Volume Number May 2023
ISSN: 1774-024X (Print)
19 01 ISSN: 1969-6213 (Online)
www.eurointervention.com
EuroIntervention
EXPERT CONSENSUS
26 The 17th expert consensus document of the
European Bifurcation Club — techniques to
preserve access to the side branch during
stepwise provisional stenting
M. Pan, G. Stankovic, et al
37 Management of coronary artery disease in
patients undergoing transcatheter aortic valve
implantation. A clinical consensus statement
from the European Association of Percutaneous
Cardiovascular Interventions in collaboration
with the ESC Working Group on Cardiovascular
Surgery
G. Tarantini, L. Sondergaard, et al
53 Radiation protection for healthcare professionals
working in catheterisation laboratories during
pregnancy: a statement of the European
Association of Percutaneous Cardiovascular
Interventions (EAPCI) in collaboration with the
European Heart Rhythm Association (EHRA), the
European Association of Cardiovascular Imaging
(EACVI), the ESC Regulatory Affairs Committee
and Women as One
S. Manzo-Silberman, A. Chieffo, et al
CORONARY INTERVENTIONS
63 Single antiplatelet therapy directly after
percutaneous coronary intervention in non-ST-
segment elevation acute coronary syndrome
patients: the OPTICA study
N.M.R. van der Sangen, J.P.S. Henriques, et al
73 Ultrasound-guided femoral access in patients
with vascular closure devices: a prespecified
analysis of the randomised UNIVERSAL trial
M.-A. d’Entremont, S.S. Jolly, et al
80 Changes in post-PCI optimisation strategies with
post-procedural FFR followed by IVUS
T. Neleman, J. Daemen, et al
INTERVENTIONS FOR VALVULAR
DISEASE AND HEART FAILURE
83 Clinical outcomes of the ACURATE neo2
transcatheter heart valve: a prospective,
multicentre, observational, post-market
surveillance study
W.-K. Kim, L. Sondergaard, et al
93 A bench study of balloon-expandable valves for
the treatment of self-expanding valve failure
M. Akodad, J. Sathananthan, et al
103 Oesophageal and gastric injuries caused by
transoesophageal probe manipulation in patients
undergoing transcatheter edge-to-edge repair
for tricuspid regurgitation
T. Kuecken, C. Butter, et al
EDITORIALS
13 The conundrum of percutaneous coronary
intervention without aspirin: a call for clarity
R. Piccolo, G. Esposito
15 A UNIVERSAL call for the optimisation of
vascular closure devices
H.L. Dauerman, T. Gupta
18 ACURATE neo2: jack of all trades or master of
none?
J.-M. Sinning
20 Continuously renewing and at the cutting edge:
Welcome to EuroPCR 2023!
T. Cuisset, J. Fajadet, et al
DEBATE
23 Invasive functional testing in the cath lab as
a routine investigation in INOCA: pros and cons
B. De Bruyne, N. Curzen, et al
 EDITORIAL

EuroIntervention 2023
MAY 2023
VOLUME 19, Issue 1

The new European Bifurcation Club expert

consensus document; an EAPCI/ESC expert
consensus on the management of coronary
artery disease in patients undergoing TAVI;
an EAPCI position statement on radiation
protection for healthcare workers during
pregnancy; debating invasive coronary
testing in INOCA patients; single
antiplatelet therapy after PCI; ultrasound-
guided femoral access in the UNIVERSAL
trial; oesophageal and gastric injuries after
tricuspid TEER; and more
Davide Capodanno, Editor-in-Chief

A few months ago, I wrote an editorial about ChatGPT, a  chatbot that I thought
was an interesting and niche discovery. However, I couldn’t foresee the revolution this
technology has caused – and which everyone is now talking about – nor the fear that
has accompanied this attention. As with all new technologies, the classic trajectory
of enthusiasm followed by habituation, annoyance, suspicion, and fear may apply to
ChatGPT. Nevertheless, I believe this technology is here to stay and could make our
lives easier.
What impresses me about ChatGPT are the many spin-offs already generated from
GPT-4, the latest iteration, promising to accompany us in any playful or non-playful
activity. Artificial intelligence is bringing about a rapid revolution, with potential appli-
cations in dozens, if not hundreds of different fields. At the time I’m writing to you,

1
EuroIntervention 2023

things are moving so fast that I find it hard not only to imagine the future but also to
understand the present.
As an example of an unexpected application, think of EuroPCR, which now offers sev-
eral sessions designed by faculty acting as “producers”. This year, I was asked to write
one on multivessel disease, and while I designed my session many months ago – so you
shouldn’t worry if you think that it was accomplished using artificial intelligence behind
the scripting – I recently discovered that it could have been done that way. You could
easily educate ChatGPT to write a logical, fluid and coherent session, organising and cri-
tiquing the content. Of course, you must feed the bot with learning objectives, key takea-
ways, and the structure of your idea, but the bot learns rapidly, very rapidly.
Although it still requires human input, it is a romantic, and probably unrealistic, notion
to believe this will always be the only way to produce something of educational value.
ChatGPT may still be primitive in producing content, but it is already strong in organisa-
tion and coherence. We, as humans, will be able to focus on more creative and futuristic
projects while the bot will handle basic tasks.
Isn’t this what we call progress, after all?
But right now, this is the month of EuroPCR, and as usual, there is a special issue of
the Journal to describe (and for those attending the Course, they will be able to actually
hold and touch the Journal, as they will receive the traditional free copy).
We’ll begin with a  debate, and for this issue, we’ve invited four authors who, while
they concur that ischaemia with non-obstructive coronary arteries (INOCA) is often mis-
managed, part ways on the routine use of invasive coronary testing for this condition.
Bernard De Bruyne and Marta Belmonte argue that in a world where we can offer a thor-
ough functional investigation of the coronary microcirculation, we should, especially
given the technical and theoretical advances in the domain. In contrast, Nick Curzen and
Richard J. Jabbour raise concerns about the limitations and the risk-benefit ratio of wire-
based testing, as well as the concurrent advances in non-invasive testing, suggesting that
wire-based testing is not yet optimised nor fully reliable.
As we said, it is the EuroPCR 2023 edition, and we have not one but three expert con-
sensus papers for you.
First, in coronary interventions, we begin with the European Bifurcation Club’s 17th
expert consensus document in which authors Manuel Pan, Goran Stankovic and colleagues
present the various techniques used to preserve access to the side branch during step-
wise provisional stenting. The authors discuss the evidence, old and new, on jailed wires,
and then, survey current approaches to side branch rewiring and the existing rescue
strategies, including discussions on advances in single and dual lumen microcatheters,
rewiring in challenging anatomies and more. They demonstrate that while restoring side
branch patency can be difficult, stepwise provisional stenting can be adopted for most
complex bifurcation lesions.
Our next expert consensus, in interventions for valvular disease, is a  collaboration of
the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and the
European Society of Cardiology (ESC) Working Group on Cardiovascular Surgery in which
authors Giuseppe Tarantini, Lars Sondergaard and colleagues discuss the management of
coronary artery disease in patients with severe aortic stenosis undergoing transcatheter
aortic valve implantation (TAVI). After a  review of the available evidence on the topic,
they propose a rationale for both the preprocedural diagnostic evaluation and the indica-
tions for percutaneous revascularisation in this patient population, including a discussion
on the choice of transcatheter heart valves (THV) and commissural alignment techniques
for future redo-TAVI.
Our third expert consensus is on the radiation exposure experienced by healthcare
professionals working in catheterisation labs during pregnancy. As we are aware, this
is a  non-negligible reality and can be a  deterrent to women pursuing careers in inter-
ventional cardiology. In an effort to improve both workplace safety and equity, Stéphane

2
 EuroIntervention 2023
Manzo-Silberman, Alaide Chieffo and colleagues present this EAPCI position statement
in collaboration with the European Heart Rhythm Association (EHRA), the European
Association of Cardiovascular Imaging (EACVI), the ESC Regulatory Affairs Committee
and Women as One on radiation risk and the current data on the experiences of cardio-
logists who continue to work in cath labs during pregnancy.
In a  clinical research article in coronary interventions, Niels M.R. van der Sangen,
José P.S. Henriques and colleagues share the results of the OPTICA study in which they
examined the safety and feasibility of ticagrelor or prasugrel monotherapy directly follow-
ing percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation
acute coronary syndrome and ask whether direct P2Y12 inhibitor monotherapy is a feas-
ible alternative to dual antiplatelet therapy. The results from this pilot trial show no
overt safety concerns and indicate that large-scale randomised trials are warranted. In an
accompanying editorial, Raffaele Piccolo and Giovanni Esposito discuss both the limita-
tions and the potential that this proof-of-concept study suggests.
Next in coronary interventions, Marc-André d’Entremont, Sanjit S. Jolly and colleagues
look at the safety of ultrasound-guided femoral access for patients receiving a  vascular
closure device. In their subgroup analysis of the UNIVERSAL trial, they show that at
30 days there were fewer bleeding and vascular complications for patients who had ultra-
sound-guided versus non-ultrasound-guided femoral access. In an accompanying editorial
Harold L. Dauerman and Tanush Gupta discuss these results and the revival of interest in
femoral access in the context of two other recent trials.
In a  research correspondence, Tara Neleman, Joost Daemen and colleagues report on
changes in operator-defined optimisation strategies within the FFR REACT trial after dis-
closure of the post-PCI fractional flow reserve (FFR) pullback data and before intravas-
cular ultrasound acquisition. Through a dedicated questionnaire given to operators, they
found that the optimisation strategy was altered in over 53% of vessels after intravascu-
lar ultrasound evaluation, as compared to the planned treatment strategy based on FFR
pullback data alone.
In interventions for valvular disease and heart failure, Won-Keun Kim, Lars Sondergaard
and colleagues present the ACURATE neo2 post-market clinical follow-up study, look-
ing at patients with severe aortic stenosis and at high operative risk treated with the
ACURATE neo2 transcatheter aortic valve in routine clinical practice. The study included
30-day primary safety endpoints of all-cause mortality and the 30-day data on hypoatten-
uated leaflet thickening, permanent pacemaker implantation, valve haemodynamics and
paravalvular leakage. This article is accompanied by an editorial by Jan-Malte Sinning.
In a translational research article, Mariama Akodad, Janarthanan Sathananthan and col-
leagues consider the use of a balloon-expandable valve for treating a failed self-expand-
ing valve. They assess the neoskirt height, degree of leaflet overhang, leaflet deflection,
THV expansion and valve performance at two different implant depths of redo-TAVI using
the SAPIEN 3 Ultra within the ACURATE neo2 THV. Redo-TAVI with the SAPIEN 3 within
an ACURATE neo2 has favourable hydrodynamics and moderate leaflet overhang, with
the design of the ACURATE neo2 facilitating coronary flow and access.
Oesophageal injuries after tricuspid transcatheter edge-to-edge repair (TEER) are
common, but what provokes them? In a  research correspondence, Tanja  Kuecken,
Christian  Butter and colleagues report on the incident rate and risk factors for both
oesophageal and gastric injury caused by echocardiographic probe manipulation during
TEER for tricuspid regurgitation. Their analysis looks at procedural duration, positional
changes and lesion location and severity with unexpected results.
And now, just before we explore the articles themselves, we’d like to turn to the special
EuroPCR editorial by the EuroPCR Course Directors, EAPCI President and PCR Chairs
in which they highlight the abundant opportunities on offer at EuroPCR 2023 (of which
this journal is the official publication). They offer a whirlwind tour of the Course educa-
tional programme, underlining how EuroPCR captures the fundamental spirit that brings
us together as a community and as health practitioners.

3
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 CONTENTS

EuroIntervention 2023
EDITORIALS
13 The conundrum of percutaneous coronary intervention without aspirin: a call for clarity
Raffaele Piccolo, Giovanni Esposito
15 A UNIVERSAL call for the optimisation of vascular closure devices
Harold L. Dauerman, Tanush Gupta
18 ACURATE neo2: jack of all trades or master of none?
Jan-Malte Sinning
20 Continuously renewing and at the cutting edge: Welcome to EuroPCR 2023!
Thomas Cuisset, Nicolas Dumonteil, Nieves Gonzalo, Emanuele Barbato, Bernard Prendergast, William Wijns, Jean Fajadet, on
behalf of the EuroPCR Course Directors, EAPCI President and PCR Chairs

DEBAT E
23 Invasive functional testing in the cath lab as a routine investigation in INOCA: pros and cons
Bernard De Bruyne, Marta Belmonte, Richard J. Jabbour, Nick Curzen

EXPERT CONSENSUS
26 The 17th expert consensus document of the European Bifurcation Club – techniques to preserve access to the side branch
during stepwise provisional stenting
Manuel Pan, Jens Flensted Lassen, Francesco Burzotta, Soledad Ojeda, Remo Albiero, Thierry Lefèvre, David Hildick-Smith,
Thomas W. Johnson, Alaide Chieffo, Adrian P. Banning, Miroslaw Ferenc, Olivier Darremont, Yiannis S. Chatzizisis, Yves Louvard,
Goran Stankovic
37 Management of coronary artery disease in patients undergoing transcatheter aortic valve implantation. A clinical consensus
statement from the European Association of Percutaneous Cardiovascular Interventions in collaboration with the ESC Working
Group on Cardiovascular Surgery
Giuseppe Tarantini, Darren Mylotte, Ivan Wong, Gintautas Bieliauskas, Martin Czerny, Nikolaos Bonaros, Alessandro Parolari,
Darius Dudek, Didier Tchétché, Hélène Eltchaninoff, Ole De Backer, Giulio Stefanini, Lars Sondergaard
53 Radiation protection for healthcare professionals working in catheterisation laboratories during pregnancy: a statement of the
European Association of Percutaneous Cardiovascular Interventions (EAPCI) in collaboration with the European Heart
Rhythm Association (EHRA), the European Association of Cardiovascular Imaging (EACVI), the ESC Regulatory Affairs
Committee and Women as One
Stéphane Manzo-Silberman, Maite Velázquez, Sonya Burgess, Sheila Sahni, Patricia Best, Roxana Mehran, Emanuela Piccaluga,
Laura Vitali-Serdoz, Amy Sarma, Israel Moshe Barbash, Josepa Mauri, Piotr Szymański, Lynne Hinterbuchner, Giulio Stefanini,
Alessia Gimelli, Pal Maurovich-Horvat, Lucas Boersma, Gill Louise Buchanan, Gianluca Pontone, Lene Holmvang, Nicole Karam,
Antoinette Neylon, Marie-Claude Morice, Christophe Leclercq, Giuseppe Tarantini, Dariusz Dudek, Alaide Chieffo

CORONARY INTERVENTIONS
CLINICAL RESEARCH
63 Single antiplatelet therapy directly after percutaneous coronary intervention in non-ST-segment elevation acute coronary
syndrome patients: the OPTICA study
Niels M.R. van der Sangen, Bimmer E.P.M. Claessen, I. Tarik Küçük, Alexander W. den Hartog, Jan Baan, Marcel A.M. Beijk,
Ronak Delewi, Tim P. van de Hoef, Paul Knaapen, Jorrit S. Lemkes, Koen M. Marques, Alexander Nap, Niels J.W. Verouden,
M. Marije Vis, Robbert J. de Winter, Wouter J. Kikkert, Yolande Appelman, José P.S. Henriques

5
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 CONTENTS

EuroIntervention 2023
CLINICAL RESEARCH
73 Ultrasound-guided femoral access in patients with vascular closure devices: a prespecified analysis of the randomised
UNIVERSAL trial
Marc-André d’Entremont, Sulaiman Alrashidi, Omar Alansari, Bradley Brochu, Laura Heenan, Elizabeth Skuriat, Jessica Tyrwhitt,
Michael Raco, Michael B. Tsang, Nicholas Valettas, James Velianou, Tej Sheth, Matthew Sibbald, Shamir R. Mehta,
Natalia Pinilla-Echeverri, Jon-David Schwalm, Madhu K. Natarajan, Andrew Kelly, Elie Akl, Sarah Tawadros, Mercedes Camargo,
Walaa Faidi, John Bauer, Rachel Moxham, James Nkurunziza, Gustavo Dutra, Jose Winter, Sanjit S. Jolly

RESEARCH CORRESPONDENCE
80 Changes in post-PCI optimisation strategies with post-procedural FFR followed by IVUS
Tara Neleman, Frederik T.W. Groenland, Annemieke C. Ziedses des Plantes, Alessandra Scoccia, Laurens J.C. van Zandvoort,
Eric Boersma, Rutger-Jan Nuis, Wijnand K. den Dekker, Roberto Diletti, Jeroen Wilschut, Felix Zijlstra, Nicolas M. Van Mieghem,
Joost Daemen

IN T E R V EN T I O N S F O R VA LV UL A R D I SE A SE A ND HE A R T FA IL UR E
CLINICAL RESEARCH
83 Clinical outcomes of the ACURATE neo2 transcatheter heart valve: a prospective, multicentre, observational, post-market
surveillance study
Won-Keun Kim, Corrado Tamburino, Helge Möllmann, Matteo Montorfano, Julia Ellert-Gregersen, Tanja K. Rudolph,
Nicolas M. Van Mieghem, Michael Hilker, Ignacio J. Amat-Santos, Christian Juhl Terkelsen, Anna Sonia Petronio, Pieter R. Stella,
Matthias Götberg, Andreas Rück, A. Markus Kasel, Ramiro Trillo, Clare Appleby, Marco Barbanti, Philipp Blanke, Rodrigo Modolo,
Dominic J. Allocco, Lars Sondergaard
TRANSLATIONAL RESEARCH
93 A bench study of balloon-expandable valves for the treatment of self-expanding valve failure
Mariama Akodad, David Meier, Stephanie Sellers, Ole De Backer, Darren Mylotte, Uri Landes, Chris Frawley, Lisa Lynch,
Gilbert H.L. Tang, Lars Sondergaard, David A. Wood, John G. Webb, Janarthanan Sathananthan

RESEARCH CORRESPONDENCE
103 Oesophageal and gastric injuries caused by transoesophageal probe manipulation in patients undergoing transcatheter
edge-to-edge repair for tricuspid regurgitation
Tanja Kuecken, Marwin Bannehr, Eleni Lalou, Johannes Lenz, Michael Zänker, Christoph Edlinger, Anja Haase-Fielitz,
Michael Neuss, Christian Butter

www Website exclusive contents: images and/or moving images

page
26 Prevention Troubleshooting

Conventional
- Preshaped wires
- Reverse wire technique
- Dual lumen microcatheter
- Angulated microcatheter
- Deflectable microcatheter
Jailed wire
Active protection Preshaped wires Angulated
CTO wires microcatheter

Risk factors:
- Plaque on the same side of the SB
- Reduced TIMI flow at the SB
- Severe % DS of bifurcation core ≥70%
Jailed balloon Balloon-stent kissing Modified - Unfavourable bifurcation angle ≥90°
- High ratio MV/SB ≥2
- Severe % DS at SB ≥90%
- Spiky carina
- RESOLVE score >10
Deflectable Rescue
microcatheter jailed balloon

Semi-inflated Jailed Corsair

Image taken from the following paper printed in this issue:

The 17th expert consensus document of the European Bifurcation Club – techniques to preserve access to the side branch during stepwise provisional stenting
M. Pan, J. Flensted Lassen, F. Burzotta, S. Ojeda, R. Albiero, T.Lefèvre, D. Hildick-Smith, T.W. Johnson, A. Chieffo, A.P. Banning, M. Ferenc,
O. Darremont, Y.S. Chatzizisis, Y. Louvard, G. Stankovic
EuroIntervention 2023;19:26-36.

7
 EDITORIAL BOARD
EuroIntervention 2023

EuroIntervention
EDITOR-IN-CHIEF
Davide Capodanno

DEPUTY EDITORS Interventional flashlights Tom Cuisset

Rasha Al-Lamee Pierre Deharo Bernard De Bruyne
Robert Byrne Luis Ortega-Paz Pim De Feyter
Nieves Gonzalo Interventional pharmacology Victoria Delgado
Michael Joner Dominick J. Angiolillo Dariusz Dudek
Darren Mylotte Piera Capranzano Run-Lin Gao
GUEST EDITOR Jolanta Siller-Matula Martine Gilard
Franz-Josef Neumann Intracoronary imaging Giulio Guagliumi
Tom Adriaenssens
David Holmes
ETHICS COMMITTEE Ziad Ali
David Kandzari
Michael Haude José-Maria De La Torre Hernandez
Alec Vahanian Upendra Kaul
Gary Mintz
Morton Kern
Lorenz Räber
ADVISORY EDITORS Ferdinand Kiemeneij
Intracoronary physiology
Ottavio Alfieri Takeshi Kimura
Fernando Alfonso Christos Bourantas
Josep Gomez-Lara Ran Kornowski
Antonio Colombo
Frederik Zimmermann Alexandra Lansky
Javier Escaned
Jean Fajadet Non-invasive imaging Thomas Lüscher
Marie-Claude Morice Daniele Andreini Michael Mack
José Luis Pomar Patrizio Lancellotti Bernhard Meier
Bernard Prendergast Philippe Pibarot Gilles Montalescot
William Wijns Meta-analyses Seung-Jung Park
Daniele Giacoppo Nicolo Piazza
SECTION EDITORS
Peripheral interventions Francesco Prati
Cardiac surgery
Piotr Musiałek Evelyn Regar
Francesco Maisano
Thomas Modine Eugenio Stabile Josep Rodés-Cabau
Clinical reviews Valvular interventions Manel Sabaté
Carlo Di Mario Mohamed Abdel-Wahab Goran Stankovic
Congenital Rodrigo Bagur Gabriel Steg
Sameer Gafoor Marco Barbanti Corrado Tamburino
Coronary interventions Ole De Backer
Marco Valgimigli
Emmanouil Brilakis Julinda Mehilli
Ron Waksman
Alaide Chieffo Fabien Praz
Giuseppe Gargiulo Joanna Wykrzykowska SOCIAL MEDIA TEAM
Valeria Paradies
Salvatore Brugaletta
Giulio Stefanini STATISTICAL EDITOR
Waqar Ahmed
e-Cardiology Sergio Buccheri
Mirvat Alasnag
Nico Bruining
Heart failure SENIOR CONSULTANT EDITORS Nicole Karam
Azeem Latib Takashi Akasaka Luis Ortega-Paz
Marco Metra Andreas Baumbach Nicola Ryan
Liesbeth Rosseel Jeroen Bax
Interventions for hypertension Colin Berry EDITOR EMERITUS
Felix Mahfoud John Bittl Patrick W. Serruys
Costas Tsioufis Alain Cribier

8
 EDITORIAL BOARD

EuroIntervention 2023
EDITORIAL CONSULTANTS
Pierfrancesco Agostoni Juan Luis Gutierrez-Chico Yukio Ozaki
Nicolas Amabile Farrel Hellig Anna Sonia Petronio
Yolande Appelman José Henriques Gianluca Pontone
Lorenzo Azzalini Dominique Himbert Jerzy Pr gowski
Martin Bergmann Lene Holmvang Bernhard Reimers
Ronald Binder James Howard Francesco Saia
Gill Louise Buchanan Hueseyin Ince Neus Salvatella
Francesco Burzotta Javaid Iqbal Giovanna Sarno
Shao-Liang Chen Nils Johnson Bruno Scheller
Bernard Chevalier Tom Johnson Jan-Malte Sinning
Bernardo Cortese Nicole Karam Christian Spaulding
Alberto Cremonesi Kostantinos Koskinas Pieter Stella
Gianmarco De Donato Vijay Kunadian Huay-Cheem Tan
Giuseppe De Luca Jacek Legutko Gilbert Tang
Josep Dens Jonathon Leipsic Gabor Toth
Luigi Di Serafino Akiko Maehara Yasushi Ueki
Gregory Ducrocq Fazila Malik Robert-Jan van Geuns
Isabelle Durand-Zaleski Fina Mauri Gerald Werner
Islam Elgendy Antonio Micari Adam Witkowski
Rodrigo Estevez-Loureiro Ghada Mikhail Wojciech Wojakowski
Neil Fam Dejan Milasinovic Bo Xu
Jens Flensted Lassen Fabian Nietlispach
Tommaso Gori Mpiko Ntsekhe
Giulio Guagliumi Andrew Ong

EUROINTERVENTION Partenariats industrie Editeur

Publication : 18 numéros par an Olivier Palayan Frédéric Doncieux
Volume 19 - N°1 - Mai 2023
Marie Torne-Celer
Facteur d’impact : 7.728 Président: Marc Doncieux.
Violaine Rauna
2021 Journal Citation Reports® Principal actionnaire :
Florian Craanen NOGA SAS
(Clarivate Analytics, 2022)
Brianan Stanley
Directeur de la publication Monica Ramos Hernandez Commission paritaire :
Marc Doncieux en cours
Coordination digitale ISSN : 1774-024X
Responsable éditoriale Ronnie Lassiaille
ISSN online : 1969-6213
Sylvie Lhoste Gregori Despeaux
Coralie Massonnié Dépôt légal à parution
Bureau de l’éditeur en Chef / Davy Bonnafous
Editor-in-Chief office Florence Petit Imprimé en Espagne
Antonio Greco Sarah Françoise par Soler T.G.
Conseiller éditorial / Local associate editor C/Enric Morera 15
Direction artistique 08950 Esplugas de Llobregat España
Laura Basile Siobhan Royer-Hardy
Assistante éditoriale / Editorial assistant Copyright © Europa Group 2023
Graphisme et mise en page
Assistante éditoriale Le contenu de EuroIntervention ne peut être
Groupe Composer : 2, impasse du Ramier reproduit sans autorisation écrite de l’éditeur.
Devia Bijkerk des Catalans - CS 38503 - 31685 Toulouse
Cedex 6 - France Europa Digital & Publishing est une marque
Coordination éditoriale
commerciale d’Europa Group
Véronique Deltort
Amy McDowell
Sheldon Heitner EuroIntervention est édité par la Société Europa Group,
Isabelle Uzielli SAS au capital de 1 080 704 euros, siège social :
Sonia Morcuende 19, allées Jean-Jaurès, 31000 Toulouse, France ,
Jane McKellow RCS Toulouse 342 066 727, APE 8230 Z.
Nikki Rubython
Noëlle Wylie MEDLINE abbreviation: EuroIntervention

9
 PCR Randomised Trials
Stay up to date with all the recent data!

Keep an eye out for updates!

With major trials including:
• Renovate-Complex PCI
• Triluminate
• Radiance III

Editors:
Pim de Feyter and Robert A. Byrne

A unique free online resource

Quick and easy access to a compilation of one-page summaries of randomised trials
in the field of interventional cardiology
All selected from among the New England Journal of Medicine, Lancet, JAMA,
BMJ, European Heart Journal, Journal of the American College of Cardiology,
Circulation, Annals of Internal Medicine, EuroIntervention, JACC Cardiovascular
Interventions and Circulation Cardiovascular Interventions

Released thanks to the support of

PCRonline.com
 AIMS AND SCOPE

EuroIntervention 2023
Aims and scope
EuroIntervention Journal is an international, English language, peer-reviewed journal whose aim is to create a forum of high-quality
research and education in the field of percutaneous and surgical cardiovascular interventions.

EuroIntervention is the official journal of EuroPCR and the European Association of Percutaneous Cardiovascular Interventions (EAPCI).
It is released 18 times a year at regular intervals in paper and electronic formats. EuroIntervention is indexed in Science Citation Index® (ISI),
SciVerse Scopus, MEDLINE®/PubMed® (Abbreviation: EuroIntervention).

IMPACT FACTOR: 7.728 2021 JOURNAL CITATION REPORTS® SCIENCE EDITION (CLARIVATE ANALYTICS, 2022)

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11
 Orsiro Mission DES ®

Orsiro DES shows lower TLF rate

compared to Xience in complex PCI patients.1*

32%
lower TLF in
complex PCI1*
Target Lesion Failure at 36 months p = 0.171

25 Orsiro
Xience

20
Target Lesion Failure (%)

18.2%
Cumulative Incidence –

15
12.6%

10

0
0 12 24 36
Time after initial procedure (months)

What would you choose

for your complex cases?
www.orsiro-mission.com

*Numerically lower TLF with Orsiro DES in comparison to Xience DP-EES, based on 3-year results from Hemetsberger et al. Complex PCI, 2022. 1.
Hemetsberger R, et al. Complex vs. non-complex percutaneous coronary intervention with newer-generation drug-eluting stents: an analysis from the
randomized BIOFLOW trials. Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-01994-4.

Clinical data conducted with Orsiro, Orsiro Mission’s predecessor device can be used to illustrate Orsiro Mission clinical outcomes.

Orsiro and Orsiro Mission are trademarks or registered trademarks of the BIOTRONIK Group of Companies.
Xience is a trademark or registered trademark of the Abbott Group of Companies.

© 2023 BIOTRONIK AG – All rights reserved.

Specifications are subject to modification, revision and improvement.

The conundrum of percutaneous coronary intervention
without aspirin: a call for clarity
Raffaele Piccolo*, MD, PhD; Giovanni Esposito, MD, PhD
Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
Aspirin is widely recognised as an essential component of
antithrombotic therapy for secondary prevention, with societal
guidelines recommending its use prior to percutaneous coronary
intervention (PCI) and for lifelong maintenance therapy thereaf-
ter. The development of more potent P2Y12 receptor inhibitors,
which provide a predictable antiplatelet effect, has led a shift in
clinical research towards monotherapy with P2Y12 receptor inhibi-
tors, without aspirin1. Aspirin discontinuation on a background
of P2Y12 receptor inhibition has been tested at varying intervals,
including 12 months, 3 to 6 months, and 1 month following PCI
in experimental arms of randomised trials. This approach presents
a potential win-win scenario, reducing the risk of both ischaemic
and bleeding events in comparison to dual antiplatelet therapy
(DAPT). Despite this, aspirin remains deeply engrained in clinical
practice, and the dogma of performing PCI without aspirin has not
been challenged by a study.
In this issue of EuroIntervention, van der Sangen and col-
leagues report on the results of the Optical Coherence
Tomography-Guided PCI with Single Antiplatelet Therapy
*Corresponding author: Department of Advanced Biomedical Sciences, University of Naples Federico II, Corso Umberto I 40,
80138 Naples, Italy. E-mail: raffaele.piccolo@unina.it
© Europa Digital & Publishing 2023. All rights reserved.
EDITORIAL
EuroIntervention 2023;19:13-14
(OPTICA) study, a pilot trial involving 75 patients with non-
ST-elevation acute coronary syndrome who underwent PCI with
new-generation drug-eluting stents2. The study assessed the use
of P2Y12 receptor inhibitor monotherapy, with ticagrelor being
used in 85% of patients, immediately after PCI completion.
Intracoronary imaging with optical coherence tomography was
used in approximately 45% of patients, although one might have
expected a wider use based on the study title. Adequate plate-
let inhibition was confirmed in all patients, except for one who
remained on DAPT after PCI. The anatomical complexity in the
study was low to moderate, with around 70% of cases being sin-
gle-lesion PCI and over 80% of patients requiring the implanta-
tion of 1-2 stents. At 6-month follow-up, adverse events occurred
at relatively low frequency, with minor bleeding being the most
DOI: 10.4244/EIJ-E-23-00017
frequent complication (6.7%), followed by repeat revascularisa-
tion in non-target vessels (5.3%), and periprocedural myocardial
infarction (2.7%). No stent thrombosis, type 1 myocardial infarc-
tion, or deaths were reported.
Article, see page 63
The opinions expressed in this article are not necessarily those of the Editors of EuroIntervention or
of the European Association of Percutaneous Cardiovascular Interventions.
13
EuroIntervention 2023;19:13-14
OPTICA is a proof-of-concept study, and therefore it is impor-
tant to acknowledge some limitations when interpreting the study
findings. Firstly, the study was not randomised and lacked a con-
trol arm, such as standard DAPT, which could have served as
a reference antiplatelet strategy. Secondly, the sample size was
considerably underpowered, with stent thrombosis, the most
feared complication associated with aspirin withdrawal, being dif-
ficult to investigate thoroughly with only 75 patients observed
up to 6 months after PCI. Although the study was planned as
a single-arm trial, it did not employ an optimal performance goal
nor a similar approach; thus, the final sample is not the result of
a power calculation nor study hypothesis. Additionally, the study
lacked an independent Data and Safety Monitoring Board, as well
as a clinical events committee. Therefore, caution should be exer-
cised when interpreting the authors’ conclusion that monotherapy
with P2Y12 inhibitors immediately after coronary stenting is feas-
ible without any overt safety concerns.
However, it is important to recognise the pioneering nature
of the OPTICA study in exploring a new field in antithrombotic
therapy for PCI patients. In this respect, the authors deserve
commendation for extending the boundaries of P2Y12 inhibitor
monotherapy to day 0 after PCI. Nevertheless, prior to bidding
adieu to aspirin after PCI, it is necessary to reflect on the pros
and cons of an aspirin-free approach in the first month follow-
ing PCI. In analogy to the decreased risk of bleeding with P2Y12
inhibitor monotherapy after a short course of DAPT, a consist-
ent benefit can be expected when this approach is applied at
an earlier timepoint. However, as the bleeding risk is propor-
tional to the duration and intensity of DAPT, the expected bene-
fit in absolute terms is not substantial for the average patient.
Conversely, for a patient at high bleeding risk or at risk of devel-
oping a bleeding complication after PCI, the benefit may be con-
siderable and clinically relevant. Despite randomised data from
about 30,000-40,000 patients showing the safety and efficacy
of P2Y12 inhibitor monotherapy, this approach is still far from
being implemented in clinical practice. Aspirin is still prescribed
Corrigendum DOI: 10.4244/EIJ-D-22-00723C
Corrigendum to: “Renal denervation in the management of hypertension in adults. A clinical
consensus statement of the ESC Council on Hypertension and the European Association of
Percutaneous Cardiovascular Interventions (EAPCI)”
EuroIntervention 2023;18:1227-1243. DOI: 10.4244/EIJ-D-22-00723
The original version of this article featured an error in the legend of Figure 2 and an error in the UHF dosage in Table 4.
These have since been updated.
The authors wish to apologise for the error.
14
to millions of patients in secondary prevention, despite the
fact that the overall data proving its efficacy are based on
only 16,000 patients enrolled in outdated randomised trials3.
Implementing changes in clinical practice is easier when they are
simple to embrace, and thus P2Y12 inhibitor monotherapy after
PCI will more likely become the mainstream approach if the
transition from DAPT is no longer required. However, a rigorous
approach is highly warranted to bring the aspirin-free strategy to
the next level. Early aspirin discontinuation in another context,
such as PCI patients requiring oral anticoagulant therapy, carries
a non-negligible higher risk of stent thrombosis when data from
all trials are pooled together. Nonetheless, here, the situation may
be different if one takes a risk with the parachute of more potent
P2Y12 inhibitors, such as ticagrelor or prasugrel. There is no way
to change clinical practice without a well-designed randomised
trial, powered for hard clinical outcomes, comparing a low dose
of aspirin versus placebo after PCI. For the time being, P2Y12
inhibitor monotherapy should continue to be commenced at least
1 month after PCI.
Conflict of interest statement
The authors have no conflicts of interest to declare.
References
1. Capodanno D, Baber U, Bhatt DL, Collet JP, Dangas G, Franchi F, Gibson CM,
Gwon HC, Kastrati A, Kimura T, Lemos PA, Lopes RD, Mehran R, O’Donoghue ML,
Rao SV, Rollini F, Serruys PW, Steg PG, Storey RF, Valgimigli M, Vranckx P,
Watanabe H, Windecker S, Angiolillo DJ. P2Y12 inhibitor monotherapy in patients
undergoing percutaneous coronary intervention. Nat Rev Cardiol. 2022;19:
829-44.
2. van der Sangen NMR, Claessen BEPM, Küçük IT, den Hartog AW, Baan J,
Beijk MAM, Delewi R, van de Hoef TP, Knaapen P, Lemkes JS, Marques KM, Nap A,
Verouden NJW, Vis MM, de Winter RJ, Kikkert WJ, Appelman Y, Henriques JPS.
Single antiplatelet therapy directly after percutaneous coronary intervention in non-ST-
segment elevation acute coronary syndrome patients: the OPTICA study.
EuroIntervention. 2023;19:63-72.
3. Antithrombotic Trialists’ (ATT) Collaboration; Baigent C, Blackwell L, Collins R,
Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C,
Roncaglioni MC, Zanchetti A. Aspirin in the primary and secondary prevention of
vascular disease: collaborative meta-analysis of individual participant data from ran-
domised trials. Lancet. 2009;373:1849-60.
© Europa Digital & Publishing 2023. All rights reserved.

A UNIVERSAL call for the optimisation of vascular closure
devices
Harold L. Dauerman*, MD; Tanush Gupta, MD
Division of Cardiology, Larner College of Medicine, University of Vermont, Burlington, VT, USA
Clinical practice guidelines give a class I recommendation to
the radial approach in preference to the femoral approach in
patients undergoing coronary angiography (CA) and percutane-
ous coronary intervention (PCI)1. However, femoral access is still
frequently utilised for large-bore access (i.e., complex PCI, percu-
taneous mechanical circulatory support, structural heart interven-
tions) or in scenarios where a transradial approach is technically
challenging or unfeasible. In the contemporary era of widespread
radial adoption, a paradoxical increase in vascular complications
with femoral artery catheterisation has been described, poten-
tially attributable to declining operator experience with non-radial
approaches2. Therefore, best practices need to be defined for safe
femoral access to achieve the best possible patient outcomes.
In this issue of EuroIntervention, d’Entremont et al3 report a pre-
specified subgroup analysis of patients utilising vascular closure
devices (VCD) within the UNIVERSAL (Routine Ultrasound
Guidance for Vascular Access for Cardiac Procedures) trial.
UNIVERSAL was an open-label, investigator-initiated, randomised
clinical trial of 621 patients referred for CA or PCI at two sites in
Canada, randomised in a 1:1 ratio to ultrasound (US)-guided (on
*Corresponding author: Division of Cardiology, McClure 1, University of Vermont Medical Center, 111 Colchester Avenue,
Burlington, VT 05401, USA. E-mail: harold.dauerman@uvmhealth.org
© Europa Digital & Publishing 2023. All rights reserved.
EDITORIAL
EuroIntervention 2023;19:15-17
the background of fluoroscopic landmarking) versus fluoroscopic-
guided femoral access. Importantly, both centres were default
radial sites; the enrolled patients were non-consecutive and fem-
oral access was selected because of either anatomical factors or
operator preference. The primary endpoint was a 30-day compos-
ite of Bleeding Academic Research Consortium (BARC) 2, 3, or
5 bleeding and major vascular complications. The UNIVERSAL
trial was negative for the primary endpoint: US guidance did not
reduce the incidence of bleeding or vascular complications: 12.9%
vs 16.1%; odds ratio (OR) 0.77, 95% confidence interval (CI):
0.49-1.204.
Article, see page 73
UNIVERSAL is one of 3 well executed, multicentre trials com-
paring US-guided versus fluoroscopic-guided access; there is
a remarkable consistency to all 3 trial primary endpoint analyses:
DOI: 10.4244/EIJ-D-23-000016
all 3 are unequivocally negative (Table 1). Despite this primary
negativity, two prior trials have suggested possible benefit for rou-
tine US guidance via secondary endpoint analysis. For example, in
the Femoral Arterial Access With Ultrasound Trial (FAUST) trial,
secondary endpoints of first-pass success rate, number of access
The opinions expressed in this article are not necessarily those of the Editors of EuroIntervention or
of the European Association of Percutaneous Cardiovascular Interventions.
15
EuroIntervention 2023;19:15-17

Table 1. Randomised trials of ultrasound-guided versus fluoroscopic approach to femoral artery access.
Sheath Key secondary Overall VCD VCD subgroup
Study/country/year Population Primary outcome
sizes (Fr) outcomes use (%) results
Seto et al5. FAUST Trial, Diagnostic or 5-7 Primary outcome: negative ↑ First-pass access; 61.6 Not reported
United States, 2010 interventional coronary/ No benefit for US ↓ vascular complications;
peripheral (N=1,004) Successful CFA cannulation; ↓ number of attempts,
86.4% vs 83.3%; p=0.17 venipunctures, and time to
access.
Nguyen et al7. SURF Diagnostic or interventional 5-7 Primary outcome for radial vs ↑ First-pass access; 37.9 Not reported
trial, Australia, 2019 coronary procedures femoral: positive, radial superior. ↓ venipunctures, access
(2X2 factorial trial of radial Primary outcome for US vs time, and difficult accesses.
vs femoral and ultrasound standard femoral access:
vs standard access; negative, no benefit for US
N=688) Composite of ACUITY major
bleeding, MACE (death, stroke, MI,
or urgent TLR), and vascular
complications at 30 days; 2.3%
vs 2.5%; p=0.76
Jolly et al4. UNIVERSAL Diagnostic or interventional 5-8 Primary outcome: negative ↑ First-pass access; 52.2 Non-randomised
trial, Canada, 2022 coronary procedures No benefit for US ↓ arterial puncture analysis for primary
(N=621) attempts and venipuncture; endpoint:
BARC 2,3, or 5 bleeding or major no Δ in time to access positive for US
vascular complications at 30
days; 12.9% vs 16.1%; p=0.25 11.8% vs 23.4%;
pinteraction=0.004
ACUITY: Acute Catheterization and Urgent Intervention Triage strategy; BARC: Bleeding Academic Research Consortium; CFA: common femoral artery; MACE: major adverse cardiovascular
events; MI: myocardial infarction; TLR: target lesion revascularisation; US: ultrasound; VCD: vascular closure device

attempts, inadvertent venipunctures, median time to access, and
vascular complications (driven by a reduction in large haemato-
mas), showed benefit for an US-guided strategy5. In this context,
UNIVERSAL is also consistent with prior trials: a prespecified
secondary endpoint or subgroup analysis suggests potential bene-
fits from US-guided femoral access not reflected in the main trial
results, namely the routine use of US-guided access specifically
benefits the subgroup of patients receiving VCDs.
In the main trial, the utilisation of VCDs was 54.7% vs 51.0%
in the US versus non-US groups, respectively. ANGIO-SEAL
(Terumo) was the most frequently utilised VCD (85.5%) with
ProGlide (Abbott; 14.5%) being used in the remainder of the
cases. In the VCD cohort, there was a significant reduction in the
composite endpoint with US guidance (11.8% vs 23.4%; OR 0.44,
95% CI: 0.23-0.82). In contrast, in the manual compression group,
there was no difference in the primary endpoint in the US ver-
sus no US groups (14.2% vs 8.6%; OR 1.76, 95% CI: 0.80-4.03;
pinteraction=0.004). The results of the current post hoc, prespecified
subgroup study suggest that the safety of femoral artery access
may hinge on US guidance, particularly in patients chosen for
VCD closure. These findings are plausible. However, this conclu-
sion contradicts the result of the main trial outcome and therefore,
further perspective is required to contextualise these subgroup
findings into clinical practice.
First, the current VCD substudy is a subgroup analysis of an
overall negative trial; therefore, the findings are hypothesis-gener-
ating. Second, VCD use was a post-randomisation variable and US
guidance might have biased the decision to use a VCD or the type
of VCD used. Therefore, the study results, especially the compari-
sons of event rates in the ANGIO-SEAL versus ProGlide groups
must be interpreted with caution. Next, the superior results in the
US arm in the VCD subgroup were driven by a 3-fold reduction
in large haematomas ≥5cm (4.1% vs 12.0%; OR 0.32, 95% CI:
0.11-0.81); there was no difference in other vascular complica-
tions (pseudoaneurysm, arteriovenous fistula, retroperitoneal hae-
matoma, limb complications) or the co-primary bleeding endpoint
between the US versus no US groups. While major bleeding has
been shown to be an independent predictor of both early and one-
year mortality, large haematomas may have less effect on 30-day
ischaemic events or 1-year all-cause mortality6. Lastly, micropunc-
ture access was not utilised in the UNIVERSAL trial and thus the
angiographic detection of arterial disease that may have precluded
VCD utilisation is not well described. There were no differences
in VCD failure rates in the US versus no US groups in the cur-
rent study. Therefore, the greater number of haematomas in the no
VCD arm were most likely due to bleeding arising from multi-
ple arterial punctures or inadvertent venipunctures (both higher in
the no US group). Whether or not a femoral angiography-guided
micropuncture approach to VCD utilisation would have improved
the results of the non-US-guided arm cannot be determined from
this study design.
The authors are to be congratulated for reinvigorating a crucial
topic in the "radial first" era where there is diminishing experience
in femoral access and closure. Therefore, the importance of defin-
ing the optimal technique in femoral access in conjunction with
VCD use cannot be overemphasised. UNIVERSAL is the first ran-
domised trial to focus on the particular subgroup of patients recei-
ving VCD and thus this subgroup analysis is of key importance
for clinical conclusions and future trial design (Table 1). US guid-
ance is mandatory in venous access procedures (for which palpable
pulse, fluoroscopic landmarks and micropuncture are of limited util-
ity) without any further trial evaluation. But can we conclude that

16

US guidance is mandatory for femoral arterial access in conjunction
with VCD utilisation? Or could the careful use of the micropuncture
technique for femoral access, with femoral angiography as a screen-
ing prior to sheath placement and ultimate VCD utilisation, provide
an equivalent strategy? Furthermore, how effective and operator-
dependent is US guidance in detecting the full extent of femoral
artery disease as compared to a mandatory femoral angiogram? And
finally, does best practice change for large-bore access with pre-
dominant ProGlide utilisation as compared to smaller sheath proce-
dures that are predominantly closed with the ANGIO-SEAL device?
This important UNIVERSAL trial subgroup analysis suggests that
fluoroscopic-guided femoral arterial access in the context of VCD
utilisation may no longer be best practice. But, to prove this, randomi-
sation not stratification is required: among patients with micropunc-
ture access with adequate angiographically defined femoral access
to permit the safe use of a VCD (femoral artery diameter of greater
than 5.0 mm diameter, not severely calcified), can we perform a mul-
ticentre randomised clinical trial to determine if the initial puncture,
guided by US versus fluoroscopy, leads to the elusive positive pri-
mary endpoint? Given the changing landscape, utilisation, and appli-
cations of femoral versus radial access, finding a conclusive answer
to this question may be more important than ever. While the findings
reported by d’Entremont et al3 do not yet mandate the use of US
guidance for femoral access prior to VCD use, they do point to a uni-
versal need for more knowledge regarding best practice in VCD use.
Conflict of interest statement
H.L. Dauerman reports consulting and research grants from
Medtronic and Boston Scientific. T. Gupta has no relevant con-
flicts of interest to declare.
Ultrasound-guided femoral access and VCD use
EuroIntervention 2023;19:15-17
References
1. Writing Committee Members; Lawton JS, Tamis-Holland JE, Bangalore S,
Bates ER, Beckie TM, Bischoff JM, Bittl JA, Cohen MG, DiMaio JM, Don CW,
Fremes SE, Gaudino MF, Goldberger ZD, Grant MC, Jaswal JB, Kurlansky PA,
Mehran R, Metkus TS Jr, Nnacheta LC, Rao SV, Sellke FW, Sharma G, Yong CM,
Zwischenberger BA. 2021 ACC/AHA/SCAI Guideline for Coronary Artery
Revascularization: Executive Summary: A Report of the American College of
Cardiology/American Heart Association Joint Committee on Clinical Practice
Guidelines. J Am Coll Cardiol. 2022;79:197-215.
2. Azzalini L, Tosin K, Chabot-Blanchet M, Avram R, Ly HQ, Gaudet B, Gallo R,
Doucet S, Tanguay JF, Ibrahim R, Grégoire JC, Crépeau J, Bonan R, de Guise P,
Nosair M, Dorval JF, Gosselin G, L’Allier PL, Guertin MC, Asgar AW, Jolicoeur EM.
The Benefits Conferred by Radial Access for Cardiac Catheterization Are Offset by
a Paradoxical Increase in the Rate of Vascular Access Site Complications With Femoral
Access: The Campeau Radial Paradox. JACC Cardiovasc Interv. 2015;8:1854-64.
3. d’Entremont M-A, Alrashidi S, Alansari O, Brochu B, Heenan L, Skuriat E,
Tyrwhitt J, Raco M, Tsang MB, Valettas N Velianou J, Sheth T, Sibbald M, Mehta SR,
Pinilla-Echeverri N, Schwalm J-D, Natarajan MK, Kelly A, Akl E, Tawadros S,
Camargo M, Faidi W, Bauer J, Moxham R, Nkurunziza J, Dutra G, Winter J, Jolly SS.
Ultrasound-guided femoral access in patients with vascular closure devices: a prespec-
ified analysis of the randomized UNIVERSAL trial. EuroIntervention. 2023;19:73-9.
4. Jolly SS, AlRashidi S, d’Entremont MA, Alansari O, Brochu B, Heenan L, Skuriat E,
Tyrwhitt J, Raco M, Tsang M, Valettas N, Velianou JL, Sheth T, Sibbald M, Mehta SR,
Pinilla-Echeverri N, Schwalm JD, Natarajan MK, Kelly A, Akl E, Tawadros S,
Camargo M, Faidi W, Bauer J, Moxham R, Nkurunziza J, Dutra G, Winter J. Routine
Ultrasonography Guidance for Femoral Vascular Access for Cardiac Procedures: The
UNIVERSAL Randomized Clinical Trial. JAMA Cardiol. 2022;7:1110-8.
5. Seto AH, Abu-Fadel MS, Sparling JM, Zacharias SJ, Daly TS, Harrison AT,
Suh WM, Vera JA, Aston CE, Winters RJ, Patel PM, Hennebry TA, Kern MJ. Real-
time ultrasound guidance facilitates femoral arterial access and reduces vascular com-
plications: FAUST (Femoral Arterial Access With Ultrasound Trial). JACC Cardiovasc
Interv. 2010;3:751-8.
6. White HD, Aylward PE, Gallo R, Bode C, Steg G, Steinhubl SR, Montalescot G;
STEEPLE Investigators. Hematomas of at least 5 cm and outcomes in patients under-
going elective percutaneous coronary intervention: insights from the SafeTy and
Efficacy of Enoxaparin in PCI patients, an internationaL randomized Evaluation
(STEEPLE) trial. Am Heart J. 2010;159:110-6.
7. Nguyen P, Makris A, Hennessy A, Jayanti S, Wang A, Park K, Chen V, Nguyen T,
Lo S, Xuan W, Leung M, Juergens C. Standard versus ultrasound-guided radial and
femoral access in coronary angiography and intervention (SURF): a randomised con-
trolled trial. EuroIntervention. 2019;15:e522-30.
17
 EDITORIAL
EuroIntervention 2023;19:18-19
ACURATE neo2: jack of all trades or master of none?
Jan-Malte Sinning*, MD, PhD, FESC
Department of Cardiology, St. Vincent Hospital Cologne, Cologne, Germany
Transcatheter aortic valve implantation (TAVI) is now indicated
across all risk categories of patients with symptomatic severe
aortic stenosis and has been proposed as a first-line option for
the majority of patients ≥75 years old. The former discussion of
whether a patient should undergo surgical aortic valve replace-
ment (SAVR) or TAVI is shifting from patient age and surgical
risk to life expectancy and the associated lifetime management of
aortic stenosis for an individual patient1.
As indications for TAVI expand to include younger and healthier
patients who are expected to outlive their initial transcatheter heart
valve (THV), understanding the long-term implications of the ini-
tial intervention is paramount, since “the first cut is the deepest”.
TAVI with a next-generation device has become a mature inter-
vention that should grant the patient high procedural safety with
low mortality and a low stroke rate, a low rate of conduction dis-
turbances, and excellent haemodynamic performance without
paravalvular leakage or leaflet thrombosis2.
DOI: 10.4244/EIJ-E-23-00012
However, for younger patients who have the realistic expectation
of the need for reintervention, the implications of the initial inter-
vention play a more pivotal role regarding durability, accessibility
of coronary arteries, and future options to overcome bioprosthetic
failure that include THV explant with SAVR or TAV-in-TAV with
*Corresponding author: Department of Cardiology, St. Vincent Hospital Cologne, Merheimer Str. 221-223, 50733 Cologne,
Germany. E-mail: jan-malte.sinning@cellitinnen.de
© Europa Digital & Publishing 2023. All rights reserved.
18
a second THV. Additionally, there are patients who have a realistic
chance of requiring a third valvular intervention. The initial treat-
ment strategy may limit reintervention options in the future1,2.
An intra-annular balloon-expandable valve has a shorter pros-
thesis stent frame with lower leaflets and skirt height, facilitat-
ing coronary access and reintervention with less risk of coronary
obstruction. When performing valve-in-valve TAVI, the leaflets
of the initial bioprosthesis are pinned into an open position by
the second THV and a so-called “neoskirt” is created, which,
for patients with low coronary height or a small aortic root can
result in sinus sequestration or direct obstruction at the coronary
ostium. Recent recommendations of higher THV implantation rel-
ative to the aortic valve annulus, to reduce the risk of conduc-
tion disturbances, may specifically limit the anatomical feasibility
of TAV-in-TAV, especially when using self-expanding valves with
a supra-annular valve position.
Most self-expanding valves have a longer prosthesis stent frame
that anchors in the native aortic annulus and the ascending aorta,
thereby hampering coronary access through prosthesis stent struts
and commissural posts that are not aligned with the coronary ostia.
However, the self-expanding design allows repositionability and
might be associated with more favourable haemodynamics.
The opinions expressed in this article are not necessarily those of the Editors of EuroIntervention or
of the European Association of Percutaneous Cardiovascular Interventions.

Taking all these considerations together, the new ACURATE
neo2 Aortic Valve System (Boston Scientific Corporation) could
be a jack of all trades: this THV consists of a self-expanding
nitinol stent frame with three porcine pericardial tissue leaflets in
a supra-annular position, without stent struts in the supra-annu-
lar position hampering access to the coronary ostia. The valve
features a self-aligning design and a novel radiopaque marker to
facilitate accurate positioning in the native aortic valve. The dou-
ble pericardial skirt is intended to prevent paravalvular leakage.
The device is currently available in three sizes for a native aortic
annulus diameter range between 21 mm and 27 mm3.
In this issue of EuroIntervention, Kim and colleagues can
be congratulated on an interesting study that enrolled 250 pre-
dominantly intermediate- to high-risk patients at 18 centres in
8 European countries. In this observational post-market surveil-
lance study, the ACURATE neo2 THV showed excellent results
with a very low rate for 30-day mortality (0.8%), stroke (0.8%),
and pacemaker implantation (6.5%)3.
Article, see page 83
The haemodynamic performance of this THV was superior
to its predecessor with none to only mild paravalvular leakage
(PVL) in 98.1% of the patients. Hypoattenuated leaflet thickening
(HALT) as the primary imaging endpoint could be detected in 50
of 204 patients with the computed tomography (CT) imaging data
available but did not lead to a significantly increased transvalvular
gradient during short-term follow-up compared to patients with-
out HALT3.
However, in 4 of 250 patients, the ACURATE neo2 THV could
not be implanted in the appropriate position due to high posi-
tioning in the aorta and subsequent THV embolisation with the
need for an immediate TAV-in-TAV procedure with a non-study
balloon-expandable valve. One of these patients died due to coro-
nary occlusion and cardiac tamponade. As the authors state in their
discussion, these results are in line with the overall embolisation
rate of approximately 1% in the TRAVEL registry. It seems that
the ACURATE neo2 THV has overcome the weakness of its pre-
decessor, the ACURATE neo, with a significantly lower PVL rate3.
Altogether, the ACURATE neo2 THV is a promising candi-
date to be an alternate THV option, in addition to the SAPIEN
(Edwards Lifesciences) and the Evolut (Medtronic) prostheses.
The ACURATE neo2 guaranteed an "event-free" TAVI proce-
dure without the “Big 5” TAVI complications: rates for disabling
ACURATE neo2
EuroIntervention 2023;19:18-19
stroke (0.0%), life-threatening bleeding (2.9%), more than mild
PVL (1.9%), acute kidney injury (0.0%), and complete heart block
(6.5%) were very low in this registry and should be reconfirmed in
a randomised controlled study. Of course, long-term data are also
needed to better understand its capabilities3,4.
Finally, a word of caution has to be said, as the results from
this registry cannot be directly compared to clinical outcomes with
other THV devices from randomised clinical trials as the authors
properly state in the limitations section. Enrolment decisions were
made per the discretion of the local Heart Team, so the possibility
of site-based differences in patient selection cannot be ruled out.
Notably, the fact that patients with severely calcified aortic valves
might have been treated with other THVs cannot be ruled out as
selection bias3.
Although the original saying is “a jack of all trades is a mas-
ter of none, but oftentimes better than a master of one”, the
ACURATE neo2 THV seems to be an interesting option, com-
bining the advantages of self-expanding and balloon-expandable
THVs in a single device. This could not only guarantee an “event-
free” TAVI procedure for the patient but also an optimised landing
zone for future interventions regarding skirt height and coronary
accessibility.
Conflict of interest statement
J.-M. Sinning is proctor for Medtronic and Boston Scientific;
receives research support from Boston Scientific, Edwards
Lifesciences, and Medtronic; and speaker honoraria from Abbott,
Abiomed, Boston Scientific, Edwards Lifesciences, and Medtronic.
References
1. Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J,
Capodanno D, Conradi L, De Bonis M, De Paulis R, Delgado V, Freemantle N,
Gilard M, Haugaa KH, Jeppsson A, Jüni P, Pierard L, Prendergast BD, Sádaba JR,
Tribouilloy C, Wojakowski W. 2021 ESC/EACTS Guidelines for the management of
valvular heart disease. EuroIntervention. 2022;17:e1126-96.
2. Tarantini G, Fovino LN. Lifetime Strategy of Patients With Aortic Stenosis: The
First Cut Is the Deepest. JACC Cardiovasc Interv. 2021;14:1727-30.
3. Kim WK, Tamburino C, Möllmann H, Montorfano M, Ellert-Gregersen J,
Rudolph TK, Van Mieghem NM, Hilker M, Amat-Santos I, Terkelsen CJ, Petronio AS,
Stella P, Götberg M, Rück A, Kasel M, Trillo R, Appleby C, Barbanti M, Blanke P,
Modolo R, Allocco DJ, Sondergaard L. Clinical outcomes of the ACURATE neo2
transcatheter heart valve: a prospective, multicenter, observational, post-market sur-
veillance study. EuroIntervention. 2023;19:83-92.
4. Grube E, Sinning JM. The “Big Five” Complications After Transcatheter Aortic
Valve Replacement. Do We Still Have to Be Afraid of Them? JACC Cardiovasc Interv.
2019;12:370-2.
19
 EDITORIAL
EuroIntervention 2023;19:20-21

Continuously renewing and at the cutting edge: Welcome to

EuroPCR 2023!
Thomas Cuisset1, MD, PhD; Nicolas Dumonteil2, MD; Nieves Gonzalo3, MD, PhD;
Emanuele Barbato4, MD, PhD; Bernard Prendergast5, DM, FRCP; William Wijns6, MD, PhD;
Jean Fajadet7* MD, PhD, FESC; on behalf of the EuroPCR Course Directors, EAPCI President and PCR Chairs.
1. Service de Cardiologie, University Hospital de La Timone, Marseille, France; 2. Groupe Cardiovasculaire Interventionnel,
Clinique Pasteur, Toulouse, France; 3. Department of Cardiology, Hospital Clínico San Carlos IdISSC and Universidad
Complutense de Madrid, Madrid, Spain; 4. Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome,
Italy; 5. Cleveland Clinic London and St Thomas’ Hospital, London, UK; 6. The Lambe Institute for Translational Medicine, The
Smart Sensors Laboratory and CURAM, Galway, University of Galway, Galway, Ireland; 7. Co-Chair PCR, Toulouse, France

What can you expect from EuroPCR this year?
Exactly what you need − more than ever before we will provide a
dedicated focus on the fundamentals of our profoundly successful
PCR educational philosophy.
What does this mean for you?
It means a Course that strives for excellence in education, with
a patient-centred approach illustrated through case-based discus-
sions. An over-arching commitment to share global experience
with a deep respect for diversity, especially with the help of mul-
tiple national societies and working groups, numerous collabo-
rations across our specialty, and our seamless integration with
EAPCI providing an invaluable contribution through their net-
work, our joint fellows course, and the announcement of key edu-
cational grants.
But it does not end here:
We continue our strong and very rewarding collaboration with
DOI: 10.4244/EIJ-E-23-00027
The PCR journey is characterised by our continued Search for
Excellence in education via multiple routes. During the Course,
the roles of each participant in every session are clearly defined
to provide maximum benefit to all. Each of the programme fac-
ulty has a specific part to play, whether they are the anchorperson,
spokesperson, discussant, procedural analyst, imaging expert or
chat master. The results of this coordination speak for themselves:
participants enjoy an effective educational experience prepared
and delivered for their needs by a collaborative team of teach-
ers. This team incorporates their years of experience within PCR,
resulting in the creation of the best possible format and mode of
delivery. Finally, the learning objectives are clearly announced at
each step and for each programme, making it easier for you - the
participant - to choose from the many available options and ensure
that you experience sessions that are most relevant for you and
your practice.
And there is so much more:

Women as One (https://womenasone.org/) – a partnership that is ­– D

 id you know that the VITAL programme is still very active in
intellectually stimulating and marks a renaissance in our approach, helping colleagues to enhance their teaching and communica-
bringing many new initiatives and companions to PCR. tion skills?

*Corresponding author: 16, chemin de Catala, 31100 Toulouse, France.

Email: jfajadet@europcr.com

© Europa Digital & Publishing 2023. All rights reserved. The opinions expressed in this article are not necessarily those of the Editors of EuroIntervention or
of the European Association of Percutaneous Cardiovascular Interventions.
20

–H  ave you participated in a simulation-based learning session?
Still one of our Course priorities, simulation-based learning is
delivered by some of our best facilitators and teachers. These
sessions (developed with the kind support of Terumo Learning
Edge) allow you to immerse yourself through team interaction
and discover how to manage rare but potentially severe compli-
cations using realistic simulation models.
– Practical sessions and simulation-based learning in imaging and
valvular interventions? The “hands-on” sessions propose numer-
ous opportunities to learn new interventions or advance your
skills in more familiar procedures. This programme, developed
in collaboration with industry partners who are active in the
coronary, valve and structural field, allows creation of a contin-
uum from device handling to procedural integration and under-
scores our philosophy - “never for the first time in a patient”.
– Imaging? Imaging integration is never overlooked, and we have
developed sessions with the help of leading interventional imag-
ing specialists that highlight both intra- and extra-vascular imag-
ing tools and their application during procedures and beyond the
cath lab.
Science and innovation as well
– The highly popular PCR Innovators Day programme is back on
Monday - the place for all stakeholders in the innovation ecosys-
tem to meet and network.
▫ The Jon de Haan competition will take place during this spe-
cial day, and we look forward to the presentation of novel
technologies that will help patients in the near future. This
competition is supported by a very generous award from the
Jon de Haan Foundation, and PCR are very grateful for their
support and engagement.
– Essential trials, hotlines and trial updates will be presented in
dedicated sessions throughout the Course.
– Trials which are deemed to have the greatest impact on our prac-
tice will be highlighted in different ways. New this year, their
value will be assessed and scrutinised with the help of the PCR
Clinical Research Team.
A timely Ethica Award
This year, the Ethica Award will be given to the “Worldwide
Emergency Medical Services” for their amazing work that enables
the timely care of STEMI patients.
The question of effective care delivery is critical today and
spotlights the work of emergency medical services and emer-
gency and intensive healthcare professionals at every point in
the system.
The incredible job accomplished in the cath labs by means of
primary angioplasty is insufficient in isolation from the rest. It is
therefore imperative that we reach out and help to coordinate early
diagnosis, safe transfer en route to care and, after the interventional
A special Course with a rejuvenated and creative team
EuroIntervention 2023;19:20-21
procedure itself, the creation of strong links between primary care
physicians and nurse-led care tracks.
Therefore, while we already have great therapies to offer, we
must strive to make them more accessible and available at a faster
pace to a greater number of patients. We can do this by helping
implement the ever-growing portfolio of life-saving procedures,
extending beyond STEMI and NSTEMI reperfusion to include
thrombectomy for stroke, thrombus retrieval for massive pulmo-
nary embolism, prevention of systemic embolism using filters or
left atrial appendage closure devices – and so much more.
The time has come to create a global system that focuses on
improving interaction between different layers of care and result-
ing in better communication between healthcare professionals and
with their patients. Every great procedure is further enabled by
careful planning and detailed information for patients and their
families, then completed by a personalised follow-up in collabora-
tion with referring colleagues and primary care physicians.
Expanding access to life-saving procedures and transforming the
patient experience into an informed continuum of optimal care is one
of our principal objectives, and EuroPCR (and its associated PCR
Courses) are committed to playing a proactive role in this essential
aspect of an effective healthcare system, namely its proper delivery.
Value education – online or in-person
And this is why, even if you are not in Paris at the Course itself,
a rich and broad spectrum of “On demand” content will be gener-
ated and made available worldwide for those who cannot be pre-
sent with us. This will be available throughout the week of the
Course (and for the following month) and represents a continu-
ously available resource for you and your colleagues.
New this year, programme evaluation will be organised with
the help of graders from the Next Gen group, as well as hundreds
of PCR companions who volunteered to evaluate sessions while
attending. This assessment will allow us to determine which ses-
sions were the best (and not to be missed). In turn, this informa-
tion will be made available to enrich our educational offering and
provide essential feedback to the session delivery team.
EuroIntervention will of course be present with simultaneous
publications and a refreshed PCR-EAPCI Textbook (with 3 new and
up to 10 updated chapters) will add to this unique educational enter-
prise, providing contemporary and comprehensive content and visu-
als as well as additional opportunities for critical clinical reference.
The week in Paris promises to be exciting, energetic and stimulat-
ing - and will definitely reward the time you take away from home
and daily work. The teams at Europa Organisation have once again
done a wonderful job in carefully designing the most enabling envi-
ronment for our exchanges. We thank them for their dedication and
for providing such superb service to our community.
So, whether you attend onsite or online – join the PCR compan-
ionship – we very much look forward to welcoming you!
21
 Exploring
lnterventional Cardiology
Together
Membership
• Wide array of membership benefits
• Strong worldwide community

Education
• Webinars
• Certification
• Grants
• Fellows course

(j) EAPCI
Research & Publications
• Eurolntervention Journal
• PCR - EAPCI Textbook
• Atlas in interventional cardiology
• Registries

Congresses
• EuroPCR
Advocacy • PCR London Valves
• Valve for Life
• Patients Focus Initiative

• Join us today (t)ESC

European Society
www.escardio.org/EAPCI of Cardiology
 DEB AT E

EuroIntervention 2023;19:23-25
Invasive functional testing in the cath lab as a routine
investigation in INOCA: pros and cons
Bernard De Bruyne1*, MD, PhD; Marta Belmonte1, MD; Richard J. Jabbour2,3, MBBS, PhD, MRCP;
Nick Curzen2,3**, BM(Hons), PhD, FRCP
1. Cardiovascular Center Aalst, Aalst, Belgium; 2. University of Southampton Faculty of Medicine, Southampton, UK;
3. Coronary Research Group, University Hospital Southampton NHS Foundation Trust, Southampton, UK

Introduction symptoms. When coronary arteries are “non-obstructive” on inva-

While invasive coronary angiography can evaluate epicardial
coronary arteries in patients with suspected ischaemia, it may not
be sufficient for those with ischaemia and non-obstructed coro-
nary arteries (INOCA). In these cases, a more accurate diagnostic
approach involving invasive functional testing can be considered.
However, the routine use of invasive functional testing in INOCA
patients is still an area of debate due to uncertainties surround-
ing its diagnostic value, optimal thresholds, cost-effectiveness, and
therapeutic implications.
Pros
Bernard De Bruyne, MD, PhD; Marta Belmonte, MD
The goal of invasive coronary angiography is to identify the cause
of a patient’s symptoms that are possibly related to myocardial
ischaemia. Yet the epicardial coronary arteries we can “see” on
sive coronary angiography in patients with anginal chest pain
(ANOCA), coronary microvascular dysfunction (CMD) is too
often the convenient excuse for treatment failure. Then, without
any documentation of microvascular function, the patient is dis-
charged with a shrug of the shoulders and the diagnosis “it’s likely
the microcirculation”, a judgement often as mysterious for the
patient as it is for the physician.
Nowadays, there is no reason to deny patients a thorough func-
tional investigation of their entire coronary arterial system, includ-
ing the microcirculation, especially when their complaints are
debilitating, convincing and recurring.
Why?
VOLUME OF THE MICROVASCULAR COMPARTMENT
The epicardial arteries are the tip of the iceberg1, with the microvascular
DOI: 10.4244/EIJ-E-23-00008

angiography represent only a small portion of the total coronary compartment constituting 90% of the volume of the coronary circula-
arterial volume. Accordingly, coronary angiography overlooks tion2. This alone leads us to believe that it must be the site of patho-
several other reasons for myocardial ischaemia and its related logical mechanisms that contribute to limited myocardial perfusion.

*Corresponding author: Cardiovascular Center Aalst, OLV-Clinic, Moorselbaan, 164, B-9300 Aalst, Belgium.
E-mail: bernard.de.bruyne@olvz-aalst.be
**Corresponding author: Coronary Research Group, University Hospital Southampton NHS Trust, Tremona Road, Southampton,
SO16 6YD, United Kingdom. E-mail: Nick.Curzen@uhs.nhs.uk

© Europa Digital & Publishing 2023. All rights reserved. The opinions expressed in this article are not necessarily those of the Editors of EuroIntervention or
of the European Association of Percutaneous Cardiovascular Interventions.
23
EuroIntervention 2023;19:23-25
FREQUENCY OF THE PROBLEM
The reported prevalence of CMD varies from 15 to 75%, depend-
ing on patient selection and the definition3. More pragmatically,
approximately half of the patients with anginal chest pain and
signs of myocardial ischaemia have no evidence of epicardial
obstruction on invasive coronary angiography. This mainly illus-
trates that 50% of patients, while having a sizable pretest likeli-
hood of myocardial ischaemia, leave the catheterisation laboratory
without a diagnosis. It is precisely in this cohort of patients that
additional testing in the catheterisation laboratory is desirable4.
QUANTITATIVE MEASUREMENTS OF CMD ARE AVAILABLE
Until recently, assessing the microcirculation in the catheterisation
laboratory was either difficult, imprecise, or both.
Technical advances have been made that enable quantifica-
tion of microvascular resistance – the quintessential metric of the
microcirculation. The method used is based on continuous ther-
modilution, measuring volumetric flow (in mL/min) and absolute
microvascular resistance (in Wood Units) in a safe and largely
operator-independent manner5.
Theoretical progress has been made as well. Based on the
awareness that microvascular resistance at rest very often does not
correspond to true resting resistance, the concept of microvascular
resistance reserve has been proposed as a specific index for the
microcirculation6. At this time, highly precise and comprehensive
measurements of this type can only be achieved in the catheterisa-
tion laboratory. Therefore, in a medical world touting “precision
medicine”, there is no good reason for a patient with debilitating
symptoms and no obstructive coronary arteries to leave the room
Cons
Nick Curzen, BM(Hons), PhD, FRCP;
Richard J. Jabbour, MBBS, PhD, MRCP
Despite the recent pioneering studies demonstrating the high pre-
valence of ischaemia with non-obstructed coronary artery dis-
ease (INOCA) and the ability to use intracoronary (i.c.) tests to
describe abnormalities of the coronary circulation that are assoc-
iated with the symptoms and outcomes in these patients, several
factors prevent this being appropriate as routine clinical practice
at the current time.
First, the available i.c. wire-based tests themselves have impor-
tant limitations. Specifically, the inter- and intra-test reproducibil-
ity for standard parameters is not ideal for a routine investigation.
For example, recent data from Demir et al highlight the discrep-
ant output for thermodilution and Doppler-flow methods in terms
of coronary flow reserve (CFR) and hyperaemic microvascular
resistance/index of microvascular resistance (IMR) values8, which
is a particular concern given the current concept that there can
be binary cut-off values in this clinical context. In particular, the
24
without a full quantification of the function of his/her coronary
circulation.
MANAGEMENT
Data from the CorMicA7 trial have demonstrated that patients ran-
domised to receive specific management (including cardiac reha-
bilitation) guided by a functional testing-facilitated diagnosis of
CMD, spastic angina, or both, show robust and clinically rele-
vant improvement in patient-reported angina and quality of life.
Equally important, in CorMicA, patients deemed to have non-car-
diac symptoms were asked to de-escalate their medications. This
type of management should preferably be conducted in the setting
of a dedicated “ANOCA clinic”.
In conclusion, as interventional cardiologists, we should recog-
nise that epicardial disease represents only one of several pheno-
types in patients with angina and/or signs of myocardial ischaemia.
When patients present with no obstructive coronary arteries and
debilitating symptoms, it is our responsibility to provide them
with as complete a diagnosis as possible.
Conflict of interest statement
B. De Bruyne has an institutional consulting relationship with
Boston Scientific, Abbott Vascular, CathWorks, Siemens, GE
Healthcare, and Coroventis Research; has received institutional
research grants from Abbott Vascular, Coroventis Research,
CathWorks, and Boston Scientific; and holds minor equi-
ties in Philips, Siemens, GE Healthcare, Edwards Lifesciences,
HeartFlow, Opsens, and Celiad. M. Belmonte has no conflicts of
interest to declare.
validity of the cut-off values that are now applied when these tests
are used in clinical practice is questionable and demands more
investigation: for example, the notion that the dynamic function
of the microvasculature could be dichotomised by a single cut-off
for CFR and IMR is very challenging and biologically implau-
sible. The complex interaction between the epicardial, pre-arteri-
ole, arteriole and capillary segments is likely to yield a biological
spectrum of abnormality, thus, raising concerns that a patient with
apparently “normal” CFR and IMR, with negative fractional flow
reserve, could be reassured inappropriately based upon these arti-
ficial thresholds.
Second, the risk-benefit ratio for such testing on a routine basis
remains unacceptable. Despite fascinating preliminary data sug-
gesting that endotypes of INOCA can be identified and therapy
“tailored” accordingly7, the fact is that, as things stand, the menu
for such personalised therapy consists of the same standard pool
of tablets that we try routinely for all angina patients anyway.
Meanwhile, the introduction of a pressure wire into the distal
coronary artery carries a risk of important complications (usually

mediated by dissection) of around 2%9. Positive studies of specific
pharmacological agents targeting potential mediators of micro-
vascular dysfunction, such as endothelin antagonists10, are surely
required before it is possible to justify routine tests of this type?
Third, we require more information about the extent of coro-
nary microvascular dysfunction and, specifically, its distribu-
tion. For example, based upon current evidence, can we be sure
that a “negative” result for INOCA in the left anterior descend-
ing artery territory also excludes abnormality in the circumflex
and right coronary artery territories in the same individual? The
appetite for i.c. wire-mediated testing for INOCA, even among
its strongest advocates, is likely to be significantly dampened if
a 2- or 3-territory i.c. survey is required in each patient to provide
comprehensive reassurance.
Finally, the rapid advance in angiography-derived and non-
invasive assessment of the microcirculation11 may leapfrog cur-
rent i.c. wire technology into routine practice, simply because of
References
1.Taqueti VR. Coronary flow reserve: a versatile tool for interrogating pathophysio-
logy, and a reliable marker of cardiovascular outcomes and mortality. Eur Heart J.
2022;43:1594-6.
2. Feher A, Sinusas AJ. Quantitative Assessment of Coronary Microvascular Function:
Dynamic Single-Photon Emission Computed Tomography, Positron Emission
Tomography, Ultrasound, Computed Tomography, and Magnetic Resonance Imaging.
Circ Cardiovasc Imaging. 2017;10:e006427.
3. Mileva N, Nagumo S, Mizukami T, Sonck J, Berry C, Gallinoro E, Monizzi G,
Candreva A, Munhoz D, Vassilev D, Penicka M, Barbato E, De Bruyne B, Collet C.
Prevalence of Coronary Microvascular Disease and Coronary Vasospasm in Patients
with Nonobstructive Coronary Artery Disease: Systematic Review and Meta-analysis.
J Am Heart Assoc. 2022;11:e023207.
4. Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AHEM, Prescott E,
Karam N, Appelman Y, Fraccaro C, Louise Buchanan G, Manzo-Silberman S,
Al-Lamee R, Regar E, Lansky A, Abbott JD, Badimon L, Duncker DJ, Mehran R,
Capodanno D, Baumbach A. An EAPCI Expert Consensus Document on Ischaemia
with Non-Obstructive Coronary Arteries in Collaboration with European Society of
Cardiology Working Group on Coronary Pathophysiology & Microcirculation
Endorsed by Coronary Vasomotor Disorders International Study Group. Eur Heart J.
2020;41:3504-20.
5. Xaplanteris P, Fournier S, Keulards DCJ, Adjedj J, Ciccarelli G, Milkas A,
Pellicano M, Van’t Veer M, Barbato E, Pijls NHJ, De Bruyne B. Catheter-Based
Measurements of Absolute Coronary Blood Flow and Microvascular Resistance:
Feasibility, Safety, and Reproducibility in Humans. Circ Cardiovasc Interv.
2018;11:e006194.
6. De Bruyne B, Pijls NHJ, Gallinoro E, Candreva A, Fournier S, Keulards DCJ,
Sonck J, Van’t Veer M, Barbato E, Bartunek J, Vanderheyden M, Wyffels E, De Vos A,
El Farissi M, Tonino PAL, Muller O, Collet C, Fearon WF. Microvascular Resistance
Routine invasive functional testing in INOCA
EuroIntervention 2023;19:23-25
their potential to offer information on 3 territories in a quicker and
safer fashion.
In summary, we are on the (exciting) threshold of providing a per-
sonalised approach to the diagnosis and management of the spectrum
of conditions lumped together as INOCA, which represents a major
step forward for a population who have been routinely mismanaged
in the past. However, we need more information about the optimal
diagnostic tests and their thresholds for abnormality, and especially
regarding the efficacy of bespoke novel therapies, before i.c. wire-
based tests are ready and justifiable for routine clinical practice.
Conflict of interest statement
N. Curzen has received unrestricted research grants from Boston
Scientific, Haemonetics, HeartFlow, and Beckmann Coulter;
travel sponsorship from Edwards, Abbott and Boston Scientific;
and speaker fees/consultancy from Abbott, and Boston Scientific.
R.J. Jabbour has no conflicts of interest to declare.
Reserve for Assessment of Coronary Microvascular Function: JACC Technology
Corner. J Am Coll Cardiol. 2021;78:1541-9.
7. Ford TJ, Stanley B, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H,
Shaukat A, Lindsay M, Robertson K, Hood S, McGeoch R, McDade R, Yii E, Sidik N,
McCartney P, Corcoran D, Collison D, Rush C, McConnachie A, Touyz RM,
Oldroyd KG, Berry C. Stratified Medical Therapy Using Invasive Coronary Function
Testing in Angina: The CorMicA Trial. J Am Coll Cardiol. 2018;72:2841-55.
8. Demir OM, Boerhout CKM, de Waard GA, van de Hoef TP, Patel N, Beijk MAM,
Williams R, Rahman H, Everaars H; Oxford Acute Myocardial Infarction (OxAMI)
Study; Kharbanda RK, Knaapen P, van Royen N, Piek JJ, Perera D. Comparison of
Doppler Flow Velocity and Thermodilution Derived Indexes of Coronary Physiology.
JACC Cardiovasc Interv. 2022;15:1060-70.
9. Stables RH, Mullen LJ, Elguindy M, Nicholas Z, Aboul-Enien YH, Kemp I,
O’Kane P, Hobson A, Johnson TW, Khan SQ, Wheatcroft SB, Garg S, Zaman AG,
Mamas MA, Nolan J, Jadhav S, Berry C, Watkins S, Hildick-Smith D, Gunn J,
Conway D, Hoye A, Fazal IA, Hanratty CG, De Bruyne B, Curzen N. Routine Pressure
Wire Assessment Versus Conventional Angiography in the Management of Patients
With Coronary Artery Disease: The RIPCORD 2 Trial. Circulation. 2022;146:687-98.
10. Morrow AJ, Ford TJ, Mangion K, Kotecha T, Rakhit R, Galasko G, Hoole S,
Davenport A, Kharbanda R, Ferreira VM, Shanmuganathan M, Chiribiri A, Perera D,
Rahman H, Arnold JR, Greenwood JP, Fisher M, Husmeier D, Hill NA, Luo X,
Williams N, Miller L, Dempster J, Macfarlane PW, Welsh P, Sattar N, Whittaker A,
Connachie AM, Padmanabhan S, Berry C. Rationale and design of the Medical
Research Council’s Precision Medicine with Zibotentan in Microvascular Angina
(PRIZE) trial. Am Heart J. 2020;229:70-80.
11. Zhou J, Onuma Y, Garg S, Kotoku N, Kageyama S, Masuda S, Ninomiya K, Huo Y,
Reiber JHC, Tu S, Piek JJ, Escaned J, Perera D, Bourantas C, Yan H, W Serruys P.
Angiography derived assessment of the coronary microcirculation: is it ready for prime
time? Expert Rev Cardiovasc Ther. 20:549-66.
25
 CORONARY INTERVENTIONS
CONSENSUS
EuroIntervention 2023;19:26-36

The 17th expert consensus document of the European

Bifurcation Club – techniques to preserve access to the side
branch during stepwise provisional stenting
Manuel Pan1, MD, PhD; Jens Flensted Lassen2*, MD, PhD; Francesco Burzotta3, MD, PhD;
Soledad Ojeda1, MD, PhD; Remo Albiero4, MD; Thierry Lefèvre5, MD; David Hildick-Smith6, MD;
Thomas W. Johnson7, MD; Alaide Chieffo8, MD; Adrian P. Banning9, MD, PhD; Miroslaw Ferenc10, MD, PhD;
Olivier Darremont11, MD; Yiannis S. Chatzizisis12, MD, PhD; Yves Louvard5, MD; Goran Stankovic13, MD, PhD
1. Department of Cardiology, Reina Sofia Hospital, University of Cordoba (IMIBIC), Cordoba, Spain; 2. Department of
Cardiology B, Odense University Hospital & University of Southern Denmark, Odense C, Denmark; 3. Institute of Cardiology,
Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy; 4. Interventional
Cardiology Unit, Ospedale Civile di Sondrio, Sondrio, Italy; 5. Ramsay Générale de Santé - Institut Cardiovasculaire Paris Sud,
Hôpital Privé Jacques Cartier, Massy, France; 6. Sussex Cardiac Centre, Royal Sussex County Hospital, Brighton and Sussex
University Hospitals Trust, Brighton, UK; 7. Department of Cardiology, Bristol Heart Institute, University Hospitals Bristol and
Weston NHSFT & University of Bristol, Bristol, UK; 8. Interventional Cardiology Unit, San Raffaele Scientific Institute, Milan,
Italy; 9. Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, Oxford, UK;
10. Division of Cardiology and Angiology II, University Heart Center Freiburg-Bad Krozingen, Bad Krozingen, Germany;
11. Clinique Saint-Augustin, Bordeaux, France; 12. Cardiovascular Division, University of Nebraska Medical Center, Omaha,
NE, USA; 13. Department of Cardiology, Clinical Center of Serbia, and Faculty of Medicine, University of Belgrade, Belgrade,
Serbia

KEYWORDS
Abstract
Provisional stenting has become the default technique for the treatment of most coronary bifurcation lesions.
However, the side branch (SB) can become compromised after main vessel (MV) stenting and restoring
• bifurcation
SB patency can be difficult in challenging anatomies. Angiographic and intracoronary imaging criteria can
• side branch
predict the risk of side branch closure and may encourage use of side branch protection strategies. These
occlusion
protective approaches provide strategies to avoid SB closure or overcome compromise following MV stent-
• side branch
ing, minimising periprocedural injury. In this article, we analyse the strategies of SB preservation discussed
preservation
and developed during the most recent European Bifurcation Club (EBC) meetings.
DOI: 10.4244/EIJ-D-23-00124

*Corresponding author: Department of Cardiology B, Odense University Hospital, J. B. Winsløwsvej 4, Indgang 20,
4. sal, DK-5000 Odense C, Denmark. E-mail: Jens.flensted.lassen@rsyd.dk

© Europa Digital & Publishing 2023. All rights reserved. SUBMITTED ON 15/02/2023 - REVISION RECEIVED ON 1st 14/03/2023 / 2nd 28/03/2023 - ACCEPTED ON 28/03/2023

26

Abbreviations
CTO chronic total occlusion
EBC European Bifurcation Club
IVUS intravascular ultrasound
MV main vessel
OCT optimal coherence tomography
OTW over-the-wire
QCA quantitative coronary angiography
SB side branch
Introduction
Provisional stenting has become the default technique for the treat-
ment of most coronary bifurcation lesions. This strategy has also
been called the simple approach; however, sometimes the proce-
dure is not so simple – the side branch (SB) can occlude after
main vessel (MV) stenting in up to 6-18% of cases1-5. Restoring
SB patency can be difficult, and the fear of having to deal with
this situation may persuade operators to adopt an elective two-
stent strategy despite anatomical suitability for stepwise provi-
sional stenting. There are many ways to protect and restore side
branch flow. In this article, we analyse the strategies of SB pre-
servation during provisional stenting discussed in the last meeting
of the European Bifurcation Club (EBC).
SB relevance
Consistent with the Bifurcation Academic Research Consortium
(Bif-ARC) consensus6, an SB should be defined as “relevant” if
the reference vessel diameter is ≥2.0  mm and represents a  signi-
ficant territory (>10%) of the myocardium, impacting prognosis.
In the consensus6, an algorithm with a few scores to determine
SB relevance has been proposed. The minimum requirement to
assess the relevance of an SB is a baseline coronary angiogram
in 2 orthogonal views, which allows indirect measurements (SB
length, anatomical scores) that are surrogates of the SB-related
myocardial mass. In this respect, an SB length ≥73 mm is assumed
to supply ≥10% of myocardial mass7. However, in common prac-
tice, many operators consider a relevant SB a vessel ≥2.0 mm that
they are unwilling to lose in the context of a specific patient ana-
tomy. If the SB is considered relevant, then steps should be taken
to protect it.
Predictors of SB occlusion
The mechanism of SB occlusion is a combination of carina shift
and longitudinal plaque shift. However, the most prevalent cause
of SB occlusion is over-dilatation of the distal part of the MV stent
during the initial implantation. This is most prevalent in anatomies
that are already predisposed to SB closure. To avoid this risk, it
is crucial to implant the first stent according to the diameter of
the distal MV and to finalise the implantation with the proximal
optimisation technique (POT) above the carina level. The predis-
posing factors for SB occlusion have been identified in several
studies. By intravascular ultrasound (IVUS), a carina with a spiky
morphology (an “eyebrow” sign) has been found to be a powerful
Preserving SB access during provisional stenting
EuroIntervention 2023;19:26-36
predictor of ostial SB damage after MV stent implantation8. By
optimal coherence tomography (OCT), high lipid content of the
MV lesion and a contralateral location of lipid in the bifurcation
area can contribute to SB occlusion after provisional stenting9.
A narrower carina tip angle, a shorter length between the proximal
branching point to the carina tip and calcified plaque in the MV
have also been proposed as OCT factors for SB complication10,11.
Other angiographic characteristics have been reported as predictors
of SB occlusion, such as the diameter stenosis in both branches,
lesion length, bifurcation angle or a thrombus-containing lesion12.
A risk stratification score system (the RESOLVE [Risk prEdiction
of Side branch OccLusion in coronary bifurcation interVEntion]
score) was developed to help predict side branch occlusion4. This
score includes 6 independent variables with different weights in
the model: plaque distribution (on the opposing or same side of
the SB), Thrombolysis in Myocardial Infarction (TIMI) flow grade
of the MV before stenting, preprocedural diameter stenosis of the
bifurcation core (%), bifurcation angle, diameter ratio between
MV/SB and diameter stenosis of the SB before MV stenting (%).
Patients with a score ≥10 points are considered a high-risk group,
with a probability of SB occlusion close to 20%. A theoretical
limitation of this score is the inclusion of 4 quantitative coronary
angiography (QCA) parameters. QCA is objective but rarely used
prospectively in clinical practice. A modified score (V-RESOLVE)
has subsequently been developed, where the 4 angiographic vari-
ables are calculated by visual estimation13.
Although other variables may influence the risk of SB occlu-
sion, and an individualised assessment should be performed,
these scores can help in the risk stratification and identification
of patients who need additional attention paid to SB protection.
The importance of the jailed wire technique: old
and new evidence
PREVIOUS RECOMMENDATIONS
The jailed wire technique consists of leaving a wire in the SB
while implanting a stent in the MV (Central illustration). This
manoeuvre has been recommended in previous EBC consensus
documents14-17 as it has the following potential advantages:
– The technique helps to keep the SB open, and, in case of occlu-
sion, the guidewire is the only marker of the SB ostium.
– It facilitates access to the SB by favourably changing the angle
of the bifurcation.
– The jailed wire can provide anchoring of the guide catheter
which facilitate balloon crossing through the stent struts to the
SB.
– In case of SB occlusion, the jailed wire can be used to pass
a low-profile balloon (or penetrative microcatheter) between the
stent and the vessel wall to restore SB flow. The intervention
can then be completed with the inverted crush or any other tech-
nique18,19 (Figure 1).
These recommendations have been supported by the experience of
expert operators and by some observational studies20. The risk of
wire fracture is very low12,21, and although cases of this have been
27
EuroIntervention 2023;19:26-36

EuroIntervention

CENTRAL ILLUSTRATION Preserving SB access during provisional stenting.

Prevention Troubleshooting

Conventional
- Preshaped wires
- Reverse wire technique
- Dual lumen microcatheter
- Angulated microcatheter
- Deflectable microcatheter
Jailed wire
Active protection Preshaped wires Angulated
CTO wires microcatheter

Risk factors:
- Plaque on the same side of the SB
- Reduced TIMI flow at the SB
- Severe % DS of bifurcation core ≥70%
Jailed balloon Balloon-stent kissing Modified - Unfavourable bifurcation angle ≥90°
- High ratio MV/SB ≥2
- Severe % DS at SB ≥90%
- Spiky carina
- RESOLVE score >10
Deflectable Rescue
microcatheter jailed balloon

Semi-inflated Jailed Corsair

CTO: chronic total occlusion; DS: diameter stenosis; MV: main vessel; RESOLVE: Risk prEdiction of Side branch OccLusion in coronary
bifurcation intervention; SB: side branch; TIMI: Thrombolysis in Myocardial Infarction

Figure 1. Inverted crush as a rescue technique for acute side branch occlusion. A, B) Baseline angiography, lateral (A) and spider (B) views,
showing a severe bifurcation lesion at the distal LM (Medina 1,1,1). C) Acute LCx occlusion after LM-LAD stent implantation. Jailed
guidewire at LCx (arrows). D) Abluminal inflation of a balloon at LCx advanced through the jailed wire (after previous low-profile balloon
dilation). E) Patent LCx while the stent at the LAD remains crushed. F) DES implantation from LM to LCx artery (inverted crush technique).
G) Rewiring of the LAD and final kissing balloon inflation. H) Final angiographic result. DES: drug-eluting stent; LAD: left anterior
descending artery; LCx: left circumflex artery; LM: left main

28

described22-24, the advantages of this technique outweigh the risks.
Long jailed segments (>15-20 mm), especially in calcified vessels,
should be avoided, but if significant resistance is encountered in
attempted jailed wire removal, several techniques exist to ensure
safe removal. Firstly, interaction between the guiding catheter and
the proximal stent edge must be avoided, if ostial, through dis-
engagement of the catheter from the artery. The guide and side
branch wires may be withdrawn together while maintaining the
main vessel and the unjailed side branch wire in place. Once the
side branch wire is free, the guide catheter can be slowly read-
vanced over the existing two wires. If necessary, the passage of
a balloon through the lumen of the main vessel stent can provide
increased stability and allow more controlled retrograde traction
on the jailed wire. Failing that, a balloon catheter can be used on
the jailed wire to release contact with the main vessel stent, using
the SB rescue technique25.
NEW EVIDENCE
Recent publications have strengthened the previous
recommendations for more complex bifurcation lesions. In
a series of bifurcation-chronic total occlusion (CTO) lesions26
mainly treated with provisional stenting, the inability to protect
the SB with a wire was linked to procedural failure and a higher
incidence of periprocedural myocardial infarction. In the COBIS
III Registry12, SB wire jailing before MV stenting was associated
with a significantly lower rate of final SB occlusion in patients
with stenosis at the SB and MV ≥60%, but not in overall bifurca-
tion lesions. They did not therefore recommend routine SB wire
jailing for all bifurcation lesions treated with the provisional stent-
ing strategy, but only for complex bifurcations lesions with severe
stenosis of the SB or MV. In the EBC MAIN Study27, failure to
rewire a side vessel was more common when jailed wires were
Figure 2. Examples of difficult SB wiring in bifurcation lesions due to severe stenoses and unfavourable angulation of the SB origin in relation
to the MV. A and C) LAD/diagonal branch. B) LCx/obtuse marginal. The dotted lines show the theoretical trajectory of the wire. Appropriately
preshaped wire tips or any of the techniques described in the text will be needed to wire the MV and SB. LAD: left anterior descending artery;
LCx: left circumflex artery; MV: main vessel; SB: side branch
Preserving SB access during provisional stenting
EuroIntervention 2023;19:26-36
not used. Today, although there is consensus on the need for jailed
wires, there is no definite consensus on the anatomies in which
a jailed wire is essential. Some operators think that MV predilation
hints at how the SB might behave after MB stenting. Accordingly,
in cases of SB compromise after MV predilation, wiring of the SB
should always be performed.
SB wiring in challenging anatomies
During provisional stenting, baseline SB wiring, as mentioned
above, is recommended. After MV stenting and POT, SB rewiring
can be required to perform a kissing balloon inflation (KBI) and/
or to implant a second stent if there is severe stenosis or occlusion
of the side branch origin17.
Baseline SB wiring in challenging anatomies
SB wiring can be challenging in certain anatomical conditions
(Figure 2), such as extreme vessel tortuosity, extreme angulation
of the origin of the SB in relation to the MV, or severe steno-
sis in both the SB and MV. In this context, it is crucial to select
the optimal view to see each ostium of the bifurcation. Several
techniques are available to address and overcome these situations
(Central illustration):
1. Preshape the tip of the wire according to the bifurcation ana-
tomy. The curves typically used for this purpose are: 1) a single
bend with a short (2-3 mm) tip, 2) a single bend with a long
(4-6 mm) tip, 3) a single wide-angled bend and 4) a double-
bend shape28. If SB wiring using these curves fails, the opera-
tor can use more sophisticated techniques which are described
below.
2. The reverse wire technique: for this technique, two sharp curves
are created at the guidewire tip: a long proximal one, which
should create a loop in the distal MV and an opposite short
29
EuroIntervention 2023;19:26-36

distal one, which should engage the SB ostium during the wire
pullback29. This technique can be facilitated using a dual lumen
or angulated microcatheter.
3. Dual lumen microcatheters. A dual lumen microcatheter is par-
ticularly useful for a bifurcated CTO lesion (Figure 3), a tortu-
ous SB ostial lesion, and tricky bifurcation angles (Figure 2),
which require back-up force and directional SB wiring. Several
models are currently available (Table 1). The external diameter
at the tip and at the distal shaft, as well as the distance between
the tip and the over-the-wire (OTW) lumen exit port are vari-
able among the different models (Table 1). For SB wiring, the
MV wire is introduced into the monorail lumen, and the whole
catheter is advanced up to the level of the SB ostium. The OTW
exit port should be adequately orientated facing the SB ori-
gin, thus facilitating the passage of a second wire towards the
SB. Sometimes, the OTW exit port becomes misoriented, and
the operator must retrieve the microcatheter with the SB wire
inside, try to rotate the system and then advance it again, check-
ing the location of the OTW exit port. This manoeuvre can be
repeated until the right position is achieved. These microcath-
eters are especially useful in coronary bifurcation lesions assoc-
iated with a CTO (Figure 3), as they facilitate wire passage
through long segments of dissection, without risk of subinti-
mal dissection extension (Figure 3). It is important to note that
the use of a dual lumen microcatheter alters the properties of
the selected guidewire, increasing the penetrative force through
added support. Operators should therefore be aware of the risk
of vessel injury.
4. 
Dedicated single lumen angulated microcatheters. The
SuperCross Angled Tip Microcatheter (Teleflex) is available
in 130 and 150 cm lengths with different tip angles. The 120°
model is the most frequently used for extreme SB angulations30
(Figure 4). The recommended steps for SB access are:
– Deliver the SuperCross distally to the bifurcation over the MV
wire,
– Pull back the wire within the SuperCross,
– Pull back the SuperCross while torquing the tip towards the
SB origin,
– Re-advance a new wire to cross the SB ostium.
This technique may be easier in Medina X,0,X bifurcation

lesions where the SuperCross may be rotated at the level of
the distal MV. On the contrary, in Medina X,1,X bifurcation
lesions, the orientation of the SuperCross in front of the SB ori-
gin can be more complicated because of a lack of space at the
level of the SB ostium. These devices should be managed with
care to avoid the possibility of wall damage/dissection while the
dispositive is being rotated.
5. 
Deflectable tip single lumen microcatheters. The Venture
(Teleflex) wire-control catheter has a radiopaque 8 mm distal
tip that can be deflected up to 90º with a clockwise torque shaft

Figure 3. Dual lumen microcatheter in bifurcation lesions associated with CTO. Example of a right coronary artery CTO with a bifurcation at
the distal cap and a long proximal dissected segment (arrows). A) Wire into the true lumen of the posterior descending artery. B) Dual lumen
microcatheter to pass a new guidewire into the posterolateral branch. C) Final angiographic result after provisional stenting. CTO: coronary
chronic total occlusion

Table 1. Dual lumen microcatheters.

Outer Distance to
Usable Outer diameter, Outer diameter, Tip to OTW port Tip to Rx port
Name Manufacturer diameter, radiopaque
length, cm distal shaft (Fr) proximal shaft (Fr) distance, mm distance, mm
tip (Fr) marker, mm
FineDuo Terumo 140 1.4 0.5 2.9 3.2 6.5 210
Sasuke Asahi 145 1.5 4 2.5 x 3.3 3.2 6.5 200
Twin-Pass Teleflex 135 2.0 1 & 20 2.7 x 3.4 2.9 20 210
Twin-Pass Torque Teleflex 135 2.1 1&7 3.5 3.1 7 (10º) 220
NHancer Rx dual IMDS 135 1.5 Tip & 6.5 2.3 x 3.3 2.6 6.5 180
8 &12 (opposite
ReCross Dual IMDS 140 1.5 Tip, 8 & 12 2.3 x 3.3 2.6 x 3.4 Only OTW
directions)
Crusade Kaneka 140 2.2 1 2.9 3.2 6.5 210
OTW: over-the-wire; Rx: rapid exchange

30
 Preserving SB access during provisional stenting

EuroIntervention 2023;19:26-36
Figure 4. Angulated microcatheter in difficult baseline SB wiring. Severe bifurcation lesion involving the left circumflex artery/marginal
branch (Medina 1,1,1). A) Baseline angiography. B) Failure to cross with preshaped conventional wire. C) An angulated microcatheter
(SuperCross 120º) was placed distally to the bifurcation, and after a pull back and smooth torquing, the tip was oriented towards the SB
origin, facilitating the wiring. D) Final result after provisional stenting. SB: side branch

in the proximal part of the catheter. The catheter is advanced
to the bifurcation lesion in its straight configuration along the
guidewire. Once the target is reached, the tip is deflected to the
desired angle to access the SB ostium. Once the guidewire has
been advanced into the SB, the torque shaft may be turned anti-
clockwise to straighten the tip before withdrawing the catheter.
The success rate of this device, following failure of conven-
tional techniques, is approximately 85%31,32.
6. The balloon block and support technique. This technique is not
generally recommended but can be used if dedicated single or
dual microcatheters are unavailable. In cases with significant
angulation between the SB and MV, the SB guidewire usually
prolapses into the distal MV instead of the SB despite an appro-
priate tip shape. To mitigate this risk, an uninflated balloon may
be placed in the distal MV, close to the carina. Once the tip of
the SB guidewire reaches the level of the SB ostium, the MV
balloon is inflated to temporarily block the distal MV facilitat-
ing the advancement of the guidewire into the SB33.
7. MV balloon predilation. This is considered the “last resort”
strategy to wire the SB28. Indeed, this technique is not advis-
able in the vast majority of bifurcation lesions as it may cause
plaque and carina shift, ultimately resulting in SB occlusion.
Nevertheless, MV balloon predilation with a small balloon can
be considered in highly selected bifurcation lesions when all
other options have failed. Unfavourable anatomies, such as
those with large plaque burden in both the MV and SB and
a wide angle, may prevent the advancement of any appropri-
ately curved wire or device at the bifurcation lesion site. In this
situation, gentle predilation of the proximal MV may create
enough space to successfully advance and manipulate an angu-
lated catheter or an appropriately shaped wire toward the SB.
In case of severely calcified lesions, MV rotational atherectomy
may be a good alternative to MV balloon predilation. In a bifur-
cation subgroup analysis of the PREPARE-CALC Trial, rota-
tional atherectomy in the MV resulted in fewer compromised
SBs at the end of the procedure, as compared with a strategy of
MV balloon dilatation using a scoring/cutting balloon34.
SB rewiring after MV stenting in challenging
anatomies
In the provisional stenting approach, further interventions to the
SB may be required following MV stent implantation. SB rewiring
can be technically complex because of the baseline anatomy and/
or severity of the stenosis at the SB origin after MV stenting. The
most challenging situation is occlusion of a severely angulated SB.
SB REWIRING IS FACILITATED BY SOME PRELIMINARY
MANOEUVRES
– Leave a wire in the SB during MV stent implantation (jailed
wire technique).
– POT should be performed before SB rewiring to reduce the risk
of accidental wiring outside the stent in the main vessel. This
manoeuvre should be performed in accordance with the EBC’s
previous recommendations17,35. A too distal position of the bal-
loon when the bifurcation is not perfectly visualised can cause
SB occlusion.
– Consider inverted provisional stenting when SB access is more
difficult than MV access.
– SB balloon predilation before MV stenting. This approach is not
generally recommended, but it may be useful in a severely calci-
fied or angulated side branch stenosis, or when access to the side
branch is difficult, or when side branch flow is impaired after

31
EuroIntervention 2023;19:26-36
wiring35. This strategy could have the following advantages36,37:
a) it could increase the ostial lumen and, thus, facilitate rewir-
ing of the SB; b) it could help to maintain side branch flow after
MV stent implantation; c) it could be a definitive procedure on
the SB and avoid distortion of the main vessel stent. However,
side branch dissection is more common with this technique27 and
may prevent rewiring and lead to adverse outcomes.
SB REWIRING THROUGH THE MV STENT STRUTS
Most of the techniques described above may be useful in this situ-
ation, with some variations (Central illustration).
1. Guidewire tip configuration for crossing the MV stent side
cells, as well as the type of wire, depends on the preferences of
the operator. A single wide-angled bend or a double-bend shape
seem to be the most popular options for this purpose. Pulling
back the wire from the distal MV and allowing it to drop into
the SB increases the success rate and the chance of distal strut
crossing.
2. The reverse wire technique is less useful for SB rewiring than for
initial SB wiring. In contrast, angulated and deflectable tip cath-
eters may be more effective than they are in baseline conditions
(Figure  5, Figure  6). The large MV lumen created by the stent
allows the rotation and manipulation of these catheters to direct
their tip toward the SB ostium. At the same time, they provide
good support if there is resistance crossing the SB ostial stenosis/
occlusion. Dual lumen microcatheters are also useful in this con-
text to avoid abluminal wire crossing17 and facilitate SB wiring.
3. If an important SB becomes occluded and side branch wir-
ing attempts are not successful, an initial re-POT should be
Figure 5. Deflectable tip catheter for occluded SB rewiring after MV stenting. A) Bifurcation lesion with a critical stenosis at the diagonal
branch origin. B) SB occlusion after main vessel stent implantation with the jailed wire at the diagonal branch. C) The Venture catheter was
properly oriented and deflected to facilitate the SB rewiring. D) Final result after provisional stenting. MV: main vessel; SB: side branch
32
undertaken to ensure full stent strut expansion, followed by
further attempts to recross. If, however, these strategies fail,
a “rescue” balloon can be advanced behind the stent along the
jailed wire into the side vessel18,38 (Figure 1). As an alternative,
a Corsair (ASAHI) catheter can be used for this purpose (Figure
7). Depending on the ability to maintain SB patency and to
rewire the side branch with patency restored, the procedure may
progress to a stepwise provisional stenting strategy (with T and
small protrusion [TAP] technique if needed) (Figure  7), or an
inverted crush technique (with or without double-kissing). The
rewiring to the dissected branch along the jailed balloon (Real
JAB) technique presented by Kinosita at the 2022 EBC meet-
ing39 is a modification of the above-described “rescue” balloon
technique. It was designed to ensure wire insertion into the true
lumen of a dissected SB. It consists of inflating the jailed bal-
loon at the true lumen of the SB, while a second wire is inserted
into the SB through the MV stent struts. Immediately after bal-
loon deflation, the wire is advanced to try and reach the SB
true lumen.
4. The use of dedicated CTO wires provides another rescue strat-
egy for SB rewiring after SB occlusion, although with a higher
risk of vessel injury and subintimal tracking with risk of vessel
closure.
SB jailed balloon technique and active SB
protection
The jailed wire technique is known to reduce but not eliminate
the risk of transient or persistent SB occlusion. For this reason,
the jailed balloon technique was developed and first described
 Preserving SB access during provisional stenting

EuroIntervention 2023;19:26-36
Figure 6. Angulated microcatheter (SuperCross 120º) to rescue SB closure. Diffuse lesion at the LAD involving a diagonal branch (Medina
1,1,0). A) Baseline angiography. B) Acute SB occlusion after LAD stent implantation (jailed wire at diagonal branch). C) The microcatheter
can be more easily manipulated and oriented than in the example of Figure 4 because the MV distal segment is wider (already stented).
D) Final angiographic result after stent implantation at diagonal branch and final kissing balloon. LAD: left anterior descending artery;
MV: main vessel; SB: side branch

by Burzotta et al40. This technique involves the placement of an
uninflated balloon in the SB during MV stenting. The uninflated
balloon remains jailed under the MV stent after its deployment,
reducing both carina and plaque shifts due to its presence. If
the SB flow is preserved after MV stenting, the jailed balloon is
removed, uninflated. If the SB is occluded after MV stenting, the
SB jailed balloon is inflated to restore the flow in the SB.
Following the original description40, additional modifications
have been reported41 (Central illustration), including: 1) bal-
loon-stent kissing technique42,43; 2) modified jailed balloon tech-
nique44,45; 3) semi-inflated balloon technique46; 4) double-kissing
inflation outside the stent47; 5) jailed Corsair technique48,49. The
balloon-stent kissing technique requires a balloon with adequate
length that is appropriately sized, to approximate or be smaller
than the SB reference vessel diameter, to be advanced into the
SB. The MV stent is then advanced to the correct position at the
bifurcation site. The jailed SB balloon is inflated first at low pres-
sure (6-8 atm), while the MV stent is deployed at nominal pres-
sure. The SB balloon is then deflated and removed, leaving the
wire in the SB. Finally, the stent balloon is fully inflated to cor-
rect any stent deformation, per the conventional technique. At this
point, the procedure continues per the conventional provisional
stenting strategy. None of the four subtle variations mentioned
above44-47 have demonstrated superiority over the balloon-stent
kissing technique.
Observational studies have shown that all these modalities of
jailed SB balloon techniques for complex, true bifurcation lesions
offer good, immediate procedural success, with excellent SB
protection that prevents SB occlusion during the procedure, and
with good immediate clinical outcome in patients treated with the
provisional stenting approach. Table 2 describes SB protection and
rescue techniques.
Although the jailed SB balloon technique has demonstrated its
efficacy in protecting the SB in complex bifurcations treated by
provisional stenting, the standard jailed SB wire technique is eas-
ier to perform. The two techniques have been compared in a ran-
domised trial. The CIT-RESOLVE Trial50 included 335 patients
with high risk of SB occlusion randomised to either the conven-
tional strategy with the jailed SB wire technique or the SB protec-
tion strategy with the jailed SB balloon. The study demonstrated
that the active SB protection strategy was superior to the conven-
tional strategy and was associated with a significantly lower inci-
dence of SB occlusion and loss of SB flow immediately after full
apposition of the MV stent. However, a subgroup analysis demon-
strated no significant difference in major adverse cardiac events
(MACE) at 1-year follow-up51. A meta-analysis comparing active
versus conventional SB protection has been recently published52.
This analysis consisted of 1,174 patients with bifurcation lesions
treated with either strategy. The authors concluded that the active
SB protection strategy in bifurcation lesions was associated with
reduced SB deterioration, but it did not decrease procedural myo-
cardial infarction or improve the long-term prognosis.
Conclusions
Stepwise provisional stenting can be adopted for most complex
bifurcation lesions. However, side branch occlusion after main

33
EuroIntervention 2023;19:26-36

Figure 7. Corsair catheter used for SB rescue following the unsuccessful passage of a small balloon on a jailed wire behind the MV stent.
A) Baseline anatomy LAD/D1 (Medina 1,1,1). B) D1 occlusion after LAD stenting. A small balloon cannot cross behind the stent through the
jailed wire. C) A Corsair microcatheter crosses behind the stent on the jailed wire. D) Small balloon on a jailed SB wire and protective balloon
inside the stent. E) TAP stenting. F) Final result after new SB rewiring, TAP and kissing balloon inflation. D1: first diagonal; MV: main
vessel; LAD: left anterior descending artery. TAP: T and protrusion

Table 2. Side branch protection and rescue techniques.

TECHNIQUE
Jailed wire
Jailed balloon protection
Jailed microcatheter (including jailed
Corsair)
Inflated jailed balloon protection
(including modified jailed balloon and
balloon-stent kissing)
Semi-inflated jailed balloon protection
Rescue balloon jailing
Rescue microcatheter jailing
MV: main vessel; SB: side branch
WHEN TO APPLY
Before MV stenting
Before MV stenting
Before MV stenting
Before MV stenting
Before MV stenting
After MV stenting, in the case
of SB occlusion (or jailed wire
entrapment)
After MV stenting, in the case
of SB occlusion (or jailed wire
entrapment)
DESCRIPTION
Wire placement in the SB
Small-diameter balloon placed in the SB and kept uninflated during
MV stent deployment
Microcatheter placed in the SB and kept uninflated during MV stent
deployment
Small-diameter balloon (with different degrees of protrusion in the
MV) placed in the SB and kept inflated during MV stent deployment
Small-diameter balloon placed in the SB and inflated at low
atmospheres during MV stent deployment
Small-diameter balloon advancement and inflation over the jailed
wire
High-penetration microcatheter advancement over the jailed wire

vessel stenting can occur and is not always straightforward to fix.
Use of angiographic and intracoronary imaging criteria to predict
the risk of side branch closure may encourage use of side branch
protection strategies. These protection approaches have been dis-
cussed and developed following several EBC meetings and provide
strategies to avoid SB closure or overcome compromise following
MV stenting, minimising periprocedural injury and ensuring a dur-
able outcome for patients with bifurcation coronary lesions.
Conflict of interest statement
M. Pan has received speaker fees from Abbott, Terumo, and
Volcano. J.F. Lassen has received speaker fees from Medtronic,
Boston Scientific, Biotronik, Abbott, and Biosensors. F. Burzotta
has received speaker fees from Medtronic, Abiomed, Abbott, and
Terumo. S. Ojeda has received consulting fees from Medtronic
and Edwards Lifesciences; and speaker fees from Philips and
World Medical. R. Albiero has received speaker fees from

34

Medtronic and Abbott. T. Lefèvre has received speaker or proc-
torship fees from Abbott, Boston Scientific, Terumo, and Edwards
Lifesciences. D. Hildick-Smith disclosed advisory board/con-
sultancy/research funding from Terumo, Medtronic, Abbott, and
Boston Scientific. T.W. Johnson has received speaker fees from
Abbott, Boston Scientific, Medtronic, and Terumo; and insti-
tutional funding for fellowships from Boston Scientific and
Terumo. A. Chieffo has received speaker fees from Abiomed
and GADA. A.P. Banning received institutional funding of a fel-
lowship from Boston Scientific; and has received speaker fees
from Boston Scientific, Abbott, Medtronic, Philips/Volcano, and
Miracor. O. Darremont has received speaker fees from Edwards
Lifesciences. Y.S. Chatzizisis has received speaker fees/consul-
tancy/research funding from Boston Scientific and Medtronic.
G. Stankovic has received speaker fees from Medtronic, Abbott,
Boston Scientific, and Terumo. The other authors have no con-
flicts of interest to declare.
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 IN T E R V E N T I O N S F O R VA LV U L A R D I S E A S E A N D H E A R T FA I L U R E
EXPERT CONSENSUS

EuroIntervention 2023;19:37-52 published online ahead of print February 2023

Management of coronary artery disease in patients
undergoing transcatheter aortic valve implantation. A clinical
consensus statement from the European Association of
Percutaneous Cardiovascular Interventions in collaboration
with the ESC Working Group on Cardiovascular Surgery
Giuseppe Tarantini1*, MD, PhD; Gilbert Tang2, MD, MSc, MBA; Luca Nai Fovino1, MD, PhD;
Daniel Blackman3, MD; Nicolas M. Van Mieghem4, MD, PhD; Won-Keun Kim5, MD;
Nicole Karam6, MD, PhD; Pedro Carrilho-Ferreira7, MD; Stephane Fournier8, MD; Jerzy Pręgowski9, MD;
Chiara Fraccaro1, MD, PhD; Flavien Vincent10, MD; Rui Campante Teles11, MD, PhD; Darren Mylotte12, MD;
Ivan Wong13, MD; Gintautas Bieliauskas13, MD; Martin Czerny14, MD; Nikolaos Bonaros15, MD;
Alessandro Parolari16, MD, PhD; Darius Dudek17,18, MD, PhD; Didier Tchétché19, MD;
Hélène Eltchaninoff20, MD, PhD; Ole De Backer13, MD, PhD; Giulio Stefanini21, MD, PhD; Lars Sondergaard13,
MD, PhD
The authors’ affiliations can be found in the Appendix paragraph.

GUEST EDITOR: Franz-Josef Neumann, MD; Department of Cardiology and Angiology II, University Heart Center
Freiburg - Bad Krozingen, Bad Krozingen, Germany

KEYWORDS
Abstract
Significant coronary artery disease (CAD) is a frequent finding in patients with severe aortic stenosis under-
going transcatheter aortic valve implantation (TAVI), and the management of these two conditions becomes
• aortic stenosis
of particular importance with the extension of the procedure to younger and lower-risk patients. Yet, the
• coronary artery
preprocedural diagnostic evaluation and the indications for treatment of significant CAD in TAVI candi-
disease
dates remain a matter of debate. In this clinical consensus statement, a group of experts from the European
• TAVI
Association of Percutaneous Cardiovascular Interventions (EAPCI) in collaboration with the European
Society of Cardiology (ESC) Working Group on Cardiovascular Surgery aims to review the available evi-
dence on the topic and proposes a rationale for the diagnostic evaluation and indications for percutane-
ous revascularisation of CAD in patients with severe aortic stenosis undergoing transcatheter treatment.
Moreover, it also focuses on commissural alignment of transcatheter heart valves and coronary re-access
after TAVI and redo-TAVI.
DOI: 10.4244/EIJ-D-22-00958

*Corresponding author: Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Via Giustiniani 2,
35128 Padova, Italy. E-mail: giuseppe.tarantini.1@gmail.com

© Europa Digital & Publishing 2023. All rights reserved. SUBMITTED ON 31/10/2022- REVISION RECEIVED ON 1st 10/12/2022 / 2nd 11/01/2023 - ACCEPTED ON 19/01/2023

37
EuroIntervention 2023;19:37-52

Abbreviations
ACS acute coronary syndrome
AS aortic stenosis
BASILICA Bioprosthetic or native Aortic Scallop Intentional
Laceration to prevent Iatrogenic Coronary Artery
obstruction
CABG coronary artery bypass grafting
CAD coronary artery disease
CMR cardiac magnetic resonance
EAPCI European Association of Percutaneous
Cardiovascular Interventions
FFR fractional flow reserve
ICA invasive coronary angiography
iFR instantaneous wave-free ratio
MSCT multislice computed tomography
PCI percutaneous coronary intervention
SAVR surgical aortic valve replacement
TAVI transcatheter aortic valve implantation
THV transcatheter heart valve
Introduction
Transcatheter aortic valve implantation (TAVI) is an established
therapy for elderly patients with severe symptomatic aortic valve
stenosis (AS), irrespective of surgical risk1-3. The burden of coro-
nary artery disease (CAD) is significant in patients with severe AS
and may impact both the procedural risk as well as the post-proce-
dural prognosis of the patient. Randomised clinical trials and large
registries have reported that around half of subjects undergoing
TAVI have CAD, although the prevalence decreases in line with
the reduction in age and surgical risk profiles4-17 (Figure 1). Yet,
it should be noted that patients with severe CAD (i.e., SYNTAX
score >22, left main CAD) and those with a recent percutaneous
coronary intervention (PCI) were excluded from intermediate- and
low-risk TAVI trials. Despite TAVI having reached its maturity as
the preferred treatment in most patients with tricuspid AS and who
are >75 years of age, the preprocedural diagnostic evaluation and
indications for treatment of significant CAD in TAVI candidates
remain a matter of debate.
Regarding diagnosis, both anatomical and haemodynamic
assessments are the mainstay of CAD evaluation. Coronary angio-
graphy remains the standard anatomical assessment of CAD in
TAVI candidates. Meanwhile, computed tomography angiography,
already used routinely for preprocedural planning, has emerged as
a reasonable alternative to screen for CAD before TAVI. Few data
exist on the invasive haemodynamic assessment (fractional flow
reserve [FFR] or instantaneous wave-free ratio [iFR]) of CAD in
TAVI patients. Patients with severe AS have systolic left ventricular
(LV) outflow obstruction, elevated LV end-diastolic pressures, and
significant LV hypertrophy – all of which will preferentially reduce
systolic over diastolic coronary blood flow18 (Figure 2) and, hence,
impact the invasive physiological measurement.
With respect to CAD treatment, while coronary artery bypass
grafting (CABG) at the time of surgical aortic valve replacement
(SAVR) is considered the gold standard in surgical candidates with
concomitant significant CAD, treatment algorithms for significant
asymptomatic CAD in TAVI candidates vary considerably across
different institutions, as no consensus exists on the workup nor the
management of CAD in patients undergoing TAVI. The guidelines
give some recommendations, but the level of evidence is low and
based on non-randomised data1. Thus, whether performing PCI
before TAVI offers clinical benefit in patients with significant but
asymptomatic CAD remains unclear.

Prevalence of CAD (%)

100

80

60

40

20

0
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Figure 1. Prevalence of coronary artery disease (CAD) in patients treated with transcatheter aortic valve implantation as reported in
randomised clinical trials (blue columns) and real-world registries (red columns). STS/ACC TVT:  Society of Thoracic Surgeons/American
College of Cardiology Transcatheter Valve Therapy

38

Figure 2. Systolic coronary flow before and after TAVI. TAVI: transcatheter aortic valve implantation. Reproduced with permission18.
Another important point is represented by the unplanned need
for coronary intervention after TAVI. This concern increases as
TAVI expands to younger patients with longer life expectancy.
In these patients, the possible progression of CAD as well as
the occurrence of an acute coronary syndrome (ACS) or delayed
coronary occlusion makes the issue of coronary re-access after
TAVI clinically relevant. Preservation of coronary access dur-
ing the index TAVI procedure as well as the essentials of obtain-
ing coronary access in the presence of a transcatheter heart valve
(THV) are paramount for future invasive coronary diagnostics and
interventions.
Objectives
This position paper, developed by a group of international
experts invited by the European Association of Percutaneous
Cardiovascular Interventions (EAPCI) Scientific Documents and
Initiatives Committee, aims to provide a rational and practical
approach to the management of CAD in patients with sympto-
matic severe AS undergoing TAVI. Specifically, it is focused on
the diagnosis and treatment of significant CAD in TAVI candi-
dates, as well as on THV commissural alignment and coronary
re-access after TAVI and redo-TAVI, with each considered topic
based on literature review .
Diagnostic evaluation of CAD in patients
undergoing TAVI
INVASIVE CORONARY ANGIOGRAPHY
Invasive coronary angiography (ICA) remains the current stand-
ard of care in the assessment of CAD among patients undergoing
TAVI and has several benefits. Firstly, elderly patients scheduled
for TAVI often have coronary arteries with a significant burden
of calcium – limiting the diagnostic performance of coronary CT
angiography19. Secondly, clinical practice guidelines on valvular
heart disease recommend that decisions on coronary revasculari-
sation be based primarily on the angiographic degree of disease
severity1,20. Thirdly, in cases of intermediate CAD severity, ICA
may allow immediate invasive physiological and imaging assess-
ment of CAD, as well as the potential to proceed directly to PCI
in the same sitting, where appropriate.
CAD management in TAVI
EuroIntervention 2023;19:37-52
Current clinical practice guidelines do not address the timing of
ICA in patients undergoing TAVI20. Most operators perform ICA
in advance of the TAVI procedure to minimise procedure time and
contrast volume, as well as to inform the Heart Team on the need
for revascularisation, which could influence the choice between
SAVR+CABG versus TAVI+PCI. However, concomitant ICA at
the time of TAVI may be considered in patients who are not surgi-
cal candidates and/or with a low probability of significant CAD.
However, ICA does have disadvantages, including an increased
risk of vascular complications, contrast nephropathy, additional bur-
den on the healthcare system and a potential to delay the treatment
of AS. Current clinical practice guidelines recommend ICA for the
assessment of CAD prior to consideration of either SAVR or TAVI
– particularly in patients with a history of cardiovascular disease,
with at least one cardiovascular risk factor, suspected myocardial
ischaemia, LV systolic dysfunction, or men >40 years of age and
postmenopausal women (Class I, Level of Evidence [LoE] C)1.
INVASIVE CORONARY PHYSIOLOGY ASSESSMENT
Invasive physiological assessment of coronary lesions using FFR
or iFR is an established and well-validated approach to guide PCI
and has a Class 1, LoE A recommendation in international guide-
lines. However, there are no randomised trial data and only limited
observational studies addressing invasive physiological assess-
ment in patients with severe AS.
Aortic stenosis generates LV pressure overload, leading to ven-
tricular remodelling and hypertrophy. The consequent increase in
LV mass and intracavity pressure induces changes in coronary
anatomy and physiology which potentially impact the assessment
of ischaemia using both FFR and iFR (Table 1)21,22.
Furthermore, while the safety of both intracoronary and intrave-
nous adenosine has been demonstrated in numerous studies18,23-25,
some data suggest that its effect may be blunted in patients with
AS, leading to a potential underestimation of the severity of coro-
nary artery stenosis with FFR18. Moreover, AS acts as an effective
tandem lesion downstream of an epicardial coronary stenosis, and
this might represent another pitfall of FFR in this setting.
Studies that evaluated the impact of severe AS on FFR, by per-
forming pressure wire assessment both before and after TAVI,
39
EuroIntervention 2023;19:37-52
Table 1. Effects of aortic stenosis on coronary anatomy and
physiology.
Effects of AS on coronary artery anatomy and physiology
Reduction in stroke volume, systolic and mean arterial pressure,
which may cause reduced coronary perfusion pressure
Decreased density of coronary microvasculature
Attenuated and delayed systolic forward compression wave of
coronary blood flow
Increased resting diastolic backward expansion wave
Reduction in resting microvascular resistance, with inability to
reduce further in response to hyperaemia
Upregulation of vasoactive factors, leading to increased resting
blood flow
Microvascular dysfunction impairing hyperaemic response
Reversal of normal endocardial-epicardial blood flow ratio at rest
Reduced diastolic coronary perfusion phase
Attenuated coronary flow reserve
have presented conflicting findings. While some investigations
have shown a reduction in FFR immediately after TAVI, with
a further decline in the long term attributable to increased systolic
hyperaemic flow26,27, an increase in FFR immediately after TAVI
has also been described28. The largest available study to date found
no significant overall change in FFR values after TAVI, but while
lesions with a positive baseline FFR decreased after TAVI, nega-
tive values increased. However, the changes in FFR were small
and only affected the indication for revascularisation in a minor-
ity of lesions24.
iFR may represent a better option in patients with AS since it
does not require adenosine and is independent of systolic flow.
However, observational data are also inconsistent. While several
studies found no significant changes in iFR immediately before
and after TAVI18,27, the same authors reported significant differ-
ences, leading to a change in the indication for intervention in
more than a quarter of patients29. Limited data on the correla-
tion of invasive coronary physiology assessment with clinical
outcomes in AS patients are promising, but long-term data are
scarce30. Some studies have suggested that the cut-off values for
physiological assessment of coronary lesions which correlate with
clinical outcomes differ in patients with AS25. However, current
evidence is inconclusive, hence use of the conventional thresholds
of FFR ≤0.80 and iFR ≤0.89 is advisable.
Overall, further research on the clinical value of invasive cor-
onary physiology in the context of severe AS is needed, par-
ticularly for validation of (non-) hyperaemic cut-offs to guide
revascularisation.
NON-INVASIVE CAD ASSESSMENT
Avoiding ICA by a non-invasive assessment of CAD in TAVI
patients is appealing. Multislice computed tomography (MSCT) is
routine prior to TAVI for procedural planning. The MSCT may be
used for concomitant CT coronary angiography (CTCA), allowing
for an evaluation of CAD without a significant additional burden
40
to the patient or healthcare system, and may potentially expedite
the treatment of AS.
CTCA might be considered in patients with a low pretest prob-
ability of CAD and in whom reasonable image quality is expected.
Given that the prevalence of significant CAD among elderly
TAVI recipients approaches 50%31, including prior PCI in 20%32,
and that significant coronary calcification is frequent, CTCA is
unlikely to be of adequate diagnostic quality for the majority of
pre-TAVI CAD assessments33.
Another study found it was possible to use the pre-TAVI MSCT
to evaluate the presence of significant CAD in 76.3% of their
TAVI cohort, while 21.7% required ICA due to suboptimal CT
imaging or clinically significant disease on MSCT34. There was
no significant difference in 30-day or 1-year major adverse car-
diac events between patients who required ICA and those who did
not. A contemporary meta-analysis including 7 studies and 1,275
TAVI patients compared the diagnostic accuracy of the pre-TAVI
MSCT to ICA35. The pooled sensitivity, specificity, and positive
(PPV) and negative predictive values (NPV) of the non-invasive
approach were 95%, 65%, 71% and 94%, respectively.
Fractional flow reserve-computed tomography (FFR-CT) pro-
vides both anatomical and functional assessments of coronary
arteries and substantially improved diagnostic accuracy in a recent
prospective comparison with invasive FFR in 42 patients (68 ves-
sels) with severe AS36. The CT data were interpretable in 92.3%
of patients; sensitivity, specificity, PPV and NPV were 73.9%,
78.4%, 68.0%, and 82.9%, respectively.
These data suggest that pre-TAVI CTCA, potentially in combi-
nation with FFR-CT, may offer potential advantages in time, cost,
and risk and may become an alternative first-line screening strat-
egy in selected subsets of AS patients.
Cardiac magnetic resonance (CMR) imaging can be used to
evaluate myocardial perfusion, myocardial viability, and proximal
coronary anatomy and can provide important prognostic informa-
tion such as the extent of myocardial fibrosis and characterisation
of LV remodelling37. A single, small study showed a high sensitiv-
ity and specificity for stress-perfusion CMR when compared to
ICA in 23 patients with severe AS38. Notably, adenosine stress-
perfusion was performed without complications despite the pres-
ence of severe AS. When compared to MSCT, however, the CMR
scan is technically more challenging and represents an additional
step in the pre-TAVI pathway; hence, it should be reserved for
specific indications, rather than as part of a routine workup39.
Consensus points:
1) Invasive coronary angiography should remain the mainstay of
CAD assessment in the majority of TAVI candidates.
2) Assessment of coronary artery disease by means of pre-TAVI
CTCA may be considered in younger patients with a low car-
diovascular risk profile.
3) More data are needed to assess the clinical value of invasive
coronary physiology assessment in patients with severe aortic
stenosis.

Management of CAD in patients undergoing
TAVI
While it is clear that AS patients presenting with an ACS should
undergo revascularisation of the culprit vessel, many questions
still linger about the management of significant stable CAD
in subjects undergoing TAVI. Should PCI be pursued in every
patient with severe stable CAD? Should it be performed before,
during or after TAVI? What is the role of physiology-guided
PCI in the setting of AS? Should we always aim for complete
revascularisation?
PCI IN PATIENTS WITH STABLE CAD UNDERGOING TAVI
A meta-analysis of observational studies including over
5,000 patients comparing the outcomes of patients with CAD
undergoing TAVI with versus without prior PCI found no bene-
fit from routine PCI before TAVI for either 30-day major adverse
cardiovascular events (MACE; death, myocardial infarction, stroke,
acute kidney injury) or one-year mortality40. The ACTIVATION
(PercutAneous Coronary inTervention prIor to transcatheter aor-
tic VAlve implantaTION) non-inferiority trial is the only ran-
domised study comparing a PCI versus no-PCI strategy in patients
with severe symptomatic AS and significant CAD41. In this study,
the primary composite endpoint of all-cause death and rehospi-
talisation occurred in 41.5% of the PCI arm and 44.0% of the no-
PCI arm (the requirement for non-inferiority was not met), with
a higher incidence of bleeding in the PCI arm41. Nevertheless, the
results of the ACTIVATION trial should be viewed in the light
of its many limitations (e.g., the study was underpowered for the
primary endpoint, it included only subjects with stable CAD – of
whom 69% were completely asymptomatic – and more than two
thirds of patients had single-vessel CAD).
In the Evolut Low Risk trial, fewer patients with CAD received
PCI with TAVI than SAVR with CABG, with similar mortality,
disabling stroke, or myocardial infarction at 2 years (Kini A, et al.
Two-year outcomes following TAVI or SAVR in patients stratified
by need for revascularisation. PCR London Valves 2021. https://
eposter.europa-organisation.com/2021/pcrvalves/index/slide/
abstract/44. Last accessed: 6 February 2023).
Management may be based on the clinical presentation, with
PCI performed in patients with angina. However, this approach
can be challenging given the overlap between AS- and CAD-
related symptoms. The location of the coronary stenosis may also
be important in selecting which patients should undergo PCI. In
the French national registry of TAVI (FRANCE 2), only significant
lesions of the left anterior descending artery (LAD) were assoc-
iated with increased 3-year mortality (hazard ratio [HR]: 1.42,
95% confidence interval [CI]: 1.10-1.87)42. However, all these
approaches deserve validation in future large-scale randomised tri-
als, and several studies are ongoing, including COMPLETE TAVR
(ClinicalTrials.gov: NCT04634240). As of today, according to the
ESC/European Association for Cardio-Thoracic Surgery (EACTS)
Clinical Practice Guidelines on Myocardial Revascularization, PCI
should be considered in patients undergoing TAVI with a coronary
CAD management in TAVI
EuroIntervention 2023;19:37-52
artery diameter stenosis >70% in proximal segments (Class IIa,
LoE C)20.
The approach to percutaneous coronary revascularisation in
patients undergoing TAVI suggested by this consensus was devel-
oped based on the available literature, which largely refers to
patients older than 75 years of age. Yet, guideline recommendations
regarding coronary revascularisation in TAVI patients do not dif-
fer in subjects <75 versus >75 years of age. The presence of CAD,
together with the life expectancy of the patient undergoing TAVI,
should be weighted by the Heart Team with regard to the choice of
transcatheter heart valve (THV), aiming at preserving future coro-
nary access and the possibility of repeat TAVI.
Notably, guidelines and surgical consensus state that in patients
undergoing SAVR, revascularisation of proximal significant CAD
should be pursued (LoE C). A more extensive revascularisation
is usually performed with the surgical approach in order to avoid
a repeat sternotomy. Yet, the mortality risk of SAVR+CABG
is higher than that of SAVR alone. In this regard, it should be
acknowledged that robust evidence for a definitive recommen-
dation about indication and completeness of revascularisation is
lacking also for the surgical approach.
TIMING OF PCI
The optimal timing of PCI (before vs concomitant vs after TAVI)
in patients undergoing TAVI remains uncertain, and the available
evidence is based on retrospective registry data only. Each strategy
has its pros and cons (Table 2).
The potential challenges in reaccessing the coronary arteries
after TAVI have been suggested as a reason to advise systematic
PCI before TAVI. This strategy is supported by a study where
failure to access the coronary arteries was reported in 17.9% of
patients treated with a certain THV platform43. Concordantly, PCI
is mostly performed before THV implantation – either as a staged
or concomitant procedure44-47. According to an American nation-
wide sample of 22,344 patients, in-hospital mortality was higher
if TAVI and PCI were performed during the same hospitalisation
(10.7% vs 4.6%; p<0.001)48. However, the authors could not dif-
ferentiate if both procedures were staged or concomitant, nor if
PCI was planned or performed urgently because of ischaemic
complications during or after TAVI. A substudy of the SURTAVI
trial showed similar rates of all-cause mortality and stroke but
a lower rate of acute kidney injury in patients undergoing staged
as compared to concomitant PCI49. A meta-analysis of 5 observa-
tional reports, including 1,634 patients, showed that concomitant
TAVI and PCI procedures were associated with similar 30-day and
1-year mortality as compared to isolated TAVI44. Recently, Ochiai
et al reported a single-centre experience with 2-year follow-up of
258 patients who underwent elective PCI before TAVI (n=143),
simultaneously with TAVI (n=77) or post-TAVI (n=38), and found
no differences in clinical outcomes50.
Cannulation of the coronary ostia may be more challenging
after TAVI, especially after implantation of self-expanding THVs
with a supra-annular leaflet position51,52. In a group of 41 patients
41
EuroIntervention 2023;19:37-52
Table 2. Advantages and disadvantages of different PCI timing in patients undergoing TAVI.
PCI before TAVI
Advantages - Easier coronary access (especially for
self-expanding THV with a supra-
annular leaflet position)
- Lower risk of ischaemia-induced
haemodynamic instability (i.e.,
during rapid pacing)
- Reduced contrast use compared with
concomitant PCI and TAVI
Disadvantages - Less reliable FFR/iFR assessments of
borderline lesions
- Higher risk of haemodynamic
instability due to AS
AS: aortic stenosis; AKI: acute kidney injury; DAPT: dual antiplatelet therapy; FFR: fractional flow reserve; iFR: instantaneous wave-free ratio; LV: left
ventricular; PCI: percutaneous coronary intervention; TAVI: transcatheter aortic valve implantation; THV: transcatheter heart valve
implanted with balloon-expandable valves who underwent angio-
graphy/PCI both before and after TAVI, there were no differ-
ences in the rate of successful selective coronary cannulation
or any procedural variables (i.e., duration or contrast volume)53.
Zivelonghi et al performed successful angiography in 65 out of
66 subjects after TAVI (25 self-expanding THVs with a supra-
annular leaflet position and 41 balloon-expandable THVs with an
intra-annular leaflet position); only one artery was not accessible
because of a high implantation of an Evolut R (Medtronic) THV54.
However, Blumenstein et al reported that selective cannulation
of the coronary ostium was feasible in all patients who received
balloon-expandable valves but only in 3 out of 15 treated with
supra-annular self-expanding prostheses55.
Thus, decision-making on PCI in patients scheduled for TAVI
should be based on patient characteristics, including the presence
or absence of angina, CAD severity, lesion location and complex-
ity, and type of implanted THV. The evidence base is limited but,
in general, does not support routine PCI prior to TAVI in asympto-
matic lesions and suggests that when PCI is performed, a separate
staged procedure prior to TAVI is preferable.
The ongoing 900-patient TAVI PCI Trial (ClinicalTrials.gov:
NCT04310046) randomises patients 1:1 to FFR-guided PCI
1-45 days before or after implantation of a SAPIEN 3 (Edwards
Lifesciences) THV. This study will also inform current practice on
the value of invasive coronary physiological assessment of inter-
mediate coronary lesions in AS patients, as a second iFR meas-
urement in the group undergoing PCI after TAVI is planned. The
aforementioned COMPLETE TAVR trial is currently randomis-
ing 4,000 TAVI patients with severe CAD (i.e., at least one coro-
nary artery lesion of ≥70% visual angiographic diameter stenosis
in a native segment that is at least 2.5 mm in diameter, exclud-
ing chronic total occlusions) to staged complete revascularisation
after TAVI with a balloon-expandable valve versus medical man-
agement alone.
ANGIOGRAPHY-GUIDED VERSUS PHYSIOLOGY-GUIDED PCI
Angiography alone versus physiology-guided revascularisa-
tion was compared in a propensity score-matched analysis of
42
PCI after TAVI Combined PCI and TAVI
- More reliable FFR/iFR of intermediate - Use of the same arterial access
lesions - Lower cost
- Lower risk of haemodynamic
instability during complex PCI (i.e.,
with rotational atherectomy and
impaired LV function)
- Reduced contrast use compared with
concomitant PCI and TAVI
- More challenging and potentially - Larger amount of contrast and higher
compromised coronary access risk of AKI
- Less stability and support of the - Prolonged procedure
coronary guiding catheter - Need for DAPT at the time of TAVI,
- Potential THV dislodgement hence increased bleeding risk
 
318 patients with AS. Following FFR, the number of diseased
vessels was downgraded (from 1.85±0.97 to 1.48±1.00; p<0.01)
and significantly lower than in the angiography-alone group
(1.48±1.00 vs 1.80±0.97; p<0.01) without significant differences
in MACE at 5 years56.
The FAITAVI (Functional Assessment In TAVI; ClinicalTrials.
gov: NCT03360591) trial is randomising patients with severe
AS and CAD to percutaneous myocardial revascularisation
dictated according to an angiography-guided versus physio-
logy-guided (i.e., FFR/iFR) strategy and evaluating the incidence
of MACE, bleeding and target lesion failure at 24 months. The
TCW Trial (TransCatheter Valve and Vessels; ClinicalTrials.gov:
NCT03424941) is a prospective, randomised, controlled, open-
label, multicentre, international, non-inferiority trial of patients
with multivessel disease and AS. Patients will be randomised in
a 1:1 fashion to TAVI and FFR-guided PCI (experimental arm)
and CABG and SAVR (comparative arm).
At present, there are no randomised studies comparing com-
plete versus incomplete revascularisation in patients with stable
CAD undergoing TAVI. Thus, no recommendations can be made.
A Heart Team-based decision of the most appropriate revasculari-
sation strategy for TAVI patients should be aimed for in all cases.
ANTITHROMBOTIC THERAPY POST-TAVI AND PCI
Antithrombotic therapy after TAVI remains a field of rapidly
evolving evidence. Recent data suggest that monotherapy (either
single antiplatelet therapy [SAPT] or oral anticoagulant therapy
[OAC]) is associated with better clinical outcomes than dual
therapy (dual antiplatelet therapy [DAPT] or SAPT+OAC)57,58.
Consequently, the standard treatment after TAVI is aspirin, while
patients with an indication for OAC should receive this as mono-
therapy. However, treatment should also be adjusted to patient-
specific factors such as CAD, and in particular recent PCI, with
DAPT prescribed according to existing clinical practice guidelines
for patients with recent acute coronary syndromes and/or PCI. The
balance between the benefit of reduction of ischaemic events and
the risk of bleeding remains the major determinant in decision-
making, as TAVI patients often have concomitant high bleeding

risk factors including age >75 years59. According to those guide-
lines, in patients with high bleeding risk and no indication for
OAC, DAPT for 3 months should be followed by SAPT. When
long-term OAC is indicated, triple therapy should be stopped after
1 week and followed by OAC+SAPT for 6 months. In cases of
high or very high bleeding risk, triple therapy should be avoided,
and SAPT+OAC can be withheld after 1-3 months and followed
by OAC alone60.
Consensus points:
1) P CI before TAVI should be performed in patients with severe
CAD (i.e., coronary artery diameter stenosis >70%, >50% for
the left main) only in proximal segments, particularly if pre-
senting with an acute coronary syndrome, symptoms of angina
pectoris or subocclusive lesions (i.e., >90% diameter stenosis).
2) The timing of PCI with respect to the TAVI procedure should
be based on clinical presentation, the patient’s anatomical char-
acteristics and coronary lesion complexity.
3) If PCI is planned after TAVI, the THV choice (i.e., low-frame
versus high-frame) and implantation technique (i.e., commis-
sural alignment) should be aimed at preserving easy coronary
access.
Coronary access and TAVI
NEED FOR CORONARY ACCESS AFTER TAVI AND CLINICAL
INDICATIONS
Data from large-scale TAVI registries show that ICA and/or PCI
may be required in approximately 2% of TAVI patients within
the first year after TAVI52,61,62. ICA is performed in up to 16% of
TAVI patients within 5 years of follow-up, and approximately 5%
of these patients undergo PCI of one or more coronary lesions63.
Around two-thirds of post-TAVI ICA/PCI procedures are performed
in the setting of ACS, mainly due to unstable angina or non-ST-
segment elevation myocardial infarction, whereas silent ischaemia,
stable angina or workup for heart failure serves as an indication
for the remaining 1/3 of cases52,61,63. However, even though histori-
cally the reported frequency of ICA/PCI procedures after TAVI is
low, this may change, due not only to the recently introduced more
conservative strategy for asymptomatic lesions but also to the treat-
ment being used more frequently in younger patients with longer
life expectancies who may eventually develop symptomatic CAD.
TRANSCATHETER HEART VALVE SELECTION AND IMPACT
ON FUTURE CORONARY ACCESS
The choice of THV is subject to multiple factors including the
patient's individual anatomical suitability, availability, and oper-
ator experience64. The overarching purpose of an optimal THV
selection must be to achieve the best possible immediate out-
come with the least likelihood of major complications. However,
in view of improved procedural results in recent years, long-term
considerations, including THV durability, feasibility of redo-TAVI,
conduction abnormalities, and the possibility for future coronary
access, also become important.
CAD management in TAVI
EuroIntervention 2023;19:37-52
THV design, in particular the stent frame height and leaflet
position, can affect future coronary access. Thus, familiarity with
available THV devices is essential, including for interventional
cardiologists not performing TAVI (Figure 3, Figure 4). This is
particularly important, since in SAVR, native leaflets are resected
and surgeons routinely align the surgical valve commissural posts
to native commissures to make coronary access straightforward65.
However, commissural alignment has not been uniformly per-
formed in TAVI, and certain THV designs may make coronary
access more challenging.
The balloon-expandable SAPIEN 3 and SAPIEN 3 Ultra
(Edwards Lifesciences) THVs have a low stent-frame height (15.5-
22.5 mm, according to valve size) with an upper row of open cells
as well as an intra-annular leaflet position. Accordingly, coronary
cannulation is often possible either above the outflow of the THV
or through the large cells in the upper row of the stent, depend-
ing on the THV implant depth in relation to the patient’s anatomy.
The stent frame of the self-expanding Evolut R, Pro and Pro+
(Medtronic) THVs extends beyond the coronary ostia. The leaflets
are supra-annular with a 26 mm commissural post height from the
THV inflow. Therefore, coronary access is achieved in most cases
through the diamond-shaped prosthesis frame cells.
The self-expanding ACURATE neo and neo2 (Boston Scientific)
THVs with a supra-annular leaflet position have a commissural
post height of 25-31 mm, according to valve type and size, but
have an open-cell architecture in the upper part of the frame that
allows easier access to the coronary ostia.
The Portico and Navitor (Abbott) THVs with an intra-annular
leaflet position have a tall stent-frame design with a commissural
post height of 21-25 mm and an open-cell design.
It should be noted that, more than the commissural post height
per se, what influences coronary access after TAVI (and after redo-
TAVI) is the THV leaflet height with respect to the recommended
annular positioning, which is lowest for the SAPIEN 3/Ultra and
highest for the Evolut R/Pro THVs (Figure 3).
Importantly, coronary access after TAVI is also influenced by
several critical anatomical factors, such as sinus sizes (particularly
in relationship to the THV size), height and width of the sinotubu-
lar junction (STJ), and coronary location in terms of the height and
relation with native commissures.
Available data on coronary access following TAVI demonstrate
an overall high success rate of coronary engagement (Table  3),
which is reassuring and suggests that coronary access should
not be the decisive factor in the THV selection algorithm61,66,67.
Nonetheless, there is increasing evidence in the literature that
high stent-frame THVs with a supra-annular leaflet position are
more challenging in regard to selective coronary cannulation,
especially in the case of severe commissural misalignment68 or
a high implant THV position69 – the latter being pursued for most
THV types to reduce rates of permanent pacemaker implanta-
tion70-73.
Coronary access may be even more challenging in the case of
TAVI in surgical bioprostheses (TAV-in-SAV) or TAVI-in-TAVI
43
EuroIntervention 2023;19:37-52

Figure 3. THV leaflet height with respect to recommended annular positioning. THV: transcatheter heart valve

Figure 4. Coronary access according to valve design and implantation depth. Coronary engagement after previous SAPIEN 3 (A) implantation
is commonly feasible with standard catheters, and the access route may be least impaired (green arrow); engagement across the stent frame
(red arrow) may become necessary only in the case of high THV positioning or low coronary take-off. Potential access routes for the
ACURATE neo valve (B) may be via the stabilisation arches (red arrow) or from outside the valve frame (dotted green arrow). The common
access route in tall-frame valves ([C] Portico/Navitor; [D] Evolut) is across the uncovered stent struts above the leaflet plane (red arrows),
whereas, especially in patients with a wide sinotubular junction or sinus of Valsalva, an access route from outside the valve frame (dotted
green arrows) may be an alternative. The lower leaflet position and the larger cells of the Portico/Navitor THV stent frame may facilitate
coronary catheterisation in comparison with the Evolut platform. Regardless of the THV type, correct commissural alignment of the prosthesis
will usually facilitate coronary access. THV: transcatheter heart valve

procedures74. In these specific situations, altered sinus geometry,
the neoskirt of the leaflets from the first THV being pushed aside
by the second THV, and commissural misalignment are factors
that may contribute to compromising the engagement of the coro-
nary arteries in up to half of cases68,75. Catheters may also interact
with the THV leaflets, which, in the extreme case of leaflet pin-
ning, may lead to acute haemodynamic compromise.
COMMISSURAL ALIGNMENT WITH DIFFERENT TYPES OF
TRANSCATHETER HEART VALVES
Alignment of the THV commissures with the native aortic valve
commissures is essential to avoid overlap with the coronary ostia
and optimally preserve coronary access.
The JenaValve and J-Valve (JenaValve Technology) are based on
leaflet rather than annular anchoring, and commissural alignment is
both necessary and inevitable as part of the implantation process76.
Commissural alignment should always be pursued when
implanting a tall-frame THV. It has been shown to improve the
success rate of selective coronary angiography (CA) after TAVI,
as well as reducing the contrast volume and procedure time77.
However, for most of the THVs currently used, alignment of the
commissures can only be approximated and requires specific pre-
procedural planning and procedural techniques. Even with com-
missural alignment techniques, failure to achieve coronary access
post-TAVI remains more frequent for THVs with a supra-annular
leaflet position.
Commissural alignment also has implications for redo-TAVI,
Specifically, without commissural alignment, the use of leaf-
let modification techniques such as BASILICA (Bioprosthetic or
native Aortic Scallop Intentional Laceration to prevent Iatrogenic
Coronary Artery obstruction) to prevent coronary obstruction will
not be possible78.

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 CAD management in TAVI

EuroIntervention 2023;19:37-52
Table 3. Feasibility of coronary access with different THV in available studies.
RCA CA RCA CA LCA CA LCA CA PCI, n;
Study author, year Valve type (n) ACS
success selective success selective success, %
Blumenstein et al. 201555 SAPIEN XT (n=19)
CoreValve (n=10)
13.3% 94.3% 77.1% 97.1% 79.4% n=8; 100%
ACURATE (n=4)
Other (n=2)
Boukantar et al. 201766 CoreValve (n=16) 43.8% 58% 16% 75% 44% n=7; 85.7%
Htun et al. 201767 CoreValve (n=28) 90.0% 100% 90% 100% 97% n=29; 100%
Zivelonghi et al. 201754 Evolut R (n=25)
0% 100% 94% 98% 97% n=17; 100%
SAPIEN 3 (n=41)
Tanaka et al. 201961 CoreValve/Evolut (n=41) 56.5% 50% 31.3% 87.5% 57.1% n=30; 93.3%
Ferreira-Neto et al. 201953 SAPIEN XT (n=28) 64.3% 100% 81.5% 100% 82.6% n=13; 100%
Couture et al. 202097 Evolut R/PRO (n=10) 10.0% NA 60% NA 40% n=2; 50%
Nai Fovino et al. 202052 SAPIEN XT/3 (n=36)
CoreValve/Evolut R/Pro (n=8) 100% IA 94% IA 100% IA 97% IA
35.0% n=26; 96.2%
Jena (n=2) vs 75% SA vs 25% SA vs 100% SA vs 50% SA
Lotus (n=2)
Barbanti et al. 202051 SAPIEN (n=96)
Evolut (n=123)
0% 96.0% 88.0% 95.3% 68.3% n=0; 0%
ACURATE (n=72)
Portico (n=9)
Kim et al. 202198 SAPIEN (n=201)
ACURATE (n=62)
CoreValve/Evolut (n=140) 100% 98.3% 71.6% 99.3% 79.3% n=243; 91.4%
Portico (n=16)
Other (n=30)
ACS: acute coronary syndrome; IA: intra-annular; CA: coronary access; LCA: left coronary artery; PCI: percutaneous coronary intervention; RCA: right
coronary artery; SA: supra-annular; TAVI: transcatheter aortic valve implantation; THV: transcatheter heart valve

There are three general overarching principles to improve com-
missural alignment during TAVI79:
1. Preprocedurally, to identify by CT scan a patient-specific
fluoroscopic projection (C-arm angulation) in which the native
aortic valve commissures can be identified – specifically, the
right and left (RL) coronary cusp overlap view or the 3-cusp
coplanar view (Figure 5).
2. To know the THV-specific fluoroscopic markers which enable
identification of the prosthetic neocommissures when the bio-
prosthesis is still crimped prior to deployment (Figure 6).
3. To know the possible manoeuvres of THV orientation dur-
ing deployment, so that one of the neocommissures are placed
where the right coronary cusp and left coronary cusp are over-
lapping (Figure 7).
Radiopaque markers with different THV devices:
A) Edwards SAPIEN iterations and Myval (Meril Life).
After valve deployment, neocommissures are identified by
3 “double lines” between the hexagonal crowns at the top
cells. However, there is no way of identifying the commissures
before deployment; hence, predictable commissural align-
ment with these THVs is not possible. Moreover, crimping
the SAPIEN 3 THV at specific orientations seems to have no
impact on commissural alignment80.
B) CoreValve/Evolut (Medtronic) iterations.
After valve deployment, the C-paddle on the Evolut corre-
sponds to one commissure, but this marker cannot be seen
under fluoroscopy before deployment. However, as per the
manufacturer’s recommendations, the valve is routinely
loaded with a prespecified angle of 90° between the C-paddle
and the radiopaque “hat” marker of the capsule, which thus
becomes a “surrogate” marker. Commissural alignment is
defined as favourable if the hat marker is positioned in the
centre-front (CF) orientation when the valve is deployed in
RL cusp overlap view (putting the C-paddle to the right of
the screen after complete deployment). This usually corre-
sponds to the hat marker at the outer curve (OC) in left ante-
rior oblique three-cusp view, or CF in the RL cusp overlap
view81-83. During the introduction of the delivery system, ori-
entation of the flush port at 3 o’clock will provide an approxi-
mate initial alignment.
C) ACURATE neo/neo2. The 3 commissural posts are easily iden-
tifiable on the fluoroscopic view once the valve is deployed
and are in line with 3 “free stent struts”. Favourable commis-
sural alignment is reached if the valve is deployed with one
isolated post and the corresponding free stent strut, which are
visible under fluoroscopy, facing the right side of the fluoro-
scopic screen in RL cusp overlap view. Orientation of the
flush port of the delivery catheter at 6 o’clock provides initial
approximate commissural alignment79.
D) Portico/Navitor THV. As above, the Portico and Navitor THVs
have 3 fluorogenic commissural posts, one of which should be
isolated and aligned to the right of the screen in the RL cusp
overlap view during deployment; although, it should be noted
that visualisation of the commissural posts on fluoroscopy can
be difficult. No general rules on how to insert the delivery sys-
tem can be made79.

45
EuroIntervention 2023;19:37-52

Figure 5. The S-curve of different fluoroscopic working views for transcatheter aortic valve deployment. The S-curve identifies infinite
patient-specific fluoroscopic projections in which the 3 aortic cusps are aligned on the same plane. Among them, there are 3 projections where
the 3 cusps are equidistant (NRL, LNR and RLN) and 3 other projections where 2 of 3 cusps are overlapping (RL cusp overlap, LN cusp
overlap, NR cusp overlap). The most widely used implanting views are the 3-cusp coplanar view NRL and the RL cusp overlap view.
CAU: caudal; CRA: cranial; L: left coronary cusp; LAO: left anterior oblique; LCA: left coronary artery; N: non-coronary cusp; R: right
coronary cusp; RAO: right anterior oblique; RCA: right coronary artery

Figure 6. THV-specific fluoroscopic markers of the THV commissural posts. THV-specific fluoroscopic markers identifying prosthetic
neocommissures in different types of expanded and crimped THVs. A) CoreValve Evolut platform; B) ACURATE neo2 platform; C) Portico/
Navitor platform. THV: transcatheter heart valve. Adapted with permission from79.

TIPS AND TRICKS FOR CORONARY ACCESS AFTER TAVI •P

WITH DIFFERENT VALVE TYPES
Coronary access after TAVI may be challenging, particularly in
patients treated before the adoption of commissural alignment
techniques.
A prospective MSCT post-TAVI theoretical study suggested
that 10-20% of patients present an increased risk of compromised
coronary access84.
The challenge of engaging the coronary ostia varies according
to the aortic root and STJ anatomy, sinus sizes, coronary take-
off height and position, THV design and height, and commissural
alignment85,86. Several strategies may be considered:
• Usually, implantation of a low-frame THV with an intra-annular
leaflet position in a subcoronary position does not require any
modification to the coronary cannulation technique.
reprocedural planning is especially important when THVs
are implanted in a partially supracoronary position, most often
seen when the implant position is high, and/or in patients
with a shallow sinus of Valsalva and a low coronary take-off
height54,87. This is observed specifically with tall-frame self-
expanding valves but also when a balloon-expandable valve is
implanted with the top edge of the frame above a low STJ.
Use of the left radial or transfemoral approach might facili-
tate traversing the stent frame. Operators may need to adapt
their catheter choice for coronary cannulation according to
specific anatomies and the aortic root/THV relation. Selective
intubation is usually best achieved with smaller catheter sizes,
such as Judkins Left 3.5 or 4.0, Judkins Right 4.0, Amplatz
2.0 (Cordis), Ikari 1.0 (or 1.5) (Terumo) or 3DRC (Medtronic)
catheters, or mammary catheters62,86,88.

46
 CAD management in TAVI

EuroIntervention 2023;19:37-52
Figure 7. Implantation steps to obtain commissural alignment with different type of THVs. The figure shows the suggested rotation of the
delivery system at the time of insertion (A, B, C), the expected fluoroscopic view of radiopaque markers in the RL cusp overlap view when the
THV is still crimped (D, E, F) and the final fluoroscopic view after valve deployment in the same RL cusp overlap view (G, H, I) when
implanting different THVs pursuing commissural alignment. If, before valve deployment, the fluoroscopic view is different from expected in the
cusp overlap view, the operator should slowly torque the delivery catheter clockwise in order to obtain the desired orientation. Even if a gentle
torque could be attempted with the THV at the level of the aortic valve, with the CoreValve platform, it is advisable to perform this manoeuvre
only in the descending aorta to facilitate torquing force transmission through the delivery system. CF: central front; LAO: left anterior
oblique; OC: outer curve; THV: transcatheter heart valve. Adapted with permission from79.

• In cases with difficult access, the use of intracoronary guide-
wires facilitates selective CA, as demonstrated in a prospective
consecutive registry that performed FFR after TAVI54. If PCI is
needed, catheter extensions can improve support in case of non-
selective cannulation89.
• The guide should be disengaged from the ostium, preferably over
a wire, avoiding excessive force, as it can kink the catheter or
dislodge the THV. If necessary, the use of an angioplasty bal-
loon may help.
Consensus points:
1) C oronary access after TAVI will be become increasingly com-
mon given the expansion of TAVI to younger and lower-risk
patients and the high prevalence of CAD among patients under-
going TAVI.
2) Although the reported success rate of coronary access after TAVI
remains high, we advise that the feasibility of coronary access,
based on pre-TAVI imaging evaluation, should be considered in
the decision-making process when choosing a transcatheter valve
during index TAVI, in patients with previously treated CAD or with
moderate CAD that may require revascularisation in the future.
3) Given the reduction in the physical barrier of a commissural
post facing a coronary orifice when commissural (or coronary)
alignment is achieved in TAVI, is advisable to aim for commis-
sural (or coronary) alignment in all TAVI cases, particularly in
patients where lifetime management of CAD and aortic valve
reintervention would be important. Doing so would increase the
feasibility of coronary access and redo-TAVI.
4) Specific tips and tricks on coronary access after TAVI are
reviewed elsewhere86.
5) Non-selective aortic root angiography might be a good starting
point to identify the relationship between the THV and coronary
artery origins, particularly in the absence of post-TAVI CT imaging.
Coronary access after TAVI-in-TAVI
With the expansion of TAVI towards lower-risk and younger sub-
jects, an increasing proportion of patients is likely to outlive THV
durability and need redo-TAVI.

47
EuroIntervention 2023;19:37-52
The implantation of a second THV will cause the leaflets of the
first bioprosthesis to be displaced, creating a neoskirt extending
from the inflow part of the stent frame to the top of the commissural
posts69,90-94 (Figure 3). Notably, the height of the neoskirt will also be
influenced by the THV implantation depth. Thus, coronary access
impairment after TAVI-in-TAVI will depend on 1) the coronary
take-off height in relation to the neoskirt, 2) the distance between
the THV stent frame and the aortic wall above the coronary ostia.
Accordingly, the first THV choice will determine coronary access
impairment after TAVI-in-TAVI, as different prostheses have differ-
ent neoskirt heights. In a highly selected cohort of patients undergoing
TAVI-in-TAVI in tertiary care centres, with THVs with both supra- and
intra-annular leaflet positions, the incidence of coronary obstruction after
TAVI-in-TAVI was as low as 0.9%95. However, this incidence is expected
to be significantly higher in an unselected TAVI-in-TAVI population.
Figure 8 depicts possible coronary access scenarios after
TAVI-in-TAVI.
A) Coronary ostia are located above the neoskirt. This scenario
is more likely with a short stent frame with an intra-annular
leaflet position as compared to a tall stent frame with a supra-
annular leaflet position. No issues with coronary access are
expected with the implantation of a short stent frame THV or
an aligned tall-frame THV at the time of TAVI-in-TAVI.
B) Coronary ostia are located below the neoskirt, but the sino-
tubular junction is wide. If there is enough space to navigate
a coronary catheter between the aortic wall and the THV stent
frame (>2 mm), coronary access after TAVI-in-TAVI will be
Figure 8. Coronary access after TAVI-in-TAVI with different
combinations of SAPIEN and CoreValve/Evolut transcatheter heart
valves, depending on aortic root anatomy. STJ: sinotubular junction;
TAVI: transcatheter aortic valve implantation. Adapted with
permission from90.
48
possible, albeit difficult, if two THVs with a small-cell stent
frame design are implanted and not perfectly aligned.
C) Coronary ostia are located below the neoskirt in the setting of
a small sinotubular junction. If the distance between the stent
frame and the aortic wall is <2 mm, the implantation of a second
THV will make coronary access impossible. If the displaced leaf-
lets of the first THV are in contact with the aortic wall, TAVI-in-
TAVI is likely to cause sinus sequestration (i.e., impaired blood
flow below the STJ level because the displaced leaflets are in
contact with the aortic wall) and possibly coronary obstruction.
This scenario is more likely if a high stent frame with supra-
annular leaflets is implanted at the time of the first TAVI.
Coronary access after TAVI in degenerated
surgical aortic valves
Factors affecting the feasibility of coronary access after valve-in-
valve (ViV) TAVI are largely similar to those related to TAVI-in-
TAVI. The height of the neoskirt is determined by the length of
the degenerated surgical aortic bioprosthesis’ leaflets. Thus, coro-
nary access after ViV-TAVI is expected to be more challenging
with supra-annular versus intra-annular degenerated surgical aor-
tic valves and stentless bioprosthesis or stented with externally
mounted leaflets versus stented with internally mounted leaflets.
Moreover, coronary access after ViV-TAVI is more difficult in the
setting of a small aortic root with low coronary ostia. As for TAVI
in the native aortic valve, the choice of an intra-annular THV and
the commissural alignment of a supra-annular THV will reduce
the risk of coronary access impairment after ViV-TAVI.
Risk of coronary obstruction
A detailed description of coronary protection techniques during TAVI
is beyond the scope of this document. Briefly, different techniques
may be adopted to mitigate the risk of coronary obstruction during
TAVI in the native aortic valve. Coronary protection with a guide-
wire with/without an undeployed stent is advisable when coronary
ostia are low and the presence of a bulky leaflet is expected to inter-
fere with coronary perfusion after the valve is deployed. The same
technique can be adopted in ViV-TAVI or redo-TAVI if the neoskirt is
above one or both coronary ostia and the distance between the valve
frame and the coronary ostium is <4 mm. After THV implantation,
coronary perfusion should be assessed and, if impaired, chimney
stenting should be performed. Leaflet modification techniques such
as BASILICA78 may also be adopted in cases at high risk of coronary
obstruction; however, neocommissural alignment of the index THV
with the native aortic valve should be preprocedurally assessed, as the
effectiveness of such a procedure will be reduced in case of severe
misalignment of the index THV artery (yet, if the risk is sinus seques-
tration, BASILICA may suffice in providing adequate flow into the
sinus for coronary perfusion even with a misaligned THV). Finally,
with regard to redo-TAVI, a low implantation of a THV with a short
stent frame inside a degenerated tall-frame THV will leave a degree
of leaflet overhang, lowering the height of the neoskirt without
impacting on the hydrodynamic performance of the second THV96.

Conclusions
Since CAD and AS often coexist, the evaluation and manage-
ment of CAD in TAVI candidates is of paramount importance,
particularly with the extension of the procedure to younger and
lower-risk patients. Invasive coronary angiography remains the
mainstay for CAD diagnosis, although CTCA might be consid-
ered for initial screening, particularly in patients at low risk for
CAD. The role of coronary invasive physiology assessment needs
to be further clarified. In patients undergoing TAVI, PCI should
be performed in the setting of severe CAD with the involvement
of proximal vessel segments or in patients with angina, preferably
before THV implantation, and in particular if a THV with supra-
annular leaflets is selected. The THV choice affects future coro-
nary access after TAVI. Commissural alignment techniques should
be routinely adopted to optimise coronary access.
Appendix. Authors’ affiliations
1. Department of Cardiac, Thoracic and Vascular Sciences and
Public Health, University of Padova, Padova, Italy; 2. Department
of Cardiovascular Surgery, Mount Sinai Health System, New York,
NY, USA; 3. Leeds Teaching Hospitals NHS Trust, University
of Leeds, Leeds, UK; 4. Thoraxcenter, Erasmus University
Medical Center, Rotterdam, the Netherlands; 5. Kerckhoff Heart
Center, Bad Nauheim, Germany; 6. Department of Cardiology,
Hôpital Européen Georges-Pompidou, Paris, France; 7. Serviço
de Cardiologia, Hospital de Santa Maria, CHULN, and Centro
de Cardiologia da Universidade de Lisboa, Faculdade de
Medicina de Lisboa, Centro Académico de Medicina de Lisboa,
Lisbon, Portugal; 8. Lausanne University Center Hospital,
Lausanne, Switzerland; 9. National Institute of Cardiology,
Warsaw, Poland; 10. Division of Cardiology, Centre Hospitalier
Régional Universitaire de Lille, Lille, France; 11. Hospital de
Santa Cruz, CEDOC, Nova Medical School, Lisbon, Portugal;
12. Department of Cardiology, University Hospital Galway,
Galway, Ireland; 13. Department of Cardiology, Rigshospitalet,
University of Copenhagen, Copenhagen, Denmark; 14. University
Heart Center Freiburg-Bad Krozingen, Bad Krozingen, Germany;
15. Department of Cardiac Surgery, Medical University of
Innsbruck, Innsbruck, Austria; 16. Department of Biomedical
Sciences for Health, University of Milano, Milan, Italy and
University Cardiac Surgery, Policlinico San Donato IRCCS, Milan,
Italy; 17. Institute of Cardiology, Jagiellonian University Medical
College, Krakow, Poland; 18. Maria Cecilia Hospital, GVM Care
& Research, Cotignola (RA), Ravenna, Italy; 19. Clinique Pasteur,
Toulouse, France; 20. Department of Cardiology, CHU Rouen,
France; 21. Department of Biomedical Sciences, Humanitas
University, IRCCS Humanitas Research Hospital, Rozzano-Milan,
Italy
Guest Editor
This paper was guest edited by Franz-Josef Neumann, MD;
Department of Cardiology and Angiology II, University Heart
Center Freiburg - Bad Krozingen, Bad Krozingen, Germany.
CAD management in TAVI
EuroIntervention 2023;19:37-52
Conflict of interest statement
G. Tarantini reports lecture fees from Medtronic, Edwards
Lifesciences, Abbott Vascular, and Boston Scientific. H. Eltchaninoff
reports lecture fees from Edwards Lifesciences. D. Blackman reports
consulting and lecture fees from Medtronic, Edwards Lifesciences,
Abbott Vascular, and Boston Scientific. N. Bonaros reports lec-
ture fees from Edwards Lifesciences and Medtronic. N. Karam
reports consulting and lecture fees from Medtronic, Edwards
Lifesciences, and Abbott Vascular. D. Mylotte reports consulting
fees from Medtronic, Boston Scientific, and MicroPort. P. Carrilho-
Ferreira reports lecture fees from Biotronik and Medtronic. N. Van
Mieghem reports consulting fees from Biotronik, Boston Scientific,
Abbott Vascular, Medtronic, PulseCath BV, and Abiomed; and
research grants from Abbott Vascular, Edwards Lifesciences,
Boston Scientific, Abiomed, Medtronic, PulseCath BV, Amgen,
and Daiichi Sankyo. W-K. Kim reports lecture fees from Abbott,
Boston Scientific, Edwards Lifesciences, Medtronic, and Meril Life
Sciences. G. Tang is a physician proctor, physician advisory board
member and consultant for Medtronic; physician advisory board
member and consultant for Abbott Structural Heart; physician advi-
sory board member for JenaValve; consultant for NeoChord; and
has received speaker honoraria from Siemens Healthineers. O. De
Backer received institutional research grants and consulting fees
from Abbott, Boston Scientific, and Medtronic. L. Sondergaard
received consultant fees and/or institutional research grants from
Abbott, Boston Scientific, Medtronic, and SMT. The other authors
have no conflicts of interest to declare. The Guest Editor reports
lecture fees paid to his institution from Amgen, Bayer Healthcare,
Biotronik, Boehringer Ingelheim, Boston Scientific, Daiichi Sankyo,
Edwards Lifesciences, Ferrer, Pfizer, and Novartis; and consultancy
fees paid to his institution from Boehringer.
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 CORONARY INTERVENTIONS
EXPERT CONSENSUS

EuroIntervention 2023;19:53-62 published online ahead of print November 2022

Radiation protection for healthcare professionals working in
catheterisation laboratories during pregnancy: a statement of
the European Association of Percutaneous Cardiovascular
Interventions (EAPCI) in collaboration with the European
Heart Rhythm Association (EHRA), the European Association
of Cardiovascular Imaging (EACVI), the ESC Regulatory
Affairs Committee and Women as One
Stéphane Manzo-Silberman1*, MD; Maite Velázquez2, MD; Sonya Burgess3, MBChB, PhD;
Sheila Sahni4, MD; Patricia Best5, MD; Roxana Mehran6, MD; Emanuela Piccaluga7, MD;
Laura Vitali-Serdoz8, MD, PhD; Amy Sarma9, MD; Israel Moshe Barbash10, MD; Josepa Mauri11, MD;
Piotr Szymański12, MD, PhD; Lynne Hinterbuchner13, BScN; Giulio Stefanini14, MD, PhD;
Alessia Gimelli15, MD; Pal Maurovich-Horvat16, MD; Lucas Boersma17, MD; Gill Louise Buchanan18, MD;
Gianluca Pontone19, MD, PhD; Lene Holmvang20, MD, DMSc; Nicole Karam21, MD, PhD;
Antoinette Neylon22, MD; Marie-Claude Morice23, MD; Christophe Leclercq24, MD, PhD;
Giuseppe Tarantini25, MD, PhD; Dariusz Dudek26, MD, PhD; Alaide Chieffo27, MD

The authors’ affiliations can be found in the Appendix paragraph.

S. Manzo-Silberman and M. Velázquez contributed equally to this manuscript.

KEYWORDS
Abstract
The European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Heart
Rhythm Association (EHRA), the European Association of Cardiovascular Imaging (EACVI), the European
• gender issues
Society of Cardiology (ESC) Regulatory Affairs Committee and Women as One support continuous review
• radiation
and improvement, not only in the practice of assuring patients a high quality of care but also in providing
protection
health professionals with support documents to help them in their career and enhance gender equity. Recent
• training and
surveys have revealed that radiation exposure is commonly reported as the primary barrier for women pur-
education
suing a career in interventional cardiology or cardiac electrophysiology (EP). The fear of foetal exposure
to radiation during pregnancy may lead to a prolonged interruption in their career. Accordingly, this joint
statement aims to provide a clear statement on radiation risk and the existing data on the experience of
radiation-exposed cardiologists who continue to work in catheterisation laboratories (cath labs) throughout
their pregnancies. In order to reduce the barrier preventing women from accessing these careers, increased
knowledge in the community is warranted. Finally, by going beyond simple observations and review of the
literature, our document suggests proposals for improving workplace safety and for encouraging equity.
DOI: 10.4244/EIJ-D-22-00407

*Corresponding author: Hôpital de la Pitié-Salpêtrière, APHP, Sorbonne Université, 47-83 bd de l'Hôpital,

75651 PARIS cedex 13. E-mail: stephane.manzosilberman@aphp.fr

© Europa Digital & Publishing 2023. All rights reserved. SUBMITTED ON 28/04/2022 - REVISION RECEIVED ON 1st 18/07/2022 / 2nd 14/09/2022 - ACCEPTED ON 19/09/2022

53
EuroIntervention 2023;19:53-62
Abbreviations
AZF azoospermia factor
EAPCI European Association of Percutaneous Cardiovascular
Interventions
EP electrophysiology
EU European Union
ICRP International Commission on Radiological Protection
SCAI Society for Cardiovascular Angiography and
Interventions
mGy milligray
mSv millisievert
Introduction
Why is a collaborative statement on radiation exposure during preg-
nancy required? Interventional cardiology and electrophysiology
are the two subspecialities with the lowest female representation in
cardiology1-4. Radiation exposure is commonly identified as a major
barrier for women considering a career in interventional cardiology
and electrophysiology4,5, and concerns regarding occupational radia-
tion exposure during pregnancy are likely to lead to missed career
development opportunities6. Amongst European Union countries,
there are substantial variations in occupational radiation regulations
and practices, despite the recent definition of safe dose limits and
safety standards for foetal exposure from the European Directive, as
well as the repeal of previous Euratom directives7. The 2011 Society
for Cardiovascular Angiography and Interventions (SCAI) and 2017
European Heart Rhythm Association consensus documents and 2018
European Association of Percutaneous Cardiovascular Interventions
(EAPCI) survey report2,8,9 endorse the safe continuation of work
with occupational radiation exposure while pregnant; yet, in some
EU countries, pregnant women are not permitted to work in the car-
diac catheterisation laboratory, while in other EU countries, poli-
cies are more permissive10 (Table 1). Nevertheless, there remains
a lack of precise data on the real risks to the foetus and awareness
of the existing directives, not only amongst heads of departments
but also amongst women working as physicians in interventional
cardiology11. Therefore, while European, North American, Japanese,
and Australian directives allow women to work if closely monitored
with an abdominal dosimeter to ensure that the foetus does not
exceed recommended dose limits during pregnancy, in some coun-
tries, pregnant women are not allowed to work. There is also a dis-
parity regarding the maximum foetal dose allowed across countries:
1 mSv in Europe7, Australia12 and Israel, 2 mSv in Japan and 5 mSv
in the US13 (Table 1). This lack of knowledge that persists among
the interventional and electrophysiology communities contributes to
workforce gender disparity. In order to reduce barriers preventing
women from accessing a career in interventional cardiology, there
should be clear statements on radiation risk and data collection on
the current experiences of radiation-exposed cardiologists who con-
tinue to work in catheterisation laboratories throughout their preg-
nancies. The aim of the present document is to provide data and
clear information on radiation risk in order to overcome the “radia-
tion barrier”.
54
Risks: biological evidence of radiation exposure
during pregnancy
Ionising radiation exposure during pregnancy and the potential
impact of prenatal radiation is a major concern for women in the
cardiac catheterisation laboratory14,15.
Prenatal radiation risks include pregnancy loss, congenital mal-
formations, developmental delay, and carcinogenesis. Some risks
are dependent on the radiation dose. These hazards can be sto-
chastic, including the risk of childhood cancer and genetic disor-
ders16,17, or deterministic, which have a radiation dose threshold,
such as intrauterine growth retardation, miscarriage, and congeni-
tal defects17. The greatest risk of pregnancy loss from radiation
exposure is during the first 2 weeks of pregnancy, while between
2-8 weeks after conception, the embryo is most susceptible to
the development of congenital malformations because this is the
period of organogenesis18.
Table 2 shows the main deterministic irradiation effects on the
embryo/foetus at each pregnancy stage. As can be appreciated
in the table, the foetal radiation doses that have been related to
the occurrence of abortion, malformations or intelligence quo-
tient reductions are 100 times higher than those allowed during
the entire pregnancy for an interventional cardiologist. Since the
threshold dose for these deterministic effects is well above that
which an invasive or interventional cardiologist would receive
under a protective apron, the use of standard radiation protec-
tion techniques would result in negligible risk to the foetus. With
respect to stochastic effects, which have no threshold dose, the
embryo/foetus is assumed to be at about the same risk for poten-
tial carcinogenic effects of radiation as children throughout most
of the pregnancy13. Table 3 shows the spontaneous probability of
a newborn having a congenital malformation or childhood cancer
and how this probability has a negligible increase when the occu-
pational exposure range of the mother respects the 1, 2 or 5 mSv
limits during pregnancy9,19.
However, understanding the mechanisms that underlie the patho-
genesis of radiation-induced birth defects is difficult since possible
radiation damages are linked to a multifactorial process which has
not been well researched. There are no randomised trials assess-
ing the risks of prenatal radiation. The most conclusive studies
have been on massive radiation exposure such as after the atomic
bombs used in World War II. There have also been estimates
made from population studies of prenatal radiation exposure. The
probability that a child will be born with a congenital abnormal-
ity or cancer increases from 4.07% with background radiation to
4.078% with 1 mSv conceptus exposure and to 4.12% with 5 mSv
exposure20. There are no studies that show an increased risk of
non-cancerous effects from prenatal radiation exposure below
50 mSv21. Occupational radiation exposure during pregnancy
is regulated in Europe by directives from both the EU and each
country, and in the USA by federal and state law, which take into
account the recommendations from the International Commission
on Radiological Protection (ICRP)13. The current National Council
on Radiation Protection and Measurements (NCRP) recommends
 Radiation protection for pregnant healthcare professionals

EuroIntervention 2023;19:53-62
Table 1. Current legal requirements: EU, UK, USA, Australia, Israel. Overview of the current EU regulations and their local application
demonstrating a general trend in more restrictive applicative directives usually limiting access to the catheterisation/electrophysiology
lab and allowing a discretional power to the X-ray surveillance experts. Overview of the current non-EU regulation with focus on the UK,
USA, Australia and Israel.
The European
Exposure during
Directive 2013/59/
pregnancy Exposure during In-hospital discretionary
Euratom, Art.10 has COUNTRY LAW
(cumulative dose breastfeeding allowance
been adopted in your
over the pregnancy)
Country. YES/NO
AUSTRIA YES YES Not allowed Not allowed NA
BELGIUM YES ARBIS 20-07-2001 Yes, should be <1 mSv Yes, allowed Risk analysis of occupational
and ALARA exposure for every pregnant woman
with arbitrary allowance according to
the X-ray surveillance expert.
CYPRUS YES 2018 Yes, should be <1 mSv Yes, allowed NA
DENMARK YES BEK nr 669 af 01/07/2019 (equivalent to Yes, should be <1 mSv Ok, but exposure NA
EU directive) after pregnancy is should be limited
recognised − special
dosimetry is encouraged
(day-to-day monitoring)
FRANCE YES Articles D. 4152-5 and R. 4451-45 of Yes, should be <1 mSv No specific Possibility of shifting the pregnant
French Labour Code indications woman to an occupation with less
radiation exposure or keeping her in
her current assignment if the total
expected radiation dose between
pregnancy confirmation and
childbirth is <1 mSv
GERMANY YES Strahlenschutzgesetz (StrlSchG): German Yes, should be <1 mSv, Yes, allowed Risk analysis of occupational
Radiation Protection Law dated June 27, weekly monitoring exposure for every pregnant woman
2017 (Federal Law Gazette Part I, with arbitrary allowance according to
p. 1,966), last amended by Article 2 of the the X-ray surveillance expert.
law of May 20, 2021 (Federal Law Gazette
Part I p. 1,194): §78
Strahlenschutzverordnung (StrlSchV):
German Radiation Protection Ordinance
dated November 29, 2018 (Federal Law
Gazette Part I, p. 2,034-2,036), last
amended by Article 6 of the law of May 20,
2021 (Federal Law Gazette Part I p. 1,194):
§55
HUNGARY YES, in a restricted Government Decree 487/2015 (XII. 30.) on Not allowed Not allowed The pregnant woman shall have her
manner (no exposure the protection against ionising radiation work reorganised to avoid any risk
when pregnant/ and the corresponding licensing, reporting (including infections, radiation, etc.).
breastfeeding) (notification) and inspection system The pregnant woman cannot be
dismissed/suspended because of her
status.
IRELAND YES RADIOLOGICAL PROTECTION ACT 1991 Yes, should be <1 mSv Yes, allowed NA
(IONISING RADIATION) REGULATIONS 2019
ITALY YES, in a restricted DL 101 July 2020 Not allowed Not allowed Not allowed
manner (no exposure
when pregnant/
breastfeeding)
NETHERLANDS YES Yes, should be <1 mSv Yes, allowed Risk analysis of occupational
exposure for every pregnant woman
with arbitrary allowance according to
the X-ray surveillance expert
PORTUGAL YES (108/2018, 102/2009, 10 September Not allowed Not allowed Not allowed
article 69) 102/2009
ROMANIA YES LAW 154/2015 Not allowed Not allowed The employer must change the
working conditions, so that there is
no radiation exposure
SLOVENIA ZVISJV-1, December 2017 Yes, should be <1 mSv, Yes, allowed Institution is obliged to organise a
monthly monitoring different workplace or reorganise
working time under exposure so the
goal <1 mSv can be met

55
EuroIntervention 2023;19:53-62

Table 1. Current legal requirements: EU, UK, USA, Australia, Israel. Overview of the current EU regulations and their local application
demonstrating a general trend in more restrictive applicative directives usually limiting access to the catheterisation/electrophysiology
lab and allowing a discretional power to the X-ray surveillance experts. Overview of the current non-EU regulation with focus on the UK,
USA, Australia and Israel (cont'd).
The European
Exposure during
Directive 2013/59/
pregnancy Exposure during In-hospital discretionary
Euratom, Art.10 has COUNTRY LAW
(cumulative dose breastfeeding allowance
been adopted in your
over the pregnancy)
Country. YES/NO
SPAIN YES, current laws, Royal Decree 298/2009, of 6th March, Yes, should be <1 mSv, Yes, allowed. Even though current law allows
although enacted before which modifies the Royal Decree 39/1997, monthly monitoring During the women to work provided the dose is
this directive was of 17th January breastfeeding <1 mSv for the whole pregnancy, in
issued, are in period the worker some cases, the the X-ray
accordance with it will not be surveillance department or the
employed in a job occupational risk department do not
with radionuclides allow a woman to work
and contaminants
SWEDEN YES SFS 2018:396 Yes, should be <1 mSv Yes, allowed How a foetal dose below 1 mSv is
ensured is up to the authority, i.e.,
the public healthcare provider. There
may be different ways of calculating
the foetal dose between hospitals.
Currently a factor of 5 is used.
NON-EU
AUSTRALIA NO, the current Australian Radiation Protection and Yes, dose to foetus Yes, allowed (no NA
Australian codes and Nuclear Safety Agency Radiation should be <1 mSv from threshold
standards are based on Protection Diagnostic and Interventional declaration of pregnancy specified)
the 2020 guidelines of Cardiology, series 14.1. Australian to delivery
the International Radiation Health Committee. 2008
Commission on Ionising
Radiation Protection
(ICNIRP)
ISRAEL NO 1992 Law by the Ministry of Labor, Social Yes, dose should be Yes, allowed. No At 4 months pregnancy − medical
Affairs and Social Services <1 mSv/9 months limitations examination by occupational
medicine
UK YES The Ionising Radiation Regulations 2017 1 mSv limit None for radiation 1 mSv limit
(IRR 17) (only radionuclides
and
contaminants)
USA Pregnancy Individual states have Pregnant Workers No legal specifications No legal Yes
Discrimination Act and Fairness laws regarding exposure. specifications
the American Disabilities regarding
Act: pregnant workers NCRP recommends a exposure
have a legal right to dose <5 mSv/9 months
work adjustments that
allow them to do their
job without jeopardising
their health
ALARA: as low as reasonably achievable; NA: not applicable; NCRP: National Council on Radiation Protection and Measurements

a monthly maximal exposure of <0.5 mSv, and the ICRP recom-
mends a dose <1 mSv for the entire pregnancy. The limit of safe
foetal radiation exposure of 1 mSv throughout pregnancy for the
EU member states is based on the Directive 96/29/Euratom, which
establishes that the protection of the foetus shall be comparable
to that provided for members of the public, and thus it should not
receive more than 1 mSv/year9. However, in the USA, regulation
is less restrictive, and the NCRP in Report No. 174 recommends
limiting occupational exposure of the foetus to not exceed 5 mSv
throughout the entire pregnancy and 0.5 mSv per month of the
pregnancy. This is because, in the USA, American employers are
required to treat their female employees equally with respect to
“pregnancy, childbirth or related medical conditions”. Therefore,
the radioprotection policies for pregnant workers in the USA prior-
itise the pregnant worker’s rights from an anti-discriminatory per-
spective, while the European legislation policies prioritise mostly
the safety rights of the unborn child9. In any case, the general
instructions of the European directives continue stating that, once
the woman has declared pregnancy, the employer must ensure that
the equivalent dose limit for a foetus remains ≤1 mSv. Thus, while
pregnancy does not require removing the exposed professional
from work, a careful review of working conditions in order to
comply with current regulations is warranted. However, nowadays
there are still countries in the EU which prevent pregnant staff

56
 Radiation protection for pregnant healthcare professionals

EuroIntervention 2023;19:53-62
Table 2. Main deterministic/stochastic irradiation effects on the embryo/foetus at each pregnancy stage (Adapted from9).
Risk at occupational
Doses at which effects
Pregnancy stage Main irradiation effect dose (range ≤1-5 mSv Spontaneous risk24
have been described
exposure to the mother)
Preconception gonadal Has not been shown to result
irradiation in increased cancer or
malformations in children13
Preimplantation Abortion Doses over 100 mGy25 Death of the conceptus Risk of spontaneous
(First two weeks due to radiation is not abortion in known
post-conception) described28 pregnant women 1/7

Period of major organogenesis
(weeks 3-8 post-conception)
Early foetal period (weeks
8-25 post-conception)
Third trimester
Risk of malformation or
growth retardation
Risk of reducing the
intelligence quotient
Risk of malformation, growth
retardation or reduced
intelligence quotient not
expected
Possible fatal or non-fatal
cancer of any type (solid
tumours and leukaemia)
Dose threshold of around
100 mGy26
Dose threshold of around
120-200 mGy weeks
8-15 Dose threshold of
around 500 mGy weeks
16-25
Lifetime cancer risk
following in utero
exposure will be similar
to that following radiation
in early childhood
Not expected below Risk of major
100 mGy26 congenital
malformations 1/33
Risk of growth
retardation 1/33
Doses under 100 mGy
and in the mother’s
occupational exposure
range (<5 mSv) would be
of no practical
significance26
Lifetime cancer risk Risk of childhood
around 1/500 for 5 mSv leukaemia per year
in utero exposure27,28, and 1/25,000/year
1/2,500 for 1 mSv in
utero exposure27,28

Table 3. Probability of a child to be born with a congenital the more so when those professionals include pregnant women.
malformation or to develop childhood cancer spontaneously and Furthermore, operators can use the same technique to measure
after ionising radiation exposure (summarised from20). radiation exposure prior to pregnancy in order to estimate the
Probability of likely occupational risk during pregnancy. Since the first trimes-
Probability of ter is when the conceptus is at highest risk to radiation exposure
Foetal dose a child having
Probability of a child a child
added to the a congenital and since most women may not know they are pregnant during
having a congenital developing
background malformation or this time, it is important to practise universal radiation safety at
malformation (%)29,30 childhood
radiation (mSv) childhood all times.
cancer (%)29,31
cancer (%)32
Although the foetal radiation doses that have been related to the
0
(spontaneous risk)
4.000 0.070 4.070 occurrence of malformations/childhood cancer are much higher
0.5 4.001 0.074 4.072
than those allowed for the entire pregnancy for an interventional
cardiologist10, little information is available in the literature on the
1 4.002 0.079 4.078
dose received by pregnant employees exposed to ionising radia-
2.5 4.005 0.092 4.090
tion. In order for interventional and EP cardiologists to make
5 4.010 0.110 4.120
informed decisions, we encourage national interventional and EP
10 4.020 0.160 4.170
societies to collect and publish data regarding radiation exposure
and pregnancy outcomes in pregnant cardiologists working in the
from working in the cath lab. Thus, we encourage the national cath/EP labs.
interventional and electrophysiology (EP) societies of those coun- Finally, the impact of radiation exposure on men should also
tries to work together with their national health system authori- be considered. In fact, chronic occupational radiation exposure
ties to promote changes in regulation and to repeal sexist laws among male workers is correlated with a higher prevalence of low
that disincentive women to choose interventional subspecialities birth weight in offspring and instability in the Y chromosome azo-
and expose the foetus to unnecessary risks by promoting late preg- ospermia factor c (AZFc) region, responsible for male infertility22.
nancy declaration.
The amount of radiation exposure to the conceptus is meas- Proposal for better practice
ured by wearing a radiation badge under a lead apron at waist Operators using fluoroscopy must be guided by the “as low as
level. This amount should be assessed in all professionals who reasonably achievable” (ALARA) principle, in which the obten-
work in an environment with ionising radiation exposure, but all tion of optimal images must be balanced with prodecure safety.

57
EuroIntervention 2023;19:53-62
The practice of radiation safety is grounded in an understanding
of external radiation protection measures as well as technical con-
siderations in operating the X-ray system. Minimising a pregnant
operator’s radiation exposure follows similar principles to general
working practices in a radiation environment. Scatter radiation
emitted from the patient is the greatest source of radiation expo-
sure to the operator and personnel. Therefore, methods to reduce
radiation exposure to the patient will automatically reduce opera-
tor and personnel exposure. Furthermore, appropriate standardised
operating procedures must be in place to prevent unintentional
exposure.
The three fundamentals of radiation safety to an operator include
1) time, 2) distance and 3) shielding and dosimeter monitoring.
Time refers to the amount of time the operator spends using the
X-ray system, where less usage equals less radiation exposure23.
Operators must maximise their distance from the X-ray source as
radiation intensity follows the inverse square law: if the operator’s
distance from the X-ray source increases from 40 cm to 80 cm,
radiation intensity reduces by a factor of 4. Shielding is used in
the form of personal, tableside or external protection with each
form having a degree of lead equivalence defining its radiation
protective effect. Personal shielding includes a lead apron with or
without shoulder covers for breast shielding, a thyroid collar and
lead glasses. The lead apron should be of at least 0.35 mm thick-
ness, attenuating approximately 95-96% of the scatter radiation.
The use of 0.5 mm thickness attenuates 98.0-99.5% of the scatter
radiation dose. An overhead movable lead shield of 1 mm thick-
ness positioned close to the patient and between the operator and
the entry of the X-ray source can reduce radiation exposure by
95%. Available data show that the majority of foetal radiation dose
exposure rarely exceeds 0.3 mSv (Table 4, Table 5). The key prin-
ciples of radiation safety for pregnant staff are summarised in the
Central illustration.
Proposal for encouraging equity
The root causes of gender disparity in cardiology are numerous
but related mainly to societal and cultural norms concerning the
role of women. This is most apparent regarding parenting and
family planning for women during training and early career, espe-
cially in invasive subspecialities. As medicine witnesses a cultural
shift that overlaps with the changing societal biases towards gen-
der, paradigm changes in practices must occur to increase female
representation and narrow gender inequalities among trainees and
faculty in invasive cardiology subspecialities.
The first change should target medical schools’ curricula, intro-
ducing medical students to clinical cardiology and supporting
students interested in invasive cardiology subspecialities regard-
less of race or sex. Commonly heard fallacies must be clarified,
particularly the ones related to the impact of radiation on wom-
en’s fertility and conception. Institutions should improve radia-
tion counselling to address employees’ concerns adequately and
train them in safe practices that minimise radiation exposure.
Concurrently, efforts must be made to convert the workplace
58
into a friendlier environment for families, especially pregnant
interventionists. For instance, lighter protective garments must
be introduced to avoid additional physical burdens on pregnant
women and ensure that these protection suits are adjustable as the
foetus grows. Emerging technologies to minimise radiation expo-
sure in male and female operators (i.e., tailored shielding, lead
offloading, robotics, 3-dimensional mapping systems in invasive
electrophysiology, etc.) should be introduced in contemporary
catheterisation laboratories. Furthermore, coverage for women
who become parents during training should be implemented pro-
actively, and standardised, so that the burden of guilt for the preg-
nant interventionalist is lifted and so that this becomes routine
practice rather than an inconvenience to the rest of the trainees.
These measures can include increased pay for those covering,
as well as curricular advances to ensure that training for these
women is not prolonged.
Providing active dosimeters to help reduce exposure would be
an important step and would protect not only pregnant women but
all operators.
Indeed, gender equity should be a common interest for both
men and women. Male role models and mentors need to show
support based on talent and accomplishments irrespective of
gender. The Pygmalion effect, where prejudiced expectations
impact outcomes, needs to be of less influence when recruiting
or collaborating with female colleagues. Highly qualified female
interventionists should be assumed to be as equally apt as their
male counterparts in performing the job and should be offered
similar opportunities with equal pay. There must be a joint effort
to revoke gender as a criterion for promotion or leadership. The
only way to achieve equity is through a collaborative leadership
that ensures equality between men and women at all career and
life stages.
Conclusions
Fear of foetal exposure to ionising radiation during pregnancy
remains a barrier for women who wish to pursue a career in inter-
ventional cardiology. International expert commission recommen-
dations and European directives clearly state that pregnant women
can continue to work in an ionising radiation environment pro-
viding that the foetus does not exceed certain dose thresholds.
Moreover, data from practice, although scarce, confirm radiation
doses to be well below these limits. Despite this, many countries
apply inappropriately restrictive directives. Specific institutional
radiation protection programs should be established to help to
overcome radiation barriers by including specific safety require-
ments for everyone; this would also ensure safe exposure during
pregnancy. Key opinion makers in cardiovascular societies and
ancillary institutions should promote awareness at both the local
and national level to ensure a level playing field and a friendly
environment for pregnant interventionists. This would help to
facilitate the continuation of interventional work during pregnancy
and go towards eliminating this cause of gender inequity in inva-
sive cardiology subspecialities.
 Radiation protection for pregnant healthcare professionals

EuroIntervention 2023;19:53-62
Table 4. Current published and unpublished data from practice or indirect studies.
Author Settings Attitude during pregnancy and dose received Outcome
Spain Interventional cardiologists Background radiation in 80% of all pregnancies, 0.2 mSv in one 4 normal pregnancy outcomes,
(Velázquez et al, 201710) and electrophysiologists (n=5) pregnancy 1 pregnancy with placental insufficiency
New Zealand* Multiple trainees and Unpublished accounts of case-by-case and monthly foetal monitoring Normal pregnancy outcomes reported
(Unpublished anecdotal interventional cardiologists in with radiation dose well below safe pregnancy thresholds*
accounts only) New Zealand
Australia* Multiple trainees and Unpublished accounts of case-by-case and monthly foetal monitoring Pregnancy outcomes consistent with
(unpublished anecdotal interventional cardiologists in with radiation dose well below safe pregnancy thresholds. those of the general population were
accounts only) Australia (n=11) In detail: Of 19 female interventional cardiologists (IC) in Australia reported
(*Burgess S; on behalf of and New Zealand2, 13/19 (68%) known to the author* were directly
Women in Interventional contacted by phone or email, 11/13 responded (85%). Amongst
Cardiology of Australia and responders 11/11 (100%) had at least one pregnancy during
New Zealand (WIICAN). advanced training, fellowship or consultancy. A total of
Unpublished data on pregancy 21 pregnancies were included. Amongst responders, during 86% of
in Female Interventional all pregnancies, doctors, including 82% of IC, remained in the cath
Cardiologists of Australia and lab with appropriate shielding and without any adjustment of
New Zealand 2021) schedule or cath lab exclusion. Of the remaining 2 IC, one doctor was
excluded from weeks 8-15 in 1 of 2 pregnancies but remained in the
lab without exclusion for her other pregnancy, and the remaining
doctor chose to self-exclude from the catheterisation laboratory from
approximately 6-9 weeks.
All 11/11 responders (100%) reported dose monitoring at the time of
their pregnancies with radiation doses well below thresholds for safe
pregnancy as defined by Australian and New Zealand policy and
standards.
USA Prospective study (n=30) of The calculated average dose to pregnant interventional radiologists
(Marx MV et al 199233) interventional radiologists and (in 1992) over a 40-week pregnancy with two layers of lead=0.4 mSv
trainees (not pregnant, male dose calculated to be 1.3 mSv with one layer of lead (NCRP
and female) occupational foetal dose limit=5 mSv)
France Questionnaire among the 14/26 women had children. Half of them continued to work during the Outcomes not reported
(Vautrin et al34) female population in first trimester of pregnancy, and 2 continued until 7 months. Four
interventional cardiology in wore an additional lead apron for double lead protection of the
France (n=14) abdomen. Dose received was not asked in the questionnaire.
USA Survey of the women in 47% of women tried to avoid pregnancy during periods when they Outcomes not reported
(Sarma AA et al6) cardiology section of the would be exposed to radiation and 57% of women experienced
American College of Cardiology radiation during a pregnancy, without a difference between trainees
(n=501 women) (49%) vs attending physicians (58%; p=0.28). Those under 50 at the
time of the survey were actually more likely to have avoided
pregnancy during periods of radiation exposure as compared with
those >50 (50% vs 39%; p=0.03), suggesting that younger
cardiologists are more concerned about radiation.
Women were relatively uninformed about whether their department
had an official policy regarding radiation exposure during pregnancy:
34% saying they didn’t know if their department had a policy, 32%
reporting that their department did not, and 34% reporting that their
department did (no difference between women >50 years of age and
women <50 years of age, potentially limiting senior cardiologists
from providing mentorship on this issue to younger colleagues).
Among women who experienced pregnancy radiation exposure, only
20% used foetal radiation badges, 24% used additional lead, and
42% increased their distance from radiation sources. Thus, despite
a high rate of concern, pregnant cardiologists underuse radiation
reduction and monitoring strategies. Dose received during
pregnancies was not asked in the survey.
*Published and unpublished data from interventional cardiologists that continued to work in the cardiac catheterisation laboratories during their pregnancies. While numerous interventional
cardiologists from Europe, North America, Australia and New Zealand report safely working and training throughout pregnancy without interruption using various radiation monitoring
techniques, little published data exist.

Conflict of interest statement
S. Manzo-Silberman has received consulting fees from Bayer,
Organon, and Exeltis; lecture fees from Bayer, BMS, Exeltis, and
Organon; and has served on the adjudication board for a study for
Biotronik. S. Burgess received a research a grant from Women as
One for a radiation safety project (paid to her to university research
fund), and has received speaker honoraria from AstraZeneca,
Women as One, Pfizer, and Novartis. S. Sahni has received lec-
ture fees from Abbott Vascular. P. Best has served as co-Chair of
SCAI-WIN and Chair of the SCAI CME Oversight Committee,
and is a member at Mission Lifeline. R. Mehran reports institu-
tional research payments from Abbott, Abiomed, Alleviant Medical,
AM-Pharma, Amgen, Applied Therapeutics, Arena, AstraZeneca,
AtriCure, Bayer, Biosensors, Biotronik, Boston Scientific,

59
EuroIntervention 2023;19:53-62

Table 5. Unpublished data from practice.

Pregnancies with radiation Means of reducing foetal Equivalent dose received during
Country Outcome
exposure, standard shift radiation exposure pregnancy
Spain 15 pregnancies/11 Standard 1 vest+1 skirt 7/15 Background radiation 8/15 14 pregnancies: normal
interventional cardiologists Extra skirt or gonadal protection 0.2 mSv 2/15 outcome
shield 8/15 <1 mSv 3/15 1 pregnancy: placental
insufficiency
Don’t recall 2/15
France 8 pregnancies/5 interventional Standard 1 vest+1 skirt 5/8 7/8 pregnancies: background Normal pregnancy
cardiologists Extra removable on-wheels shield radiation outcomes reported for
protection 3/8 0.23 mSv in one pregnancy all pregnancies

EuroIntervention

CENTRAL ILLUSTRATION Managing the radiation safety of pregnant staff.

RADIATION OUTFIT 3 FUNDAMENTALS OF RADIATION SAFETY

Lead apron that provides at
least 0.35 mm lead TIME
Spend less time on the pedal
equivalency throughout the
entire pregnancy DISTANCE
Increase the distance
Pregnancy-tailored lead from X-ray source
apron SHIELDING
Block scattered radiation
Movable lead shields of from the patient
1 mm-thickness between
the operator and the entry of The institution must provide an abdominal dosimeter:
the X-ray source – Worn under the lead at waist level
– Monthly reading from dosimeter
Use of novel radiation – Real-time radiation dose monitor
shielding systems – Consider an active dosimeter if primary operator
– Legal dose limits for the entire gestation:
– 1 mSv EU-Australia-Israel
Use of new models of cath – 5 mSv US
labs utilising low radiation
XR imaging technologies

(adapted from Women as One https://rad.womenasone.org)

Bristol-Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept
Medical, CSL Behring, Cytosorbents, Daiichi Sankyo, Element
Science, Faraday, Humacyte, Idorsia, Janssen, Magenta, Medtronic,
Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, RenalPro, RM
Global, Shockwave, Vivasure, and Zoll; personal fees from Cine-
Med Research Institute and WebMD; has equity <1% in Applied
Therapeutics, Elixir Medical, Stel, and ControlRad (spouse); is on
the Scientific Advisory Board of AMA; is on the Board of Trustees
of the American College of Cardiology; is a Women in Innovations
Committee Member for SCAI; is Associate Editor of JAMA; and is
a member of the Cardiovascular Research Foundation faculty (no
fee). L. Vitali-Serdoz has received lecture fees from Abbott Vascular
and Medtronic. A. Sarma has received a grant from CRICO
Patient Safety Award. J. Mauri is a stakeholder of CERC CRO.
P. Szymański has received lecture fees from Novartis and Abbott
Vascular. G. Stefanini has received institutional grant support from
Boston Scientific paid to his institution and, has received lecture
fees from Abbott Vascular, Boston Scientific, and Pfizer/BMS.
A. Gimelli has served on the Pfizer Advisory Board for amyloidosis
and the GE Healthcare Advisory Board for the safety of regaden-
oson in paediatric patients. P. Maurovich-Horvat is shareholder of
Neumann Medical Ltd. L. Boersma has received consulting fees
from Medtronic, Boston Scientific, Adagio, Philips, and Abbott
paid to his institution; has served in the Committee of Science
and Innovation for the Dutch Society of Cardiology, as Associate
Editor of Europace (no fee) and in the EHRA Scientific Documents
Committee (no fee). G.L. Buchanan has received support for attend-
ing meetings and/or travel from Menarini. G. Pontone has received
grants from GE Healthcare, Bracco, Boehringer Ingleheim, and
HeartFlow; has received consulting and lecture fees from GE
Healthcare, Bracco, and Boehringer; and payment for expert tes-
timony from GE Healthcare. L. Holmvang has received lecture
fees from MicroPort and Bayer, and support for attending meetings
from Abbott. N. Karam has received consulting fees from Abbott
Vascular, Medtronic, and Edwards Lifesciences; has received lec-
ture fees from Abbott Vascular and Edwards Lifesciences; has
received support for attending meetings from Abbott Vascular; and
has served on an advisory board for Medtronic. A. Neylon holds
shares/stock options in CERC Europe. M-C. Morice is CEO and
shareholder of CERC (not involved in this article) and is a minor
shareholder of Electroducer. G. Tarantini has received consult-
ing fees from Medtronic, GADA, Edwards Lifesciences, Boston

60

Scientific, and Abbott Vascular; and has received lectures fees
from Medtronic, GADA, Edwards Lifesciences, Boston Scientific,
and Abbott Vascular. A. Chieffo has received consulting fees from
Abiomed; and speaker fees from Abiomed, Abbott Vascular, and
Biosensors; and has served on an advisory board for Shockwave
Medical. The other authors have no conflicts of interest to declare.
Appendix. Authors’ affiliations
1. ACTION Study Group, Sorbonne University, Institute of Cardiology,
Hôpital Pitié-Salpêtrière (AP-HP), Paris, France and Women as One;
2. Department of Cardiology, University Hospital 12 de Octubre,
Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid,
Spain and CIBERCV, Madrid, Spain; 3. Department of Cardiology,
Nepean Hospital, the University of Sydney, NSW, Australia and Women
as One; 4. Hackensack Meridian Health Medical Group, Clark, NJ,
USA; 5. Department of Cardiology, Mayo Clinic, Rochester, MN,
USA; 6. The Zena and Michael A. Wiener Cardiovascular Institute,
Icahn School of Medicine at Mount Sinai, New York, NY, USA;
7. Cardiology Department, Ospedale Niguarda Ca' Granda, Milano,
Italy; 8. Department of Cardiology, Klinikum Fuerth, Teaching Hospital
of Erlangen-Nuernberg University, Fuerth, Germany; 9. Department
of Cardiology, Massachusetts General Hospital, Boston, MA, USA;
10. Interventional Cardiology Unit, Leviev Heart Institute, Sheba Medical
Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;
11. Cardiology Department, Hospital Universitari Germans Trias i
Pujol, Badalona, Spain; 12. Centre for Postgraduate Medical Education,
Warsaw and Centre for Clinical Cardiology, CSK MSWiA Hospital,
Warsaw, Poland; 13. Department of Cardiology, Landeskrankenhaus
Salzburg − Universitätsklinikum der Paracelsus Medizinischen
Privatuniversität, Salzburg, Austria; 14. Humanitas Clinical and
Research Center IRCCS, Rozzano-Milan, Italy; 15. Fondazione Toscana
Gabriele Monasterio, Imaging Department, Pisa, Italy; 16. Semmelweis
University, Budapest, Hungary; 17. Department of Cardiology,
St. Antonius Hospital, Nieuwegein, the Netherlands; 18. Department
of Cardiology, North Cumbria Integrated Care NHS Foundation Trust,
Carlisle, UK; 19. Centro Cardiologico Monzino IRCCS, Milan Italy;
20. Department of Cardiology, Rigshospitalet, Copenhagen University
Hospital, Copenhagen, Denmark; 21. Université de Paris, PARCC,
INSERM, European Georges Pompidou Hospital, Paris, France;
22. Institut Cardiovasculaire Paris Sud, Massy, France; 23. ICPS,
Ramsay Générale de Santé and CERC Massy, France; 24. Department
of Cardiology and Vascular Diseases, C.H.U. Pontchaillou, Rennes,
France; 25. Department of Cardiac, Thoracic and Vascular Science,
University of Padova, Padova, Italy; 26. Institute of Cardiology,
Jagiellonian University Medical College, Krakow, Poland and Maria
Cecilia Hospital GVM, Cotignola RA, Italy; 27. IRCCS San Raffaele
Scientific Institute, Milan Italy.
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31. Jablon S, Kato H. Childhood cancer in relation to prenatal exposure to atomic
bomb radiation. Lancet. 1970;2:1000-3.
32. Wagner LK, Hayman LA. Pregnancy and women radiologists. Radiology. 1982;
145:559-62.
33. Marx MV, Niklason L, Mauger EA. Occupational radiation exposure to interven-
tional radiologists: a prospective study. J Vasc Interv Radiol. 1992;3:597-606.
34. Vautrin E, Marlière S, Bellemain-Appaix A, Gilard M, Manzo-Silberman S;
Intervention’elles group. Women in interventional cardiology: The French experience.
Ann Cardiol Angeiol (Paris). 2016;65:468-71.
 CORONARY INTERVENTIONS
CLINICAL RESEARCH

EuroIntervention 2023;19:63-72 published online ahead of print February 2023

Single antiplatelet therapy directly after percutaneous
coronary intervention in non-ST-segment elevation acute
coronary syndrome patients: the OPTICA study
Niels M.R. van der Sangen1, MD; Bimmer E.P.M. Claessen1, MD, PhD; I. Tarik Küçük1, MD;
Alexander W. den Hartog1, MD, PhD; Jan Baan1, MD, PhD; Marcel A.M. Beijk1, MD, PhD;
Ronak Delewi1, MD, PhD; Tim P. van de Hoef1, MD, PhD; Paul Knaapen2, MD, PhD;
Jorrit S. Lemkes2, MD, PhD; Koen M. Marques2, MD, PhD; Alexander Nap2, MD, PhD;
Niels J.W. Verouden2, MD, PhD; M. Marije Vis1, MD, PhD; Robbert J. de Winter1, MD, PhD;
Wouter J. Kikkert2, MD, PhD; Yolande Appelman2, MD, PhD; José P.S. Henriques1*, MD, PhD
1. Department of Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the
Netherlands; 2. Department of Cardiology, Amsterdam UMC, Vrije University (VU), Amsterdam Cardiovascular Sciences,
Amsterdam, the Netherlands
This paper also includes supplementary data published online at: https://eurointervention.pcronline.com/doi/10.4244/EIJ-D-22-00886

KEYWORDS
Abstract
Background: Early P2Y12 inhibitor monotherapy has emerged as a promising alternative to 12 months of
dual antiplatelet therapy following percutaneous coronary intervention (PCI).
• ACS/NSTE-ACS
Aims: In this single-arm pilot study, we evaluated the feasibility and safety of ticagrelor or prasugrel
• adjunctive
monotherapy directly following PCI in patients with non-ST-segment elevation acute coronary syndrome
pharmacotherapy
(NSTE-ACS).
• bleeding
Methods: Patients received a loading dose of ticagrelor or prasugrel before undergoing platelet function
• myocardial
testing and subsequent PCI using new-generation drug-eluting stents. The stent result was adjudicated with
infarction
optical coherence tomography in the first 35 patients. Ticagrelor or prasugrel monotherapy was contin-
• stent thrombosis
ued for 12 months. The primary ischaemic endpoint was the composite of all-cause mortality, myocardial
infarction, definite or probable stent thrombosis or stroke within 6 months. The primary bleeding endpoint
was Bleeding Academic Research Consortium type 2, 3 or 5 bleeding within 6 months.
Results: From March 2021 to March 2022, 125 patients were enrolled, of whom 75 ultimately met all in-
and exclusion criteria (mean age 64.5 years, 29.3% women). Overall, 70 out of 75 (93.3%) patients were
treated with ticagrelor or prasugrel monotherapy directly following PCI. The primary ischaemic endpoint
DOI: 10.4244/EIJ-D-22-00886

occurred in 3 (4.0%) patients within 6 months. No cases of stent thrombosis or spontaneous myocardial
infarction occurred. The primary bleeding endpoint occurred in 7 (9.3%) patients within 6 months.
Conclusions: This study provides first-in-human evidence that P2Y12 inhibitor monotherapy directly fol-
lowing PCI for NSTE-ACS is feasible, without any overt safety concerns, and highlights the need for ran-
domised controlled trials comparing direct P2Y12 inhibitor monotherapy with the current standard of care.

*Corresponding author: Department of Cardiology, Amsterdam UMC, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
E-mail: j.p.henriques@amsterdamumc.nl

© Europa Digital & Publishing 2023. All rights reserved. SUBMITTED ON 09/10/2022 - REVISION RECEIVED ON 11/11/2022 - ACCEPTED ON 11/12/2022

63
EuroIntervention 2023;19:63-72
Abbreviations
ACS acute coronary syndrome
BARC Bleeding Academic Research Consortium
CCS chronic coronary syndrome
DAPT dual antiplatelet therapy
DES drug-eluting stent
MI myocardial infarction
NSTE-ACS non-ST-segment elevation acute coronary syndrome
NSTEMI non-ST-segment elevation myocardial infarction
OCT optical coherence tomography
PCI percutaneous coronary intervention
PRU P2Y12 reaction units
Introduction
In patients with non-ST-segment elevation acute coronary syndrome
(NSTE-ACS) who undergo percutaneous coronary intervention
(PCI), 12 months of dual antiplatelet therapy (DAPT) consisting
of aspirin and a P2Y12 inhibitor is the current standard of care1.
However, the reduction in ischaemic events as a result of DAPT is
at least partly counterbalanced by an increase in bleeding. Contrary
to popular belief, these bleeding events are far from harmless
and are associated with increased mortality2. In fact, the mortal-
ity risk associated with major bleeding is equal to the risk associ-
ated with recurrent myocardial infarction (MI)3. Hence, identifying
the antithrombotic approach with the best trade-off between ischae-
mic and bleeding events remains a matter of intense investigation.
Traditionally, novel antithrombotic strategies have predominantly
been tested on a background of aspirin, but aspirin itself is also
associated with increased bleeding, challenging the paradigm that
this agent should remain the cornerstone of antithrombotic treat-
ment4. In recent years, several large-scale randomised controlled
trials have demonstrated that early aspirin withdrawal (i.e., P2Y12
inhibitor monotherapy) can significantly reduce bleeding without an
increase in either stent-related or non-stent-related ischaemic events5-
10
. However, all these trials included at least 1 to 3 months of DAPT
before switching to P2Y12 inhibitor monotherapy, whereas the aver-
age daily bleeding risk is highest during this early period following
PCI11. Therefore, given the recent advances in stent technology and
the introduction of potent P2Y12 inhibitors (i.e., ticagrelor and pra-
sugrel), we set out to explore if direct P2Y12 inhibitor monotherapy
was feasible and safe in patients with NSTE-ACS undergoing PCI12-14.
Editorial, see page 13
Methods
STUDY DESIGN
The Optical Coherence Tomography-Guided PCI with Single-
Antiplatelet Therapy (OPTICA) study (ClinicalTrials.gov:
NCT04766437) was a single-arm pilot study with 75 patients to
evaluate the feasibility and safety of P2Y12 inhibitor monotherapy
using ticagrelor or prasugrel directly following PCI using new-
generation drug-eluting stents (DES). The study was conducted in
the two affiliated hospitals of the Amsterdam University Medical
Center. Both hospitals are high-volume, tertiary PCI centres situated
64
in Amsterdam, the Netherlands. To enhance patient safety, all
patients underwent platelet function testing before PCI, and the first
35 patients underwent optical coherence tomography (OCT) imaging
after PCI. A stopping rule based on the occurrence of stent thrombo-
sis was incorporated into the study design. If two or more cases of
stent thrombosis occurred, patient enrolment would be prematurely
halted, and patients on ticagrelor or prasugrel monotherapy would
be switched to the current standard of care: 12 months of DAPT.
All study participants provided written informed consent prior to
undergoing any study-specific procedures. An independent data and
safety monitoring board provided external oversight to ensure the
safety of the study participants. The institutional review boards of
both participating centres approved the study protocol.
STUDY PARTICIPANTS
Complete inclusion and exclusion criteria are shown in
Supplementary Table 1. Patients presenting with acute chest pain (or
equivalent symptoms) without persistent ST-segment elevation (i.e.,
NSTE-ACS) who were scheduled for coronary angiography and
possible (ad hoc) PCI using new-generation DES were screened and
considered eligible for the study. Diagnosis was classified as non-
ST-segment elevation myocardial infarction (NSTEMI) or unstable
angina based on the diagnostic criteria outlined in current guide-
lines1. In short, patients were diagnosed with NSTEMI in the pres-
ence of a rise and/or fall pattern of troponin with at least one value
above the 99th percentile of the upper reference limit. If patients did
not have elevated troponin levels or a rise and/or fall pattern, they
were diagnosed with unstable angina. Patients with an allergy or
contraindication to both ticagrelor and prasugrel were excluded, as
were patients requiring chronic oral anticoagulant therapy. Patients
who had an overriding indication for DAPT (e.g., recent PCI or
ACS) and patients requiring complex PCI were also excluded.
Complex PCI was defined as PCI of left main disease, chronic
total occlusion, a bifurcation lesion requiring two-stent treatment,
a saphenous or arterial graft lesion, or severely calcified lesions.
ANTIPLATELET THERAPY BEFORE PCI
Patients received a loading dose of 180 mg ticagrelor or 60 mg
prasugrel at least two hours prior to the index PCI. The agent of
choice was at the discretion of the treating physician. If patients
were on a chronic aspirin regimen or received an aspirin loading
dose (e.g., in the ambulance) prior to inclusion in the study, aspirin
was discontinued on the day of the index PCI at the latest. In line
with current guidelines, patients were treated with 2.5 mg fonda-
parinux subcutaneously once daily alongside ticagrelor or prasug-
rel until revascularisation1.
PLATELET FUNCTION TESTING
Platelet reactivity was assessed using the VerifyNow system
(Werfen) and expressed as P2Y12 reaction units (PRU). High plate-
let reactivity was defined as PRU ≥208, in line with expert consen-
sus15. Blood samples for platelet function testing were collected at
least two hours after administration of the ticagrelor or prasugrel

loading dose using 2 ml blood containers (VACUETTE 9NC coag-
ulation sodium citrate 3.2%; Greiner Bio-One). Blood samples
were drawn from a venous cannula or arterial sheath at the start of
coronary angiography. Blood samples were subsequently processed
by trained research staff in accordance with the manufacturer’s
instructions. Blood samples were analysed within 30 minutes after
sample collection to reduce the risk of error measurements due to
extra platelet activation, haemolysis, or coagulation.
INDEX PCI AND ADJUDICATION OF STENT RESULT
All patients received a weight-adjusted dose of unfractionated
heparin during coronary angiography and an additional dose after
60 minutes if the activated clotting time fell below 250 seconds.
Index PCI was performed with the intention to treat the culprit
vessel using new-generation DES. In case of multiple lesions,
the decision for direct revascularisation of non-culprit lesions
or a staged approach was at the discretion of the treating phy-
sician. Directly following PCI, the stent result was adjudicated
based on the criteria shown in Supplementary Table 2. In the first
35 patients, the stent result was adjudicated per protocol using
OCT imaging. An imaging catheter (Dragonfly OPTIS; Abbott)
was positioned distal to the target lesion(s) and pulled back to the
aorta at an automatic speed of 36 mm/s. OCT-guided stent optimi-
sation (e.g., in case of stent malapposition) was encouraged. The
use of OCT imaging in the remaining 40 patients was at the dis-
cretion of the treating physician.
ANTIPLATELET THERAPY AFTER PCI
Patients with adequate inhibition of platelet reactivity and an opti-
mal stent result continued to receive 90 mg ticagrelor twice daily
or 10 mg prasugrel once daily without concurrent aspirin for up
to 12 months. Of note, prasugrel dose reduction (5 mg instead
of 10 mg once daily) was not allowed under the study protocol.
Therefore, patients with an indication for prasugrel dose reduction
(i.e., patients aged ≥75 years or with a body weight <60 kg) were
solely treated with ticagrelor. In the case of high platelet reactivity
or a suboptimal stent result, aspirin was added to the antiplatelet
regimen. Prior to hospital discharge, all patients were informed
about the importance of medication adherence. Patients with
agent-specific side effects were allowed to switch from ticagrelor
to prasugrel or vice versa during follow-up. In case both prasugrel
and ticagrelor were contraindicated or not tolerated, clopidogrel in
combination with aspirin was considered as the preferred alterna-
tive antiplatelet regimen. If patients developed atrial fibrillation or
another indication for chronic oral anticoagulant therapy during
follow-up, an oral anticoagulant in combination with clopidogrel
for up to 12 months was recommended. Switching between P2Y12
inhibitors was done according to the algorithm recommended by
the European Society of Cardiology16.
FOLLOW-UP
Clinical follow-up was performed at 1, 3, 6 and 12 months by
telephone contact. Patients also attended in-person visits at the
Single antiplatelet therapy directly after PCI
EuroIntervention 2023;19:63-72
outpatient clinic at regular intervals. During follow-up, investi-
gators assessed the occurrence of any adverse events, including
ischaemic and bleeding events. Furthermore, patient-reported
treatment adherence was checked at each follow-up and treatment
adherence was corroborated by prescription refill data reported by
the pharmacy. Any modification to the antiplatelet regimen dur-
ing follow-up was documented, including the date and reason for
modification.
STUDY ENDPOINTS
The primary ischaemic endpoint was the composite of all-cause
mortality, MI, definite or probable stent thrombosis, or stroke
within 6 months following PCI. MI was defined according to the
fourth universal definition, whereas stent thrombosis was classi-
fied according to the Academic Research Consortium criteria17,18.
The primary bleeding endpoint was major or minor bleeding
defined as Bleeding Academic Research Consortium (BARC)
type 2, 3 or 5 bleeding within 6 months following PCI19. BARC
type 3 or 5 bleeding was considered major bleeding, while type 2
was considered minor bleeding. All primary endpoints were adju-
dicated by two authors (NMRS and BEPMC), who had full access
to the patients’ health records. Secondary endpoints included any
repeat revascularisation and the individual components of the pri-
mary endpoints within 6 months following PCI.
STATISTICAL ANALYSIS
The primary objective of our study was descriptive in nature.
Therefore, no formal sample size calculation was performed.
Continuous variables were reported as mean±standard deviation
(SD) or median with interquartile range (IQR) as appropriate.
Categorical variables were reported as frequency and percentage
(%). Cumulative incidences of the primary ischaemic and bleed-
ing endpoints were assessed using Kaplan-Meier estimates at
6 months. Data from patients who did not have a primary end-
point event between the index PCI and 6 months were censored
at the time of death (except for the ischaemic endpoint), time of
last follow-up or 6 months, whichever came first. Analyses of the
primary ischaemic and bleeding endpoints were performed in the
intention-to-treat population, which consisted of all patients who
met the in- and exclusion criteria. Statistical analyses were per-
formed using SPSS version 26 (IBM).
Results
PATIENT INCLUSION
From March 2021 to March 2022, 125 out of 144 screened patients
provided informed consent for participation in the study. The in-
and exclusion criteria were reassessed during coronary angiogra-
phy and PCI, ultimately leading to the inclusion of 75 patients.
The most common reasons for exclusion after enrolment were no
significant coronary artery stenosis during coronary angiography,
conservative management (e.g., target vessel was too small for
intervention) or complex PCI. A detailed flowchart is provided in
Figure 1.
65
EuroIntervention 2023;19:63-72

144 patients screened

19 patients screened but not enrolled

14 declined to participate
2 pretreated with clopidogrel
2 proceeded directly to PCI
1 unavailable for follow-up

125 patients enrolled

50 patients enrolled but not included
21 no significant coronary artery stenosis
9 conservative treatment
9 complex PCI
4 coronary artery bypass grafting
2 PCI using (drug-coated) balloon only
2 coronary angiography not performed
3 other reasons
75 patients included

Figure 1. Study flowchart. PCI: percutaneous coronary intervention

BASELINE CHARACTERISTICS Table 1. Baseline characteristics.

Baseline characteristics are shown in Table 1. The mean age at N=75
the time of enrolment was 64.5±11.6 years, and 29.3% of patients Demographic characteristics
were female. Eighteen patients (24.0%) had diabetes mellitus, Age (yrs) 64.5±11.6
and 28.0% of patients were active smokers at the time of enrol- Body mass index (kg/m2)* 28.2±4.5
ment. Only 16.0% of patients had undergone a PCI prior to the Female sex 22 (29.3%)
index procedure. The majority of patients (85.3%) presented with Cardiovascular risk factors
NSTEMI, while all other patients (14.7%) were diagnosed with Current smokers 21 (28.0%)
unstable angina. New ischaemic ECG changes, predominantly Hypertension 43 (57.3%)
T-wave inversions and ST-segment depressions, were present in Dyslipidaemia 32 (42.7%)
over half of all patients (57.3%). Patients were discharged from Diabetes mellitus 18 (24.0%)
the hospital after a median of 3 days (IQR: 2 to 5). At the time of Insulin-dependent 5 (6.7%)
admission, 15 patients (20.0%) were on a chronic aspirin regimen, Family history of coronary artery disease 20 (26.7%)
and 55 patients (73.3%) received an aspirin loading dose, most Medical history
often in the ambulance, before undergoing PCI. Prior MI 7 (9.3%)
Prior stroke or TIA 4 (5.3%)
PLATELET FUNCTION TESTING Prior PCI 12 (16.0%)
Figure 2 provides an overview of the individual PRU measure- Prior CABG 0 (0.0%)
ments. Before the index procedure, 67 (89.3%) and 8 (10.7%) Chronic obstructive pulmonary disease 3 (4.0%)
patients received an oral loading dose of ticagrelor or prasugrel, Peripheral vascular disease 1 (1.3%)
respectively. All patients, with the exception of one, had ade- Renal insufficiency †
7 (9.3%)
quate inhibition of platelet reactivity with a median PRU value Major bleeding 1 (1.3%)
of 6 (IQR: 2 to 28). In the only patient without adequate inhibi- Clinical presentation
tion of platelet reactivity, high platelet reactivity was possibly due Unstable angina 11 (14.7%)
to a short interval (54 min) between the prasugrel loading dose NSTEMI 64 (85.3%)
and platelet function testing. However, this was not confirmed by New ischaemic ECG changes‡ 43 (57.3%)
repeated platelet function testing. Median PRU values did not dif- Days in hospital (days) 3 (2-5)
fer between patients treated with ticagrelor or prasugrel (6 [IQR: 2 Values are presented as mean±standard deviation, median (IQR) or
number of patients (percentage). *Body mass index was missing in
to 28] vs 3 [IQR: 2 to 79]; p=0.97). 5 cases (6.7%). †Renal insufficiency was defined as an estimated
glomerular filtration rate <60 ml/min/1.73 m2. ‡New ischaemic ECG
changes included transient ST-segment elevation, persistent or transient
PROCEDURAL CHARACTERISTICS ST-segment depression, T-wave inversion, flat T waves, or
Procedural characteristics are shown in Table 2. Most patients pseudonormalisation of T waves. CABG: coronary artery bypass grafting;
ECG: electrocardiogram; MI: myocardial infarction; NSTEMI: non-ST-
underwent PCI via radial access (96.0%), and, per the study design, segment elevation myocardial infarction; PCI: percutaneous coronary
all included patients were treated with at least one new-generation intervention; TIA: transient ischaemic attack

66
 Single antiplatelet therapy directly after PCI

EuroIntervention 2023;19:63-72
400 DES. Eighteen patients (24.0%) underwent multivessel PCI and
Prasugrel
29.3% of patients had more than one treated lesion during the
Ticagrelor
index procedure. The median number of implanted stents per
300 patient was 1 (IQR: 1 to 2), and the median total stent length was
33 mm (IQR: 20 to 46). The median minimum stent diameter was
P2Y12 reaction units

3.00 mm (IQR: 2.75 to 3.50). Almost half of all patients (45.3%)

underwent OCT imaging during the index procedure. OCT-guided
200 HPR
stent optimisation was performed in 10 patients (13.3%) through
post-dilatation (10.7%) or additional stenting (2.7%). After the
procedure, Thrombolysis in Myocardial Infarction (TIMI) flow
100
grade 3 was achieved in 106 out of 106 of lesions (100%). Still,
four patients (5.3%) had a suboptimal stent result or were other-
wise deemed unsuitable for ticagrelor or prasugrel monotherapy
0 by the treating physician. Two of these four patients had an action-
able edge dissection, which was complicated in the first case by
Figure 2. Scatterplot of individual P2Y12 reaction unit measurements. temporary no-reflow and in the second case required additional
The horizontal line represents the median P2Y12 reaction unit value,
stenting of the distal left main. One patient had a total stent length
and the whiskers represent the 25th and 75th percentile range. The
of 172 mm, and one patient had a severely tortuous stent trajec-
dotted line represents the threshold for high platelet reactivity.
tory. Alongside the one patient with high platelet reactivity, these
HPR: high platelet reactivity
patients remained on DAPT following PCI. Hence, 70 (93.3%)
patients were treated with ticagrelor or prasugrel monotherapy
Table 2. Procedural characteristics. directly following PCI.
N=75
Vascular access site per patient OUTCOMES
Radial 72 (96.0%) All included patients completed 6 months of follow-up. Clinical out-
Femoral 3 (4.0%) comes within this timeframe are presented in Table 3. The primary
Treated vessel(s) ischaemic endpoint occurred in 3 patients (4.0%) within 6 months
Left main coronary artery 1 (1.3%)
following PCI. Two patients (2.7%) suffered from a coronary inter-
vention-related MI (Type 4a) due to temporary occlusion of a sep-
Left anterior descending coronary artery 45 (60.0%)
tal and diagonal side branch, respectively, during the index PCI. In
Left circumflex coronary artery 24 (32.0%)
both cases, side branch occlusion was caused by plaque shift and
Right coronary artery* 23 (30.7%)
not thrombus formation. One patient (1.3%), who had undergone
Two or more vessels treated †
18 (24.0%)
PCI of the proximal to distal left anterior descending artery (LAD)
Lesions treated per patient 1 (1-2)
and ostial to mid-ramus circumflex artery (RCx) 53 days before,
1 lesion 53 (70.7%)
suffered from a Type 2 MI due to severe hypertension. During the
2 lesions 13 (17.3%) index procedure, intermediate lesions in the right coronary artery
≥3 lesions 9 (12.0%) (RCA) and ostial LAD were treated conservatively. The stent result
Number of stents used per patient 1 (1-2) in the LAD and RCx was good upon repeat coronary angiography,
1 stent 49 (65.3%) with no angiographic evidence of thrombus, and both the instanta-
2 stents 12 (16.0%) neous wave-free ratio and fractional flow reserve measurements of
≥3 stents 14 (18.7%) the remaining ostial LAD and RCA lesions were negative. No cases
Total stent length per patient (mm) 33 (20-46) of stent thrombosis or spontaneous MI (i.e., Type 1 MI) occurred
Minimum stent diameter per patient (mm) 3.00 (2.75-3.50) within 6 months. The primary bleeding endpoint occurred in seven
Procedure time (min) 43 (33-65) patients (9.3%) within 6 months. Two patients (2.7%) had a major
Antiplatelet regimen directly following procedure bleeding event. One patient suffered from ocular bleeding related
Ticagrelor monotherapy 64 (85.3%) to macular degeneration 60 days after the index procedure. Another
Prasugrel monotherapy 6 (8.0%)
patient required a blood transfusion due to a significant drop in
haemoglobin 71 days after the index procedure, presumably caused
Other‡ 5 (6.7%)
by chronic bleeding from Cameron lesions identified during gas-
Values are presented as median (IQR) or number of patients
(percentage). *Right coronary artery includes right posterolateral branch, troscopy. Out of the seven minor bleeding events which occurred
left anterior descending includes diagonal branches, left circumflex artery
in five patients (6.7%), four were access-site related, one was oro-
includes marginal branches. †Two or more vessels treated during index
procedure. ‡One patient was treated with prasugrel and aspirin (1.3%) pharyngeal, one was nasal and one was traumatic. Four patients
and four patients were treated with ticagrelor and aspirin (5.3%).
(5.3%) underwent repeat revascularisation within 6 months. All

67
EuroIntervention 2023;19:63-72

Table 3. Clinical outcomes at 6-month follow-up. revascularisations were non-target vessel related, and two out of
N=75 the four procedures were part of a planned staged procedure. All
patients undergoing elective, non-target vessel revascularisation
Primary ischaemic endpoint* 3 (4.0%)
continued ticagrelor or prasugrel monotherapy unless the proce-
All-cause death 0 (0.0%)
dure was considered complex (e.g., PCI of chronic total occlusion).
Cardiac death 0 (0.0%)
Four other patients (5.3%) also underwent repeat coronary angio-
Non-cardiac death 0 (0.0%)
graphy within 6 months, indicated by either recurrent or persistent
Myocardial infarction 3 (4.0%)
angina or dyspnoea, all without evidence of new stent-related (or
Type 1 0 (0.0%)
non-stent-related) stenosis.
Type 2 1 (1.3%)
Type 3 0 (0.0%)
MEDICATION ADHERENCE
Type 4a 2 (2.7%)
Adherence to the study regimen is shown in Figure 3. Directly
Type 4b 0 (0.0%)
following PCI, 93.3% of patients were on ticagrelor or prasugrel
Type 4c 0 (0.0%) monotherapy. At 1, 3 and 6 months, 89.3%, 85.3% and 82.7% of
Type 5 0 (0.0%) patients remained on ticagrelor or prasugrel monotherapy, respec-
Probable or definite stent thrombosis 0 (0.0%) tively. During follow-up, 24 treatment modifications occurred in
Definite 0 (0.0%) 20 (26.7%) patients after a median follow-up of 60 days (IQR: 32
Probable 0 (0.0%) to 130). Eleven (14.7%) patients switched from ticagrelor to pras-
Stroke 0 (0.0%) ugrel monotherapy during follow-up, mainly due to presumed side
Ischaemic 0 (0.0%) effects of ticagrelor. For similar reasons four patients (5.3%) in
Haemorrhagic 0 (0.0%) whom prasugrel was contraindicated, mainly because the patients
Unknown 0 (0.0%) were 75 years old or older, switched from ticagrelor monother-
Primary bleeding endpoint †
7 (9.3%) apy to clopidogrel and aspirin. Two patients (2.7%) switched from
BARC type 2 bleeding 5 (6.7%) ticagrelor monotherapy to ticagrelor and aspirin after complex,
BARC type 3 bleeding 2 (2.7%) non-target vessel revascularisation during follow-up, and two
BARC type 5 bleeding 0 (0.0%) patients (2.7%) switched to clopidogrel and an oral anticoagulant
Secondary endpoints due to new onset atrial fibrillation. An overview of all treatment
Repeat revascularisation 4 (5.3%) modifications is provided in Supplementary Table 3.
Target lesion revascularisation 0 (0.0%)
Target vessel revascularisation 0 (0.0%)
Discussion
Our pilot study was designed to examine the feasibility and safety
Non-target vessel revascularisation 4 (5.3%)
of P2Y12 inhibitor monotherapy using ticagrelor or prasugrel
Values are presented as number of patients and Kaplan–Meier estimates
of the cumulative incidence of the clinical endpoints. *The primary directly after PCI in patients with NSTE-ACS. P2Y12 inhibitor
ischaemic endpoint was the composite of all-cause mortality, myocardial
monotherapy was feasible in most patients and, more importantly,
infarction, definite or probable stent thrombosis or stroke within
6 months following PCI. †The primary bleeding endpoint was major or not associated with any overt safety concerns given the absence of
minor bleeding defined as Bleeding Academic Research Consortium type
2, 3 or 5 bleeding within 6 months following PCI. BARC: Bleeding
stent thrombosis and spontaneous MI within the first six months
Academic Research Consortium; PCI: percutaneous coroanry intervention of follow-up (Central illustration). Although other investigators

75
P2Y12- inhibitor monotherapy
60 Ticagrelor monotherapy
Prasugrel monotherapy
No. of patients (n)

45 Ticagrelor and aspirin

Prasugrel and aspirin
Clopidogrel and aspirin
30 Clopidogrel and OAC

15

0
CI rg
e th th
s
th
s
th
s
th
s
th
s
rP ha on on on on on on
te isc
m m m m m m
Af d 1 2 3 4 5 6
At

Figure 3. Antithrombotic treatment during follow-up. OAC: oral anticoagulant

68
 Single antiplatelet therapy directly after PCI

EuroIntervention 2023;19:63-72
EuroIntervention

CENTRAL ILLUSTRATION Ticagrelor or prasugrel monotherapy directly after percutaneous coronary intervention for
acute coronary syndrome without ST-segment elevation.

75 (100%) patients included

5 (6.7%) patients treated with dual antiplatelet therapy

4 (5.3%) suboptimal stent result
1 (1.3%) inadequate inhibition of platelet reactivity
70 (93.3%) patients treated with
ticagrelor or prasugrel monotherapy

75 (100%) patients included in the

intention-to-treat analysis

3 (4.0%) patients met the primary ischaemic endpoint 7 (9.3%) patients met the primary bleeding endpoint
2 (2.7%) Type 4a myocardial infarction* 2 (2.7%) major bleeding events
1 (1.3%) Type 2 myocardial infarction* 5 (6.7%) minor bleeding events

P2Y12 inhibitor monotherapy directly after PCI for non-ST-segment elevation ACS is feasible and not associated
with any overt safety concerns given the absence of stent thrombosis and spontaneous Ml during follow-up
*In all cases myocardial infarction classification was corroborated by angiographic findings during (repeat) coronary angiography.
ACS: acute coronary syndrome; MI: myocardial infarction; PCI: percutaneous coronary intervention

have previously shown that direct P2Y12 inhibitor monotherapy
using prasugrel was feasible and safe in patients undergoing PCI
for chronic coronary syndrome (CCS), our pilot study is the first
to examine aspirin withdrawal directly after PCI for NSTE-ACS20.
This pilot study was only possible because of the recent advances
made in stent technology and the advent of potent P2Y12 inhibi-
tors. Compared to early-generation DES, the new-generation DES
used in the present study have thinner struts and better biocompat-
ible polymers21. These technological advances in combination with
improved stent implantation techniques have led to a very low rate
of stent-related adverse events22. In the present era, stent thrombo-
sis is most often a consequence of suboptimal stent deployment
and not device thrombogenicity, limiting the need for prolonged
DAPT after successful stent implantation23. Furthermore, potent
P2Y12 inhibitors such as ticagrelor and prasugrel exert a stronger
and more reliable inhibitory effect on platelet aggregation com-
pared to clopidogrel24. Pharmacological studies have demon-
strated that the antithrombotic potency of ticagrelor and prasugrel
alone is similar to the potency of ticagrelor or prasugrel combined
with aspirin, providing a mechanistic rationale for P2Y12 inhibi-
tor monotherapy25,26. In the TWILIGHT (Ticagrelor with Aspirin
or Alone in High-Risk Patients after Coronary Intervention)
Platelet Sub-study, data on thrombogenicity under dynamic flow
conditions showed that the antithrombotic potency of ticagrelor
monotherapy was similar to that of ticagrelor combined with aspi-
rin in high-risk patients undergoing PCI25. Similarly, Armstrong
et al used platelet-rich plasma from healthy volunteers to demon-
strate that prasugrel induces a potent inhibition of platelet aggre-
gation even without aspirin and that the addition of aspirin does
not further increase the inhibition of platelet aggregation26.
In recent years, six randomised controlled trials, including over
thirty-five thousand patients, have examined the clinical effects
of early P2Y12 inhibitor monotherapy after PCI for CCS and
ACS. In contrast to our study, the other trials included at least 1
to 3 months of DAPT before switching to P2Y12 inhibitor mono-
therapy. Overall, five of these six trials showed that early P2Y12
inhibitor monotherapy reduced clinically relevant bleeding6-10.
Only in the GLOBAL LEADERS trial, ticagrelor monotherapy
for 23 months preceded by 1 month of DAPT did not reduce
major bleeding compared to aspirin monotherapy for 12 months
preceded by 12 months of DAPT5. Three out of six trials con-
ducted a formal non-inferiority analysis with regard to ischae-
mic events and all three trials met their prespecified criteria for
non-inferiority6,7,9. In the pivotal TWILIGHT trial, the rate of all-
cause mortality, MI or stroke was similar in patients treated with
ticagrelor monotherapy and DAPT (3.9% vs 3.9%, hazard ratio

69
EuroIntervention 2023;19:63-72
[HR] 0.99, 95% confidence interval [CI]: 0.78-1.25; PNI<0.001)9.
Conversely, the STOPDAPT-2 ACS (ShorT and OPtimal Duration
of Dual AntiPlatelet Therapy-2 Study for the Patients With ACS)
trial failed to attest the non-inferiority of clopidogrel monotherapy
after 1 to 2 months compared to 12 months of DAPT with regard
to the net clinical benefit endpoint consisting of cardiovascular
death, MI, stroke, stent thrombosis and TIMI major or minor
bleeding (3.2% vs 2.8%, HR 1.14, 95% CI: 0.80-1.62; PNI=0.06).
Notably, the composite of cardiovascular death, MI, stroke and
stent thrombosis was numerically higher in the clopidogrel mono-
therapy group (2.8% vs 1.9%, HR 1.50, 95% CI: 0.99-2.26)10.
Importantly, current guidelines only recommend clopidogrel for
ACS patients when prasugrel and ticagrelor are contraindicated
or cannot be tolerated1. Possibly, clopidogrel is therefore also less
suitable as an agent of choice in the setting of monotherapy com-
pared to ticagrelor and prasugrel.
The ASET (Acetyl Salicylic Elimination Trial) Pilot Study was
the first to examine the feasibility and safety of prasugrel mon-
otherapy directly following everolimus-eluting stent implanta-
tion in patients with CCS and low anatomic complexity20. In the
ASET Pilot Study, 201 patients were treated with DAPT prior
to the index procedure and started prasugrel directly after PCI.
Overall, 98.5% of patients were adherent to prasugrel monother-
apy, and there were no cases of stent thrombosis or spontaneous
MI at 3-month follow-up. One patient (0.5%) suffered from a fatal
intracranial bleeding in the days following PCI, although the over-
all rate of bleeding (BARC type 1 to 5) was extremely low at
0.5%. The bleeding rate in our study was higher, but most bleed-
ing events were minor and primarily access-site related. The ASET
investigators maximised safety by applying stringent patient selec-
tion focused on enrolling only low-risk patients. Consequently,
patients were possibly not only at low ischaemic risk, but also at
low bleeding risk. Currently, the ASET investigators are evaluat-
ing direct prasugrel monotherapy in a larger cohort of 400 patients
undergoing PCI for CCS and NSTE-ACS in the ASET JAPAN
Pilot Study (ClinicalTrials.gov: NCT05117866).
Ultimately, large-scale randomised controlled trials will need to
examine the efficacy and safety of direct P2Y12 inhibitor mono-
therapy compared to the current standard of care; 12 months of
DAPT. Currently, both the LEGACY (Less Bleeding by Omitting
Aspirin in Non-ST-segment Elevation Acute Coronary Syndrome
Patients; ClinicalTrials.gov: NCT05125276) and NEOMINDSET
(PercutaNEOus Coronary Intervention Followed by Monotherapy
INstead of Dual Antiplatelet Therapy in the SETting of Acute
Coronary Syndromes; ClinicalTrials.gov: NCT04360720) trials
are comparing direct P2Y12 inhibitor monotherapy to conventional
DAPT in patients undergoing PCI for ACS. Importantly, both tri-
als allow for prasugrel monotherapy in the study design. Thus far,
ticagrelor has been predominantly used in trials evaluating P2Y12
inhibitor monotherapy, and experience with prasugrel in this set-
ting has been limited27. However, treatment modifications in trials
evaluating different antithrombotic strategies are common, with
approximately 10-15% of all patients altering treatment during
70
follow-up5,9,28. Prasugrel could serve as an alternative in patients
not tolerating ticagrelor29,30. For example, in this pilot study,
eleven patients (14.7%) were switched from ticagrelor to prasugrel
monotherapy and were therefore able to continue P2Y12 inhibitor
monotherapy.
Limitations
This study has several limitations. First, there was no compara-
tor or control group. Therefore, it is not possible to draw conclu-
sions in terms of the safety and efficacy of ticagrelor or prasugrel
monotherapy compared to the current standard of care; 12 months
of DAPT. Second, important exclusion criteria such as the exclu-
sion of complex PCI should be considered when extrapolating
the results to a more general population. Third, all patients in the
present study underwent platelet function testing, which is not
reflective of daily clinical practice. Still, high platelet reactivity
in prasugrel- or ticagrelor-treated patients was rare in our study,
consistent with the literature31. Therefore, routine platelet function
testing in future randomised controlled trials and daily clinical
practice might not be necessary. Fourth, almost half of the patients
in the present study underwent OCT-guided PCI, minimising the
risk of ischaemic events post-PCI since the stent result is strongly
associated with stent-related ischaemic events during follow-up23.
Finally, the endpoints were adjudicated by two authors and not an
independent clinical event committee.
Conclusions
Completely omitting aspirin after successful PCI in NSTE-ACS is
feasible and not associated with any overt safety concerns given
the absence of stent thrombosis and spontaneous MI within the
first six months of follow-up. Larger randomised controlled trials
are warranted to compare the efficacy and safety of completely
omitting aspirin with 12 months of DAPT.
Impact on daily practice
Twelve months of dual antiplatelet therapy (DAPT) has long
been the standard of care after percutaneous coronary inter-
vention (PCI) for acute coronary syndrome (ACS) without
ST-segment elevation, but early or even direct P2Y12 inhibitor
monotherapy has emerged as a promising alternative that can
possibly reduce bleeding without a trade-off in efficacy. Our
pilot study is the first to examine aspirin withdrawal directly
after PCI for ACS without ST-segment elevation but was limited
in sample size and did not include a control group. Ultimately,
large-scale randomised controlled trials will need to confirm the
efficacy and safety of direct P2Y12 inhibitor monotherapy com-
pared to 12 months of DAPT.
Acknowledgements
The investigators would like to thank Dr E.K. Arkenbout and
Dr R.J. van der Schaaf for serving as members of the data and
safety monitoring board.

Funding
The OPTICA pilot study was funded by the Amsterdam UMC
(Amsterdam, the Netherlands) and received in-kind contributions
from Werfen (Barcelona, Spain) and Abbott Vascular (CA, USA).
Conflict of interest statement
M.A.M. Beijk received a research grant from Actelion (Johnson
& Johnson). W.J. Kikkert received a research grant from
AstraZeneca. Y. Appelman received a research grant from the
Dutch Heart Foundation. J.P.S. Henriques received research
grants from Abbott Vascular, AstraZeneca, B. Braun, Getinge,
Ferrer, Infraredx, and ZonMw. The other authors have no con-
flicts of interest to declare.
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Supplementary data
Supplementary Table 1. Inclusion and exclusion criteria.
Supplementary Table 2. Adjudication of stent result.
Supplementary Table 3. Treatment modifications during follow-
up sorted by time until treatment modification.
The supplementary data are published online at:
https://eurointervention.pcronline.com/
doi/10.4244/EIJ-D-22-00886
 CORONARY INTERVENTIONS
CLINICAL RESEARCH

EuroIntervention 2023;19:73-79 published online ahead of print February 2023

Ultrasound-guided femoral access in patients with vascular
closure devices: a prespecified analysis of the randomised
UNIVERSAL trial
Marc-André d’Entremont1,2, MD, MPH; Sulaiman Alrashidi3,4,5, MD; Omar Alansari3,4,5, MD;
Bradley Brochu6, MD; Laura Heenan2, MSc; Elizabeth Skuriat2, MSc; Jessica Tyrwhitt2, BSc;
Michael Raco3,4,5, MD; Michael B. Tsang3,4,5, MD, MSc; Nicholas Valettas3,4,5, MD, MASc;
James Velianou3,4,5, MD; Tej Sheth2,3,4,5, MD; Matthew Sibbald3,4,5, MD, PhD; Shamir R. Mehta2,3,4,5, MD, MSc;
Natalia Pinilla-Echeverri2,3,4,5, MD, MSc; Jon-David Schwalm2,3,4,5, MD, MSc;
Madhu K. Natarajan2,3,4,5, MD, MSc; Andrew Kelly3,4,5, MD; Elie Akl7, MD; Sarah Tawadros4, MBBCh;
Mercedes Camargo4, MD, MASc; Walaa Faidi4, MSc; John Bauer4, BMRSc; Rachel Moxham4, BSc;
James Nkurunziza3,4,5, MD; Gustavo Dutra3,4, MD; Jose Winter8, MD; Sanjit S. Jolly2,3,4,5*, MD, MSc
1. Centre Hospitalier Universitaire de Sherbrooke (CHUS), Sherbrooke, QC, Canada; 2. Population Health Research Institute,
Hamilton, ON, Canada; 3. McMaster University, Hamilton, ON, Canada; 4. Hamilton Health Sciences, Hamilton, ON, Canada;
5. Niagara Health, St. Catharines, ON, Canada; 6. CK Hui Heart Centre, Royal Alexandra Hospital, Edmonton, AB, Canada;
7. McGill University Faculty of Medicine and Health Sciences, Montreal, QC, Canada; 8. Clinica Alemana De Santiago,
Universidad de Desarrollo, Santiago, Chile
This paper also includes supplementary data published online at: https://eurointervention.pcronline.com/doi/10.4244/EIJ-D-22-01130

KEYWORDS
Abstract
Background: Whether ultrasound (US)-guided femoral access compared to femoral access without US
guidance decreases access site complications in patients receiving a vascular closure device (VCD) is
• access site
unclear.
• bleeding
Aims: We aimed to compare the safety of VCD in patients undergoing US-guided versus non-US-guided
• femoral
femoral arterial access for coronary procedures.
Methods: We performed a prespecified subgroup analysis of the UNIVERSAL trial, a multicentre ran-
domised controlled trial of 1:1 US-guided femoral access versus non-US-guided femoral access, stratified
for planned VCD use, for coronary procedures on a background of fluoroscopic landmarking. The primary
endpoint was a composite of major Bleeding Academic Research Consortium 2, 3 or 5 bleeding and vas-
cular complications at 30 days.
Results: Of 621 patients, 328 (52.8%) received a VCD (86% ANGIO-SEAL, 14% ProGlide). In patients
who received a VCD, those randomised to US-guided femoral access compared to non-US-guided fem-
oral access experienced a reduction in major bleeding or vascular complications (20/170 [11.8%] vs
37/158 [23.4%], odds ratio [OR] 0.44, 95% confidence interval [CI]: 0.23-0.82). In patients who did not
DOI: 10.4244/EIJ-D-22-01130

receive a VCD, there was no difference between the US- and non-US-guided femoral access groups, respec-
tively (20/141 [14.2%] vs 13/152 [8.6%], OR 1.76, 95% CI: 0.80-4.03; interaction p=0.004).
Conclusions: In patients receiving a VCD after coronary procedures, US-guided femoral access was
associated with fewer bleeding and vascular complications compared to femoral access without US guid-
ance. US guidance for femoral access may be particularly beneficial when VCD are used.

*Corresponding author: Population Health Research Institute, Hamilton General Hospital, 237 Barton Street East, Hamilton,
ON L8L 2X2, Canada. E-mail: sanjit.jolly@phri.ca

© Europa Digital & Publishing 2023. All rights reserved. SUBMITTED ON 24/12/2022 - REVISION RECEIVED ON 29/01/2023 - ACCEPTED ON 08/02/2023

73
EuroIntervention 2023;19:73-79
Abbreviations
BARC Bleeding Academic Research Consortium
CI confidence interval
OR odds ratio
PCI percutaneous coronary intervention
US ultrasound
VCD vascular closure device
Introduction
Transradial access reduces major vascular complications and
access site bleeding compared to transfemoral access in patients
undergoing coronary angiography or percutaneous coronary inter-
ventions (PCI) and is therefore recommended1. However, femoral
access is still indicated in larger bore procedures, in procedures
where radial access failure has occurred, and bilateral internal
mammary coronary graft angiography. Vascular and bleeding
complications in femoral access can occur because of high or low
punctures, multiple punctures, or inadequate haemostasis tech-
nique2. Studies have demonstrated that vascular closure devices
(VCD) are associated with a reduced time to haemostasis and
reduced time to ambulation, with no difference in the incidence of
vascular injury or mortality compared to manual compression3-5.
Given the ubiquitous use of vascular closure devices for femoral
access to optimise patient comfort and increase workflow, strate-
gies to decrease vascular closure device complications are clini-
cally important.
The UNIVERSAL trial, which randomised 621 patients, strati-
fied by planned VCD use, to ultrasound (US) versus no US for
femoral access, did not demonstrate a significant difference for
the primary composite outcome of major bleeding or vascular
complications6. In patients receiving a VCD, we hypothesised
that patients with US-guided femoral access would experience
fewer access site complications than patients without US-guided
femoral access. The present study aims to explore the association
between US-guided femoral access and VCD use on bleeding and
vascular complications in the prespecified VCD subgroups of the
UNIVERSAL trial.
Editorial, see page 15
Methods
STUDY DESIGN AND PATIENTS
The Routine Ultrasound Guidance for Vascular Access for
Cardiac Procedures (UNIVERSAL) trial was a multicentre, open-
label, investigator-driven, randomised clinical trial comparing
US-guided femoral access versus no US for coronary procedures
on a background of fluoroscopic landmarking for the primary
composite endpoint of major bleeding and vascular complications
(ClinicalTrials.gov: NCT03537118)6. The details of the design of
the trial have been previously published7. Patients were eligible
if referred for coronary angiogram or PCI with planned femo-
ral access. Exclusion criteria were minimal: 1) age 18 years or
younger, 2) ST-elevation myocardial infarction as the initial pres-
entation, and 3) absence of a palpable femoral pulse. Eligible
74
patients were randomised 1:1, stratified by planned VCD use, to
femoral access with either US or no US. The subgroup analyses
were performed by actual post-randomisation VCD use in patients
randomised to US versus no US as specified in the protocol. Of
note, US was used only to guide the femoral puncture and not to
subsequently guide the VCD deployment.
The Population Health Research Institute, a joint institute of
McMaster University and Hamilton Health Sciences, conducted
the UNIVERSAL trial. The trial was approved by the ethics com-
mittee at each participating centre.
CLINICAL STUDY OUTCOMES
The primary outcome was the composite of Bleeding Academic
Research Consortium (BARC) 2, 3, or 5 bleeding or major vas-
cular complications, including femoral artery pseudoaneurysm,
arteriovenous fistula, retroperitoneal bleed, large haematoma more
than 5 cm in diameter, or an ischaemic limb requiring intervention
or surgery at 30 days.
A blinded investigator evaluated the presence of major bleeding
or vascular complications at discharge. Furthermore, investigators
blinded to allocation completed a comprehensive medical record
review and telephone follow-up within 30 days of the index procedure.
ANGIOGRAPHIC CORE LABORATORY EVALUATION
Femoral angiograms were reviewed by blinded research person-
nel in the angiographic core laboratory at the Hamilton General
Hospital, Hamilton, Canada. We reported the location of the fem-
oral bifurcation, the presence of common femoral artery calcifi-
cation, the successful cannulation of the common femoral artery,
active bleeding, and the presence of femoral artery dissection.
STATISTICAL ANALYSIS
We presented continuous variables with normal distributions
as means with standard deviations and compared groups using
the Student’s t-test. We presented categorical variables as abso-
lute frequencies and percentages and compared groups using the
chi-square or Fisher’s exact test as appropriate. For the main
outcomes, odds ratios (OR) with 95% confidence intervals (CI)
were calculated. We calculated interactions between VCD sub-
groups and treatment allocation, using the Breslow-Day test of
homogeneity, for the primary outcome, major bleeding alone,
and vascular complications alone. We similarly analysed the
different types of VCD. Two-tailed p-values <0.05 were con-
sidered statistically significant. We did not adjust for multiplic-
ity. All analyses were performed using SAS version 9.4 (SAS
Institute).
Results
BASELINE CHARACTERISTICS
As demonstrated in Figure 1, 311 patients were allocated to US
compared to 310 patients who were allocated to no US on a back-
ground of fluoroscopic guidance. No patients were lost to follow-
up. A total of 170 of 311 (54.7%) patients in the US arm received

Randomised (n=621)
Allocated to US guidance (n=311)
– Procedure cancelled (n=1)
– Radial access only due to physician decision (n=2)
– Second femoral access used (n=5)
– Cross-over to fluoroscopic guidance alone due to
physician decision (n=1)
Lost to follow-up (n=0)
Included in intention-to-treat analysis (n=311)
US-guided TFA/VCD US-guided TFA/no VCD
subgroup subgroup
(n=170) (n=141)
Figure 1. CONSORT diagram for the UNIVERSAL trial with vascular closure device subgroups. TFA: transfemoral access; US: ultrasound;
VCD: vascular closure device
a VCD, compared to 158 of 310 (51.0%) patients in the no US
arm, for a total of 328 VCD patients.
The baseline characteristics were well balanced between sub-
groups when comparing US guidance to no US guidance, after
stratification for VCD use (Table 1). In the VCD subgroup, the
patients had a mean age of 70 years, 84 (25.6%) were female, and
they had a mean body mass index of 29.4 kg/m2. The VCD sub-
group had a comorbid population: 178 (54.2%) had a prior myo-
cardial infarction, 170 (51.8%) had a previous PCI, 177 (54.0%)
had prior coronary artery bypass surgery, 131 (39.9%) had diabe-
tes mellitus, 43 (13.1%) had peripheral artery disease, 49 (14.9%)
had atrial fibrillation, with similar rates of comorbidities in the
no VCD group. Chronic total occlusion PCI was performed in 60
(18.3%) patients in the VCD subgroup.
PROCEDURAL CHARACTERISTICS AND CORE LABORATORY
DATA IN VCD PATIENTS
A 6 Fr introducer was used for most accesses (n=246/332,
74.1%), and 141 of 172 (82.0%) US-guided accesses compared
to 143 of 160 (89.4%) of non-US-guided accesses received an
ANGIO-SEAL (Terumo) device (Table 2). Closure device fail-
ures according to access site were similar in both groups, with
16/172 (9.3%) failures in the US-guided subgroup and 11/160
(6.9%) failures in the non-US-guided subgroup (p=0.42)
(Supplementary Table 1).
Successful cannulation of the common femoral artery (above
the bifurcation and below the inferior epigastric artery) occurred
in 148/169 (87.6%) of the US-guided femoral access sites com-
pared to 141/156 (90.4%) of the non-US-guided femoral access
sites (p=0.42) (Supplementary Table 2).
Ultrasound for vascular closure in femoral access
EuroIntervention 2023;19:73-79
Allocated to no US guidance (n=310)
– Procedure cancelled (n=1)
– Radial access only due to physician decision (n=2)
Allocation – Second femoral access used (n=4)
– Cross-over to ultrasound + fluoroscopic guidance due to
physician decision (n=7)
Follow-up Lost to follow-up (n=0)
Included in intention-to-treat analysis (n=310)
Analysis
Non-US-guided TFA/VCD Non-US-guided TFA/no VCD
subgroup subgroup
(n=158) (n=152)
MAIN OUTCOMES
In patients who received a VCD, those who were randomised to
US-guided femoral access compared to non-US-guided femo-
ral access experienced a reduction in major bleeding or vascular
complications (20/170 [11.8%] vs 37/158 [23.4%], OR 0.44, 95%
CI: 0.23-0.82). In patients who did not receive a VCD, there was
no difference between the US-guided and non-US-guided femo-
ral access subgroups (20/141 [14.2%] vs 13/152 [8.6%], OR 1.76,
95% CI: 0.80-4.03). We observed significant interaction (interac-
tion p=0.004) (Figure 2). More specifically, patients receiving an
ANGIO-SEAL who were randomised to the US group experienced
significantly fewer access site complications than patients who
were randomised to the no US group (OR 0.33, 95% CI: 0.15-
0.71). This effect was non-significant for the ProGlide (Abbott)
VCD, with the caveat of wide confidence intervals (OR 0.74, 95%
CI: 0.17-3.31). There was no significant interaction (interaction
p=0.29).
When considering individual outcomes in patients who received
a VCD, US-randomised patients had fewer major vascular com-
plications than no US patients (7/170 [4.1%] vs 21/158 [13.3%],
OR 0.28, 95% CI: 0.10-0.71). This beneficial effect of US was not
observed in patients who did not receive a VCD (13/141 [9.2%] vs
8/152 [5.3%], OR 1.82, 95% CI: 0.68-5.25; interaction p=0.004).
However, in patients who received a VCD, those randomised to
US guidance did not experience a decrease in major bleeding as
compared to those randomised to no US guidance (16/170 [9.4%]
vs 24/158 [15.2%], OR 0.58, 95% CI: 0.28-1.19). Similarly,
in patients who did not receive a VCD, those randomised to
US-guided femoral access did not fare better than their non-US-
guided counterparts (15/141 [10.6%] vs 9/152 [5.9%] OR 1.89,
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EuroIntervention 2023;19:73-79

Table 1. Baseline characteristics.

Vascular closure device use No vascular closure device
(n=328) (n=293)
Variables p-value p-value
US-guided Non-US-guided US-guided Non-US-guided
(n=170) (n=158) (n=141) (n=152)
Demographics and comorbidities
Age (years) 69.89±10.14 69.63±10.40 0.82 71.15±10.14 71.71±10.25 0.64
Female sex 41 (24.1%) 43 (27.2%) 0.52 39 (27.7%) 35 (23.0%) 0.36
BMI1 (kg/m2) 29.91±6.01 28.79±6.35 0.10 28.99±6.08 28.90±6.60 0.90
Hypertension 144 (84.7%) 141 (89.2%) 0.22 120 (85.1%) 133 (87.5%) 0.55
Dyslipidaemia 147 (86.5%) 140 (88.6%) 0.56 126 (89.4%) 142 (93.4%) 0.21
Diabetes 74 (43.5%) 57 (36.1%) 0.17 59 (41.8%) 71 (46.7%) 0.40
Current smoker 27 (15.9%) 30 (19.0%) 0.46 13 (9.2%) 22 (14.5%) 0.17
Previous myocardial infarction 88 (51.8%) 90 (57.0%) 0.35 68 (48.2%) 73 (48.0%) 0.76
Previous PCI 87 (51.2%) 83 (52.5%) 0.81 53 (37.6%) 55 (36.2%) 0.80
Previous CABG 92 (54.1%) 85 (53.8%) 0.95 86 (61.0%) 90 (59.2%) 0.76
Previous stroke/TIA 15 (8.8%) 13 (8.2%) 0.85 10 (7.1%) 20 (13.2%) 0.09
Peripheral vascular disease 24 (14.1%) 19 (12.0%) 0.44 33 (23.4%) 34 (22.4%) 0.83
Atrial fibrillation 31 (18.2%) 18 (11.4%) 0.08 27 (19.2%) 39 (25.7%) 0.18
Chronic kidney disease 20 (11.8%) 17 (10.8%) 0.77 30 (21.3%) 26 (17.1%) 0.36
PCI performed during procedure 97 (57.1%) 92 (58.2%) 0.83 37 (26.2%) 36 (23.7%) 0.61
Indication for procedure
Atypical chest pain 20 (11.8%) 15 (9.5%) 0.51 17 (12.1%) 31 (20.4%) 0.05
Stable angina 54 (31.8%) 33 (20.9%) 0.03 34 (24.1%) 35 (23.0%) 0.83
Silent ischaemia 3 (1.8%) 3 (1.9%) 1.0 5 (3.6%) 6 (4.0%) 1.0
Unstable angina 21 (12.4%) 11 (7.0%) 0.10 16 (11.4%) 7 (4.6%) 0.03
NSTEMI 30 (17.7%) 38 (24.1%) 0.15 24 (17.0%) 31 (20.4%) 0.46
Planned PCI 14 (8.2%) 9 (5.7%) 0.37 6 (4.3%) 3 (2.0%) 0.32
CTO PCI 27 (15.9%) 33 (20.9%) 0.24 15 (10.6%) 13 (8.6%) 0.54
Valvular assessment 2 (1.2%) 2 (1.3%) 1.0 7 (5.0%) 1 (0.7%) 0.61
Other 11 (6.5%) 18 (11.4%) 0.12 25 (17.7%) 33 (21.7%) 0.46
Medications at baseline
Aspirin 153 (90.0%) 143 (90.5%) 0.88 105 (74.5%) 119 (78.3%) 0.44
Plavix 82 (48.2%) 70 (44.3%) 0.51 47 (33.3%) 51 (33.6%) 0.97
Ticagrelor 19 (11.2%) 28 (17.7%) 0.09 14 (9.9%) 9 (5.9%) 0.20
Prasugrel 0 (0.0%) 0 (0.0%) 1.0 0 (0.0%) 0 (0.0%) 1.0
Warfarin 6 (3.5%) 1 (0.6%) 0.12 7 (5.0%) 10 (6.6%) 0.55
NOAC 18 (10.6%) 15 (9.5%) 0.74 20 (14.2%) 26 (17.1%) 0.49
Fondaparinux 16 (9.4%) 11 (7.0%) 0.42 5 (3.6%) 7 (4.6%) 0.77
Unfractionated heparin 2 (1.2%) 7 (4.4%) 0.09 5 (3.6%) 8 (5.3%) 0.58
Low-molecular-weight heparin 2 (1.2%) 0 (0.0%) 0.50 5 (3.6%) 1 (0.7%) 0.11
Bivalirudin 1 (0.6%) 0 (0.0%) 1.0 0 (0.0%) 0 (0.0%) 1.0
GP IIa/IIIb inhibitors 0 (0.0%) 0 (0.0%) 1.0 0 (0.0%) 0 (0.0%) 1.0
Anticoagulation during procedure
UFH use 114 (67.1%) 112 (70.9%) 0.48 44 (31.2%) 58 (38.2%) 0.21
Total dose of heparin (PCI procedure) 8,078.1±3,151.7 7,443.5±2,837.7 0.06 7,494.4±3,396.0 7,705.6±2,615.8 0.55
Final ACT 295.73±110.76 293.76±102.72 0.87 243.92±94.64 259.44±98.69 0.17
Data are expressed as mean±standard deviation (SD) or n (%). 12 patients had missing BMI values. ACT: activated clotting time; BMI: body mass index;
CABG: coronary artery bypass graft; CTO: chronic total occlusion; GP: glycoprotein; NOAC: non-vitamin K antagonist oral anticoagulants; NSTEMI:
non-ST-segment elevation myocardial infarction; PCI: percutaneous coronary intervention; TIA: transient ischaemic attack; UFH: unfractionated heparin;
US: ultrasound

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 Ultrasound for vascular closure in femoral access

EuroIntervention 2023;19:73-79
Table 2. Procedural characteristics in patients receiving a and VCD existed, with benefit for US use. One explanation for
vascular closure device (by access site, as chronic total the finding was that in the UNIVERSAL trial, patients randomised
occlusion procedures may have had two access sites). to US-guided femoral access had fewer attempts for arterial punc-
US-guided Non-US-guided ture (1.16 vs 1.43; p<0.001) and fewer venipunctures (3.1% vs
Variables p-value 11.7%; p<0.001). These data are consistent with previous meta-
(n=172) (n=160)
Right-sided femoral access 165 (95.9%) 152 (95.0%) 0.68 analyses8,9. Reducing the number of arterial punctures is essential,
Introducer 5 Fr 0 (0.0%) 0 (0.0%) 1.0 as a VCD will only close one puncture site and will not mitigate
size
6 Fr 127 (73.8%) 119 (74.4%) 0.91 venous bleeding. This hypothesis may be supported by our finding
7 Fr 37 (21.5%) 37 (23.1%) 0.72
that large haematomas were more frequent in patients receiving
VCD to close non-US-guided punctures compared to US-guided
8 Fr 7 (4.1%) 2 (1.3%) 0.17
punctures. Conversely, manual compression may decrease bleed-
Type of ANGIO-SEAL 141 (82.0%) 143 (89.4%) 0.06
closure ing from multiple arterial and venous punctures. US-guided fem-
ProGlide 29 (16.9%) 17 (10.6%) 0.10
device oral access allows the operator to avoid heavily calcified and
Other/missing 2 (1.2%) 0 (0.0%) 0.50
diseased areas, allowing for safer and more efficacious deploy-
Data are expressed as n (%).
ment of a VCD10. However, we found that there was no difference
in the rate of VCD failure between US- and non-US-guided femo-
95% CI: 0.74-5.07). There was, however, significant interac- ral access. Previous randomised data demonstrated an increase in
tion (interaction p=0.034). Haematomas of more than 5 cm were the efficacy of haemostasis with VCD use without a trade-off in
approximately 3-fold more frequent in the VCD subgroup of safety, providing a strong rationale for the routine use of VCD
patients randomised to no US compared to those randomised to over manual compression4,11. Our data strengthens this rationale
US (4.1% vs 12.0%, OR 0.32, 95% CI: 0.11-0.81) (Supplementary by suggesting that VCD use can be even safer with US-guided
Table 3). femoral access and that operators should routinely use US-guided
femoral access when a VCD closure strategy is planned.
Discussion While the UNIVERSAL trial results were neutral, the updated
In patients who received a VCD, US- compared to non-US-guided meta-analysis of 9 randomised controlled trials including
femoral access reduced the composite of major bleeding or vas- 4,410 patients comparing US-guided femoral access to non-US-
cular complications in patients undergoing coronary angiography guided femoral access demonstrated a significant 42% relative risk
or PCI. This is likely the most important subgroup finding of the reduction in vascular complications or major bleeding, favouring
UNIVERSAL trial, as randomisation was stratified for intention to US guidance6. Therefore, we cannot assume that the benefit of US
use a VCD. We also observed a reduction in major vascular com- guidance only exists for patients receiving VCD.
plications with US in this subgroup but not a reduction in BARC In the ISAR-CLOSURE trial, 3,015 patients were randomly
2, 3 or 5 major bleeding. assigned to a VCD group, and 1,509 patients were assigned to
Importantly, we prespecified this subgroup and stratified the manual compression. The primary endpoint occurred in 208
randomisation process according to planned VCD use. Before the (6.9%) patients assigned to a VCD and 119 (7.9%) assigned
trial, we believed that a significant interaction between US use to manual compression (p for non-inferiority <0.001)4. The

US and fluoroscopy Fluoroscopy Odds ratio p-value for

Subgroup events/total (%) events/total (%) (95% CI) interaction
Actual VCD use for the primary composite outcome
(vascular or major bleeding complications)
Yes 20/170 (11.8) 37/158 (23.4) 0.44 (0.23-0.82) 0.004
No 20/141 (14.2) 13/152 (8.6) 1.76 (0.80-4.03)
Type of VCD use for the primary composite outcome
ANGIO-SEAL 12/140 (8.6) 31/141 (22.0) 0.33 (0.15-0.71) 0.29
ProGlide 8/28 (28.6) 6/17 (35.3) 0.74 (0.17-3.31)
Actual VCD use for vascular complications
Yes 7/170 (4.1) 21/158 (13.3) 0.28 (0.10-0.71) 0.004
No 13/141 (9.2) 8/152 (5.3) 1.82 (0.68-5.25)
Actual VCD use for major bleeding complications
Yes 16/170 (9.4) 24/158 (15.2) 0.58 (0.28-1.19) 0.034
No 15/141 (10.6) 9/152 (5.9) 1.89 (0.74-5.07)

0 0.5 1 1.5 2 2.5

Odds ratio (95% CI)

Figure 2. Main outcomes. CI: confidence interval; US: ultrasound; VCD: vascular closure device

77
EuroIntervention 2023;19:73-79
notably higher event rate for patients receiving a VCD in the
UNIVERSAL trial is likely multifactorial: 1) ISAR-CLOSURE
patients only underwent diagnostic angiography while 262/621
(42.2%) UNIVERSAL patients underwent PCI; 2) ISAR-
CLOSURE patients only had 6 Fr introducers while 121/621
(19.5%) UNIVERSAL patients had introducers larger than 6 Fr;
3) ISAR-CLOSURE only recruited elective diagnostic patients
while 178/621 (28.7%) of UNIVERSAL patients had non-ST-seg-
ment elevation acute coronary syndromes; and 4) UNIVERSAL
included BARC 2 bleeding while no equivalent event definition
was used in the ISAR-CLOSURE trial. Of note, BARC 2 bleeding
accounted for most of the events in UNIVERSAL.
We did not observe a significant difference in successful cannu-
lation of the common femoral artery, consistent with the FAUST
Trial12. One possible explanation is the effect of trainees transi-
tioning through their learning curve, as half of the procedures
were performed by interventional fellows. Another plausible
explanation is that certain operators may have deliberately or inad-
vertently cannulated the femoral artery in a suboptimal location to
avoid diseased or heavily calcified segments of the common femo-
ral artery. Nevertheless, formal education and rigorous training are
essential to developing and maintaining proper techniques.
We caution against comparisons of event rates between differ-
ent closure devices in our study, as these were not randomised, and
the choice may have been biased by operator and patient charac-
teristics12. Nevertheless, the ProGlide VCD is typically associated
with a higher learning curve than the ANGIO-SEAL, and the high
rate of trainee participation in the UNIVERSAL trial may have
impacted the outcomes13.
The benefit of US in femoral access, demonstrated by the
present analysis and the meta-analysis, does not obviate the
superiority of transradial access over transfemoral access. The
randomised controlled 2x2 factorial SURF trial of US versus
no US and transfemoral versus transradial access demonstrated
that transradial access was superior to transfemoral access for
the primary outcome of major bleeding, major adverse cardio-
vascular events comprising death, stroke, myocardial infarction,
urgent target lesion revascularisation, or major vascular compli-
cations at 30 days. While US increased procedural efficiency, it
did not reduce the primary outcome, even in the transfemoral
subgroup14.
Limitations
The present study has several limitations. First, subgroup analyses
should be considered hypothesis-generating. Second, as VCD
use was a post-randomisation variable, US guidance may have
biased the decision to use a VCD. However, as the patient ran-
domisation was stratified by planned VCD use, baseline charac-
teristics, procedural characteristics, and core laboratory findings
were well balanced between the US-guided and non-US-guided
subgroups receiving a VCD. Furthermore, even with potential
selection bias, bailout to manual compression was a safe alterna-
tive, as demonstrated in our study. Third, the majority of the VCD
78
used in the trial were ANGIO-SEAL devices, reducing the exter-
nal validity of the results to all VCD. Fourth, the micropuncture
technique was not used in the UNIVERSAL trial. However, it is
plausible that using micropuncture needles mitigates the poten-
tially deleterious effect of more inadvertent arterial punctures
associated with no US use. Fifth, we did not provide a standard-
ised definition for device failure to study investigators and cau-
tion against overinterpretation. Finally, as for the UNIVERSAL
trial, the outcomes were primarily driven by BARC 2 bleeding,
which is of less clinical importance than BARC 3 or 5 bleeding
or vascular complications. However, a trial adequately powered
for these outcomes would have required a substantial increase in
the study sample size.
Conclusions
In patients receiving VCD after coronary procedures, US-guided
compared to non-US-guided femoral access was associated with
fewer major bleeding and vascular complications. US may be par-
ticularly beneficial when a vascular closure device is used.
Impact on daily practice
It is unknown whether ultrasound-guided femoral access
reduces access site complications in the subgroup of patients
receiving a vascular closure device. In patients who received
a VCD, those randomised to US-guided femoral access com-
pared to non-US-guided femoral access experienced a reduction
in major bleeding or vascular complications (20/170 [11.8%] vs
37/158 [23.4%], OR 0.44, 95% CI: 0.23-0.82). In patients who
did not receive a VCD, there was no difference between the
US-guided and non-US-guided femoral access groups (20/141
[14.2%] vs 13/152 [8.6%], OR 1.76, 95% CI: 0.80-4.03; inter-
action p=0.004). Education and training of current and future
interventional cardiologists with ultrasound for femoral access
is needed.
Acknowledgements
The authors would like to acknowledge the Hamilton Health
Sciences and Population Health Research Institute clinical and
research personnel for their dedication to the UNIVERSAL trial.
Funding
Funding was provided by grants from the Hamilton Health
Sciences Foundation and McMaster University, Division of
Cardiology.
Conflict of interest statement
J. Velianou reports receiving grants or contracts, consulting fees, and
payment or honoraria for lectures, presentations, speakers’ bureaus,
or educational events from Edwards Lifesciences; and reports recei-
ving payment for participation on a Data Safety Monitoring Board
or advisory board from Edwards Lifesciences. M. Sibbald reports
receiving payment or honoraria for lectures, presentations, speakers’

bureaus, manuscript writing or educational events from Abbott and
Philips. S.S. Jolly reports receiving grants or contracts from Boston
Scientific; and payment or honoraria for lectures, presentations,
speakers’ bureaus, manuscript writing or educational events from
Penumbra. The other authors have no conflicts of interest to declare.
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3. Robertson L, Andras A, Colgan F, Jackson R. Vascular closure devices for femoral
arterial puncture site haemostasis. Cochrane Database Syst Rev. 2016;3:CD009541.
4. Schulz-Schupke S, Helde S, Gewalt S, Ibrahim T, Linhardt M, Haas K, Hoppe K,
Böttiger C, Groha P, Bradaric C, Schmidt R, Bott-Flügel L, Ott I, Goedel J, Byrne RA,
Schneider S, Burgdorf C, Morath T, Kufner S, Joner M, Cassese S, Hoppmann P,
Hengstenberg C, Pache J, Fusaro M, Massberg S, Mehilli J, Schunkert H, Laugwitz KL,
Kastrati A; Instrumental Sealing of Arterial Puncture Site —CLOSURE Device vs
Manual Compression (ISAR-CLOSURE) Trial Investigators. Comparison of vascular
closure devices vs manual compression after femoral artery puncture: the ISAR-
CLOSURE randomized clinical trial. JAMA. 2014;312:1981-7.
5. Dahal K, Rijal J, Shahukhal R, Sharma S, Watti H, Azrin M, Katikaneni P, Jimenez E,
Tandon N, Modi K, Lee J. Comparison of manual compression and vascular hemosta-
sis devices after coronary angiography or percutaneous coronary intervention through
femoral artery access: A meta-analysis of randomized controlled trials. Cardiovasc
Revasc Med. 2018;19:151-62.
6. Jolly SS, AlRashidi S, d'Entremont MA, Alansari O, Brochu B, Heenan L, Skuriat E,
Tyrwhitt J, Raco M, Tsang M, Valettas N, Velianou JL, Sheth T, Sibbald M, Mehta SR,
Pinilla-Echeverri N, Schwalm JD, Natarajan MK, Kelly A, Akl E, Tawadros S,
Camargo M, Faidi W, Bauer J, Moxham R, Nkurunziza J, Dutra G, Winter J. Routine
Ultrasonography Guidance for Femoral Vascular Access for Cardiac Procedures: The
UNIVERSAL Randomized Clinical Trial. JAMA Cardiol. 2022;7:1110-8.
7. Alrashidi S, d’Entremont M-A, Alansari O, Winter J, Brochu B, Heenan L, Skuriat E,
Tyrwhitt J, Raco M, Tsang MB, Valettas N, Velianou J, Sheth T, Sibbald M, Mehta SR,
Pinilla-Echeverri N, Schwalm JD, Natarajan MK, Kelly A, Akl E, Tawadros S,
Camargo M, Faidi W, Dutra G, Jolly SS. Design and Rationale of Routine UltrasouNd
GuIdance for Vascular AccEss foR Cardiac Procedures: A Randomized TriaL
(UNIVERSAL). CJC Open. 2022;4:1074-80.
Ultrasound for vascular closure in femoral access
EuroIntervention 2023;19:73-79
8. Sorrentino S, Nguyen P, Salerno N, Polimeni A, Sabatino J, Makris A, Hennessy A,
Giustino G, Spaccarotella C, Mongiardo A, De Rosa S, Juergens C, Indolfi C. Standard
Versus Ultrasound-Guided Cannulation of the Femoral Artery in Patients Undergoing
Invasive Procedures: A Meta-Analysis of Randomized Controlled Trials. J Clin Med.
2020;9:677.
9. Rashid MK, Sahami N, Singh, Winter J, Sheth T, Jolly SS. Ultrasound Guidance in
Femoral Artery Catheterization: A Systematic Review and a Meta-Analysis of
Randomized Controlled Trials. J Invasive Cardiol. 2019;31:E192-8.
10. Bangalore S, Barsness GW, Dangas GD, Kern MJ, Rao SV, Shore-Lesserson L,
Tamis-Holland JE. Evidence-Based Practices in the Cardiac Catheterization
Laboratory: A Scientific Statement From the American Heart Association. Circulation.
2021;144:e107-19.
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Hjort J, Thuesen L, Terkelsen CJ, Christiansen EH, Bøtker HE, Kristensen SD,
Lassen JF; CLOSE-UP study group. Randomised comparison of manual compression
and FemoSeal vascular closure device for closure after femoral artery access coronary
angiography: the CLOSure dEvices Used in everyday Practice (CLOSE-UP) study.
EuroIntervention. 2014;10:183-90.
12. Seto AH, Abu-Fadel MS, Sparling JM, Zacharias SJ, Daly TS, Harrison AT,
Suh WM, Vera JA, Aston CE, Winters RJ, Patel PM, Hennebry TA, Kern MJ. Real-
time ultrasound guidance facilitates femoral arterial access and reduces vascular com-
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Interv. 2010;3:751-8.
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e147-56.
14. Nguyen P, Makris A, Hennessy A, Jayanti S, Wang A, Park K, Chen V, Nguyen T,
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trolled trial. EuroIntervention. 2019;15:e522-30.
Supplementary data
Supplementary Table 1. Vascular closure device failure (by access
site).
Supplementary Table 2.  Core laboratory findings in patients
receiving a vascular closure device (by access site).
Supplementary Table 3. Vascular complications, large haemato-
mas, and BARC 2 bleeding in US-guided vs non-US-guided fem-
oral access by VCD use.
The supplementary data are published online at:
https://eurointervention.pcronline.com/
doi/10.4244/EIJ-D-22-01130
79
 CORONARY INTERVENTIONS
RESEARCH CORRESPONDENCE
EuroIntervention 2023;19:80-82 published online ahead of print February 2023

Changes in post-PCI optimisation strategies with post-

procedural FFR followed by IVUS
Tara Neleman, BSc; Frederik T.W. Groenland, MD; Annemieke C. Ziedses des Plantes, BSc;
Alessandra Scoccia, MD; Laurens J.C. van Zandvoort, PhD; Eric Boersma, PhD; Rutger-Jan Nuis, MD, PhD;
Wijnand K. den Dekker, MD, PhD; Roberto Diletti, MD, PhD; Jeroen Wilschut, MD; Felix Zijlstra, MD, PhD;
Nicolas M. Van Mieghem, MD, PhD; Joost Daemen*, MD, PhD
Department of Cardiology, Thorax Center, Erasmus University Medical Center, Rotterdam, the Netherlands
This paper also includes supplementary data published online at: https://eurointervention.pcronline.com/doi/10.4244/EIJ-D-22-00755

Suboptimal post-percutaneous coronary intervention (PCI) frac-
tional flow reserve (FFR) values have been related to target vessel
failure1. In the randomised FFR REACT trial, intravascular ultra-
sound (IVUS)-guided PCI optimisation in patients with a post-PCI
FFR <0.90 significantly improved post-PCI FFR values2. The aim
of this prespecified subanalysis was to assess the impact of post-
PCI IVUS findings in addition to FFR pullback data on opera-
tor-defined optimisation strategies, assessed through a dedicated
questionnaire.
The rationale and design of the FFR REACT trial have been
published previously2. In brief, patients with an angiographically
successful PCI and a post-PCI FFR <0.90 were randomised (1:1)
to either IVUS-guided optimisation or no further treatment (the
control arm). In the present subanalysis, only patients randomised
to the IVUS-guided optimisation arm with complete IVUS imag-
ing were included. The trial was approved by the local ethics com-
mittee, and all patients provided written informed consent.
Data on the optimisation strategy were routinely collected using
DOI: 10.4244/EIJ-D-22-00755
the initial stent combined with additional stenting, or 4) no addi-
tional treatment. These results were compared to the final optimi-
sation strategy performed after careful post-PCI IVUS evaluation.
Statistical analyses were carried out using SPSS statistics version
28.0 (IBM), and a two-sided p-value <0.05 was considered statis-
tically significant.
A total of 145 patients (152 vessels) were randomised to the
IVUS-guided optimisation arm, of which 136 patients (143 ves-
sels) had complete IVUS imaging. The median age was 66 (25th-
75th percentile 59-72) years, and 86.0% of patients were male.
A total of 73.4% of vessels were left main or left anterior descend-
ing coronary arteries (LM/LAD). The mean post-PCI FFR after
angiographically successful PCI (before additional optimisation)
was 0.83±0.05 and ranged from 0.56 to 0.89 (25th-75th percentile
0.80-0.87). According to the questionnaire, based on the FFR pull-
back data, operators would have performed additional optimisa-
tion in 81/143 (56.6%) vessels. Post-dilatation was considered in
38/143 (26.6%) vessels, additional stenting (without optimisation

a dedicated questionnaire directly after disclosure of the post-
PCI FFR pullback data and before IVUS acquisition. To “would
you perform additional treatment?”, the possible response options
were 1) post-dilatation (of the initial stent), 2) additional stent-
ing (without optimisation of the initial stent), 3) post-dilatation of
of the initial stent) in 42/143 (29.4%) vessels, and post-dilatation
of the initial stent combined with additional stenting in 1/143
(0.7%) vessels (Figure 1A). Following IVUS evaluation, post-dil-
atation was performed in 49/143 (34.3%) vessels, additional stent-
ing in 24/143 (16.8%) vessels, and post-dilatation of the initial

*Corresponding author: Department of Cardiology, Erasmus University Medical Center, PO Box 2040, 3000 CA Rotterdam, the
Netherlands. E-mail: j.daemen@erasmusmc.nl

© Europa Digital & Publishing 2023. All rights reserved. SUBMITTED ON 26/08/2022 - REVISION RECEIVED ON 1st 03/11/2022 / 2nd 05/12/2022 - ACCEPTED ON 19/12/2022

80
 Effects of post-PCI IVUS on optimisation strategies

stent combined with additional stenting in 25/143 (17.5%) vessels
(Figure 1A).
Overall, the optimisation strategy was altered in 76/143 (53.1%)
vessels after IVUS evaluation as compared to the planned treat-
ment strategy based on FFR pullback data alone (p<0.001)
(Figure  1B). More specifically, 32/62 (51.6%) vessels that were
considered for conservative treatment based on FFR pullback find-
ings received optimisation following IVUS evaluation (resulting
in a  limited increase in the post-PCI FFR: ΔFFR 0.015±0.060;
p=0.13), whereas 15/81 (18.5%) vessels that were originally
scheduled to receive optimisation were deferred from optimisa-
tion based on the post-PCI IVUS findings. Of note, concordance
between FFR and IVUS with respect to any post-dilatation and
any stenting was 69.2% and 72.1%, respectively (Supplementary
Table 1).
Finally, the frequency of an altered optimisation strategy
by IVUS analysis did not differ between LM/LAD vessels and
non-LM/LAD vessels (53.3% vs 52.6%, respectively; p=0.94)
(Supplementary Table 2).
Our findings demonstrate that, within the FFR REACT trial,
IVUS evaluation significantly changed the final optimisation strat-
egy applied in patients with a post-PCI FFR <0.90 as compared to
what would have been done based on post-PCI FFR pullback data
alone. As such, the proportion of cases within our study in which
EuroIntervention 2023;19:80-82
PCI optimisation was performed (98/143, 68.5%) was substan-
tially higher compared to previous studies reporting on PCI opti-
misation based on FFR (pullback) data alone (34.5%-43.0%)3,4.
To date, a significant body of evidence related to intracoronary
imaging has contributed to clear recommendations for achieving
optimal PCI5. Conversely, practical and validated cut-off values
for optimisation based on post-PCI physiological pullback data
alone are scarce, illustrating the need for future studies address-
ing the relationship between post-PCI FFR, intravascular imaging
findings, additional optimisation and improved patient outcome.
Limitations of the present analysis include the absence of motor-
ised FFR pullback data and use of the recently introduced pullback
pressure gradient, precluding any discrimination between (phys-
iologically defined) focal and diffuse disease. In addition, there
were no predefined cut-offs for FFR-based optimisation. Finally,
post-PCI FFR measurements were performed with a microcathe-
ter, which could have led to slightly lower post-PCI FFR values.
To conclude, in patients with a post-PCI FFR <0.90, findings
from post-PCI IVUS imaging alter the optimisation strategy in
more than 50% of cases as compared to a treatment strategy based
on post-PCI FFR pullback data alone. Ongoing follow-up of the
FFR REACT trial and future dedicated studies should further shed
light on whether imaging-guided PCI optimisation improves out-
comes in patients with a post-PCI FFR <0.90.

A B
Treatment strategy based on post-PCI FFR results Changes in optimisation strategy following IVUS evaluation
(questionnaire response, n=143) Change in treatment in 53.1% of vessels (76/143; p<0.001)
100
n=1; 1% 8.1% 13.2%
90
6.5%
10.5% 35.7%
Percentage of vessels (%)

80
n=42;
29% n=62; 70
37.1%
43% 60
n=38;
27%
50
57.9% 100%
35.7%
40

30
Actual treatment strategy based on IVUS findings 48.4% 9.5%
20
(n=143)
10 18.4% 19.0%
0
n=25;
No additional Post-dilatation Additional Additional
18% n=45; treatment (initial stent) stenting without stenting and
n=24; 31% optimisation of initial post-dilatation
stent of initial stent
17% n=62 n=38 n=42 n=1
n=49;
34%
Treatment strategy based on post-PCI FFR results (questionnaire response)
Actual treatment strategy based on IVUS findings
No additional treatment Additional stenting without
post-dilatation of initial stent No additional treatment Additional stenting without
Post-dilatation (initial stent) Additional stenting and post-dilatation of initial stent
post-dilatation of initial stent Post-dilatation (initial stent) Additional stenting and
post-dilatation of initial stent

Figure 1. Change in treatment strategy after IVUS evaluation. A) The treatment strategies according to post-PCI FFR (questionnaire answers,
upper pie chart) and the actual treatment strategy based on IVUS findings (lower pie chart). B) The proportion of vessels in which the
treatment strategy was altered after IVUS evaluation, stratified by the proposed post-PCI FFR treatment strategy. FFR: fractional flow
reserve; IVUS: intravascular ultrasound; PCI: percutaneous coronary intervention

81
EuroIntervention 2023;19:80-82
Funding
This work was funded by institutional research support from
ACIST Medical Systems, Inc.
Conflict of interest statement
J. Daemen received institutional grant/research support from
AstraZeneca, Abbott Vascular, Boston Scientific, ACIST
Medical Systems, Medtronic, Pie Medical, and ReCor Medical;
and consultancy and speaker fees from Abbott Vascular,
Abiomed, ACIST Medical Systems, Boston Scientific,
PulseCath, Pie Medical, Siemens Healthcare, and Medtronic.
N. Van Mieghem received institutional research grant sup-
port from Abbott Vascular, Biotronik, Boston Scientific,
Medtronic, Edwards Lifesciences, and Daiichi Sankyo; and
consultancy fees from Abbott, Boston Scientific, Medtronic,
Abiomed, PulseCath BV, Daiichi Sankyo, Teleflex, and Amgen.
T. Neleman received institutional grant support from ACIST
Medical Systems. R. Diletti received institutional grant support
from ACIST Medical Systems. The other authors have no con-
flicts of interest to declare.
References
1. Li SJ, Ge Z, Kan J, Zhang JJ, Ye F, Kwan TW, Santoso T, Yang S, Sheiban I,
Qian XS, Tian NL, Rab TS, Tao L, Chen SL. Cutoff Value and Long-Term Prediction
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Witberg KT, Groenland FTW, Cummins P, Lenzen MJ, Boersma E, Nuis RJ, den
Dekker WK, Diletti R, Wilschut J, Zijlstra F, Van Mieghem NM, Daemen J. FFR-
Guided PCI Optimization Directed by High-Definition IVUS Versus Standard of Care:
The FFR REACT Trial. JACC Cardiovasc Interv. 2022;15:1595-607. 
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McEntegart M, Good R, Robertson K, O'Boyle P, Davie A, Khan A, Hood S, Eteiba H,
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2021;42:4656-68. 
4. Uretsky BF, Agarwal SK, Vallurupalli S, Al-Hawwas M, Hasan R, Miller K,
Hakeem A. Prospective Evaluation of the Strategy of Functionally Optimized Coronary
Intervention. J Am Heart Assoc. 2020;9:e015073.
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Improving PCI Outcomes Using Postprocedural Physiology and Intravascular
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Supplementary data
Supplementary Table 1. Agreement between FFR and IVUS per
treatment option.
Supplementary Table 2. Changes in optimisation strategy strati-
fied per vessel.
The supplementary data are published online at:
https://eurointervention.pcronline.com/
doi/10.4244/EIJ-D-22-00755
 IN T E R V E N T I O N S F O R VA LV U L A R D I S E A S E A N D H E A R T FA I L U R E
CLINICAL RESEARCH

EuroIntervention 2023;19:83-92 published online ahead of print November 2022

Clinical outcomes of the ACURATE neo2 transcatheter heart
valve: a prospective, multicentre, observational, post-market
surveillance study
Won-Keun Kim1, MD; Corrado Tamburino2, MD, PhD; Helge Möllmann3, MD; Matteo Montorfano4, MD;
Julia Ellert-Gregersen5, MD; Tanja K. Rudolph6, MD; Nicolas M. Van Mieghem7, MD, PhD;
Michael Hilker8, MD; Ignacio J. Amat-Santos9, MD, PhD; Christian Juhl Terkelsen10, MD, DMSc;
Anna Sonia Petronio11, MD; Pieter R. Stella12, MD, PhD; Matthias Götberg13, MD, PhD;
Andreas Rück14, MD, PhD; A. Markus Kasel15, MD; Ramiro Trillo16, MD; Clare Appleby17, MBChB, PhD;
Marco Barbanti2, MD; Philipp Blanke18, MD; Rodrigo Modolo19, MD, PhD; Dominic J. Allocco19, MD;
Lars Sondergaard20*, MD, DMSc

The authors’ affiliations can be found in the Appendix paragraph.

This paper also includes supplementary data published online at: https://eurointervention.pcronline.com/doi/10.4244/EIJ-D-22-00914

KEYWORDS
Abstract
Background: The next-generation ACURATE neo2 transcatheter aortic valve was designed for simplified
implantation and to mitigate the risk of paravalvular leak (PVL) compared to the earlier device.
• aortic stenosis
Aims: We sought to collect clinical outcomes and device performance data, including echocardiography
• femoral
and 4-dimensional computed tomography (4D-CT) data, with the ACURATE neo2 transcatheter heart valve
• MSCT
in patients with severe aortic stenosis (AS).
• TAVI
Methods: The ACURATE neo2 Post-Market Clinical Follow-up (PMCF) Study is a single-arm, multicen-
• transoesophageal
tre study of patients with severe AS treated in routine clinical practice. The primary safety endpoint was all-
echocardiogram
cause mortality at 30 days. The primary imaging endpoint was hypoattenuated leaflet thickening (HALT),
measured by core laboratory-adjudicated 4D-CT at 30 days. Secondary endpoints included Valve Academic
Research Consortium safety endpoints, procedural success, and evaluation of valve performance via core
laboratory-adjudicated echocardiography.
Results: The study enrolled 250 patients at 18 European centres (mean age: 80.8 years; 63.6% female;
mean Society of Thoracic Surgeons score: 2.9±2.0%); 246 patients (98.4%) were successfully treated with
the ACURATE neo2. The 30-day rates for mortality and disabling stroke were 0.8% and 0%, respectively.
The new permanent pacemaker implantation rate was 6.5%. HALT >50% was present in 9.3% of patients
DOI: 10.4244/EIJ-D-22-00914

at 30 days. Valve haemodynamics improved from baseline to 30 days (mean aortic valve gradient: from
47.6±14.5 mmHg to 8.6±3.9 mmHg; mean aortic valve area: from 0.7±0.2 cm2 to 1.6±0.4 cm2). At 30 days,
PVL was evaluated as none/trace in 79.2% of patients, mild in 18.9%, moderate in 1.9%, and severe in 0%.
Conclusions: The study results support the safety and efficacy of transcatheter aortic valve implantation
with the ACURATE neo2 in patients in routine clinical practice.

*Corresponding author: Department of Cardiology, Rigshospitalet Blegdamsvej 9, 2100 Copenhagen, Denmark.

E-mail: Lars.Soendergaard.01@regionh.dk

© Europa Digital & Publishing 2023. All rights reserved. SUBMITTED ON 18/10/2022 - REVISION RECEIVED ON 10/11/2022 - ACCEPTED ON 22/11/2022

83
EuroIntervention 2023;19:83-92
Abbreviations
4D-CT 4-dimensional computed tomography
AS aortic stenosis
CEC clinical events committee
EOA effective orifice area
eGFR estimated glomerular filtration rate
HALT hypoattenuated leaflet thrombosis
NYHA New York Heart Association
PMCF post-market clinical follow-up
PVL paravalvular leak
STS Society of Thoracic Surgeons
TAVI transcatheter aortic valve implantation
THV transcatheter heart valve
TTE transthoracic echocardiography
VARC Valve Academic Research Consortium
Introduction
Studies have demonstrated that transcatheter aortic valve implanta-
tion (TAVI) with the first-generation ACURATE neo transcatheter
heart valve (THV; Boston Scientific) is a safe and effective treatment
for patients with aortic stenosis (AS)1-3. However, recent compara-
tive studies have noted higher rates of paravalvular leakage (PVL)
with the ACURATE neo compared with other TAVI devices4,5.
The next-generation ACURATE neo2 THV (Boston Scientific)
features an improved sealing skirt with active sealing technology
designed to mitigate PVL and a radiopaque marker for the facili-
tation of accurate THV positioning during implantation6. Early
results from the prospective, multicentre ACURATE Neo AS clini-
cal study demonstrated a favourable safety profile and improve-
ment in valve haemodynamics in a selected patient population
treated with the ACURATE neo26. The goal of the ACURATE
neo2 Post Market Clinical Follow-up (PMCF) Study was to collect
real-world safety and imaging data with the ACURATE neo2 THV
when used to treat patients with severe AS in routine clinical prac-
tice. The study employed 4-dimensional computed tomography
(4D-CT) imaging to assess the prevalence of hypoattenuated leaf-
let thickening (HALT) and reduced leaflet mobility and its rela-
tionship, if any, to clinical events.
This report presents the 30-day clinical outcomes and the com-
puted tomography and echocardiographic results from the study,
including the primary endpoints for safety and subclinical leaflet
thrombosis.
Editorial, see page 18
Methods
The ACURATE neo2 aortic valve system consists of a self-
expanding nitinol stent frame with three porcine pericardial tissue
leaflets in a supra-annular position, and inner and outer porcine
pericardium skirts6. The valve features a self-aligning design and
a novel radiopaque marker to facilitate accurate positioning in
the native aortic valve. The upper crown on the valve reduces the
risk of coronary occlusion, while the lower crown reduces contact
with the conduction system tissue, lowering the risk of conduction
84
disturbances. Finally, the double-pericardium skirt is intended to
reduce paravalvular leak. The device is currently available in 3
sizes (small [S], medium [M], and large [L]), intended for a native
aortic annulus diameter range between 21 mm and 27 mm.
STUDY DESIGN
ACURATE neo2 PMCF is a prospective, open-label, single-
arm, multicentre, observational post-market surveillance study.
All patients signed an informed consent form prior to enrolment.
A patient was considered enrolled once an attempt was made to
insert the ACURATE neo2 transfemoral delivery system. This
study adhered to the principles set forth in the Declaration of
Helsinki and all applicable local and country regulations. The
study is registered at ClinicalTrials.gov: NCT04655248.
The study sponsor (Boston Scientific) had a role in the study
design and conduct, including data collection and analysis, and in
the preparation of the manuscript. The principal investigators (L.
Sondergaard and W-K. Kim) had unrestricted access to the data
and wrote the manuscript first draft; all authors provided a critical
review of the manuscript content.
PATIENTS
Patients with severe aortic stenosis and who were deemed treata-
ble with the ACURATE neo2 THV were approached to participate
in the study. No specific inclusion criteria were set for this post-
market surveillance study. In order to enrol patients who would
be able to participate in the CT-imaging portion of the study,
exclusion criteria were 1) prior aortic bioprosthesis valve, 2)
chronic kidney disease stage IV or V (defined as eGFR <30 mL/
min/1.73 m2), 3) atrial fibrillation that could not be controlled to
a ventricular response rate <60 beats per minute to allow for high-
quality 4D-CT, or 4) expected need for chronic anticoagulation
therapy post-procedure (short-term anticoagulation post-procedure
was permissible, but all imaging assessments were performed
30 days after discontinuation of anticoagulation).
Valve implantation was performed per the ACURATE neo2
instructions for use and local standard of care. As per the instruc-
tions for use, implantation of the ACURATE neo2 should be pre-
ceded by balloon dilation of the stenotic native aortic valve. Aortic
annulus sizing was determined per site-based CT measures; the
final THV size was at the operators’ discretion. Patients were
recommended to be treated with aspirin and/or a P2Y12 inhibi-
tor for at least 1 month following valve implantation, with subse-
quent antiplatelet therapy per the treating investigator’s discretion.
Combination treatment with oral anticoagulation and dual anti-
platelet therapy was not recommended.
Follow-up occurred per local standard of care at predischarge and
30 days and will continue annually from 1 up to 5 years post-index
procedure. Additionally, all implanted patients were to undergo tran-
sthoracic echocardiography (TTE) predischarge and at 30 days post-
TAVI, as well as 4D-CT imaging at 30 days. Echocardiography and
4D-CT imaging will be repeated at 1-year follow-up for eligible
patients. Enrolled patients who were not treated with an ACURATE

neo2 THV in the aortic position were followed for safety up to
30 days after the initial attempted index procedure but did not
undergo imaging, and patients who required a second transcatheter
valve or conversion to surgery during the index procedure will con-
tinue to be followed for safety for 1 year but are not required to
undergo protocol-mandated imaging assessment.
ENDPOINTS
The primary safety endpoint was all-cause mortality at 30 days.
The primary imaging endpoint was HALT, as measured by 4D-CT
at 30 days. Secondary endpoints were based on Valve Academic
Research Consortium (VARC)-2 guidelines7. Per the study proto-
col, prosthetic aortic valve performance was evaluated via TTE
predischarge and at 30 days post-TAVI, including an assessment
of the effective orifice area (EOA), the mean and peak aortic gra-
dients, and aortic regurgitation. Additionally, functional status per
the New York Heart Association (NYHA) classification was eval-
uated at baseline and 30 days.
Adverse events (death, stroke, bleeding, major vascular com-
plications, and hospitalisation for valve-related symptoms or
worsening congestive heart failure) were adjudicated by an inde-
pendent clinical events committee (CEC). Echocardiographic
imaging evaluation at discharge and 30 days was performed by an
independent echocardiographic core laboratory (MedStar, USA)
according to the American Society of Echocardiography guide-
lines (available at www.asecho.org); 4D-CT data were evaluated
by an independent CT core laboratory (Department of Radiology,
The University of British Columbia, Vancouver, BC, Canada)
according to published guidelines8.
STATISTICAL ANALYSES
Baseline, procedural, and follow-up data were expressed as
mean±standard deviation (n) for continuous variables and as percent-
age (n/N) for categorical variables. The primary safety endpoint and
safety outcomes were analysed in the intention-to-treat population,
Intention-to-treat
n=250
Withdrew consent
n=12 Device not in
correct position
Death <30 days
n=2
30-day clinical follow-up
or death
94% (236/250)
Figure 1. Patient disposition up to 30 days. Four patients did not have a study valve implanted in the correct position and, per protocol, did
not undergo 30-day imaging but were followed for clinical safety. 4D-CT: 4-dimensional computed tomography; TTE: transthoracic
echocardiography
ACURATE neo2 PMCF study
EuroIntervention 2023;19:83-92
which consisted of all enrolled patients regardless of whether the
ACURATE neo2 THV was implanted; outcomes at 30 days were
evaluated in patients who experienced a CEC-adjudicated event up
to 30 days post-procedure or who were event-free, with their last
follow-up at least 23 days post-procedure. Imaging outcomes were
analysed in the implanted population, which consisted of all enrolled
patients who were successfully implanted with an ACURATE neo2
THV. Event rates are shown as proportions for follow-up up to
30 days, and no formal statistical testing was prespecified for this
single-arm study. All statistical analyses were performed using the
SAS System software, version 9.4 or later (SAS Institute).
Results
STUDY FLOW AND PATIENTS
The study enrolled 250 patients at 18 centres in 8 European coun-
tries between December 2020 and January 2022 (Supplementary
Table  1). For all patients, the local Heart Team agreed that the
patient had an approved indication for TAVI and that TAVI
with the ACURATE neo2 THV was appropriate. Among these,
246 patients (98.4%) had successful implantation of the THV
(defined as successful vascular access, delivery, and deployment
of the valve with successful retrieval of the delivery system), com-
prising the implanted population (Figure  1). Per protocol, only
patients with a device implanted in the correct position under-
went imaging; among patients with successful implantation of
the ACURATE neo2, 91% (224/246) had 30-day TTE and 83%
(204/246) had 30-day 4D-CT performed. Clinical follow-up data
were available at 30 days for 94% (236/250) of patients.
Baseline demographics and patient characteristics are shown
in Table  1. The mean age of patients was 81 years, with 64%
female, a baseline Society of Thoracic Surgeons (STS) risk score
of 2.9±2.0%, and 52.0% were considered NYHA Class III or IV.
Based on operator assessment, approximately two-thirds of patients
were considered to be at either high/extreme (31.2% [7/250]) or
intermediate (31.6% [79/250]) surgical risk. Based on CT core
30-day TTE
performed
91% (224/246)
Successfully implanted
98% (246/250)
30-day 4D-CT
performed
83% (204/246)
n=4
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EuroIntervention 2023;19:83-92

laboratory assessment, the native valve morphology was tricuspid Table 1. Baseline demographics and patient characteristics (cont'd).
in 98.4% of patients and bicuspid in 1.6% of patients. The mean ITT population
baseline aortic valve area was 0.7±0.2 cm2 and the mean baseline (N=250)
aortic valve gradient was 47.6±14.5 mmHg. Additional baseline Baseline Aortic valve area, cm2 0.7±0.2 (237)
echocardiographic and CT measurements are shown in Table 1. echocardiography
Aortic valve gradient, mmHg 47.6±14.5 (240)
(site reported)
Left ventricular ejection fraction, % 56.5±8.6 (244)
PROCEDURAL RESULTS
Screening CT Bicuspid native valve morphology 1.6% (4/250)
Procedural details are presented in Table  2. As noted above, (core laboratory)
Systolic annular Perimeter (mm) 73.5±5.1 (216)
4 patients did not have an ACURATE neo2 THV implanted in measurements
the correct position; in all of these cases, this was due to valve Perimeter-
derived 23.4±1.6 (216)
embolisation in the aortic direction (pursuant to use of an over- diameter (mm)
sized THV in a small anatomy [n=1], and positioning the THV Area (mm2) 416.6±58.9 (216)
too high in the annulus [n=3]). In 3 of the 4 patients a non-study Right coronary artery height (mm) 16.0±3.1 (243)
balloon-expandable THV was successfully implanted in the aor-
Valve leaflet None 0.4% (1/244)
tic position. In the remaining patient a non-study balloon-expand- calcification
Mild 6.6% (16/244)
able THV was implanted in the aortic position in a TAV-in-TAV
Moderate 75.0% (183/244)
Severe 18.0% (44/244)
Annulus None 67.6% (165/244)
Table 1. Baseline demographics and patient characteristics. calcification
Mild 12.3% (30/244)
ITT population
Moderate 14.8% (36/244)
(N=250)
Severe 5.3% (13/244)
Patient Age, mean (years) 80.8±6.2
characteristics LVOT None 70.5% (170/241)
Sex, female 63.6% (159/250)
calcification
Diabetes, medically treated 24.0% (60/250) Mild 14.1% (34/241)

Hypertension 80.8% (202/250) Moderate 11.2% (27/241)

Coronary artery disease 40.8% (102/250) Severe 4.1% (10/241)

History of atrial fibrillation 4.4% (11/250) Values are means±standard deviation (n) or percentages (n/N). CT: computed tomography;
ITT: intention-to-treat population; LVOT: left ventricular outflow tract; NYHA: New York Heart
History of stroke 5.2% (13/250) Association Functional Class; STS: Society of Thoracic Surgeons
Prior pacemaker at baseline 6.0% (15/250)
Pre-existing conduction abnormality 13.3% (33/248)
Atrioventricular block I 42.4% (14/33) procedure; however, this patient experienced cardiac tamponade
Atrioventricular block II – Type 2 3.0% (1/33) and left main coronary occlusion and died during the procedure.
Left bundle branch block 33.3% (11/33) The most common valve size implanted was medium (42%
Right bundle branch block 36.4% (12/33) of patients). In most patients (77.6%), the ACURATE neo2 was
Left anterior fascicular block 15.2% (5/33) implanted using a 3-cusp view; 22.4% of cases used a cusp-over-
NYHA I 8.4% (21/250) lap view. There was an attempt at commissural alignment in 174
Functional
II 38.8% (97/250) patients. There were no cases with unplanned use of cardiopul-
Class
III 51.2% (128/250)
monary bypass or conversion to surgery during the procedure. In
a post hoc analysis, 93% of patients met the criteria for VARC-3
IV 0.8% (2/250)
device success9 (Supplementary Table  2). Ten percent of proce-
Unknown 0.8% (2/250)
dures used a concomitant cerebral embolic protection device. At
Risk assessments Mean STS score (%) 2.9±2.0 (143)
hospital discharge, 89% (218/246) of patients were treated with
STS score STS score <3% 68.5% (98/143)
(category) aspirin, 33% (81/246) with a P2Y12 inhibitor, 25% (60/246) with
STS score ≥3%
to <8%
28.7% (41/143) dual antiplatelet therapy, and 14% (35/246) with anticoagulants.
At 30 days, 90% of patients (209/233) were treated with aspirin,
STS score ≥8% 2.8% (4/143)
31% (73/233) with a P2Y12 inhibitor, 24% (55/233) with dual anti-
EuroSCORE II (%) 3.3±2.8 (201)
platelet therapy, and 5% (11/233) with anticoagulants.
Operative risk High operative
31.2% (78/250)
group (as per risk
Heart Team PRIMARY ENDPOINTS
Intermediate
assessment) 31.6% (79/250)
operative risk The primary safety endpoint of 30-day all-cause mortality was
Low operative
37.2% (93/250)
0.8% (2/250) (Central illustration, Table  3). One patient expe-
risk
rienced haemodynamic instability from bleeding of unknown

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EuroIntervention 2023;19:83-92
Table 2. Procedural characteristics. aetiology, leading to circulatory arrest and resulting in death on
ITT population (N=250) day 4 post-procedure. The second patient died post-index proce-
Successful vascular access, delivery, dure following the aforementioned THV embolisation and unsuc-
and deployment of valve with successful 98.4% (246/250) cessful TAV-in-TAV. For the primary imaging endpoint, HALT
retrieval of delivery system*
was detected in 50 of 204 patients with imaging data available
Conversion to surgery 0% (0/250)
(24.5%). Among those, HALT severity was >75% in 8 patients
Unplanned cardiopulmonary bypass
0% (0/250) (3.9%) and >50% to 75% in 11 patients (5.4%) (Central illustra-
performed
TAV-in-TAV 0.4% (1/250)
tion). In the 50 patients exhibiting some degree of HALT, there
Second valve deployed (non
was evidence of restricted leaflet mobility in one leaflet in 46.9%
1.2% (3/250)
TAV-in-TAV) of patients, in two leaflets in 36.7% of patients, and in all three
Anaesthesia type General anaesthesia 7.6% (19/250) leaflets in 14.3% of patients. The presence of HALT was not
Conscious sedation 92.4% (231/250) detected in any patients who were on oral anticoagulant therapy.
Total procedure time, min 63.2±32.3 (245) The mean aortic valve gradient was not increased in patients with
Total fluoroscopy time, min 16.1±9.5 (248) HALT (HALT: 7.2±2.7 mmHg; no HALT: 8.8±3.7 mmHg).
Total contrast media used
113.9±91.2 (248)
for procedure (mL)
OTHER CLINICAL ENDPOINTS
Predilation balloon aortic valvuloplasty
performed
96.8% (242/250) Additional safety assessments at discharge and 30 days are shown
Rapid pacing using during valve
in Table  3; 245/250 patients (98.0%) were evaluable for safety
46.0% (115/250)
deployment at 30 days. The overall rates of adverse events up to 30 days
Embolic protection device used 10.4% (26/250) included 0.8% stroke (2/245, both non-disabling), 2.9% life-
Post-dilatation performed 26.0% (65/250) threating/disabling bleeding (7/245), and 0.4% repeat procedure
Implanted Small 26.0% (64/246) for valve-related dysfunction (1/245). Major vascular compli-
ACURATE neo2 Medium 42.3% (104/246) cations were reported in 3.3% of patients; all were access site-
valve size
Large 31.7% (78/246) related. Permanent pacemaker implantation was required in 15 of
Valve malpositioning 1.6% (4/250) 231 (6.5%) pacemaker-naïve patients. Of the patients implanted
Valve embolisation 1.6% (4/250) with a new pacemaker, 6 patients (40%) had evidence of a con-
Major vascular complication 3.2% (8/250) duction disturbance at baseline (right bundle branch block [n=5];
Cardiac tamponade (≤3 days after index
0.4% (1/250) second-degree atrioventricular block [n=1]).
procedure)
At 30 days, 51.0% (107/210) of patients were NYHA Class I,
Acute kidney injury (Stage 2 or 3) 0% (0/250)
41.0% (86/210) were Class II, and 8.1% (17/210) were Class III;
Values are site-reported means±standard deviations (n) or percentages
(n/N). Binary rates.*4 patients were implanted with a non-study device no patients were Class IV. Overall, 71% of patients improved
following embolisation of the ACURATE neo2 valve during implantation. by at least 1 functional class from baseline to 30 days, and 20%
ITT: intention-to-treat; TAV-in-TAV: transcatheter aortic valve in valve
implantation improved by at least 2 classes.

EuroIntervention

CENTRAL ILLUSTRATION The ACURATE neo2 PMCF observational post-market surveillance study collected clinical
outcomes and device performance data in 250 patients with severe aortic stenosis and at high operative risk who were
treated with the ACURATE neo2 aortic valve system in routine clinical practice.

ACURATE neo2 30-day outcomes HALT at 30 days

post-market study Primary imaging endpoint
98.1%
HALT severity

8.3% ≤25%
No Any
HALT HALT 6.9% >25% to 50%
75.5% 24.5%
0.8% 0.8% 0.0% 6.5% 5.4% >50% to 75%

Death Stroke Acute New PVL 3.9% >75%

Primary kidney permanent ≤mild
safety endpoint injury pacemaker
(n=2/250) (n=204)

HALT: hypoattenuated leaflet thickening; PVL: paravalvular leak

87
EuroIntervention 2023;19:83-92

Table 3. Safety outcomes up to 30 days (ITT population; N=250). 100 2.0

1.6±0.4 1.6±0.4

Mean aortic valve area (cm2) ●

Mean aortic gradient (mmHg) ◆
Event Discharge/7 days 30 days* (n=138) (n=127)
80 1.6
All-cause mortality 0.4% (1) 0.8% (2)
Cardiovascular mortality 0.4% (1) 0.8% (2) 60 47.6±14.5 1.2
(n=240)
All stroke 0.4% (1) 0.8% (2)
40 0.8
Disabling stroke 0.0% (0) 0.0% (0)
0.7±0.2 9.7±5.4
Non-disabling stroke 0.4% (1) 0.8% (2) 20 (n=237) (n=192) 8.6±3.9 0.4
Bleeding Life-threatening or
(n=180)
2.0% (5) 2.9% (7)
disabling 0 0.0
Major 2.4% (6) 2.4% (6) Baseline Discharge 30 days

Myocardial infarction 0.8% (2)† 0.8% (2)

Figure 2. Valve haemodynamics in the implanted population. Mean
Repeat procedure for valve- aortic gradient and aortic valve area were evaluated by an
0.4% (1) 0.4% (1)
related dysfunction
echocardiography core laboratory at baseline, discharge, and
Hospitalisation for valve-related
symptoms or worsening 0% (0) 0% (0)
30 days in patients successfully implanted with the ACURATE neo2
congestive heart failure (n=246).
Prosthetic aortic valve thrombosis‡ 0.4% (1) 0.4% (1)
Prosthetic aortic valve Patients in the study demonstrated a high rate of procedural suc-
0.0% (0) 0.4% (1)
endocarditis
cess (98.4%) and a favourable safety profile. The primary safety
Newly Among all patients 5.2% (13) 6.1% (15)
implanted endpoint of 30-day all-cause mortality was 0.8%. This rate was
Among pacemaker-
permanent similar to or better than previously observed in studies that evalu-
naïve patients 5.5% (13) 6.5% (15)
pacemaker
(n=235) ated the ACURATE alongside other THVs4,5,10,11, or with contem-
Values are percentages (n). Binary rates. *245 patients were evaluable porary devices in other large post-approval THV registries (2.2%
for safety at 30 days (defined as subjects who experience a CEC-
adjudicated event up to 30 days post-procedure or who were event-free with SAPIEN 3 [Edwards Lifesciences] in the SOURCE 3 reg-
with last follow-up at least 23 days post-procedure). †Periprocedural istry12; 0.0% with SAPIEN 3 Ultra in the S3U registry13; 4.8%
(≤72 hours post-index procedure). ‡Occurred in a non-study valve that
was implanted subsequent to ACURATE neo2 valve embolisation. with Evolut PRO [Medtronic] in the FORWARD PRO registry14;
CEC: clinical events committee; ITT: intention-to-treat 2.6% with Portico [Abbott] in the CONFIDENCE Registry15).
Likewise, the 30-day rates of disabling stroke (0.0%) and acute
HAEMODYNAMIC PERFORMANCE kidney injury (0.0%) in patients treated with the ACURATE neo2
The mean aortic valve area improved from 0.7±0.2 cm2 at baseline in this study were lower than those reported for the ACURATE
to 1.6±0.4 cm2 at both discharge/7 days and at 30 days (Figure 2). neo or its contemporary competitors in the aforementioned THV
The mean aortic valve gradient decreased from 47.6±14.5 mmHg studies and registries. Four patients (1.6%) experienced embolisa-
at baseline to 9.7±5.4 mmHg at discharge/7 days and then to tion of the THV; this incidence of embolisation is in line with the
8.6±3.9 mmHg at 30 days (Figure  2). Results were similar in findings from the TRAVEL Registry, a multicentre TAVI cohort of
a paired analysis of patients with evaluable echocardiographic over 29,000 patients, wherein valve embolisation and migration
data available at all timepoints (Supplementary Figure  1). occurred in approximately 1% of cases overall, and in 1.4% with
Among all patients with core laboratory-evaluable echocardio- non-balloon-expandable THV in particular16. The 6.5% rate of
grams, PVL was evaluated as none/trace in 79.2% of patients, new pacemaker implantation in this study is lower than the range
mild in 18.9%, moderate in 1.9%, and severe in 0% (Figure 3A). previously reported for the first-generation ACURATE neo (8.3%
Results were similar in a paired analysis of 121 patients who had to 12%)1,4,5,10,11 and comparable to the rates for the ACURATE
evaluable echocardiograms at both discharge/7 days and 30 days neo2 in the recent NEOPRO-2 and ITAL-neo registries (8.0% and
(Figure  3B). In the paired analysis, most patients (77%) exhib- 7.6%, respectively)17,18.
ited stability in PVL (i.e., no interindividual change) between Patients in the ACURATE neo2 PMCF Study exhibited early
discharge and 30 days. haemodynamic improvements at discharge, which were maintained
up to 30-day follow-up. At 30 days, paravalvular leak was mild
Discussion or less in 98% of patients and moderate in 1.9% of patients, with
In this post-market registry of patients with aortic stenosis treated no patients exhibiting greater than moderate PVL. In contrast, the
in routine clinical practice with the ACURATE neo2 THV, a clin- 30-day rate of moderate or greater PVL observed with the prior-gen-
ical events committee adjudicated VARC-2 adverse events, and eration ACURATE neo in the recent SCOPE I and SCOPE II stud-
core laboratories were employed for echocardiographic analyses ies was 9.4% and 9.6%, respectively4,5 (Figure 3C). The results of
related to haemodynamic performance, as well as for 4D-CT imag- the current study are comparable to the rates of moderate or greater
ing to provide insight into the prevalence of HALT and restricted PVL 30 days after ACURATE neo2 implantation in the ACURATE
leaflet motion in a real-world setting. Neo AS study (3.0%)6, the NEOPRO/NEOPRO-2 registry (2.0%)17,

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 ACURATE neo2 PMCF study

EuroIntervention 2023;19:83-92
A All implanted patients B Paired population (n=121)

0.6 1.9 0.8 1.7

22.2 18.9 22.3 15.7
evaluable echocardiograms

Paravalvular leak
Percentage of

Severe
Mod-severe
Moderate
77.2 79.2 Mild 76.9 82.6
None/trace

Discharge/7d 30 days Discharge/7d 30 days

(n=171) (n=159)

C ≥ Moderate PVL 30 days post-TAVI

11.2
9.4 9.6
Percentage of patients

5.2 5.0
3.5
2.0 1.9

NEOPRO NEOPRO-2 SCOPE I* SCOPE II* ITAL-neo NEOPRO-2 ITAL-neo ACURATE

neo2 PMCF

ACURATE neo ACURATE neo2

*In the SCOPE I and SCOPE II studies, PVL was assessed at hospital discharge

Figure 3. Paravalvular leak. Paravalvular leak was assessed at hospital discharge or 7 days (whichever came first) and 30 days in (A) all
patients successfully implanted with the ACURATE neo2 (n=246) and (B) the paired population of patients with evaluable echocardiograms
at both discharge/7 days and 30 days (n=121). C) The rate of moderate or greater PVL at 30 days was higher in patients treated with the
prior-generation ACURATE neo device compared with the next-generation ACURATE neo2 THV. PMCF: post-market clinical follow-up;
PVL: paravalvular leak; TAVI: transcatheter aortic valve implantation; THV: transcatheter heart valve.

and the ITAL-neo registry (3.5%)18. The substantial improvement in
PVL can be attributed, in large part, to the active sealing technology
of the improved sealing skirt on the ACURATE neo2. This type
of improvement in PVL, coincident with device design progres-
sion, has also been noted for other THVs19-21. As has been observed
with the ACURATE neo, factors related to improvements in patient
selection, sizing, and implant technique may also have played a role
in the reduction of PVL rates22,23.
In recent years, there has been increased interest in the use of
4D-CT to characterise HALT, which manifests as hypoattenuat-
ing thickening typically localised to the valve periphery and base
of the leaflet, with a subjective grading scale used to describe the
extent of leaflet involvement8. Data from studies to date have been
variable with regard to the impact of HALT or restricted leaf-
let mobility on clinical outcomes and the utility of treatment for
HALT in improving outcomes24,25. Recent meta-analyses have sug-
gested there is an association between imaging findings and major
adverse cardiac and cerebrovascular events26,27. While prospective
studies have not confirmed that HALT affects patients’ clinical
outcomes, there is a concern that it may potentially impact valve
durability and increase thrombotic complication rates8,28,29.
The primary imaging endpoint of the ACURATE neo2 PMCF
Study was evidence of any degree of HALT at 30 days post-TAVI.
Published studies have found that post-TAVI HALT typically
occurs in 10-15% of patients, although in some cases the rate is
as high as 35-40%24. In the current study, 24.5% of patients exhib-
ited some degree of HALT, with the severity of HALT >50% in
9.3% of patients. Of the patients with HALT, virtually all exhibited
some degree of restricted leaflet mobility, but there were no evident
clinical implications. In general, patients demonstrated improved
valve haemodynamics, and the mean gradient was not increased
in patients with HALT. The small sample size in this study (n=50
patients with HALT) makes it difficult to characterise the relation-
ship between HALT and gradient; additional CT analysis in a larger
population may provide additional insight. There were no unusual
safety signals in patients with HALT during 30 days of follow-up

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EuroIntervention 2023;19:83-92
– no patients experienced a stroke, and there was only one case of
prosthetic valve thrombosis. In the short follow-up time frame for
this study, it was not possible to evaluate whether HALT had an
impact on valve durability or longer-term clinical outcomes. More
in-depth analyses of the CT results are ongoing.
Limitations
As a single-arm study with only 250 patients, the results from this
registry cannot be directly compared to clinical outcomes with
other THV devices. Enrolment decisions were made per the discre-
tion of the local Heart Team, thus the possibility of site-based dif-
ferences in patient selection cannot be ruled out. It should be noted
that this study was conducted during the COVID-19 pandemic,
which may have affected site activation and enrolment, as well
as limited clinical follow-up for some endpoints or at some sites,
due to pandemic-related restrictions. The study did not require
routine neurological assessment by an independent neurological
professional; thus, it is possible that cerebrovascular complications
may have been underreported. Although the study employed core
laboratories for the evaluation of echocardiographic and CT data,
in some cases the data collected were not analysable due to poor
image quality or other technical issues, leading to a reduced sam-
ple size available for follow-up. To date, only short-term (30-day)
follow-up data are available; however, patients will continue to be
followed for 5 years, with echocardiographic and 4D-CT evalua-
tions repeated at 1 year and analysed by the core laboratories.
Conclusions
The ACURATE neo2 PMCF Study results support the safety and
efficacy of transfemoral TAVI with the ACURATE neo2 THV in
routine clinical practice. Patients exhibited early improvements in
valve haemodynamics that were maintained up to 30 days, with
low rates of new pacemaker implantation and paravalvular leak.
Impact on daily practice
The first-generation ACURATE neo transcatheter heart valve
(THV) is a safe and effective treatment for aortic stenosis; how-
ever, higher rates of paravalvular leakage (PVL) have been
reported compared with other THVs. In this study of the next-
generation ACURATE neo2 THV, which features improved
sealing designed to mitigate PVL and a radiopaque marker
for precise positioning, patients had a low pacemaker implan-
tation rate, early improvements in valve haemodynamics that
were maintained up to 30 days, and a low rate of moderate or
greater PVL. The ACURATE neo2 PMCF Study results support
the safety and efficacy of TAVI with the ACURATE neo2 in
patients in routine clinical practice.
Appendix. Authors’ affiliations
1. Kerckhoff-Klinik GmbH, Bad Nauheim, Germany; 2. Division
of Cardiology, Azienda Ospedaliero Universitaria Policlinico-
San Marco, Catania, Italy; 3. St. Johannes Hospital Dortmund,
90
Dortmund, Germany; 4. Interventional Cardiology Unit IRCCS
San Raffaele Scientific Institute, Milan, Italy; 5. Department of
Cardiology, Odense University Hospital, Odense, Denmark; 6. Heart
and Diabetes Center North Rhine-Westphalia, Bad Oeynhausen,
Germany; 7. Erasmus Medical Center, Rotterdam, the Netherlands;
8. Universitätsklinik Regensburg, Regensburg, Germany;
9. Hospital Clínico Universitario de Valladolid, Valladolid, Spain;
10. Aarhus University Hospital, Aarhus, Denmark; 11. Azienda
Ospedaliero Universitaria Pisana, Pisa, Italy; 12. University
Medical Center Utrecht, Utrecht, the Netherlands; 13. Department
of Cardiology, Skane University Hospital, Lund University, Lund,
Sweden; 14. Karolinska University Hospital, Stockholm, Sweden;
15. Universitätsspital Zürich, Zürich, Switzerland; 16. Complejo
Hospitalario Universitario de Santiago, Santiago de Compostela,
Spain and Centro de Investigación Biomedica en Red Enfermedades
Cardiovasculares, Madrid, Spain; 17. Liverpool Heart and Chest
Hospital, Liverpool, UK; 18. Department of Radiology, St Paul's
Hospital & University of British Columbia, Vancouver, BC, Canada;
19. Boston Scientific Corporation, Marlborough, MA, USA; 20. The
Heart Center, Rigshospitalet, Copenhagen, Demark
Acknowledgements
The authors wish to acknowledge Songtao Jiang, MS (Boston
Scientific) for statistical support and MaryEllen Carlile Klusacek,
PhD (Boston Scientific) for assistance with manuscript preparation.
Funding
The ACURATE neo2 PMCF Study was sponsored and funded by
Boston Scientific Corporation (Marlborough, MA, USA). The data
and study protocol for this clinical trial may be made available to
other researchers in accordance with Boston Scientific’s data shar-
ing policy (http://www.bostonscientific.com/en-US/data-sharing-
requests.html).
Conflict of interest statement
W-K. Kim reports personal fees from Boston Scientific, Edwards
Lifesciences, Abbott, Medtronic, and Meril. C. Tamburino is
a consultant for Medtronic. H. Möllmann reports speaker/proctor/
advisor honoraria from Abbott, Boston Scientific, and Edwards
Lifesciences. M. Montorfano reports consultant fees from Abbott,
Boston Scientific, Kardia, and Medtronic. T.K. Rudolph has received
speaker honoraria from Boston Scientific. N.M. Van Mieghem
reports consulting fees/honoraria from Daiichi Sankyo, Abiomed,
Anteris, Amgen, and Teleflex; and research grants from Medtronic,
Boston Scientific, ACIST, PulseCath, Edwards Lifesciences, and
Abbott Vascular. M. Hilker has participated on advisory boards
for and received proctor fees from Boston Scientific. I. Amat-
Santos is a proctor for Boston Scientific, Medtronic, and Meril
Life. C.J. Terkelsen reports proctor/speaker fees from Edwards
Lifesciences, Meril, Boston Scientific, and Terumo. A.S. Petronio
reports research funds from Medtronic, Boston Scientific, and
Abbott; and is a consultant for Medtronic, Boston Scientific, and
Abbott. M. Götberg serves as a proctor for Boston Scientific and

reports consulting honoraria from Boston Scientific. A. Rück reports
advisory board participation for Edwards Lifesciences and Boston
Scientific; lecture fees from Abbott, Edwards Lifesciences, and
Boston Scientific; consulting for ANTERIS; and has received insti-
tutional research support from Boston Scientific. R. Trillo serves
as a proctor for Medtronic and Boston Scientific. M. Barbanti is
a consultant for Edwards Lifesciences, Medtronic, and Boston
Scientific. P. Blanke is a consultant to Edwards Lifesciences; and
has provided institutional CT Core Laboratory services for Boston
Scientific, Medtronic, Edwards Lifesciences, and Abbott, for which
no direct personal compensation was received. R. Modolo is an
employee and shareholder of Boston Scientific. D.J. Allocco is an
employee and shareholder of Boston Scientific. L. Sondergaard has
received consultant fees and/or institutional research grants from
Abbott, Boston Scientific, Medtronic, and SMT. The other authors
have no conflicts of interest to declare.
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Supplementary data
Supplementary Table 1. Enrolment by site.
Supplementary Table 2. VARC-3 device success.
Supplementary Figure 1. Valve haemodynamics in the paired
population.
The supplementary data are published online at:
https://eurointervention.pcronline.com/
doi/10.4244/EIJ-D-22-00914
 IN T E R V E N T I O N S F O R VA LV U L A R D I S E A S E A N D H E A R T FA I L U R E
T R A N S L AT I O N A L R E S E A R C H

EuroIntervention 2023;19:93-102 published online ahead of print January 2023

A bench study of balloon-expandable valves for the treatment
of self-expanding valve failure
Mariama Akodad1,2,3,4, MD, PhD; David Meier1,2,3, MD; Stephanie Sellers1,2,3, PhD; Ole De Backer5, MD;
Darren Mylotte6, MD; Uri Landes7, MD; Chris Frawley8, BEng; Lisa Lynch8, MSc;
Gilbert H.L. Tang9, MD, MSc, MBA; Lars Sondergaard5, MD, DMSc; David A. Wood1,2,3, MD;
John G. Webb1,2,3, MD; Janarthanan Sathananthan1,2,3*, MPH, MBChB
1. Centre for Heart Valve Innovation, St Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada; 2. Centre for
Cardiovascular Innovation, University of British Columbia, Vancouver, BC, Canada; 3. Cardiovascular Translational
Laboratory, Centre for Heart Lung Innovation & Providence Research, Vancouver, BC, Canada; 4. Institut Cardiovasculaire
Paris Sud, Hôpital privé Jacques-Cartier, Ramsay Santé, Massy, France; 5. Department of Cardiology, The Heart Centre,
Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 6. Department of Cardiology, National University of
Ireland, Galway, (NUIG), Galway, Ireland; 7. Edith Wolfson Medical Center, Holon, Israel and Tel-Aviv University, Tel-Aviv,
Israel; 8. Boston Scientific Corporation, Marlborough, MA, USA; 9. Department of Cardiovascular Surgery, Mount Sinai
Hospital, New York, NY, USA
This paper also includes supplementary data published online at: https://eurointervention.pcronline.com/doi/10.4244/EIJ-D-22-00769

KEYWORDS
Abstract
Background: Coronary obstruction and access are concerns in patients undergoing redo transcatheter aor-
tic valve implantation (TAVI).
• aortic stenosis
Aims: We sought to assess the neoskirt height, leaflet overhang, leaflet deflection,and transcatheter heart
• other
valve (THV) expansion and performance, at 2 different implant depths, of the SAPIEN 3 Ultra (S3U)
• TAVI
within the ACURATE neo2 (ACn2) THV.
Methods: An in vitro study was performed with a 23 mm S3U deployed within a small (S) ACn2 and
a 26 mm S3U deployed within a medium (M) and a large (L) ACn2. The S3U outflow was positioned at the
top of the ACn2 crown (low implant) and at the base of the commissural post of the ACn2 (high implant).
Testing was performed under physiological conditions as per ISO-5840-3 standard.
Results: The neoskirt height was shorter when the S3U outflow was positioned at a low implantation depth
(S: 9.6 mm, M: 12.2 mm, L: 13.8 mm vs S: 15.2 mm, M: 15.1 mm, L: 17.8 mm ACn2 for high implants).
Hydrodynamic performance was acceptable for all configurations. Leaflet overhang was <50% for all con-
figurations except the low implant of the 26 mm S3U in the L ACn2 (77.6%). There was a gap from the
side of the neoskirt to the outer border of the THV frame which was >2 mm for all configurations. The
DOI: 10.4244/EIJ-D-22-00769

S3U was underexpanded for all configurations, and the achieved area was 77.9%-92.9% of the expected
nominal area.
Conclusions: Redo TAVI with an S3U within an ACn2 has favourable hydrodynamics and moderate leaf-
let overhang. Importantly, the design of the ACn2 results in a neoskirt that is not deflected all the way to the
outer dimensions of the THV, hence creating a space that facilitates coronary flow and access.

*Corresponding author: St. Paul’s Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.
E-mail: jsathananthan@providencehealth.bc.ca

© Europa Digital & Publishing 2023. All rights reserved. SUBMITTED ON 31/08/2022 - REVISION RECEIVED ON 1st 01/11/2022 / 2nd 04/11/2022 - ACCEPTED ON 08/11/2022

93
EuroIntervention 2023;19:93-102
Abbreviations
ACn2 ACURATE neo2
EOA effective orifice area
RF regurgitant fraction
S3U SAPIEN 3 Ultra
TAVI transcatheter aortic valve implantation
THV transcatheter heart valve
Introduction
Transcatheter heart valves (THV) may fail and repeat interven-
tion may be required1,2. Redo transcatheter aortic valve implanta-
tion (TAVI), when feasible, has been shown to be an acceptable
treatment for THV failure3,4. There are several considerations
when performing redo TAVI, including the implant depth of the
index THV, the index THV expansion, leaflet overhang and the
neoskirt height5. Importantly, different failed THV designs may
have unique technical considerations in order to optimise results
following redo TAVI. There is currently limited clinical experi-
ence to guide THV choice and implant position. In lieu of limited
clinical data, bench testing can provide insights.
A concern with redo TAVI is the creation of a neoskirt, where
the leaflets of the failed valve are pushed outward by the new
THV, creating a tube graft which may lead to coronary obstruction
or impede future coronary access5,6. Neoskirt heights are typically
greater in tall-frame THV with supra-annular leaflets but may vary
across different supra-annular THV designs. The degree of leaf-
let deflection, which refers to the distance from the neoskirt to
the edge of the THV frame, may also vary across THV designs.
A THV design where the leaflets are not maximally deflected to
the edge of the THV frame may mitigate coronary obstruction.
A recent study showed that a low SAPIEN 3 (S3; Edwards
Lifesciences) THV implant within a failed Evolut R (Medtronic)
results in a lower neoskirt height without compromising the THV
hydrodynamic performance, despite a higher degree of leaflet
overhang5. The ACURATE neo2 (ACn2) is another commercially
available tall-frame valve that has unique design features where
the upper segment of the valve has an incomplete frame with
3 stabilisation arches. There is an upper crown which is designed
to push down on the native leaflets7. Redo TAVI in the ACn2 is
poorly understood.
We performed an in vitro study to assess valve performance,
functional neoskirt height, leaflet overhang, leaflet deflection,
THV expansion and hydrodynamic performance when implanting
an S3 Ultra (S3U) THV within an ACn2 THV at different implan-
tation positions.
Methods
STUDY METHODS
In vitro testing was performed in collaboration with the
Cardiovascular Translational Laboratory (Vancouver, Canada) and
Boston Scientific (Galway, Ireland). This study was performed
under physiologic test conditions with no human or animal par-
ticipants, and ethics approval was not required.
94
VALVES
The ACn2 was used as the index “failed” valve, and small (S),
medium (M) and large (L) ACn2 sizes were evaluated (3 ACn2
valves in total). The ACn2 THV incorporates a self-expanding
nitinol frame, supra-annular leaflets and an active PV seal which
is 60% larger than the prior-generation ACURATE neo (ACn)
valve7. Compared to the previous ACn THV, the ACn2 is designed
with a lower commissural post leaflet attachment (3 mm lower
for the S and M, and 2 mm lower for the L ACn2) and scalloped
leaflets with a shorter-than-expected neoskirt. The upper segment
of the valve has an incomplete frame with 3 stabilisation arches,
and the upper crown is designed to push down on the native leaf-
lets. The edge of the upper crown represents the outer edge of
the THV frame. The height of the ACn2 across the sizes ranges
between 48 and 51 mm. The ACn2 waist diameters are 23 mm,
25 mm and 27 mm for the S, M and L THV, respectively. The
ACn2 is designed to be routinely implanted at a 7 mm implanta-
tion depth. This gives an effective skirt height of 8 mm above the
annular plane, as the total skirt height is 15 mm for all sizes7. The
latest-generation S3U device was designed to allow a larger area
of surface contact with the native valve (up to 50%) with a higher
polyethylene terephthalate outer skirt (>40% higher compared to
the S3 device)8.
REDO TAVI CONFIGURATIONS
Redo TAVI configurations were performed using a 23 mm S3U
within an S ACn2, a 26 mm S3U within an M ACn2, and a 26 mm
S3U within an L ACn2 (3 S3U valves in total). The S3U was
implanted at 2 different positions for each size configuration.
Positioning was based on the S3U outflow to either the 1) top
of the upper crown as a low position, or 2) to the base of the
marker of the stabilisation arches as a high position (Figure  1).
All S3U valves were deployed with nominal volume per manu-
facturer recommendations, and new valves were used for low and
high implants in the same redo TAVI configurations.
NEO-SKIRT AND FUNCTIONAL NEO-SKIRT
The neoskirt height was defined as the distance between the ACn2
THV inflow and the pinned leaflet-free edge height of the ACn2
THV at the outflow of the S3U THV. The neoskirt height was
determined using the Smartscope (OGP) vision-based measure-
ment system. As the ACn2 is designed to be implanted routinely
at a depth of 7 mm, the functional neoskirt height was meas-
ured by subtracting 7 mm from the total neoskirt as this portion
of the valve would be positioned in the left ventricular outflow
tract, below the annular plane, and hence pose no risk to coronary
obstruction. The functional neoskirt height was calculated for each
configuration at each implantation depth.
LEAFLET OVERHANG
The percentage of leaflet overhang was defined as the percent-
age of orifice blockage due to the inward flexing of the unpinned
portion of the ACn2 THV leaflets during the diastolic phase
 Balloon-expandable valve for ACURATE neo2 failure

EuroIntervention 2023;19:93-102
A B

Stabilisation arch
Functional neoskirt
Maximal neoskirt

C D

7 mm implant depth

Figure 1. Study methodology. A) ACn2 landmarks (blue line: top of the ACn2 upper crown, blue circles: base of the ACn2 commissural tab),
maximal neoskirt height (red lines and arrow); functional neoskirt height measurements (red and green lines, green arrow) subtracting 7 mm
based on manufacturer-recommended implantation depth, and edge of the THV frame (black vertical line); B) S3U at the 2 implantation
positions based on S3U outflow at the top of the ACn2 crowns (low implant) and at the base of the ACn2 commissural tab (high implant);
C) Vivitro pulse duplicator for hydrodynamic assessment and (D) ACn2 THV example positioned in a holder for testing. ACn2: ACURATE
neo2; S3U: SAPIEN 3 Ultra; THV: transcatheter heart valve

(Figure  2A). The baseline orifice area (i.e., inner diameter at the
base of index valve) was traced using ImageJ software (National
Institutes of Health Image) of the still diastolic images obtained
from the hydrodynamic test videos using the “polygon selections”
tool within the software and displayed in mm by setting the scale
to a known distance and calculating it using the “analyse/meas-
ure” tool. The leaflet overhang orifice area was determined by
tracing the flexed leaflet edge of an index valve and determining
the orifice area. The derived leaflet area was defined as follows:
the baseline orifice area − the leaflet overhang orifice area. The %
leaflet overhang was defined as the following: the derived leaflet
area/baseline orifice area x 100.
DEGREE OF LEAFLET DEFLECTION RELATIVE TO THV
FRAME
In some configurations of redo TAVI the leaflets may not be
deflected up to the outer border of the THV frame. This pheno-
menon was defined by outlining the outer border of the ACn2
(edge of the upper crown) and calculating the distance and the
area between this border and the neoskirt. Area measurements are
reported in mm2 and distance in mm (Figure 2B, Figure 2C).
HYDRODYNAMIC ASSESSMENT
A pulse duplicator test system (Vivitro Laboratories) was used to
assess hydrodynamic performance for all redo TAVI configurations.
The index ACn2 THV were placed in a holder fabricated from sili-
cone (Figure 1). The holder compliance was chosen in accordance
with ISO 5840-3:20219. The ACn2 valves were fixed in the gas-
kets, which had diameters that were representative of the upper
limit of the respective indicated patient annular range per ACn2
instructions for use (i.e., the ACn2 S was deployed in a 22 mm
diameter gasket, the ACn2 M was deployed in a 24 mm diameter
gasket, and the ACn2 L was deployed in a 26 mm diameter gasket).
The lowest interference between the 2 THV was chosen because it
was deemed to be the worst case scenario for inter-THV leakage
and stability. The test medium used for this study was 40% glycerol
containing saline solution with a target viscosity of 3.8 centipoise to
approximate the viscosity of blood. Results were taken for 20 con-
secutive cycles, repeated 3 times and then averaged. High-speed
video filming was performed to assess the index valve kinematics
from the outflow and inflow ends. Pulsatile forward flow perfor-
mance was measured at a nominal beat rate of 70±1 beats/min,
systolic duration of 35±5%, mean aortic pressure of 100±2 mmHg,
and simulated cardiac output of 5.0±0.1 L/min. The mean gradient
(mmHg), regurgitant fraction (%), and effective orifice area (EOA;
cm2) were assessed. The maximum allowable regurgitant fraction
in accordance with ISO 5840-3 is <20%. The total regurgitant frac-
tion, which included closing and intervalvular regurgitation post-S3
closure, was assessed. The EOA was computed according to a sim-
plified version of the Bernoulli equation, as previously described
in ISO 58409.
ACN2 AND SAPIEN 3 ULTRA FRAME EXPANSION AFTER
REDO TAVI
The baseline diameter of the index ACn2 THV were measured at
the level of the inflow, mid-portion and S3U outflow pinning posi-
tions to assess the risk of sinus sequestration and potential contact
with the sinotubular junction. The change in radii was reported to
maintain consistency with the “valve-to-coronary” measurements
being taken as part of the patient screening process.
The S3U area and diameter after nominal inflation were meas-
ured by micro-computed tomography at the level of the inflow,

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EuroIntervention 2023;19:93-102

A B C

Figure 2. Leaflet overhang and leaflet deflection. A) Example of measurements made to determine the degree of leaflet overhang (%) of the
“failed” index THV leaflets (X=total area in blue, Y=area between the white dots; leaflet overhang=(Y/X)*100); B) Distance (black arrow)
from top of the neoskirt (red line) to the edge of the ACn2 THV frame in the high S3U implant position;C) Distance (black arrow) from top of
the neoskirt (red line) to the edge of the ACn2 THV frame in the low S3U implant position. ACn2: ACURATE neo2; S3U: SAPIEN 3 Ultra;
THV: transcatheter heart valve

mid-portion and S3U outflow pinning positions to assess the S3U
expansion when implanted within the ACn2 THV.
The expanded diameter and increase in radius after redo TAVI
were assessed for all S3U THV within ACn2 THV configurations.
ACn2 and S3U THV diameters were measured using an Optical
Comparator (Micro-Vu) for measurement.
VGSTUDIO MAX (Volume Graphics) was used to analyse, seg-
ment and measure the computed tomography reconstructed data of
each of these redo TAVI configurations.
High-resolution photography was performed at a prespecified
magnification and a fixed camera height. High-speed video from
hydrodynamic testing was also performed5,10.

PROTOCOL IMAGING STATISTICS

Multimodality imaging, including fluoroscopy, was performed
using the General Electric OEC 9900 Elite Mobile C-arm X-ray
system, and micro-computed tomography and high-resolution
photography were performed for each THV at each implanta-
tion configuration with the Keyence Digital Microscope. Micro-
computed tomography was performed using a continuous Cone
Beam quick scan to reduce dehydration of the valve tissue includ-
ing 1,200 projections with 3.98 magnification, 536,365 mm focus
detector distance and 135,000 mm focus object distance with
a voltage current of 110 kV and a current of 200.0 µA. Frame rate
detector exposure was 5 Hz with an exposure time of 200,000 ms.
The radii increase, diameter increase and leaflet pinning heights, also
referred to as neoskirt heights, are expressed in mm. The index leaf-
let overhang is reported as a percentage relative to baseline orifice.
The hydrodynamic variables, EOA, pressure gradients, and total
regurgitation fraction are reported as mean±standard deviation (SD).
Results
FUNCTIONAL NEO-SKIRT
The S3U THV implanted within the ACn2 THV resulted in func-
tional neoskirt heights ranging between 9.6 mm and 17.8 mm
(Table  1). The functional neoskirt heights were shortest in the

Table 1. Neoskirt height, leaflet overhang and leaflet deflection with variable implant depths.
Leaflet
Implant depth Neoskirt Functional Leaflet Leaflet
ACn2 S3U deflection
(S3 outflow) height (mm) neoskirt (mm) overhang (%) deflection (mm)
area (mm2)
S 23 mm Low 16.6 9.6 34.7 2.7 6.8
High 22.2 15.2 28.8 3.9 34.4
M 26 mm Low 19.2 12.2 48.1 2.7 13.8
High 22.1 15.1 30.1 2.3 22.8
L 26 mm Low 20.5 13.5 77.6 2.6 15.1
High 24.8 17.8 27.6 2.2 9.5
Note: 0% overhang is indicative of full pinning of ACn2 index leaflets. The functional neoskirt height was measured by subtracting 7 mm from the total
neoskirt height as the ACn2 is designed to be implanted routinely at an implanted depth of 7 mm, this portion of the valve would be positioned in the left
ventricular outflow tract and hence pose no risk to coronary obstruction. ACn2: ACURATE neo2; L: large; M: medium; S: small S3U: SAPIEN 3 Ultra

96

low implantation positions, with the lowest value (9.6 mm) for the
23 mm S3U THV in the S ACn2 THV. Higher functional neoskirt
heights were noted in the high implantation position, with the high-
est value (17.8 mm) obtained for the 26 mm S3U THV implanted
in the L ACn2 THV. A lower implant position can reduce the func-
tional neoskirt height by as much as 8.2 mm as compared to high
implantation (Figure 3, Figure 4, Central illustration).
LEAFLET OVERHANG
The degree of leaflet overhang and impact on leaflet kinematics
had minimal variation by the S3U THV implant position within
the ACn2 THV except for the low implant of the 26 mm S3U
within the L ACn2 (Table  1, Figure  3, Figure  4). Leaflet over-
hang ranged from 28.8% to 77.6% across various implant posi-
tions (Central illustration). Greater leaflet overhang was observed
when the S3U THV outflow was implanted low within the ACn2
THV, and higher S3U implants within the ACn2 THV reduced
the degree of leaflet overhang. Similar and mild degrees of leaflet
overhang across the different THV size combinations were high-
lighted in high implants.
Low implant
23 mm S3U in small ACn2
20.69 mm
20.25 mm
20.94 mm
26 mm S3U in medium ACn2
23.58 mm
22.69 mm
24.43 mm
26 mm S3U in large ACn2
24.77 mm
23.90 mm
24.38 mm
Figure 3. S3U THV diameter expansion at the outflow, midportion and inflow at different implant positions for each configuration.
ACn2: ACURATE neo2; S3U: SAPIEN 3 Ultra; THV: transcatheter heart valve
Balloon-expandable valve for ACURATE neo2 failure
EuroIntervention 2023;19:93-102
DEGREE OF LEAFLET DEFLECTION RELATIVE TO THV FRAME
The distance from the neoskirt to the outer edge of the THV frame
ranged from 2.2 mm for the high implant of the 26 mm S3U in the
M ACn2 THV to 3.9 mm for the high implant of the 23 mm S3U
in the S ACn2 THV (Table  1, Central illustration). The area of
leaflet deflection relative to the THV frame ranged from 6.8 mm2
for the 23 mm S3U placed low in the S ACn2 THV to 34.4 mm2
for the high implant of the 23 mm S3U in the S ACn2 THV.
HYDRODYNAMIC ASSESSMENT
Hydrodynamic performances were within accepted standards as
per ISO 5840-3 guidelines, with the mean gradient being slightly
lower in the high S3U implant. A regurgitant fraction <20% was
demonstrated for all tested configurations (Table 2).
ACN2 AND SAPIEN 3 ULTRA FRAME EXPANSION AFTER
REDO TAVI
The increase in the dimensions of the ACn2 THV after S3U THV
deployment are found in Supplementary Table 1, with a maximal
increase in radius of 0.2 mm across tested configurations.
High implant
21.41 mm
20.64 mm
21.07 mm
24.10 mm
22.95 mm
22.98 mm
24.70 mm
23.68 mm
24.44 mm
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EuroIntervention 2023;19:93-102

Low implant High implant

Increase in ACn2 radius Increase in ACn2 radius

Neoskirt Neoskirt
9.6 mm 15.2 mm
23 mm S3U in S ACn2
+O mm +O mm

34.7% leaflet overhang 28.8% leaflet overhang

Increase in ACn2 radius Increase in ACn2 radius

Neoskirt Neoskirt
12.2 mm 15.1 mm
26 mm S3U in M ACn2 +O mm +O mm

48.8% leaflet overhang 30.1% leaflet overhang

Increase in ACn2 radius Increase in ACn2 radius

Neoskirt Neoskirt
13.5 mm 17.8 mm
26 mm S3U in L ACn2 +O mm +O.2 mm

77.6% leaflet overhang 27.6% leaflet overhang

Figure 4. Redo TAVI test configurations of different-sized SAPIEN 3 Ultra within ACn2 THV. The neoskirt height, degree of leaflet
overhang (%) and increase in the ACn2 radius (mm) after redo TAVI with SAPIEN 3 Ultra in ACn2 for each THV size are outlined.
ACn2: ACURATE neo2; L: large; M: medium; S: small; S3U: SAPIEN 3 Ultra; THV: transcatheter heart valve

S3U diameter expansion at the inflow, mid-portion and the out-
flow are highlighted in Supplementary Table  2. The S3U THV
was underexpanded for all THV configurations, predominantly at
the mid-portion. S3U THV underexpansion was more significant
for the 26 mm S3U in the M ACn2 at the mid-portion for the low
implant position (77.9%). S3U THV area expansion was better for
the 26 mm S3U in the L ACn2 at the outflow in the high implant
position (92.9%).
Discussion
There is currently limited guidance or clinical experience on
THV choice or positioning when performing redo TAVI. In a tall
frame, where the leaflets are in a supra-annular position, there
may be increased concern for coronary obstruction, given the
potential tall neoskirt that is created following placement of the
new THV. However, not all tall-frame valves necessarily carry
the same risk. In the case of a failed ACn2, redo TAVI with
another supra-annular THV may potentially, in some cases, result
in a taller neoskirt, increasing the risk of coronary obstruction
and could lead to challenging coronary access5. This approach
is likely undesirable for many patients. However, use of a short-
frame valve for the redo THV may mitigate these risks. In this
study we evaluated the use of an S3U THV positioned within an
ACn2 THV as a potential treatment method for a failed ACn2
THV. We demonstrated that this strategy was associated with
a favourable neoskirt height and hydrodynamics for most config-
urations, despite the presence of leaflet overhang. Some consid-
erations for the ACn2 which may potentially facilitate redo TAVI

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 Balloon-expandable valve for ACURATE neo2 failure

EuroIntervention 2023;19:93-102
EuroIntervention

CENTRAL ILLUSTRATION Technical implications of redo-TAVI with the SAPIEN 3 Ultra in ACn2 THV at different implant
positions.

Low implant High implant

S3U outflow at the top of S3U outflow at the base of

the ACn2 upper crown the ACn2 commissural post

23 mm S3U THV in a small ACn2 and 26 mm S3U in a medium/large ACn2 THV

Distance from neo-skirt to Functional neoskirt height

THV frame edge

A 2.2-3.9 mm gap was observed which may Neoskirt height of 9.6-17.8 mm when accounting
facilitate coronary flow and access for the recommended 7 mm implant depth

Leaflet overhang S3U expansion

Leaflet overhang of 28.8-77.6% with low implant S3U underexpansion was noted
resulting in a greater degree of leaflet overhang of 77.9-92.9% of S3U THV nominal area

ACn2: ACURATE neo2; S3U: SAPIEN 3 Ultra; TAVI: transcatheter aortic valve implantation; THV: transcatheter heart valve

with an S3U and mitigate coronary obstruction are 1) the initial
implant depth of the failed ACn2, and 2) the degree of leaflet
deflection relative to the THV frame.
The ACn2, as per manufacturer recommendations, has a tar-
get depth of 7 mm routinely for all cases in the 3-cusp coplanar
view. Unlike other self-expanding valves, such as in the Evolut
Platform for which a high implant is recommended, a higher
implant is not recommended for the ACn2. Prior bench studies
of neoskirt heights across different THV platforms have meas-
ured the neoskirt height from the inflow of the valve to the top
of the pinned leaflet5,6. This technique was adopted to maintain
a consistent technique but is limited as it does not account for
the implant depth of the THV. In the case of the ACn2, the func-
tional neoskirt is shorter when considering a standard implant
depth of 7 mm. In addition, the degree of leaflet deflection rela-
tive to the THV frame also has an impact on the risk of coronary

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EuroIntervention 2023;19:93-102
Table 2. Functional performance of SAPIEN 3 Ultra THV at
variable implant depths.
Implant EOA Mean gradient
ACn2 S3U
depth (cm2) (mmHg)
fraction (%)
S 23 mm Low 1.9±0.02 16.7±0.3
High 1.9±0.01 15.1±0.2
M 26 mm Low 2.3±0.01 11.5±0.1
High 2.3±0.01 11.2±0.08
L 26 mm Low 2.5±0.01 11.1±0.08
High 2.5±0.02 10.7±0.2
Note: Acceptable EOA values for certain annular diameters have been linear interpolated from
ISO 5840-3:2021 specifications using adjacent deployed valve diameter. ACn2: ACURATE
neo2; EOA: effective orifice area; L: large; M: medium; S: small; S3U: SAPIEN 3 Ultra
obstruction. Most THV have a complete frame, and the leaf-
let is deflected all the way to the frame, forming the neoskirt.
However, the ACn2 is designed with an incomplete frame and an
upper crown which marks what could be considered the edge of
the THV frame7. Redo TAVI in the ACn2 with the S3U results in
a neoskirt that does not extend all the way to the end of the upper
crown, and hence this creates a gap which would help mitigate
the risk of coronary obstruction and facilitate future coronary
access.
When performing redo TAVI using an S3U THV in an index
ACn2 THV, aligning the S3U outflow to landmarks on the index
THV frame will provide a better method to determine the expected
neoskirt height. Moreover, as previously described, alignment
according to the THV outflow is more predictable, as the S3U
THV is foreshortened most appreciably from the inflow side5.
Implanters may wish to tailor their implant position to balance the
degree of leaflet overhang and the neoskirt height. In this study,
the position of the S3U THV in an index ACn2 THV had a mod-
erate impact on leaflet overhang. In particular, the degree of leaf-
let overhang was <50% for all configurations except for the low
implant of the 26 mm S3U in the L ACn2. In comparison, a simi-
lar analysis demonstrated severe leaflet overhang (up to 94%)
when an S3 was implanted low in an Evolut THV5. While this
study was performed using new THV, it could be anticipated that
similar results can be achieved in patients without significant cal-
cification. However, in severely degenerated leaflets with a sten-
otic mechanism, residual new outflow obstruction may occur in
the case of a low implant of the new THV with significant leaf-
let overhang as well as the potential for thrombosis in cases of
impaired flow.
We found that lower implantation of a short-frame THV within
an ACn2 resulted in a reduction in the functional neoskirt height.
In the present study, micro-computed tomography measure-
ments demonstrated that the S3U was underexpanded for all con-
figurations when implanted within the ACn2, irrespective of the
implant position. The mid-segment of the THV was more likely
to be underexpanded. S3U THV have been shown to be underex-
panded in routine valve-in-valve or native anatomy11. However,
100
THV underexpansion may result in a range of leaflet pinwheeling
and impact THV function and durability10,11. The impact of THV
Total underexpansion on the risk of hypoattenuated leaflet thickening
remains unknown to date although THV underexpansion has been
regurgitant
shown to be associated with blood stasis in experimental mod-
14.9±0.7 els12. Late valvuloplasty, as a staged procedure, has been shown
12.7±0.5 to be feasible in native annulus and valve-in-valve configurations
17.3±0.7 to improve THV expansion. However, post-dilatation of 2 THV
15.1±0.6 metallic frames following redo TAVI may be challenging and
19.4±0.5 may not allow further THV expansion11. Thus, the final degree
17.2±0.4 of required oversizing of the new THV has to be addressed when
considering redo TAVI and may be based on individual patient
anatomy.
Ultimately, there is no ideal THV design or implant position
that would be considered optimal for all patients. Rather, sev-
eral factors will influence redo TAVI including patient anatomy,
the position of the failed index THV and the choice of the new
THV design. All these factors must be considered when consid-
ering redo TAVI in a failed supra-annular THV. As TAVI contin-
ues to expand in younger patients, it will be even more important
to determine the optimal treatment modality in the context of
a patient’s lifetime and anticipated life expectancy13,14. Heart
Teams must carefully consider appropriate treatment options
(TAVI vs surgery), THV type and implant technique in these
patients15,16. Anatomic factors and index THV choice may pre-
clude some patients from future redo TAVI, and these patients
may be better managed with TAVI explant and surgery1,2,17,18.
The index THV choice and feasibility of future redo TAVI will
be crucial for Heart Teams to consider at the time of the first
procedure.
Study limitations
Bench testing design may not reflect physiological conditions in
clinical practice. Indeed, the index valves were new, and hence in
a degenerated in vivo failed valve which is calcified, the leaflet
overhang and the paravalvular leak, as well as the mean gradient,
may vary compared to the present study. Similarly, in vivo expan-
sion of the index THV may vary compared to a bench model, and
intervalvular leak between the 2 THV may vary following redo
TAVI. Additionally, a holder was used to simulate the anatomy but
may not reflect patient anatomy with elliptical annuli and did not
allow an assessment of THV expansion at the level of the holder
(ACn2 inflow). While the majority of configurations had favour-
able hydrodynamic performance, leaflet overhang and neoskirt
height may have important short- and long-term clinical implica-
tions which were not assessed in this study. In vivo, leaflet over-
hang may lead to THV dysfunction and impaired neo-sinus flow
with a potential impact on redo THV degeneration and thrombo-
sis. Finally, all data were provided assuming a 7 mm implantation
depth of the ACn2 THV. In clinical practice, the implant depth
may vary and potentially may be higher, which would slightly
increase the neoskirt height compared to what is described in this
study. Additionally, in the case of the medium ACn2, a 23 mm

S3U could have been implanted instead of a 26 mm S3U.
Unfortunately, this configuration could not be tested in this study
due to challenges with acquiring THV for bench testing. Use of
a smaller 23 mm S3U in a medium ACn2 could have led to less
underexpansion of the S3U.
Conclusions
Redo TAVI with an S3U within an index ACn2 has favourable
S3U THV hydrodynamics and mild to moderate leaflet over-
hang. Importantly, the unique design of the ACn2 results in
a neoskirt that is not deflected all the way to the outer dimen-
sions of the lower crown, hence creating a space that may bet-
ter preserve coronary flow and access. The impact of S3U frame
underexpansion and leaflet overhang in the low implant position
on valve haemodynamics and durability will need further clini-
cal evaluation.
Impact on daily practice
Placement of an S3U THV within an index ACn2 THV results
in an acceptable functional neoskirt height with no significant
compromise to the S3U valve function and mild-to-moderate
leaflet overhang, regardless of the implant depth. The S3U THV
was routinely underexpanded. The long-term implications
of redo TAVI on THV performance and durability will be
assessed in clinical studies. The feasibility of coronary access
and impact of THV underexpansion following redo TAVI will
also be assessed in future studies.
Conflict of interest statement
M. Akodad has received research funding from Medtronic,
Biotronik, MUSE Explore, and Federation Française de
Cardiologie. D. Meier is supported by the Swiss National
Science Foundation (grant P2LAP3_199561). S. Sellers is
a consultant for Providence Health Care, Edwards Lifesciences,
and Medtronic. O.  De Backer received research grants
from Boston Scientific. D. Mylotte is consultant for Boston
Scientific, MDT, and MicroPort. C. Frawley is an employee
of Boston Scientific in research and development engineer-
ing. L. Lynch is an employee of Boston Scientific in research
and development engineering. G. Tang is a physician proc-
tor and consultant for Medtronic; a consultant and physician
advisory board member for Abbott Structural Heart; a con-
sultant for NeoChord; and physician advisory board member
for JenaValve. D. Wood is a consultant and receives unre-
stricted grant support from Medtronic, Edwards Lifesciences,
and Abbott Vascular. L. Sondergaard has received consultant
fees and/or institutional research grants from Abbott, Boston
Scientific, Medtronic, and SMT. J.G. Webb is a consultant
for Edwards Lifesciences. J. Sathananthan is a consultant for
Edwards Lifesciences, Medtronic, and Boston Scientific; and
has received speaking fees from Edwards Lifesciences and
NVT. The other authors have no conflicts of interest to declare.
Balloon-expandable valve for ACURATE neo2 failure
EuroIntervention 2023;19:93-102
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 IN T E R V E N T I O N S F O R VA LV U L A R D I S E A S E A N D H E A R T FA I L U R E
RESEARCH CORRESPONDENCE

EuroIntervention 2023;19:103-104 published online ahead of print March 2023

Oesophageal and gastric injuries caused by
transoesophageal probe manipulation in patients undergoing
transcatheter edge-to-edge repair for tricuspid regurgitation
Tanja Kuecken1,2*, MD; Marwin Bannehr1,2, MD; Eleni Lalou1,2, MD; Johannes Lenz2,3, MD;
Michael Zänker2,3, MD; Christoph Edlinger1,2, MD; Anja Haase-Fielitz1,2,4, PharmD; Michael Neuss1,2, MD;
Christian Butter1,2, MD
1. Department of Cardiology, University Hospital Heart Centre Brandenburg, Brandenburg Medical School (MHB) Theodor
Fontane, Neuruppin, Germany; 2. Faculty of Health Sciences Brandenburg, Neuruppin, Germany; 3. Department for
Gastroenterology, University Hospital Heart Centre Brandenburg, Brandenburg Medical School (MHB) Theodor Fontane,
Neuruppin, Germany; 4. Institute of Social Medicine and Health System Research, Otto von Guericke University Magdeburg,
Magdeburg, Germany

In recent years, treatment with transcatheter edge-to-edge repair
(TEER) for tricuspid regurgitation has increased rapidly1-3. For
optimal guidance, the transoesophageal echocardiographic probe
has to be moved between transgastric and various oesophageal
positions4. Patients undergoing this procedure appear to be at
higher risk for gastric bleeding, possibly because of increased vul-
nerability of the gastrointestinal mucosa. The probe manipulation
during tricuspid TEER may further increase the risk for bleeding.
The purpose of this study was to determine the prevalence and risk
factors for injury caused by transoesophageal echocardiography
probe manipulation during TEER for tricuspid regurgitation.
In this single-centre, retrospective, observational cohort study,
we analysed data from all consecutive adult patients between
November 2020 and July 2022 undergoing TEER for tricus-
pid regurgitation at our centre. All patients received gastroscopy
before and after tricuspid TEER per protocol. Endoscopic findings
were categorised into four groups (1: no lesion; 2: minor lesion;
3: major lesion; 4: endoscopic therapy necessary). Patients with
either oesophageal and/or gastric lesions (groups 2-4) and those
significant differences in clinical characteristics between both
groups concerning age, sex, pacemaker/defibrillator leads,
ascites, European System for Cardiac Operative Risk Evaluation
(EuroSCORE), diabetes, coronary heart disease, renal function, left
ventricular ejection fraction, tricuspid regurgitation or the number
of clips applied. Twenty-four patients (60%) had post-intervention
gastric or oesophageal lesions (group 2-4), and 8 patients (20%)
required endoscopic haemoclip therapy (group 4). The lesions were
predominantly mid-oesophageal (62.5% of group 4) (Figure  1).
Sixteen patients had no sign of injury at all (group 1). The pro-
cedural characteristics of tricuspid TEER did not differ between
patients with lesions and those without lesions (mean procedure
time 83.2 min±30.8 min vs 82.5 min±29.5 min; p=0.94; number
of echocardiographic probe positional changes [oesophageal to
transgastric] 6.9±2.6 vs 6.1±2.9; p=0.19; number of applied clips;
1.75±0.57 vs 1.83±0.56; p=0.65; reduction of tricuspid regurgita-
tion; 1.75±0.57 vs 1.83±0.56; p=0.65). Arterial hypertension was
more frequent (p=0.01) and body mass index (BMI) was lower
(p=0.04) in patients with postinterventional injuries.
DOI: 10.4244/EIJ-D-22-01070

without injuries (group 1) were compared with regard to clini-
cal characteristics and procedural features, including positional
changes of the echocardiographic probe.
Overall, 40 patients were included in this analysis; the mean
age was 78.7 (±6.9) years, and 45% were male. There were no
The rate of major bleeding complications in the setting of TEER
for tricuspid regurgitation is reported in the literature to be approxi-
mately 11%1, which is in line with the severe upper gastric bleeding
found in our study. Of the patients receiving endoscopic haemo-
clips, there was bleeding in five cases (12.5%): two patients had

*Corresponding author: Department of Cardiology, University Hospital Heart Centre Brandenburg, Ladeburger Straße 17,
16321 Bernau bei Berlin, Germany. E-mail: tanja.kuecken@immanuelalbertinen.de

© Europa Digital & Publishing 2023. All rights reserved. SUBMITTED ON 03/12/2022 - REVISION RECEIVED ON 1st 24/02/2023 / 2nd 02/03/2023 - ACCEPTED ON 03/03/2023

103
EuroIntervention 2023;19:103-104
Minor lesions n=12
Major lesions n=4
Haemoclip necessary n=8
Figure 1. Distribution of injuries caused by the echocardiographic probe manipulation during tricuspid transcatheter edge-to-edge repair
(TEER) (n=24).
active bleeding, three patients had vessel stumps. The remain-
ing three patients received prophylactic haemoclip therapy due to
the physician’s individual decision. Compared with patients docu-
mented in the TRILUMINATE trial, our patient cohort had a higher
EuroSCORE II and may, therefore, have been significantly frailer
(8.7% vs 16.8%). Two patients had lesions in the hypopharynx, and
three had lesions in the upper oesophagus. These lesions were prob-
ably caused by the probe intubation and not by the procedure itself.
We expected major lesions in the cardia and upper gastric areas,
due to the frequent positional changes between the transgastric
and mid-oesophageal areas4. Contrary to our assumption, most
lesions were found in the mid-oesophageal region. Moreover,
most lesions requiring a haemoclip intervention also occurred
in the mid-oesophageal region at 25-32 cm from the dental arch
(62.5%, 5/8 of group 4). This is probably because there is less
space in the oesophagus compared to the stomach and each move-
ment of the probe may have a greater impact on the mucosa.
Injuries of the oesophagus have been described for left-sided
heart procedures, such as left atrial appendage closure or mitral
TEER, by Freitas-Ferraz et al5. In contrast to their results, the
procedure duration and positional changes did not predict
lesions. Pre-existing gastritis was not a significant predictor of
lesions after tricuspid TEER. The high prevalence of injuries
following TEER for tricuspid regurgitation highlights the need
to identify risk factors for potential bleeding and injury. In our
study, we found more lesions in patients with arterial hyperten-
sion and lower BMI.
This is a retrospective, monocentric, cohort study. However, our
study findings point to a possibly underappreciated complication
with potentially life-threatening implications for an evolving ther-
apy, especially in frail patients. The pressure applied to the mucosa
by the transoesophageal echocardiography probe and the length of
time the pressure is applied could themselves be potential risk fac-
tors for injuries. There are techniques to measure applied pressure
104
Distribution of lesions
after tricuspid TEER (n=24/40)
Hypopharynx
cervical-19 cm
Upper oesophagus
20-24 cm
Middle oesophagus
25-32 cm
Lower oesophagus
32-40 cm
Cardia
40 cm
0 4 8 12 16
number of patients with lesions (n)
with ablation catheters; this might help to clarify the problem of
pressure points in future studies. Further investigations are needed
to identify potential risk factors.
Injuries during TEER for tricuspid regurgitation of the mid-
oesophageal region caused by the echocardiographic ultrasound
probe manipulation do not seem to be predicted by the number of
probe positional changes or the procedure duration in our small
cohort. However, injuries of the oesophagus after tricuspid TEER
are nonetheless common and more awareness should be brought to
this subject; gastric injuries are less common.
Funding
This study was funded by the Brandenburg Medical School
(MHB) publication fund supported by DFG.
Conflict of interest statement
The authors have no conflicts of interest to declare.
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