Risk assessment in pulmonary arterial hypertension: Insights from the GRIPHON study.

BACKGROUND: Approaches to risk assessment in pulmonary arterial hypertension (PAH) include the noninvasive French risk assessment approach (number of low-risk criteria based on the European Society of Cardiology and European Respiratory Society guidelines) and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) 2.0 risk calculator. The prognostic and predictive value of these methods for morbidity/mortality was evaluated in the predominantly prevalent population of GRIPHON, the largest randomized controlled trial in PAH. METHODS: GRIPHON randomized 1,156 patients with PAH to selexipag or placebo. Post-hoc analyses were performed on the primary composite end-point of morbidity/mortality by the number of low-risk criteria (World Health Organization functional class I-II; 6-minute walk distance >440 m; N-terminal pro-brain natriuretic peptide <300 ng/liter) and REVEAL 2.0 risk category. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazard models. RESULTS: Both the number of low-risk criteria and the REVEAL 2.0 risk category were prognostic for morbidity/mortality at baseline and any time-point during the study. Patients with 3 low-risk criteria at baseline had a 94% reduced risk of morbidity/mortality compared to patients with 0 low-risk criteria and were all categorized as low-risk by REVEAL 2.0. The treatment effect of selexipag on morbidity/mortality was consistent irrespective of the number of low-risk criteria or the REVEAL 2.0 risk category at any time-point during the study. Selexipag-treated patients were more likely to increase their number of low-risk criteria from baseline to week 26 than placebo-treated patients (odds ratio 1.69, p = 0.0002); similar results were observed for REVEAL 2.0 risk score. CONCLUSIONS: These results support the association between risk profile and long-term outcome and suggest that selexipag treatment may improve risk profile.

Diagnosis and differential assessment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is diagnosed by various investigations that are essential for making the diagnosis, and by additional tests to clarify the category of pulmonary hypertension (PH). A diagnostic algorithm can guide the evaluation of PH, but like all guidelines the algorithm can be modified according to specific clinical circumstances. Most patients are diagnosed as the result of an evaluation of symptoms, whereas others are diagnosed during screening of asymptomatic populations at risk. Right heart catheterization (RHC) must be performed in patients with suspected PH to establish the diagnosis and document pulmonary hemodynamics. Before initiation of medical therapy, assessment of acute vasoreactivity (during catheterization) is necessary to determine the appropriate therapy for an individual patient. An acute response is generally defined as a decrease in mean pulmonary arterial pressure of at least 10 mm Hg with the mean pulmonary arterial pressure decreasing to 40 mm Hg or below, accompanied by a normal or high cardiac output. After PAH is diagnosed, disease severity should be assessed in order to accurately determine risk:benefit profiles for various therapeutic options. Useful tools to predict outcome include functional class, exercise capacity, pulmonary hemodynamics, acute vasoreactivity, right ventricular function, as well as brain natriuretic peptide, endothelin-1, uric acid, and troponin levels. Repeating these tests serially on treatment is useful for monitoring the response to a given therapy. Close follow-up at a center specializing in management of PH is recommended, with careful periodic reassessment and adjustment of therapy.