Heat Stopping

‘Heart Stopping ‘

Issue 2940 October 28^th

‘Would you have an operation to fix a hole in your heart even though no one is sure if the benefits outweigh the risks ?’

The facts

1 in 4 of us is walking around with septal defects (a type of congenital heart disease) it can lead to strokes, migraines, decompression sickness in divers and perhaps other issues.

Strokes occur as blood leaks through the hole in the heart bypasses the lungs, where small blood clots would normally be filtered out. This means the clots may end up reaching the brain (or other parts of the body) potentially triggering a stroke.

It is relatively easy to fix the hole surgically so why do we not fix more people’s hearts?

That is what doctors cannot agree on, some argue that the operation does more harm than good; the condition has potentially devastating consequences. So why is such a heart problem with such potential devastating conditions so common?

The septal defects are a result of our time in the womb during which the blood flows by the completely different route. An unborn baby doesn’t use its lungs to breathe it instead gets all its oxygen through the placentae. As a result a fetal heart has an opening between the right and left upper chambers (atrial) known as the foramen ovale to bypass the lungs? When the baby is born and takes its first breaths, a flap closes over the hole- at least in most people. For about one in four of us however the hole stays open, either all the time or more commonly it gapes open when the pressure rises in the chest, such as during a coughing fit, or straining to defecate (hahaha) or when lifting something heavy. This is known as a patent (open) foramen ovale or PFO and is shown the the picture bellow. Remember that these septal defects caused by the foramen ovale as specific to holes in the atrial (atrial septal defects).

While having little initial effect upon the day to day life of a sufferer doctors worry that this hole allows things to sneak through which would normally be filtered out be the lungs, things such as blood clots. Normally small blood clots get stuck in the lungs and dissolve harmlessly however, should the clot pass by the lungs, it might lodge in a blood vessel elsewhere in the body, maybe the brain causing a stroke after all the leading cause of strokes is blockage of blood flow.

Strokes are an especial public health problem. One in five of us will suffer a stroke in our life time and they are the current cause of disability in the western world (with depression coming a close second).

The evidence or the linking of congenital heart disease and strokes first mounted in the 1990s when various studies suggested that arterial septal defects are present in 40% to 60% of people who had unexplained strokes. It is also important to remember that only 25% of the population is thought to have PFO which has led to many leading stroke experts to believe that PFO must somehow play a role.

The detection of a PFO is easy once you suspect that it is there. A vein in the subjects arm is injected with tiny bubbles, too small to do any harm. The microbubbles travel to the heart where the can be imaged using ultrasound. Patients are asked to hold their breath and bear down forcing the flap open. If the bubbles can be imaged passing to the lungs then the Foramen ovale has naturally shut and all is well. However should the bubble be detected traveling to the left side of the heart then it suggest that the PFO is still open (it could also be the result of a ventricular septal defect however this is diagnosed most often by a heart murmur).

The first reaction of many when a hole in such a vital organ is found is often to plug it. This used to mean open heart surgery, but medicine has moved on and devices have been devolved that can close the heart without the need for the opening of the chest. One such device is shaped like a tiny umbrella which is pushed into the groin, threaded up into the heart by a wire, then opened up and left in place while the wire is withdrawn. Eventually, tissue grows over it, thus sealing the flap.

As the confidence in the safety of this operation in PFO closure grew it became increasingly offered to people who had, had unexplained strokes, in hope of reducing their chance of having another stroke. Note that this would be as well as or instead of the standard treatment of blood-thinning medicines or other drug treatments. Yet unlike the drugs, no trials have been done to demonstrate the operation would achieve the intended goal, and doctor’s opinions differed about how often the procedure should be carried out. The most enthusiastic tend to be the cardiologists who carry out the procedure perhaps influenced by their close relationship with the manufactures of the device.

Soon the closure became an operation for divers too, after research revealed that people who are prone to decompression sickness are more likely to have large or permanently open flaps.. Divers get the bends when bubbles of nitrogen form in the blood as they ascend, leading to symptoms ranging from itching and joint pain to strokes and paralysis. Normally the nitrogen is gradually breathed out through the lungs, as long as the divers ascend slowly enough. In people with PFO’s the bubbles might bypass the lungs, making the bends more likely as the diver struggles up a ladder with wet heavy kit on.

Patent foramen ovales were also suspect of causing migraines, specifically the kind accompanied by strange visual disturbances known as aura. People who get migraines with aura are twice as likely to have PFO as the rest of the population and about six times as likely to have a large opening. Although the cause of migraines is unknown is unknown the current theory is that a PFO allows whatever causes migraines is allowed to bypass the lungs and reach the brain. Doctors found that migraines with aura tended to disappear in people-le who had their PFO closed for other reasons.

So a trial was set up. Funded by Starflex a company that was the producer of a new closure device (that’s was a good idea I’m sure they didn’t have any personal interest on the results of the trail). It was the first large trial to test PFO closure against people having shame operations. In this trial patients who had, had the trail were compared with those who experienced a placebo- they were put under a general antithetic and an incision made. This in fact was the first large scale study of its kind which had involved a placebo group, where both the patients and the doctors who assessed the outcomes were kept in the dark about whether patients had, had the real operation or not. The results did not show the outcome wanted. Not only did the data show that the device failed to stop people having migraines, but it also caused a higher rate of heart problems than you would expect with this procedure; in two cases the device came loose in the heart, which could have been fatal.

The trial was also the centre of a libel case against one of the principle investigators, Peter Wilmshurst. At a cardiology conference, Wilmshurst said to a reporter that in some patients, the device may not have completely close their PFO’s and that there were flaws in the way that the trial was conducted. See link http://www.theguardian.com/science/2010/dec/01/company-suing-peter-wilmshurst-libel

Starflex’s manufacture NMT Medical sued, in case Wilmshurst’s comments helped spur the on-going campaign to reform UK libel law. Fortunately for Wilmshurst, the company went bankrupt before the case could reach court. Wilmshurst said on the matter ‘‘ We need to take into account both the benefit of the closure and the risk’’ ‘’ Often there is little or no benefit and a significant risk ‘’ . After all no surgical procedure is completely safe, during PFO closure there is an estimated 1 in 100 chance of complications. That maybe not seem like much but if you did 1000 operations then it is likely that you would have 100 people for that group how experienced complications which could range from bruising or damage of the blood vessels to the device falling out. There is even the risk that the operation could trigger another stroke, if a blood clot or air bubble travels through the PFO as the device is pushed through.

The migraine trial also highlights problems with the industry in a wider context. Medical device manufactures, unlike drug companies do not have to prove that their products work all they have to pass is a safety test. In the US medical devices are subject to the same trials that drug companies have to comply to but as seen in the article ‘rethinking depression’ the companies still don’t have to publish the results of negative trials. However in the US there is much more ‘’off label’’ use where devices are used despite not having gone through the official approval process for that particular kind of operation. Doctors in the US tend to be more gung ho about medical inovations than there UK counter parts which could help explain why the US carries out some 8000 patent foramen ovale closures a year, which is more than 10 times the UK numbers  despite having 5 times the population.

It is believed that the best way to resolve uncertainties over the procedures risks and benefits are further randomised trials. In January of 2013 only one trial had been published involving Starflex , this trial found no significant difference between the rate of subsequent strokes after surgical or drug treatment. There were criticisms however that the studies design meant that it could have underestimated the benefits of the intervention. Since then only two further trials have been published and even the most favourable could be taken as evidence to both support of criticises the procedure depending on which ways the data was crunched.

‘If the patent Forman ovale closure device were a drug we would just walk away ‘says neurologist Clay Johnston of the University of California SF. At the moment all doctors can do is to perform the surgery on those who most need it, which is determined by questioning patients closely to see if they have another risk factors that could have caused there stroke.

In the UK, official guidelines now say that the operation should only take place at a few specialist centres that keep good records, so that the resulting data can be pooled. While this is not a randomised trial it still provides much needed data on the individuals who have the procedure and the outcomes that the procedure has on their health.

This case has brought to our attention that some of the products for which we use in potentially lifesaving operations we need definitive evidence from bigger and better trials about the effects and the outcomes that they have in a much wider and transparent environment.