Evolution of Molecular Biomarkers in Acute Heart Failure Induced by Shock

Study Overview
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Brief Summary
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The relationship between shock, ischemia and reperfusion (I/R) injury, hemodynamic instability, systemic inflammatory response syndrome and multiorgan failure has been extensively investigated, but there is no consensus on the trigger mechanisms of tissue injury at the molecular level. Current therapies are targeted to reduce symptoms of shock and multiorgan damage but they are unable to act at the beginning of the cascade, because of the lack of a model explaining the molecular basis of shock induced tissue injury and ensuing organ damage. The present observational study is aimed at identifying the molecular triggers of acute heart failure (HF) induced by shock and to identify inflammatory mediators and markers that are activated in shock, with a particular emphasis on the role of uncontrolled proteolytic activity.

Official Title
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Multiscale Approach to Describe the Evolution of Molecular Biomarkers in Acute Heart Failure Induced by Shock

Conditions
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Acute Heart Failure, Shock

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For patients in septic shock, Severity: SOFA score > 5 For patients in cardiogenic shock, Severity: SOFA score > 5 First blood sample available within 16 hours from admission to the ICU. Only community medical acquired septic shock. We include patients with shock symptoms and shock diagnosis occurring within the first 48 hours from hospital admission Informed Consent available Exclusion Criteria: Risk of rapidly fatal illness and death within 24 hours Patients already enrolled in other interventional studies N > 4 units of red blood cells transfused Patients treated with plasma or whole blood Active hematological malignancy Metastatic cancer Immunodepression, including transplant patients: HIV+, constitutive immune system deficiency, immunosuppressive therapy, systemic corticosteroids (aerosols allowed) Patients with pre-existing end stage renal disease needing renal replacement therapy (RRT). The introduction of continuous veno-venous hemofiltration (CVVH), from the day of admission onward is allowed. Cardiac surgery patients Cirrhosis Child C

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hemorrhagic Shock<br>Hypovolemic shock characterized by: Hypotension: systolic blood pressure < 90 mm Hg or a drop of > 40 mm Hg from baseline or mean arterial pressure < 70 mm Hg persisting despite adequate fluid resuscitation. Rapid loss of significant amount of blood Lactate levels ≥ 2 mmol/L | |
| Cardiogenic shock<br>State of inadequate circulation of blood because of ventricular failure due to acute cardiac conditions, concomitant presence of: Hypotension: systolic blood pressure < 90 mm Hg or a drop of > 40 mm Hg from baseline or mean arterial pressure < 70 mm Hg persisting despite adequate fluid resuscitation. Need for a continuous infusion of inotropic drugs Cardiac Index <2.2 L/min/m2 or use of inotropic drugs (dobutamine/isoprenaline/phosphodiesterase inhibitors or levosimendan) Signs of reduced heart function Cardiac overload or altered left/right ventricular function | |
| Septic shock<br>Septic shock is defined as sepsis-induced hypotension, defined as systolic blood pressure < 90 mm Hg or a drop of > 40 mm Hg from baseline or mean arterial pressure < 70 mm Hg persisting despite adequate fluid resuscitation. Only community medical acquired sepsis with a sepsis onset within 48 hours from hospital admission (i.e. different from nosocomial infection). Lactate levels ≥ 2mmol/L. | |
| control group<br>The control group will consist on: 5 healthy blood donors: serving only for the purposes of obtaining reference values for proteomics analysis a cohort of 20 patients hospitalized for sepsis OR cardiac syndromes not developing shock: will be recruited from patients admitted to the hospital during the study period. The clinical status of the patients will be assessed during hospitalization to ascertain shock and AHF development. Shock development will be an exclusion criteria. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression/occurrence of acute heart failure and changes in omics markers in acute phase of shock | The clinical endpoint will be Acute Heart Failure (AHF), assessed by a pool of measures/estimates of cardiac function and filling pressures, based on cardiac output monitoring, inotropic drugs requirements, left and right ventricles assessment using echocardiography. The molecular biomarkers changes will be evaluated by means of proteomics, transcriptomics and metabolomics analysis of blood samples collected at the ICU admission and within 48hr after admission. | within 48 hr after admission in ICU (acute phase of shock) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression/Occurence of Acute Heart Failure and changes in omics markers in survivors | The clinical endpoints will be: The Acute Heart Failure (AHF) assessed by a pool of measures/estimates of cardiac function and filling pressures, based on cardiac output monitoring, inotropic drugs requirements, left and right ventricles assessment using echocardiography. AHF will be at evaluated within 7 days after ICU admission. Mechanical ventilation (MV)-free days or organ support (vasopressor, continuous renal replacement therapy (CRRT), etc.) free-days Survival to ICU Prognosis at discharge from the ICU (objective - dead or alive, morbidities - and subjective) Prognosis at discharge from the hospital (objective - dead or alive, morbidities - and subjective). The changes in molecular biomarkers will be evaluated by means of proteomics, transcriptomics and metabolomics analysis of blood samples collected within 7 days after ICU admission | within 7 days after admission in ICU (patient stabilization) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiovascular instability, shock, heart failure, inflammation, biomarkers, metabolic pathways, proteolysis