title: Protein biomarkers identify patients unlikely to benefit from primary prevention implantable cardioverter defibrillators: findings from the Prospective Observational Study of Implantable Cardioverter Defibrillators (PROSE-ICD).
abstract: BACKGROUND
  Primary prevention implantable cardioverter defibrillators (ICDs) reduce all-cause mortality, but the benefits are heterogeneous. Current risk stratification based on left ventricular ejection fraction has limited discrimination power. We hypothesize that biomarkers for inflammation, neurohumoral activation, and cardiac injury can predict appropriate shocks and all-cause mortality in patients with primary prevention ICDs.
  
  
  RESULTS
  The Prospective Observational Study of Implantable Cardioverter Defibrillators (PROSe-ICD) enrolled 1189 patients with systolic heart failure who underwent ICD implantation for primary prevention of sudden cardiac death. The primary end point was an ICD shock for adjudicated ventricular tachyarrhythmia. The secondary end point was all-cause mortality. After a median follow-up of 4.0 years, 137 subjects experienced an appropriate ICD shock and 343 participants died (incidence rates of 3.2 and 5.8 per 100 person-years, respectively). In multivariable-adjusted models, higher interleukin-6 levels increased the risk of appropriate ICD shocks. In contrast, C-reactive protein, interleukin-6, tumor necrosis factor-α receptor II, pro-brain natriuretic peptide (pro-BNP), and cardiac troponin T showed significant linear trends for increased risk of all-cause mortality across quartiles. A score combining these 5 biomarkers identified patients who were much more likely to die than to receive an appropriate shock from the ICD.
  
  
  CONCLUSIONS
  An increase in serum biomarkers of inflammation, neurohumoral activation, and myocardial injury increased the risk for death but poorly predicted the likelihood of an ICD shock. These findings highlight the potential importance of serum-based biomarkers in identifying patients who are unlikely to benefit from primary prevention ICDs.
  
  
  BACKGROUND
  clinicaltrials.gov; Unique Identifier: NCT00733590.
authors.affiliation: From the Department of Medicine (A.C., E.B.-C., D.D., B.B., S.N., D.D.S., J.E.M., G.F.T.) and the Welch Center for Prevention, Epidemiology and Clinical Research (Y.Z., E.G.), Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, DC (Z.E.); Medical College of Virginia, Richmond (K.A.E.); and University of Maryland, Baltimore (T.D.).
authors.forename: Alan
authors.initials: A
authors.lastname: Cheng
authors.affiliation: From the Department of Medicine (A.C., E.B.-C., D.D., B.B., S.N., D.D.S., J.E.M., G.F.T.) and the Welch Center for Prevention, Epidemiology and Clinical Research (Y.Z., E.G.), Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, DC (Z.E.); Medical College of Virginia, Richmond (K.A.E.); and University of Maryland, Baltimore (T.D.).
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Department of Medicine (A.C., E.B.-C., D.D., B.B., S.N., D.D.S., J.E.M., G.F.T.) and the Welch Center for Prevention, Epidemiology and Clinical Research (Y.Z., E.G.), Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, DC (Z.E.); Medical College of Virginia, Richmond (K.A.E.); and University of Maryland, Baltimore (T.D.).
authors.forename: Elena
authors.initials: E
authors.lastname: Blasco-Colmenares
authors.affiliation: From the Department of Medicine (A.C., E.B.-C., D.D., B.B., S.N., D.D.S., J.E.M., G.F.T.) and the Welch Center for Prevention, Epidemiology and Clinical Research (Y.Z., E.G.), Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, DC (Z.E.); Medical College of Virginia, Richmond (K.A.E.); and University of Maryland, Baltimore (T.D.).
authors.forename: Darshan
authors.initials: D
authors.lastname: Dalal
authors.affiliation: From the Department of Medicine (A.C., E.B.-C., D.D., B.B., S.N., D.D.S., J.E.M., G.F.T.) and the Welch Center for Prevention, Epidemiology and Clinical Research (Y.Z., E.G.), Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, DC (Z.E.); Medical College of Virginia, Richmond (K.A.E.); and University of Maryland, Baltimore (T.D.).
authors.forename: Barbara
authors.initials: B
authors.lastname: Butcher
authors.affiliation: From the Department of Medicine (A.C., E.B.-C., D.D., B.B., S.N., D.D.S., J.E.M., G.F.T.) and the Welch Center for Prevention, Epidemiology and Clinical Research (Y.Z., E.G.), Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, DC (Z.E.); Medical College of Virginia, Richmond (K.A.E.); and University of Maryland, Baltimore (T.D.).
authors.forename: Sanaz
authors.initials: S
authors.lastname: Norgard
authors.affiliation: From the Department of Medicine (A.C., E.B.-C., D.D., B.B., S.N., D.D.S., J.E.M., G.F.T.) and the Welch Center for Prevention, Epidemiology and Clinical Research (Y.Z., E.G.), Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, DC (Z.E.); Medical College of Virginia, Richmond (K.A.E.); and University of Maryland, Baltimore (T.D.).
authors.forename: Zayd
authors.initials: Z
authors.lastname: Eldadah
authors.affiliation: From the Department of Medicine (A.C., E.B.-C., D.D., B.B., S.N., D.D.S., J.E.M., G.F.T.) and the Welch Center for Prevention, Epidemiology and Clinical Research (Y.Z., E.G.), Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, DC (Z.E.); Medical College of Virginia, Richmond (K.A.E.); and University of Maryland, Baltimore (T.D.).
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Ellenbogen
authors.affiliation: From the Department of Medicine (A.C., E.B.-C., D.D., B.B., S.N., D.D.S., J.E.M., G.F.T.) and the Welch Center for Prevention, Epidemiology and Clinical Research (Y.Z., E.G.), Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, DC (Z.E.); Medical College of Virginia, Richmond (K.A.E.); and University of Maryland, Baltimore (T.D.).
authors.forename: Timm
authors.initials: T
authors.lastname: Dickfeld
authors.affiliation: From the Department of Medicine (A.C., E.B.-C., D.D., B.B., S.N., D.D.S., J.E.M., G.F.T.) and the Welch Center for Prevention, Epidemiology and Clinical Research (Y.Z., E.G.), Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, DC (Z.E.); Medical College of Virginia, Richmond (K.A.E.); and University of Maryland, Baltimore (T.D.).
authors.forename: David D
authors.initials: DD
authors.lastname: Spragg
authors.affiliation: From the Department of Medicine (A.C., E.B.-C., D.D., B.B., S.N., D.D.S., J.E.M., G.F.T.) and the Welch Center for Prevention, Epidemiology and Clinical Research (Y.Z., E.G.), Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, DC (Z.E.); Medical College of Virginia, Richmond (K.A.E.); and University of Maryland, Baltimore (T.D.).
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Marine
authors.affiliation: From the Department of Medicine (A.C., E.B.-C., D.D., B.B., S.N., D.D.S., J.E.M., G.F.T.) and the Welch Center for Prevention, Epidemiology and Clinical Research (Y.Z., E.G.), Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, DC (Z.E.); Medical College of Virginia, Richmond (K.A.E.); and University of Maryland, Baltimore (T.D.).
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
authors.affiliation: From the Department of Medicine (A.C., E.B.-C., D.D., B.B., S.N., D.D.S., J.E.M., G.F.T.) and the Welch Center for Prevention, Epidemiology and Clinical Research (Y.Z., E.G.), Johns Hopkins Medical Institutions, Baltimore, MD; Washington Hospital Center, DC (Z.E.); Medical College of Virginia, Richmond (K.A.E.); and University of Maryland, Baltimore (T.D.). gtomaseli@jhmi.edu.
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Tomaselli
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D016009:Chi-Square Distribution; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control*; D017147:Defibrillators, Implantable; D004554:Electric Countershock / Q000295:instrumentation*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009206:Myocardium / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000097:blood; D018579:Patient Selection; D011237:Predictive Value of Tests; D011322:Primary Prevention / Q000295:instrumentation* / Q000379:methods; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D018836:Inflammation Mediators; D011498:Protein Precursors; D020097:Natriuretic Peptide, Brain
keywords: arrhythmias, cardiac; death, sudden, cardiac; defibrillators, implantable; inflammation; prevention & control