Primary pulmonary hypertension (PPH) is a rare disease that affects approximately 2-3 patients per million worldwide each year and is responsible for about 125-150 deaths per year in the United States. In most cases, PPH untreated is rapidly fatal.

The average time to diagnosis in patients with PPH is two years. The presumed reason is due to that fact that an extensive workup is necessary to elucidate the cause of a patient's elevated pulmonary artery pressure, and the early symptoms are non-specific. Survival in patients with PPH who are untreated is approximately 30% at 3 years.

Common symptoms of PPH are shortness of breath, weakness, and fainting episodes. Women are more likely to be symptomatic than men.

Because of the common presence of antinuclear antibodies (ANA) in the sera of some patients with PPH, it is often difficult to say with certainty that these patients have PPH and that the elevated pulmonary artery pressures are not due to a secondary cause, which may not yet be clinically apparent. In addition, patients with PPH may have nonspecific clinical rheumatologic findings such as Raynaud's phenomenon or arthritis, making the differentiation of PPH from secondary pulmonary hypertension even more difficult. Drugs and PPH

Ingested substances can have adverse effects on the pulmonary circulation. This so-called "dietary pulmonary hypertension" is considered a subset of PPH. Culprit dietary substances include appetite-suppressants, and oral contraceptives.

Recently, an association between the appetite suppressant fenfluramine and PPH has been reported. This prompted a recent study of the use of anorexic drugs as a class and their relation to PPH. This study found a six-fold risk of PPH in patients that had ever used anorexic drugs to lose weight. In patients that used these agents for at least three months, the risk was increased twenty-three-fold. This is especially alarming, because the FDA had recently approved dexfenfluramine for use in obese patients. The approval committee felt that the risks of obesity outweighed the risk of developing PPH, yet this conclusion has been challenged by many experts. Currently, the whole class of diet drugs is under scrutiny because of recent reports of valvular heart disease, another recently discovered serious danger of diet drugs.

The treatment of PPH includes the use of anticoagulant therapy to reduce the incidence of thrombosis within the pulmonary vasculature. Although anticoagulation therapy has never been proven in a randomized prospective long-term trial, several studies have shown that survival is increased in PPH patients treated with anticoagulant therapy. Digoxin therapy has been recommended in PPH patients with right ventricular failure to improve right ventricular function. Diuretics are especially useful in managing peripheral edema, and oxygen supplementation is used routinely in patients with resting or exercise-induced low oxygen levels.

Calcium channel blockers are the most widely-used class of drugs in PPH. The use of these drugs has produced reductions in pulmonary pressures and improved quality of life and survival in patients with PPH.

Currently, a precise dosage-adjustment algorithm does not exist for patients with PPH for patients on vasodilator therapy. Patients are monitored as outpatients with frequent physical exams, and histories are focused on heart failure symptoms and side effects of medications.

As a result of these recent discoveries, newer forms of therapy have recently emerged as alternatives or adjuncts to currently available treatment modalities for PPH. Epoprostenol (EPO), also called Flolan, is an analogue of a naturally occurring vasodilator found in the body, and has recently been approved by the FDA for use in patients with PPH.

EPO is given as a continuous intravenous infusion via a permanent catheter, using a small battery-powered infusion pump worn at the hip or carried in a backpack. Initial dosing is done under close observation in the intensive care unit, with right heart flotation catheter in place.

Recently published results of EPO use in PPH patients show improvements in pulmonary artery hemodynamics and survival. Many patients who would not have survived the wait for lung transplantation were able to undergo transplantation when a donor was made available. Still others had a marked reduction in PVR to nearly normal values, many becoming asymptomatic with long-term EPO use.

The use of EPO is reserved for patients with severe disease, those who are considered for lung transplantation, with severe right ventricular failure (class III and IV NYHA Classification) and reduced cardiac output, with severe limitation of daily activities . This is primarily due to its high cost (about $100,000/yr per patient) and the risks associated with a permanent indwelling central venous catheter.

Two newer therapies, Remodulin (treprostinil) click here , and Tracleer (bosentan) click here have been recently approved, and offer alternatives to Flolan therapy.

Lung transplantation for PPH

Double or single lung transplantation, with or without simultaneous heart transplantation has improved the survival of patients with severe symptoms and signs of PPH. Currently, patients are placed on a transplantation waiting list only if symptoms and signs of PPH are severe.

The one-year survival of PPH patients after lung transplantation is approximately 65%.

Future directions

As newer insights develop into elucidating the causes and mechanisms underlying PPH, newer forms of therapy are emerging as alternatives or adjuncts to intravenous EPO. Our center is involved in several trials using new drugs. Press here for more information.

Click here for additional information on "what is PAH" from the National Heart, Lung, and Blood Institute (NHLBI).