The Importance of Wnt-signaling After Cardiac Surgery

The Importance of Wnt-signaling in the Pathobiology of Systemic Inflammation and Organ Dysfunction After Cardiac Surgery

Cardiac surgery saves lives when patients suffer from cardiac disease. Local inflammation is important for tissue repair and wound healing after such an operation. Inflammation starts already when the patient is treated in the intensive care unit. When inflammatory proteins (cytokines) are released into the circulation, they cause also a systemic inflammation, which alerts the immune system of the body and activates defence mechanisms (=adaptive response). In some patients, systemic inflammation is out of control thereby causing organ dysfunctions, shock, and in the most severe cases even death (=maladaptive response). The aim of this study is to investigate the early phase of inflammation after the operation. Repeated blood samples will be taken of patients undergoing cardiac surgery to describe the patterns and dynamics of inflammation proteins. A better understanding of these mechanisms will potentially lead to improved treatment of patients after cardiac surgery.

Study Overview

• Status: Completed
• Conditions: Inflammation; Thoracic Surgery
• Intervention / Treatment: Other: Blood sampling

Detailed Description

The aim of this project is to understand early inflammation mechanisms after cardiac surgery. Therefore, repeated blood samples of patients undergoing cardiac surgery will be taken. Patients are selected after "open" cardiac surgery (via sternotomy), when when they require postoperative care in the cardiovascular intensive care unit. The blood samples will be analysed in collaboration with the Inflammation Research Unit of the Department of Internal Medicine at the University Hospital Zurich.

• Study Type: Observational
• Enrollment (Actual): 64

Contacts and Locations

Study Locations

• Switzerland
  • Zürich, Switzerland
    • 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 after open cardiac surgery

Description

Inclusion Criteria:

• Cardiac surgery via sternotomy
• Coronary-bypass bypass surgery with or without valve surgery
• Postoperative hospitalisation in the cardio-surgical ICU
• Available informed consent

Exclusion Criteria:

• Preoperative infections (e.g. endocarditis)
• Preoperative use of steroids or other immunosuppression

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; Coronary artery bypass surgery off-pump (n=24)	Other: Blood sampling; Five Timepoints: baseline (pre-operative), ICU admission, 4 hours after ICU admission, 8 hours after ICU admission, 48 hours after ICU admission
2; Coronary artery bypass surgery on-pump (n=16)	Other: Blood sampling; Five Timepoints: baseline (pre-operative), ICU admission, 4 hours after ICU admission, 8 hours after ICU admission, 48 hours after ICU admission
3; Coronary artery bypass surgery plus valve surgery (n=20)	Other: Blood sampling; Five Timepoints: baseline (pre-operative), ICU admission, 4 hours after ICU admission, 8 hours after ICU admission, 48 hours after ICU admission

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of Wnt5a (ng/ml)	Measured by a commercially available ELISA	Up to 48 hours after ICU admission
Plasma concentration of sFRP1 (ng/ml)	Measured by a commercially available ELISA	Up to 48 hours after ICU admission
Plasma concentration of sFRP5 (ng/ml)	Measured by a commercially available ELISA	Up to 48 hours after ICU admission
Plasma concentration of WIF-1 (pg/ml)	Measured by a commercially available ELISA	Up to 48 hours after ICU admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily fluid balance (ml)	Routine parameter taken from charts	Up to 48 hours after ICU admission
Occurrence of complications (yes/no): composite endpoint of hemodynamic instability (defined as norepinephrine concentration = or > 0.1mcg/kg/min), delirium (defined as ICDSC score = or > 4), infections	Routine parameter taken from charts	Up to 7 days after ICU admission
Length of ICU stay (days)	Routine parameter taken from charts	Up to 4 weeks

Collaborators and Investigators

• Sponsor: Alain Rudiger
• Collaborators: University of Zurich
• Investigators: Principal Investigator: Alain Rudiger, MD, University of Zurich

Publications and helpful links

General Publications

• Hauffe T, Kruger B, Bettex D, Rudiger A. Shock Management for Cardio-surgical ICU Patients - The Golden Hours. Card Fail Rev. 2015 Oct;1(2):75-82. doi: 10.15420/cfr.2015.1.2.75.
• Hauffe T, Kruger B, Bettex D, Rudiger A. Shock Management for Cardio-surgical Intensive Care Unit Patient: The Silver Days. Card Fail Rev. 2016 May;2(1):56-62. doi: 10.15420/cfr.2015:27:2.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): April 1, 2022
• Study Completion (Actual): April 1, 2022

Study Registration Dates

• First Submitted: June 21, 2019
• First Submitted That Met QC Criteria: August 13, 2019
• First Posted (Actual): August 15, 2019

Study Record Updates

• Last Update Posted (Actual): July 21, 2022
• Last Update Submitted That Met QC Criteria: July 18, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Inflammation; Cytokines; WNT; Cardio-pulmonary bypass; Cardia surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: Wnt-study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No