Durata: Questioning the 99%

One of Many St. Jude Ad Trucks Seen at HRS 2012 Scientific Sessions

The boxing match about the safety of St. Jude Medical's newer Durata defibrillator lead reliability continues to spark interest in the EP community.  In one corner is the supporter of the reliability claims made by St. Jude, respected EP and lead explanter Charles Love, MD from Ohio State University Medical Center.  In the opposite corner this morning on Cardiobrief, comes respected ICD-watchdog Robert Hauser, MD:

Cardiobrief:  "Unfortunately, Dr. Greenberg was unable to attend today, but St. Jude’s Dr. Carlson stood bravely in the breach (no pun intended) to describe the performance of St. Jude’s 3500+ Durata leads in its OPTIMUM registry. Follow up was 2.4 years, and my only comment is that 2.4 years in my view is an early experience, not a mid-term experience. The event free survival was >99%. Excluding dislodgments and perforations, which may be operator dependent, there were only 5 lead mechanical problems, namely conductor fractures, in over 8400 implant years. Now this is truly spectacular. There were no inside-out insulation abrasions and no all-cause abrasions. But I have to say, that the Durata leads that I have been looking at in the FDA’s MAUDE database must not have been included in this study."

I'm starting to see the makings of a Tyson/Holyfield match.

-Wes

Truth and Consequences: The St. Jude Riata ICD Lead Recall and It's Possible Implications for Durata

Today, a remarkable tour de force essay on the St. Jude Medical Riata defibrillator lead recall controvery written by Edward J Schloss, MD, director of cardiac electrophysiology at Christ Hosptial in Cincinnati, OH, appears at Cardiobrief.   It is a must-read for all of us interested in the management of patients with the current class of St. Jude defibrillator leads.
In the essay, he reviews two opposing views on the industry handling of this recall, one published as a perspective piece in the New England Journal of Medicine by Robert Hauser, MD, and the other, a rebuttal piece published by St. Jude Medical's Chief Medical Officer and Senior Vice President of Clinical Affairs, Mark D. Carlson, MD. The article reviews the engineering changes made to the Riata line of leads in its evolution to the Durata defibrillator leads and expresses clear concerns about disclosure of all available information regarding lead characteristics to implanting physicians.

This piece is a must-read for electrophysiologists and industry personnel involved in the care of these complicated patients. Schloss concludes:

Anyone who has been in the business of cardiac rhythm management has struggled with the problems of device failures. Because most of these only occur years after FDA approval, having a system for early detection of excess or unique failures is critical.

Industry response to these failures is also critical. Clear, honest acknowledgement of the problem is essential. We also need quick action to define the scope of the problem and create an action plan. These measures go a long way to maintaining the confidence of everyone involved, including, but not limited to, physicians, hospitals, patients, and the investment community.

Every time we, the implanting physicians, implant a medical device, we are taking a measured risk that must be outweighed by its benefits. Understanding this true risk, especially in newer devices, is extremely difficult. By becoming a student of the engineering process of these devices, we can become better equipped to make good decisions for our patients.

We are only now learning the scope of the problem with Riata and Riata ST. The lead mechanical failures and externalizations of this lead may only first occur four to five years after implant. Since Durata leads are only now approaching that interval, it is not surprising that we have not seen many troubling signals with this lead. It remains to be seen what the future holds. Until we have longer experience and collect more data, it us up to individual doctors to educate themselves with available clinical and engineering data so they are equipped to make good decisions.

Go now. Read it all. You will learn something.

-Wes

PS: John Mandrola, MD, a co-editor of Dr. Schloss's piece, also offers an excellent overview of concerns that confront electrophysiologists regarding the Riata/Riata ST lead recall over at theHeart.org.

What's the Difference Between MRI-Safe and Conventional Pacemaker Leads?

... a little thicker, certainly, but otherwise (at least on the surface), not too much:

The recently-approved MRI-safe active-fixation lead from Medtronic (left lead in each frame) is compared to their conventional active-fixation lead. The arrow denotes the radio-opaque marker that can been seen on x-ray to identify the type of lead in the patient's body. A fluoro image of the two leads is shown below, again with Medtronic's MRI-safe lead on the left:

While the engineering hurdles were no-doubt considerable to make an MRI-safe pacemaker lead, given the growing body of evidence that newer pacemakers (when carefully monitored) can be scanned in MRI machines, I suspect the biggest difference in these leads is not their design per se, but rather the regulatory paperwork (and research) that had to be completed to document their safety.

Of course, the fact that CMS would not pay for MRI scans performed on patients with pacemakers before the advent of these newer devices probably also limited the number of scans performed.

-Wes

St. Jude Responds to WSJ Article

Here's a copy of St. Jude's response to the WSJ article regarding their Riata leads. It provides a "sneak preview" into an upcoming December PACE article.

-Wes

Defibrillator Lead Recalls: Industry and Clinical Implications

Medtronic’s most recent defibrillator lead recall will have profound implications (Wall Street Journal: subscription required) for the medical device industry as a whole:

"The events surrounding the Medtronic recall expose a hole in the U.S.’s medical safety system: Medical devices are regulated under different standards from those applied to prescription drugs. The Food and Drug Administration requires that almost all new medications be tested in human trials before they go on the market. But some devices, like the Sprint Fidelis leads, are subject to lighter guidelines because they are considered modifications of earlier products. The FDA, in most cases, also doesn't mandate major studies of medical devices after they've hit the market.

As a result, both the federal agency and the company were handicapped in evaluating whether a widespread public health threat was emerging.”

The broad market penetration of a these life-saving devices and the minimal safety data required for their approval, the FDA’s entire 510(k) device exemption and GMP (Good Manufacturing Practices) product development processes are now being reviewed. Even the smallest widget being developed that might be implanted in a patient and is sterilized (so-called Class II devices), be it cardiovascular, orthopedic, or otherwise, will be coming under ever-increasing scrutiny. This, in turn, will inevitably slow development and raise costs. What is clear now is that efforts to improve patient safety, already underway, will not be allowed to maintain the status quo.

But for those of us in this field, the defibrillator lead recall has even more far-reaching implications clinically. The recommendation of defibrillators for “primary prevention” of sudden arrhythmic death in those felt to be at high risk and whom have not yet had such an arrhythmia needs to be reviewed in light of these recent developments. (ed. comment: For lay readers, "Primary prevention" refers to patients who have not yet had an incidence or episode of a particular medical condition – in this case an abnormally rapid heart rhythm known as ventricular tachycardia (VT) or ventricular fibrillation (VF), often leading to sudden cardiac arrest (SCA) or sudden cardiac death (SCD). "Secondary prevention" refers to patients who have survived these conditions, and receive a particular therapy in response to the episode. Secondary prevention trials, such as AVID, CASH and CIDS, have shown a significant mortality benefit for patients who receive ICDs over those who receive just drug therapy.)

While there are excellent prospective, randomized data extolling the virtues of implanting implantable cardiac defibrillators (ICDs) in patients with markedly reduced ejection fractions (see the MADIT-II and SCD-HeFT data), these data were obtained with older device systems. (ed comment: Again, for the lay reader, the "ejection fraction" is the percentage of blood ejected from the heart with each beat - normal is over 50%) We are now left to wonder: should we be using older technology for our patients when recommending defibrillator implantation? After all, this is where we have the clinical data. Or do the newer advances of the more sophisticated devices (that might still be subject to later recalls but contain newer advanced features that we assume will provide better device oversight) warrant abandoning more conservative, evidenced-based medicine in the presumed interest of patient safety? Should new, expensive clinical trials be developed for these newer devices as well?

It is helpful to remember the raw data from the SCD-HeFT trial: there were 829 patients implanted with ICDs. Of those patients, 259 (31%) were shocked for ANY cause, and 177 (68% of those shocked) were shock appropriately for ventricular tachycardia or ventricular fibrillation. Therefore, the annual rate of shocks was 7.5% and the annual rate of appropriate shocks in these patients was 5.1%. Further, the number of deaths in the three arms studied were as follows: placebo (no therapy) 244 deaths, Amiodarone (medical therapy only) 240 deaths, ICD therapy 182 deaths. Would a faulty lead have changed the frequency of shock data? Certainly. Would it have changed the mortality data? Even if we added 5 deaths (as was potentially seen with the Sprint Fidelis lead) to the ICD arm of SCD-HeFT, it seems unlikely.

Nonetheless, given the recent recall, I suspect that we will see increased resistance by referring physicians to recommend these devices for primary prevention of arrhythmias. This is an inevitable outcome of such a massive recall, much like the later revelation of the propensity of stent thrombosis in drug-eluting stents. But like that scenario, there will still be appropriate patients in whom devices are warranted for primary prevention like those with markedly reduced left ventricular ejection fractions less than 25%. It’s just that the benefit for patients with higher ejection fractions in the 30-35% range may now be viewed more skeptically.

-Wes

More on Medtronic's Sprint Fidelis Advisory

With the issuance of the Medtronic's Sprint Fidelis lead advisory (on defibrillator lead models 6930, 6931, 6948, 6949) issued today, our office has already received over 50 calls with excellent questions. Understandably, people are concerned, so I thought I would take a moment to review the issues of the recall and answer a few of the more common questions.

Why would Medtronic have tried to design a thinner (6.6 Fr) lead, when their larger lead already had a fairly good track record for performance?

With the advent of biventricular defibrillators, that require three leads (one for the atrium, one for the right ventricle and one for the left ventricle), there is limited space in the subclavian and axillary vein. With the additional lead requirement of biventricular pacing, it was hoped that the smaller lead size would permit fewer vascular complications.

Why did Medtronic decide to voluntarily withdraw the Sprint Fidelis leads from the market?

There had already been a recognition my Medtronic and others that the lead may have a higher failure rate than prior lead models. An article in the journal Heart Rhythm also noted a higher-than-expected early fracture rate for this lead, but initial failures appeared clustered in certain centers. Hence, it was uncertain whether the failures were from implant technical issues or the lead design itself. Upon review of Medtronic’s ongoing quality review at their 30-month assessment, they felt the 2.3% failure rate sufficiently exceeded the complication rate of former leads (<1% failure rate) and decided to withdraw the lead, even though the fracture rate had not yet reached statistical significance. The trend, it seemed, suggested it would eventually reach significance.

What kind of problems can arise as a result of a lead malfunction?

The Sprint Fidelis lead contains four wires. Two of these wires are used for the rate sensing and pacing function of the lead, while the other two high-voltage wires are used for the shock-delivery function of the defibrillator system. If a fracture of one of the pacing/sensing leads were to fracture, typically noise is detected by the device as the wires rub together, and this might be interpreted by the device as an abnormal heart rhythm which, if it occurs long enough, could cause the device to deliver an inappropriate shock. Alternatively, a fractured pace/sense lead could lead to failure of the device to effectively pace the heart. If a shocking coil were fractured, while it might not effect the pacing or sensing feature of the device, it could lead to ineffective shock delivery during rapid heart rhythms, leading to ineffective termination of the arrhythmia.

Have deaths occurred from the lead malfunction?

Five deaths have been reported on the FDA's Maude database that are not related to infection of the device and may have been attributable to lead malfunction. Several instances of device undersensing of arrhythmias have been reported to the FDA database, and at least one episode of recurent shocks that may have contributed to death, but the details of these deaths have been limited.

I have a Sprint Fidelis lead. Should I have it replaced?

It is important to remember that a very small number of complications of this lead have occurred. The total complication rate with this lead was been 2.3% of the implanted devices to date. 97.7% of the leads implanted are performing correctly at this time. Because removal of the lead has a relatively high 1.4-7.3% mortality risk associated with their removal, it is generally not recommended these leads be removed at this time. If a lead fracture should occur, then placement of a new lead adjacent to the existing lead and leaving the old lead in place is usually recommended rather than extraction of the old lead with new lead implantation. Certainly, there may be circumstances where lead extraction is required, but these should be reviewed with your doctor.

Additional surveillance will be required to see how the remaining leads perform in the future. For now, most of us are recommending that the Patient Alert features on a patient’s defibrillator system be programmed to make them more sensitive to changes in lead impedance (a resistance measurement that might precede lead failure). Patients should make the appointments with their device clinic. The urgency of this reprogramming is generally up to the patient, but should probably be performed within the next 30-60 days.

Additional physician information, including parameters for programming the patient alert features can be found at http://www.medtronic.com/fidelis/physician-letter.html.

Information from Medtronic Regarding the Fidelis Advisory can be found at http://www.medtronic.com/fidelis.

-Wes

New York Times article on the lead advisory.

Medtronic to Pull Its Most Popular Defibrillator Lead

Tomorrow, Medtronic will begin notifying patients and doctors that they will be voluntarily stop selling their most popular thin defibrillator lead, the Sprint Fidelis (Models 6949, 6930, 6931, 6948), because of a higher-than expected failure rate from lead fractures.

According to Medtronic, over 268,000 of these leads have been implanted worldwide. The Sprint Fidelis lead has had a 97.7% reliability rate, but this has fallen well-below the 99.1% reliability rate of their thicker Sprint Quattro lead. Consequently, they will be withdrawing the Sprint Fidelis defibrillator lead from the market.

For patients already implanted with the lead, it is not expected that leads will require explantation, but Medtronic will be advising careful follow-up of the lead, including changing some warning parameters (so called "Patient Alerts") on their devices in hope of detecting lead fractures earlier. It seems higher-than expected impedances were identified just before lead failure in the rate sensing or defibrillator coil wires from the lead. When a lead fractures, noise is detected by the defibrillator due to intermittent "make-break" connections in the wire(s) of the lead, occassionally leading to shocks delivered at inappropriate times. Should patients experience recurrent unexpected shocks, they should seek evaluation by their implanting physicians immediately. For patients who do not receive such shocks, ongoing monitoring of the lead should occur at regular intervals, and if an impedance change or evidence of noise is detected on the lead, Medtronic is recommending a new lead be inserted.

Since the "Dear Doctor" letter will be issued tomorrow, we'll stand by to see the official recommendations from Medtronic.

-Wes

Update: Wall Street Journal (subscription required).

Press release.

Follow-up recommendations also added. -Wes

Pacemaker Leads: Is Ping the Thing?

Imagine having no pacemaker wire between the pacemaker pulse generator and the heart. It seems it has happened:

(theheart.org) A remote ultrasound energy source may one day replace implanted pacing leads in permanent pacemakers, results from a pilot study suggest [1]. Dr Kathy L Lee (University of Hong Kong, China) and colleagues used an ultrasound transducer on the chest wall to transmit energy to a receiver electrode on the tip of a transvenously placed electrophysiology catheter in 24 patients, reporting their results in the August 28, 2007 issue of the Journal of the American College of Cardiology.

The system, says Lee, "works by transfer of energy in different forms: ultrasound energy is transmitted through the chest wall to a receiver in the heart, and the energy is transferred back into electrical energy for direct myocardial stimulation or pacing. Conventionally, the electrical impulse is delivered via a pacing lead; with transfer of ultrasound energy, no pacing lead is required. . . . When this technique is mature enough for clinical use, it should be less burdensome, as less hardware is implanted."

...

The authors tested their ultrasound transducer and receiver electrode during or immediately following clinical electrophysiology procedures in 24 patients, testing a total of 80 pacing sites in the right atrium, right ventricle, and left ventricle; two additional sites were excluded from testing because ultrasound energy could not be consistently "captured" by the receiver electrode. Ultrasound energy from the transducer was amplitude-adjusted and transmitted at levels ranging from 313 kHz to 385 kHz. The receiver electrode, containing circuitry to convert the ultrasound energy to electrical energy, was positioned on the tip of a steerable bipolar electrophysiology catheter. Lee et al report that pacing was successfully achieved at all 80 test sites and consistently achieved at 77 sites, with no adverse events and no patient discomfort. Mean distance between the transducer and receiver was 11.3 cm but ranged from 5.3 to 22.5 cm."

It seems the frequencies used might have interference issues with conventional cell phone technologies in its present form, but this report demonstrates an important "proof of concept" of the application and has exciting ramifications for future pacemaker technologies.

-Wes


Reference: Lee KL, Lau CP, Tse HF, et al. First human demonstration of cardiac stimulation with transcutaneous ultrasound energy delivery: Implications for wireless pacing with implantable devices. J Am Coll Cardiol 2007; 50:877-883.