Biomarker-based diagnosis of pacemaker and implantable cardioverter defibrillator pocket infections: A prospective, multicentre, case-control evaluation

PLoS One. 2017 Mar 6;12(3):e0172384. doi: 10.1371/journal.pone.0172384. eCollection 2017.

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.

Conclusion: 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.

Clinical trial registration: clinicaltrials.gov identifier: NCT01619267.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers*
  • C-Reactive Protein
  • Calcitonin / blood
  • Case-Control Studies
  • Defibrillators, Implantable / adverse effects*
  • Female
  • Humans
  • Leukocyte Count
  • Male
  • Prospective Studies
  • Prosthesis-Related Infections / diagnosis*
  • Prosthesis-Related Infections / etiology*
  • ROC Curve
  • Reference Values
  • Workflow

Substances

  • Biomarkers
  • Calcitonin
  • C-Reactive Protein

Associated data

  • ClinicalTrials.gov/NCT01619267

Grants and funding

The German Heart Centre received an unearmarked grant of 10,000 EUR by Biotronik GmbH to support research activities in the broad field of cardiac rhythm management and cardiac devices. The funder had no role in selection of the research topic, study design, datacollection and analysis, decision to publish, or preparation of the manuscript. This research grant was used to purchase the required reagent kits for processing the blood samples and analysing the biomarkers.