Traci Stewart, RN, MSN
UI Heart and Vascular Center, Pulmonary Hypertension Program
University of Iowa Hospitals and Clinics

Creation Date: April 2007
Last Revision Date: April 2007
Peer Review Status: Internally Peer Reviewed

Definition of Pulmonary Hypertension (PH)
By hemodynamic definition, PH is present when mean pulmonary artery pressures exceed 25 mmHg at rest or 30 mmHg with activity. As pressure in the pulmonary arteries increases, the right side of the heart enlarges leading to volume overload and eventually to death.

When pulmonary pressures are elevated due to changes in the pulmonary arteries, it is known as pulmonary arterial hypertension (PAH). When PAH exists, excess endothelin and inadequate nitric oxide and prostacylin are produced by the endothelial cells lining the pulmonary arteries. This imbalance of chemicals leads to increased vasoconstriction, smooth muscle hypertrophy, and cell proliferation in the pulmonary arteries causing further damage and increased pulmonary artery pressures. PAH can be associated with medical conditions such as connective tissue disease (scleroderma or lupus), chronic liver disease, or HIV. When no known underlying disease can be determined, this rare condition is called idiopathic PAH.

PH can result from pulmonary venous hypertension from heart conditions such as cardiomyopathy, left-sided heart failure or valvular disease. PH can occur due to low oxygen levels, scaring in the lungs, or damage to the lung airways (emphysema, interstitial lung disease, or emphysema) or secondary to a pulmonary embolism or chronic thromboembolic disease. When PH occurs due to these conditions, treatment of the underlying disease process is essential.

Symptoms
Symptoms of pulmonary hypertension include dyspnea, fatigue, cough, lightheadedness, syncope, angina, and signs of volume overload such as lower extremity edema and ascites. Since PH is a rare disease, often these symptoms become quite severe before a diagnosis is made.

Diagnosis
Specific testing is necessary to identify or exclude causes of PH. An electrocardiogram (EKG), chest x-ray, echocardiogram, ventilation perfusion scan, and pulmonary function tests help to eliminate secondary causes of pulmonary hypertension. Blood tests including thyroid function and serology for ANA and HIV can help determine associated causes of PAH. Pulmonary angiography, computed tomography scans, and polysomnography may be beneficial in diagnosing PH. Finally, a right heart catheterization (RHC) is necessary to diagnose and determine the severity of the PH and right-sided heart failure. A RHC can also exclude congenital heart defects and measure the pressure reactivity to vasodilating medications.

Treatment
Treating PAH with medications that dilate the pulmonary arteries can improve symptoms and the strain on the right heart. Conventional medications such as anticoagulants, oral inotropes, and diuretics are considered. When hypoxia is present, supplemental oxygen can prevent further vasoconstriction of the pulmonary arteries. If the pulmonary arteries react to vasodilating medications, a challenge with high dose calcium channel blockers may be beneficial.

Advanced therapies work by counteracting the chemical imbalance leading to excessive vasoconstriction. Epoprostenol (Flolan) works as a potent vasodilator in the pulmonary and systemic circulation by imitating endogenous prostacyclin. Flolan is delivered as a continuous intravenous infusion through a central line. Since Flolan has a very short half-life (3-5 minutes), a pump ensures this medication is delivered at a slow, continuous rate because this medication can not be interrupted. Due to side effects and developed tolerance of the medication, frequent dose adjustments are necessary. Flolan requires daily reconstitution and must be kept chilled. Flolan can have side effects of flushing, nausea, diarrhea, headaches, and jaw pain and can be complicated by central line infections.

Treprostinil (Remodulin) is a prostacylin analog and can be administered as a continuous subcutaneous or intravenous infusion. Dose escalation and side effects are similar to Flolan. However, Remodulin requires less frequent mixing, has a longer half-life, and is stable at room temperature. Iloprost (Ventavis) is an inhaled form of prostacyclin. Treatments lasting 10 minutes are delivered 6-9 times while awake with a special device called an I-NEB. The most common side effects of Ventavis include cough and hypotension.

Bosentan (Tracleer) is an endothelin receptor antagonist (ERA) that blocks the vasoconstrictive effects of endothelin. Endothelin is made in the lung and is found in higher levels in PH patients contributing to elevated pulmonary artery pressures. Tracleer is an oral medication taken twice a day. Because of potential liver toxicity, liver function tests must be checked monthly. Volume retention and anemia can be worsened by Tracleer.

Sildenafil (Viagra/Revatio) is a phosphodiesterase type 5 inhibitor which dilates the pulmonary arteries by prolonging the effects of nitric oxide. Revatio has been marketed as an oral tablet given three times a day for PH. Side effects include lightheadedness, headache, and indigestion or acid reflux.

Lung transplantation is a surgical intervention considered for treatment of PAH. Due to the shortage of organs and progression of PH, the physician and patient continually evaluate and discuss the timing of transplant evaluation.

Further research is ongoing to look for ways to improve PAH treatment options. Currently the FDA is reviewing two alternative ERA receptor specific medications. Industry sponsored trials are ongoing to evaluate clinical response to combination therapy and national databases are collecting information to evaluate survival, diagnosis, and treatment patterns in individuals with PAH.

Visit UI Heart and Vascular Center's Pulmonary Hypertension Program for more information.