Pulmonary Hypertension Support Group

Although the terms primary pulmonary hypertension (meaning of unknown cause) and secondary pulmonary hypertension (meaning due to another medical condition) still persist in materials disseminated to patients and the general public, these terms have largely been abandoned in the medical literature. This change has occurred because the older dichotomous classification did not reflect pathophysiology or outcome. It led to erroneous therapeutic decisions, i.e. treat "primary" pulmonary hypertension only. This in turn led to therapeutic nihilism for many patients labeled "secondary" pulmonary hypertension, and could have contributed to their deaths. The term "primary pulmonary hypertension" has now been replaced with "idiopathic pulmonary arterial hypertension". The terms "primary" and "secondary" pulmonary hypertension should not be used any longer.

A history usually reveals gradual onset of shortness of breath, fatigue, non-productive cough, angina pectoris, fainting or syncope, peripheral edema (swelling of the limbs, especially around the ankles and feet), and rarely hemoptysis (coughing up blood). Pulmonary arterial hypertension (PAH) typically does not present with orthopnea or paroxysmal nocturnal dyspnea, while pulmonary venous hypertension typically does.

In order to establish the cause, the physician will generally conduct a thorough medical history. A detailed family history is taken to determine whether the disease might be familial. A history of exposure to cocaine, methamphetamine, alcohol leading to cirrhosis, and smoking leading to emphysema are considered significant. Physical examination is performed to look for typical signs of pulmonary hypertension including a loud P2 (pulmonic valve closure sound), (para)sternal heave, jugular venous distension, pedal edema, ascites, hepatojugular reflux, clubbing etc. Physical examination evidence of tricuspid insufficiency is also sought and, if present, is consistent with the presence of long-standing pulmonary hypertension.

Treatment is determined by whether the PH is arterial, venous, hypoxic, thromboembolic, or miscellaneous. Since pulmonary venous hypertension is synonymous with congestive heart failure, the treatment is to optimize left ventricular function by the use of diuretics, beta blockers, ACE inhibitors, etc., or to repair/replace the mitral valve or aortic valve.

In PAH, lifestyle changes, digoxin, diuretics, oral anticoagulants, and oxygen therapy are considered conventional therapy, but have never been proven to be beneficial in a randomized, prospective manner.

High dose calcium channel blockers are useful in only 5% of IPAH patients who are vasoreactive by Swan-Ganz catheter. Unfortunately, calcium channel blockers have been largely misused, being prescribed to many patients with non-vasoreactive PAH, leading to excess morbidity and mortality.

Three major pathways are involved in abnormal proliferation and contraction of the smooth-muscle cells of the pulmonary artery in patients with pulmonary arterial hypertension. These pathways correspond to important therapeutic targets in this condition and play a role in determining which of three classes of drugs ? endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclin derivatives ? will be used.

Prostacyclin (prostaglandin I2) is commonly considered the most effective treatment for PAH. Epoprostenol (synthetic prostacyclin, marketed as Flolan?) is given via continuous infusion that requires a semi-permanent central venous catheter. This delivery system can cause sepsis and thrombosis. Flolan? is unstable, and therefore has to be kept on ice during administration. Since it has a half-life of 3 to 5 minutes, the infusion has to be continuous (24/7), and interruption can be fatal. Other prostanoids have therefore been developed. Treprostinil (Remodulin?) can be given intravenously or subcutaneously, but the subcutaneous form can be very painful. Iloprost (Ilomedin?) is also used in Europe intravenously and has a longer half life. Iloprost (marketed as Ventavis?) is the only inhaled form of prostacyclin approved for use in the US and Europe. This form of administration has the advantage of selective deposition in the lungs with less systemic side effects.

The dual (ETA and ETB) endothelin receptor antagonist bosentan (marketed as Tracleer?) was approved in 2001. Two selective endothelin receptor antagonists (ETA only) are in the final stages of approval: sitaxsentan and ambrisentan. Sildenafil, a selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5), was approved for the treatment of PAH in 2005. It is marketed for PAH as Revatio?. Tadalafil (currently marketed as Cialis? for erectile dysfunction) is currently is Phase III trials. Vasoactive intestinal peptide by inhalation should enter clinical trials for PAH in 2007. PRX-08066 is a serotonin antagonist currently being developed for hypoxic pulmonary hypertension.

Atrial septostomy is a surgical procedure that creates a communication between the right and left atria. It relieves pressure on the right side of the heart, but at the cost of lower oxygen levels in blood (hypoxia). It is best performed in experienced centers. Lung transplantation cures pulmonary arterial hypertension, but leaves the patient with the complications of transplantation, and a survival of about 5 years.

Pulmonary thromboendarterectomy (PTE) is a surgical procedure that is used for chronic thromboembolic pulmonary hypertension. It is the surgical removal of an organized thrombus (clot) along with the lining of the pulmonary artery; it is a large and very difficult procedure that is currently performed in a few select centers. Case series show remarkable success in most patients.

Treatment for hypoxic and miscellaneous varieties of pulmonary hypertension have not been established. However, studies of several agents are currently enrolling patients. Many physicians will treat these diseases with the same medications as for PAH, until better options become available.