COronary Microcirculation and Troponin Elevation in Septic Shock (COMTESS)

June 25, 2025 updated by: Jonas Persson, Karolinska Institutet

Coronary Microcirculation and Troponin Elevation in Septic Shock

Plasma cardiac troponin (cTn) elevation is an indicator of increased mortality in patients with sepsis yet the underlying cause of troponin elevation in sepsis is not known. The COMTESS study investigates whether elevated high-sensitive cardiac Troponin T (hs-cTnT) levels in hemodynamically unstable patients with sepsis can be explained by an underlying coronary artery disease or a process within the coronary microcirculation. Fifty patients with sepsis and with hs-cTnT elevation (>15 ng/L) will undergo coronary angiography, including an assessment of coronary flow using a method called thermo-dilution to record the index of microcirculatory resistance (IMR) in the left anterior descending artery (LAD). The relationship between IMR and hs-cTnT will subsequently be analysed. It is important to identify the underlying causes of elevated cTn during sepsis to target further research with an aim to improve the survival in patients suffering from this condition.

Study Overview

Status

Completed

Conditions

Detailed Description

Severe sepsis and septic shock are frequent primary causes of morbidity and mortality in intensive care units worldwide with a mortality rate of 28.3 - 41.1%. Our research group has previously shown that increasing level of high-sensitive cardiac troponin T (hs-cTnT) taken in sepsis patients is associated with 30-day and one-year mortality. Importantly, our group showed that hs-cTnT is also associated with mortality during the convalescence phase (30-365-day) in sepsis survivors.

Serum cardiac troponin (cTn) measurement is used to detect myocardial injury in patients with acute ischemic heart disease. Cardiac-specific troponins (troponin I and T) are, under normal physiological conditions, only detectable in the blood in small concentrations. In the event of myocyte damage, cardiac-specific troponins I and T enter the systemic circulation and can be detected and measured using modern immunoassay methods. This has led to the use of these biomarkers to identify both the presence and even estimated extent of myocardial injury which can then in turn facilitate an early risk stratification and identification of patients suitable for coronary intervention. Since 2018, the high-sensitive cardiac troponin assays have become the recommended assays for use within the clinical setting. In stark contrast to the treatment of patients with acute myocardial infarction and elevated cTn levels, there are currently no clinical guidelines to help physicians treat, investigate or follow-up sepsis patients with sepsis-related myocardial injury.

The COMTESS study is a pioneering observational prospective clinical study of 50 critically ill sepsis patients with a sampled hs-cTnT >15 ng/L investigating the relationship between hs-cTnT level and concurrent microvascular dysfunction. Following informed consent, coronary angiography with measurements of coronary flow reserve (CFR), basal resistance index (BRI) and index of microcirculatory resistance (IMR) using thermo-dilution in the left anterior descending artery (LAD) is performed in each patient to ascertain underlying coronary microvascular dysfunction (CMVD). Fractional flow reserve (FFR) will be measured in cases where there is a coronary stenosis in the LAD. A research echocardiography is also performed on day 2-10 to examine right and left ventricular function.

Our primary hypothesis is that increasing level of hs-cTnT is associated with increasing level of CMVD in patients with sepsis and that myocardial injury thus contributes to excess death in sepsis and sepsis-survivors. The mechanisms behind myocardial injury in sepsis are not known. Disturbed sublingual microcirculatory alterations are associated with mortality in septic shock, but whether these alterations in proxy vessels translates to clinically relevant CMVD and myocardial injury in patients with sepsis is not known.

The physiological properties of endothelial cells (ECs) in the microcirculation are dependent on a complex carbohydrate-rich layer covering the EC luminal surface called the glycocalyx. Studies have shown that the disseminated dysfunctional immune response which is the hallmark of sepsis causes glycocalyx and EC injury and widespread coagulopathy leading to microvascular thrombosis. Pro-thrombotic components (e.g., neutrophile extracellular traps [NETs], and prothrombin) and components from EC and glycocalyx damage (e.g., Syndecan-1, thrombomodulin) can subsequently be analysed in plasma. Elevated level of Syndecan-1 in sepsis is associated with greater risk of death. Blood samples will be drawn during the coronary angiography for each patient and will be stored in a biobank. Our aim is to investigate if there is an association between plasma level of different microvascular components in relation to IMR level.

Study Type

Observational

Enrollment (Actual)

62

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Stockholm, Sweden, 182 88
        • Karolinska Institutet, Danderyd University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Sepsis- or septic shock-patients with a life expectancy of >1year and non-normal high-sensitive cardiac troponin T values (>15 ng/L)

Description

Inclusion Criteria:

  • Patients fulfilling the Sepsis-3 definition of and diagnostic criteria for sepsis or septic shock
  • Age 40 - 85 years
  • Life expectancy > 1 year
  • hs-cTnT values >15 ng/L

Exclusion Criteria:

  • pregnancy
  • previous medical history of coronary artery by-pass grafting
  • heart transplant
  • previously verified ejection fraction (EF) ≤39% prior to hospital admission
  • Hypertrophic cardiomyopathy (Septum > 15 mm)
  • severe aortic stenosis
  • amyloidosis or sarcoidosis with myocardial engagement
  • estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 prior to hospital admission
  • asthma
  • infectious endocarditis
  • a medical history of abdominal, thoracic, or orthopaedic surgery within the last three months prior to hospital admission.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relationship between hs-cTnT and IMR
Time Frame: Day 2-10 from the onset of sepsis symptoms.
Spline regression between the highest hs-cTnT at 0-72 hrs from vasopressor initiation and IMR at day 2-10 from sepsis onset
Day 2-10 from the onset of sepsis symptoms.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relationship between hs-cTnT and CFR
Time Frame: Day 2-10 from the onset of sepsis symptoms.
Spline regression between the highest log hs-cTnT at 0-72 hrs from vasopressor initiation and CFR at day 2-10 from sepsis onset
Day 2-10 from the onset of sepsis symptoms.
Relationship between hs-cTnT and BRI
Time Frame: Day 2-10 from the onset of sepsis symptoms
Spline regression between the highest hs-cTnT at 0-72 hrs from vasopressor initiation and and BRI at day 2-10 from sepsis onset
Day 2-10 from the onset of sepsis symptoms
Relationship between hs-cTnT and number of diseased epicardial coronary vessels
Time Frame: Day 2-10 from the onset of sepsis symptoms
ANOVA for the relationship between the highest hs-cTnT at 0-72 hrs from vasopressor initiation and number of diseased epicardial coronary vessels
Day 2-10 from the onset of sepsis symptoms
Relationship between hs-cTnT and Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX)-score
Time Frame: Day 2-10 from the onset of sepsis symptoms
Spline regression between the highest hs-cTnT at 0-72 hrs from vasopressor initiation and SYNTAX-score
Day 2-10 from the onset of sepsis symptoms
Relationship between hs-cTnT and left ventricular end diastolic pressure (LVEDP)
Time Frame: Day 2-10 from the onset of sepsis symptoms
Spline regression between the highest hs-cTnT at 0-72 hrs from vasopressor initiation and LVEDP (mmHg)
Day 2-10 from the onset of sepsis symptoms
Relationship between hs-cTnT and Tricuspid annular plane systolic excursion (TAPSE)
Time Frame: Day 2-10 from the onset of sepsis symptoms
Spline regression between the highest hs-cTnT at 0-72 hrs and Tricuspid annular plane systolic excursion TAPSE (mm)
Day 2-10 from the onset of sepsis symptoms
Relationship between hs-cTnT and echocardiographic measurements of left ventricular global strain
Time Frame: Day 2-10 from the onset of sepsis symptoms
Spline regression between the highest hs-cTnT at 0-72 hrs from vasopressor initiation and left ventricular global strain from speckle tracking (units)
Day 2-10 from the onset of sepsis symptoms
Relationship between hs-cTnT and echocardiographic measurements of left diastolic dysfunction
Time Frame: Day 2-10 from the onset of sepsis symptoms
ANOVA between the highest hs-cTnT at 0-72 hrs from vasopressor initiation and left ventricular diastolic function grouping (none; grade I, impaired relaxation; grade II, pseudonormalization; grade III, restrictive filling)
Day 2-10 from the onset of sepsis symptoms
Relationship between measures of endothelial dysfunction and IMR
Time Frame: Day 2-10 from the onset of sepsis symptoms
Spline regression between plasma levels of syndecan-1 and IMR (units)
Day 2-10 from the onset of sepsis symptoms
Relationship between measures NETs and IMR
Time Frame: Day 2-10 from the onset of sepsis symptoms
Spline regression between NETs in plasma and IMR
Day 2-10 from the onset of sepsis symptoms

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Karolinska Institutet

Investigators

  • Principal Investigator: Jonas Persson, MD, PhD, Karolinska Institutet Danderyd University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 13, 2019

Primary Completion (Actual)

December 20, 2024

Study Completion (Actual)

February 28, 2025

Study Registration Dates

First Submitted

February 16, 2024

First Submitted That Met QC Criteria

March 2, 2024

First Posted (Actual)

March 5, 2024

Study Record Updates

Last Update Posted (Actual)

June 29, 2025

Last Update Submitted That Met QC Criteria

June 25, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018/1891-31

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Will be provided upon reasonable request.

IPD Sharing Time Frame

Will be provided upon reasonable request

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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