Inflammatory Mediator Profiles During Heart Valve Replacement Surgery (Remove-Pilot)

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

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.

Study Overview

• Status: Completed
• Conditions: Infective Endocarditis; Valvular Heart Disease
• Intervention / Treatment: Procedure: Blood sample collection; Other: Assessment of signs of organ dysfunction

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.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Germany
  • Thuringia
    • Jena, Thuringia, Germany, 07747
      • Center for Clinical Studies, Jena University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with infective endocarditis or valvular heart disease, undergoing cardiac surgery with cardiopulmonary bypass

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Infective endocarditis; 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; 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; Other: Assessment 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; Other Names: SOFA score
Valvular heart disease; 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; 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; Other: Assessment 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; Other Names: SOFA score

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathogen genotyping	Identification of circulating pathogens	Before and during intervention at the heart valve
Resistance transcripts	Abundance of bacterial transcripts encoding antibiotic resistance in blood	During intervention at the heart valve

Collaborators and Investigators

• Sponsor: Jena University Hospital
• Collaborators: Thermo Fisher Scientific, Inc
• Investigators: Study Chair: Frank M Brunkhorst, MD, Jena University Hospital

Publications and helpful links

General Publications

• Diab M, Tasar R, Sponholz C, Lehmann T, Pletz MW, Bauer M, Brunkhorst FM, Doenst T. Changes in inflammatory and vasoactive mediator profiles during valvular surgery with or without infective endocarditis: A case control pilot study. PLoS One. 2020 Feb 3;15(2):e0228286. doi: 10.1371/journal.pone.0228286. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2016
• Primary Completion (ACTUAL): February 1, 2017
• Study Completion (ACTUAL): February 1, 2017

Study Registration Dates

• First Submitted: March 23, 2016
• First Submitted That Met QC Criteria: March 29, 2016
• First Posted (ESTIMATE): April 4, 2016

Study Record Updates

• Last Update Posted (ACTUAL): June 24, 2019
• Last Update Submitted That Met QC Criteria: June 21, 2019
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Cardiovascular Infections; Heart Diseases; Heart Valve Diseases; Endocarditis, Bacterial; Endocarditis
• Other Study ID Numbers: ZKS0071

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO