This article is reprinted from "The Gray Sheet" – November 19, 2007
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FDA plans to release new PMA guidelines for pacemaker and implantable defibrillator leads in 2008 to give manufacturers more guidance on bench testing.
"We're bringing the document up to what companies are doing already, which is a larger battery of tests," Megan Moynahan, chief of CDRH's Pacing, Defibrillator and Leads review branch told "The Gray Sheet."
The 2008 guidance document, developed over the last several years, addresses premarket development of pacemaker leads, but will also be a "a good jumping off point" for ICD leads, Moynahan says. The products are under increasing scrutiny in the medical community following last month's recall of Medtronic's 7-French diameter Sprint Fidelis lead and reports of similar concerns with St. Jude Medical's competing thin ICD lead.
The guidance will recommend more mechanical and electrical bench testing. In special cases, animal or clinical testing might be necessary, she said. Also, "there's a lot of interest in looking at the postmarket surveillance requirements for both pacing and defibrillator leads," Moynahan said.
Recent reports illustrate the importance of rigorous testing of ICD leads, which Moynahan says "tend to be less reliable" than pacemaker leads.
Fidelis Problems Show Difficulty Of Lead Testing
In October Medtronic stopped sales of Sprint Fidelis in response to evidence that the lead had a higher failure rate than the firm's older Sprint Quattro leads (1"The Gray Sheet" Oct. 22, 2007, p. 3).
"In any product area, not just ICD leads, there's a bit of disconnect between what bench testing can show you and whether bench testing is predictive of clinical performance," Moynahan said. "I think Sprint Fidelis is a good example of a situation where the bench testing did not predict the clinical performance. ... It probably had something to do with how well those bench tests were performed."
"Clinical testing is needed when there's no bench or animal testing that can help establish reasonable assurance of safety or effectiveness, for example if you have a new fixation method," Moynahan explained. "The only way to do that is to look at the devices after they've been implanted."
Medtronic's Fidelis and Quattro leads are iterations of Medtronic's Transvene lead system approved by FDA in 1993. The leads have been sold in the U.S. since 2004 and 2000, respectively.
FDA approved the leads based on animal and bench testing data. The agency required clinical data on Quattro only, but Medtronic conducted two human studies on Fidelis as well.
Fidelis' two multicenter studies followed about 80 patients, evaluating the general performance of the leads as well as physician handling. Typical follow-up was 30 days, but averaged up to six months in one of the studies. The trials were not meant to look at long-term product performance, Medtronic said.
Medtronic says it is still exploring design changes and other upgrades to improve the reliability of the Fidelis leads and hopes to have them back on the market in the next 18 months.
St. Jude's Riata Leads Scrutinized
St. Jude Medical's Riata family of ICD leads is the subject of recent physician reports of perforation of the right ventricle wall with the lead tip.
Over the past year, reports appeared in the Pacing and Clinical Electrophysiology journal (PACE) and HeartRhythm, the journal of the Heart Rhythm Society. Most recently, four new cases were published on PACE's Web site Nov. 12.
"It was only when multiple case reports emerged from different geographic areas and were submitted for publication that editors recognized a problem that seemed to be neither isolated nor rare," wrote Stephen C. Vlay, M.D., Stony Brook University Health Sciences Center, in an editorial that will accompany the physician reports in the January issue of PACE.
The articles describe two cases of right ventricular wall perforation reported by researchers in the Czech Republic, as well as a case of a 71-year-old woman where the lead penetrated within 7 millimeters of the skin's surface, and a report from cardiologists in Nebraska of delayed lead perforation a month after implantation.
CDRH's Manufacturer and User Facility Device Experience Database (MAUDE) lists 15 cases of perforation with the Riata lead, including one reported death, but Vlay worries the event may still be underreported.
Perforation is a risk with all pacemaker and ICD leads, and is listed in Riata's product manual and labeling, but the latest reported cases are especially disturbing to Vlay. "This is happening in different parts of the country and different parts of the world, and it's happening to experienced operators," he told "The Gray Sheet."
With smaller leads like Riata, lead body construction, insulation thickness and stiffness at the tip could all be risk factors for perforation, Vlay says.
"The bottom line is: we don't know the answer," he said. He urges physicians and patients not to panic, but rather to continue gathering information through adverse event reports and long-term patient follow-up. Vlay especially recommends physicians use FDA's 2MedWatch adverse event reporting system, to learn the true scope of the problem.
"Does this affect a certain type of individual, a certain type of heart disease? These are the things that need to be analyzed," Vlay said.
FDA's Moynahan agreed that perforation rates deserve continued scrutiny. "I wouldn't call it a 'failure mode' per say, but high perforation rates may be a problem with the design of a lead," she said. "It's one of the areas that have a lot of underreporting in our postmarket surveillance systems."
Registries Show Low Perforation Rates - St. Jude
St. Jude maintains that its registry data show a very low risk of perforation. Returned product analysis and incident reports showed a perforation rate of 0.086% for more than 121,000 Riata leads, which compares favorably to the published rates of 0.6% to 5.2% for ICD leads in general, St. Jude said.
The firm's analysis will appear in the December issue of PACE, with data from the returned product analysis and the ACT and OPTIMUM registries.
Riata's perforation rate was 0.34% in St. Jude's 5,500-patient ACT registry and 0.33% in its 2,877-patient OPTIMUM registry. Field reports show a slightly higher perforation rate for the smaller 7-French Riata lead of 0.16% compared to 0.06% for the 8-French Riata lead.
A third registry, SCORE, began enrolling in June and will collect long-term performance and reliability data on all the firm's implanted cardiovascular rhythm management products.
On an Oct. 29 conference call sponsored by Bear Stearns, Eric Fain, president of St. Jude's Cardiac Rhythm Management division, stressed that other factors besides lead design could be contributing to the perforation rates, including patient characteristics and implant technique (3"The Gray Sheet" Nov. 5, 2007, p. 13).
"Placing a lead and the complications that can occur from placing a lead is very much operator dependent," Roger Freedman, University of Utah Health Sciences Center, a member of St. Jude's lead medical advisory board, said on the call. "I think that the implant technique is probably the most important, with lead design being the second most important."
Ranjit Suri, M.D., New York Hospital Queens, disagrees. "Why would these people who have been doing something a particular way for a long time all of a sudden have these difficulties?" Suri said in an interview. "I would say, in large measure, it was the design."
In a letter to the editor published in HeartRhythm in September, Suri and colleague Seth Keller, M.D., said that in their experience, Riata is more prone to perforation and should not be used in routine practice. Suri's center stopped routinely implanting the Riata leads more than year ago.
Suri says he is concerned about all smaller leads. "Obviously one is attracted to them because they're easier to thread," Suri said. "But nine [French] to seven [French] is not that huge a downsizing, maybe just a hair easier to place. Any lead that's downsized may be at increased risk of failure. They have to be more susceptible to metal fatigue."
The 9-French Medtronic Quattro lead is now Suri's "workhorse," because of its longer track record, he says.
- Jessica Bylander
