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Cardiogenic Shock Integrated PHenotyping for Event Reduction

Recruiting
Conditions
Heart Failure
Interventions
Diagnostic Test: ELISA
Registration Number
NCT04323371
Lead Sponsor
Niguarda Hospital
Brief Summary

The purpose of this study is to better understand the time course of different biological mechanisms involved in acute decompensated heart failure complicated by cardiogenic shock throughout the evaluation of changes and the relationship among markers of inflammation (IL-6) and markers of increased endothelial permeability (Ang-2) or endothelial glycocalyx perturbation (Syndecan-1 and HS) and throughout a targeted metabolomic approach.

Detailed Description

Cardiogenic shock (CS) is a heterogenous syndrome with in-hospital mortality up to 60%, that, unfortunately, has remained stagnant over the time, despite observed improvements with pharmacological and non-pharmacological approach, even though only in terms of haemodynamic stabilization.

While very early mortality in CS is largely related to sudden and severe circulation failure, subsequent death is strongly influenced by activation of neurohumoral and inflammatory response leading to multiorgan failure. Previous studies on CS have almost exclusively been focused on CS following an acute coronary syndrome (ACS). Patients with acutely decompensated heart failure (ADHF) represent a different pathophysiologic phenotype compared with acute coronary syndrome (ACS) patients, which may lead to a differential response to device therapy.

In the face of complex biological phenomena guidelines are incapable of distinguishing the underlying pathophysiological mechanisms and give us input to standardize, whereas there is an unmet need for a personalized medicine.

The evaluation of changes and the relationship among markers of inflammation (IL-6) and markers of increased endothelial permeability (Ang-2) or endothelial glycocalyx perturbation (Syndecan-1 and HS) and an exploratory analysis throughout targeted metabolomics may help us to better understand the time course of different biological mechanisms involved in CS.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
26
Inclusion Criteria
  • Age ≥ 18 and < 75, men and women;
    1. Systolic blood pressure (SBP) < 90mmHg or mean arterial pressure (MAP) < 60 mmHg, after an appropriate fluid challenge if there is no sign of overt fluid overload; OR 2) need of vasoactive agents to maintain SBP > 90 mmHg or MAP > 60 mmHg.
  • Reduced ejection fraction (left ventricle systolic function ≤35%).
  • Moreover, eligible patients have to fit at least ONE of the following criteria/items of overt hypoperfusion: altered state of consciousness; sweaty and cold skin; mixed venous oxygen saturation < 60%; arterial lactates > 2 mmol/L; oliguria < 0.5 ml/Kg/h for at least 6 hours.
  • Eligible patients shouldn't have contraindications to heart replacement therapy (HRT).
Exclusion Criteria

The participant will not be enrolled if ANY of the following criteria will be detected:

  • Cardiogenic shock symptoms beyond 6 hours.
  • Septic shock with evident septic focus.
  • Cardiogenic shock due to acute myocardial infarction.
  • Cardiogenic shock due to acute myocarditis.
  • Cardiogenic shock due to pulmonary thromboembolism.
  • Reiterating major arrhythmias: VT or VF or AF, with ventricular rate > 160 bpm.
  • Severe aortic valve disease.
  • Obstructive hypertrophic cardiomyopathy or constrictive pericarditis or severe heart failure due to congenital heart disease
  • Severe peripheral vascular disease that contraindicates mechanical support insertion.
  • Cardiogenic shock secondary to either cardiac or non-cardiac surgery.
  • Comorbidities with ominous prognosis (life expectancy < 1 year).
  • Estimated glomerular filtration rate severely impaired before enrolment (eGFR<30 ml/min/1.73 m2) or severe chronic obstructive pulmonary disease (COPD) or liver cirrhosis.
  • Pregnant, lactating or subjects planning pregnancy during the course of the trial.

Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Acute decompensated heart failureELISApatients admitted with Acute decompensated heart failure Complicated by cardiogenic shock
Primary Outcome Measures
NameTimeMethod
Value of Syndecan-13 years

Endothelial glycocalyx perturbation. Unit of measure: ng/mL.

Value of Interleukin 6 (IL-6)3 years

Markers of inflammation. Unit of measure: pg/mL.

Value of Angiopoietin 2 (Ang-2)3 years

Markers of endothelial permeability. Unit of measure: ng/mL.

Value of Heparan sulfate (HS)3 years

Endothelial glycocalyx perturbation: Unit of measure: ug/mL.

Metabolomics profiling3 years

Exporatory assessment of targeted metabolomics through the quantification of almost 180 molecules, including acylcarnitines, amino acids and biogenic amines, hexoside, sphingolipids and glycerophospholipids.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

🇮🇹

Milano, Italy

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