Infective Endocarditis, Valvular Heart Disease
Conditions
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.
Interventions
PROCEDUREBlood sample collection
Drawing of 10 ml blood at inclusion, at the time of CPB connection, 60 min under CPB, at the time of CPB disconnection, 6, 24 and 48 hours post-surgery
OTHERAssessment of signs of organ dysfunction
Assessment of signs of organ dysfunction based on medical data prior to surgery, 24 and 48 hours post-surgery, and at the time of ICU discharge
Sponsors
Thermo Fisher Scientific, Inc
Jena University Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 10 | 24 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 Procalcitonin | 24 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 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 1 | 24 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 Tumor Necrosis Factor (TNF) alpha | 24 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) 1beta | 24 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 Interleukin (IL) 6 | 24 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) 18 | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | Plasma Levels of IL 18 over time |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| In-hospital mortality | 30 days after surgery | Post-surgical mortality over 30 days |
| Area under the plasma concentration versus time curve (AUC) of pro-Adrenomedullin | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | Plasma Levels of pro-Adrenomedullin |
| Area under the plasma concentration versus time curve (AUC) of pro-Arginine vasopressin | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | Plasma Levels of pro-Arginine vasopressin |
| Area under the plasma concentration versus time curve (AUC) of pro-Atrial natriuretic peptide | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | Plasma Levels of pro-Atrial natriuretic peptide |
| SOFA Score | 24 h before and 24 and 48 h after surgical intervention | Changes in SOFA scores after surgery, as compared to pre-surgery baseline |
| Renal replacement therapy | Over 7 days following surgery | Use and duration of renal replacement therapy |
| Concomitant medication | During and 48 h upon completion of surgical intervention | Cumulative doses of applied vasopressors, corticosteroids and prostaglandins |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pathogen genotyping | Before and during intervention at the heart valve | Identification of circulating pathogens |
| Resistance transcripts | During intervention at the heart valve | Abundance of bacterial transcripts encoding antibiotic resistance in blood |
Countries
Germany
Outcome results
None listed