Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: Identifying systemic sclerosis as a unique phenotype

Background: REVEAL (the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) is the largest US cohort of patients with pulmonary arterial hypertension (PAH) confirmed by right-sided heart catheterization (RHC), providing a more comprehensive subgroup characterization than previously possible. We used REVEAL to analyze the clinical features of patients with connective tissue disease-associated PAH (CTD-APAH). Methods: All newly and previously diagnosed patients with World Health Organization (WHO) group 1 PAH meeting RHC criteria at 54 US centers were consecutively enrolled. Cross-sectional and 1-year mortality and hospitalization analyses from time of enrollment compared CTD-APAH to idiopathic disease and systemic sclerosis (SSc) to systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA). Results: Compared with patients with idiopathic disease (n = 1,251), patients with CTD-APAH (n = 641) had better hemodynamics and favorable right ventricular echocardiographic findings but a higher prevalence of pericardial effusions, lower 6-min walk distance (300.5 ± 118.0 vs 329.4 ± 134.7 m, P = .01), higher B-type natriuretic peptide (BNP) levels (432.8 ± 789.1 vs 245.6 ± 427.2 pg/mL, P<.0001), and lower diffusing capacity of carbon monoxide (DLCO) (44.9% ± 18.0% vs 63.6% ± 22.1% predicted, P<.0001). One-year survival and freedom from hospitalization were lower in the CTD-APAH group (86% vs 93%, P<.0001; 67% vs 73%, P = .03). Compared with patients with SSc-APAH (n = 399), those with other CTDs (SLE, n = 110; MCTD, n = 52; RA, n = 28) had similar hemodynamics; however, patients with SSc-APAH had the highest BNP levels (552.2 ± 977.8 pg/mL), lowest DLCO (41.2% ± 16.3% predicted), and poorest 1-year survival (82% vs 94% in SLE-APAH, 88% in MCTD-APAH, and 96% in RA-APAH). Conclusions: Patients with SSc-APAH demonstrate a unique phenotype with the highest BNP levels, lowest DLCO, and poorest survival of all CTD-APAH subgroups. Trial registry: ClinicalTrials.gov; No.: NCT00370214; URL: clinicaltrials.gov.