Closing a Hole in the Heart to Stop Migraines
An undiagnosed heart defect, present in 25% of all migraine sufferers, may be the cause of their headaches.
For the millions of Americans who experience migraines, any relief is welcome. These debilitating recurring headaches—often accompanied by visual disturbances, sensitivity to light and sound, nausea, and dizziness—can bring someone’s world to a stop.
What causes migraines remains poorly understood. But in some cases, the headache symptoms have been linked to a common hole in the heart called a patent foramen ovale, or PFO. Since 2000, numerous medical reports have indicated that repairing the hole can bring lasting migraine relief. But it doesn’t work for everyone. Because PFO is so common in the population, for some, the presence of a PFO is simply a coincidental finding and is unrelated to the headaches. Closing the holes in those patients will provide no headache relief. Early trials designed to prove that PFO closure was a proper treatment for migraines failed: there was no way for the researchers to determine if study subjects had the coincidental or the "causal" PFOs.
A Possible Solution
Robert Sommer, MD, and Barbara Robbins, FNP-BC, from the Columbia Interventional Cardiovascular Care program at Columbia University Irving Medical Center, have been working toward unraveling this mystery since 2011.
“We've known about the migraine-PFO relationship for more than 20 years,” says Sommer. “But since we didn't have any way of figuring out which PFO to treat, it was pretty hard to be enthusiastic about a heart procedure that we knew might not help.”
Robbins, a former Neurology nurse practitioner, adds, "We thought that if closing the PFO eliminated the migraine symptoms, that some substance from the right side of the heart must be crossing to the left side to reach the brain triggering the headaches. It's similar to how blood clots from the right side rarely cross a PFO and cause stroke.”
In fact, it was the relationship between stroke and PFOs that led Sommer and Robbins to their discovery about the migraines.
“Back in 2011, the principal stroke preventative treatment in patients with PFO was aspirin,” says Robbins. “But within a short period of time, purely by chance, we had a few PFO-stroke patients who couldn't take aspirin. We offered them a medication called clopidogrel (Plavix) as an alternative blood thinner to prevent clot formation.”
The team found that the treatment worked well as a stroke preventive and came with a surprising additional benefit: some patients taking Plavix reported that their migraines had been greatly reduced—or had stopped altogether.
“They came back six months later and said, ‘It's so weird. Since you started me on that medicine, my migraine headaches have completely gone away.’ And we saw that in a couple of patients in a row,” says Sommer.
After hearing this from a number of PFO-stroke patients taking clopidogrel, Sommer and Robbins felt there was a connection worth exploring. And after some consideration, they came up with a possible explanation based on how Plavix and similar medications work.
"We know that Plavix inhibits the platelets in the blood from making their usual array of chemicals and other substances, which are ordinarily filtered in the lungs. We surmised that reducing the amounts of those toxins from the right side of the heart, must have reduced the amount crossing the PFO and reaching the brain, similar to how closing the hole would reduce the amount reaching the brain," says Sommer.
From that point forward, the team treated hundreds of migraine-PFO patients with clopidogrel and related medications and showed that up to two-thirds of the patients had a reduction or elimination of their headache symptoms. Further, the response to the medication predicted, with a near perfect correlation, the response to the subsequent PFO closure. The team’s results were published in the medical journal Neurology in 2018.
"Not only did we find a potential new treatment for migraines, but we identified a test to pick out the patients who would benefit from PFO closure," says Robbins.
Next Steps
Currently, PFO closure has not yet won FDA approval as a treatment for migraine relief. To prove their theories and observations to the FDA and to Neurologists, Sommer and Robbins began working with WL Gore, the maker of the CARDIOFORM Septal Occluder (an FDA-approved PFO closure device) and national headache neurology leaders to develop the protocol for the Gore RELIEF Clinical Study (reliefclinicalstudy.com). Dr. Sommer is the lead Cardiology Investigator for the study.
For this medical trial, people with severe migraines will be screened for a PFO. Those who have one will undergo testing with either a platelet-inhibiting blood thinner or a placebo pill to see how their headaches respond. Only patients who respond well to the antiplatelet medication will be allowed to advance to the closure procedure portion of the study, where under heavy sedation, some will get the hole closed and some will not. When they wake up, they will not know what happened during the procedure. Each patient’s headache frequency after the procedure will be compared to their baseline.
"If the patients who underwent closure do much better than those who had the hole left open, we will be able to conclude not only that PFO closure can work for treating migraines, but that we now have a reliable way to pick the right patients," says Sommer.
Sommer is collaborating with David Dodick, MD, former Chief of Headache Neurology at the Mayo Clinic in Scottsdale, Arizona. Columbia University is one of 35 national sites for the RELIEF study. “We were significantly delayed by COVID-19. But now the study is getting started all over the country,” says Sommer.
Medication vs Closure: Lasting Migraine Relief?
So, if Plavix and related drugs work, why bother with a procedure? Why not just stay on Plavix?
“These patients have spent so much of their lives taking medications, either as a migraine preventative or for relief when the headaches begin,” says Robbins. “While the antiplatelet drugs may be effective, they can have some unpleasant side effects and restrictions. They could continue on the Plavix as a headache preventative, but they might also want to consider a one-time, pain-free, low-risk procedure that might have the same benefits and give up taking medicine altogether. ”
The article is written by Robert Sommer, MD, and Barbara Robbins, FNP-BC, from the Columbia Interventional Cardiovascular Care program at Columbia University. This article is intended to provide you context, background, and a brief introduction to the GORE RELIEF research study. The article contains opinions and anecdotal accounts from Dr. Sommer, and Nurse Practitioner, Robbins. Individuals considering voluntary participation should refer to the Informed Consent Form for detailed information before joining.