Structural Valve Intervention Research Program

Theme leader

Associate Professor Dion Stub

Structural and Coronary Interventional Cardiologist A/Prof Dion Stub is passionate about novel therapies in the treatment of valvular heart disease, damage or disease pertaining to the four valves that regulate blood flow through the heart’s chambers. He holds a particular interest in transcatheter aortic valve implantation (TAVI), a minimally invasive procedure to replace thickened aortic valves that can't fully open.

As part of his clinical fellowship training he spent two years as a post-doctorate clinical fellow, first at the University of Washington in Seattle, and then working with Prof John Webb, an international pioneer in TAVI, at St Paul’s Hospital in Vancouver.

Here in Melbourne, together with fellow Cardiologists A/Prof Tony Walton and Dr Shane Nanayakkara, A/Prof Dion Stub helped established the ACE Consortium, a collaborative structural heart registry involving the Alfred, Cabrini and Epworth hospitals. The registry allows monitoring and assessing clinical outcomes data for all interventional structural heart procedures across the three sites, driving measurable quality improvement in outcomes.

This is now the largest combined investigator-led structural heart procedure registry in Australia, and is currently running the largest randomised investigator-initiated study of TAVI in Australia (ACE PROTAVI).

ACE PROTAVI

A randomised, double blind placebo-controlled trial in patients undergoing TAVI, comparing routine protamine administration versus selective protamine administration.

Chief Investigators

PIs A/Prof Tony Walton, A/Prof Dion Stub, Dr Shane Nanayakkara

Funding source

Epworth and Cabrini Research Grants

Estimated completion date

June 2024

Background

Minimally invasive TAVI procedures involve a replacement aortic valve being implanted through a catheter from the groin, offering fast and painless recovery compared to open heart surgery. A small but real risk of TAVI is major blood loss from the incision site, as blood thinning agents such as heparin are used routinely during the procedure.

This risk may be reduced by neutralising heparin’s effects through injection with its antagonist protamine following procedures. The use of protamine currently is at the Cardiologist’s discretion; there are no formal treatment guidelines, and many elect not to deliver post-procedural protamine.

Aim

The ACE PROTAVI study is designed to deliver robust evidence that will inform future guidelines around protamine use after TAVI, with the potential to improve clinical outcomes for patients, and reduce wastage of resources.

Specifically, it will determine if routine protamine administration, compared with selective protamine administration, reduces the risk of procedural haemostasis failure and reduces the time to haemostasis (TTH): elapsed time after sheath removal and first observed and confirmed arterial haemostasis.

Methods

A randomised, double blind placebo-controlled trial in patients undergoing TAVI, comparing routine protamine administration versus selective protamine administration.

Study sites include the Alfred Hospital, Cabrini Hospital and Epworth Hospital.

Outputs to date

Baratchi S, Zaldivia MTK, Wallert M, Loseff-Silver J, Al-Aryahi S, Zamani J, Thurgood P, Salim A, Htun NM, Stub D, Vahidi P, Duffy SJ, Walton A, Nguyen TH, Jaworowski A, Khoshmanesh K, Peter K. Transcatheter Aortic Valve Implantation Represents an Anti-Inflammatory Therapy Via Reduction of Shear Stress-Induced, Piezo-1-Mediated Monocyte Activation. Circulation. 2020 Sep 15;142(11):1092-1105. doi: 10.1161/CIRCULATIONAHA.120.045536.

Zhou JY, Liew D, Duffy SJ, Walton A, Htun N, Stub D. Cost-Effectiveness of Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients With Severe Aortic Stenosis. Heart Lung Circ. 2021 Apr;30(4):547-554. doi: 10.1016/j.hlc.2020.09.934.

Navani RV, Quine EJ, Duffy SJ, Htun NM, Nanayakkara S, Walton AS, Stub D. Relation of Preprocedure Platelet-to-Lymphocyte Ratio and Major Adverse Cardiovascular Events Following Transcatheter Aortic Valve Implantation for Aortic Stenosis. Am J Cardiol. 2022 Jan 15;163:65-70. doi: 10.1016/j.amjcard.2021.10.008.

Zhou J, Liew D, Duffy SJ, Walton A, Htun N, Stub D. Cost-effectiveness of transcatheter aortic valve implantation compared to surgical aortic valve replacement in the intermediate surgical risk population. Int J Cardiol. 2019 Nov 1;294:17-22. doi: 10.1016/j.ijcard.2019.06.057. Epub 2019 Jun 21. PMID: 31255453.