As many as 26 percent of us have holes in our hearts.
This hole, found in the wall between the heart's two upper chambers, is called a patent foramen ovale, or PFO, and most of the time, it isn't a cause for concern. But sometimes, a PFO can be the cause of a stroke.
In about 40 percent of strokes, patients don't have heart arrhythmias, blood clots or any other identifiable cause. In these patients, PFOs may be to blame.
The question of whether or not doctors should close PFOs in patients who have had strokes has been a hot-button issue for cardiologists and neurologists treating stroke patients for years. But a new study called the CLOSURE trial suggests that closing PFOs may be no better in preventing future strokes than treating patients with medication, a treatment route that is less costly and without the inherent risks of a medical procedure.
The study, published today in the New England Journal of Medicine, looked at 909 patients between the ages of 18 and 60 who had a PFO and had suffered a stroke without another apparent cause, called a cryptogenic stroke. About half of the patients went on medical therapy. The other half took medication and had their PFOs closed -- doctors threaded a catheter through a vein to the heart and plugged the hole with a small device called a STARFlex.
When researchers compared the two groups, they found that the risk of having another stroke was almost equal for both groups. Within two years of the procedure, 2.9 percent of the patients with closed PFOs had a stroke, compared with 3.1 percent of patients taking medication alone.
Dr. Anthony Furlan, the study's lead author and chairman of neurology at University Hospitals Case Medical Center in Cleveland, said the evidence just isn't there to support a PFO closure procedure over simply giving patients medication.
"We're not saying there are no patients who should have the hole closed, but we are saying the selection criteria have to be radically refined," he said. Ideally, a patient would be under age 45, have a very large hole in their heart and a heart defect called an atrial septal aneurysm.
So if both treatments are equally effective, what's wrong with closing PFOs? Furlan said the procedure is costly and poses some risks for patients. According to the study, 13 patients had major vascular complications in the two years after their procedures, and 23 had atrial fibrillation, a heart arrhythmia that can be dangerous if left untreated. Only three patients taking medication alone had atrial fibrillation.
Many doctors welcomed the results of the CLOSURE trial, saying it provides real evidence about the choices doctors can give their patients.
"It has been taught and practiced for years that closing PFOs in patients with cryptogenic strokes is helpful," said Dr. Colin Barker, an assistant professor of cardiovascular medicine at the University of Texas Health Science Center. "This study shows the lack of benefit of this intervention."
"Hopefully it will significantly reduce the number of PFO closures that are being done off-label," said Dr. Amie Hsia, Medical Director of the Stroke Center at MedStar Washington Hospital Center in Washington, D.C.
But the study is drawing fire from other doctors who say the trial had several flaws.
Although the study included more than 900 patients, some doctors say that researchers would need about 4,000 patients to draw significant conclusions on whether or not closing PFOs is an effective way to prevent recurrent strokes. The study also included patients who had other stroke risk factors, making it difficult to tell whether the PFO alone was the cause.
Some critics also say the STARFlex device used to close PFOs in the trial is inferior to other available devices. The STARFlex device is no longer available since its manufacturer, NMT Medical, went bankrupt in 2011.
Furlan, the lead author, didn't dispute the critics who called the CLOSURE trial flawed, but he said it is so far the best information available comparing the effectiveness of PFO closure to medication.
"Still, it's psychologically hard to say well, why not close the hole? Intuitively, that seems to make sense. But when you test it out, you have trouble finding the hard evidence," he said.
Many doctors frequently recommend closing PFOs in patients, saying the procedure is not only safe and effective, but also gives patients peace of mind that a potential problem is solved.
Melissa Smith, a 42 year-old mother of three, had her PFO closed while participating in the CLOSURE trial. Before the procedure, she had a mini-stroke that caused numbness on one side of her body. Her doctor discovered she had a PFO and told her it would put her at a higher risk for strokes in the future.
"The thought that something bigger could be lurking did make me feel unsure and anxious," Smith said.
Smith said she was relieved when one of her doctor's told her about the CLOSURE trial and that it was possible that she could have her PFO closed with a device that did not require open-heart surgery. "I knew [the device] was not FDA approved, but it was less invasive [than the alternative]."
Dr. Jonathan Tobis, director of interventional cardiology at the Ronald Reagan UCLA Medical Center and an investigator in upcoming trials studying PFOs, said that relieving a patient's fears about their heart is a major factor in his decisions to close PFOs. He said the outcome of the CLOSURE trial is not enough to dissuade him from closing PFOs in some of his patients.
"I'd still consider placing one just for the anxiety-lowering effect," Tobis said.
Currently, the U.S. Food and Drug Administration has not approved any device for closing PFOs, including the STAR Flex device used in the trial. But many doctors use devices off-label.
"During the 9 years it took for the results of this trial to be reported, approximately 80,000 patients have had a patent foramen ovale closed with the use of a device at an average cost of $10,000 per procedure, said Dr. Claiborne Johnston, of the Clinical and Translational Science Institute at the University of California, San Francisco, in an editorial published with the study.
Many doctors still say the results of the CLOSURE trial don't rule out closing PFOs. Doctors should assess each patient individually and determine the best option.
"Remember, the study does not say that medicines are better than closure; it says that they both prevent another stroke equally as well," said Dr. Rafael Gonzalez, division director of cardiology at Scott and White Hospital in Round Rock, Texas. "It leaves clinicians options on how best to treat the patients."
Two future trials are currently underway that will also compare PFO closure to medication therapy.