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

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

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.

Study Overview

• Status: Unknown
• Conditions: Transcatheter Aortic Valve Implantation Prosnosis and Complications
• Intervention / Treatment: Diagnostic test: venous blood withdrawl

Detailed Description

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.

REFERENCES:

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2. Theroux P, Armstrong PW, Mahaffey KW, Hochman JS, Malloy KJ, Rollins S, Nicolau JC, Lavoie J, Luong TM, Burchenal J, Granger CB. Prognostic significance of blood markers of inflammation in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty and effects of pexelizumab, a C5 inhibitor: a substudy of the COMMA trial. Eur Heart J 2005;26:1964-1970.
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7. Clarizia NA, Manlhiot C, Schwartz SM, et al. Improved outcomes associated with intraoperative steroid use in high-risk pediatric cardiac surgery. Ann Thorac Surg. 2011;91(4):1222-1227.
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10. Sinning JM1, Scheer AC, Adenauer V, Ghanem A, Hammerstingl C, Schueler R, Müller C, Vasa-Nicotera M, Grube E, Nickenig G, Werner N. Systemic inflammatory response syndrome predicts increased mortality in patients after transcatheter aortic valve implantation. Eur Heart J. 2012 Jun;33(12):1459-68.
11. Masson JB1, Kovac J, Schuler G, Ye J, Cheung A, Kapadia S, Tuzcu ME, Kodali S, Leon MB, Webb JG. Transcatheter aortic valve implantation: review of the nature, management, and avoidance of procedural complications. JACC Cardiovasc Interv. 2009 Sep;2(9):811-20.
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• Study Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

Study Locations

• Israel
  • Tel Aviv, Israel
    • Recruiting
    • Tel Aviv Medical Center
    • Contact: Zach Rozenbaum, MD; Phone Number: 972-3-6973313; Email: zachr@tlvmc.gov.il
    • Principal Investigator: Zach Rozenbaum, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All patients who undergo TAVR

Description

Inclusion Criteria:

• 18 years of age and older
• Capable of giving informed consent
• Undergoing TAVR

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group; patients undergoin transcatheter aortic valve implantation	Diagnostic test: venous blood withdrawl; patients will be asked for a venous blood sample
Control group; patient undergoing diagnostic coronary angiography	Diagnostic test: venous blood withdrawl; patients will be asked for a venous blood sample

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 1, 2017
• Primary Completion (ANTICIPATED): August 1, 2017
• Study Completion (ANTICIPATED): December 1, 2017

Study Registration Dates

• First Submitted: February 8, 2017
• First Submitted That Met QC Criteria: February 8, 2017
• First Posted (ESTIMATE): February 9, 2017

Study Record Updates

• Last Update Posted (ESTIMATE): February 9, 2017
• Last Update Submitted That Met QC Criteria: February 8, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: TAVR; tryptse; mast
• Other Study ID Numbers: 0678-15-TLV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Only the principle investigator will have access to IPD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No