title: Biomarker-based diagnosis of pacemaker and implantable cardioverter defibrillator pocket infections: A prospective, multicentre, case-control evaluation.
abstract: BACKGROUND
  The use of cardiac implantable electronic devices (CIED) has risen steadily, yet the rate of cardiac device infections (CDI) has disproportionately increased. Amongst all cardiac device infections, the pocket infection is the most challenging diagnosis. Therefore, we aimed to improve diagnosis of such pocket infection by identifying relevant biomarkers.
  
  
  METHODS
  We enrolled 25 consecutive patients with invasively and microbiologically confirmed pocket infection. None of the patients had any confounding conditions. Pre-operative levels of 14 biomarkers were compared in infected and control (n = 50) patients. Our selected biomarkers included white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), lipopolysaccharide binding protein, high-sensitivity C-reactive protein (HS-CRP), polymorphonuclear-elastase, presepsin, various interleukins, tumor necrosis factor α (TNF-α), and granulocyte macrophage colony-stimulating factor (GM-CSF).
  
  
  RESULTS
  Of the 25 patients with isolated pocket infection (70±13years, 76% male, 40% ICDs), none presented with leukocytosis. In contrast, they had higher serum levels of HS-CRP (p = 0.019) and PCT (p = 0.010) than control patients. Median PCT-level was 0.06 ng/mL (IQR 0.03-0.07 ng/mL) in the study group versus 0.03 ng/mL (IQR 0.02-0.04 ng/mL) in controls. An optimized PCT cut-off value of 0.05 ng/mL suggests pocket infection with a sensitivity of 60% and specificity of 82%. In addition TNF-α- and GM-CSF-levels were lower in the study group. Other biomarkers did not differ between groups.
  
  
  CONCLUSIONS
  Diagnosis of isolated pocket infections requires clinical awareness, physical examination, evaluation of blood cultures and echocardiography assessment. Nevertheless, measurement of PCT- and HS-CRP-levels can aid diagnosis. However, no conclusion can be drawn from normal WBC-values.
  
  
  BACKGROUND
  clinicaltrials.gov identifier: NCT01619267.
authors.affiliation: Klinik für Herz- und Kreislauferkrankungen, Abteilung für Elektrophysiologie, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
authors.forename: Carsten
authors.identifier: http://orcid.org/0000-0002-1693-6474
authors.initials: C
authors.lastname: Lennerz
authors.affiliation: Department of Internal Medicine, Division of Cardiology, University Hospital Dubrava, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Vrazic
authors.affiliation: Institut für Medizinische Statistik und Epidemiologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Haller
authors.affiliation: Institut für Laboratoriumsmedizin, Deutsches Herzzentrum München, Faculty of Medicine, Technische Universität München, Munich, Germany.
authors.forename: Siegmund
authors.initials: S
authors.lastname: Braun
authors.affiliation: Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Petzold
authors.affiliation: Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Ott
authors.affiliation: Klinik für Herz- und Kreislauferkrankungen, Abteilung für Elektrophysiologie, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Lennerz
authors.affiliation: Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Michel
authors.affiliation: Klinik für Herz- und Kreislauferkrankungen, Abteilung für Elektrophysiologie, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Blažek
authors.affiliation: Klinik für Herz- und Kreislauferkrankungen, Abteilung für Elektrophysiologie, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
authors.forename: Isabel
authors.initials: I
authors.lastname: Deisenhofer
authors.affiliation: Cardiovascular Research Institute and Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Whittaker
authors.affiliation: Klinik für Herz- und Kreislauferkrankungen, Abteilung für Elektrophysiologie, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Kolb
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002097:C-Reactive Protein; D002116:Calcitonin / Q000097:blood; D016022:Case-Control Studies; D017147:Defibrillators, Implantable / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D011446:Prospective Studies; D016459:Prosthesis-Related Infections / Q000175:diagnosis* / Q000209:etiology*; D012372:ROC Curve; D012016:Reference Values; D057188:Workflow
chemical_list: D015415:Biomarkers; D002116:Calcitonin; D002097:C-Reactive Protein