SIST EN ISO 5840-3:2021

SLOVENSKI STANDARD
01-marec-2021
Nadomešča:
SIST EN ISO 5840-3:2013
Vsadki (implantati) za srce in ožilje - Proteze za srčno zaklopko - 3. del:
Nadomestki srčne zaklopke, vsajeni (implantirani) s transkatetrsko metodo (ISO
5840-3:2021)
Cardiovascular implants - Cardiac valve prostheses - Part 3: Heart valve substitutes
implanted by transcatheter techniques (ISO 5840-3:2021)
Herz- und Gefäßimplantate - Herzklappenprothesen - Teil 3: Durch minimal-invasive
Methoden implantierter Herzklappenersatz (ISO 5840-3:2021)
Implants cardiovasculaires - Prothèses valvulaires - Partie 3: Valves cardiaques de
substitution implantées par des techniques transcathéter (ISO 5840-3:2021)
Ta slovenski standard je istoveten z: EN ISO 5840-3:2021
ICS:
11.040.40 Implantanti za kirurgijo, Implants for surgery,
protetiko in ortetiko prosthetics and orthotics
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.

EN ISO 5840-3
EUROPEAN STANDARD
NORME EUROPÉENNE
February 2021
EUROPÄISCHE NORM
ICS 11.040.40 Supersedes EN ISO 5840-3:2013
English Version
Cardiovascular implants - Cardiac valve prostheses - Part
3: Heart valve substitutes implanted by transcatheter
techniques (ISO 5840-3:2021)
Implants cardiovasculaires - Prothèses valvulaires - Herz- und Gefäßimplantate - Herzklappenprothesen -
Partie 3: Valves cardiaques de substitution implantées Teil 3: Durch minimal-invasive Methoden
par des techniques transcathéter (ISO 5840-3:2021) implantierter Herzklappenersatz (ISO 5840-3:2021)
This European Standard was approved by CEN on 22 September 2020.

CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this
European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references
concerning such national standards may be obtained on application to the CEN-CENELEC Management Centre or to any CEN
member.
This European Standard exists in three official versions (English, French, German). A version in any other language made by
translation under the responsibility of a CEN member into its own language and notified to the CEN-CENELEC Management
Centre has the same status as the official versions.

CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia,
Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway,
Poland, Portugal, Republic of North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION

EUROPÄISCHES KOMITEE FÜR NORMUNG

CEN-CENELEC Management Centre: Rue de la Science 23, B-1040 Brussels
© 2021 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 5840-3:2021 E
worldwide for CEN national Members.

Contents Page
European foreword . 3

European foreword
This document (EN ISO 5840-3:2021) has been prepared by Technical Committee ISO/TC 150
"Implants for surgery" in collaboration with Technical Committee CEN/TC 285 “Non-active surgical
implants” the secretariat of which is held by DIN.
This European Standard shall be given the status of a national standard, either by publication of an
identical text or by endorsement, at the latest by August 2021, and conflicting national standards shall
be withdrawn at the latest by August 2021.
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. CEN shall not be held responsible for identifying any or all such patent rights.
This document supersedes EN ISO 5840-3:2013.
According to the CEN-CENELEC Internal Regulations, the national standards organizations of the
following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria,
Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland,
Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Republic of
North Macedonia, Romania, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the
United Kingdom.
Endorsement notice
The text of ISO 5840-3:2021 has been approved by CEN as EN ISO 5840-3:2021 without any
modification.
INTERNATIONAL ISO
STANDARD 5840-3
Second edition
2021-01
Cardiovascular implants — Cardiac
valve prostheses —
Part 3:
Heart valve substitutes implanted by
transcatheter techniques
Implants cardiovasculaires — Prothèses valvulaires —
Partie 3: Valves cardiaques de substitution implantées par des
techniques transcathéter
Reference number
ISO 5840-3:2021(E)
©
ISO 2021
ISO 5840-3:2021(E)
© ISO 2021
All rights reserved. Unless otherwise specified, or required in the context of its implementation, no part of this publication may
be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, including photocopying, or posting
on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address
below or ISO’s member body in the country of the requester.
ISO copyright office
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CH-1214 Vernier, Geneva
Phone: +41 22 749 01 11
Email: copyright@iso.org
Website: www.iso.org
Published in Switzerland
ii © ISO 2021 – All rights reserved

ISO 5840-3:2021(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Abbreviations. 4
5 Fundamental requirements . 5
6 Device description . 5
6.1 General . 5
6.2 Intended use . 6
6.3 Design inputs . 6
6.3.1 Operational specifications . 6
6.3.2 Performance specifications . 6
6.3.3 Implant procedure. 7
6.3.4 Packaging, labelling and sterilization . 7
6.4 Design outputs . 7
6.5 Design transfer (manufacturing verification/validation) . 7
6.6 Risk management . 7
7 Design verification and validation . 8
7.1 General requirements . 8
7.2 In vitro assessment . 8
7.2.1 General. 8
7.2.2 Test conditions, sample selection and reporting requirements . 8
7.2.3 Material property assessment . 8
7.2.4 Hydrodynamic performance assessment . 8
7.2.5 Structural performance assessment .10
7.2.6 Design- or procedure-specific testing.10
7.2.7 Device MRI compatibility .12
7.2.8 Simulated use.12
7.2.9 Human factors and usability assessment .12
7.2.10 Implant thrombogenic and haemolytic potential assessment .12
7.3 Preclinical in vivo evaluation .12
7.3.1 General.12
7.3.2 Overall requirements .13
7.3.3 Methods .14
7.3.4 Test report .15
7.4 Clinical investigations .16
7.4.1 General.16
7.4.2 Study considerations .17
7.4.3 Study endpoints .18
7.4.4 Ethical considerations .19
7.4.5 Pivotal studies: Distribution of subjects and investigators .19
7.4.6 Statistical considerations including sample size and duration .20
7.4.7 Patient selection criteria .22
7.4.8 Valve thrombosis prevention .22
7.4.9 Clinical data requirements .23
Annex A (informative) Description of the transcatheter heart valve system .28
Annex B (informative) Transcatheter heart valve substitute hazard analysis example .30
Annex C (informative) Guidelines for verification of hydrodynamic performance —
Pulsatile flow testing .32
ISO 5840-3:2021(E)
Annex D (normative) Requirements for delivery system design and evaluation .40
Annex E (informative) Examples of design specific testing .42
Annex F (informative) Preclinical in vivo evaluation .44
Annex G (normative) Adverse event classification during clinical investigation .47
Annex H (informative) Multimodality imaging of TAVI and TMVI pre, peri and post-
implantation assessments — Examples .53
Bibliography .56
iv © ISO 2021 – All rights reserved

ISO 5840-3:2021(E)
Foreword
ISO (the International Organization for Standardization) is a worldwide federation of national standards
bodies (ISO member bodies). The work of preparing International Standards is normally carried out
through ISO technical committees. Each member body interested in a subject for which a technical
committee has been established has the right to be represented on that committee. International
organizations, governmental and non-governmental, in liaison with ISO, also take part in the work.
ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of
electrotechnical standardization.
The procedures used to develop this document and those intended for its further maintenance are
described in the ISO/IEC Directives, Part 1. In particular, the different approval criteria needed for the
different types of ISO documents should be noted. This document was drafted in accordance with the
editorial rules of the ISO/IEC Directives, Part 2 (see www .iso .org/ directives).
Attention is drawn to the possibility that some of the elements of this document may be the subject of
patent rights. ISO shall not be held responsible for identifying any or all such patent rights. Details of
any patent rights identified during the development of the document will be in the Introduction and/or
on the ISO list of patent declarations received (see www .iso .org/ patents).
Any trade name used in this document is information given for the convenience of users and does not
constitute an endorsement.
For an explanation of the voluntary nature of standards, the meaning of ISO specific terms and
expressions related to conformity assessment, as well as information about ISO's adherence to the
World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT), see www .iso .org/
iso/ foreword .html.
This document was prepared by Technical Committee ISO/TC 150, Implants for surgery, Subcommittee
SC 2, Cardiovascular implants and extracorporeal systems, in collaboration with the European Committee
for Standardization (CEN) Technical Committee CEN/TC 285, Non-active surgical implants, in accordance
with the Agreement on technical cooperation between ISO and CEN (Vienna Agreement).
This second edition cancels and replaces the first edition (ISO 5840-3:2013), which has been technically
revised.
The main changes compared to the previous edition are as follows: the engineering and clinical
requirements in the ISO 5840 series have been updated to current specifications and integrated and
harmonized across all parts.
A list of all parts in the ISO 5840 series can be found on the ISO website.
Any feedback or questions on this document should be directed to the user’s national standards body. A
complete listing of these bodies can be found at www .iso .org/ members .html.
ISO 5840-3:2021(E)
Introduction
This document has been prepared for transcatheter heart valve substitutes with emphasis on providing
guidance for in vitro testing, preclinical in vivo and clinical evaluations, reporting of all in vitro,
preclinical in vivo, and clinical evaluations and labelling and packaging of the device. This process is
intended to clarify the required procedures prior to market release and to enable prompt identification
and management of any subsequent issues.
This document is used in conjunction with ISO 5840-1 and ISO 5840-2.
vi © ISO 2021 – All rights reserved

INTERNATIONAL STANDARD ISO 5840-3:2021(E)
Cardiovascular implants — Cardiac valve prostheses —
Part 3:
Heart valve substitutes implanted by transcatheter
techniques
1 Scope
This document is applicable to all devices intended for implantation as a transcatheter heart valve
substitute.
This document is applicable to transcatheter heart valve substitutes and to the accessory devices,
packaging and labelling required for their implantation and for determining the appropriate size of
heart valve substitute to be implanted.
This document establishes an approach for verifying/validating the design and manufacture of
a transcatheter heart valve substitute through risk management. The selection of appropriate
verification/validation tests and methods are to be derived from the risk assessment. The tests can
include those to assess the physical, chemical, biological and mechanical properties of heart valve
substitutes and of their materials and components. The tests can also include those for preclinical in
vivo evaluation and clinical evaluation of the finished heart valve substitute.
This document defines operational conditions and performance requirements for transcatheter heart
valve substitutes where adequate scientific and/or clinical evidence exists for their justification.
This document includes considerations for implantation of a transcatheter heart valve substitute inside
a pre-existing prosthetic device (e.g. valve-in-valve and valve-in-ring configurations).
2 Normative references
The following documents are referred to in the text in such a way that some or all of their content
constitutes requirements of this document. For dated references, only the edition cited applies. For
undated references, the latest edition of the referenced document (including any amendments) applies.
ISO 5840-1:2021, Cardiovascular implants — Cardiac valve prostheses — Part 1: General requirements
ISO 10993-2, Biological evaluation of medical devices — Part 2: Animal welfare requirements
ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
ISO 14630, Non-active surgical implants — General requirements
ISO 14971, Medical devices — Application of risk management to medical devices
IEC 62366 (all parts), Medical devices — Application of usability engineering to medical devices
3 Terms and definitions
For the purposes of this document, the terms and definitions given in ISO 5840-1:2021 and the
following apply.
ISO and IEC maintain terminological databases for use in standardization at the following addresses:
— ISO Online browsing platform: available at https:// www .iso .org/ obp
ISO 5840-3:2021(E)
— IEC Electropedia: available at http:// www .electropedia .org/
3.1
acute assessment
intra-procedural and immediate post-procedural results used to assess in vivo safety and performance
Note 1 to entry: All animals entered into acute, short-term assessment will remain under general anaesthesia for
the duration of the study.
3.2
chronic assessment
long-term results following the procedure used to assess chronic in vivo safety and performance after
the animal has recovered from anaesthesia
Note 1 to entry: The endpoints and durations of these studies should be determined by risk analysis.
3.3
delivery approach
anatomical access used to deliver the implant to the implant site (e.g. transfemoral, transapical,
transseptal)
3.4
delivery system
catheter or other system used to deliver the implant to the implant site
3.5
device migration
detectable movement or displacement of the heart valve substitute from its original position within the
implant position and without device embolization
3.6
loading
crimping
process to affix or attach a transcatheter heart valve substitute onto a delivery device and collapse
the valve (i.e. reduce its diameter) for insertion via the delivery system (3.4) (e.g. catheter), performed
either during manufacture or in the clinic
3.7
neo-LVOT
neo-left ventricular outflow tract
region between native anterior mitral leaflet/ transcatheter mitral valve implantation (TMVI) and
septal wall, proximal to the aortic valve (see Figure 1)
2 © ISO 2021 – All rights reserved

ISO 5840-3:2021(E)
Key
1 TMVI
2 native anterior mitral leaflet
3 neo-LVOT
4 septal wall
Figure 1 — Neo-LVOT formation behind a mitral leaflet
3.8
neo-sinus
region between implanted transcatheter aortic valve leaflet and native aortic leaflet/leaflet of existing
bioprosthetic valve (see Figure 2)
ISO 5840-3:2021(E)
Key
1 transcatheter aortic valve implantation (TAVI) leaflet
2 native leaflet
3 neo-sinus
4 native sinus
a
The arrow indicates the direction of the forward flow.
Figure 2 — Neo-sinus formation behind an aortic leaflet
3.9
repositioning
change in implant position of a partially- or fully-deployed transcatheter heart valve substitute via a
transcatheter technique, possibly requiring full or partial recapturing of the device
3.10
retrieval
removal of a partially- or fully-deployed transcatheter heart valve substitute via a transcatheter
technique
3.11
transcatheter heart valve system
implantable transcatheter device, delivery system (3.4), accessories, packaging, labels and
instructions for use
3.12
valve-in-ring
implantation of a transcatheter heart valve substitute into a pre-existing annuloplasty ring
3.13
valve-in-valve
implantation of a transcatheter heart valve substitute into a pre-existing heart valve substitute
4 Abbreviations
For the purposes of this document, the following abbreviations apply.
4 © ISO 2021 – All rights reserved

ISO 5840-3:2021(E)
AE adverse event
AWT accelerated wear testing
CIP clinical investigation plan
COF chronic outward force
CT computed tomography
ECG electrocardiogram
EOA effective orifice area
IFU instructions for use
LA left atrium
LAA left atrial appendage
LV left ventricle, left ventricular
LVOT left ventricular outflow tract
MRI magnetic resonance imaging
MR mitral regurgitation
PMCF post-market clinical follow-up
PVL paravalvular leakage
RMS root mean square
SAE serious adverse event
TAVI transcatheter aortic valve implantation [also known as transcatheter aortic valve
replacement (TAVR)]
TEE transoesophageal echo
TMVI transcatheter mitral valve implantation [also known as transcatheter mitral valve
replacement (TMVR)]
TTE transthoracic echo
ViV valve-in-valve
ViR valve-in-ring
5 Fundamental requirements
See ISO 5840-1:2021, Clause 5.
6 Device description
6.1 General
See ISO 5840-1:2021, 6.1.
ISO 5840-3:2021(E)
6.2 Intended use
See ISO 5840-1:2021, 6.2.
6.3 Design inputs
6.3.1 Operational specifications
See ISO 5840-1:2021, 6.3.1.
6.3.2 Performance specifications
6.3.2.1 General
See ISO 5840-1:2021, 6.3.2 for general requirements. Specific transcatheter system requirements are
listed in 6.3.2.2 to 6.3.2.4. See Reference [18] for information relevant to TMVI.
6.3.2.2 Transcatheter heart valve system
The design attributes to meet the intended performance of the transcatheter heart valve system shall
take into account at least the following:
a) the visibility of the transcatheter heart valve system under fluoroscopy or other imaging modalities;
b) the deliverability and implantability in the target population.
6.3.2.3 Implantable device
The intended performance of the transcatheter heart valve substitute shall include, but not be limited
to the following:
a) the ability to be consistently, accurately and safely loaded onto the delivery system;
b) the ability to be consistently, accurately and safely deployed;
c) the ability to be safely retrieved and/or repositioned (if applicable);
d) the ability to ensure effective fixation or anchoring within the implant site;
e) the ability to maintain structural and functional integrity throughout the anticipated lifetime of
the device;
f) the ability to conform or interact with anatomical structures within the implant site (e.g. in the
aortic position, there is potential for interaction with the coronary ostia, the anterior mitral leaflet
and the conduction system; in the mitral position, there is potential for interaction with the aortic
root, LA, LAA, LVOT and the subvalvular apparatus);
g) the ability to conform or interact with previously implanted device (e.g. surgical valve, annuloplasty
ring, transcatheter valve, valve docking device), if applicable;
h) the ability to allow forward flow with an acceptably small mean pressure difference in all
anticipated configurations;
i) the ability to prevent retrograde flow with acceptably small regurgitation, including paravalvular
leakage;
j) the ability to resist migration and embolization;
k) the ability to avoid haemolysis;
l) the ability to resist thrombus formation;
6 © ISO 2021 – All rights reserved

ISO 5840-3:2021(E)
m) biocompatibility;
n) the ability to maintain its functionality and sterility for a reasonable shelf life prior to implantation;
o) reproducibility of function.
6.3.2.4 Delivery system
In addition to the requirements in Annex D, the design attributes to meet the intended performance of
the delivery system shall include, but are not limited to, the following:
a) the ability to permit consistent, accurate and safe access, delivery, placement and deployment of
the transcatheter heart valve substitute to the intended implant site;
b) the ability to permit consistent and safe withdrawal;
c) the ability to resist haemolysis;
d) the ability to resist thrombus formation;
e) the ability to resist blood loss (haemostasis);
f) the ability to recapture, retrieve, reposition and/or remove the transcatheter heart valve substitute
(if applicable);
g) the ability to resist particulate generation.
6.3.3 Implant procedure
See ISO 5840-1:2021, 6.3.3.
6.3.4 Packaging, labelling and sterilization
See ISO 5840-1:2021, 6.3.4.
The manufacturer shall provide information and guidance (e.g. imaging modalities and sizing
procedure) in the labelling to allow for appropriate preparation of the implant site (e.g. balloon
valvuloplasty), selection of appropriate implant size and implantation of the transcatheter heart valve
substitute. The manufacturer shall also provide MRI compatibility information in the labelling.
Annex A contains a list of terms that may be used in describing transcatheter heart valve system
components.
6.4 Design outputs
See ISO 5840-1:2021, 6.4. See Reference [18] for information relevant to TMVI.
6.5 Design transfer (manufacturing verification/validation)
See ISO 5840-1:2021, 6.5.
6.6 Risk management
See ISO 5840-1:2021, 6.6.
Annex B contains a hazard analysis example specific to transcatheter heart valve substitutes that can
serve as the basis for a risk analysis.
ISO 5840-3:2021(E)
7 Design verification and validation
7.1 General requirements
In vitro assessment shall be used to mitigate the risks identified in the risk analysis. General
requirements that are applicable to all heart valve systems are provided in ISO 5840-1:2021,7.1. Specific
considerations for transcatheter heart valve substitutes are provided in this document. See Reference
[18] for information relevant to TMVI.
7.2 In vitro assessment
7.2.1 General
The requirements shall be as specified in ISO 5840-1:2021, 7.2.
7.2.2 Test conditions, sample selection and reporting requirements
The requirements shall be as specified in ISO 5840-1:2021, 7.2.2.
For transcatheter valves, the steps of crimping or loading the implant into/onto a delivery catheter
and tracking through simulated delivery pathways shall be followed in accordance with the IFU. The
implant shall be maintained in the crimped configuration for a duration that mimics the worst-case
expected clinical procedure time. If retrieval and repositioning is indicated for the implant in the IFU,
the maximum allowable number of re-sheathing/recapturing and deployment cycles specified shall be
simulated. Any deviations of the test articles from the finished device shall be justified. The test articles
selected shall fully represent the total size range of the implant, the delivery system and accessories.
7.2.3 Material property assessment
7.2.3.1 General
The requirements shall be as specified in ISO 5840-1:2021, 7.2.3.
7.2.3.2 Biological safety
The requirements shall be as specified in ISO 5840-1:2021, 7.2.3.2.
7.2.3.3 Material and mechanical property testing
The requirements shall be as specified in ISO 5840-1:2021, 7.2.3.3.
For ViV and ViR indications, consideration shall be given to the material properties of the existing
prosthesis, including bioprosthetic valve leaflet calcification, and their interactions with the materials
of the transcatheter heart valve system.
7.2.4 Hydrodynamic performance assessment
Hydrodynamic testing shall be performed to provide information on the fluid dynamic performance
of the transcatheter heart valve substitute. The implant shall be deployed using the loading and
deployment steps in accordance with the product specification and appropriately placed into the test
chamber to simulate the device placement at the intended implant site. The device shall be inspected
after loading, recapturing and/or deployment prior to fixturing and testing. ISO 5840-1:2021, Annex I
provides guidelines for conducting and reporting steady-flow hydrodynamic tests. Guidelines for
conducting and reporting of pulsatile hydrodynamic tests are provided in Annex C. For pulsatile flow
testing, the performance of the pulse duplicator shall be characterized. See C.2.3.2 for guidelines
related to pulse duplicator characterization. The measurement accuracy and repeatability of the test
system(s) shall be evaluated and documented. The hydrodynamic waveforms produced by the pulse
8 © ISO 2021 – All rights reserved

ISO 5840-3:2021(E)
duplicator shall reasonably simulate physiological conditions. Representative waveforms used to
generate hydrodynamic test results shall be documented in the test report. Reference [27] provides
characteristics of reasonable aortic and mitral waveforms.
For transcatheter aortic valve substitutes, testing shall be performed to compare the hydrodynamic
performance of the device to the minimum performance requirements provided in Table 1. Guidelines
for designing test fixtures and test parameters are provided in Annex C and C.2.4. Testing shall be
carried out on at least three transcatheter heart valve substitutes of each size in each configuration
using requirements defined in Table C.2. The minimum performance requirements in Table 1 are
provided as a function of deployed valve diameter within implant site (in mm). In addition, testing
at challenge conditions shall also be considered to evaluate the device performance over a range of
anticipated implant configurations (see Annex C and C.2.4.4 for examples of challenge conditions for
transcatheter aortic valve substitutes).
For transcatheter mitral valve substitutes, testing shall be performed to compare the hydrodynamic
performance of the device to the minimum performance requirements provided in Table 2. Guidelines
for designing test fixtures and test parameters are provided in Annex C and C.2.5. Testing shall be
carried out on at least three transcatheter heart valve substitutes of each size in each configuration
using requirements defined in Table C.3. The minimum performance requirements in Table 2 are
provided as a function of area-derived valve diameter (in mm).
For ViV and ViR indications, hydrodynamic testing shall be conducted in representative configurations
of the pre-existing prosthetic devices to compare the device hydrodynamic performance to the
minimum performance requirements provided in Tables 1 and 2.
The minimum performance values contained in Tables 1 and 2 reflect requirements against which heart
valves substitutes under test shall be evaluated. If a device does not meet these minimum performance
requirements, acceptability of the in vitro test results shall be justified by the manufacturer.
The minimum in vitro performance requirements in Tables 1 and 2 correspond to the following nominal
pulsatile flow conditions: beat rate = 70 cycles/min, simulated cardiac output = 5,0 l/min, and systolic
duration = 35 % at normotensive conditions, as specified in ISO 5840-1:2021, Table 3 or Table 4. These
pulsatile flow conditions are based on a healthy normal adult and might not be applicable for paediatric
device evaluation (see ISO 5840-1:2021, Annex E for paediatric parameters).
Table 1 — Minimum in vitro hydrodynamic device performance requirements, aortic
Deployed valve diameter within implant site
mm
Parameter
17 19 21 23 25 27 29 31
EOA (cm ) greater than or equal to 0,70 0,85 1,05 1,25 1,45 1,70 1,95 2,25
Regurgitant fraction (% of forward flow
a
volume) less than or equal to
a
For in vitro testing, regurgitant fraction includes closing volume, transvalvular leakage and paravalvular leakage volume.
Table 2 — Minimum in vitro hydrodynamic device performance requirements, mitral
Deployed area-derived valve diameter within implant site
mm
Parameter
23 25 27 29 31 ≥33
2 a
EOA (cm ) greater than or equal to 1,05 1,25 1,45 1,65 1,90 2,15
Regurgitant fraction (% of forward flow
b
volume) less than or equal to
a
For measured mean pressure gradients ≤2 mmHg, computing of EOA is not required.
b
For in vitro testing, regurgitant fraction includes closing volume, transvalvular leakage and paravalvular leakage volume.
For transcatheter pulmonary and tricuspid valve substitutes and paediatric devices, minimum
performance requirements are not provided in this document; however, the manufacturer shall justify
ISO 5840-3:2021(E)
the acceptability of hydrodynamic performance of the devices. The test chamber shall be representative
of the critical aspects of the target implant site (e.g. compliance, geometry, native valve or pre-existing
prosthetic device) for the target patient population.
For all transcatheter valve substitutes, additional hydrodynamic characterization testing shall be
conducted over a range of test conditions as described in Annex C and C.2.6.
7.2.5 Structural performance assessment
7.2.5.1 General
The requirements shall be as specified in ISO 5840-1:2021, 7.2.5.
7.2.5.2 Implant durability assessment
The requirements shall be as specified in ISO 5840-1:2021, 7.2.5.2.
For ViV and ViR indications, testing shall be conducted in devices that are representative of the
anticipated range of configurations.
7.2.5.3 Device structural component fatigue assessment
See ISO 5840-1:2021, 7.2.5.3.
7.2.5.4 Component corrosion assessment
See ISO 5840-1:2021, 7.2.5.4.
For ViV and ViR indications, the manufacturer shall consider all interactions with the pre-existing
device in terms of corrosion potential (e.g. galvanic corrosion, fretting corrosion).
7.2.6 Design- or procedure-specific testing
7.2.6.1 General
The following design evaluation requirements shall apply as appropriate. Justification shall be provided
for those requirements that are deemed not applicable to a particular design. Additional design
evaluation requirements might be applicable as per ISO 25539-1. The manufacturer shall define all
applicable requirements based on the results of the risk assessment for the specific device design. See
Annex E for examples of design specific evaluation requirements to be considered.
7.2.6.2 Device migration resistance
The ability of the implanted device to remain in the target implant site (e.g. native valve or pre-existing
prosthesis) shall be assessed under simulated operating conditions. Consideration shall be given to
variation in deployed shape, deployed size as prescribed in the product specification, implanted depth,
implant site characteristics (e.g. native valve, degree and distribution of calcification) and mechanical
properties (e.g. compliance) along with consideration for surrounding anatomical structures (e.g.
native leaflets, LVOT). For ViV and ViR indications, the manufacturer shall consider simulated
operating conditions of the existing device and all interactions with the existing device in terms of
device migration potential. The pressure conditions specified in ISO 5840-1:2021, Tables 3 and 4, and
other loading conditions, shall be considered as applicable. See ISO 5840-1:2021, Annex E for guidelines
regarding suggested test conditions for the paediatric population.
10 © ISO 2021 – All rights reserved

ISO 5840-3:2021(E)
7.2.6.3 Implant foreshortening (length to diameter)
The manufacturer shall determine the decrease in length of the implant between the catheter-loaded
condition and the deployed diameters up to the maximum labelled diameter (see ASTM F2081 for
guidance). The results shall be reported in terms of a percentage of the loaded length as shown below:
P = 100 × (l / l )
f c l
where
P is the percentage of foreshortening;
f
l is the change in length;
c
l is the loaded length;
l
7.2.6.4 Crush resistance
The manufacturer shall determine the ability of the support structure to resist permanent deformation
due to crushing loads acting at the intended implant site over a diameter range per the product
specification. For non-circular devices, an account shall be taken of the specific use range of the device
as it relates to the intended annulus geometry (e.g. anterior to posterior dimension or commissure to
commissure as it relates to the mitral annulus). This is accomplished by the following evaluations:
— the crush resistance test with a radially applied load measures the ability of the support structure
to resist permanent deformation when subjected to a circumferentially uniform radial load;
— the crush resistance test using parallel plates measures the ability of the support structure to resist
permanent deformation along the entire length of the device when subjected to a load applied over
the length of the device.
7.2.6.5 Recoil
The manufacturer shall determine the amount of elastic recoil in device diameter (percentage of device
diameter reduction) after implant expansion. This shall be assessed against the recommended sizing
given in the product specification. See ASTM F2079 for guidance.
7.2.6.6 Radial resistive force (RRF)
The manufacturer shall characterize the force exerted by the support structure as it resists radial
compression from its maximum diameter to its minimum crimped diameter as shown in the device
specification. See ASTM F3067 for guidance. Consideration shall be given to the effect of multiple
crimping or retrieval steps as appropriate for the device. For non-symmetric devices, the perimeter
change or other dimensions shall be considered.
7.2.6.7 Chronic outward force
The manufacturer shall characterize the force exerted by the support structure as it attempts to
expand to its maximum unconstrained diameter after being radially compressed to its minimum
crimped diameter per the device specification. See ASTM F3067 for guidance. Depending on the support
structure design, the COF might be different in different regions of the support structure and shall
be evaluated accordingly. Consideration shall be given to the effect of multiple crimping or retrieval
steps as appropriate for the device. Non-symmetric devices shall consider perimeter change or other
dimensions.
ISO 5840-3:2021(E)
7.2.6.8 Delivery system design evaluation requirements
The manufacturer shall define and justify all applicable requirements based on the results of
...