GOLDILOCS
Genomic determinants of outcome in cardiogenic shock
Overview
Genomic determinants of outcome in cardiogenic shock
As with other critical illness syndromes (e.g. sepsis, ARDS) the host
response to the clinically defined syndrome of cardiogenic shock may be heterogeneous, with two or more biological endotypes associated with differential outcomes (in both the short
and longer term) and treatment responses.
Thus, identification of biological markers of susceptibility to, and outcome from CS may identify groups of patients who would either optimally respond to supportive therapies such as mechanical circulatory support; or in whom such expensive and resource consuming interventions may be futile 14.
In addition, an improved understanding of the biological pathways associated with cardiogenic shock susceptibility,severity or outcome may identify novel therapeutic targets for intervention 14. Finally,
identification of subgroups of patients with differential outcomes or responses to mechanical circulatory support may help enrich future clinical trials of current or emerging therapies in cardiogenic shock, facilitating study design and recruitment, which has hitherto been challenging
Inclusion criteria
AMI with CS
• Presentation within 24 hours of onset of ACS symptoms.
• CS can only be secondary to ACS (Type 1 MI STEMI or N-STEMI)
• Planned or completed revascularisation of culprit coronary artery
• CS will be defined by:
• Systolic blood pressure <90 mmHg for at least 30 minutes or a requirement
for a continuous infusion of vasopressor or inotropic therapy to maintain
systolic blood pressure > 90 mmHg.
• Clinical signs of pulmonary congestion, or signs of impaired organ perfusion
with at least one of the following manifestations:
o altered mental status.
o cold and clammy skin and limbs.
o oliguria with a urine output of less than 30 ml per hour.
o elevated arterial lactate level of >2.0 mmol per litre.
Samples will also be collected from 2 additional patient cohorts as a control /
comparator group:
AMI without CS
● Patients presenting within 24 hours of onset of ACS symptoms but without CS
with evidence of left anterior descending coronary artery disease at angiography
Non-Ischemic CS
● Patients presenting with non-ischaemic aetiologies of CS i.e., inflammatory
acute cardiomyopathy/ septic cardiomyopathy/ myocarditis (Clinical diagnosis as
confirmed by attending clinician based on clinical history, ECG changes,
echocardiography, low likelihood of culprit coronary disease/normal coronary arteries,
troponin rise, CRP. MRI not required for diagnosis.)
Exclusion criteria
Any of the inclusion criteria not met and:
• Age <18 and ≥80 years.
• Unwilling to provide informed consent or appropriate consent from a
nominated consultee or personal consultee
• Significant systemic illness resulting in life expectancy < 12 months
• Known dementia of any severity
• Comorbidity with life expectancy <12 months.
• Out-of-hospital cardiac arrest (OHCA) and any of the following:
o No return of spontaneous circulation (ongoing resuscitation effort)
o pH <7
o Without bystander CPR within 10 minutes of collapse
• Patients with a Haemoglobin level of <8g/dl at enrolment
• Co-enrolment in any study that may impact upon gene expression
CS Arms
• Echocardiographic evidence of mechanical cause for CS: e.g. ventricular
septal defect, LV-free wall rupture, ischaemic mitral regurgitation.
• Shock predominantly due to another cause (e.g refractory septic vasoplegia,
septic shock, haemorrhagic/hypovolaemic shock, anaphylaxis, and
obstructive shock).
• Arterial lactate level of <2.0 mmol per litre.
Intervention
Blood collected at time 0, 24 hours and day 5
