EN ISO 5840-1:2021

SLOVENSKI STANDARD
01-marec-2021
Nadomešča:
SIST EN ISO 5840-1:2015
Vsadki (implantati) za srce in ožilje - Proteze za srčno zaklopko - 1. del: Splošne
zahteve (ISO 5840-1:2021)
Cardiovascular implants - Cardiac valve prostheses - Part 1: General requirements (ISO
5840-1:2021)
Herz- und Gefäßimplantate - Herzklappenprothesen - Teil 1: Allgemeine Anforderungen
(ISO 5840-1:2021)
Implants cardiovasculaires - Prothèses valvulaires - Partie 1: Exigences générales (ISO
5840-1:2021)
Ta slovenski standard je istoveten z: EN ISO 5840-1:2021
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 5840-1
EUROPEAN STANDARD
NORME EUROPÉENNE
February 2021
EUROPÄISCHE NORM
ICS 11.040.40 Supersedes EN ISO 5840-1:2015
English Version
Cardiovascular implants - Cardiac valve prostheses - Part
1: General requirements (ISO 5840-1:2021)
Implants cardiovasculaires - Prothèses valvulaires - Herz- und Gefäßimplantate - Herzklappenprothesen -
Partie 1: Exigences générales (ISO 5840-1:2021) Teil 1: Allgemeine Anforderungen (ISO 5840-1:2021)
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 5840-1:2021 E
worldwide for CEN national Members.

Contents Page
European foreword . 3

European foreword
This document (EN ISO 5840-1:2021) 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 5840-1:2015.
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 5840-1:2021 has been approved by CEN as EN ISO 5840-1:2021 without any
modification.
INTERNATIONAL ISO
STANDARD 5840-1
Second edition
2021-01
Cardiovascular implants — Cardiac
valve prostheses —
Part 1:
General requirements
Implants cardiovasculaires — Prothèses valvulaires —
Partie 1: Exigences générales
Reference number
ISO 5840-1:2021(E)
©
ISO 2021
ISO 5840-1:2021(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
CP 401 • Ch. de Blandonnet 8
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 5840-1:2021(E)
Contents Page
Foreword .v
Introduction .vi
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 2
4 Abbreviations.15
5 Fundamental requirements .15
6 Device description .16
6.1 General .16
6.2 Intended use .16
6.3 Design inputs .16
6.3.1 Operational specifications .16
6.3.2 Performance specifications .17
6.3.3 Implant procedure.17
6.3.4 Packaging, labelling, and sterilization .17
6.4 Design outputs .18
6.5 Design transfer (manufacturing verification/validation) .18
6.6 Risk management .18
7 Design verification and validation .18
7.1 General requirements .18
7.2 In vitro assessment .18
7.2.1 General.18
7.2.2 Test conditions, sample selection and reporting requirements .19
7.2.3 Material property assessment .20
7.2.4 Hydrodynamic performance assessment .21
7.2.5 Structural performance assessment .21
7.2.6 Design- or procedure-specific testing.23
7.2.7 Device MRI compatibility .23
7.2.8 Simulated use.23
7.2.9 Human factors/usability assessment .23
7.2.10 Implant thrombogenic and haemolytic potential assessment .23
7.3 Preclinical in vivo evaluation .24
7.4 Clinical investigations .24
Annex A (informative) Rationale for the provisions of ISO 5840-1 .25
Annex B (normative) Packaging .28
Annex C (normative) Product labels, instructions for use, and training .29
Annex D (normative) Sterilization .32
Annex E (normative) In vitro test guidelines for paediatric devices .33
Annex F (informative) Corrosion assessment .37
Annex G (informative) Echocardiographic protocol .40
Annex H (informative) Assessment of implant thrombogenic and haemolytic potential .42
Annex I (informative) Guidelines for hydrodynamic performance characterization by
steady flow testing .53
Annex J (normative) Durability testing.60
Annex K (informative) Fatigue assessment .68
Annex L (normative) Clinical investigation endpoints for heart valve replacement devices .73
ISO 5840-1:2021(E)
Bibliography .76
iv © ISO 2021 – All rights reserved

ISO 5840-1:2021(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 5840-1:2015), 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 5840-1:2021(E)
Introduction
There is, as yet, no heart valve substitute which can be regarded as ideal.
The ISO 5840 series has been prepared by a group well aware of the issues associated with heart valve
substitutes and their development. In several areas, the provisions of the ISO 5840 series deliberately
have not been specified to encourage development and innovation. It does specify the types of tests,
provides guidance for test methods and test apparatuses and requires documentation of test methods
and results. The areas with which the ISO 5840 series are concerned are those which ensure that
associated risks to the patient and other users of the device have been adequately mitigated, facilitate
quality assurance, aid the clinician in choosing a heart valve substitute, and ensure that the device
is presented in a convenient form. Emphasis has been placed on specifying types of in vitro testing,
preclinical in vivo and clinical evaluations, reporting of all in vitro, preclinical in vivo, and clinical
evaluations, and the labelling and packaging of the device. Such a process involving in vitro, preclinical
in vivo, and clinical evaluations is intended to clarify the required procedures prior to market release
and to enable prompt identification and management of any subsequent problems.
With regard to in vitro testing and reporting, apart from basic material testing for mechanical, physical,
chemical, and biocompatibility characteristics, the ISO 5840 series also covers important hydrodynamic
and durability characteristics of heart valve substitutes and systems required for their implantation.
The ISO 5840 series does not specify exact test methods for hydrodynamic and durability testing, but it
offers guidelines for the test apparatus.
The ISO 5840 series is intended to be revised, updated, and/or amended as knowledge and techniques
in heart valve substitute technology improve.
This document is used in conjunction with ISO 5840-2 and ISO 5840-3.
vi © ISO 2021 – All rights reserved

INTERNATIONAL STANDARD ISO 5840-1:2021(E)
Cardiovascular implants — Cardiac valve prostheses —
Part 1:
General requirements
1 Scope
This document is applicable to heart valve substitutes intended for implantation and provides general
requirements. Subsequent parts of the ISO 5840 series provide specific requirements.
This document is applicable to newly developed and modified heart valve substitutes and to the
accessory devices, packaging, and labelling required for their implantation and for determining the
appropriate size of the heart valve substitute to be implanted.
ISO 5840-1 outlines an approach for verifying/validating the design and manufacture of a heart valve
substitute through risk management. The selection of appropriate qualification tests and methods
are 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.
ISO 5840-1 defines operational conditions for heart valve substitutes.
ISO 5840-1 furthermore defines terms that are also applicable to ISO 5840-2 and ISO 5840-3.
ISO 5840-1 does not provide requirements specific to homografts, tissue engineered heart valves
(e.g. valves intended to regenerate in vivo), and heart valve substitutes designed for implantation in
circulatory support devices. Some of the provisions of ISO 5840-1 can be applied to valves made from
human tissue that is rendered non-viable.
NOTE A rationale for the provisions of ISO 5840-1 is given in Annex A.
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 5840-2, Cardiovascular implants — Cardiac valve prostheses —Part 2: Surgically implanted heart valve
substitutes
ISO 5840-3, Cardiovascular implants — Cardiac valve prostheses —Part 3: Heart valve substitutes
implanted by transcatheter techniques
ISO 10993-1, Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk
management process
ISO 11135, Sterilization of health-care products — Ethylene oxide — Requirements for the development,
validation and routine control of a sterilization process for medical devices
ISO 11137 (all parts), Sterilization of health care products — Radiation
ISO 11607 (all parts), Packaging for terminally sterilized medical devices
ISO 13485, Medical devices — Quality management systems — Requirements for regulatory purposes
ISO 5840-1:2021(E)
ISO 14155, Clinical investigation of medical devices for human subjects — Good clinical practice
ISO 14160, Sterilization of health care products — Liquid chemical sterilizing agents for single-use medical
devices utilizing animal tissues and their derivatives — Requirements for characterization, development,
validation and routine control of a sterilization process for medical devices
ISO 14630, Non-active surgical implants — General requirements
ISO 14937, Sterilization of health care products — General requirements for characterization of a sterilizing
agent and the development, validation and routine control of a sterilization process for medical devices
ISO 14971, Medical devices — Application of risk management to medical devices
ISO 15223-1, Symbols to be used with medical device labels, labelling and information to be supplied —
Part 1: General requirements
ISO 22442 (all parts), Medical devices utilizing animal tissues and their derivatives
IEC 62366 (all parts), Medical Devices — Application of usability engineering to medical devices
3 Terms and definitions
For the purposes of this document, the following terms and definitions 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
— IEC Electropedia: available at http:// www .electropedia .org/
3.1
accessory
device-specific tool that is required to assist in the implantation of the heart valve substitute (3.30)
3.2
adverse event
AE
untoward medical occurrence in a study subject which does not necessarily have a causal relationship
with study treatment
Note 1 to entry: An AE can be an unfavourable and unintended sign (including an abnormal laboratory finding),
symptom, or disease, temporary or permanent, whether or not related to the heart valve substitute (3.30) or
implantation procedure.
3.3
area-derived valve diameter
D
A
calculated valve diameter based on area (A) of the device [i.e. a “D-Shaped” transcatheter mitral valve
implantation (TMVI) device; refer to Figure 1]: D = 4 A/π
A
Note 1 to entry: This approach is typically used for labelling the sizes of TMVI devices where valves are designed
for a noncircular geometry.
2 © ISO 2021 – All rights reserved

ISO 5840-1:2021(E)
Key
1 area of valve
D = 4 A/π
A
D = area-derived diameter
A
Figure 1 — Area-derived valve diameter for a non-circular device
3.4
arterial end diastolic pressure
minimum value of the arterial pressure during diastole
3.5
arterial peak systolic pressure
maximum value of the arterial pressure during systole (3.68)
3.6
back pressure
differential pressure across the valve during the closed phase
3.7
body surface area
BSA
total surface area (m ) of the human body
Note 1 to entry: This can be calculated (Mosteller's formula) as the square root of the product of the weight in kg
and the height in cm divided by 3 600 (see Reference [26]).
3.8
cardiac output
CO
stroke volume (3.64) times heart rate
3.9
closing volume
portion of the regurgitant volume (3.49) that is associated with the dynamics of valve closure during a
single cycle (3.13)
Note 1 to entry: See Figure 2.
Note 2 to entry: The volume of flow occurring between end of systole (3.23) and start of leakage (3.59) for aortic
and pulmonary positions; between end of diastole (3.21) and start of leakage for mitral and tricuspid positions.
3.10
coating
thin-film material that is applied to an element of a heart valve system (3.31) to modify its surface
physical or chemical properties
ISO 5840-1:2021(E)
3.11
compliance
relationship between change in diameter and change in pressure of a deformable tubular structure (e.g.
aorta, conduit) defined in ISO 5840 (all parts) as
()rr−×100
C= ×100%
rp×−()p
12 1
where
C is the compliance in units of % radial change/100 mmHg;
p is the diastolic pressure, in mmHg;
p is the systolic pressure, in mmHg;
r is the inner radius at p , in millimetres;
1 1
r is the inner radius at p , in millimetres.
2 2
Note 1 to entry: See ISO 25539-1.
Key
X time 1 closing volume
Y flowrate 2 leakage volume
NOTE The total regurgitant volume is the sum of the closing volume and the leakage volume.
Figure 2 — Schematic representation of flow waveform, regurgitant volumes, and end of
closure determination for one cycle
4 © ISO 2021 – All rights reserved

ISO 5840-1:2021(E)
3.12
control valve
heart valve substitute for preclinical and clinical evaluations of similar design and constructed of
similar material as the investigational device
Note 1 to entry: The control valve should have a known clinical history.
3.13
cycle
complete sequence in the action of a heart valve substitute (3.30) under pulsatile-flow conditions
3.14
cycle rate
beat rate
number of complete cycles (3.13) per unit of time usually expressed as cycles per minute (cycles/min or
beats/min [bpm])
3.15
design verification
establishment by objective evidence that the design output meets the design input requirements
3.16
design validation
establishment by objective evidence that device specifications conform with user needs and intended
use(s) (3.33)
3.17
device embolization
dislodgement from the intended and documented original position to an unintended and non-
therapeutic location
3.18
device failure
inability of a device to perform its intended function
3.19
diastole
diastolic duration
portion of cardiac cycle time corresponding to ventricular filling
Note 1 to entry: Refer to Figure 3 and Figure 4.
3.20
effective orifice area
EOA
orifice area that has been derived from flow and pressure or velocity data
Note 1 to entry: For in vitro testing, EOA is defined as:
q
v
RMS
A =
eo
Δp
51,6×
ρ
where
A is the effective orifice area (cm );
eo
is the root mean square forward flow (3.54) (ml/s) during the positive differential pressure peri-
q
V
RMS
od (3.44);
is the mean pressure difference (measured during the positive differential pressure period)
Δp
(mmHg);
ISO 5840-1:2021(E)
ρ is the density of the test fluid (g/cm ).
3.21
end of diastole
ED
end of forward flow (zero crossing of flow to negative) for mitral and tricuspid positions
Note 1 to entry: ED corresponds to the start of valve closure (SC) for the mitral and tricuspid positions. Refer to
Figure 3 and Figure 4.
3.22
end of positive differential pressure
EPDP
second crossing of aortic and left ventricular pressure waveforms for aortic position; second crossing
of pulmonary and right ventricular pressure waveforms for pulmonary position; second crossing of
atrial and ventricular pressure waveforms for mitral and tricuspid position
Note 1 to entry: Refer to Figure 3 and Figure 4.
3.23
end of systole
ES
end of forward flow (zero crossing of flow to negative) for aortic and pulmonary positions
Note 1 to entry: ES corresponds to the start of valve closure (SC) for the aortic and pulmonary positions. Refer to
Figures 3 a) and 4 a).
3.24
end of closure
EC
point in the cardiac cycle at which the valve is fully closed
Note 1 to entry: EC corresponds to the first zero crossing of the flow waveform from negative to positive flow.
Note 2 to entry: If there is no zero crossing from negative to positive flow, EC can be defined from a linear
extrapolation of the maximum slope of the flow to the zero line (refer to Figure 2).
Note 3 to entry: Refer to Figure 3 and Figure 4.
3.25
failure mode
mechanism of device failure (3.18)
Note 1 to entry: Support structure fracture, calcification, and prolapse are examples of failure modes.
3.26
flexible valve
heart valve substitute (3.30) wherein the occluder (3.42) is flexible under physiological conditions (e.g.
bioprostheses)
Note 1 to entry: The orifice ring might or might not be flexible.
3.27
follow-up
continued assessment of patients who have received the heart valve substitute (3.30)
3.28
forward flow volume
volume of flow ejected through the heart valve substitute (3.30) between start of systole (3.61) and end
of systole (3.23) for aortic and pulmonary positions; between start of diastole (3.58) and end of diastole
(3.21) for mitral and tricuspid positions
6 © ISO 2021 – All rights reserved

ISO 5840-1:2021(E)
3.29
fracture
complete separation of any structural component of the heart valve substitute (3.30) that was
previously intact
3.30
heart valve substitute
device used to replace the function of a native valve of the heart
3.31
heart valve system
set of elements provided to replace the native heart valve, consisting of the heart valve substitute,
accessories (3.1), packaging, labelling, and instructions
3.32
implant site
implant position
intended location of heart valve substitute (3.30) implantation or deployment
3.33
intended use
use of a product or process in accordance with the specifications, instructions, and information
provided by the manufacturer
3.34
Kaplan-Meier method
statistical approach for calculating event rates over time when the actual dates of events for each
person in the population are known
3.35
leakage volume
portion of the regurgitant volume (3.49) which is associated with leakage during the closed phase of a
valve in a single cycle (3.13) and is the sum of the transvalvular leakage volume (3.71) and paravalvular
leakage volume (3.45)
Note 1 to entry: Leakage volume is the volume of flow occurring between end of closure (3.24) and start of systole
(3.61) for aortic and pulmonary positions; between end of closure and start of diastole (3.58) for mitral and
tricuspid positions.
3.36
linearized rate
total number of events divided by the total time under evaluation
Note 1 to entry: Generally, the rate is expressed in terms of percent per patient year.
3.37
major bleeding
episode of major internal or external bleeding that causes death, hospitalization, or permanent injury
(e.g. vision loss) or necessitates transfusion
3.38
major paravalvular leak
paravalvular leakage leading to or causing any of the following: death or reintervention; heart failure
requiring additional medication; moderate or severe regurgitation; or haemolytic anaemia
3.39
mean arterial pressure
time-averaged arithmetic mean value of the arterial pressure during one cycle (3.13)
ISO 5840-1:2021(E)
3.40
mean pressure difference
mean pressure gradient
time-averaged arithmetic mean value of the pressure difference across a heart valve substitute (3.30)
during the positive differential pressure period of the cycle (3.13)
3.41
non-structural valve dysfunction
abnormality extrinsic to the heart valve substitute (3.30) that results in stenosis, regurgitation, and/or
haemolytic anaemia
Note 1 to entry: Examples include entrapment by pannus, tissue or suture; paravalvular leak; inappropriate sizing
or positioning, residual leak or obstruction after implantation and clinically important haemolytic anaemia.
This definition excludes infection or thrombosis of the heart valve substitute and intrinsic factors, which cause
structural valve deterioration (3.65). See Reference [14].
3.42
occluder
leaflet
component that inhibits backflow
3.43
pannus
ingrowth of tissue onto or around the heart valve substitute (3.30) which can interfere with normal
functioning
3.44
positive differential pressure period
time period between start of positive differential pressure and end of positive differential pressure
3.45
paravalvular leakage volume
portion of the leakage volume (3.35) that is associated with leakage around the closed heart valve
substitute during a single cycle (3.13)
3.46
prosthetic endocarditis
infection involving a heart valve substitute (3.30)
Note 1 to entry: See Reference [23].
3.47
reference valve
heart valve substitute (3.30) with an established clinical experience used for comparative in vitro
evaluations
Note 1 to entry: The reference valve should approximate the test heart valve substitute in type (if available),
configuration, and size; it may be an earlier model of the same valve, if it fulfils the necessary conditions. The
characteristics of the reference valve should be well documented with clinical data.
3.48
regurgitant fraction
regurgitant volume (3.49) expressed as a percentage of the forward flow volume (3.28)
3.49
regurgitant volume
volume of fluid that flows through a heart valve substitute (3.30) in the reverse direction during one
cycle (3.13) and is the sum of the closing volume (3.9) and the leakage volume (3.35)
Note 1 to entry: Clinically, it might only be possible to measure the leakage volume and might not include the
closing volume.
8 © ISO 2021 – All rights reserved

ISO 5840-1:2021(E)
Note 2 to entry: See Figure 2.
3.50
rigid valve
rigid heart valve substitute
heart valve substitute (3.30) wherein the occluder(s) (3.42) and orifice ring are non-flexible under
physiological conditions (e.g. mechanical heart valves)
3.51
risk
combination of the probability of occurrence of harm and the severity (3.56) of that harm
[SOURCE: ISO 14971:2019, 3.18]
3.52
risk analysis
systematic use of available information to identify hazards and to estimate the associated risks (3.51)
[SOURCE: ISO 14971:2019, 3.19, modified — the word "associated" was added.]
3.53
risk assessment
overall process comprising a risk analysis (3.52) and a risk evaluation
[SOURCE: ISO 14971:2019, 3.20]
3.54
root mean square forward flow
RMS forward flow
square root of the integral of the volume flow rate waveform squared during the positive differential
pressure interval of the forward flow phase used to calculate the EOA
Note 1 to entry: Defining the time interval for flow and pressure measurement as the positive pressure period of
the forward flow interval for EOA computation provides repeatable and consistent results for comparison to the
minimum device performance requirements.
Note 2 to entry: This is calculated using the following formula:
t
qt() dt
v
∫
t
q =
v
RMS
tt−
where
q
is the root mean square forward flow during the positive differential pressure period;
v
RMS
qt() is the instantaneous flow at time (t);
V
t is the time at the start of the positive differential pressure period (3.44);
t is the time at the end of the positive differential pressure period.
Note 3 to entry: The rationale for use of q is that the instantaneous pressure difference is proportional to
v
RMS
the square of instantaneous flow rate and it is the mean pressure difference (3.43) that is required.
Note 4 to entry: See Figure 3 for representative aortic and mitral flow and pressure waveforms from in vitro
testing. See Figure 4 for representative pulmonary and tricuspid flow and pressure waveforms from in vitro
testing.
ISO 5840-1:2021(E)
a)  Aortic valve
b)  Mitral valve
Key
1 aortic pressure A forward flow period
2 left ventricular pressure B closing flow period
3 left atrial pressure C leakage flow period
4 aortic flow rate D positive pressure differential period
5 mitral flow rate
NOTE Dashed vertical lines relate to the flow trace. Solid vertical lines relate to the pressure traces.
Figure 3 — Schematic representation of aortic and mitral flow and pressure waveforms versus
time from in vitro testing
10 © ISO 2021 – All rights reserved

ISO 5840-1:2021(E)
a) Pulmonary valve
ISO 5840-1:2021(E)
b) Tricuspid valve
Key
1 pulmonary pressure A forward flow period
2 right ventricular pressure B closing flow period
3 right atrial pressure C leakage flow period
4 pulmonary flow rate D positive pressure differential period
5 tricuspid flow rate
NOTE Dashed vertical lines relate to the flow trace. Solid vertical lines relate to the pressure traces.
Figure 4 — Schematic representation of pulmonary and tricuspid flow and pressure waveforms
versus time from in vitro testing
3.55
safety
freedom from an unacceptable risk
[SOURCE: ISO 14971:2019, 3.26]
3.56
severity
measure of the possible consequences of a hazard
[SOURCE: ISO 14971:2019, 3.27]
3.57
simulated cardiac output
forward flow volume (3.28) times the heart rate
Note 1 to entry: For in vitro testing, simulated cardiac output (3.8) rather than cardiac output is used:
o = v × r
sc ff b
Note 2 to entry: where
12 © ISO 2021 – All rights reserved

ISO 5840-1:2021(E)
o is the simulated cardiac output;
sc
v is the forward flow volume;
ff
r is the beat rate.
b
3.58
start of diastole
SD
beginning of the forward flow (zero crossing of flow to positive) for mitral and tricuspid positions
Note 1 to entry: Refer to Figure 3 and Figure 4.
3.59
start of leakage
SL
end of closure
Note 1 to entry: Refer to Figure 3 and Figure 4.
3.60
start of positive differential pressure
SPDP
first point in the cardiac cycle at which the pressure on the inflow side of the valve exceeds the pressure
on the outflow side
Note 1 to entry: SPDP can be determined as the first crossing of the aortic and left ventricular pressure waveforms
for the aortic valve position; the first crossing of the pulmonary and right ventricular pressure waveforms for the
pulmonary valve position; or the first crossing of the atrial and ventricular pressure waveforms for the mitral
and tricuspid positions. Refer to Figure 3 and Figure 4.
3.61
start of systole
SS
beginning of the forward flow (zero crossing of flow to positive) for aortic and pulmonary positions
Note 1 to entry: Refer to Figure 3 and Figure 4.
3.62
sterility assurance level
SAL
probability of a single viable microorganism occurring on an item after sterilization (3.63)
Note 1 to entry: It is expressed as the negative exponent to the base 10.
[SOURCE: ISO 11139:2018, 3.275]
3.63
sterilization
validated process used to render a product free from viable microorganisms
Note 1 to entry: In a sterilization process, the rate of microbial inactivation is exponential and thus, the survival
of a microorganism on an individual item can be expressed in terms of probability (3.63). While this probability
can be reduced to a very low number, it can never be reduced to zero.
Note 2 to entry: See 3.62.
[SOURCE: ISO 11139:2018, 3.277, modified — the word "nature" was changed to "rate" and Note 2 to
entry was added.]
ISO 5840-1:2021(E)
3.64
stroke volume
SV
volume of blood pumped by a ventricle in one systolic contraction
3.65
structural valve deterioration
SVD
change in the function of a heart valve substitute (3.30) resulting from an intrinsic abnormality that
causes stenosis or regurgitation
Note 1 to entry: This definition includes intrinsic changes such as wear, fatigue failure, stress fracture, occluder
escape, suture line disruption of components of the prosthesis, calcification, cavitation erosion, leaflet tear,
leaflet abrasion, stent creep, and fabric tear. It excludes extrinsic changes, which cause non-structural valve
dysfunction (3.41).
3.66
support structure
structural components (e.g. stent, frame, housing) of a heart valve substitute (3.30) that houses the
occluder(s) (3.42) and supports valve loading
Note 1 to entry: For a transcatheter valve or a sutureless surgical valve, the support structure may also anchor
the valve within the implant site.
3.67
surgical heart valve substitute
heart valve substitute (3.30) generally requiring direct visualization and cardiopulmonary bypass for
implantation
3.68
systolic duration
systole
portion of a cardiac cycle time corresponding to ventricular contraction
Note 1 to entry: See Figure 3 and Figure 4 for in vitro definition.
3.69
thromboembolism
embolic event involving a clot(s) that occurs in the absence of infection
Note 1 to entry: Thromboembolism might be manifested by a neurological event or an embolic event to another
organ or limb (e.g. ocular, coronary, mesenteric, femoral).
3.70
transcatheter heart valve substitute
heart valve substitute (3.30) delivered through a catheter and implanted in a manner generally not
involving direct visualization and generally involving a beating heart
3.71
transvalvular leakage volume
component of the leakage volume (3.35) that is associated with leakage through the closed valve during
a single cycle (3.13)
3.72
usability
characteristic of the user interface that facilitates use and thereby establishes effectiveness, efficiency,
and user satisfaction in the intended use environment
[SOURCE: IEC 62366-1:2015, 3.16, modified — Note 1 to entry has been deleted.]
14 © ISO 2021 – All rights reserved

ISO 5840-1:2021(E)
3.73
valve thrombosis
thrombus, not caused by infection, attached to or adjacent to the heart valve substitute
4 Abbreviations
For the purposes of this document, the following abbreviations apply.
AP anterio-posterior
AWT accelerated wear testing
BSA body surface area
CT computed tomography
DPIV digital particle image velocimetry
ECG electrocardiogram
EOA effective orifice area
FEA finite element analysis
IEC international electrotechnical commission
IFU instructions for use
LDV laser Doppler velocimetry
LV left ventricle, left ventricular
LVOT left ventr
...