Inflammatory Mediator Profiles During Heart Valve Replacement Surgery

Study Overview
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Brief Summary
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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
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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.

Official Title
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Inflammatory and Vasoactive Mediator Profiles and Pathogen Characterization During Heart Valve Replacement Surgery

Conditions
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Infective Endocarditis, Valvular Heart Disease

Intervention / Treatment
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* Procedure: Blood sample collection
* Other: Assessment of signs of organ dysfunction


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Infective endocarditis<br>Blood 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 | Procedure: Blood sample collection<br>* 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<br>Other: Assessment of signs of organ dysfunction<br>* 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<br>* Other names: SOFA score;|
| Valvular heart disease<br>Blood 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 | Procedure: Blood sample collection<br>* 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<br>Other: Assessment of signs of organ dysfunction<br>* 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<br>* Other names: SOFA score;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of Procalcitonin | Plasma levels of Procalcitonin over time | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | 
| Area under the plasma concentration versus time curve (AUC) of C-reactive Protein (CRP) | Plasma Levels of CRP over time | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | 
| Area under the plasma concentration versus time curve (AUC) of Endothelin 1 | Plasma Levels of Endothelin 1 over time | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | 
| Area under the plasma concentration versus time curve (AUC) of Tumor Necrosis Factor (TNF) alpha | Plasma Levels of TNF alpha over time | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | 
| Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 1beta | Plasma Levels of IL 1beta over time | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | 
| Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 6 | Plasma Levels of IL 6 over time | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | 
| Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 10 | Plasma Levels of IL 10 over time | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | 
| Area under the plasma concentration versus time curve (AUC) of Interleukin (IL) 18 | Plasma Levels of IL 18 over time | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of pro-Adrenomedullin | Plasma Levels of pro-Adrenomedullin | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | 
| Area under the plasma concentration versus time curve (AUC) of pro-Arginine vasopressin | Plasma Levels of pro-Arginine vasopressin | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | 
| Area under the plasma concentration versus time curve (AUC) of pro-Atrial natriuretic peptide | Plasma Levels of pro-Atrial natriuretic peptide | 24 h before surgery - connection/disconnection of CPB - 24 and 48 h post-surgery | 
| SOFA Score | Changes in SOFA scores after surgery, as compared to pre-surgery baseline | 24 h before and 24 and 48 h after surgical intervention | 
| Renal replacement therapy | Use and duration of renal replacement therapy | Over 7 days following surgery | 
| Concomitant medication | Cumulative doses of applied vasopressors, corticosteroids and prostaglandins | During and 48 h upon completion of surgical intervention | 
| In-hospital mortality | Post-surgical mortality over 30 days | 30 days after surgery |