Genomic Determinants of Outcome in Cardiogenic Shock

Recruiting

• Conditions: Cardiogenic Shock
• Interventions: Other: Observational study

• Registration Number: NCT05728359
• Lead Sponsor: Barts & The London NHS Trust

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.

Detailed Description

This is a prospective observational cohort study in 8-10 cardiac centres across Europe. We will recruit patients presenting with acute myocardial infarction (AMI) and CS who are supported medically (n=100); with extracorporeal membrane oxygenation (n=50); and with the Impella Device (n=50). We will also enrol patients who present with either AMI and no evidence of CS (n=50) or CS due to non-ischaemic pathologies (e.g. myocarditis: n=50) as comparators. The recruitment target is 300 patients.

Study Timeline

• Study Start: 2022-08-08
• Study First Submitted: 2022-09-22
• Study First Submitted QC: 2023-02-13
• Study First Posted: 2023-02-15
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-21
• Last Update Posted: 2024-10-22
• Primary Completion: 2025-11-01
• Study Completion: 2025-11-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• All of the following are required for inclusion following screening:

  • 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.

Exclusion Criteria

• Any of the inclusion criteria not met and:

  1. Unwilling to provide informed consent.

  2. 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.

  3. Age <18 and ≥80 years.

  4. Shock from another cause (sepsis, haemorrhagic/hypovolaemic shock, anaphylaxis, etc).

  5. Significant systemic illness

  6. Known dementia of any severity

  7. Comorbidity with life expectancy <12 months.

  8. Out-of-hospital cardiac arrest (OHCA) and any of the following:

     1. No return of spontaneous circulation (ongoing resuscitation effort)
     2. pH <7
     3. Without bystander CPR within 10 minutes of collapse

  9. Arterial lactate level of <2.0 mmol per litre.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
MI without cardiogenic shock	Observational study	Patients presenting with acute myocardial infarction and cardiogenic shock as a control comparator
Non ischemic Cardiogenic Shock ie myocarditis	Observational study	Patients presenting with myocarditis and cardiogenic shock as a control comparator
Cardiogenic shock and MI	Observational study	Patients presenting with acute myocardial infarction and cardiogenic shock who are supported medically (ie. inotropes +/- intra aortic balloon pump only). N=50
Cardiogenic shock and MI wtih Impella	Observational study	Patients presenting with acute myocardial infarction and cardiogenic shock who are supported medically with Impella. N=50
Cardiogenic shock and MI wtih ECMO	Observational study	Patients presenting with acute myocardial infarction and cardiogenic shock who are supported medically with ECMO (+/- LV unloading device). N=50

Primary Outcome Measures

Name	Time	Method
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	through study completion, an average of 5 days	This will be achieved through bloods sample collection, analysis and linked to the patient's clinical diagnosis and outcome.

Secondary Outcome Measures

Name	Time	Method
Determine the extent to which the signatures and drivers of a dysfunctional immune response in CS are shared with other critical illness syndromes.	through study completion, an average of 5 days	Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.
Identify transcriptomic and chemokine/cytokine signatures at presentation that improve prognostic accuracy in patients with CS	through study completion, an average of 5 days	Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.
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	Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.
Correlate recently identified clinical phenotypes of CS with transcriptomic and inflammatory mediator signatures.	through study completion, an average of 5 days	Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.
Identity novel therapeutic targets that might modulate the dysfunctional immune response to CS - "drug discovery"	through study completion, an average of 5 days	Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.
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	Bloods samples will be collected from patients during their hospital stay and corresponding analysis performed.

Trial Locations

Locations (1)

Barts Health NHS trust; 🇬🇧 London, United Kingdom