An Evidence-Based Screening Algorithm for Pulmonary Arterial Hypertension in Systemic Sclerosis: The DETECT Study

Abstract

Background/Purpose: Pulmonary arterial hypertension (PAH) is a leading cause of mortality and late-stage morbidity in systemic sclerosis (SSc). Current PAH screening recommendations are consensus-based and their clinical application results in high false positive rates. The rate of missed diagnoses has never been determined. The DETECT study aimed to develop an evidence-based screening algorithm for PAH in SSc patients that would limit the number of missed PAH diagnoses. Methods: In this prospective, multicenter, cross-sectional observational cohort study [NCT00706082], adult patients with SSc for >3 years, a diffusing capacity of the lung for carbon monoxide (DLCO) <60% of predicted, and no previous diagnosis of pulmonary hypertension underwent multiple non-invasive screening tests followed by diagnostic right heart catheterization (RHC). Univariable and multivariable analyses selected the best discriminatory variables for identifying PAH, which were assessed for clinical plausibility and feasibility and incorporated into a two-step internally validated screening algorithm. Results: Of 466 SSc patients, 19% (n=87) had RHC-confirmed PAH and 69% (n=321) had normal pulmonary arterial pressure (PAP). PAH was mild (mean PAP 32.5 [30.7-34.3] mm Hg; 64.4% WHO functional class I or II). Six simple screening tests (forced vital capacity [% predicted]/DLCO [% predicted]; current/past telangiectasias; anti-centromere antibody; N-terminal pro-brain natriuretic peptide; uric acid; right axis deviation on electrocardiography) were used in step 1 of the algorithm to derive a risk prediction score with pre-defined high sensitivity (to minimize the rate of missed PAH diagnoses) and to inform a decision to refer to echocardiography. Right atrial area and tricuspid regurgitation jet velocity were added in step 2 (with pre-defined low specificity) to determine referral to RHC. The DETECT algorithm, with step 1 sensitivity 97% and step 2 specificity 35%, resulted in a rate of missed PAH diagnoses of 4% requiring RHC in 62% of patients. When the current ERS/ESC screening recommendations were applied, the missed diagnoses and the RHC referral rates were 29% and 40%, respectively. Conclusion: The two-step algorithm is a sensitive non-invasive screening tool for detection of PAH in SSc which addresses resource utilization of RHC, identifies less advanced disease and, most importantly, minimizes missed diagnoses. This is an evidence-based approach to revise standards of care in SSc patients.