Cardiogenic Shock
Conditions
Keywords
ACS,, Cardiogenic Shock, ECMO, Impella, Gene Expression, Endotype
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.
Interventions
OTHERObservational study
Blood sampling and clinical data collection
Sponsors
University of Oxford
Barts & The London NHS Trust
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United Kingdom
Contacts
Primary ContactAlastair Proudfoot
Backup ContactMervyn Andiapen
Outcome results
None listed