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Inflammatory Mediator Profiles During Heart Valve Replacement Surgery

Completed
Conditions
Valvular Heart Disease
Infective Endocarditis
Interventions
Procedure: Blood sample collection
Other: Assessment of signs of organ dysfunction
Registration Number
NCT02727413
Lead Sponsor
Jena University Hospital
Brief Summary

The study aims at the comparative examination of pre-, intra- and post-operative release profiles of inflammatory and vasoactive mediators in patients undergoing heart valve surgery under cardiopulmonary bypass (CPB) due to either infectious endocarditis or degenerative valvular heart disease. Specific attention will focus on the distinction between mediator release associated with infection and that resulting from CPB. Concomitantly identification and characterization of infectious pathogens in the circulation and in valvular samples will be carried out, together with the search for resistance-coding transcripts.

Detailed Description

Exaggerated release of inflammatory mediators and endogenous vasoactive substances resulting from the coincident infection and surgical stress plays a role in post-operative organ failure and altered immune defense, thus contributing to unfavorable post-operative outcome.

Cardiopulmonary bypass (CPB) itself, even in the absence of IE, has been shown to modify cytokine and vasoactive mediator release and may cause organ failure. Tracing of release profiles of inflammatory cytokines and vasoactive mediators and their correlation with postoperative organ dysfunction in cardiac surgery for IE or non-IE patients aims at the assessment of the prognostic validity of these biomarkers and the evaluation of measures for their pro-active clearance during the surgical intervention.

Induction of inflammatory mediators and their temporal release profile may vary depending on the involved pathogens, which cannot be always identified by conventional techniques (blood culture). Since it is conceivable that identification of the involved pathogen could explain differences in cytokine secretory patterns in IE, use of advanced molecular technologies (NGS) will support the clarification of such relations. Analysis of transcripts encoding inflammatory and vasoactive mediators in blood cells will enable the surveillance of temporal oscillations in their profiles during the observation time frame. Transcriptome analysis of identified putative pathogens can also disclose features of antibiotic resistance.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
Inclusion Criteria
  • signed informed consent
  • age > 18
  • confirmed diagnosis of infective endocarditis or valvular heart disease
  • scheduled surgical Intervention with CPB use
Exclusion Criteria
  • glucocorticoid dosage above Cushing threshold
  • severe neutropenia (below 1000/mm3)
  • immunosuppression or immunomodulatory therapy
  • pregnancy

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Infective endocarditisAssessment of signs of organ dysfunctionBlood sample collection and assessment of signs of organ dysfunction in patients diagnosed with infective endocarditis in accordance with Duke criteria and scheduled for valve surgery
Valvular heart diseaseBlood sample collectionBlood sample collection and assessment of signs of organ dysfunction in patients diagnosed with valvular heart disease, with no signs of infection, scheduled for valve replacement surgery
Infective endocarditisBlood sample collectionBlood sample collection and assessment of signs of organ dysfunction in patients diagnosed with infective endocarditis in accordance with Duke criteria and scheduled for valve surgery
Valvular heart diseaseAssessment of signs of organ dysfunctionBlood sample collection and assessment of signs of organ dysfunction in patients diagnosed with valvular heart disease, with no signs of infection, scheduled for valve replacement surgery
Primary Outcome Measures
NameTimeMethod
Area under the plasma concentration versus time curve (AUC) of C-reactive Protein (CRP)24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery

Plasma Levels of CRP over time

Area under the plasma concentration versus time curve (AUC) of Endothelin 124 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery

Plasma Levels of Endothelin 1 over time

Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 1024 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery

Plasma Levels of IL 10 over time

Area under the plasma concentration versus time curve (AUC) of Tumor Necrosis Factor (TNF) alpha24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery

Plasma Levels of TNF alpha over time

Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 1beta24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery

Plasma Levels of IL 1beta over time

Area under the plasma concentration versus time curve (AUC) of Procalcitonin24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery

Plasma levels of Procalcitonin over time

Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 624 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery

Plasma Levels of IL 6 over time

Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 1824 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery

Plasma Levels of IL 18 over time

Secondary Outcome Measures
NameTimeMethod
Area under the plasma concentration versus time curve (AUC) of pro-Atrial natriuretic peptide24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery

Plasma Levels of pro-Atrial natriuretic peptide

Area under the plasma concentration versus time curve (AUC) of pro-Adrenomedullin24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery

Plasma Levels of pro-Adrenomedullin

SOFA Score24 h before and 24 and 48 h after surgical intervention

Changes in SOFA scores after surgery, as compared to pre-surgery baseline

Concomitant medicationDuring and 48 h upon completion of surgical intervention

Cumulative doses of applied vasopressors, corticosteroids and prostaglandins

Renal replacement therapyOver 7 days following surgery

Use and duration of renal replacement therapy

Area under the plasma concentration versus time curve (AUC) of pro-Arginine vasopressin24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery

Plasma Levels of pro-Arginine vasopressin

In-hospital mortality30 days after surgery

Post-surgical mortality over 30 days

Trial Locations

Locations (1)

Center for Clinical Studies, Jena University Hospital

🇩🇪

Jena, Thuringia, Germany

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