Remote Ischemic Preconditioning in Patients Undergoing Isolated Aortic Valve Replacement Surgery

Study Overview
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Brief Summary
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The goal is to investigate the efficacy, safety and possible neuro- and cardioprotective effects of remote ischemic preconditioning (RIPC) in adult cardiac patients undergoing isolated aortic valve replacement surgery with a biological prosthesis. Neuropsychological evaluation preoperatively and at 30d after surgery will establish if there are any differences in neuropsychological performance between groups. A large array of biochemical markers will be analyzed from plasma samples taken at different time points. Additionally skin biopsies from the lower limb will be taken before and after performing RIPC on said limb. During the venous cannulation phase a atrial biopsy will be taken. The biochemical markers from plasma and tissue samples will be used to asses brain tissue damage, inflammation and cardiac tissue damage between groups. This will be a single center prospective randomized study with two groups. A intervention group (RIPC) and a control group. Study size is: 40 patients in total, 20 patients per group.

Official Title
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Remote Ischemic Preconditioning in Patients Undergoing Isolated Aortic Valve Replacement Surgery With a Biological Prosthesis: A Single Center Randomized Prospective Study

Conditions
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Aortic Valve Disease, Myocardial Ischemia

Intervention / Treatment
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* Procedure: Remote ischemic preconditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-emergency aortic valve replacement with a biological prosthesis with perfusion and cardiac arrest Exclusion Criteria: Recent myocardial infarction Carotid stenosis requiring intervention Any other concomitant surgical procedure Increased troponin baseline before surgery Critical ischemia of lower limbs Peripheral arterial disease (ASO, media sclerosis) Morbid obesity (Incompatible cuff-to-thigh diameter) Severe heart insufficiency Moderate to severe venous insufficiency lower limbs Recent acute stroke <90d Difference in cardioplegic protocol Diseased aorta in epiaortic ultrasound

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 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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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remote ischemic preconditioning<br>Patient will undergo normal isolated aortic valve replacement surgery with a biological prosthesis and a preoperative lower leg remote ischemic preconditioning(RIPC) phase. | Procedure: Remote ischemic preconditioning<br>* A blood pressure cuff is placed around the right leg on the level of the thigh. Randomization is performed after this, using sealed envelopes with covariate balancing for age and sex. Regardless of the outcome of the randomization the cuff is left in place so as not to give any indication of which group the patient belongs to. If the patient is randomized into the remote ischemic preconditioning group (RIPC) then four (4) cycles of five (5) minute inflation are given after induction. Each cycle is followed by a five (5) minute interval of reperfusion. Cuff pressure should be 200mgHg at least (RRsyt + 100mmgHg) during the inflation periods.<br>|
| No Intervention: Control group<br>Patient will undergo normal isolated aortic valve replacement surgery with a biological prosthesis | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychological assesment | Investigators will use a neuropsychological test battery to test our subject pre- and post-operatively. A qualified psychologist will administer the test battery. The test battery will be relatively simple but still have several different tests. These tests will include but are not limited to: - Trail Making test A & B (TMT) | 1 month postoperatively | 
| Neuropsychological assesment | Digit Span test | 1 month postoperatively | 
| Neuropsychological assesment | Rey Auditory Verbal Learning Test (RAVLT) | 1 month postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammation markers analysed from plasma and tissue samples | A bioplex/multiplex assay of systemic inflammatory response markers and other cytokines including but not limited to: Tumor Necrosis Factor-a, Interleukin-1b, -2, -4, -5, -6. C-Reactive Protein, Hypoxia inducible Factor -1. | A day before surgery, during surgery, 24hour and 48hour postoperatively | 
| Tissue specific markers analysed from plasma | A bioplex/multiplex assay of neuronal and cardiac tissue specific biomarkers including but not limited to: S-100b, Glial Fibrillary acidic protein, Neuron Specific enolase, Troponin-I, Brain Natriuretic Peptide, Creatinine Kinase - MB | A day before surgery, during surgery, 24hour and 48hour postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Remote ischemic preconditioning, Neuroprotection