American College of Cardiology

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February 15, 2005

“What we observed is that after closing the opening between heart atria, there was a dramatic reduction in the incidence of migraine headaches in those patients who had complained of headaches prior to the inter-atrial closure procedure,” said Jonathan Tobis at the University of California in Los Angeles.

Dr. Tobis and his colleagues, including lead author Babak Azarbal, M.D., reviewed 89 cases in which a device was threaded through a catheter into an abnormal intra-atrial opening. Almost half the patients (37 of 89) reported suffering migraine headaches before the procedure. By contrast, only 12 percent of the general population reports suffering migraines. Three months after the procedure, three-quarters of the migraine sufferers (28 of 37) reported their migraines were gone or significantly improved.

In the second study, Mark Reisman, M.D., and his colleagues in Seattle, Wash., reviewed 162 cases of patients who underwent a transcatheter procedure to close an intra-atrial opening because they had suffered a stroke or transient ischemic attack. A type of intra-atrial opening known as patent foramen ovale is associated with these attacks.

“The results were extraordinary. We’ve been able to see a significant number of patients who have had not just a reduction in the frequency of headaches but actually complete relief,” said Mark Reisman, M.D. at Swedish Medical Center in Seattle, Wash. “This study further supports a link between a common heart abnormality and migraine headache.”

Of the 162 patients studied, 57 (35 percent) reported suffering migraines before undergoing the procedure. A year after the procedure, the researchers contacted 50 of the migraine suffers. More than half (28 of 50) said their migraines were gone and another seven patients said the frequency of migraine attacks had dropped by more than 50 percent.

Although many migraine suffers are eager for any procedure that could offer them potential relief from the debilitating attack, both Dr. Reisman and Dr. Tobis stressed that randomized, controlled clinical trials are needed before recommending heart procedures as a possible migraine treatment. They also noted that there are migraine suffers who do not have heart abnormalities, and people with intra-atrial holes who do not suffer migraines; so the link seen in these studies, even if confirmed, does not explain all migraines.

The studies involved patients receiving treatment for patent foramen ovale or atrial septal defect. Patent foramen ovale (PFO) is a flap valve that allows blood to flow directly from the right atrium to the left atrium of the fetal heart when oxygen is supplied from the mother and the developing lungs are not yet in use. After birth, when a newborn begins breathing and blood flows through the lungs, blood pressure increases on the left side of the heart, which generally holds the PFO flap closed. Although the flap is usually permanently shut by the first birthday, one person in five still has an open PFO into adulthood. Atrial septal defect is an abnormal opening through the muscle wall (septum) that separates the left and right atria of the heart.

Dr. Reisman said his team decided to look into possible links between heart abnormalities and migraines after patients began spontaneously telling them that their headaches had disappeared after the catheter procedures.

“This is a huge leap in our understanding about the potential causes of migraine headaches. For centuries there have been explanations for migraine headaches that run the gamut from demons to vascular spasm. However, there has been no good scientific explanation for these headaches,” Dr. Tobis said.

These studies were not designed to uncover how a hole in the wall between heart chambers could cause migraines, but researchers have some suspicions. The blood normally circulates through the lungs on its way from the right atrium to the left atrium, but the atrial wall hole short-circuits that usual route. So the researchers said future studies should look for signs of impurities or tiny clots passing through the intra-atrial hole that may be filtered or metabolized by the lungs in a person with normal circulation.

Because of the dramatic nature of the changes reported by patients in these observational studies, Dr. Reisman said a more definitive clinical trial could be done with in a couple of years.

“The population for this study would be patients who suffer from frequent and severe migraines, those who are unresponsive to current medications or have significant side effects due to the medications. That would be the population to focus on,” he said.

In an editorial in the journal, Sotirios Tsimikas, M.D., at the University of California in San Diego, cautioned that while these studies provide a strong rationale for further investigation, a healthy skepticism should be in place until randomized, controlled trials are performed.

“From the migraine patient perspective, I would suggest patients stay tuned for more studies before we know whether this may be of benefit. Patients with severe migraines and PFO may consider enrolling in trials that will be forthcoming in the future,” Dr. Tsimikas said. “This is the first chapter in a very interesting story that may have a happy ending where some migraine patients may ultimately benefit from closure of patent foramen ovale or atrial septal defects. It also suggests new hypotheses on how migraines occur, and this is exciting from a research perspective.”

Spencer King, M.D., at the Fuqua Heart Center in Atlanta, who read the paper by Azarbal et al. but was not connected with the research team, said the study results support the observations of others who noted improvements in migraine symptoms following the closure of intra-atrial holes.

“There are many examples, however, of treatments that relieve symptomatic conditions but are not effective when subjected to randomized trials. There does not seem to be any question that many patients are better, but it is less clear that closure of the defect is the reason. A double-blind randomized trial will be difficult to do but will be necessary,” Dr. King said.

John A. Bittl, M.D., at the Munroe Regional Medical Center in Ocala, Florida, who read the paper by Reisman et al., but is also independent of the research team, called the results provocative, but urged caution.

“The study constitutes a very low level of evidence, however, because it is a retrospective, uncontrolled, questionnaire study that is subject to all types of biases on the part of the patients and study staff,” Dr. Bittl said. “Additional evidence of efficacy of closing PFOs as treatment for migraine headaches awaits confirmation from additional observational studies, but final proof awaits truly controlled studies that may be difficult to perform.”

Dr. Tobis said that he will be the cardiology principal investigator for a future randomized clinical trial sponsored by the manufacturer of one of the PFO occluder devices used in the procedure, but that the company (AGA Medical Corporation) did not provide funding for this study.

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