Tryptase Level as a Marker of Complications in Transcatheter Aortic Valve Replacement

Study Overview
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Brief Summary
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An association between mast cells and outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) has not been studied to our knowledge. We aim to characterize tryptase levels dynamics during TAVR; Demonstrate whether tryptase level post-TAVR can be used as a prognostic marker.

Detailed Description
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Inflammation is known to have a detrimental effect on outcome of patients with myocardial infarction (MI) [1, 2] as well as reperfusion injury (RI) [3]. Previous trials have shown correlation between the extent of an inflammatory response and postoperative complications and worse outcomes in patients undergoing cardiac surgery [4, 5, 6, 7] including valve replacement [8]. Transcatheter aortic valve replacement (TAVR) may be associated with inflammation [5, 9] as well. A few possible mechanisms may be responsible, such as tissue injury due to mechanical trauma, vascular complications, and possible suboptimal organ perfusion due to bleeding, ventricular pacing, balloon valvuloplasty, deployment, post-dilatation, or repositioning of the valve prosthesis [10]. Accumulating data show that peri-procedural inflammation is associated with worse outcomes and complications of TAVR [11, 12, 13, 14, 15], and may predict increased mortality in patients after TAVR [16, 17, 18, 19, 20]. Inflammation is a complex process and includes many types of cells including mast cells. The association between mast cells, as part of the inflammatory process, and RI has been thoroughly studied. Mast cells have been linked to RI in many organs [21], contributing to insult to the myocardium. This association has been suggested from animal models [22, 23, 24] as well as recent human trials which showed that tryptase, an abundant protease found in mast cell granules, is elevated in ST segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI) [25]. Therefore, it is reasonable to assume that mast cells may have a role in the inflammation process involved in patients undergoing TAVR. Moreover, such association with mast cells may be used to predict adverse outcomes. To our knowledge, an association between mast cells and outcomes of patients undergoing TAVR has not been studied. METHODS Peripheral venous blood from 30 patients undergoing TAVR will be withdrawn to examine tryptase levels, as a marker of mast cell activity. Blood samples will be taken at 0 hours (before the procedure) and a second sample will be taken up to 2 hours post-procedure. CRP will be examined in each patient pre and post TAVR. Tryptase levels will be examined in 10 patients undergoing diagnostic coronary angiography. PRIMARY OBJECTIVE We aim to: 1. Characterize tryptase levels dynamics during TAVR 2. Demonstrate whether tryptase level post-TAVR can be used as a prognostic marker. Primary outcome - mortality at 1 year Secondary outcomes - Major complications at 7 days and 30 days, including death, major stroke, acute kidney injury, paravalvular regurgitation, permanent pacemaker implantation, coronary artery obstruction, heart block, vascular injury, pericardial hemorrhage. 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Ischemia reperfusion injury and histamine release in isolated and perfused guinea-pig heart: pharmacological interventions. Agents Actions. 1990 Apr;30(1-2):198-201 Frangogiannis NG1, Perrard JL, Mendoza LH, Burns AR, Lindsey ML, Ballantyne CM, Michael LH, Smith CW, Entman ML. Stem cell factor induction is associated with mast cell accumulation after canine myocardial ischemia and reperfusion. Circulation. 1998 Aug 18;98(7):687-98. Shaomin Chen, Di Mu, Ming Cui, Chuan Ren, Shu Zhang, Lijun Guo, and Wei Gao. Dynamic changes and clinical significance of serum tryptase levels in STEMI patients treated with primary PCI. Biomarkers. 2014 Nov;19(7):620-4.

Official Title
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Tryptase Levels as a Marker of Mast Cell Activity and the Prognostic Implication in Patients Post Transcatheter Aortic Valve Replacement

Conditions
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Transcatheter Aortic Valve Implantation Prosnosis and Complications

Intervention / Treatment
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* Diagnostic Test: venous blood withdrawl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age and older Capable of giving informed consent Undergoing TAVR Exclusion Criteria: None

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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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 |
| --- | --- |
| Study group<br>patients undergoin transcatheter aortic valve implantation | Diagnostic Test: venous blood withdrawl<br>* patients will be asked for a venous blood sample<br>|
| Control group<br>patient undergoing diagnostic coronary angiography | Diagnostic Test: venous blood withdrawl<br>* patients will be asked for a venous blood sample<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | mortality | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | mortality at 7 and 30 days | 7 and 30 days | 
| Complications | Post procedural complications - major stroke, acute kidney injury, paravalvular regurgitation, permanent pacemaker implantation, coronary artery obstruction, heart block, vascular injury, pericardial hemorrhage | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TAVR, tryptse, mast