COronary Microcirculation and Troponin Elevation in Septic Shock

NCT06294730 | Completed

• 1 other identifier: 2018/1891-31
• Study Type: observational
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sepsis; Myocardial Injury; Coronary Microvascular Dysfunction; Endothelial Dysfunction

Keywords

sepsis; cardiac troponin; myocardial injury; coronary microvascular dysfunction; Index of microcirculatory resistance; survival

Outcome Measures

Primary Outcomes (1)

• Relationship between hs-cTnT and IMR

  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 Outcomes (10)

• Relationship between hs-cTnT and CFR

  Day 2-10 from the onset of sepsis symptoms.

• Relationship between hs-cTnT and BRI

  Day 2-10 from the onset of sepsis symptoms

• Relationship between hs-cTnT 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

  Day 2-10 from the onset of sepsis symptoms

• Relationship between hs-cTnT and left ventricular end diastolic pressure (LVEDP)

  Day 2-10 from the onset of sepsis symptoms

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Karolinska Institutet: lead

Study Sites (1)

Karolinska Institutet, Danderyd University Hospital

Stockholm, 182 88, Sweden

Location

Related Publications (16)

• Lorstad S, Shekarestan S, Jernberg T, Tehrani S, Astrand P, Gille-Johnson P, Persson J. First Sampled High-Sensitive Cardiac Troponin T is Associated With One-Year Mortality in Sepsis Patients and 30- to 365-Day Mortality in Sepsis Survivors. Am J Med. 2023 Aug;136(8):814-823.e8. doi: 10.1016/j.amjmed.2023.04.029. Epub 2023 May 6.

  PMID: 37156347 BACKGROUND

• Levy MM, Artigas A, Phillips GS, Rhodes A, Beale R, Osborn T, Vincent JL, Townsend S, Lemeshow S, Dellinger RP. Outcomes of the Surviving Sepsis Campaign in intensive care units in the USA and Europe: a prospective cohort study. Lancet Infect Dis. 2012 Dec;12(12):919-24. doi: 10.1016/S1473-3099(12)70239-6. Epub 2012 Oct 26.

  PMID: 23103175 BACKGROUND

• Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018 Oct 30;72(18):2231-2264. doi: 10.1016/j.jacc.2018.08.1038. Epub 2018 Aug 25. No abstract available.

  PMID: 30153967 BACKGROUND

• Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ, Juni P, Kastrati A, Koller A, Kristensen SD, Niebauer J, Richter DJ, Seferovic PM, Sibbing D, Stefanini GG, Windecker S, Yadav R, Zembala MO; ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019 Jan 7;40(2):87-165. doi: 10.1093/eurheartj/ehy394. No abstract available.

  PMID: 30165437 BACKGROUND

• Fearon WF, Nakamura M, Lee DP, Rezaee M, Vagelos RH, Hunt SA, Fitzgerald PJ, Yock PG, Yeung AC. Simultaneous assessment of fractional and coronary flow reserves in cardiac transplant recipients: Physiologic Investigation for Transplant Arteriopathy (PITA Study). Circulation. 2003 Sep 30;108(13):1605-10. doi: 10.1161/01.CIR.0000091116.84926.6F. Epub 2003 Sep 8.

  PMID: 12963639 BACKGROUND

• De Bruyne B, Pijls NH, Smith L, Wievegg M, Heyndrickx GR. Coronary thermodilution to assess flow reserve: experimental validation. Circulation. 2001 Oct 23;104(17):2003-6. doi: 10.1161/hc4201.099223.

  PMID: 11673336 BACKGROUND

• Fearon WF, Balsam LB, Farouque HM, Caffarelli AD, Robbins RC, Fitzgerald PJ, Yock PG, Yeung AC. Novel index for invasively assessing the coronary microcirculation. Circulation. 2003 Jul 1;107(25):3129-32. doi: 10.1161/01.CIR.0000080700.98607.D1. Epub 2003 Jun 23.

  PMID: 12821539 BACKGROUND

• Aarnoudse W, Fearon WF, Manoharan G, Geven M, van de Vosse F, Rutten M, De Bruyne B, Pijls NH. Epicardial stenosis severity does not affect minimal microcirculatory resistance. Circulation. 2004 Oct 12;110(15):2137-42. doi: 10.1161/01.CIR.0000143893.18451.0E. Epub 2004 Oct 4.

  PMID: 15466646 BACKGROUND

• Fearon WF, Aarnoudse W, Pijls NH, De Bruyne B, Balsam LB, Cooke DT, Robbins RC, Fitzgerald PJ, Yeung AC, Yock PG. Microvascular resistance is not influenced by epicardial coronary artery stenosis severity: experimental validation. Circulation. 2004 May 18;109(19):2269-72. doi: 10.1161/01.CIR.0000128669.99355.CB. Epub 2004 May 10.

  PMID: 15136503 BACKGROUND

• Ong P, Camici PG, Beltrame JF, Crea F, Shimokawa H, Sechtem U, Kaski JC, Bairey Merz CN; Coronary Vasomotion Disorders International Study Group (COVADIS). International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 2018 Jan 1;250:16-20. doi: 10.1016/j.ijcard.2017.08.068. Epub 2017 Sep 8.

  PMID: 29031990 BACKGROUND

• De Backer D, Donadello K, Sakr Y, Ospina-Tascon G, Salgado D, Scolletta S, Vincent JL. Microcirculatory alterations in patients with severe sepsis: impact of time of assessment and relationship with outcome. Crit Care Med. 2013 Mar;41(3):791-9. doi: 10.1097/CCM.0b013e3182742e8b.

  PMID: 23318492 BACKGROUND

• Fernandez-Sarmiento J, Molina CF, Salazar-Pelaez LM, Florez S, Alarcon-Forero LC, Sarta M, Hernandez-Sarmiento R, Villar JC. Biomarkers of Glycocalyx Injury and Endothelial Activation are Associated with Clinical Outcomes in Patients with Sepsis: A Systematic Review and Meta-Analysis. J Intensive Care Med. 2023 Jan;38(1):95-105. doi: 10.1177/08850666221109186. Epub 2022 Jun 19.

  PMID: 35722738 BACKGROUND

• Piotti A, Novelli D, Meessen JMTA, Ferlicca D, Coppolecchia S, Marino A, Salati G, Savioli M, Grasselli G, Bellani G, Pesenti A, Masson S, Caironi P, Gattinoni L, Gobbi M, Fracasso C, Latini R; ALBIOS Investigators. Endothelial damage in septic shock patients as evidenced by circulating syndecan-1, sphingosine-1-phosphate and soluble VE-cadherin: a substudy of ALBIOS. Crit Care. 2021 Mar 19;25(1):113. doi: 10.1186/s13054-021-03545-1.

  PMID: 33741039 BACKGROUND

• Sun T, Wang Y, Wu X, Cai Y, Zhai T, Zhan Q. Prognostic Value of Syndecan-1 in the Prediction of Sepsis-Related Complications and Mortality: A Meta-Analysis. Front Public Health. 2022 Apr 11;10:870065. doi: 10.3389/fpubh.2022.870065. eCollection 2022.

  PMID: 35480580 BACKGROUND

• Colicchia M, Perrella G, Gant P, Rayes J. Novel mechanisms of thrombo-inflammation during infection: spotlight on neutrophil extracellular trap-mediated platelet activation. Res Pract Thromb Haemost. 2023 Mar 11;7(2):100116. doi: 10.1016/j.rpth.2023.100116. eCollection 2023 Feb.

  PMID: 37063765 BACKGROUND

• Cox D. Sepsis - it is all about the platelets. Front Immunol. 2023 Jun 7;14:1210219. doi: 10.3389/fimmu.2023.1210219. eCollection 2023.

  PMID: 37350961 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral plasma, serum and whole blood

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jonas Persson, MD, PhD

  Karolinska Institutet Danderyd University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 16, 2024
• First Posted: March 5, 2024
• Study Start: June 13, 2019
• Primary Completion: December 20, 2024
• Study Completion: February 28, 2025
• Last Updated: June 29, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Will be provided upon reasonable request

Locations

SE (1)