Approach Considerations
The therapy for group 3 pulmonary hypertension is primarily directed at the treatment of the underlying disease. Effective therapy should be instituted in the early stages, before irreversible changes in pulmonary vasculature occur. Once the cause of group 3 pulmonary hypertension has been established, management consists of specific interventional therapy, specific medical therapy, or general supportive therapy.
The use of a continuous positive airway pressure (CPAP) device in patients with obstructive sleep apnea has shown to significantly decrease the mean pulmonary artery pressures, suggesting potential reversibility of pulmonary hypertension upon treatment of obstructive sleep apnea. [20, 30]
Inhaled vasodilators are thought to improve ventilation-perfusion matching in patients with chronic obstructive pulmonary disease (COPD) by improving perfusion to well-ventilated areas of lung, primarily in the apices. [2] Results from the ASPIRE registry demonstrated that 19% of patients with severe pulmonary hypertension associated with COPD identified arbitrarily as having an objective response to vasodilator therapy based on improvements in WHO functional class or a greater than 20% fall in pulmonary vascular resistance had a superior survival compared with nonresponders and may represent a phenotype in which there is a greater degree of potentially treatment-responsive vasculopathy compared with emphysematous obliteration of the pulmonary microvascular bed. [31]
Preliminary data with inhaled iloprost, a prostacyclin analogue, appear promising, although frequent inhalations are required. Similarly, the use of almitrine, a drug that enhances pulmonary hypoxic vasoconstriction, increases the partial pressure of oxygen (Pa02) in COPD patients from 52 mm Hg to 59 mm Hg. However, ventilation-perfusion matching is worsened by systemic vasodilators and calcium channel blockers. [2, 32, 33]
Bosentan, an endothelin-1 receptor antagonist traditionally used to treat group 1 pulmonary arterial hypertension, was shown to negatively affect gas exchange in a randomized controlled trial performed on COPD patients. [34] Despite these discouraging results, traditional group 1 pulmonary arterial hypertension treatment may confer some benefit to COPD patients with “out-of-proportion” pulmonary hypertension, defined as mean pulmonary artery pressure 35-40 mm Hg or greater and relatively preserved lung function that cannot explain prominent dyspnea and fatigue. [32] However, more clinical trials are necessary to evaluate treatment efficacy in this specific subgroup of group 3 pulmonary hypertension patients.
Balloon atrial septostomy has been used with success in patients without evidence of right ventricular failure. The benefit (improved exercise function) occurs at the cost of a fall in arterial oxygen saturation (SaO2). The technique has been performed via a femoral catheter, with a Brockenbrough septal needle and Mansfield balloons to dilate the septostomy.
Oxygen Supplementation
Oxygen has proved beneficial for reducing patient mortality in selected patients with pulmonary hypertension. Two large trials demonstrated a definite mortality benefit for patients with COPD, the most common cause of pulmonary hypertension. Survival rates are highest in COPD patients who have less severe pulmonary hypertension, patients in whom the pulmonary arterial pressure decreases, or patients in whom exercise capacity improves with oxygen therapy.
Although long-term study results are not available, it appears that oxygen administration may also benefit other groups of patients with pulmonary hypertension. Accordingly, long-term oxygen therapy should be prescribed for patients whose arterial oxygen tension (PaO2) is lower than 55 mm Hg at rest from any cause, those who have desaturation during exercise, and those who perform better on oxygen therapy.
Medicare indications for continuous long-term oxygen therapy include the following:
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PaO 2 of 55 mm Hg or less or SaO 2 of 88% or less
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PaO 2 of 56-59 mm Hg or SaO 2 of 89%, in the presence of evidence of cor pulmonale, right-sided heart failure, or erythrocytosis (hematocrit >55%)
Lung Transplantation
Although lung transplantation is reserved for patients with severe pulmonary hypertension, a number of secondary pulmonary hypertension patients have undergone successful transplantation at several centers. These patients had secondary pulmonary hypertension due to collagen-vascular disease, drug-induced pulmonary hypertension, or pulmonary veno-occlusive disease. The stability of the underlying causative disorder and the ability of the patient to tolerate an extensive operation are prerequisites. Heart-lung transplantation has been performed in patients with secondary pulmonary hypertension due to congenital cardiac disease or severe left ventricular dysfunction.
Although lung transplantation has historically been the treatment of choice for severe pulmonary arterial hypertension, at present it is typically needed only for patients who are still in New York Heart Association (NYHA) functional class IV after 3 months of therapy with epoprostenol. The long-term outcomes of lung transplantation remain disappointing, with 50% survival at 5 years.
