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

Abstract

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.

Figure 1.

Enrollment algorithm, designed to ensure that all of the patients included in our analysis met the strict criteria of World Health Organization group 1 PAH. CTD-APAH = connective tissue disease-associated pulmonary arterial hypertension; HRCT = high-resolution CT; ILD = interstitial lung disease; IPAH = idiopathic pulmonary arterial hypertension; PAH = pulmonary arterial hypertension; PCWP = pulmonary capillary wedge pressure; REVEAL = Registry to Evaluate Early and Long-term PAH Disease Management; TLC = total lung capacity determined by pulmonary function testing.

Figure 2.

Kaplan-Meier curves of 12-month survival and freedom from all-cause hospitalization in IPAH vs CTD-APAH cohorts. A, Patients with CTD-APAH had a worse survival (86% vs 93%, P < .0001). B, Lower freedom from hospitalization rate (67% vs 73%, P = .03). See Figure 1 legend for expansion of abbreviations.

Figure 3.

Kaplan-Meier curves of 12-month survival in SSc-APAH, SLE-APAH, MCTD-APAH, and RA-APAH. Patients with SSc-APAH had a worse 12-month survival compared with A and C. A, Patients with SLE-APAH (82% vs 94%, P = .0009). C, Patients with RA-APAH (82% vs 96%, P = .01). B, However, patients with SSc-APAH and MCTD-APAH displayed similar 12-month survival outcomes (82% vs 88%, P = .53). MCTD-APAH = mixed connective tissue disease-associated PAH; RA-APAH = rheumatoid arthritis-associated PAH; SLE-APAH = systemic lupus erythematosus-associated PAH; SSc-APAH = systemic sclerosis-associated PAH. See Figure 1 legend for expansion of other abbreviations.