Clinical trial at UNC investigates if treating hole in heart helps prevent stroke

By TOM HUGHES
UNC School of Medicine

CHAPEL HILL -- A new landmark clinical trial under way at the University of North Carolina at Chapel Hill seeks to determine whether treating stroke patients for a hole in the heart will reduce their chance of having a second stroke.

"The era of therapeutic nihilism, or a helpless and hopeless attitude toward stroke therapy, is past," said Dr. Walter Tan, an assistant professor in the divisions of cardiology and radiology at UNC’s School of Medicine. "There is cautious optimism now with emerging device and drug strategies that have good potential for preventing recurrent stroke."

One type of hole between the right and left sides of the heart, called "patent foramen ovale" or PFO, is a fairly common congenital heart defect in the general population. When doctors look for such holes in healthy patients, they can find them in 10 percent to 30 percent of patients.

Most people who have one never experience any problems. But when doctors look for a PFO in patients who have suffered a stroke or transient ischemic attack, also called a TIA or warning stroke, they find that up to 50 percent have one. A PFO can allow a blood clot or other material that would normally be cleaned out in the lungs to move into the left side of the heart and then into the brain, where it could cause a stroke or TIA.

In patients who have had a stroke but no cause could be found, those with a PFO are at higher risk to have another stroke than those who do not have a PFO. Researchers think the PFO defect could be a contributing factor in more than 100,000 patients a year who have suffered a stroke or TIA.

This raises the question of whether actively treating PFOs in patients who have had a stroke can help prevent them from having another stroke, the leading cause of disability nationwide and the third leading cause of death. Researchers at UNC’s School of Medicine and more than 100 other stroke and interventional cardiology centers nationwide are participating in a clinical trial aimed at answering that question.

The trial, called CLOSURE I, seeks to enroll 1,600 patients. Half of these patients will be treated by closing their PFOs using the proprietary STARFlex implant, a device manufactured by Boston-based NMT Medical Inc. STARFlex consists of a pair of flat, square mesh "umbrellas" that are compressed into a small plastic tube, called a catheter. The catheter is then inserted into a vein through a small incision in the groin and threaded into the heart to the site of the hole. There one umbrella opens on either side of the hole, sealing it shut. The entire procedure usually takes between 30 and 60 minutes. Then new heart tissue grows over the implant, encasing it in about six months.

The other half of patients in the study will be given blood-thinning medications. Researchers will then monitor both groups of patients over two years to determine how well they do and what their risk for recurrent stroke is.

"That, hopefully, will answer the question as to whether we should be closing these holes at all. If so, is this the device we should be using? And if not, then what kind of medication should we be using for these folks?" said Dr. Ana Felix, an assistant professor in the department of neurology and UNC’s principal investigator for the study.

Felix will recruit stroke patients for the study at UNC Hospitals and oversee their follow-up. To be eligible, patients must have a PFO and have suffered a stroke or TIA, and all possible causes of the stroke other than the hole in the heart must have been ruled out.

"The best approach is still prevention, and any therapy should be built on the foundation of diet and regular exercise that should be inculcated in our young," said Tan, who also is UNC’s lead interventional cardiologist investigator.

Tan will be in charge of performing the implantation procedures, called catheterizations, and directing the device therapy of UNC patients in the study.

The study’s overall principal investigator is Dr. Anthony Furlan, director of the stroke program at the Cleveland Clinic. The lead interventional cardiologist in the study is Dr. Mark Reisman, director of cardiovascular research at Swedish Medical Center in Seattle. The Harvard Clinical Research Institute in Boston will conduct data management and analysis under the direction of Dr. Richard Kuntz.

The U.S. Food and Drug Administration has approved use of the STARFlex implant in the clinical trial, but has not approved the device for general use. However, it is commercially available in Europe. NMT Medical’s septal closure technologies have been used to close more than 10,000 PFOs worldwide.

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Note: Contact Felix at (919) 966-5547 or FelixA@glial.med.unc.edu.

School of Medicine contact: Stephanie Crayton-Robinson, (919) 966-2860 or scrayton@med.unc.edu