title: Clinical and serum-based markers are associated with death within 1 year of de novo implant in primary prevention ICD recipients.
abstract: BACKGROUND
  Implantable cardioverter-defibrillator (ICD) implantation is contraindicated in those with <1-year life expectancy.
  
  
  OBJECTIVE
  The aim of this study was to develop a risk prediction score for 1-year mortality in patients with primary prevention ICDs and to determine the incremental improvement in discrimination when serum-based biomarkers are added to traditional clinical variables.
  
  
  METHODS
  We analyzed data from the Prospective Observational Study of Implantable Cardioverter-Defibrillators, a large prospective observational study of patients undergoing primary prevention ICD implantation who were extensively phenotyped for clinical and serum-based biomarkers. We identified variables predicting 1-year mortality and synthesized them into a comprehensive risk scoring construct using backward selection.
  
  
  RESULTS
  Of 1189 patients deemed by their treating physicians as having a reasonable 1-year life expectancy, 62 (5.2%) patients died within 1 year of ICD implantation. The risk score, composed of 6 clinical factors (age ≥75 years, New York Heart Association class III/IV, atrial fibrillation, estimated glomerular filtration rate <30 mL/min/1.73 m(2), diabetes, and use of diuretics), had good discrimination (area under the curve 0.77) for 1-year mortality. Addition of 3 biomarkers (tumor necrosis factor α receptor II, pro-brain natriuretic peptide, and cardiac troponin T) further improved model discrimination to 0.82. Patients with 0-1, 2-3, 4-6, or 7-9 risk factors had 1-year mortality rates of 0.8%, 2.7%, 16.1%, and 46.2%, respectively.
  
  
  CONCLUSIONS
  Individuals with more comorbidities and elevation of specific serum biomarkers were at increased risk of all-cause mortality despite being deemed as having a reasonable 1-year life expectancy. A simple risk score composed of readily available clinical data and serum biomarkers may better identify patients at high risk of early mortality and improve patient selection and counseling for primary prevention ICD therapy.
authors.affiliation: Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Departments of Epidemiology and Medicine, and Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University Bloomberg School of Public Health.
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Elena
authors.initials: E
authors.lastname: Blasco-Colmenares
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Darshan
authors.initials: D
authors.lastname: Dalal
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Butcher
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Norgard
authors.affiliation: AMC Heart Centre, Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Fleur V Y
authors.initials: FV
authors.lastname: Tjong
authors.affiliation: Washington Hospital Center, Washington, DC.
authors.forename: Zayd
authors.initials: Z
authors.lastname: Eldadah
authors.affiliation: University of Maryland, Baltimore, Maryland.
authors.forename: Timm
authors.initials: T
authors.lastname: Dickfeld
authors.affiliation: Medical College of Virginia, Richmond, Virginia.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Ellenbogen
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Marine
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Tomaselli
authors.affiliation: Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: alcheng@jhmi.edu.
authors.forename: Alan
authors.initials: A
authors.lastname: Cheng
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D052279:Creatine Kinase, MB Form / Q000097:blood; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000517:prevention & control*; D017147:Defibrillators, Implantable; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000401:mortality / Q000628:therapy; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009426:Netherlands / Q000453:epidemiology; D010446:Peptide Fragments / Q000097:blood; D011322:Primary Prevention / Q000379:methods*; D011379:Prognosis; D011446:Prospective Studies; D011498:Protein Precursors; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D020107:Troponin T / Q000097:blood; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011498:Protein Precursors; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D052279:Creatine Kinase, MB Form
keywords: Early mortality; ICD shock; Implantable cardioverter-defibrillator; Primary prevention; Sudden cardiac death