Genomic Determinants of Outcome in Cardiogenic Shock

NCT05728359 | Recruiting

• 1 other identifier: 290406
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this project is to understand the heterogeneity of both the immune consequences and treatment responses in CS. We will explore this heterogeneity through identification of transcriptomic sub-phenotypes and their association with outcomes, including therapeutic responses.

Conditions

Cardiogenic Shock

Keywords

ACS,; Cardiogenic Shock; ECMO; Impella; Gene Expression; Endotype

Outcome Measures

Primary Outcomes (1)

• The primary aim is to better understand the heterogeneity of the immune consequences and treatment responses in CS through identification of transcriptomic sub-phenotypes and their association with in-hospital mortality

  This will be achieved through bloods sample collection, analysis and linked to the patient's clinical diagnosis and outcome.

  through study completion, an average of 5 days

Secondary Outcomes (6)

• Identify transcriptomic (and chemokine/cytokine) signatures at presentation that elucidate the pathobiology of CS and examine their subsequent evolution.

  through study completion, an average of 5 days

• Correlate recently identified clinical phenotypes of CS with transcriptomic and inflammatory mediator signatures.

  through study completion, an average of 5 days

• Identify transcriptomic and chemokine/cytokine signatures at presentation that improve prognostic accuracy in patients with CS

  through study completion, an average of 5 days

• Investigate inter-individual heterogeneity in the dynamic transcriptomic response to CS through an eQTL mapping approach and identify context- specific regulatory genetic variants involving gene networks central to the pathogenesis of CS.

  through study completion, an average of 5 days

• Identity novel therapeutic targets that might modulate the dysfunctional immune response to CS - "drug discovery"

  through study completion, an average of 5 days

Study Arms (5)

Cardiogenic shock and MI

Patients presenting with acute myocardial infarction and cardiogenic shock who are supported medically (ie. inotropes +/- intra aortic balloon pump only). N=50

Other: Observational study

Cardiogenic shock and MI wtih ECMO

Patients presenting with acute myocardial infarction and cardiogenic shock who are supported medically with ECMO (+/- LV unloading device). N=50

Other: Observational study

Cardiogenic shock and MI wtih Impella

Patients presenting with acute myocardial infarction and cardiogenic shock who are supported medically with Impella. N=50

Other: Observational study

MI without cardiogenic shock

Patients presenting with acute myocardial infarction and cardiogenic shock as a control comparator

Other: Observational study

Non ischemic Cardiogenic Shock ie myocarditis

Patients presenting with myocarditis and cardiogenic shock as a control comparator

Other: Observational study

Interventions

Observational study OTHER

Blood sampling and clinical data collection

Cardiogenic shock and MI; Cardiogenic shock and MI wtih ECMO; Cardiogenic shock and MI wtih Impella; MI without cardiogenic shock; Non ischemic Cardiogenic Shock ie myocarditis

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All patients presenting to recruiting sites who fulfil study inclusion criteria and have no exclusion, will be considered. The majority of patients will be present through the heart attack centres and pathways. Some patients will, however, develop cardiogenic shock (CS) during their admission. These patients will be recruited from the coronary care units, intensive care units or cardiology wards and will be identified by clinicians who will alert research staff.

You may qualify if:

• Willing to provide informed consent or appropriate consent from a nominated consultee or personal consultee
• Presentation within 24 hours of onset of ACS symptoms.
• CS can only be secondary to ACS (Type 1 MI STEMI or N-STEMI) or myocarditis
• Planned or completed revascularisation of culprit coronary artery
• CS will be defined by:
• Systolic blood pressure \<90 mmHg for at least 30 minutes
• A requirement for a continuous infusion of vasopressor or inotropic therapy to maintain systolic blood pressure \> 90 mmHg.
• Clinical signs of pulmonary congestion, plus signs of impaired organ perfusion with at least one of the following manifestations:
• altered mental status.
• cold and clammy skin and limbs.
• oliguria with a urine output of less than 30 ml per hour.
• elevated arterial lactate level of \>2.0 mmol per litre.

You may not qualify if:

• Unwilling to provide informed consent.
• Echocardiographic evidence (recorded within 90 mins of end of PCI procedure) of mechanical cause for CS: eg ventricular septal defect, LV-free wall rupture, ischaemic mitral regurgitation.
• Age \<18 and ≥80 years.
• Shock from another cause (sepsis, haemorrhagic/hypovolaemic shock, anaphylaxis, etc).
• Significant systemic illness
• Known dementia of any severity
• Comorbidity with life expectancy \<12 months.
• Out-of-hospital cardiac arrest (OHCA) and any of the following:
• No return of spontaneous circulation (ongoing resuscitation effort)
• pH \<7
• Without bystander CPR within 10 minutes of collapse
• Arterial lactate level of \<2.0 mmol per litre.

Sponsors & Collaborators

• Barts & The London NHS Trust: lead
• University of Oxford: collaborator

Study Sites (1)

Barts Health NHS trust

London, United Kingdom

RECRUITING

Related Publications (4)

• Maslove DM, Tang B, Shankar-Hari M, Lawler PR, Angus DC, Baillie JK, Baron RM, Bauer M, Buchman TG, Calfee CS, Dos Santos CC, Giamarellos-Bourboulis EJ, Gordon AC, Kellum JA, Knight JC, Leligdowicz A, McAuley DF, McLean AS, Menon DK, Meyer NJ, Moldawer LL, Reddy K, Reilly JP, Russell JA, Sevransky JE, Seymour CW, Shapiro NI, Singer M, Summers C, Sweeney TE, Thompson BT, van der Poll T, Venkatesh B, Walley KR, Walsh TS, Ware LB, Wong HR, Zador ZE, Marshall JC. Redefining critical illness. Nat Med. 2022 Jun;28(6):1141-1148. doi: 10.1038/s41591-022-01843-x. Epub 2022 Jun 17.

  PMID: 35715504 BACKGROUND

• Davenport EE, Burnham KL, Radhakrishnan J, Humburg P, Hutton P, Mills TC, Rautanen A, Gordon AC, Garrard C, Hill AV, Hinds CJ, Knight JC. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med. 2016 Apr;4(4):259-71. doi: 10.1016/S2213-2600(16)00046-1. Epub 2016 Feb 23.

  PMID: 26917434 BACKGROUND

• Toma A, Dos Santos C, Burzynska B, Gora M, Kiliszek M, Stickle N, Kirsten H, Kosyakovsky LB, Wang B, van Diepen S, Epelman S, Szekely Y, Marshall JC, Billia F, Lawler PR. Diversity in the Expressed Genomic Host Response to Myocardial Infarction. Circ Res. 2022 Jun 24;131(1):106-108. doi: 10.1161/CIRCRESAHA.121.318391. Epub 2022 May 9. No abstract available.

  PMID: 35534922 BACKGROUND

• Cano-Gamez K, Burnham KL, Goh C, Allcock A, Malick ZH, Overend L, Kwok A, Smith DA, Peters-Sengers H, Antcliffe D; GAinS Investigators; McKechnie S, Scicluna BP, van der Poll T, Gordon AC, Hinds CJ, Davenport EE, Knight JC, Webster N, Galley H, Taylor J, Hall S, Addison J, Roughton S, Tennant H, Guleri A, Waddington N, Arawwawala D, Durcan J, Short A, Swan K, Williams S, Smolen S, Mitchell-Inwang C, Gordon T, Errington E, Templeton M, Venatesh P, Ward G, McCauley M, Baudouin S, Higham C, Soar J, Grier S, Hall E, Brett S, Kitson D, Wilson R, Mountford L, Moreno J, Hall P, Hewlett J, McKechnie S, Garrard C, Millo J, Young D, Hutton P, Parsons P, Smiths A, Faras-Arraya R, Soar J, Raymode P, Thompson J, Bowrey S, Kazembe S, Rich N, Andreou P, Hales D, Roberts E, Fletcher S, Rosbergen M, Glister G, Cuesta JM, Bion J, Millar J, Perry EJ, Willis H, Mitchell N, Ruel S, Carrera R, Wilde J, Nilson A, Lees S, Kapila A, Jacques N, Atkinson J, Brown A, Prowse H, Krige A, Bland M, Bullock L, Harrison D, Mills G, Humphreys J, Armitage K, Laha S, Baldwin J, Walsh A, Doherty N, Drage S, Ortiz-Ruiz de Gordoa L, Lowes S, Higham C, Walsh H, Calder V, Swan C, Payne H, Higgins D, Andrews S, Mappleback S, Hind C, Garrard C, Watson D, McLees E, Purdy A, Stotz M, Ochelli-Okpue A, Bonner S, Whitehead I, Hugil K, Goodridge V, Cawthor L, Kuper M, Pahary S, Bellingan G, Marshall R, Montgomery H, Ryu JH, Bercades G, Boluda S, Bentley A, Mccalman K, Jefferies F, Knight J, Davenport E, Burnham K, Maugeri N, Radhakrishnan J, Mi Y, Allcock A, Goh C. An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression. Sci Transl Med. 2022 Nov 2;14(669):eabq4433. doi: 10.1126/scitranslmed.abq4433. Epub 2022 Nov 2.

  PMID: 36322631 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

We will collect blood samples (18ml per time-point) at research-specific time points Plasma will be extracted from spun blood in appropriate blood collection tubes (EDTA, 2x3mL), aliquoted and stored at -80°C. DNA will be extracted from the Buffy Layer of spun whole human blood. RNA from human whole blood (1x3ml) will be collected into a Tempus tube. Whole blood will be added to Cytodelics to allow cellular fixation and subsequent analysis.

MeSH Terms

Conditions

Shock, Cardiogenic

Interventions

Observation

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Alastair Proudfoot

  Barts Heath NHS trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alastair Proudfoot

CONTACT

02037658707; alastair.proudfoot1@nhs.net

Mervyn Andiapen

CONTACT

02037658707; mervyn.andiapen@nhs.net

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Month
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2022
• First Posted: February 15, 2023
• Study Start: August 8, 2022
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)