Pulmonary Hypertension – Diagnosis, Symptoms, and Treatment

What is Pulmonary Hypertension?

Pulmonary hypertension is a form of high blood pressure that specifically affects the blood vessels of the lungs. The major vessel affected is the pulmonary artery that carries blood from the right side of the heart to the lungs. 

Pulmonary hypertension may occur without a clear reason or may be caused by conditions such as left-sided heart failure, pulmonary embolism, chronic obstructive pulmonary disease (COPD), or obstructive sleep apnea (OSA). The major complication of pulmonary hypertension is damage to the right heart due to the increased pressures it must pump against when pushing blood into the lungs.

Patients with pulmonary hypertension often have difficulty breathing and may develop swelling in the legs.  This disease is associated with a high amount of morbidity and mortality even when aggressively treated.

What Causes Pulmonary Hypertension?

Pulmonary hypertension is caused by elevated blood pressure in the pulmonary artery.  Blood gets to this artery through the following process: blood in the peripheral veins carries unoxygenated red blood cells through the venous system, which drains into the right side of the heart.  Your right ventricle then pumps blood into the lungs via the pulmonary artery.  This process is critical for oxygenation of the red blood cells and the delivery of oxygen to the vital organs and tissues.  Once red cells are oxygenated in the lungs, they then travel to the left side of the heart and are pumped out to other organs via the left ventricle.

Low levels of oxygen in the lungs - due to chronic obstructive pulmonary disease (COPD), pulmonary embolism, or left-sided heart failure (pulmonary edema) – causes the pulmonary artery to constrict.  The right ventricle now needs to pump harder to overcome the increased resistance of the pulmonary artery.  Over time, the right ventricle begins to change in response to this pressure and may ultimately fail.  This results in a backup of fluid, causing swelling in the legs and occasionally the abdominal cavity.

Pulmonary embolism – a blood clot traveling to the pulmonary artery – can also lead to pulmonary hypertension and right heart failure. Since blood clots typically occur suddenly this process leads to a dramatic and sudden onset of symptoms as opposed to the slow onset typically seen with more chronic causes of pulmonary hypertension.

How Common is Pulmonary Hypertension?

Pulmonary hypertension is a very rare condition, only around 500 - 1000 new cases of pulmonary hypertension occur in the United States each year. Many of these cases are due to heart failure, those that result from an issue within the lungs themselves are even more rare with 1 to 2 cases per million people per year in the U.S. 

 The mean age of diagnosis is 50 years and females are more often affected than males.  The 3-year survival for pulmonary hypertension is estimated at 48%.

Signs and Symptoms

The signs and symptoms associated with pulmary hypertension vary signfificantly based on the process that is increasing the blood pressure within the lungs. There are a set of symptoms that are present in almost every type of pulmonary hypertension, these are:

• Difficulty breathing
• Shortness of breath with exertion
• Chest pain

In severe cases signs of right heart failure will develop in patients, even if they have no history of heart failure. Swelling of the lower extremities is the most common sign of right heart failure in patients with pulmonary hypertension. 

Diagnosis

The diagnosis of pulmonary hypertension is complex and relies on several imaging studies, blood tests, and procedures. 

Your doctor will typically obtain a chest x-ray to evaluate for lung disease and assess cardiac size.  They will also usually obtain an ECG (electrocardiogram) to evaluate the electrical activity of the heart.  An ultrasound of the heart (echocardiogram) will be obtained to evaluate cardiac structure and function. The pressures within the pulmonary arteries of the lungs can also be estimated with an echocardiogram. 

Pulmonary hypertension secondary to pulmonary embolism is a medical emergency and requires hospitalization – your doctor will typically obtain a lower extremity ultrasound with Doppler studies to evaluate for deep vein thrombosis (venous blood clot in the leg).  They will also usually order a CT angiogram of the chest – this study evaluates the pulmonary vasculature and can identify a pulmonary embolism.

The definitive diagnosis of pulmonary arterial hypertension is made by a procedure called a right heart catheterization.  During this study, your pulmonologist or cardiologist will insert a catheter into a large vein (femoral vein) in the groin and advance it until it reaches the chambers of the heart.  This catheter measures the pressure in the chambers of the heart and the pulmonary artery.  Specialized hospitals will often perform a study called the vasoreactivity test during right heart catheterization – this can help guide doctors on the most beneficial therapy in patients with certain forms of pulmonary hypertension.

Commonly ordered blood tests in patients with pulmonary hypertension include a CMP (comprehensive metabolic panel), CBC (complete blood cell count), thyroid function tests (TSH, free T4), and coagulation studies (PT/INR, PTT).  They will also usually check your cholesterol levels and screen for diabetes.

If you have a pulmonary embolism, they will often perform age-appropriate cancer screening (e.g., colonoscopy, mammogram) and may evaluate you for thrombotic disorders such as factor V Leiden, prothrombin mutation, and factor C and S deficiency. As these mutations or a cancer anywhere in the body can increase your risk for blood clots.

Pulmonary Hypertension Treatment

The treatment of pulmonary hypertension is a delicate balance of reducing the pressure in the lungs and right side of the heart without causing significant effects elsewhere in the body. 

Patients that have signs of right heart failure typically benefit from diuretic therapy intended to reduce the amount of fluid in the body. Lasix (Furosemide) or Bumex (Bumetanide) are the two most common medications used for this purpose.  Patients with pulmonary hypertension secondary to a pulmonary embolism usually require treatment with anticoagulant therapy intended to prevent further blood clots. Coumadin (Warfarin), Xarelto (Rivaroxaban), Eliquis (Apixaban), or Pradaxa (Dabigatran) are the most common medications used to prevent blood clots.

Patients with positive vasoreactivity testing during right heart catheterization may improve with calcium channel blockers such as Norvasc (Amlodipine) or Procardia (Nifedipine) Which work to dilate the blood vessels in both the body and the lungs, decreasing the pressure in the lungs.

There are a large number of specialized medications that require close monitoring and regular changes in dosage. These are generally used only if you are experiencing severe or gradually progressing pulmonary hypertension. The vast majority of people with severe pulmonary hypertension will be on supplemental oxygen along with oral medications such as:

• Endothelin receptor antagonists
  • Letairis (Ambrisentan)
  • Tracleer (Bosentan)
  • Opsumit (Macitentan)
• Phosphodiesterase inhibitors such as Revatio (Sildenafil) or Adcirca (Tadalafil)
• Guanylate cyclase stimulants such as Adempas (riociguat)
• Oral prostacyclin pathway agonists such as Uptravi (selexipag)

Severe cases may require treatment with one of the following agents:

• Veletri (intravenous epoprostenol)
• Ventavis (inhaled iloprost)