Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk stratification equation

Abstract

The aim of the present study was to determine contemporary survival in pulmonary arterial hypertension (PAH), and to investigate whether or not the National Institutes of Health (NIH) equation remains an accurate predictor of survival. In 576 patients with PAH referred during 1991-2007, observed survival was described using the Kaplan-Meier method. In patients with idiopathic, familial and anorexigen-associated PAH (n = 247), observed versus NIH equation predicted survival was compared. A new survival prediction equation was developed using exponential regression analysis. The observed 1-, 3- and 5-yr survival in the total cohort were 86, 69 and 61%, respectively. In patients with idiopathic, familial and anorexigen-associated PAH, the observed 1-, 3- and 5-yr survival (92, 75 and 66%, respectively) were significantly higher than the predicted survival (65, 43 and 32%, respectively). The new equation (P(t) = e(-A(x,y,z)t), where P(t) is probability of survival, t the time interval in years, A(x,y,z) = e((-1.270-0.0148x+0.0402y-0.361z)), x the mean pulmonary artery pressure, y the mean right atrial pressure and z the cardiac index) performed well when applied to published contemporary studies of survival in PAH. Contemporary survival in the PAH cohort was better than that predicted by the NIH registry equation. The NIH equation underestimated survival in idiopathic, familial and anorexigen-associated PAH. Once prospectively validated, the new equation may be used to determine prognosis.

FIGURE 1.

Study flow diagram. PAH: pulmonary arterial hypertension;${\overline{P}}_{\text{RA}}$: mean right atrial pressure;${\overline{P}}_{\text{pa}}$: mean pulmonary arterial pressure; CI: cardiac index; NIH: National Institutes of Health.

FIGURE 2.

Survival in idiopathic, familial and anorexigen-associated pulmonary arterial hypertension (PAH) subgroup (––––; n=282) versus PAH associated with connective tissue disease, congenital heart disease, portal hypertension and HIV (APAH; ------; n = 294) (p=0.03 (log-rank test)).

FIGURE 3.

Observed (-------; 95% confidence interval: ·····) versus predicted survival using the Pulmonary Hypertension Connection (–––––) and National Institutes of Health (– – –) equations in patients with idiopathic, familial and anorexigen-associated pulmonary arterial hypertension.

FIGURE 4.

Observed (––––) versus predicted (------) survival using the new equation with data from published pulmonary arterial hypertension (PAH) cohorts: a) survival with first-line bosentan in patients with primary pulmonary hypertension [8]; and b, c) survival in patients with class III idiopathic PAH treated with first-line oral bosentan (b) compared with a historical cohort of patients started on intravenous epoprostenol (c) [20].