Unique Predictors of Mortality in Patients With Pulmonary Arterial Hypertension Associated With Systemic Sclerosis in the REVEAL Registry

Abstract

BACKGROUND:Patients with pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-APAH) experience higher mortality rates than patients with idiopathic disease and those with other connective tissue diseases (CTD-APAH). We sought to identify unique predictors of mortality associated with SSc-APAH in the CTD-APAH population.METHODS:The Registry to Evaluate Early and Long-Term PAH Management (REVEAL Registry) is a multicenter, prospective US-based registry of patients with previously and newly diagnosed (enrollment within 90 days of diagnostic right-sided heart catheterization) PAH. Cox regression models evaluated all previously identified candidate predictors of mortality in the overall REVEAL Registry population to identify significant predictors of mortality in the SSc-APAH (n = 500) vs non-SSc-CTD-APAH (n = 304) populations.RESULTS:Three-year survival rates in the previously diagnosed and newly diagnosed SSc-APAH group were 61.4% ± 2.7% and 51.2% ± 4.0%, respectively, compared with 80.9% ± 2.7% and 76.4% ± 4.6%, respectively, in the non-SSc-CTD-APAH group (P < .001). In multivariate analyses, men aged > 60 years, systolic BP (SBP) ≤ 110 mm Hg, 6-min walk distance (6MWD) < 165 m, mean right atrial pressure (mRAP) > 20 mm Hg within 1 year, and pulmonary vascular resistance (PVR) > 32 Wood units remained unique predictors of mortality in the SSc-APAH group; 6MWD ≥ 440 m was protective in the non-SSc-CTD-APAH group, but not the SSc-APAH group.CONCLUSIONS:Patients with SSc-APAH have higher mortality rates than patients with non-SSc-CTD-APAH. Identifying patients with SSc-APAH who are at a particularly high risk of death, including elderly men and patients with low baseline SBP or 6MWD, or markedly elevated mRAP or PVR, will enable physicians to identify patients who may benefit from closer monitoring and more aggressive treatment.TRIAL REGISTRY:ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov

Electrocardiographic detection of pulmonary hypertension in patients with systemic sclerosis using the ventricular gradient

“…This is comparable with other studies reporting 3-year survival rates around 50% for this patient population [27,33].…”

Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial

“…12 By contrast, non-SSc-CTD-PAH patients exhibit similar survival curves to patients with iPAH when receiving PAH-targeted therapy. 13 The attenuated response, particularly in the short-term trials, has led to suggestions that 6MWD testing may not be an appropriate endpoint for patients with SSc-PAH. 14 An increased prevalence of veno-occlusive disease, 15 occult left heart involvement, 16 associated lung disease 17 and musculoskeletal involvement 14 in patients labelled as having SSc-PAH are proposed as potential explanations for the apparent attenuated response.…”

Monitoring and Diagnostic Approaches for Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis

“…2 In the REVEAL registry, in addition to age and male gender, the following were also significant predictors of mortality in patients with SSc-PAH: low baseline systolic blood pressure, poor exercise capacity, increased mean right atrial pressure, and increased PVR. 70 As mentioned earlier, NT-proBNP is highly relevant for screening and diagnosis, and has been shown to be a predictor of mortality in some cohorts. 71 A 10-fold increase in NT-proBNP levels has been associated with a 3-fold increased risk of death in a UK cohort.…”