Update of screening and diagnostic modalities for connective tissue disease-associated pulmonary arterial hypertension

Objective: Pulmonary arterial hypertension (PAH) has high morbidity and mortality in connective tissue diseases (CTDs), especially systemic sclerosis (SSc). In this systematic review, we provide an update on screening measures for early detection of PAH in CTD. Methods: Manuscripts published between July 2012 and October 2017, which incorporated screening measures to identify patients with PAH by right heart catheterization, were identified. Risk of bias was assessed using the QUADAS-2 tool. Results: The systematic review resulted in 1514 unique citations and 22 manuscripts were included for final review; the majority of manuscripts had a lower risk of bias based on the QUADAS-2 tool. There were 16 SSc cohort studies and 6 case-control studies (SSc 4, SLE 2). Four SSc cohort studies evaluated transthoracic echocardiography (TTE) only. Eight SSc cohort studies evaluated composite measures including ASIG, DETECT, and a combination of tricuspid regurgitation velocity (TRV) and PFT variables. DETECT and ASIG had greater sensitivity and negative predictive value (NPV) compared to the 2009 ESC/ERS guidelines in different cohorts. The addition of PFT variables, such as DLCO or FVC/ DLCO ratio, to TRV, resulted in greater sensitivity and NPV compared to TRV alone. Conclusion: Current screening for PAH in CTDs is centered on SSc. Data continues to support the use of TTE and provides additional evidence for use of composite measures.