title: The role of cystatin C as a biomarker for prognosis in pulmonary arterial hypertension due to congenital heart disease.
abstract: BACKGROUND
  Adults with pulmonary arterial hypertension due to congenital heart disease (PAH-CHD) have a poor prognosis. Identifying patients with a high risk for clinical events and death is important because their prognosis can be improved by intensifying their treatment. Cystatin C, a novel cardiac biomarker, correlates with right ventricular dimensions in patients with idiopathic PAH, giving it potential to determine prognosis in PAH-CHD patients. We investigated the predictive value of cystatin C for long-term mortality and clinical events.
  
  
  METHODS
  Fifty-nine PAH-CHD patients (mean age 42 SD 13 years, 42% male) were included in this prospective observational study, with cystatin C measurements between 2005 and 2015 on the outpatient clinic. Patients were evaluated with a standardized evaluation protocol including laboratory, functional and echocardiographic variables. Clinical events comprised worsening functional classification, worsening heart failure, symptomatic hyperviscosity, haemoptysis and arrhythmia. We used Cox regression to determine predictors for mortality and clinical events.
  
  
  RESULTS
  Mean follow-up was 4.4years, during which 12 (20%) patients died. Cystatin C (HR 1.3, p<0.001), creatinine (HR 1.2, p<0.001), NT-pro-BNP (HR 2.0, p=0.012), hs-troponin T (HR 1.9, p=0.005), 6-MWD (HR 0.8, p=0.044) and TAPSE (HR 0.8, p<0.001) predicted mortality. Similar results were found for the prediction of clinical events. When adjusted for NT-pro-BNP or glomerular filtration rate in multivariate analysis, cystatin C remained predictive for mortality.
  
  
  CONCLUSIONS
  Cystatin C, a novel cardiac biomarker, predicts long-term mortality and clinical events in patients with PAH-CHD. Consequently, cystatin C may attribute to clinical decision making regarding treatment intensity.
authors.affiliation: Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands; ICIN - Netherlands Heart Institute, Utrecht, The Netherlands.
authors.forename: Ilja M
authors.initials: IM
authors.lastname: Blok
authors.affiliation: Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands; ICIN - Netherlands Heart Institute, Utrecht, The Netherlands.
authors.forename: Annelieke C M J
authors.initials: AC
authors.lastname: van Riel
authors.affiliation: Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Schuuring
authors.affiliation: Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Rianne H A C M
authors.initials: RH
authors.lastname: de Bruin-Bon
authors.affiliation: Department of Cardiology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Arie P J
authors.initials: AP
authors.lastname: van Dijk
authors.affiliation: Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Elke S
authors.initials: ES
authors.lastname: Hoendermis
authors.affiliation: Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.affiliation: Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands; ICIN - Netherlands Heart Institute, Utrecht, The Netherlands.
authors.forename: Barbara J M
authors.initials: BJ
authors.lastname: Mulder
authors.affiliation: Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: b.j.bouma@amc.nl.
authors.forename: Berto J
authors.initials: BJ
authors.lastname: Bouma
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D055316:Cystatin C / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006330:Heart Defects, Congenital / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D055316:Cystatin C
keywords: Biomarkers; Congenital heart disease; Cystatin C; Mortality; Pulmonary arterial hypertension