Integrated biomarker phenotyping to reduce complications from cardiogenic shock

Cardiogenic Shock Integrated PHenotyping for Event Reduction

This project tests whether measuring inflammation, endothelial injury markers, and targeted metabolite patterns in adults with acute heart failure and cardiogenic shock can reveal biological changes that help guide care.

Quick facts

• Study type: Observational
• Enrollment: 26 (estimated)
• Ages: 18 Years to 74 Years
• Sex: All
• Sponsor: Niguarda Hospital (Academic / other)
• Locations: 1 site (Milan)
• Trial ID: NCT04323371 on ClinicalTrials.gov

What this trial studies

This is an observational cohort study of adults with acute decompensated heart failure complicated by cardiogenic shock, focused on the early time course of biological changes. Investigators will collect serial blood samples during initial hospitalization to measure inflammatory markers (IL-6), endothelial permeability markers (Angiopoietin-2), glycocalyx perturbation markers (Syndecan-1 and heparan sulfate), and perform targeted metabolomic profiling. All biomarker assays use established laboratory methods such as ELISA and mass-spectrometry–based metabolomics. The goal is to map relationships among these pathways to identify distinct biological phenotypes that may explain variable outcomes and suggest personalized approaches to management.

Who should consider this trial

Good fit: Adults aged 18–74 with acute decompensated heart failure, reduced left ventricular ejection fraction (≤35%), and early cardiogenic shock (hypotension or need for vasoactive support with signs of hypoperfusion) who are eligible for heart replacement therapy are the intended participants.

Not a fit: Patients with cardiogenic shock due to acute myocardial infarction, septic shock, symptoms present for more than six hours, or those with contraindications to heart replacement therapy are excluded and unlikely to benefit from the findings.

Why it matters

Potential benefit: If successful, this work could identify biomarker patterns that help predict who is at highest risk and ultimately guide earlier, more personalized treatments to prevent organ failure.

How similar studies have performed: Prior research has linked IL-6 and Ang-2 to worse outcomes in shock, but combining serial endothelial, inflammatory, and targeted metabolomic phenotyping in non-ACS cardiogenic shock is relatively novel and not yet validated in large cohorts.

Eligibility criteria

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

Where this trial is running

Milan

• Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda — Milan, Italy (Recruiting)

Study contacts

• Study coordinator: Nuccia Morici, MD

Conditions Heart Failure; heart failure; cardiogenic shock; endothelial glycocalyx; Angiopoietin-2; Metabolomics