Cardioprotective Effect of RIPC in Patients Undergoing TAVI

Study Overview
=================
Brief Summary
-----------------
We aim to investigate whether RIPC (remote ischemic preconditioning) is effective in the TAVI setting to reduce post-procedural myocardial damage and improve patient outcome. Accordingly, we aim to investigate whether RIPC can be introduced as an integral part of the TAVI procedure, in order to reduce post-procedural myocardial damage and potentially improve patient outcome.

Detailed Description
-----------------
Transcatheter aortic valve implantation (TAVI) is associated to myocardial injury, defined as post-procedural cardiac troponin (cTn) elevation. Earlier experiences have shown that myocardial damage can be encountered in a percentage of patients that varies from 1.5% to 17%, depending on the access route (transfemoral and transapical, respectively). The degree of rise in cTn after TAVI emerged as an independent predictor of mortality. Remote ischaemic preconditioning (RIPC) consists of brief episodes of ischaemia applied to remote organs or tissues and has shown to result in a significant reduction in postoperative troponin levels in cardiac and non-cardiac surgery patients. Lately, growing evidence suggests that post-procedural troponin decreases due to RIPC application protocols protocols and is associated with improved outcome. The patients will be divided into two Groups. In Group 1, RIPS will be induced with three cycles of Inflation of a blood-pressure cuff on the left arm to 200 mmHg for 5 min., followed by 5 min. of reperfusion while the cuff is deflated. In controls (Group 2), the cuff will be placed around the left arm without being inflated.

Official Title
-----------------
The CARE-TAVI Study: Cardioprotective Effect of Remote Ischemic Preconditioning in Patients Undergoing Transcatheter Aortic Valve Implantation

Conditions
-----------------
Effectivity of RIPC in Outcomes of TAVI Procedure

Intervention / Treatment
-----------------
* Other: without RIPC
* Procedure: RIPC


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Indication for elective TAVI following Heart Team discussion Stable hemodynamic conditions without circulatory support or catecholamines Exclusion Criteria: Myocardial infarction at least 3 months before enrollment Stroke/TIA at least 3 months before enrollment Severe chronic kidney disease (defined as a baseline serum creatinine of > 1.5 mg/dl or an estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73 m2 ) PCI at least 3 months before enrollment Abnormal (>99th percentile of laboratory cut-off) baseline values of biomarkers of myocardial ischemia (i.e. TnT, CK-MB) Abnormal NSE values at baseline (local laboratory cut-off values)
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: with RIPC<br>RIPC will be induced with three cycles of inflation of a blood-pressure cuff on the left arm to 200 mm Hg for 5 min, followed by 5 min of reperfusion while cuff deflated | Procedure: RIPC<br>* RIPC will be induced with three cycles of inflation of a blood-pressure cuff on the left arm to 200 mm Hg for 5 min, followed by 5 min of reperfusion while cuff deflated<br>* Other names: remote ischemic preconditioning;|
| Sham Comparator: without RIPC<br>the cuff will be placed around the left arm without being inflated | Other: without RIPC<br>* the cuff will be placed around the left arm without being inflated<br>* Other names: no remote ischemic preconditioning;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| post-procedural myocardial injury, defined by the geometric mean (95% CI) of the area under the curve (AUC) for cTnT | Change in cardiac troponine T (cTnT) | 72 hours after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-procedural myocardial injury | defined by the geometric mean (95% CI) of the area under the curve (AUC) for CK-MB | 72 hours after intervention | 
| Post-procedural acute kidney injury | defined according to the VARC 2 criteria | 72 hours after intervention | 
| Post-procedural brain injury | defined by the geometric mean (95% CI) of the area under the curve (AUC) for NSE | 72 hours after intervention | 
| composite of major adverse cardiac and cerebrovascular events | including death, postoperative myocardial infarction and cerebrovascular accident or stroke | discharge, at 30 days and at 1 year |