EN ISO 5840:2005

SLOVENSKI STANDARD
01-februar-2006
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SIST EN 12006-1:2000
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Cardiovascular implants - Cardiac valve prostheses (ISO 5840:2005)
Herz- und Gefäßimplantate - Herzklappenprothesen (ISO 5840:2005)
Implants cardiovasculaires - Protheses valvulaires (ISO 5840:2005)
Ta slovenski standard je istoveten z: EN ISO 5840:2005
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.

EUROPEAN STANDARD
EN ISO 5840
NORME EUROPÉENNE
EUROPÄISCHE NORM
December 2005
ICS 11.040.40 Supersedes EN 12006-1:1999
English Version
Cardiovascular implants - Cardiac valve prostheses (ISO
5840:2005)
Implants cardiovasculaires - Prothèses valvulaires (ISO Herz- und Gefäßimplantate - Herzklappenprothesen (ISO
5840:2005) 5840:2005)
This European Standard was approved by CEN on 28 February 2005.
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 Central Secretariat 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 Central Secretariat has the same status as the official
versions.
CEN members are the national standards bodies of Austria, Belgium, Cyprus, Czech Republic, Denmark, Estonia, Finland, France,
Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Slovakia,
Slovenia, Spain, Sweden, Switzerland and United Kingdom.
EUROPEAN COMMITTEE FOR STANDARDIZATION
COMITÉ EUROPÉEN DE NORMALISATION
EUROPÄISCHES KOMITEE FÜR NORMUNG
Management Centre: rue de Stassart, 36  B-1050 Brussels
© 2005 CEN All rights of exploitation in any form and by any means reserved Ref. No. EN ISO 5840:2005: E
worldwide for CEN national Members.

Foreword
The text of ISO 5840:2005 has been prepared by Technical Committee ISO/TC 150 "Implants for surgery" of
the International Organization for Standardization (ISO) and has been taken over as EN ISO 5840:2005 by
Technical Committee CEN/TC 285 "Non-active surgical implants", the secretariat of which is held by NEN.

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 June 2006, and conflicting national standards shall be withdrawn at
the latest by June 2006.
This document supersedes EN 12006-1:1999.

This document has been prepared under a mandate given to CEN by the European Commission and the
European Free Trade Association, and supports essential requirements of EU Directive(s).

For relationship with EU Directive(s), see informative Annex ZA, which is an integral part of this document.

According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following
countries are bound to implement this European Standard: Austria, Belgium, Cyprus, Czech Republic,
Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland
and United Kingdom.
Endorsement notice
The text of ISO 5840:2005 has been approved by CEN as EN ISO 5840:2005 without any modifications.

ANNEX ZA
(informative)
Relationship between this International Standard and the Essential
Requirements of EU Directive 93/42

By agreement between ISO and CEN, this CEN annex is included in the DIS and the FDIS but will not
appear in the published ISO standard.

This International Standard has been prepared under a mandate given to CEN by the European Commission
to provide one means of conforming to Essential Requirements of the New Approach Directive 93/42.

Once this standard is cited in the Official Journal of the European Communities under that Directive and has
been implemented as a national standard in at least one Member State, compliance with the normative
clauses of this standard given in Table ZA.1 confers, within the limits of the scope of this standard, a
presumption of conformity with the corresponding Essential Requirements of that Directive and associated
EFTA regulations.
Table ZA.1 — Correspondence between this International Standard and Directive 93/42
Clauses/Subclauses Essential Requirements Qualifying remarks/Notes
of the Standard of Directive 93/42
5 1, 2, 3, 6
6.1 1, 3
6.2.1 and 6.2.2 3, 4 Procedure for quality system (design input) aiming at
supporting general ERs 3 and 4
6.2.3 with annex P 3, 5, 8.1, 8.3
6.2.3 with annex Q 13.1, 13.3, 13.4, 13.5, 13.6
6.2.3 with annex S 8.1, 8.3, 8.4
6.3 and 6.4 Elements of procedure for Quality system aiming at
supporting all safety and performance ERs
6.5 Elements of procedure for risk management
7.1, 7.2.1 Elements of procedure for quality system aiming at
supporting all safety and performance ERs
7.2.2 1, 7.1, 8.2, 9.2, 12.7.1
7.2.3 3, 4
7.2.4 3, 4, 9.2, 12.7.1
7.3 1, 6 Preclinical in vivo evaluation also aims at reducing the
risks for human subjects undergoing clinical
investigations
7.4 with annex R 14
WARNING: Other requirements and other EU Directives may be applicable to the product(s) falling within
the scope of this standard.
INTERNATIONAL ISO
STANDARD 5840
Fourth edition
2005-03-01
Cardiovascular implants — Cardiac valve
prostheses
Implants cardiovasculaires — Prothèses valvulaires

Reference number
ISO 5840:2005(E)
©
ISO 2005
ISO 5840:2005(E)
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ii © ISO 2005 – All rights reserved

ISO 5840:2005(E)
Contents Page
Foreword. v
Introduction . vi
1 Scope. 1
2 Normative references. 1
3 Terms and definitions. 2
4 Abbreviations. 10
5 Fundamental requirements. 11
6 Device description. 11
6.1 Intended use. 11
6.2 Design inputs. 11
6.2.1 Operational specifications. 11
6.2.2 Performance specifications. 12
6.2.3 Packaging, labelling, and sterilization . 13
6.3 Design outputs. 13
6.3.1 General. 13
6.3.2 Examples of components of some heart valve substitutes . 13
6.4 Design transfer (manufacturing qualification). 14
6.5 Risk management. 14
6.5.1 Hazard identification. 14
6.5.2 Failure mode identification. 14
6.5.3 Risk estimation. 15
6.5.4 Risk evaluation. 15
6.5.5 Risk control. 15
6.5.6 Risk review. 15
7 Verification testing and analysis/Design validation . 15
7.1 General requirements. 15
7.2 In vitro assessment. 16
7.2.1 Test conditions, sample selection and reporting requirements . 16
7.2.2 Material property assessment. 16
7.2.3 Hydrodynamic performance assessment. 17
7.2.4 Structural performance assessment. 18
7.3 Preclinical in vivo evaluation. 19
7.3.1 Overall requirements. 19
7.3.2 Methods. 20
7.3.3 Test report. 20
7.4 Clinical investigation. 21
7.4.1 Principle. 21
7.4.2 General. 21
7.4.3 Number of institutions. 21
7.4.4 Number of patients . 21
7.4.5 Duration of the study. 22
7.4.6 Clinical data requirements. 22
7.4.7 Clinical investigation report. 24
Annex A (informative) Rationale for the provisions of this International Standard . 26
Annex B (informative) Heart valve substitute hazards, associated failure modes and
evaluation methods . 29
Annex C (informative) Risk assessment guidelines . 31
ISO 5840:2005(E)
Annex D (informative) Examples and definitions of some physical and material properties of heart
valve substitutes and their components .38
Annex E (informative) Statistical procedures when using performance criteria .43
Annex F (informative) In vitro procedures for testing unstented or similar valves
in compliant chambers .44
Annex G (informative) Preclinical in vivo tests.46
Annex H (informative) Echocardiographic protocol.49
Annex I (informative) Description of the heart valve substitute.52
Annex J (informative) Figures of examples of components of some heart valve substitutes .54
Annex K (informative) Examples of standards applicable to testing of materials and components
of some heart valve substitutes.57
Annex L (informative) Guidelines for verification of hydrodynamic performance .63
Annex M (informative) Durability testing.69
Annex N (informative) Examples of design specific testing.71
Annex O (informative) Fatigue assessment .73
Annex P (normative) Packaging.77
Annex Q (normative) Labelling and instructions for use .78
Annex R (normative) Methods of evaluating clinical data.80
Annex S (normative) Sterilization .82
Bibliography.83

iv © ISO 2005 – All rights reserved

ISO 5840:2005(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.
International Standards are drafted in accordance with the rules given in the ISO/IEC Directives, Part 2.
The main task of technical committees is to prepare International Standards. Draft International Standards
adopted by the technical committees are circulated to the member bodies for voting. Publication as an
International Standard requires approval by at least 75 % of the member bodies casting a vote.
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.
ISO 5840 was prepared by Technical Committee ISO/TC 150, Implants for surgery, Subcommittee SC 2,
Cardiovascular implants and extracorporeal systems.
This fourth edition cancels and replaces the third edition (ISO 5840:1996), which has been technically revised
to include risk management.
ISO 5840:2005(E)
Introduction
There is, as yet, no heart valve substitute that can be regarded as ideal.
This International Standard has been prepared by a group well aware of the problems associated with heart
valve substitutes and their development. In several areas, the provisions of this International Standard have
been deliberately left open as there has been no wish to inhibit development and innovation. It does specify
types of tests, test methods and/or requirements for test apparatus, and requires documentation of test
methods and results. The areas with which this International Standard is concerned are those which will
ensure that associated risks to the patient and other users of the device have been adequately mitigated,
facilitate quality assurance, aid the surgeon in choosing a heart valve substitute, and ensure that the device
will be presented at the operating table in a convenient form. Emphasis has been placed on specifying types
of in vitro testing, on preclinical in vivo and clinical evaluations, on reporting of all in vitro, preclinical in vivo
and clinical evaluations and on 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, this International Standard also covers important hydrodynamic
and durability characteristics of heart valve substitutes. The exact test methods for hydrodynamic and
durability testing have not been specified, but guidelines for the test apparatus are given.
This International Standard is incomplete in several areas. It is intended to be revised, updated, and/or
amended, as knowledge and techniques in heart valve substitute technology improve.
Annexes A to S provide supplementary information, the content of Annexes P to S being necessary for the
application of this International Standard.

vi © ISO 2005 – All rights reserved

INTERNATIONAL STANDARD ISO 5840:2005(E)

Cardiovascular implants — Cardiac valve prostheses
1 Scope
1.1 This International Standard is applicable to all devices intended for implantation in human hearts, as a
heart valve substitute.
1.2 This International Standard is applicable to both 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 heart valve substitute to be implanted.
1.3 This International Standard outlines an approach for qualifying 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 may include those to assess the physical, chemical, biological
and mechanical properties of heart valve substitutes and of their materials and components. The tests may
also include those for pre-clinical in vivo evaluation and clinical evaluation of the finished heart valve substitute.
1.4 This International Standard imposes design specifications and minimum performance specifications for
heart valve substitutes where adequate scientific and/or clinical evidence exists for their justification.
1.5 This International Standard excludes heart valve substitutes designed for implantation in artificial hearts
or heart assist devices.
NOTE A rationale for the provisions of this International Standard is given in Annex A.
2 Normative references
The following referenced documents are indispensable for the application 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 8601:2000, Data elements and interchange formats — Information interchange — Representation of
dates and times
ISO 10993-1:1997, Biological evaluation of medical devices — Part 1: Evaluation and testing
ISO 10993-2:1992, Biological evaluation of medical devices — Part 2: Animal welfare requirements
ISO 11134:1994, Sterilization of health care products — Requirements for validation and routine control —
Industrial moist heat sterilization
ISO 11135:1994, Medical devices — Validation and routine control of ethylene oxide sterilization
ISO 11137:1995, Sterilization of health care products — Requirements for validation and routine control —
Radiation sterilization
ISO 11607:2003, Packaging for terminally sterilized medical devices
ISO 13485, Medical devices — Quality management systems — Requirements for regulatory purposes
ISO 14155-1:2003, Clinical investigation of medical devices for human subjects — Part 1: General requirements
ISO 5840:2005(E)
ISO 14160, Sterilization of single-use medical devices incorporating materials of animal origin — Validation
and routine control of sterilization by liquid chemical sterilants
1)
ISO 14630:— , Non-active surgical implants — General requirements
ISO 14937:2000, 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 14971:2000, Medical devices — Application of risk management to medical devices
EN 12442-1, Animal tissues and their derivatives utilized in the manufacture of medical devices — Part 1:
Analysis and management of risk
EN 12442-2, Animal tissues and their derivatives utilized in the manufacture of medical devices — Part 2:
Controls on sourcing, collection and handling
EN 12442-3, Animal tissues and their derivatives utilized in the manufacture of medical devices — Part 3:
Validation of the elimination and/or inactivation of viruses and transmissible agents
Guidelines for reporting morbidity and mortality after cardiac valvular operations, American Association for
Thoracic Surgery, European Association for Cardiothoracic Surgery, Society of Thoracic Surgeons, Annals of
Thoracic Surgery, 62, pp. 932-935, 1996
3 Terms and definitions
For the purposes of this document, the following terms and definitions apply.
3.1
accessories
device-specific tools that are required to assist in the implantation of the heart valve substitute
3.2
actuarial
statistical technique for estimating survival curves prior to the death of the last member of a cohort
NOTE Some examples are the “Kaplan-Meier” technique and the “life-table” technique.
3.3
anticoagulant-related haemorrhage
internal or external bleeding that causes death or stroke, or that requires transfusion, operation or
hospitalization
NOTE This definition is restricted to patients who are receiving anticoagulants and/or antiplatelet drugs, and excludes
minor bleeding events.
3.4
arterial diastolic pressure
minimum value of the arterial pressure during diastole
3.5
arterial peak systolic pressure
maximum value of the arterial pressure during systole

1) To be published. (Revision of ISO 14630:1997)
2 © ISO 2005 – All rights reserved

ISO 5840:2005(E)
3.6
back pressure
differential pressure applied across the closed valve
3.7
blood-equivalent fluid
fluid whose physical properties, e.g. specific gravity, viscosity, approximate those of blood
3.8
closing volume
component of the regurgitant volume that is associated with the dynamics of valve closure during a single
cycle
See Figure 1.
3.9
control valve
heart valve substitute for preclinical and clinical evaluations of similar design and constructed of similar
material as the investigational device
NOTE The control valve should have a known clinical history.

Key
X time
Y flowrate
1 closing volume
2 leakage volume
Figure 1 — Schematic representation of flow waveform and regurgitant volumes for one cycle
ISO 5840:2005(E)
3.10
cumulative incidence
statistical technique where events other than death can be described by the occurrence of the event over time
without including death of the subjects
NOTE Cumulative incidence is also known as ‘actual’ analysis.
3.11
cycle
one complete sequence in the action of a heart valve substitute under pulsatile-flow conditions
3.12
cycle rate
number of complete cycles per unit of time, usually expressed as cycles per minute (cycles/min)
3.13
design verification
establishment by objective evidence that the design output meets the design input requirements
3.14
design validation
establishment by objective evidence that device specifications conform with user needs and intended use(s)
3.15
effective orifice area
A
EO
orifice area that has been derived from flow and pressure or velocity data
3.16
failure
inability of a device to perform its intended function at any point during its intended lifetime
NOTE The inability to perform the intended function may manifest itself as a reduced operating effectiveness and/or
as hazards.
3.17
failure mode
mechanism of failure which can result in a hazard
NOTE Stent fracture, calcification and prolapse are examples of failure modes.
3.18
flexible heart valve substitute
heart valve substitute wherein the occluder is flexible under physiological conditions
NOTE The orifice ring may or may not be flexible. This category was previously known as biological heart valve
substitute because of the biological source of the flexible occluder(s) but, at a minimum, should also include flexible
polymer occluder(s).
3.19
forward-flow phase
portion of the cycle time during which forward flow occurs through a heart valve substitute
3.20
hazard
known or potential source of harm which results from a given failure mode
4 © ISO 2005 – All rights reserved

ISO 5840:2005(E)
3.21
harm
physical injury or damage to the health of the patient or end-user of the device
[14]
NOTE Adapted from ISO/IEC Guide 51:1999 , definition 3.3.
3.22
heart valve substitute
device used to replace or supplement a natural valve of the heart
See also 3.18 and 3.48, and examples in Figures J.1, J.2, J.3, J.4 and J.5.
3.23
intended use
use of a product, process or service in accordance with the specifications, instructions and information
provided by the manufacturer
3.24
internal orifice area
IOA
numerical indication of the area within a prosthetic heart valve through which blood flows
See Figure 2.
3.25
intra-annular sewing ring
sewing ring designed to secure the heart valve wholly or mostly within the patient’s tissue annulus
See Figure 2. See also 3.24, 3.66 and 3.70.
3.26
intrasupra-annular sewing ring
sewing ring designed to secure a portion of the valve or sewing ring above the patient’s tissue annulus and
also some portion of the valve within the patient’s tissue annulus
See Figure 2. See also 3.24, 3.66 and 3.70.

intra-annular intrasupra-annular supra-annular
Key
1 IOA
2 TAD
3 ESRD
ISO 5840:2005(E)
Figure 2 — Designation of dimensions of heart valve substitute sewing ring configurations
3.27
isolated (aortic or mitral) heart valve substitute
implantation of single heart valve substitute excluding patients who have a second heart valve substitute in a
different anatomical position
NOTE Concomitant procedures, including valve repair, coronary artery bypass, and ascending aortic aneurysm
repair, are not relevant to this definition. See 7.4.4.
3.28
leakage volume
component of the regurgitant volume which is associated with leakage through the closed valve during a
single cycle
NOTE The point of separation between the closing and leakage volumes is obtained according to a defined and
stated criterion (the linear extrapolation shown in Figure 1 is just an example).
3.29
linearized rate
linearized rate for a complication is the total number of events divided by the total time under evaluation
NOTE Generally, the rate is expressed in terms of percent per patient year.
3.30
long term follow-up
continued (after regulatory approval) periodic assessment of patients who have received the heart valve
substitute during the clinical evaluation
3.31
manufacturer
organization with responsibility for the design, manufacture, packaging or labelling of a medical device,
assembling a system, or adapting a medical device before it is placed on the market, regardless of whether
these operations are carried out by the organization or on their behalf by a third party
3.32
mean arterial pressure
time-averaged arithmetic mean value of the arterial pressure during one cycle
3.33
mean pressure difference
time-averaged arithmetic mean value of the pressure difference across a heart valve substitute during the
forward-flow phase of the cycle
NOTE The use of “mean pressure gradient” for this term is deprecated.
3.34
nonstructural dysfunction
abnormality resulting in stenosis or regurgitation of the heart valve substitute that is not intrinsic to the valve
itself
NOTE This dysfunction is exclusive of valve thrombosis, systemic embolus or infection diagnosed at re-operation,
autopsy or in vivo investigation. Examples include entrapment by pannus or suture, paravalvular leak, inappropriate sizing,
and significant haemolytic anaemia.
3.35
occluder
component(s) of a heart valve substitute, such as rigid or flexible leaflets, discs, and balls, that move(s) to
inhibit backflow
6 © ISO 2005 – All rights reserved

ISO 5840:2005(E)
NOTE The occluders of flexible heart valve substitutes are typically called “leaflets” or “cusps”.
3.36
operative mortality
death from any cause during operation or within 30 d of the operation
3.37
outflow tract profile height
maximum distance that the valve extends axially into the outflow tract in the open or closed position,
whichever is greater, measured from the valve structure intended to mate with the top (atrial or aortic side) of
the patient's annulus
3.38
pannus
ingrowth of tissue into the heart valve substitute which may interfere with normal functioning
3.39
paravalvular leak
clinically or haemodynamically detectable defect between the heart valve substitute and the patient's annulus
NOTE The term “perivalvular” is deprecated.
3.40
probability
statistical likelihood that a specific event will occur
3.41
process validation
establishing, by objective evidence, that a process consistently produces a result or product that meets its
predetermined specifications
3.42
profile height
maximal axial dimension of a heart valve substitute in the open or closed position, whichever is greater
3.43
prosthetic valve endocarditis
infection involving a heart valve substitute
NOTE Diagnosis is based on customary clinical criteria, including an appropriate combination of positive blood
cultures, clinical signs (fever, new or altered cardiac murmurs, splenomegaly, systemic embolus or immunopathologic
lesions) and/or histologic confirmation of endocarditis at reoperation or autopsy. Morbidity associated with active infection
such as valve thrombosis, embolus or paravalvular leak is included under this category and is not included in other
categories of morbidity.
3.44
quasi-real time durability testing
long-term durability testing performed at a cycle rate between normal and high normal (up to 200 cycles/min)
3.45
reference valve
heart valve substitute used to assess the conditions established in the in vitro tests used to evaluate the test
heart valve substitute
NOTE The reference valve should approximate the test heart valve substitute in type, configuration and tissue
annulus diameter; it may be an earlier model of the same valve, if it fulfills the necessary conditions. The characteristics of
the reference valve should be well documented with clinical data.
ISO 5840:2005(E)
3.46
regurgitant fraction
regurgitant volume expressed as a percentage of the stroke volume
3.47
regurgitant volume
volume of fluid that flows through a heart valve substitute in the reverse direction during one cycle and is the
sum of the closing volume and the leakage volume
See Figure 1.
3.48
rigid heart valve substitute
heart valve substitute wherein the occluder(s) and orifice ring are non-flexible under physiological conditions
NOTE This category was previously known as mechanical heart valve substitute. Materials of construction of the rigid
components of rigid heart valve substitutes have historically been metals, pyrolytic carbon and polymers.
3.49
risk
combination of the probability of occurrence of harm and the severity of that harm
[14]
[ISO/IEC Guide 51:1999 , definition 3.2]
3.50
risk analysis
systematic use of available information to identify hazards and to estimate the associated risks
[14]
NOTE Adapted from ISO/IEC Guide 51:1999 , definition 3.10.
3.51
risk assessment
overall process comprising a risk analysis and a risk evaluation
[14]
[ISO/IEC Guide 51:1999 , definition 3.12]
3.52
risk control
process through which decisions are reached and protective measures are implemented for reducing risks to,
or maintaining risks within, specified levels
3.53
risk estimation
process used to assign values to the probability and consequences of a risk
3.54
risk evaluation
judgment, on the basis of risk analysis, of whether an acceptable level of risk has been achieved in a given
context based on the current values of society
[14]
NOTE Adapted from ISO/IEC Guide 51:1999 , definitions 3.7 and 3.11.
3.55
risk management
systematic application of management policies, procedures and practices to the tasks of analysing, evaluating
and controlling risk
8 © ISO 2005 – All rights reserved

ISO 5840:2005(E)
3.56
root mean square forward flow
RMS forward flow
square root of the integral of the volume flow waveform squared
NOTE 1 This is calculated using Equation (1).
t
qt() dt
v
∫
t
q = (1)
v
RMS
tt−
where
q is root mean square forward flow;
v
RMS
q(t) is instantaneous flow at time t;
t is time at start of forward flow;
t is time at end of forward flow.
NOTE 2 The rationale for use of q is that the instantaneous pressure difference is proportional to the square of

v
RMS
instantaneous flow rate, and it is the mean pressure difference that is required.
3.57
safety
freedom from unacceptable risk
[14]
[ISO/IEC Guide 51:1999 , definition 3.1]
3.58
severity
measure of the possible consequences of a hazard
3.59
simulated cardiac output
net fluid volume forward flow per minute, through a test heart valve substitute
3.60
special processes
those processes for which the product cannot be fully verified by inspection or test
3.61
sterile
free from viable micro-organisms
3.62
sterility assurance level
SAL
probability of a viable micro-organism being present on a product after sterilization
3.63
sterilization
validated process used to render a product free from all forms of viable micro-organisms
3.64
stroke volume
volume of fluid moved through a test heart valve substitute in the forward direction during one cycle
3.65
structural deterioration
change in the function of a heart valve substitute resulting from an intrinsic abnormality that causes stenosis
or regurgitation
ISO 5840:2005(E)
NOTE This definition excludes infection or pannus overgrowth, or thrombosis of the heart valve substitute as
determined by reoperation, autopsy or in vivo investigation. It includes intrinsic changes such as wear, fatigue failure,
stress fracture, occluder escape, calcification, cavitation erosion, leaflet tear and stent creep.
3.66
supra-annular sewing ring
sewing ring designed to secure the valve wholly above the patient’s tissue annulus
See Figure 2.
3.67
systemic embolism
clot or other particulate matter, not associated with infection, originating on or near the heart valve substitute
and transported to another part of the body
NOTE Diagnosis may be indicated by a new, permanent or transient, focal or global neurologic deficit (exclusive of
haemorrhage) or by any peripheral arterial embolus unless proved to have resulted from another cause (e.g. atrial
myxoma). Patients who do not awaken post-operatively or who awaken with a stroke or myocardial infarction are excluded.
Acute myocardial infarction that occurs after operation is arbitrarily defined as an embolic event in patients with known
normal coronary arteries or who are less than 40 y of age.
3.68
tissue annulus diameter
TAD
diameter in millimetres of the smallest flow area within the patient’s valve annulus
3.69
validation
confirmation by examination and provision of objective evidence that the particular requirements for a specific
intended use can be consistently fulfilled
3.70
valve size
manufacturer's designation of a heart valve substitute which indicates the tissue annulus diameter (TAD in
millimetres) of the patient into whom the heart valve substitute is intended to be implanted (i.e., TAD =
designated valve size)
NOTE This takes into consideration the manufacturer's recommended implant position relative to the annulus and the
suture technique. See also A.7, Q.2.2 c), Q.2.3 b) and Q.2.3 g).
3.71
valve thrombosis
blood clot, not associated with infection, causing dysfunction of the heart valve substitute
NOTE Diagnosis may be proved by operation, autopsy or clinical investigation (e.g. echocardiography,
angiocardiography or magnetic resonance imaging).
3.72
verification
confirmation by examination and provision of objective evidence that specified requirements have been
fulfilled
4 Abbreviations
For the purposes of this document, the following abbreviations apply.
A Body Surface Area
BS
A Effective Orifice Area
EO
10 © ISO 2005 – All rights reserved

ISO 5840:2005(E)
AF Atrial Fibrillation
ALARP As Low As Reasonably Practicable
AWT Accelerated Wear Testing
BSE Bovine Spongiform Encephalopathy
CFD Computational Fluid Dynamics
ECG Electrocardiogram
ESRD External Sewing Ring Diameter
FEA Finite Element Analysis
FMEA Failure Mode and Effect Analysis
FTA Fault Tree Analysis
IFU Instructions For Use
INR International Normalized Ratio
IOA Internal Orifice Area
OPC Objective Performance Criteria
PROB Probability Rating
RIND Reversible Ischemic Neurological Deficits
RPN Risk Priority Number = SEV × PROB
SEV Hazard Severity Rank
SEM Scanning Electron Microscopy
TAD Tissue Annulus Diameter
5 Fundamental requirements
The manufacturer shall determine, at all stages of the product life cycle, the acceptability of the product for
clinical use. The requirements of ISO 14971 and ISO 13485 shall apply.
6 Device description
6.1 Intended use
The manufacturer shall identify the physiological condition(s) to be treated, the intended patient population,
potential adverse events and intended claims.
6.2 Design inputs
6.2.1 Operational specifications
The manufacturer shall define the operational specifications for the device, including the principles of
operation, expected device lifetime, shelf life, shipping/storage limits, and the physiological environment in
which it is intended to function. Table 1 defines the expected physiological parameters of the intended patient
population for heart valve substitutes for both normal and pathological patient conditions.
ISO 5840:2005(E)
Table 1 — Heart valve substitute operational environment
Parameter Description
Surrounding medium: Human heart/Human blood
Temperature: 34 °C to 42 °C
Heart rate: 30 beats/min to 200 beats/min
Cardiac output: 3 l/min to 15 l/min
Stroke volume: 25 ml to 100 ml
Differential pressure across
Arterial peak systolic Arterial diastolic
closed valve
Blood pressures and resultant
pressure pressure
pressure loads by patient condition: Aortic ∆p Mitral ∆p
A M
mm Hg mm Hg
mm Hg mm Hg
Normotensive 100 to 130 65 to 85 95 115
Hypotensive 60 40 50 60
Hypertensive
Stage 1 (mild) 140 to 159 90 to 99 123 150
Stage 2 (moderate) 160 to 179 100 to 109 138 170
Stage 3 (severe) 180 to 209 110-119 155 195
Stage 4 (very severe) > 210 > 120 185 210
Extreme (expected maximum
300 160 230 300
pressure for a single cycle)
6.2.2 Performance specifications
6.2.2.1 The manufacturer shall establish (i.e. define, document and implement) the clinical performance
requirements of the device and the corresponding device performance specification
...