheter by a small pump that you have to wear.
    Another form of this drug, called iloprost (Ventavis), can be inhaled through a nebulizer six to nine times a day. A nebulizer is a machine that vaporizes the medicine for you to inhale directly into your lungs.
    A third form of this drug, called treprostinil (Tyvaso, Remodulin, Orenitram), can be taken as an oral medication, or inhaled or given as an injection, usually four times a day.
  • Endothelin receptor antagonists. Endotheline is a substance naturally produced by the body that causes blood vessels to narrow and raise blood pressure. This class of medication selectively blocks the effect of endothelin on the blood vessels in your lungs, as a result lowers the pulmonary arterial pressure. This class of drugs are taken orally and acts longer in the body, so they only needs to be taken one to two times per day. They can significantly lower your pulmonary hypertension and improve your energy level and overall symptoms.
    These medications include bosentan (Tracleer), macitentan (Opsumit), and ambrisentan (Letairis, Volibris).
  • PDE5 inhibitors. Sildenafil (Revatio, Viagra) and tadalafil (Cialis, Adcirca) are sometimes used to treat pulmonary hypertension. These drugs work by relaxing the blood vessels in the lungs to allow blood to flow through more easily.
  • Soluble guanylate cyclase (SGC) stimulator. Soluble guanylate cyclase (SGC) stimulators have similar effects to PDE5 inhibitors. They mimic the effect of nitric oxide and help relax the pulmonary arteries and lower the pressure within the arteries.
  • High-dose calcium channel blockers. This class of drugs also helps relax the muscles in the walls of your blood vessels. They are more commonly used to treat systemic hypertension, the high blood pressure we commonly refer to that’s not in the lungs. Although calcium channel blockers can be effective, only a small percentage of people with pulmonary hypertension respond to them.
  • Anticoagulants. Your doctor is likely to prescribe the anticoagulant to help prevent the formation of blood clots within the narrowed pulmonary arteries. Warfarin (Coumadin, Jantoven) used to be the most commonly prescribed anticoagulant, but because warfarin has many drug interactionss with other medications and foods containing vitamin K, it is hard to keep people’s INR within therapeutic range and people on warfarin often requries weekly blood work to monitor their INR. Newer anticoagulant agents have more stable effects and do not require continuous blood monitoring and dose adjustment. Examples include rivaroxaban (Xarelto)and apixaban (Eliquis).
  • Digoxin. Your doctor may prescribe digoxin if you have arrhythmia and needs help control your heart rate. Digoxin can help the heart control its rate and pump blood more effectively.
  • Diuretics. Diuretics are commonly referred to as “water pills”. They help eliminate excess fluid from the body, which lowers blood pressure and also reduces the workload of your heart. If you have fluid build-up in your lungs (pulmonary edema), diuretics are necessary to help eliminate this fluid build-up.
  • Oxygen. Your doctor may prescribe you to breath 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.

Combination Therapies

Many clinical studies and guidelines have suggested that combining medications from different classes with different mechanisms of action can produce additive and sometimes synergistic effects. By combining therapies, the safe effect of each individual medication can often be achieved at lower doses thus minimizing side-effects.
Commonly used combination therapies include:

  • Ambrisentan plus Tadalafil
  • Bosentan plus Sildenafil
  • Bosentan plus either Epoprostenol or Treprostinil
  • Treprostinil plus either Bosentan or Sildenafil
  • Sildenafil plus Epoprostenol
  • Sildenafil plus Iloprost
  • Bosentan plus Iloprost
  • Sildenafil plus Riociguat

The combination associated with the best efficacy is Tadalafil plus Ambrisentan for patients with functional class II or III PAH, which was demonstrated by the AMBITION trial (click here to read the results of the full trial)


Surgeries are usually the last resort for people with pulmonary hypertension that can not be controlled by any medications as surgeries are often associated with serious complications.

  • Atrial septostomy. This open-heart surgery creates an opening between the upper left and right chambers of your heart (atria) to let blood flow from the right atria to the left atria to relieve the pressure on the right side of your heart. Atrial septostomy can have serious complications, including heart rhythm abnormalities (arrhythmias).
  • Transplantation. A lung or heart-lung transplant depending on the situation, 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.