Cardiovascular Phenotypes in Sepsis

NCT07442032 | Not Yet Recruiting

• 2 other identifiers: CaPSDnr 2025-04572-01
• Study Type: observational
• Target: 400
• Locations: 0 countries
• Sites: N/A

Brief Summary

This prospective observational study will investigate cardiovascular phenotypes in adults with sepsis and hemodynamic instability. Approximately 400 patients requiring vasopressor support will be enrolled across multiple hospital sites. Within 72 hours of admission, participants will undergo peripheral vascular assessments, echocardiography, and blood sampling for cardiac, endothelial, and inflammatory biomarkers. Patients will be classified according to the presence or absence of peripheral vascular dysfunction and cardiac dysfunction. The primary aim is to examine the association between these cardiovascular phenotypes and one-year mortality. Secondary aims include evaluating biomarker profiles, characterizing myocardial injury, and assessing cardiac function at a 3-month follow-up. The study seeks to improve understanding of sepsis-related cardiovascular dysfunction and support development of more individualized management strategies.

Conditions

Sepsis; Septic Shock; Cardiovascular Dysfunction; Microcirculatory Dysfunction; Troponin Elevation; Peripheral Vascular Response

Keywords

Sepsis; septic shock; cardiovascular dysfunction; microcirculatory dysfunction; cardiac biomarkers; troponin; peripheral arterial tonometry; echocardiography

Outcome Measures

Primary Outcomes (1)

• Association between cardiovascular phenotypes and one-year mortality in sepsis

  To assess the association between distinct cardiovascular phenotypes and one-year mortality in patients with sepsis. Cardiovascular phenotypes will be categorized as: (a) peripheral circulatory dysfunction (present vs. absent), (b) heart failure (present vs. absent), and (c) the combined presence of peripheral circulatory dysfunction and heart failure. One-year mortality will be analyzed according to phenotype group.

  Up to 1 year after admission to the Intermediate Care Unit (IMCU), Intensive Care Unit (ICU) or Cardiac Care Unit (CCU).

Secondary Outcomes (4)

• Association between cardiovascular phenotypes and in-hospital mortality in sepsis

  From admission to the IMCU, ICU, or CCU (baseline) until the date of in-hospital death or hospital discharge, whichever occurs first, assessed up to 90 days.

• Change in echocardiographic indices of acute ventricular function and ventriculo-arterial coupling from baseline to 3 months

  Baseline (within 72 hours of admission to the IMCU/ICU/CCU) to 3 months after baseline.

• Association of integrated cardiovascular biomarkers with one-year and in-hospital mortality in sepsis

  Up to 1 year after admission to the IMCU/ICU/CCU (baseline)

• Association between emerging cardiovascular biomarkers and myocardial injury severity in sepsis

  0-72 hours after admission to the IMCU/ICU/CCU

Other Outcomes (1)

• Cardiovascular events during one-year follow-up after critical care admission

  From admission to the IMCU/ICU/CCU through 1 year after admission

Study Arms (1)

Adults with suspected sepsis and hemodynamic instability requiring vasopressor support.

Participants are enrolled prospectively across multiple hospital sites and undergo standardized assessments of peripheral vascular function, echocardiography, and biomarker sampling. No interventions are assigned as part of the study.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients with suspected sepsis and hemodynamic instability requiring vasopressor support, recruited across multiple hospital critical care units including the Intermediate Care Unit (IMCU), Intensive Care Unit (ICU), Cardiac Care Unit (CCU) and Acute Care Unit (ACU).

You may qualify if:

• Age 18 years or older
• Suspected sepsis based on clinical evaluation and supporting laboratory findings
• Hemodynamic instability, defined as mean arterial pressure \< 65 mmHg despite adequate fluid resuscitation
• Requirement for vasopressor support

You may not qualify if:

• Lack of informed consent
• Advanced peripheral arterial disease, including: subclavian artery occlusion with vertebrobasilar symptoms, critical hand ischemia with tissue loss or non-healing wounds, multilevel occlusive disease affecting upper-extremity arteries, upper limb surgery or significant upper limb trauma within 30 days prior to admission, technical limitations preventing proper placement of the EndoPAT device (e.g., finger amputation, severe rheumatologic deformity, or marked extremity edema).

Sponsors & Collaborators

• Karolinska Institutet: lead

Related Publications (17)

• Frencken JF, van Smeden M, van de Groep K, Ong DSY, Klein Klouwenberg PMC, Juffermans N, Bonten MJM, van der Poll T, Cremer OL; MARS Consortium. Etiology of Myocardial Injury in Critically Ill Patients with Sepsis: A Cohort Study. Ann Am Thorac Soc. 2022 May;19(5):773-780. doi: 10.1513/AnnalsATS.202106-689OC.

  PMID: 34784496 BACKGROUND

• Tyden H, Lood C, Jonsen A, Gullstrand B, Kahn R, Linge P, Kumaraswamy SB, Dahlback B, Bengtsson AA. Low plasma concentrations of apolipoprotein M are associated with disease activity and endothelial dysfunction in systemic lupus erythematosus. Arthritis Res Ther. 2019 May 2;21(1):110. doi: 10.1186/s13075-019-1890-2.

  PMID: 31046824 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

• Landesberg G, Jaffe AS, Gilon D, Levin PD, Goodman S, Abu-Baih A, Beeri R, Weissman C, Sprung CL, Landesberg A. Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation*. Crit Care Med. 2014 Apr;42(4):790-800. doi: 10.1097/CCM.0000000000000107.

  PMID: 24365861 BACKGROUND

• Vallabhajosyula S, Kumar M, Pandompatam G, Sakhuja A, Kashyap R, Kashani K, Gajic O, Geske JB, Jentzer JC. Prognostic impact of isolated right ventricular dysfunction in sepsis and septic shock: an 8-year historical cohort study. Ann Intensive Care. 2017 Sep 7;7(1):94. doi: 10.1186/s13613-017-0319-9.

  PMID: 28884343 BACKGROUND

• Sanfilippo F, Corredor C, Fletcher N, Landesberg G, Benedetto U, Foex P, Cecconi M. Diastolic dysfunction and mortality in septic patients: a systematic review and meta-analysis. Intensive Care Med. 2015 Jun;41(6):1004-13. doi: 10.1007/s00134-015-3748-7. Epub 2015 Mar 24.

  PMID: 25800584 BACKGROUND

• Vallabhajosyula S, Pruthi S, Shah S, Wiley BM, Mankad SV, Jentzer JC. Basic and advanced echocardiographic evaluation of myocardial dysfunction in sepsis and septic shock. Anaesth Intensive Care. 2018 Jan;46(1):13-24. doi: 10.1177/0310057X1804600104.

  PMID: 29361252 BACKGROUND

• Jentzer JC, Lawler PR, Van Houten HK, Yao X, Kashani KB, Dunlay SM. Cardiovascular Events Among Survivors of Sepsis Hospitalization: A Retrospective Cohort Analysis. J Am Heart Assoc. 2023 Feb 7;12(3):e027813. doi: 10.1161/JAHA.122.027813. Epub 2023 Feb 1.

  PMID: 36722388 BACKGROUND

• Rosjo H, Varpula M, Hagve TA, Karlsson S, Ruokonen E, Pettila V, Omland T; FINNSEPSIS Study Group. Circulating high sensitivity troponin T in severe sepsis and septic shock: distribution, associated factors, and relation to outcome. Intensive Care Med. 2011 Jan;37(1):77-85. doi: 10.1007/s00134-010-2051-x. Epub 2010 Oct 12.

  PMID: 20938765 BACKGROUND

• 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

• Vallabhajosyula S, Sakhuja A, Geske JB, Kumar M, Poterucha JT, Kashyap R, Kashani K, Jaffe AS, Jentzer JC. Role of Admission Troponin-T and Serial Troponin-T Testing in Predicting Outcomes in Severe Sepsis and Septic Shock. J Am Heart Assoc. 2017 Sep 9;6(9):e005930. doi: 10.1161/JAHA.117.005930.

  PMID: 28889100 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

• Mair J, Lindahl B, Hammarsten O, Muller C, Giannitsis E, Huber K, Mockel M, Plebani M, Thygesen K, Jaffe AS. How is cardiac troponin released from injured myocardium? Eur Heart J Acute Cardiovasc Care. 2018 Sep;7(6):553-560. doi: 10.1177/2048872617748553. Epub 2017 Dec 27.

  PMID: 29278915 BACKGROUND

• Hammarsten O, Wernbom M, Mills NL, Mueller C. How is cardiac troponin released from cardiomyocytes? Eur Heart J Acute Cardiovasc Care. 2022 Sep 29;11(9):718-720. doi: 10.1093/ehjacc/zuac091. No abstract available.

  PMID: 35972428 BACKGROUND

• Kakihana Y, Ito T, Nakahara M, Yamaguchi K, Yasuda T. Sepsis-induced myocardial dysfunction: pathophysiology and management. J Intensive Care. 2016 Mar 23;4:22. doi: 10.1186/s40560-016-0148-1. eCollection 2016.

  PMID: 27011791 BACKGROUND

• Vincent JL, Jones G, David S, Olariu E, Cadwell KK. Frequency and mortality of septic shock in Europe and North America: a systematic review and meta-analysis. Crit Care. 2019 May 31;23(1):196. doi: 10.1186/s13054-019-2478-6.

  PMID: 31151462 BACKGROUND

• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.

  PMID: 26903338 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Venous blood samples (approximately 30 mL) will be collected within 72 hours of admission and again at the 3-month follow-up visit. Samples will be processed and stored at -80°C for later analysis of inflammatory, endothelial, glycocalyx, microvascular, and thrombotic biomarkers.

MeSH Terms

Conditions

Sepsis; Shock, Septic

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Jonas Persson, M.D., PhD

CONTACT

+46 (0) 700 891412; jonas.persson@regionstockholm.se

Samantha Lörstad, M.D.

CONTACT

+46 (0) 708 693973; samantha.rutherford-lorstad@regionstockholm.se

Study Design

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

Study Record Dates

• First Submitted: December 16, 2025
• First Posted: March 2, 2026
• Study Start: April 6, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: March 2, 2026

Record last verified: 2026-02