**12. Natural history and prognosis**

PAH has no cure. However, the rate of progression is highly variable and depends upon the type and severity of the PAH. Untreated PAH leads to right-sided heart failure and death.

Prior to the 1990s, therapeutic options were limited. The emergence of prostacyclin analogues, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and other novel drug therapies has greatly improved the outlook for patients with PAH.

For untreated IPAH, the estimated 3-year survival rate is approximately 41%. In one study of long-term continuous intravenous prostacyclin therapy, 3-year survival increased to approx‐ imately 63%. [54] With newer therapies, perhaps in combination, these figures are expected to improve further.

Less symptomatic patients in WHO class II/III, with normal right atrial and ventriclar size and pressure and can walk more than 400 meters on 6 minute walk distance (MWD) are considered lower risk group of patients for morbidity and mortality. While symptomatic patients in WHO class IV with signs of right heart failure, enlarged right atria and ventricle with right ventricular dysfunction and cannot walk more than 300 meters on 6 MWD testing are considered high risk group of pattients with pulmonary hypertension. [25], [55]

The one-year survival of patients with newly diagnosed group 1 PAH can be predicted using a risk score derived from the Registry to Evaluate Early and Long-term PAH Disease Man‐ agement (i.e. the REVEAL registry). This risk score was validated by a prospective cohort study of 504 patients with a mean 6-minute walk testing (6 MWD) of 308 m and 61.5 percent classified as WHO functional class III, which found that a risk score of 1 to 7, 8, 9, 10 to 11, and ≥ 12 correlated with one-year survival of 95, 92, 89, 72, and 66 percent, respectively. [56]

Severity of PAH – Patients with severe PAH or right heart failure (i.e., cor pulmonale) die sooner without treatment (usually within one year) than patients with mild PAH or no right heart failure. As an example, patients with IPAH and a mean right atrial pressure ≥ 20 mmHg have a median survival of approximately one month.[10]

In conclusion, age, PAH etiology, World Health Organization functional class, pericardial effusion, 6MWT distance, the need for oxygen during the 6MWT, and brain natriuretic peptide are predictors of prognosis in patients PAH receiving specific therapy and might help identify a group that could benefit from aggressive upfront therapy. [57]

Since survival in patients who fall into NYHA classes III or IV is poor (9-18 months), patients with severe symptoms and evidence of impaired cardiac function, which is refractory to conventional therapy or epoprostenol infusion should be considered for lung transplantation.
