Sizing & Labelling of Replacement Heart Valves: More Than Meets the Eye Who governs standardisation of replacement valves?

 

Tjark Ebels, Benoy Shah & John Chambers

The International Organization for Standards (called ISO in all languages) is the body responsible for setting standards. All medical devices must undergo preclinical and clinical checks before being sold commercially. This includes replacement heart valves, mitral repair rings and all transcatheter devices as well as intracoronary stents and pacemakers.

ISO was founded in 1947 following an initial meeting in London by members of the United Nations Standards Organizing Committee and the International Federation of the International Standardizing Associations. It was originally administered from a private house in Geneva. Its offices are still in Geneva, but the subcommittee on cardiovascular implants and extracorporeal systems,1 is delegated to the American National Standards Institute (ANSI), which is the National Standards Body for the USA. ANSI has subsequently delegated the administration to AAMI, an Association for the Advancement of Medical Instrumentation.2

ISO is a federation of national standards bodies, and its members are nominally the 165 standards organisations of participating countries like the British Standard Institute (BSI). It is funded by membership subscriptions and from the sale of ISO documents, such as Standards.

It produces Standards and other documents primarily on methodology. The first ISO document in 1951 was ‘Standard reference temperatures for industrial length measurement’ and in 1960 it published the standard on quantities and units recommending the SI system. In 1968 the first document on freight containers was published and in 1971 the first technical documents on the environment covering air quality and water quality. The first anti-bribery standards were published in 2016. Altogether ISO has produced 23,587 sets of new or revised standards.

There are three parts of ISO standard 5840 relevant to heart valve replacement revised from five previous editions starting from 1984, while the previous version was published in 2015. These are:

ISO 5840-1: 2021 Part 1: General requirements

ISO 5840-2: 2021 Part 2: Surgically implanted heart valve substitutes

ISO 5840-3: 2021 Part 3: Heart valve substitutes implanted by transcatheter techniques.

In addition, there is ISO Standard 5910 on Cardiac valve repair devices and a new Publicly Available Specification being written on sizing conventions. Documents are produced by a set of technical committees, subdivided into subcommittees and working groups. For heart valves the working group is ISO/TC150/SC2/WG1. New documents go through the steps of proposal, preparation, then committee discussion. The draft document is circulated to all committee members who can respond and vote via their national organization using a set proforma. The committee then meets usually for 5 days to go through the document word for word considering each comment. The general principles are discussed but also the grammar and euphony. A change is made by consensus in the working group. Participating countries vote on Final Drafts of Standards, where each country has 1 vote.3 Sometimes a presentation is made by one of the working group (e.g. on the echocardiographic diagnosis of Structural Valve Deterioration). The new document is then sent to national organisations for a vote of acceptance. Comments outside this structure in time or by other means are not allowed, so the process is well controlled.

It is clearly vital to have standards. However, there are some limitations. The committee on replacement heart valves is composed of anyone with knowledge and expertise relevant to heart valve disease: biological engineers, pathologists, surgeons, physicians, regulators including FDA or BSI and company representatives. There are no rules on what constitutes a minimum acceptable range of expertise or on the proportional breakdown between clinicians and commercial representatives. Clinicians often find it hard to take annual leave and rarely have a supportive budget to cover expenses. This favours commercial dominance. Sometimes the medical director of a company is defined as a clinician rather than a commercial representative. In the last 20 years at least 80% of the membership has been commercial. This dominance is hidden because, according to ISO rules, the identities of the working group members are never published. The standards are advisory so although the FDA, MHRA and other regulatory authorities will tend to recommend them, they may opt not to do so. Commercial concerns have obstructed some important standards, for example the need for regular echocardiograms after implantation to check for early failure since these induce a cost to manufacturers. The biggest problem, which has never been adequately solved, is the labelling of valve size. Why this is a problem is discussed by our President Dr Benoy Shah and possible solutions are given by Professor Tjark Ebels.

John Chambers

References

1. https://www.iso.org/committee/53086.html
2. the American National Standards Institute
3. https://www.iso.org/committee/53086.html?view=participation

 

The problem of valve sizing

Most people presume that a valve labelled 23 mm should fit in a patient aortic annulus 23 mm in diameter. Thus, literature reviews1 and studies of hemodynamic function2 commonly compare valves by labelled size. There was even a tendency at one time to use the label size in place of measuring the LV outflow diameter when calculating effective orifice are by the continuity equation.

 

In fact, the label size is often much bigger than the real patient annulus diameter3-5 (Figure 1). The result is that surgeons are given the impression that these valves are larger than they actually are. This contributes to patient prosthesis mismatch. Severe mismatch leads to increased early post-operative mortality if the LVEF is reduced6. In the mid-term it causes a higher incidence of heart failure7 and limits LV mass regression8. In the long-term it may also contribute to early SVD9.

Manufacturers resist correcting these labelled diameters claiming this would confuse surgeons. Instead they have tried to overcome the problem of PPM by publishing charts showing the likelihood of PPM based on the patient’s BSA and the valve label size. These use EOA derived from echocardiograms performed after implantation. This approach has been criticised10. One obvious problem is that there is an inevitable delay until these data are published. Another problem is the significant variability in echocardiographic valves11. Professor Tjark Ebels will now discuss his proposed solution.

Benoy Shah

References

3. Reisner SA, Meltzer Normal values of prosthetic valve Doppler echocardiographic parameters: A review. J Am Soc Echocardiography 1988; 1: 201-10.
4. Chan V, Kulik A, Tran A, Hendry P, Masters R, Mesana TG, Ruel M. Long-term clinical and hemodynamic performance of the Hancock II versus the Perimount aortic Circulation 2010;122:S10-S16.Blais Circulation 2003;108:983-8.
5. Christakis GT, Buth KJ, Goldman BS, Fremes SE, Rao V, Cohan G, Borger MA, Weisel Inaccurate and misleading valve sizing: A proposed standard for valve size nomenclature. Ann Thorac Surg 1998; 66: 1198-203.
6. Bonchek LI, Burlingame MW, Vazales Accuracy of sizers for aortic valve prostheses. J Thorac Cardiovasc Surg 1987; 94; 632-8.
7. Chambers J, Oo L, Naracott A, Lawford P, Blauth C. Nominal size in six bileaflet mechanical aortic valves: a comparison with orifice size and a biological J Thorac Cardiovasc Surg 2003; 125: 1388-93.
8. Circulation 2003;108:983-8
9. Milano ATS 2002;73:37-43
10. Price Heart 2013-305118
11. Flameng W, Herregods M-C, Vercalsteren M, Herijgers P, Bogaerts K, Meuris Prosthesis-patient mismatch predicts structural valve degeneration in bioprosthetic heart valves. Circulation 121, 2123–2129 (2010).
12. Vriesendorp EHJ CVI 2020
13. Dalmau MJ Interact Cardiov Thorac Surg 2006;5:263-7

What is the solution to the problem of labelling?

The key is to measure the actual size of the valve and also its hemodynamic performance on the packaging rather than data derived from echocardiography. The actual size should equal the labelled size. Manufacturers maintain relabelling valves would confuse surgeons and allegedly be too expensive. Nonetheless, this one time effort would bring size labelling in accordance with the ISO Standard. And it would immediately relate the labelled size in sync with the patient’s annulus. To print the laboratory derived EOA on the box requires the derivation of hemodynamic data with accurate flow measurements in a reproducible laboratory set-up. Not only the manufacturers but also the regulatory authorities are then needed to enforce the ISO Standard.

The two critical measures needed are “inlet orifice diameter” and “prosthesis minimal internal diameter”. ISO is going to suggest using a conical sizer for the inlet orifice of biological replacement valves. This must be of a standard mass and placed into the valve and allowed to descend under its own weight. For supra-annular mechanical valves I suggest using a calliper.

Preliminary measurements of the IOD in the aortic tissue valves mentioned above yielded considerably lower values as compared to the Labelled Sizes. For the Abbott Trifecta the differences, rounded off to whole millimetres are 2-3mm, for the Edwards Magna Ease 1-2mm, for the Medtronic Avalus 1mm, and for the Medtronic Mosaic 4-5mm.

The manufacturer provides a set of valve-related sizers for each SHV model. Sizers are numbered according to the labelled sizes of the corresponding SHVs. Typically, sizers have 2 ends: a cylindrical end (barrel) to measure the annulus and guide SHV selection based on the labelled valve size, and a replica mimicking the configuration of the prosthesis. Sizing with a replica after suture placement is particularly useful because both the patient’s anatomy and the surgeon’s suturing technique influence the SHV’s final position and affect ultimate sizing. Given that the numbering of sizers follows the labelled valve size, the sizer barrel should determine the diameter of the patient’s tissue annulus. Indeed, size measured using the sizer barrel is not intended to provide direct information regarding the physical dimensions of the corresponding SHV. However, past publications have demonstrated significant differences between labelled valve size and the actual dimensions of the valve-related sizer barrel, causing even more confusion in the surgical community.

For the effective internal diameter, the valve needs to be tested under standardised conditions for example steady flow with physiological cycle rates and stroke volumes. The effective area can be calculated with an agreed formula probably the Gorlin formula. The effective internal diameter can then be back-calculated. With these two measures on the box of the replacement valve the surgeon can judge which design and size of valve will fit in the tissue annulus of the patient to give the largest effective orifice area. Diameters connect much more to the surgical frame of mind, than areas, that are commonly used in haemodynamic discussions.

Prof Tjark Ebels

References

1. Elami A, Caplan L, Rudis, How do you spell 21mm? Eur J Cardio-thor Surg 1999;16:253
2. Westaby S, Karp RB, Blackstone EH, Bishop Adult human valve dimensions and their surgical significance. Am J Cardiol 1984;53:552
3. Christakis GT, Buth KJ, Goldman BS, Fremes SE, Rao V, Cohen G, Borger MA, Weisel Inaccurate and misleading valve sizing: a proposed standard for valve size nomenclature. Ann Thorac Surg 1998;66:1198
4. Eichinger W, Däbritz S, Lange Update of the European standards for inactive surgical implants in the area of heart valve prostheses. Eur J Cardio-thor Surg 2007;32:690
5. Youdelman BA, Hirose H, Jain H et Comparison of eight prosthetic aortic valves in a cadaver model. J Thor Cardiovasc Surg 2007;134:1526
6. Bapat V, Mydin I, Chadalavada S, et al. A guide to fluoroscopic identification and design of bioprosthetic valves: a reference for valve-in-valve procedure. Catheter Cardiovasc Int 2013;81:853