The Riata ICD Lead Recall: Two Perspectives

Robert Hauser, MD published a perspective piece in the New England Journal of Medicine today entitled "Here We Go Again — Another Failure of Postmarketing Device Surveillance." In the piece, he offers these suggestions on how to detect these failures earlier:

Opportunities have emerged for automated tools to prospectively monitor multicenter device databases for early, low-frequency adverse events and to compare suspect devices with established products that have been shown to be reliable.(4) The goal is a postmarketing surveillance system that not only detects device problems early but also accumulates the data needed to guide patient care. Until such a system exists, St. Jude Medical should initiate a study with these attributes for recalled Riata and Riata ST leads and for the currently marketed Durata leads. Indeed, all manufacturers should conduct postmarketing studies of this type for marketed class III devices that sustain or support life.

It has been 3 years since the FDA launched the Sentinel Initiative, as Congress, in 2007, directed it to do.(5) The intent of this new system is to supplement the current passive adverse-event reporting with an active, real-time network capable of identifying any safety or efficacy issues soon after a new drug or device is marketed and then communicating the information in a timely manner to health care providers and the public. Creating such a system is an ambitious undertaking, and the initiative aims to gather electronic health data from 100 million people by the end of 2012. Formidable challenges lie ahead, such as setting priorities, developing analytic tools, and deciding when and how to alert the public if a safety signal is detected. Thus, we are years away from a fully operational Sentinel Network.

Jay Schloss, MD offers another thoughtful perspective on this issue in his guest post over on Cardiobrief:

It is worth noting that all high impact device failures in the cardiac rhythm device industry have occurred well after device approval. In most cases, failures have been rare events occurring many years after these devices became clinically available. The industry is littered with high profile device failures, some of which serve now as footnotes or memories from the more gray haired members of the EP community: Medtronic polyurethane pacing leads, Ventitex Cadence ICDs, and Telectronics Accufix pacing leads were all devices that failed well after they had been introduced to the market. It was through case reports from concerned doctors – not the FDA — that these problems were brought to light.

Trying to absolutely prevent the failure of medical devices through the FDA approval process would be challenging to say the least. This would require an anticipation of the potential failure mechanism before the fact to design a study that would detect said defect. Moreover, the number of patients and length of study for these trials would be daunting, impractical and quite likely prohibitively expensive.

Hauser’s call to enforce a robust active postmarket surveillance system would allow ongoing innovation and appropriately timed approval of new technology. With the ability to carefully monitor a large population of approved devices “in the field,” sentinel failures could be detected and acted upon as they occur. With public reporting of these events, doctors could draw their own conclusion of whether to keep implanting these devices and prospective studies could then be designed promptly to determine the scope of the problem. That would be a system that protects patients while still allowing innovation.

Neither author mentions how their approaches might be funded. Nor is there a clear consensus on how to determine a threshold for sounding a recall (or "advisory"). Should it be announced before a root cause of the problem is known or suspected, or after? Pulling a recall trigger too early before a root cause of the defect is identified leaves doctors and patients completely in the dark about how to manage these complicated situations. These issues are still debated today.

What is clear, though, is that the efforts to prevent such widespread recalls continue and doctors (as shown by these two perspectives) remain eager to participate in the process.

-Wes

More Troubles for St. Jude's Riata Defibrillator Leads?

From the Minneapolis Star Tribune:

Researchers in Ireland have discovered a possible problem with a heart defibrillator component made by St. Jude Medical Inc. in which wires that run from the device to the heart may poke through the outer coating of their cable.

The study looked at 212 patients in Ireland who received St. Jude's Riata defibrillator lead and found that 15 percent had suffered such an "insulation breach," which could interfere with the device's life-saving therapy. Normal screening of the device or even X-rays may not pick up the breach, and patients would have no outward clue that their lead wire may be compromised.

It should be noted that the "study" referenced in this artice was actually an abstract published in the European Heart Journal's September supplement edition. I could not find it online yet, but a copy of the source abstract can be found on CafePharma, the medical device / pharmaceutical industry representative's anonymous messaging board.

-Wes

Bristol-Myers Squibb Issues 5 mg Coumadin Tablet Recall

From the FDA today:

Bristol-Myers Squibb initiated a voluntary recall of one lot of 1,000-count bottles of Coumadin (warfarin sodium) Crystalline 5 mg tablets. Company testing of tablets from a returned bottle found a tablet to be higher in potency than expected. The lot number affected in the U.S. is 9H49374A with an expiry date of September 30, 2012. A decrease of active ingredient may increase the risk of clots which could lead to heart attack or stroke, and if there is too much active ingredient, there is an increased risk of bleeding.

So what should patients who take 5 mg tablets of Coumadin do?

Here's the FDA's recommendation from the same notice:

Patients who may have 5 mg tablets should not interrupt their therapy but should seek advice from their pharmacist to see if they have tablets originating from the affected lot and if so, should consult their physician for appropriate medical advice.

In short: call your pharmacist first. If the pharmacist where you picked up your 5 mg Coumadin tablets did not fill your prescription from the affected lot, no change in management is required.

But this is where this FDA advisory stops short. What are doctors going to recommend to patients who are taking 5mg Coumadin tablets from this lot?

If it were me, I would probably advise my patients to exchange tablets at their pharmacy for tablets from a non-affected lot and have a blood thinning level (prothrombin time or INR) checked to make sure their blood is not excessively thinned.

But, hey, that's just me.

-Wes

St. Jude Withdraws Riata Defibrillator Leads

St. Jude Medical announced they are withdrawing a portion of their thinner 7Fr Riata defibrillator lead line despite earlier glowing company reports because of a higher degree of insulation failures in the earlier design of the leads made with silicone insulation material:

The Riata and Riata ST family of silicone defibrillation leads have exhibited an insulation abrasion rate of 0.47% over 9 years of use. Silicone rubber, while representing the industry’s most commonly used defibrillation lead insulation material over the past 20 years, has been observed to be vulnerable to abrasion. Abrasion of silicone defibrillation leads is acknowledged within the clinical community as a well known clinical risk and is well documented in the literature as the number one cause of lead failure across the industry with reported failure rates ranging from 3 to 10 %. Lead insulation damage and its possible effects are also described as a potential adverse event in all silicone defibrillation lead user’s manuals, including Riata User’s manuals.

Later St. Jude lead designs with their newer "Optim" polymer insulation appear to not be affected by this action. St. Jude had hoped their Riata line of defibrillator leads could replace the niche left by Medtronic's earlier withdrawl of their downsized Sprint Fidelis defibrillator leads after Medtronic's line of 7Fr defibrillator leads experienced higher-than-expected fracture rates.

Just as with the Medtronic Sprint Fidelis defibrillator lead withdrawl, St. Jude does not recommend the affected leads be extracted. I would suspect that doctors will weigh the risks vs. benefits of placing a new defibrillator lead at the time of device battery changes.

In November 2007, the Riata line of defibrillator leads were plagued by concerns of a higher-than-average rate cardiac perforation, but these were quickly disputed by the company.

-Wes

When Doctors Decide Damages

In an interesting twist to the ongoing saga of device recalls, the Minneapolis Startribune reported that the two doctors, Robert Hauser, MD and Barry Maron, MD who first brought the Prism II ICD device malfunction to public attention by releasing their story to the New York Times in 2005, wrote a letter to the judge reviewing the plea bargain agreement and told him:

We are physicians who cared for Joshua Okrup (eds note: should be "Oukrop"), a 21 year-old college student, who died when his Guidant Prizm 2 implantable cardioverter-defibrillator (ICD) short-circuited and failed to deliver a life-saving shock. His unnecessary death was caused by a product defect that Guidant Inc. had known about for years and failed to inform patients, physicians, and the U.S. Food and Drug Administration. Accordingly, we are extremely dismayed by the U.S. Attorney General’s decision to enter into a plea agreement with Guidant LLC, rather than prosecute the company and the individuals responsible for this egregious act. On behalf of the patients who died or suffered pain and mental anguish as the direct result of Guidant’s illegal and unethical behavior, we urge you not to accept the plea agreement.

An out-of-court $296 million plea agreement is not enough it seems.

While these doctors have every right to express their opinions on the case (and certainly the actions of the company were egregious), their letter opens an interesting precedent for physicians advocating on behalf of their patients: deciding what is "just" concerning damage awards in legal matters on their behalf.

Should this be the purview of physicians?

I wonder.

What I do know is an incredible amount of good has come to the medical device industry since this story broke. Companies do a much better job of reporting problems with their devices now as evidenced by excellent product performance reports. Companies also raise flags regarding their devices MUCH earlier, perhaps even notifying patients of every advisory condition imaginable (like cosmic radiation could interact with their device memory chips) - suddenly nothing was too small to report. We have also seen the profession have a greater understanding of the need to quantify the incidence of device problems by returning all devices - normally functioning or not - to companies for ongoing quantification of device reliability to better appreciate the level of device performance we should accept as "standard." Device registries now are used routinely to track and better understand the myriad of variables that influence device performance in the real world.

Litigation is always expensive and time-consuming. I am left to wonder if ongoing court litigation versus a hefty out-of-court settlement will really provide additional benefit to to the loved ones who lost their children or, as these doctors suggest in their letter, future patients. I worry that ongoing litigation might just drag this process on for years so that future patients will have to bear the costs in the form of even higher device prices.

I admit that I do not know how much money the plaintiffs would receive with the anticipated settlement and whether that will be enough compensation for all that has happened, but irrespective of the judge's decision in this matter, I hope we can continue to move past this unfortunate incident and continue working with industry and regulators to make sure this never happens again.

-Wes

Boston Scientific Issues New ICD Advisory and Halts Sales of All ICDs

Despite the excitement of the American College of Cardiology meeting in Atlanta, Boston Scientific issued a self-reported advisory about all of their high-voltage defibrillators (pacers are not affected) stopping sales until "administrative issues" regarding a change in manufacturing processes and changes of their IS-4 lead connector. This advisory does NOT affect existing implanted devices, but rather halts the sales of further devices:

The Company has determined that some manufacturing process changes were not submitted for approval to the U.S. Food and Drug Administration (FDA). At this time, the company has identified two instances of changes that, while successfully validated, were not submitted to the FDA. Boston Scientific has informed the FDA and plans to work closely with the agency to resolve this situation as soon as possible.

The Company has no indication that the manufacturing process changes pose any risk to patient safety, and it is not recommending explantation of the devices.

Product families included in this advisory include: COGNIS®, CONFIENT™, LIVIAN™, PRIZM™, RENEWAL®, TELIGEN® and VITALITY™. The Company's pacemakers and other products are not affected by this advisory.

But the interesting part of this news is who knew first. According to theheart.org:

Analyst reports were among the first to trumpet the news, even before Boston Scientific issued its alert. Larry Biegelsen of Wells Fargo Securities predicted early this morning that the news will mean "reputational damage" for the company, despite the fact that the problem appears to be "administrative."

And here I thought the big news of the day was going to be at the meeting.

-Wes

The Importance of Blogs and Device Advisories

Yesterday, I reported on this blog the trouble Medtronic had experienced with and earlier batch of defibrillators due to a low-voltage capacitor problem from an outside supplier back in 2005 or 2006. The problem was identified in a relatively small number of devices and has not affected their devices' functionality, but the expected battery life of these batch of devices was discovered to be shorter than they had expected. A root cause analysis was undertaken and the capacitor issue was identified. After consulting their physician advisory panel, they elected to notify all doctors who implant their devices about the issue and provided the patients' names that they were aware of to doctors to help facilitate patient notification.

Importantly, there was not a press release.

Personally, I think this was a good thing. As of this moment, I was only able to find one reference to this advisory in once major newspaper, the Wall Street Journal. No doubt, the news will spread rapidly from there.

But it will not spread like a press release would: fired instantaneously to every news organization around the globe always looking for the next tidbit to report, especially tidbits that create lots of angst. Importantly, the piece from the Wall Street Journal did not include a hyperlink where patients would look up if their device was affected.

It has been interesting to also see who has been reading my blog post on this matter. Sitemeter is handy for that. At first, it was lots of hits from medtronic.com, but not too soon thereafter came guidant.com, bostonscientific.com, and the like.

There is no question that these device manufacturers are fierce competitors. As such, let's just say they like to keep things relatively private between themselves. But these device manufacturers may also use the same outside vendors for supplies, including low-voltage capacitors in their circuitry and maybe, just maybe, by getting the information out about one manufacturer's design problem, others will check their old devices as well.

So while blogs have been controvertial for their ability to spread news, good or bad, at lightning speed, the fact that they don't appear at first on the Nightly News or front page of major newspapers might just be a good thing while effectively communicating the issues to our patients (and other interested parties) without terrorizing the masses.

-Wes

Medtronic Issues New Pacemaker Advisory

Today, Medtronic began notifying physicians and patients about a new advisory (pdf) on some of their Kappa and Sigma series of pacemakers manufactured between 2000 and 2002. The defect stems from certain "voids" created in the solder joint where the attachments are made with the circuit board, causing them to fail over time. This loss of connection could lead to premature battery depletion, loss of rate response, loss of telemetry, or even no output.

Although these pacemakers were one of Medtronic's most popular pacemaker lines in early 2000-2004 with over 1.7 million devices implanted worldwide, it is estimated that only 36,900 remain actively implanted in patients. There have been two reported deaths that, while it is uncertain, may have stemmed from this problem.

According to the advisory letter, Medtronic has observed 285 Kappa devices and 131 Sigma devices affected by this issue, representing 0.49% of all Kappa devices and 0.88% of all Sigma devices implanted. It is estimated that the failure rates of Kappa pacemakers is 1.1% and Sigma pacemakers is 4.8% over the remaining lifetime of these pacemakers (the higher failure rate in the Sigma device because of its longer estimated longevity).

Physicians and patients can find if their particular device is affected by logging on to http://www.KappaSigmaSNList.medtronic.com to look up their specific serial number to see if it's affected by this advisory.

Also according to the letter, another subset of Kappa pacemakers involving an additional 96,000 devices might be affected by this defect, but at a much lower failure rate of 0.04% of the devices.

Physicians should consider replacing devices in pacemaker-dependent patients (those dependent on the device for their heart to beat). Further recommendations and information about the advisory can be found on the advisory letter issued today.

-Wes

The Challenge of Medical Device Advisories

It was a routine pacemaker implant yesterday. No big deal, really.

But there's always one point of a surgical procedure that grabs the doctor's gonads, and for device implants, it's usually gaining access to the blood vessel where the leads for a pacemaker or defibrillator are to be implanted. You see, poke too deeply, you might hit the patient's lung. Poke a half a centimeter higher toward the patient's head, you might hit the high-pressure artery rather than the low pressure vein and bleeding will compress the target vein, making it very difficult to cannulate. Don't poke deeply enough, you never get in the vessel. That's the way these procedures go. (I've already mentioned that I cheat and use a vascular ultrasound device to find the vessel. I mean, why stress, right?)

But yesterday, I encountered a "new" challenge: not being able to advance a guidewire into the vessel after I had entered it with a needle.

"What the....?" This was certainly not something I had encountered before. And that's when the rep who was in the lab said: "I wonder if that's one of those recalled SafeSheaths."

"What recalled SafeSheaths?"

"I'm not sure, but I think there was a problem that sometimes the needle hub was not aligned properly and people couldn't pass a guidewire into the vein."

"Seriously? Well that sucks," I said.

So I had to pull out the carefully placed needle and try a new one. Fortunately, the rest of the procedure went fine. But I stopped briefly later to see what existed on the Internet about this problem, and sure enough, I found this little pdf document about the problem posted way back in September, 2008. I was unaware of this problem.

I wonder, how many other advisories am I unaware of? What responsibility to distributors of medical products have to their customers? What responsibility to the manufacturers have? What did I miss?

Because all of the FDA warnings and advisories and recalls don't mean a thing if the information is not received by the end users. Unfortunately, I suspect this will always be a challenge, irrespective of the amount of money we pour into oversight bodies. Maybe, just maybe, placing information like this in the blog-o-sphere will help out another device implanter caught unaware.

-Wes

Digoxin: Another Generic Drug Recalled

First it was digitek, then generic Toprol ER, now it's digoxin from Caraco Pharmaceuticals.

Caraco Digoxin 0.125 mg is a scored round biconvex yellow tablet imprinted with “437” and Caraco Digoxin 0.25 mg is a scored round biconvex white tablet imprinted with “441.”

Fortunately, alternate generic suppliers of digoxin exist and include Actavis Totawa, Smithkline Beecham, Jerome Stevens, and West Ward.

-Wes

Reference: The FDA's electronic "Orange Book" containing Approved Drug Products With Therapeutic Equivalence Evaluations.

Medtronic Updates Doctors on Sprint Fidelis Defibrillator Lead

In anticipation of an upcoming New York Times article to run this weekend, I just received my 'dear doctor' letter from Medtronic updating the status of their advisory Sprint Fidelis defibrillator lead. Reportedly, the NYT article will highlight a recently reported study published online before print from the medical journal Heart Rhythm that describes a higher-than anticipated failure rate from the lead. These data are in contrast to other published data assembled in Medtronic's 'Dear Doctor' letter.

While there is probably no larger cardiac device concern for electrophysiologists and their affected patients, Medtronic's disclosure with patient management recommendations based on Hauser's data and others before the release of the upcoming article in the New York Times is appreciated and should assist patients and doctors as they discuss their treatment options. Importantly, Medtronic points out:

"The FDA’s MAUDE database currently has 107 Medical Device Reports (MDRs) that include allegations that the Fidelis lead may have caused or contributed to a patient death. Most of these MDRs were not initiated by medical professionals; the majority were initiated by family members or attorneys with minimal supporting data. Medtronic’s Independent Physician Quality Panel has reviewed 89 of the 107 reports. It is not possible to determine cause of death with certainty. The Panel has identified 13 patient deaths in which a Sprint Fidelis lead fracture may have been a possible or likely contributing factor.

The Panel noted that four of the 13 deaths were associated with lead extraction, highlighting the risks associated with that procedure. With the exception of the appearance of deaths associated with lead extraction, no new or unexpected trends have been observed."

So we'll see that the news article says, but one thing's for sure...

...Monday should be interesting.

-Wes

Addendum:
NYT article 13 Mar 2009: "Medtronic Links Device for Heart to 13 Deaths"

Dr. Wes: Medtronic's Sprint Fidelis Performance Lead Update - May 13, 2008
Dr. Wes: Challenges With a Lead Recall - Oct 17, 2007
Dr. Wes: More on Medtronics Sprint Fidelis Advisory - Oct 15, 2007

What Price Safety?

In February, 1996, the FDA issued this directive:

"In keeping with its commitment to speed up patient access to new medical devices, FDA is exempting 122 categories of low-risk devices from premarket review, adding to the 450 categories already exempted from such review. Since the exempted devices will no longer have to wait for premarket review, they can reach patients sooner and FDA can shift resources to more critical needs."

With the increasing complexity of implantable medical devices and a growing desire to innovate ways to manage patient's chronic medical conditions remotely, there is a need to downsize connections of leads and sensors to the computer electronics of these sophistocated devices. Until now, a standard two-electrode connection system called an "IS-1" standard has been used to connect leads and sensors to the housing of implantable cardiac devices.

For at least the past three years, the large medical device manufacturers have been developing a new 4-electrode connection system called "IS-4" that promises to supplant the IS-1 connection system. Because the medical device industry has argued that the changes to the IS-1 standard used to implement the IS-4 standard were minor, they applied for pre-market approval through the FDA's 510K exemption that does not require human clinical testing prior to market release of devices, but rather relies on historical information from existing technology supplemented by animal and specialized bench testing. While this approach has worked well for some new defibrillator leads, others have not fared so well.

Earlier, the Medtronic Sprint Fidelis defibrillator lead family, a thinner cousin of prior defibrillator leads, was released under the same 510K exemption ruling of the FDA, but subsequently recalled in October, 2007 after post-market surveillance demonstrated an increased failure rate of this lead family compared to its predecessors. Some 235,000 patients were affected.

Now, just before the release of new defibrillator leads containing the new IS-4 standard connections, Drs. Robert G. Hauser and Adrian K. Almquist of the Minneapolis Heart Institute are sounding their concerns over upcoming release, arguing that human testing should be performed before the lead is released to the public at large. They argue, in part, four concerns:

• "In our opinion, the decision by the FDA and industry to forgo premarket clinical testing of the connector is not in the best interest of patients. For starters, the four-pole connector is a complex electromechanical design that requires major changes to the ICD lead and pulse generator; it should therefore be considered an investigational technology."


• "Second, no published study has shown that the results of bench testing or testing in animals accurately predict the clinical reliability of ICD systems. If they did, recalls would be uncommon."


• "Third, there is no medically necessary reason for rapidly deploying the four-pole connector. Current connector systems have been in use for more than a decade and are performing reliably."


• "Fourth, FDA approval would allow the four-pole connection system to be used in patients without the level of informed consent that is usually required for investigational devices. After the recent Supreme Court decision in Riegel v. Medtronic, FDA approval would also leave patients without the ability to sue the manufacturer for compensation for injuries caused by a four-pole connector."

Hauser's and Almquist's concerns are being voiced at a particularly sensitive time as batteries of the devices connected to the recalled Sprint Fidelis leads are expiring. Doctors are sensitive to the particular challenges that lead revisions impart in the management of their patients since lead revisions or replacements during battery changes greatly complicates an otherise simple battery change procedure.

But the FDA, in their accompanying editorial, countered:

"When preclinical studies and existing clinical data support approval and expected long-term failure rates are low, postapproval studies may provide an appropriate means for verifying long-term device performance. Ensuring device safety does not necessarily require that every device be clinically evaluated before marketing. Approval of some implantable leads with IS-4 connectors may be appropriate without new clinical data. The FDA decides what information is needed to support an approval on the basis of its review of an individual application. This is a scientifically sound approach to protecting public health.

So which side is right in this debate?

Well, in some respects, they both are. No one can argue that patient safety should take priority in this debate, but at what cost? When we review the failure rates of even a known faulty lead like the Sprint Fidelis, its failure is only slightly higher than prior leads. For instance, the failure rate of a "good" Medtronic Model 6947 Sprint Quatro lead has a 1.9%% failure rate at 3 years, versus the 5% 3-year failure rate of the "bad" Medtronic Sprint Fidelis lead. Detecting a signficant difference of 3 percentage-point failure rate would take two fairly large patient comparison groups randomized and followed for many years to detect such a small difference in failure rate with sufficient statitical power. This would add signficant cost to devices, certainly, and would delay market release of newer innovations. The chilling effect on device development would cause every company to think long and hard before bringing any new technology to market.

But the public has grown wary of lack of regulation in many sectors of our economy, especially that portion that has been ridden roughshod by the financial sector. They are aware that the FDA needs the device manufacturers for their review fees, and hence have become skeptical of the FDA's ability to remain unbiased in their review process. They are no longer naïve about the physical and psychological toll such failures have upon patients, thanks, in part, to the unrelenting press coverage that these recalls generate ("Bad news sells best, 'cause good news is no news.") Regretably, we rarely hear about the lives saved by these devices every day.

The technology boom in medicine is under tremendous pressure to contract as health care costs continue to skyrocket and Congress looks for new ways to cut costs. The days of unfettered capitalism and quick profits in medicine are quickly coming to an end. Hitching the bandwagon to "patient safety" will be a powerful driving force for policy advocates to stifle innovation in the health care sector as we cling to the security of the known during this economic contraction.

What are the implications of the loss of post-market surveillance as a means of determining patient safety? What are the implications for costs of devices going forward? How much are we willing to spend to assure relative safety perfection? How safe is safe enough? Have not the existing standards for device approval resulted in some very beneficial and reliable systems? Must we assume there is too little value or economy to post-market surveillance to permit it's exclusive use for introducing new technology?

There's no question that Drs. Hauser and Almquist make important points. The bigger question might ultimately be: how much do we want to spend?

-Wes

References:

Hauser RG, Almquist AK. "Learning from our mistakes? Testing new ICD technology." N Engl J Med 2008;359:2517-2519.

Shein MJ, Schultz DJ. "Testing New ICD Technology," New Engl J Med 2008; 359: 2610.

Software Said To Reduce Inappropriate ICD Shocks

In October, 2007, Medtronic issued one of the largest defibrillator lead advisory alerts for their popular and thin Model 6949 Sprint Fidelis lead due to the lead's higher-than-expected fracture rate. More recently, a software patch called a Lead Integrity Alert has been developed that can be uploaded into affected patients' defibrillators in hopes of improving the detection of lead fracture conditions. The software also automatically readjusts the settings of the defibrillator to make it less prone to deliver inappropriate shocks caused by lead failure.

Today in Circulation, the efficacy of this algorithm to avoid shocks was published from in vitro testing on leads returned to the manufacturer.* Real life effectivness of the algorithm has not been tested to date. So far, the algorithm theoretically shows improvement in avoiding unnecessary shocks:

To reduce inappropriate shocks, the lead-integrity algorithm increases the number of intervals to detect (NID) ventricular fibrillation when triggered. The lead-integrity algorithm was tested on data from 15,970 patients with Fidelis leads (including 121 with clinically diagnosed fractures) and 95 other fractured leads confirmed by analysis of returned product. The effect of the NID on inappropriate shocks was tested in 92 patients with 927 shocks caused by lead fracture. Increasing the NID reduced inappropriate shocks (P<0.0001). The lead-integrity algorithm provided at least a 3-day warning of inappropriate shocks in 76% (95% CI, 66 to 84) of patients versus 55% (95% CI, 43 to 64) for optimal impedance monitoring (P=0.007). Its positive predictive value was 72% for lead fractures and 81% for lead fractures or header-connector problems requiring surgical intervention. The false-positive rate was 1 per 372 patient-years of monitoring.

The distribution of the fractures reported was also interesting:

Of the 95 patients in the RPA (returned product analysis) group, 41 (43%) had fractures of the coil conductor to the tip electrode and 54 (57%) had fractures of the cable conductor to the ring electrode. Figure 5 shows that all coil fractures occurred at the anchor sleeve, whereas 52 of the cable fractures (96%) occurred distally or at the bifurcation/trifurcation.

We are about to see a rising number of patients with these leads enter the clinical arena as their ICD batteries reach their elective replacement indicators warning us of battery depletion. Recommendations from the company have so far been few, but most suggest a relatively conservative watch and wait approach. But when the patient's ICD pocket is opened for a battery change, the opportunity to place a new, non-recalled lead presents itself and should be considered (provided of course venous access still exists in which to place the new lead).

The difficult decision will come when there is no venous access in which to place a new lead from the same side as the existing defibrillator. Should we abandon the existing side and place an entirely new system on the opposite side with new, non-recalled leads? Should we send the patient for lead extraction and replacement? Or should we re-connect the old lead and hope for the best if no other option presents itself?

These are not easy decisions.

Patients with Sprint Fidelis leads should discuss what's involved with each of these scenarios with their doctors when the time comes to replace their defibrillator battery. Hopefully, we'll have additional trend data regarding lead survival on which to base future management recommendations. But until we do, battery changes in these patient's with Sprint Fidelis leads will be anything but routine.

-Wes

*The study was funded by Medtronic.

Other information:
Medtronic's Official Sprint Fidelis Information WebSite
TheHeart.org: Updated Lead Failure Rate Information
Medtronic to Pull Its Most Popular Defibrillator Lead
More on the Medtronic's Sprint Fidelis Advisory
Medtronic's Sprint Fidelis Perfomance Lead Update

ICD Class Action: Patients 40%, Lawyers 60%

As reported in the Star Tribune regarding the faulty implantable cardiac defibrillator (ICD) battery suit settled by Medtronic from the recall of 2005:

Less than half of the Medtronic settlement has been mailed to people who received defibrillators that were recalled in 2005 because of concerns about battery failures. The rest of the disbursements remain stalled, as lawyers deal with Medicare and Medicaid issues and third-party liens.

"We wanted to get some money into the hands of the claimants while we get other issues resolved," said Dan Gustafson, a Minneapolis lawyer and co-lead counsel in the Medtronic lawsuit.

But getting 40 percent of your total damages in September 2008 from a settlement that was announced in December 2007 still rankles some of those people who wore the recalled devices.

One would think this legal wrangling would be negotiated ahead of time, but I've got to say that there's some justice being served here as lawyers get to deal with Medicare and Medicaid issues, too.

-Wes

Software Coming to Help Detect Medtronic Sprint Fidelis Lead Fractures

Sometime next week, we should be receiving software, called the "Lead Integrity Alert" that can be uploaded into existing Medtronic implantable cardiac defibrillators (ICDs) to help detect lead fractures from the recalled Sprint Fidelis (Model 6949) defibrillator leads. This software was approved by the FDA today and can be uploaded into the Medtronic's Marquis, Maximo, Virtuoso and Concerto ICD models non-invasively during a routine office visit. It is thought that such programming changes can reduce the number of patients who receive an inappropriate shock from a lead fracture before it is explanted by 38 to 40%. While not perfect, it might alert both the patient and physician earlier to a avoid unnecessary shocks should a lead fracture.

How the Software Works

There is a so-called Sensing Integrity Counter that usually trips an alert if there are greater than 300 counts of non-physiologic sensed intervals by the device. This software will lower this number to 30 or more to trigger an alert. Further, if there are an excessive number of very short "non-sustained ventricular tachycardia" sensed intervals, this also could trigger an alert. The software also allows an automatic adjustment of the "number of intervals to detect" to be automatically incremented to the next-higher detection ratio in hopes of averting a shock, while beeping six times a day (rather than once) to improve the chances a patient will notice the new alert state if tripped.

What to Do

Patients with the advisory leads will have the software automatically installed during their next routine office device check, but those who want it installed earlier should contact their doctor and inquire if the software could be installed earlier.

Realize this software only affects Medtronic ICDs. St. Jude and Boston Scientific devices are NOT affected.

-Wes

11 Sep 2008 Update: Medtronic's Info on the Lead Integrity Alert.

Medtronic's Sprint Fidelis Performance Lead Update

It's now been six months since Medtronic's lead recall of their 7-French Model 6949 Sprint Fidelis defibrillator lead in October 2007. The first update of the lead performance arrived in my office this week, dated 7 May 2008 (you can view it here). With this letter came the first trending data of the failure rates as determined by evaluation of Medtronic's Carelink follow-up database and Returned Product Analysis (RPA) reports as well.

While the number of lead failures remains relatively small and current follow-up recommendations have not changed, the failure trends, albeit early, remain concerning. It appears that a continued number of failures throughout the life of the lead can be expected. By Medtronic's analysis of a typical 1000-patient ICD clinic, over the next 12 months, nine (9) patients can be expected to have an anode or cathode failure and half of those patient's will have little warning of an impending fracture.

The implications of these recommendations are far-reaching, for it now seems the fault with the lead was not a physician implant technique problem as originally surmised, but rather a design flaw. Further, when it comes to replacing these patient's defibrillator batteries over the next four or five years, electrophysiologists will likely be advised to replace the 6949 lead with a more reliable defibrillator lead model, like the 6947, increasing the difficulty of a typical device battery change procedure.

-Wes

Digitek Recalled

"Foxglove Season" (Digitalis purpurea)

Heard about this from a patient tip after she had a problem getting a refill at the local Walgreens as they scramble to re-stock:

Actavis has issued a nationwide recall of Digitek (digoxin tablets) due to the possibility that tablets with double-thickness, containing twice the approved level of active ingredient, may have been commercially released. The existence of double strength tablets poses a risk of digitalis toxicity in patients with renal failure. Digitalis toxicity can cause nausea, vomiting, dizziness, low blood pressure, cardiac instability, bradycardia, and possible fatality. Several reports of illness and injuries have been received.

Yikes! Check your meds, folks!

-Wes

A Conversation I Never Want to Have

Mr. Smith, welcome back to the real world!

Did you know that your heart stopped earlier today, but thanks to your friendly neighborhood paramedic and a handy-dandy AED, we got it going again?

Amazing, huh?

We've done an extensive evaluation of your medical condition, Mr. Smith, and we think you need to have and ICD implanted.

What's that? Oh, an "ICD" is short for a implantable cardioverter defibrillator. It's a little device we implant under your skin that is attached to special wires we place in your heart that monitors your heart rhythm, so that should this happen again, the device can automatically detect, charge, and shock your heart back to normal rhythm lickety split.

Sound good? Great!

Now, a few things I need to ask you: we have three main manufacturers that make these devices here in the US: Medtronic, Boston Scientific, and St. Jude Medical. If those don't sound good, you can alternatively have us special-order you a device from Germany called a Biotronik device. It might cost you a bit more and I'm not sure there will always be a rep available to help check the device, but hey, we want to keep you well informed about ALL possibilities. Any preference?

What's that you say, you're not sure? Well, here's some more information:

The safety record for each of these manufacturers has been pretty good, but once in a while there have been some problems with recalls of leads and batteries of these devices. When this happens, believe it or not these suckers can explode inside your chest with lots of great big shocks and maybe even kill you. I'm not kidding. Really. Now admittedly this happens infrequently, but hey, I just want you to know about this. We want you informed. There's even legal action pending against all of the manufacturers. Did you know this? Now the FDA has all kinds of requirements that they make these device companies jump through, but you know, they've been a bit short-staffed lately. But they're getting stricker now. I mean they check everything now - heck new products? Well, they're still checking out the old ones. Oh, and those overseas plants that make parts? Well the FDA has to keep checking those too.

How often are there problems? Well, I'm so glad you asked!

Here's the manufacturers' published safety statistics for Boston Scientific, Medtronic, St. Jude. Study this information carefully. I really don't want you making the wrong decision! What's that you say? You're not sure if you should have one? But the data are so CLEAR!

Oh well, that's your decision, Mr. Smith. Never mind that you saw God earlier today.

Hey, at least I feel good you're now COMPLETELY informed!

* * *
It's easy to criticize our current system of checks and balances for medical device safety, as William H. Maisel, MD, MPH does so well in the New England Journal of Medicine this week. And while he makes some good points about the need for consideration of better overview of pre-release testing of new devices to the market, can we really expect that patients can understand all of the implications of ICD type, safety information, and implications for their care just after they've suffered an episode of aborted sudden death?

With remarkable failure to acknowledge efforts by the FDA, Heart Rhythm Society, and manufacturers already underway to improve post-market performance evaluations, he writes:

According to its mission statement, the FDA is "responsible for protecting the public health" and for "helping the public get the accurate, science-based information they need." Unfortunately, the agency is failing to fulfill that mission. In 1998, the Advisory Commission on Consumer Protection and Quality in the Health Care Industry adopted a Patients' Bill of Rights whose primary tenet is that patients have "the right to receive accurate, easily understood information to assist them in making informed decisions." Regrettably, patients considering implantation of medical devices often fail to receive critical information on device safety.

Should patients be faced with all available safety information when they present as the fictional patient above does? And what about the product performance report references that are already published, updated quarterly, and available on the web? Should they be given the opportunity to scour these data before signing their surgical consents? Should the data be updated weekly? Will patients be able to understand these data and the nuances of the recalls underway? How much more "safety data" will patient's need to absorb to meet Dr. Maisel's expectations for full "disclosure?"

Certainly, we should always strive for improved patient safety. But to suggest that efforts are not underway to assure timely reporting of post-market performance analysis flies in the face of the many countless individuals who have devoted huge personal effort and resources to continually improve this endeavor.

Maybe, just maybe, we should empower the doctors to present the data to the patient, rather than impose more governmental regulation.

No. I forgot.

In the medicine of today, bureaucracy always wins.

-Wes

The Baxter Heparin Recall

Thanks to the previous post's commenter who asked for a brief note regarding the recent Baxter pharmaceutical heparin recall. Today's Chicago Tribune front page story suggested that an unknown contaminant was possibly added to the heparin. While this makes for all kinds of intrigue, it seems to me that the authors forgot one important issue: what hospitals are doing with heparin availability in the meantime.

First, it is important to note that the recalled heparin is only in the higher dose concentrations. Importantly, other heparin is available from other manufacturers, though it might be less abundant. So I called our pharmacists, and they were nice enough to send on these steps we're implementing:

"Because of this recall we anticipate at least several weeks of short supply as other manufacturers work to get more product to the market. This will impact Evanston Northwestern Healthcare in the following ways:

1. Patients on a heparin nomogram with boluses: If a bolus dose of heparin is needed based on the aPTT result, the nurse must contact pharmacy to dispense the bolus. Pharmacy will be drawing up patient specific bolus doses to conserve available stock. Vials of heparin have been removed from general nursing unit Pyxis machines.
2. Use of standard heparin for VTE prophylaxis. This strength will be in particularly short supply. Pharmacists will be working with physicians to try to convert as many patients as possible to other prophylaxis measures, e.g., Lovenox (enoxaparin). In addition, the pharmacy will be dispensing the standard heparin prophylaxis doses from the central pharmacy as syringes after our vial stock runs out.
3. Several treatment areas that require heparin urgently will continue to have stock in Pyxis or floorstock as usual, however please be aware that it may look different than you may be used to. As always, please be sure to read medication labels carefully. The pharmacy department will be communicating with these areas as we become aware of any changes to products stocked."

Glad to see my atrial fibrillation ablation procedures can continue...

-Wes

Check Your Heparin

Two different recalls of heparin contamination were just released:

One from Baxter Pharmaceuticals:

(WSJ) The Deerfield, Ill., company began recalling the lots on Jan. 17. Baxter said it normally receives 60 to 70 reports during a given year of possible reactions to heparin, but in this instance it received about 150 such reports just so far in January, the company said Friday. The reactions include a range of symptoms, such as nausea, vomiting, dizziness, fainting, throat swelling and low blood pressure.

The company said that so far one death has occurred that "may be associated" with the heparin in question.

The units in question are called "1,000 units/mL 10mL and 30mL multi-dose vials." Baxter said it hasn't seen an increase in adverse reactions to any of its other forms of heparin.

The other recall comes pre-filled syringes from AM2 PAT, Inc., of Angier, N.C.:

(via the FDA) Two lots have been found to be contaminated with Serratia marcescens, a bacterium that can cause serious injury or death.

These syringes are manufactured by AM2 PAT under the brand names Sierra Pre-filled, Inc. and B. Braun. They are sold in fill sizes of 3mL, 5mL and 10mL and syringe sizes of 6mL and 12mL.

Consumers and health care facilities with any of the recalled, pre-filled Heparin Lock or Normal Saline IV Flush syringes should stop using the product immediately. Health care facilities should immediately quarantine the products in their inventory and return them to their distributor. Individual consumers should return them to the location from which they were received, such as a pharmacy or hospital. They should also let their health care providers know that they have been exposed to syringes recalled by FDA.

The recall affects all lots of these products. The FDA received information that Heparin Lock Flush syringes from Lot 070926H and Normal Saline IV syringes from Lot 070917A have been found to be contaminated with Serratia marcescens, and have resulted in patient infections. The U.S. Centers for Disease Control and Prevention has confirmed growth of Serratia marcescens from unopened heparin syringes.

Traditionally, Serratia marcescens, a bacterium found in water and soil has been linked to pneumonia, blood infections, and urinary tract and wound infections. Some patients exposed to the recalled syringes have developed blood infections.

Weird how these came a day apart. But don't worry, the lawyers are already on it.

-Wes

References: Baxter's recall notice.

AM2 PAT's press release.