title: Screening and diagnostic modalities for connective tissue disease-associated pulmonary arterial hypertension: a systematic review.
abstract: OBJECTIVE
  Pulmonary arterial hypertension (PAH) is a frequent complication in connective tissue diseases (CTD), especially in systemic sclerosis (SSc), and is associated with a high degree of morbidity and mortality. We undertook a systematic review for the screening tests for CTD-PAH.
  
  
  METHODS
  A systematic literature search of PAH in CTD was performed in available databases through June 2012. Our evaluation of diagnostic tests was focused on patients with PAH confirmed by right heart catheterization (RHC).
  
  
  RESULTS
  The search resulted in 2805 titles and 838 abstracts. Our final inclusion encompassed 22 articles-six of which were case-control studies and 16 were cohort studies. Twelve studies assessed the tricuspid regurgitation velocity (VTR) or equivalent right ventricular systolic pressure (RVSP) using transthoracic echocardiogram (TTE) as a threshold for RHC in patients suspected as having PAH. The screening threshold for RHC was VTR from >2.73 to >3.16 m/s without symptoms or 2.5-3.0m/s with symptoms and resulted in 20-67% of patients having RHC-proven PAH. Three studies looked at pulmonary function tests and found that a low lung diffusing capacity for carbon monoxide (DLCO) (45-70% of predicted) is associated with a 5.6-7.4% development of PAH, and a decline in DLCO% is associated with an increase in the specificity (for DLCO ≤ 60%, spec = 45%; and for DLCO ≤ 50%, spec = 90%) for PAH. Five studies assessed N-terminal prohormone of brain natriuretic peptide (NT-ProBNP), where a cutoff >239 pg/ml had a sensitivity of 90-100%.
  
  
  CONCLUSIONS
  Our systematic review revealed that most evidence exists for TTE, pulmonary function tests, and NT-ProBNP for screening and diagnosis of SSc-PAH; however, more robust studies are needed.
authors.affiliation: Department of Rheumatology, University of Michigan, Ann Arbor, MI.
authors.forename: Heather
authors.initials: H
authors.lastname: Gladue
authors.affiliation: Department of Rheumatology, University of Michigan, Ann Arbor, MI.
authors.forename: Nezam
authors.initials: N
authors.lastname: Altorok
authors.affiliation: Taubman Health Sciences, University of Michigan Library, Ann Arbor, MI.
authors.forename: Whitney
authors.initials: W
authors.lastname: Townsend
authors.affiliation: Department of Cardiology, University of Michigan, Ann Arbor, MI.
authors.forename: Vallerie
authors.initials: V
authors.lastname: McLaughlin
authors.affiliation: Department of Rheumatology, University of Michigan, Ann Arbor, MI. Electronic address: khannad@med.umich.edu.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
mesh_terms: D003240:Connective Tissue Diseases / Q000097:blood / Q000150:complications*; D004452:Echocardiography; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D012129:Respiratory Function Tests; D012680:Sensitivity and Specificity
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain