FDA Approves Novel Implanted Sensor To Monitor Heart Failure Reply

The FDA announced today that it had approved the CardioMEMS Champion HF System. The small implantable device provides daily pulmonary artery pressure measurements to guide physicians in their treatment of  NYHA Class III heart failure patients who have been hospitalized for heart failure in the previous year. The system consists of three parts: a small permanent sensor implanted in the pulmonary artery, a catheter-based delivery system, and a system that acquires and processes PA pressure measurements from the implanted monitor and transfers the data to a secure database.

Click here to read the entire post on Forbes.

 

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The Walking Dead: Renal Denervation In Europe Just Can’t Be Stopped Reply

Earlier this year the only large, well-designed trial of renal denervation– the once highly-promising catheter-based technology that was widely expected to “cure” difficult cases of resistant hypertension– failed spectacularly. Many hypertension experts believe that ultimately the technique will prove to be beneficial, but after the failure of Simplicity HTN-3 it is clear that there’s a great deal of research that needs to be performed to find out just how– or if– this novel technology should be used.

In the US this does not present a problem. The FDA has not approved renal denervation so it can only be used in a research setting. But that is not the case in Europe, where the device is available due to lower standards for device approval.

Right now Europe’s largest interventional cardiology meeting, Euro PCR, is underway in Paris. Surprisingly– or perhaps not– renal denervation is still being heavily promoted in Europe. Here is the evidence: a series of tweets by @Jeddacath, an interventional cardiologist who trained at the Brigham & Women’s Hospital in Boston and who is attending the meeting.

Click here to read the full post on Forbes.

 

Walking Dead

Guest Post: How Sure Can We Be About Optisure? 2

Editor’s Note: The following guest post is published with the permission of its author, Edward J. Schloss, MD, (Twitter ID @EJSMD) the medical director of cardiac electrophysiology at Christ Hospital in Cincinnati, OH.

How Sure Can We Be About Optisure?

by Edward J. Schloss, MD

On March 24, St. Jude Medical announced the global launch of the Optisure family of ICD leads. It’s been a while since a new ICD lead was launched, and I’m probably not the only one who was caught by surprise. I’d like to explore why this approval is important for the ICD community. First, a brief history of ICD leads from St. Jude.

FROM RIATA TO DURATA

St. Jude Medical developed its own line of ICD leads after it purchased the former ICD vendor Ventritex in 1996. The first-generation Riata lead, approved in 2001, was succeeded by the Riata ST line in 2006. These leads were distinguished, in part, by their thin diameter, permitting implantation through a 7 Fr introducer sheath. In that era, implanting physicians’ interest in a thin lead was very strong. Even the high-profile failure of the 7 Fr Medtronic Fidelis ICD lead didn’t seem to dampen that enthusiasm.

Both of St. Jude’s Riata lead families later developed problems. Reports of subacute perforation soon after implant in the Riata ST line arose in the late 2000s. A year or two later, the internal core structure of both the Riata and Riata ST leads was discovered to break down in 25% and 10%, respectively, of these leads, as evident on fluoroscopic evaluation — a process called externalization. This problem, along with noted increased electrical failures of this lead, prompted an FDA class I recall of both product lines in December 2011, in addition to intense scrutiny and discussion in the lay press, investor press, blogosphere, and academic literature.

By the time the Riata and Riata ST leads were recalled, St. Jude had already gotten approval and marketed the successors: Riata ST Optim and, later, the Durata lead. Both these leads shared design similarities with the Riata ST lead, but additional modifications were intended to prevent the failures that the predecessor lines had exhibited. To mitigate the perforation risk specifically, changes in the Durata lead were intended to minimize tip pressure to the myocardium. And both new leads had a new insulator wrapping around the silicon core from Riata ST. This Optim insulation, shown to be more resistant to abrasion, has apparently been successful at preventing the fluoroscopic externalization that had occurred with the earlier leads.

The failure of the Riata leads has been shown to be time-dependent, so the device community has expressed some concern about Durata’s future performance. In addition, FDA has continued to apply pressure, with a January 2013 warning letter about this lead, specifically noting problems detected during a California plant inspection. Early active registry studies of Durata have been highly favorable, but a limited number of Durata problems have been discussed in case reports. Noted ICD critic Dr. Robert Hauser has also reported on a series of Durata failures from the FDA MAUDE database.

INSIDE THE DURATA

The Durata and Riata ST may share some failure mechanisms. In particular, the Swerdlow case report revealed inside–out abrasion under the distal shocking coil, resulting in a short between that coil and the ring-electrode cable, and consequent oversensing. Swerdlow and the Hauser MAUDE study have suggested that a similar form of insulation failure at the proximal shocking electrode could result in failure to defibrillate. (Because Durata and Riata ST have essentially the same internal design and materials at the level of the shocking coils, it is possible that this failure mechanism will occur with the newer leads.)

Moreover, Swerdlow found evidence of disruption of the Optim layer, which he hypothesized was due to Optim degradation, possibly related to hydrolysis of the polymer and cyclical stresses during the 4 years of lead service. The long-term biostability of Optim is critical, because without the Optim layer, the Durata leads are quite similar to Riata ST.

St. Jude has staunchly defended Durata, citing the favorable active registry data and additional testing in a large bibliography on its website. The company’s independent engineering analysis concluded that Swerdlow’s lead was damaged externally as a result of the extraction tools, not Optim degradation (counter to Swerdlow’s assertion).

THE BASICS ABOUT OPTISURE

St. Jude released Optisure this week, its first new ICD lead line since Durata. The product literature describes Optisure as “providing an additional system enhancement for addressing lead complications and improving system reliability.” The company says the slightly thicker 8 Fr lead is “for physicians who prefer a larger lead diameter.”

According to St. Jude, Optisure is built on the basic design of Durata with these additional modifications:

  • 8 Fr lead body
  • additional Optim insulation at the proximal end of the lead
  • new layer of Optim insulation under the SVC shocking coil

FDA filings show Optisure was submitted for approval as a PMA (pre-market approval) supplement on 10/24/12 and approved for release on 02/21/14. The filing links back to the original PMA for the Ventritex TVL lead issued in 1996. It does not appear that a human clinical trial was performed, as is common in PMA supplement approvals.

MY ANALYSIS OF OPTISURE

I’m happy that ICD companies continue to pursue process improvement. If we ever reach the point when we think we have a lead that is “good enough,” that will be really unfortunate. I’ve continued to have some concerns about Durata. ICD lead failures in the Riata lines have not become evident until 4 years of use, and we are only recently accumulating large numbers of Durata leads that have been implanted that long. Fortunately, Optisure’s design attempts to directly address two of the feared possible failure mechanisms of the Durata lead.

First, the increased Optim thickness in the proximal lead is likely to diminish the can/lead abrasion in the pocket, and perhaps in areas of cyclical stress. I find it really ironic and satisfying to read that St. Jude is promoting Optisure “for physicians who prefer a larger lead diameter.” Back in 2010, when I criticized thin ICD leads in an HRS debate, I had a hard time getting people to agree with me. Now, going thicker is a marketing strategy. Times really have changed.

Second, the Optim layer under the proximal shocking coil should help to prevent internal shorts that could cause lead failure. This type of short, if it involves the distal high voltage cable, is especially worrisome, as it may manifest only at the time of clinical or induced ventricular fibrillation. I fear that proximal coil HV shorting may be responsible for many of the Riata and Durata lead failures and deaths documented in MAUDE database entries, such as those published by Hauser (as well as this more recent report). Having a layer of Optim between the silicone core and the SVC shocking coil should help to prevent this shorting, just as it has prevented externalization. Unfortunately, this mitigation will not change the likelihood of shorting under the RV coil (as in Swerdlow’s case) but should help overall lead reliability. St. Jude seems to feel the same way, citing Optisure’s design as an “enhancement for addressing lead complications and improving system reliability.”

WHAT’S NEXT FOR ICDs?

Getting a pacemaker or ICD lead designed, approved, and built is an enormous undertaking. The process has only become more difficult because of increasing regulatory barriers. The formerly common process of PMA supplement approval has come under greater scrutiny. ICD and LV leads that formerly might have been approved under PMA supplement now require large U.S. trials. The trials’ costs, coupled with the fear of another Fidelis or Riata debacle, appear to have stifled lead innovation. Given the development of two new of leadless pacemakers (now being implanted in Europe) and the U.S.-approved subcutaneous ICD, we may be at the beginning of the end of the era of transvenous cardiac leads.

I have to agree with Zheng and Redberg that the PMA supplement process for medical device approval is problematic. The fact that leads from Riata to Optisure were approved on the basis of a dissimilar lead developed by a different company nearly 20 years ago should be ample evidence of this argument. Should Riata leads have gone through a clinical trial? Answering yes may seem logical. The unfortunate reality, however, is that no pre-market clinical trial would have picked up this lead’s late and novel failure mechanism. Even today, I would argue that careful industry engineering and close post-market scrutiny (including FDA-mandated registries) are doing far more to help our ICD patients than any pre-market trial ever could.

Nevertheless, it is critical to improve existing products, especially ICD leads. Most of us agree these are the “weak link in the chain.” I fear that a more highly regulated environment is having the paradoxically adverse effect of forcing us to settle with what we already have. That’s why I tweeted on March 24 that the quick approval of Optisure “both surprises and pleases me.” I wonder if this lead would even have been developed if it had been forced through a long, expensive clinical trial. Would that outcome have been a good thing?

First Leadless Pacemaker Gains Approval In Europe Reply

St. Jude Medical announced on Monday that the world’s first leadless pacemaker had gained CE Mark approval in Europe. The company also announced that it was buying Nanostim, the company that developed the innovative device. The FDA recently granted conditional approval for an Investigational Device Exemption (IDE) application and a pivotal clinical trial, St. Jude also reported.

Click here to read the full story on Forbes.

 

CardioMEMS Heart Failure Device Gets Mixed Reception From FDA Advisory Panel Reply

The FDA’s Circulatory System Devices Panel sent a mixed message to the FDA today about CardioMEMS Champion HF Pressure Measurement System.  The small implantable device provides provides daily pulmonary artery pressure measurements to guide physicians in their treatment of patients with congestive heart failure.

In December 2011 the same panel voted 9-1 that the device was safe, 7-3 that the device had not been shown to be effective, and 6-4 that the benefits did not outweigh the risks. Now, two years, later, the vote wasn’t much different: the panel agreed unanimously (11-0) that the device was safe; 7-4 that it had not been shown  to be effective, and 6-4-1 that the benefits outweighed the risks.

Click here to read the full story on Forbes.

 

CardioMEMS wireless sensor with quarter

 

Realistic Expectations For New ‘Breakthrough’ Blood Pressure Technology Reply

Early trials of renal denervation, the innovative new catheter-based blood pressure lowering technology,  have resulted in extremely impressive drops in systolic blood pressure in the range of 30 mm Hg. These results have sparked a great deal of excitement in the hypertension community and stirred the interest of a multitude of medical device companies. Some experts have proclaimed renal denervation a potential “cure” for resistant hypertension, perhaps enabling a significant number of patients to eliminate all drug therapy. Other expanded uses of the technology in more moderate forms of hypertension and other diseases are under active consideration. Now, however, a new analysis of the available data suggests the troubling possibility that renal denervation may not be nearly as effective in cutting blood pressure as had been suggested in the earlier trials. Rather than reducing systolic blood pressure by 30 mm hg, the new analysis suggests that a more realistic estimate of the effect of renal denervation may be a much more modest reduction of about 11 mm Hg.

A paper published online in Heart  demonstrates that the large reductions in blood pressure seen so far in clinical trials of renal denervation may be a consequence of certain key aspects in the design of these trials. The apparent blood pressure lowering effect of renal denervation has been greatly magnified because the trials have been uncontrolled, unblinded, and have utilized office-based blood pressure measurements rather than the far more reliable and consistent ambulatory blood pressure monitoring (ABPM).

Click here to read the full story on Forbes.

Novel Leadless Pacemaker Makes Debut At HRS 2013 Reply

First results in human patients of a novel leadless pacemaker were presented last week at the HRS meeting in Denver by Vivek Reddy.  Pacemaker leads are the most common source of complications associated with pacemakers today. The self-contained device is delivered via catheter to the right ventricle, to which it is attached with a fixation mechanism.  The device is manufactured by Nanostim, Inc, a small company which is being acquired by St. Jude Medical.

Click here to read the full story on Forbes.

 

 

Leadless

 

Guest Post: Case Report Of Durata Lead Failure Raises Fresh Concerns Reply

Editor’s Note: The following guest post is published with the permission of its author,  Edward J. Schloss, MD, (Twitter ID @EJSMD) the medical director of cardiac electrophysiology at Christ Hospital in Cincinnati, OH.

Case Report Of Durata Lead Failure Raises Fresh Concerns

by Edward J. Schloss, MD

 A case report of a failed St. Jude Medical Durata ICD lead was published yesterday, raising suspicions that this lead may share some of the same potential failure mechanisms of its troubled predecessor, the Riata lead.

St. Jude’s ICD lead troubles date back to early case reports involving the Riata and Riata ST leads that ultimately led to FDA recall in December 2011.  These leads have since been well documented to be subject both to increased electrical failures and structural breakdown of the lead as has been previously reported.

St. Jude’s Durata lead was designed as a successor to the Riata ST lead and continues to be marketed and implanted.  The Durata lead shared a similar design to the predecessor Riata ST lead with the most notable difference being the addition of a outer coating made of the proprietary co-polymer Optim.  This design modification has been promoted to improve abrasion resistance.  It is hoped that this modification, would prevent the most prominent failure mechanism of the Riata family, inside-out abrasion and cable externalization.
Click to continue reading…

Should Physicians Be Business Partners With Medical Device Salesmen? Reply

Should a Florida cardiologist co-own a business running frozen yogurt shops with a medical device salesman? That’s the question raised by reporter John Dorschner in a story posted by the Miami Herald yesterday:

 

“Mark Sabbota, a Hollywood cardiologist, regularly implants $5,000 pacemakers in patients at Memorial hospitals in South Broward — generating, last year alone, more than a half-million dollars in sales for a manufacturer called St. Jude Medical.

Sabbota, public records show, also happens to be partners with a St. Jude sales rep in two corporations that run frozen yogurt shops.”

 

Click here to read the full story on Forbes.

 

English: Yogurt, Yogurtland, Frozen Desserts

 

 

FDA Releases St. Jude Warning Letter Reply

The FDA on Tuesday released the full text of a warning letter sent last week to St. Jude Medical. The company had previously disclosed the existence of the letter in an SEC filing but did not make clear the full extent of the FDA warning. The letter from the FDA is the latest in a series of setbacks, short term loans UK and challenges to the company’s Durata and Riata ICD leads.

Click here to read the full post on Forbes.

Screen Shot 2013-01-16 at 12.34.00 AM

St Jude CEO Spills The Beans On PFO Closure Trial 1

(Updated at bottom with statement from St. Jude Medical)

Dan Starks, the CEO of St Jude Medical, stated during a quarterly earnings call last week that results of the RESPECT trial of PFO closure for crytpogenic stroke were “favorable” and that the full trial results will be presented in October at the TCT meeting in Miami. But his statement raises more questions than it answers.

It should be noted that it is impossible to ascertain the actual results of the trial from his remarks. He did not even state whether the trial had met its primary endpoint, and there are always potential dangers when the full data from a large trial are analyzed. Further, when asked to confirm whether RESPECT was indeed scheduled for presentation at TCT, TCT’s Gregg Stone told CardioBrief that “the submission deadline [for late-breaking clinical trials] has not even been reached yet.”

Jonathan Tobis, an expert in PFO closure at UCLA, told CardioBrief that any evaluation of the trial should await the full presentation of the data: “this is anybody’s guess until the data is presented,” he said.

Here is the transcript of the relevant portions of the conference call:

Dan Starks (CEO): Earlier this year, we announced that we completed enrollment in our landmark RESPECT clinical trial, evaluating the benefit of PFO closure in patients who suffer from cryptogenic stroke. As a reminder, the RESPECT trial enrolled 980 patients and generated more than 2,700 patient years of experience. We expect the results of this trial to be presented at a late-breaking clinical trial session during the TCT meeting later this year.

In stark contrast to prior randomized trials of competitive PFO devices for mitigation of risk in cryptogenic stoke patients, we are confident our trial will demonstrate greater benefit and less risk in the device arm of the trial.

Michael Weinstein (JP Morgan analyst): …Dan, you mentioned that the PFO closure for stroke RESPECT trial, can you just update us on the filing of that data and that PMA with the FDA? …

Dan Starks: On the PFO closure, the submission to FDA is being prepared as we speak and there is a lot of data to analyze and prepare and organize. And so, I would be confident that the PMA submission will be in during the fourth quarter and I suspect that we would be unlikely to get that submission in before the end of the third quarter. So timing wise that’s our update.

Within that, though, one can see that we have a number – since our organization is strongly focused on preparing that submission, obviously we’re no longer blinded to the data and that was the basis for the level of confidence we’ve expressed that when the full trial results are reported at the TCT, we are optimistic that these will be favorable results.

Comment: The statement that the “trial will demonstrate greater benefit and less risk” for St. Jude’s PFO closure device is highly unusual. One danger is that the company’s initial evaluation of the results may clash with the eventual evaluation of the academic investigators, peer reviewers, other experts, and, ultimately, FDA reviewers and consultants. Companies are in no position to be objective about their own products or trials. This is why academic investigators, peer reviewers, editors, FDA reviewers and consultants, and other interested experts play important roles in discussing and ultimately judging the value of new therapies. Taking the word of a company is simply not acceptable any more.

Many companies in the past have released highly positive press releases of trials that ultimately have  been received in a far harsher light. In some of these cases, there have also been suspicions that the premature release of results could be used to affect a stock. Indeed, Starks’ statement was first reported by an analyst for Merrill Lynch, who wrote that the statement by Starks was “a major disclosure” and concluded that the statement suggests that the trial “hit its primary endpoint.” Ultimately, he wrote, the PFO closure market represents a $500 million “annual market opportunity.” Maybe. But that’s an awfully long way to go on the basis of few vague words spoken in the heat of a conference call.

Caution is warranted especially because of the sorry history of negative trials in this area. It’s possible of course that the St. Jude device is superior to the failed STARFlex Septal Closure System from the now-defunct NMT Medical, but until it can be convincingly demonstrated otherwise the burden of proof lies with those who advocate the continued use of these devices. But the Merrill analyst believes that positive results from RESPECT could spark greater usage in Europe (where the device is already available, despite the complete absence of evidence supporting its use) and greater usage in the US of “other STJ closure technologies,” since many US physicians “believe in the mechanism and the technology as a valid tool to prevent strokes.”

But let’s remember the NEJM editorial by S. Claiborne Johnston that accompanied the Closure 1 trial earlier this year in which he outlined some of the troubling issues raised by the trial. Because of off-label use of closure devices, enrollment in the trial took 5 years and forced a reduction in the sample size of the trial. He continued:

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. Even if only half these patients were treated by this method for the purpose of preventing stroke, it would suggest that during that period of time $400 million was spent on a procedure that had no apparent benefit, to say nothing of the potential clinical risks involved. By limiting the use of device closure to within the remaining clinical trials, such an expense could be curtailed and completion of these trials might be accelerated. In this setting, a strategy of withholding reimbursement for unproven device therapy unless such treatment is part of a randomized trial seems justified.

There are more reasons to be skeptical. Although Starks was quick to bring up RESPECT, he was silent about another St. Jude PFO Closure trial, the European-based PC-Trial, which was finished and had completed its followup before the RESPECT trial. To date the company has yet to release any information about the results of the trial.

The entire case, I think, highlights the importance of restoring the system whereby trial investigators, and not companies, present the results of clinical trials. It’s not a perfect system by any means. But it’s a lot better than the alternative offered here by St. Jude’s CEO.

I’ve asked for comments from St. Jude, the RESPECT trial investigators, and other experts. I’ll update this story as necessary.

Click here for a full transcript of the St. Jude conference call.

Update: Shortly after publication of the above story I received the following statement from St. Jude in response to an earlier request. I will leave it for my readers to decide whether this adequately addresses the issues I’ve raised.

St. Jude Medical has previously expressed confidence in our RESPECT program because of fundamental differences in clinical trial design, patient selection, and device design compared to competitive programs. Mr. Starks was reiterating this confidence and optimism that because of these differences, the outcomes of the RESPECT trial would be different than prior randomized trials. We have also publically indicated our intention to file the PFO PMA before the end of this year which, of course, requires the Company to have visibility into the data in order to perform the required analysis.  Mr. Starks’ statement that we are now unblinded to the data is intended to be nothing more than a reflection of the fact that we are analyzing the data for the PMA submission. In his comments, there was no specific data or endpoint information disclosed.  It would be our intention to issue a press release, including formal statements by the Steering Committee membership, at the same time the RESPECT clinical trial results are presented or published, which, as Mr. Starks indicated, will likely occur during the TCT meeting.

The PC Trial is an investigator-sponsored trial, funded by St. Jude Medical. You would need to contact the trial sponsors for further information about the presentation of results.

Single Case Report Casts New Doubts About St. Jude Durata ICD Leads 1

Editor’s Note: The following guest post is published with the permission of its author,  Edward J. Schloss, MD, (Twitter ID @EJSMD) the medical director of cardiac electrophysiology at Christ Hospital in Cincinnati, OH.

As if on cue, just as the train pulled into the Nice-Ville station for this week’s Cardiostim 2012 meeting on the French Riviera, my Twitter stream and email lit up with news about a MAUDE case report about an externalized Durata:

Non invasive programmed stimulation of icd, revealed undersensing of ventricular fibrillation after induction. Fluoroscopy of lead revealed externalization of conductors. The externalization was confirmed at lead extraction. The externalization was adjacent to the distal coil of the lead.

Wall Street reacted promptly with a 6% drop in St. Jude’s stock price on Tuesday.

Though not widely reported, this was not the first report of an externalized Durata. As I reported previously, at the Riata Lead Summit in Minneapolis in January, St. Jude presented a case of a patient in Alaska with an externalized Durata lead.  At that point, the company was able to dampen negative reaction with an analysis indicating that the externalization was caused by abrasion of the lead in an “outside-in” fashion from contact with a tricuspid valve annuloplasty ring.

Why did this new Durata story provoke such a strong reaction?

• The new MAUDE report arrived without any explanation or reaction from St. Jude Medical.  The first references came from the financial analyst community and filtered out through online sources such as Twitter and Cafepharma.com.  There have been no additional details beyond the brief summary in MAUDE .  St. Jude Medical seemed to be as surprised as everyone else. A St. Jude spokesperson told Reuters: “We will make every effort to learn more about the report as quickly as possible.”

• This is the first important new development since last month’s Heart Rhythm Society Meeting in Boston.  At that meeting, as reported in Med City News, Charles Love of Ohio State, offered a favorable perspective on Durata. This was counterbalanced by unfavorable data about the prior generation Riata lead and a scathing commentary by ICD watchdog Robert Hauser, as I then reported.

• The report comes on the eve of the Cardiostim Meeting here in Nice.  This meeting serves as a European counterpart to last month’s HRS sessions and will provide a ready forum for reaction and consensus building.

• St. Jude has waged an aggressive defense of Durata, promoting “0% Externalized Conductors” in promotional materials (see photo at bottom).  This “all-in” stance may have created lofty expectations for this lead’s performance.  Even a single unsubstantiated case report therefore could create an unfavorable reaction.

It remains to be seen if this case report will be the “tip of the iceberg” or an isolated phenomenon. Its validity is even being questioned, as FDA cannot reveal its source and the details of the report have not yet been made available.

Those of us who have followed medical device failures closely over the years should know not to react too quickly to case reports.  It seemed inevitable to me that there would be at least some Durata externalization reports given that lead’s similarity in design to the Riata ST lead. However, a single case report, or even a few cases reports, do not provide sufficient evidence to indict Durata at this time.  More information may arrive soon in the form of an expected paper from Dr. Hauser on Durata electrical failures in the MAUDE database.

(Photo of Durata promotional truck at HRS courtesy of Dr. Wes)

Robert Hauser, ICD Watchdog, Offers Viewpoint On Riata Controversy At HRS Reply

Editor’s Note: The following guest post is published with the permission of its author,  Edward J. Schloss, MD, (Twitter ID @EJSMD) the medical director of cardiac electrophysiology at Christ Hospital in Cincinnati, OH.

Robert Hauser, ICD Watchdog, Offers Viewpoint On Riata Controversy At HRS

by Edward J Schloss MD

The St. Jude Riata ICD lead controversy took center stage at last week’s Heart Rhythm Scientific Sessions in Boston, as previously reported here.  Near the end of the meeting a leading figure in the field, Dr. Robert Hauser, of the Minneapolis Heart Institute, summarized the current state of the Riata crisis and discussed its broader implications. Hauser has played key roles in the Riata and several other similar, highly disturbing cases, including those involving the Sprint Fidelis ICD leads and the Prizm 2 DR ICD device malfunction.

In a troubling revelation near the end of his talk, Hauser suggested that St. Jude’s problems may not end with the now discontinued Riata leads, and that the company’s Durata leads may have failure mechanisms not previously reported.

Hauser first discussed an abstract from Steinberg and associates from Quebec.  These investigators used chest x-rays rather than fluoroscopy to detect Riata externalizations:

They, like others, found a far higher incidence of externalized conductors than what has been reported by St. Jude Medical.  And frankly, this and other reports presented at this meeting raise serious questions about the accuracy of the data that the manufacturer has communicated to us.  What we learned today is that this externalized cable process is time dependent.  It seems to be occurring more frequently in the 1580 leads, particularly in the 8 French, and that with time we are going to see progression.  The fact that these investigators were able to use special chest radiographs to identify externalized conductors is interesting and deserves further study by comparing the sensitivity and specificity of their technique to high-resolution cine-flouroscopy

Hauser then discussed the Riata extraction experience from Royal Victoria Hospital in Belfast, and then offered some practical advice:
Click to continue reading…

Guest Post: After an Unprecedented Request for a Retraction, A Close Look at the Data 3

Editor’s Note: The following guest post is published with the permission of its author,  Edward J. Schloss, MD, (Twitter ID @EJSMD) the medical director of cardiac electrophysiology at Christ Hospital in Cincinnati, OH.

After an Unprecedented Request for a Retraction, A Close Look at the Data

by Edward J Schloss MD

Last week, St. Jude Medical took the unusual step of requesting a retraction of an article accepted for publication in Heart Rhythm Journal.  In this article Deaths Caused by the Failure of Riata and Riata ST Implantable Cardioverter-Defibrillator Leads, Dr. Robert Hauser et al analyzed patient deaths in the FDA MAUDE database associated with St. Jude Medical and Medtronic ICD leads.  This week, Dr. Douglas Zipes, Heart Rhythm editor, declined that request. (Please see my previous Cardiobrief coverage of Hauser’s article.)

In a company news release, St. Jude accused Hauser’s group of “inaccurate facts and biased analysis.”  The sub-headline reads:  “Research undercounted and excluded MAUDE data reports for Medtronic resulting in substantial factual errors.”

St. Jude’s most prominent concern revolves around the number of reported deaths in the analysis of Riata/Riata ST leads and the comparison lead, Medtronic Quattro Secure.  St. Jude wrote: “using the same search criteria outlined in the manuscript, the company has identified that Dr. Hauser’s research substantially undercounted total deaths in the MAUDE database for Quattro Secure.”  St. Jude counts 377 deaths compared to Hauser’s 62.

In an effort to clarify the reasons for this discrepancy, I undertook an independent analysis of the facts available.  My sources are the original Hauser article and the PDF file from St. Jude listing the details of their database search.  I then examined the methodology of both database searches to compare consistency of data entry.  Finally, I performed an independent review of all MAUDE database entries supplied by St. Jude and attempted to classify the 377 deaths Quattro Secure deaths identified by St. Jude into Hauser’s defined categories:  lead-related, indeterminate, and not lead-related, using the methods he described in his paper.

I hypothesized that differences in search methodology may explain the large discrepancy in numbers of deaths found by Hauser and St. Jude.

Results

The Hauser study queried the MAUDE data using the “simple search feature” entering term “Quattro Secure death.”  Results were “refined” to include only model 6947 leads.  Finally, “Reports were excluded from the study if there was no known lead problem or allegation of lead malfunction, and if a returned product analysis found no anomalies that were not caused by the explant procedure.”  With this methodology, the query returned 62 Medtronic Quattro Secure deaths.

The St. Jude data collection methodology is discussed on page one of the PDF document.  The “simple search” function specified by Hauser is not used.  Rather in the standard search fields, individual entries are made for Brand:  Quattro, Manufacturer:  Medtronic, and Event:  Death.  Results were then refined to model 6947 excluding duplicates.  Also in contrast to the Hauser data, no pre-specified exclusions were indicated. This query listed 377 Medtronic Quattro Secure deaths.

Hauser categorized his 62 deaths as 5 (8%) lead-related, 25 (40%) indeterminate, and 32 (52%) not lead-related.

St. Jude did not categorize the 377 deaths. My individual analysis found 7 (2%) lead-related, 129 (34%) indeterminate, and 241 (64%) not lead-related. (Lead-related death MDR Identifiers were 71402, 1438305, 1523151, 1760409, 1944512, 2016463, and 2025526.) I have asked St. Jude for their own analysis of the data into these categories, but have not received a reply.

Discussion

My review confirmed significant methodological differences in the database query specified by Hauser and St. Jude that may explain the differences in the numbers of deaths reported.  This stands in contrast to St. Jude’s assertion that they used “the same search criteria outlined in the manuscript.”
Click to continue reading…

Round Two: Heart Rhythm Editor Rejects St Jude Request to Retract Riata Paper Reply

Douglas Zipes, the editor of Heart Rhythm, said the journal will not retract a controversial paper that has raised new safety concerns about St. Jude’s embattled Riata leads.

On Friday (as reported here) St. Jude issued a press release alleging numerous mistakes and oversights in an article by Robert Hauser published online in Heart Rhythm linking the company’s Riata and Riata ST leads to 20 or more deaths. The company publicly asked the journal, which is published by the Heart Rhythm Society, to retract the article.

On Tuesday, the New York Times reported that Zipes stood by the journal’s peer review process and would not retract the article. Zipes said there will be “some changes” to the article “involving what he called ‘inflection’” but that “‘the bulk of the manuscript stays as it is.”

Earlier Tuesday, St. Jude continued its assault on the Hauser article by issuing a press release and posting a link to findings from the MAUDE database. The company contended that Hauser had grossly undercounted the number of deaths tied to Medtronic’s Quattro Secure lead, thereby making its own Riata leads appear far worse by comparison.

Hauser and Zipes have not responded in detail to the St. Jude accusations, but Hauser told CardioBrief on Friday that the authors “stand by the conclusion of our study.” In a series of tweets, electrophysiologist Edward J Schloss (who has published guest posts about Riata on CardioBrief), noted that Hauser and St. Jude had applied different methodologies in their search of the MAUDE database, and that St. Jude may have failed to exclude Quattro deaths with no known lead problems.

St. Jude Seeks Retraction of Hauser Article On Riata Leads 3

St. Jude Medical is seeking the retraction of an article by Robert Hauser in Heart Rhythm linking the company’s Riata and Riata ST leads to 20 or more deaths. In a press release (see below) issued on Friday afternoon, St. Jude alleges numerous mistakes and oversights in the Hauser paper.

In a brief statement to CardioBrief, Hauser wrote:

We stand by the conclusion of our study, namely: “Riata and Riata ST ICD leads appear prone to high-voltage failures that have resulted in multiple deaths.”

In response to a message thread on CafePharma,  St. Jude seeks retraction of Hauser’s manuscript, one anonymous observer started a new thread: Patients seek retraction of their STJ leads.

Dr. Wes has a great perspective on this story.

Click here to review our previous coverage of the Riata controversy.
Click here to read the St. Jude Medical press release…

St Jude Withdraws Older LV CRT Leads From Market Reply

St. Jude Medical today issued an advisory about its QuickSite and QuickFlex Left-Ventricular (LV) Leads, which connect to Cardiac Resynchronization (CRT) devices. The company said it would no longer sell these leads, but that it had received no reports of death or serious injury associated with the problem.

The problem with the LV leads closely parallels the previously-reported problem with the company’s Riata leads. In both cases, there have been reports of externalization of lead conductors with silicone insulation, though the ultimate clinical implications of the reports are unclear.

St. Jude reported that there have been only 39 confirmed cases of externalized conductors, out of 171,000 leads sold worldwide. However, based on its own analysis, the company estimates that 3-4% of QuickSite and QuickFlex leads “may exhibit externalized conductors.”

The company said its newer QuickFlex µ or Quartet LV leads were not affected by the advisory. These leads use the company’s Optim insulation, and there have no reports of externalization in these models.
Click here to read the St. Jude press release…

Guest Post: More Lessons From the Riata ICD Lead Recall 7

Editor’s Note: The following guest post is published with the permission of its author,  Edward J. Schloss, MD, (Twitter ID @EJSMD) the medical director of cardiac electrophysiology at Christ Hospital in Cincinnati, OH. This post is longer and far more technical than most of the content published on CardioBrief. Due to the extraordinary nature of the material, however, I believe this post will likely be of considerable interest to many cardiovascular healthcare professionals.

More Lessons From the Riata ICD Lead Recall

by Edward J. Schloss, MD

In an earlier guest post (What are the Lessons of the Riata ICD Lead Recall?) I summarized points from Robert Hauser’s  important perspective in the New England Journal of Medicine regarding the St. Jude Riata ICD lead recall. In this followup, I’d like to discuss St. Jude’s responses to this piece and place the arguments into a broader context.

Last week Mark Carlson MD, Chief Medical Officer of St. Jude Medical, posted a response to Hauser’s perspective, and he made similar points in a letter subsequently published in NEJM. In the original response, Carlson writes “we believe that there were inaccuracies and omissions in the editorial that are important to recognize in order to more fully understand this issue.”

Major points of disagreement in the two pieces include:

  1. Timing of the initiation of a prospective trial looking at Riata externalizations and failures.
  2. Similarities and differences between the currently marketed Durata lead and it’s recalled predecessor Riata ST.
  3. Robustness of the existing St. Jude lead surveillance systems.

Having looked at this issue in some depth, I feel it would be reasonable for me to weigh in on these matters.

Regarding the timing of the recent trial, Dr. Carlson writes:
Click to continue reading…

St Jude Medical Statement on the Riata ICD Lead Summit 2

In response to the guest post summarizing the Riata ICD Lead Summit, St. Jude Medical sent the following statement to CardioBrief:

We recognize that the phenomenon of externalized conductors presents a complex patient management scenario for physicians who may be able to visualize an anomaly, but it is important to remember that most leads with externalized conductors continue to function properly.
Click to continue reading…

New Enrollment in FAME II Halted After Interim Analysis Shows Benefits of FFR 3

Following a positive interim analysis showing that fractional flow-reserve-guided PCI was superior to optimal medical treatment, an independent Data and Safety Monitoring Board (DSMB) has recommended that patient enrollment in the ongoing FAME II trial  be stopped. The news was announced by the trial sponsor, St. Jude Medical.

FAME II (Fractional Flow Reserve-Guided Percutaneous Coronary Intervention Plus Optimal Medical Treatment Versus Optimal Medical Treatment Alone in Patients With Stable Coronary Artery Disease) investigators had planned to randomize 1,832 patients with stable coronary artery disease to either PCI guided by FFR plus optimal medical treatment (OMT) or OMT alone. At the time of the announcement 1,219 patients had been randomized.

According to the company, the DSMB recommendation was based on an increase in the risk of major adverse cardiac events (MACE) in patients randomized to OMT alone. “In particular, patients receiving OMT alone experienced a highly statistically significant increased risk of hospital readmission and urgent revascularization, and the DSMB determined that this difference was highly unlikely to change with inclusion of more patients,” the company stated. There were no significant differences in the rates of death or MI.

It should be noted that all patients in FAME II underwent FFR prior to randomization, according to the original announcement of the trial. Patients who had hemodynamically significant lesions as assessed by FFR were then randomized to PCI or OMT. The trial was designed to address the limitations of COURAGE, in which CAD patients as documented by angiography were randomized to PCI or OMT. However, the followup to COURAGE, the ISCHEMIA trial, will randomize ischemic patients to PCI or OMT without prior angiography. FAME II does not appear to address the question of which patients should undergo angiography in the first place.

Click here to read additional commentary about FAME II.

Click here to read the St. Jude press release…