title: Midregional Proadrenomedullin Improves Risk Stratification beyond Surgical Risk Scores in Patients Undergoing Transcatheter Aortic Valve Replacement.
abstract: BACKGROUND
  Conventional surgical risk scores lack accuracy in risk stratification of patients undergoing transcatheter aortic valve replacement (TAVR). Elevated levels of midregional proadrenomedullin (MR-proADM) levels are associated with adverse outcome not only in patients with manifest chronic disease states, but also in the general population.
  
  
  OBJECTIVE
  We investigated the predictive value of MR-proADM for mortality in an unselected contemporary TAVR population.
  
  
  METHODS
  We prospectively included 153 patients suffering from severe aortic stenosis who underwent TAVR from September 2013 to August 2014. This population was compared to an external validation cohort of 205 patients with severe aortic stenosis undergoing TAVR. The primary endpoint was all cause mortality.
  
  
  RESULTS
  During a median follow-up of 258 days, 17 out of 153 patients who underwent TAVR died (11%). Patients with MR-proADM levels above the 75th percentile (≥ 1.3 nmol/l) had higher mortality (31% vs. 4%, HR 8.9, 95% CI 3.0-26.0, P < 0.01), whereas patients with EuroSCORE II scores above the 75th percentile (> 6.8) only showed a trend towards higher mortality (18% vs. 9%, HR 2.1, 95% CI 0.8-5.6, P = 0.13). The Harrell's C-statistic was 0.58 (95% CI 0.45-0.82) for the EuroSCORE II, and consideration of baseline MR-proADM levels significantly improved discrimination (AUC = 0.84, 95% CI 0.71-0.92, P = 0.01). In bivariate analysis adjusted for EuroSCORE II, MR-proADM levels ≥1.3 nmol/l persisted as an independent predictor of mortality (HR 9.9, 95% CI (3.1-31.3), P <0.01) and improved the model's net reclassification index (0.89, 95% CI (0.28-1.59). These results were confirmed in the independent validation cohort.
  
  
  CONCLUSIONS
  Our study identified MR-proADM as a novel predictor of mortality in patients undergoing TAVR. In the future, MR-proADM should be added to the commonly used EuroSCORE II for better risk stratification of patients suffering from severe aortic stenosis.
authors.affiliation: Department of Cardiology, University Heart Center Zürich, Zürich, Switzerland.
authors.forename: Adam
authors.initials: A
authors.lastname: Csordas
authors.affiliation: Department of Cardiology, University Heart Center Zürich, Zürich, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Nietlispach
authors.affiliation: Department of Internal Medicine and Cardiology, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
authors.affiliation: Department of Internal Medicine and Cardiology, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Huber
authors.affiliation: Department of Internal Medicine and Cardiology, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
authors.affiliation: Department of Cardiovascular Surgery, University Heart Center Zürich, Zürich, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Maisano
authors.affiliation: Department of Cardiovascular Surgery, University Heart Center Zürich, Zürich, Switzerland.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Taramasso
authors.affiliation: Department of Internal Medicine and Cardiology, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Igal
authors.initials: I
authors.lastname: Moarof
authors.affiliation: Department of Cardiology, University Heart Center Zürich, Zürich, Switzerland.
authors.forename: Slayman
authors.initials: S
authors.lastname: Obeid
authors.affiliation: Department of Cardiology, University Heart Center Zürich, Zürich, Switzerland.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Stähli
authors.affiliation: Department of Cardiology, University Heart Center Zürich, Zürich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Cahenzly
authors.affiliation: Department of Cardiology, University Heart Center Zürich, Zürich, Switzerland.
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Binder
authors.affiliation: Department of Cardiology, Kerckhoff Heart Center, Bad Nauheim, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Liebetrau
authors.affiliation: Department of Cardiology, Kerckhoff Heart Center, Bad Nauheim, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Möllmann
authors.affiliation: Department of Cardiology, Kerckhoff Heart Center, Bad Nauheim, Germany.
authors.forename: Won-Keun
authors.initials: WK
authors.lastname: Kim
authors.affiliation: Department of Cardiology, Kerckhoff Heart Center, Bad Nauheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hamm
authors.affiliation: Department of Cardiology, University Heart Center Zürich, Zürich, Switzerland.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D001024:Aortic Valve Stenosis / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D011498:Protein Precursors / Q000378:metabolism*; D018570:Risk Assessment; D012720:Severity of Illness Index; D065467:Transcatheter Aortic Valve Replacement / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D011498:Protein Precursors; C088633:proadrenomedullin; D053607:Adrenomedullin