Paracrine Mechanisms of Bone Marrow Stem Cell Signalling in Chronic Heart Failure

Study Overview
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Brief Summary
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The investigators hypothesize that chronic heart failure is associated with a general stem cell dysfunction, which translates into reduced paracrine function of adult stem cells from patients with chronic heart failure as compared to patients with preserved systolic function.

Official Title
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Paracrine Mechanisms of Bone Marrow Stem Cell Signalling in Chronic Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Other: Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all participants: Before any study-specific procedures, the appropriate written informed consent must be obtained. Male and female older than 18 years of age. For the cardiac patients: Being accepted for cardiothoracic surgery with the use of open chest surgery A known left ventricular ejection fraction, either assessed by echocardiography, MUGA or MRI. If LVEF <40% a subject will be assigned to the chronic heart failure group, if LVEF >40% a subject will be assigned to the control group. For the non-cardiac patients: Accepted for orthopedic surgery (e.g. total hip replacement) at the department of orthopedic surgery. Exclusion Criteria: An unstable medical condition, defined as having been hospitalized for a non-cardiac condition within 4 weeks of screening, or otherwise unstable in the judgment of the investigator (e.g. at risk of complications or adverse events unrelated to study participation). Younger than 18 years of age. Clinical history of chronic kidney disease (at any point prior to registration). Any known hepatic disease. Recent (within 3 months) history of alcohol or illicit drug abuse disorder, based on self-report. Clinically significant abnormality in chemistry, hematology, or urinalysis parameters performed within the screening period. Participation in any investigational device or drug trial(s) or receiving investigational agent(s) within 30 days. Any condition (e.g. psychiatric illness, etc.) or situation that, in the investigator's opinion, could put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study. Legally incompetent adults, for which reason what so ever. For the non-cardiac patients: A known history of cardiovascular disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non heart failure patients<br>Patients without heart failure undergoing open chest surgery | Other: Surgery<br>* Patients undergoing surgery for either cardiac surgery or orthopedic surgery<br>|
| Orthopedic patients<br>Patients without heart failure undergoing orthopedic surgery | Other: Surgery<br>* Patients undergoing surgery for either cardiac surgery or orthopedic surgery<br>|
| Heart failure patients<br>Patients with heart failure undergoing open chest surgery. | Other: Surgery<br>* Patients undergoing surgery for either cardiac surgery or orthopedic surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Paracrine properties of bone marrow cells from patients with heart failure | To compare the paracrine properties of bone marrow-derived stem cells harvested from patients suffering chronic heart failure vs healthy subjects. In particular, we aim to determine if the cytoprotective, pro-angiogenic and anti-fibrotic effects mediated by bone marrow stem cells of heart failure patients are similar to those from healthy patients. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To study preconditioning of different bone marrow stem cells with different cytokines |  | 1 day | 
| To study in detail the temporal and spatial expression of paracrine factors in bone marrow stem cells in vitro, and to study the differences between bone marrow stem cells from patients with and without chronic heart failure |  | 1 day | 
| To evaluate potential molecular mechanisms involved |  | 1 day | 
| To find mechanisms to enhance expansion of different bone marrow stem cells in vitro |  | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, Bone marrow, Bone marrow mononuclear cells, Surgery, Orthopedic surgery, Cardiac surgery