The treatment algorithm for idiopathic-, heritable-, drug-induced, and connective tissue disease–associated PAH highlights the importance of cardiopulmonary comorbidities and risk strata at the time treatment is initiated and then during follow-up.
Cardiopulmonary comorbidities are conditions associated with an increased risk of left ventricular diastolic dysfunction, including obesity, hypertension, diabetes, and coronary artery disease. Pulmonary comorbidities can include signs of mild parenchymal lung disease and are often associated with a low carbon monoxide diffusing capacity (< 45% of predicted value).
The management algorithm proceeds as follows:
For patients without cardiopulmonary comorbidities and who are at low or intermediate risk, treatment of PAH with an endothelin receptor antagonist (ERA) plus a phosphodiesterase-5 (PDE5) inhibitor is recommended.
For patients without cardiopulmonary comorbidities and who are at high risk, treatment with an ERA, a PDE5 inhibitor, and either an IV or subcutaneous prostacyclin analogue (PCA) can be considered.
Patients in either of the preceding 2 categories should have regular follow-up assessment; at such follow-up, their risk should be stratified based on 4 strata (see “How risk is stratified”):
Low risk: Continue initial therapy.
Low-to-intermediate risk: Consider adding a prostacyclin receptor agonist to the initial regimen or switch to a PDE5 inhibitor or a soluble guanylate cyclase stimulator.
Intermediate-to-high or high risk: Consider adding a PCA (IV epoprostenol or IV or subcutaneous treprostinil). In addition, or alternatively, have the patient evaluated for lung transplantation.
For patients with cardiopulmonary comorbidity—in any risk category—consider oral monotherapy with a PDE5 inhibitor or an ERA. Provide regular follow-up and individualize therapy.6
Treatment for WSPH Groups 2 and 3
Treatment is focused on the underlying cause of PH:
Patients who have left heart disease with either severe pre-capillary component PH or markers of right ventricular dysfunction, or both, should be referred to a PH center.
Patients with combined pre-capillary and postcapillary PH in whom pre-capillary PH is severe should be considered for an individualized approach.
Consider prescribing the ERA bosentan in specific scenarios (eg, the Eisenmenger syndrome of left-right shunting resulting from a congenital cardiac defect) to improve exercise capacity. If PAH persists after corrected adult congenital heart disease, follow the PAH treatment algorithm for Group 1 patients (described earlier).
For patients in Group 3, those who have severe PH should be referred to a PH center.
Consider prescribing inhaled treprostinil in PH with interstitial lung disease.
Treatment for WSPH Group 4
Patients with CTEPH are the only ones for whom pulmonary endarterectomy (PEA), the treatment of choice, might be curative. Balloon angioplasty can be considered for inoperable cases6; these patients should be placed on lifelong anticoagulant therapy.
The nonspecificity of presenting symptoms of pulmonary hypertension— dyspnea, fatigue, chest pain, near syncope, syncope, lowerextremity edema—can lead to a delay in diagnosis.
Symptomatic patients who have inoperable CTEPH or persistent recurrent PH after PEA are medically managed; the agent of choice is riociguat. Patients who have undergone PEA or balloon angioplasty and those receiving pharmacotherapy should be followed long term.
Treatment for WSPH Group 5
Management of these patients focuses on associated conditions.
