Heart valve manufacturers deceive surgeons and patients

Companies that manufacture heart valves are widely mislabelling their products, which can have major consequences for patients. When a cardiac surgeon from Groningen exposed the problem, he sparked a battle that has raged for years.

Tjark Ebels, a heart surgeon at the University Medical Center Groningen, has a collection of heart valves at home. He has taken them apart piece by piece, and measured them accurately. At the end of 2014, he discovered something very wrong with several manufacturers’ valves: they were not the size they claimed to be.

About 1,500 heart valves are implanted each year in the Netherlands alone. In January 2019, the Universities of Quebec, Canada and Pernambuco, Brazil published a study showing that out of 100,000 patients, more than half received an incorrectly sized valve. The risk of mortality rises from 1 per cent to 1.5 per cent when a heart valve is too small, an additional 500 deaths per 100,000 operations. Other patients continue to suffer, and may need further surgery. The researchers conclude that it is essential for patients to be fitted with the correct valve.

‘The most important dimension, the inner diameter, is regularly many millimetres different from what’s stated on the packaging,’ Ebels explains. ‘This applies to all the major players in the market, although some are more inaccurate than others. But no manufacturer uses the correct size.’ This affects valves from Medtronic, LivaNova, Edwards Lifesciences and Abbott, amongst others.

George Schut, director of Schut Geometric Measurement Technology, meticulously measured the valves together with Ebels in October 2019. ‘I was dumbfounded,’ he says. ‘That can’t be true, can it?’

Follow the Money has presented these findings to cardiologists in recent weeks, and they have also been surprised. One, Jobst Winter, said: ‘I had no idea this was happening. Why on earth are the manufacturers doing this?’

Cardiac surgeons sometimes know about the problem. Robert Klautz, cardiac surgeon at Leiden University Medical Center and Amsterdam UMC, told us: ‘My teachers warned me decades ago: you should never presume that if it says 25 millimetres on the package, it’s true. That says it all. I was warned about this even then.’

Manufacturers’ stated dimensions are also inconsistent: company A’s 23-millimetre valve may be the same size as company B’s 25-millimetre one. ‘That’s very confusing for surgeons,’ Klautz says. ‘The manufacturers want us to believe that we can buy a larger valve from them than from their competitors. As a doctor, you want to place as large a valve as possible in patients. The bigger the valve, the less resistance and the easier it is for the blood to flow through the body.’ The crux of the matter is that the valves often turn out to be smaller than manufacturers claim.

Harmful effects for the patient
And that is risky, says Mohamed Soliman Hamad, a heart surgeon at the Catharina Hospital in Eindhoven. ‘The size determines whether the valve will function properly or not. If you place a valve that’s too small, it will cause a narrowing, making it more difficult for the blood to flow through the aorta. It’s as simple as that.’

When a patient needs a new valve, the cardiologist refers them to the surgeon, who carries out the operation and then sends them back to the cardiologist. Cardiologist Winter says: ‘Some of my patients don’t recover after valve surgery, and continue to have shortness of breath and chest pain.’ He says it is often impossible to find out whether these complaints are due to a heart valve that is too small. ‘Although the type and size are listed in the operative report, its size may not correspond to reality. This is alarming, because it is commonly known that if the valve is too small, it can cause short- and long-term problems.’

Follow the Money’s questions to suppliers received little response. LivaNova said it was following the rules, and Medtronic did not reply. Edwards Lifesciences denied there was a problem, saying: ‘It is incorrect to suggest that our valves are incorrectly labelled. We provide doctors with measurement devices that fit the valves, so we can guarantee accurate sizing for each patient.’ And Abbott responded with a platitude: ‘[We have] made recommendations regarding the correct valve sizes and treatment to ensure optimal results.’

But Ebels and Schut, who measured all the valves in detail, came to a different conclusion. Says Ebels: ‘Manufacturers may fear that patients will sue if they know that a valve that’s too small may have caused their injury’.

The international task force on valve label sizes
In 2014, Ebels submitted a proposal to the International Organization for Standardization (ISO), calling for changes in the sizes stated on packaging. The ISO is a federation of 165 national standardisation bodies that considers proposals to improve standards; each country has one vote.

The ISO working group on heart valves, representing a few cardiac surgeons (including Ebels) and manufacturers, meets to discuss new guidelines. Its membership is confidential, but documents seen by Follow the Money show that Medtronic, Boston Scientific, Abbott, LivaNova, and Edwards Lifesciences are represented.

‘Initially I was under the naive impression that manufacturers would actually adjust the size labels,’ says Ebels. ‘But after the new ISO standard was published in 2015, clearly stating that they had to change the packaging information, nothing changed.’

Ebels then tried to put the label problem on the international agenda by publications and giving lectures. In 2016, for example, he gave a presentation in Venice explaining the problem to colleagues. There, he found an ally in Duke Cameron, a heart surgeon at Massachusetts General Hospital and former head of cardiac surgery at Johns Hopkins University School of Medicine.

Cameron presented Ebels’ findings to his professional body, the American Association for Thoracic Surgery (AATS). In October 2017, along with the European Association for Cardio-Thoracic Surgery (EACTS) and the Society of Thoracic Surgeons (STS), it set up a valve labelling task force to deal with the issue and that would exert pressure by publishing recommendations from the surgeons. The task force consists of cardiac surgeons, cardiologists, the chairman of the ISO working group, and representatives of the manufacturers.

This trajectory runs parallel to the ISO working group on heart valves, which also concerns itself with labelling. Ebels is a member of both groups at that point in time.

‘We’ve been fooled’
Ebels is optimistic. At the task force’s first meeting, in Paris in February 2018, he is one of the speakers. He even thinks that he can get manufacturers onside. They seem to be aware of the damage patients can suffer if they are implanted with the wrong valve. Now I have to press ahead, Ebels thought, and emailed Domenico Pagano, the secretary general of EACTS, to ask if he could give a presentation in England about valve labelling. He gets no response.

In the spring of 2018, Ebels emails Pagano again, asking to speak on behalf of EACTS at the ISO working group’s semi-annual meeting in San Diego. ‘It would give me great pleasure if I could voice the opinion of a substantial proportion of the worlds’ cardiac surgeons,’ he wrote. ‘It would strengthen my position within the working group, and with that the position of EACTS.’

Pagano rejects the request, describing it as ‘complicated’. In September 2018, the San Diego meeting takes place. Despite not being able to speak on EACT’s behalf, Ebels manages to gain a lot of support from colleagues. And then there’s an important breakthrough: the manufacturers agree to adjust the size labels on the packaging.

In January 2019, there is another meeting in San Diego, this time of the task force. Ebels could not physically attend, but participated via a poor internet connection. When he later receives the minutes, he notes with disbelief that the valve relabelling has suddenly been dropped.

In May 2019, Ebels organises a three-day ISO working group meeting at the Amsterdam UMC to discuss the issue once again. The forty participants included only a few scientists and two surgeons, Ebels being one of them.

The outcome of the meeting was disastrous: the new labelling scheme was torpedoed. Ebels says he cannot go into detail, for confidentiality reasons, but found the arguments ‘improper’ and unscientific to say the least. The ISO’s rules specify that any change must be adopted by consensus.

The bottom line is that the relabelling has been sidetracked,’ Ebels says. ‘I was incensed that there was no consensus on this essential improvement in the care of these heart patients.’ He emailed Ruggero De Paulis, then president of EACTS, but to no avail.

Wearing two hats at once
EACTS relies heavily on the industry. During its three-day annual conference, manufacturers can promote and show their products, and pay large sums for stands, auditorium sessions, and other facilities. The 2019 conference earned it almost €5 million, and according to its annual report, the event is its main source of income. EACTS uses the money to provide grants and scholarships, give advice, sponsor studies, run courses, and publish scientific journals.

Most of the surgeons and cardiologists on the task force also act as consultants for one or more manufacturers. They participate in advisory committees, provide training for manufacturers, and carry out research sponsored by them. De Paulis is no different: he is a consultant for Medtronic and Edwards Lifesciences.

Arie Pieter Kappetein, a cardiac surgeon at Erasmus University Medical Center (Erasmus MC), was EACTS’ secretary general for 9 years until August 2017, and then became vice president of Medtronic and leader of the task force. His assistant Stuart Head was involved in writing treatment guidelines on behalf of EACTS until 2018. In February 2019, he too joined Medtronic. Both Kappetein and Head remained on the task force after their career switch, but now as industry representatives. Andras Durko has been a member of the task force since its inception, and was listed there as a cardiac surgeon, but was a physician-researcher for Kappetein, and in that capacity conducted studies sponsored by Medtronic.

Ebels protested against this state of affairs, saying that it made the official Medtronic delegation ‘too dominant’.

In the United States, doctors are required to report outside interests, and manufacturers of medicines and medical devices must enter all payments larger than $10 in the federal Open Payments Data Register. This shows that members of the task force also received fees from manufacturers (see box), and were also regularly paid for their hotels and dinners. In the Netherlands, doctors are required to report their financial relationships to the healthcare transparency register, but compliance is not monitored.

Dismissed from the task force
In May 2019, Ebels receives a call from Kappetein, now medical director of Medtronic. Shortly before, the task force had published a scientific article on the sizing of heart valves, and Ebels, its co-author, subsequently spoke with the Dutch newspaper De Telegraaf about the problem. His employer at the time, the AMC hospital, fully supported his statements in the article, but Kappetein turns out to be very angry about the publicity. ‘Medtronic felt that its interests were being harmed,’ Ebels recalls.

In the following days, an email exchange ensues between Ebels and Pagano, the secretary general of EACTS. Pagano claims that the article undermines confidence in the organisation, and is worried that it might be held liable as a result of the revelation about the valve labels. He tells Ebels that the board has decided to remove him from the task force, and demands that he refrains from interviews or statements about valve sizes in the future.

Ebels does not bow down. On 13 October 2019 he flies to Lund, Sweden for a meeting of the ISO working group, where he presents another proposal to get the box labelling corrected. He meets with resistance – again.

Eventually, the meeting reaches a meagre compromise, deciding once again to print the actual size on the packaging, but only for new or altered valves. This was a relaxation of the 2015 and 2005 editions of the standard, which, however, had never been enforced nor complied to by the same manufacturers that voluntarily agreed to the standard. The meeting also decided to set up a sub-working group to investigate methods for determining the exact size, and publish these after the release of the new standard.

The FDA backs Ebels
In the summer of 2020, the revised ISO standard is ready to be voted on. It is designed to end the lack of clarity regarding valve sizes, and the sub-working group has been working on a technical report describing how to measure them correctly. Ebels’ battle finally seemed to be bearing fruit.

In September 2020, Ebels receives a further boost: the Food and Drug Administration supports his cause. ‘I convinced the FDA by submitting scientific literature showing that many people had died from valves that were too small,’ he says. Barely five months later, on 22 January 2021, the new ISO standard is published, requiring manufacturers to include essential information, such as the correct valve size, on their packaging.

But the rule applies only to new and modified valves, not those already on the market. ‘That means that mislabelling will continue for quite a while,’ Ebels says. ‘I would have preferred existing valves to be covered as well, but we couldn’t get the manufacturers to go that far.’

Dutch authorities turn a blind eye
The case is illustrative of the way in which medical devices are regulated: the rules are scarce and flexible, professional associations are reluctant to take action, manufacturers have a finger in every pie, and national and international watchdogs are lax.

As early as 22 December 2016, Ebels raised the valve problem with Koen van der Kroef, policy officer at the Dutch ministry of Health. ‘I explained the whole story to him,’ Ebels says. Initially the ministry saw no need to intervene in any way, but the conversation ended on a positive note. ‘Van der Kroef said at first that changing European rules was a lengthy process, but later he understood that this might not be necessary. That’s how the idea arose to put new stickers on the valve boxes, and to organise this nationally.’

Soon afterwards, Ebels wondered: why don’t I just make those stickers myself? He emailed Van der Kroef, asking if the department could make stickers available to all professional organisations, so that surgeons and hospitals could add the correct information to the packaging. Van der Kroef replied that he welcomed action by the medical profession, and if that did not help, to report the matter to the healthcare inspectorate. That’s the last thing Ebels heard of him.

Two years later, Ebels once again sat down with the ministry, again without results. He then sounded the alarm to the Health and Youth Care Inspectorate (IGJ), which in 2019 turned to the Dutch Association for Thoracic Surgery. Jerry Braun, the association’s chair, said: ‘We have no reason to believe that incorrect measurements are being quoted or used. There are differences in the sizing that manufacturers use. It’s like footwear: the same foot might need a size 42 from manufacturer A, or a size 43 from manufacturer B. The shoes are the same size, and fit the foot, but the exact fitting is different.’ Ebels thinks it’s quite inappropriate to compare heart valves with shoes: ‘Patients’ lives are at stake.’

The inspectorate declines to take action against manufacturers who use wrong sizes, saying: ‘Sizing should be indicated on the packaging and based on the standards. The inspectorate has no role in drawing up or enforcing these standards.’ It suggests that this task belongs to the so-called notified bodies –companies hired by manufacturers to obtain CE marks, that are necessary to admitting their products on the European market.

On 2 November 2020, almost four years after Ebels first sounded the alarm with the ministry, it asked the National Institute for Public Health and the Environment (RIVM) to bring up the valve problem, including the option of affixing stickers with the correct information, with the Dutch standards committee for implants. The RIVM has been a member of the committee since August 2020.

Why did the ministry of Health leave the problem unaddressed for so many years? ‘Professional medical groups can include regulations about the safe use of medical devices via field standards,’ a spokesperson said. ‘The healthcare Inspectorate is responsible for overseeing product safety, and we play no role in this process.’ The RIVM has, as it turns out, not raised the subject with the committee for implants. A spokesperson for the institute could not explain why, but remarked: ‘Dr Ebels can always report the valve problem himself.’

The registration system is inadequate
It is unclear how many patients in the Netherlands have developed complications, or even died, after the implantation of incorrectly sized valves. The Inspectorate says it does not have this information, and nor does the National Heart Registry (NHR), which told us: ‘The government has decided to oblige hospitals to report implant information to the registry. [..] The process of collecting this data is currently under way, so that the implants’ performance can eventually be monitored nationally. We cannot answer your questions with the data currently available in the registry.’

Since 1 January 2019, healthcare providers are required to record with the National Implant Registry which implants are used when, and in which patients, but relevant data is often absent. Ebels has tried to investigate how many repair surgeries have had to be performed because of incorrect valve sizes, and how many patients have died as a result. ‘That study didn’t get off the ground, because the register of implanted valves didn’t contain the necessary data,’ he says.

Ebels continues: ‘Doctors and patient associations should be able to participate more in the ISO working groups: that’s where the standards are set. Government agencies must learn to enforce rather than wait to see what comes their way. And if the EU’s new medical device regulation doesn’t get the notified bodies in line soon, we’d better set up an implants department within the European Medicines Agency.’

Look-away culture
Two members of parliament who have previously spoken out against the lack of regulation regarding medical devices, are affronted upon hearing Ebels’ story. Labour Party leader Liliane Ploumen: ‘When a manufacturer knowingly provides wrong information and thus increases the risk of patient harm, the Inspectorate must act immediately. It’s incomprehensible that the ministry and the Inspectorate think it’s not their role to take action against this. They can’t shift responsibility for devices to the notified bodies – it is known that they cannot guarantee the safety of implants, and don’t have safety as their primary objective.’

Socialist Party MP Henk van Gerven agrees. ‘The Inspectorate can’t just point to the notified bodies. Its own task is absolutely clear: to supervise the quality and safety of healthcare. If these are at stake, it must act and not look away. Such laxity constitutes a risk to our public health.’ Both he and Ploumen plan to question the minister Health about the matter. FTM