A PFO is a hole between the left and right atria of the heart. These holes exists in all people before birth and they usually close shortly after birth, but not in all patients. Clinical trials have implicated PFOs as a conduit for thrombus emboli transferring from the venous to the arterial vasculature and causing strokes. 

The concept of using a transcatheter closure device to seal off the PFO to reduce cryptogenic strokes, and now called PFO-related strokes, was proven in the long-term results of RESPECT trial. These results were duplicated in the REDUCE and CLOSE trials. 

These trials looked at use of PFO closure in secondary prevention of stroke, but he said attention is now turning to use of close as a primary prevention strategy.  

"Primary prevention is a very challenging area to be able to document benefit. The population based studies have shown that having a PFO is not by itself a risk factor for having a stroke, so you can't really label it as a disease," Carroll explained. "But, can we identify patients with PFOs that have large shunts or may have atrial septal aneurysm, and maybe that wedded with another potential risk factor, such as venous thromboembolic disease, will identify a patient population that it would be worthwhile to do a clinical trials on primary prevention."

He admits defining the number of patients that would need to be treated to properly power such a study may be difficult. "But, I think most people would agree it is so much better to prevent that first stroke rather than after and finding it was PFO related," Carroll said. 

Role of neurology collaboration in PFO closure programs

At centers that do PFO closures, there is a close collaboration between interventional cardiology and neurology using a heart/brain team approach for shared decision making of what is best for a patient. 

"That collaboration with neurology is an essential part of these programs, because most of these patients that are being referred have already had a stroke and the critical issue was what was the mechanism of that stroke," Carroll said. "We have had a PFO clinic at the University of Colorado for about 20 years starting when we were enrolling in the RESPECT trial and we found the collaboration to be very useful, especially for patients. In one stop they could see both a stroke or vascular neurologist and an interventional cardiologist and get our best opinions on what caused their stroke and whether PFO close was appropriate. There has been a lot of confusion with some patients because they have one specialist tell them 'no, that's not for you,' and other tells them 'oh, you need this.' The clinical allows them to have a discussion between the two disciplines that are critical in giving people a comprehensive evaluation and an evidence based recommendation."  

He said the cardiologist also can learn a lot from the neurologists in these clinics. Carroll said he learned a lot on how to interpret brain imaging and about stroke. 

"When starting one of these programs, you need that partnership with neurologists,"Carroll explained. "We now the the level of evidence needed to show the connection with PFO and stroke, so most of my referrals now come from, neuroloigists who have that 35 year old patient with no traditional risk factors who had an embolic stroke." 

New avenues in PFO research and close technologies

PFO closure is also being looked at in a new trial as a way to reduce or eliminate migraine headaches in some patients. 

"We know anecdotally and from previous trials that PFO closure benefits some of these patients. So, it is great so see that trial moving forward and hopefully it will give some clarity to a field that has been very lacking definitive data for the role of PFO closure in migraine," Carroll said.   

Another area where closure devices may play a role is with other types of right to left shunting that cause hypoxemia   

Carroll said new PFO closure devices are also in development, which include use of bioresorbable devices so no hardware is left behind, and devices that use a strict approach. "I predict in the next five years, there will be new ways of closing PFOs," he said.