CD&D National Editor, and Staff Reports

Dr. Robert Hauser, one of the cardiologists who blew a very large whistle on Guidant (Indianapolis) in 2005, concerning the safety of its ICDs, is questioning the development and oversight of a new defibrillator technology being developed by Boston Scientific (Natick, Massachusetts) – and the other two of the cardiovascular "Big Three," Medtronic (Minneapolis) and St. Jude Medical (St. Paul, Minnesota). He is charging that this new technology is on a pathway to be approved by the FDA without sufficient testing.

Hauser, of the Minneapolis Heart Institute Foundation, is raising a warning that if the new technology is not tested in humans, the results "could be catastrophic" for patients. His concerns are addressed in the Dec. 11 issue of the New England Journal of Medicine, in an article written in collaboration with Dr. Adrian Almquist, also with the Minneapolis Heart Institute.

The new defibrillator system under development is distinguished from previous generations by having four leads, rather than the traditional two or three. The leads are thinner, in order to make them easier to implant. In the article, "Learning from Our Mistakes? Testing New ICD Technology," Hauser and Almquist argue that this is a highly significant difference – potentially making the leads prone to short-circuiting. "If high-voltage isolation is lost," the article says, "and a short circuit develops during therapeutic shock delivery, otherwise potentially lifesaving defibrillation may be ineffective." And therefore likely lethal.

The cardiologists cite last year's recall of the Sprint Fidelis lead made by Medtronic, charging that this product did not receive sufficient FDA review before approved for commercialization.

Five people implanted with the Fidelis ICD leads died because of fracturing, a problem found to be much more frequent than the expected risk parameters. The leads were subsequently pulled from the market, with class actions filed against the company.

Hauser and Almquest say they are raising issues about how extensive and adequate the testing of the new leads will be and highlighting the complex changes in technology described in lengthy documentation materials. And the two cardiologists also suggest that the manufacturers may be attempting to push a new product into a $5 billion-plus market that has been stagnating a bit recently.

The concerns raised by the two cardiologists is countered in the same issue of the NEJM by Daniel Schultz, MD, head of the FDA Center for Devices and Radiological Health, in a letter to the editor.

He says that the agency "has made no absolute decision" concerning the matter. But he adds: "The agency 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." The information that could best test the reliability of the leads, he said, could be non-human studies, such as bench testing.

Medtronic released a statement agreeing with that position, saying that lab testing "provides the opportunity to test a large number of devices and to stress them beyond what they will see in clinical application." It said that existing leads were approved on the basis of laboratory and animal testing, rather than testing in humans.

An organization obviously concerned with this issue, and likely to serve as a watchdog on the regulatory process for the new technology, is the Heart Rhythm Society (HRS; Washington).

In their article, the two cardiologists note that the FDA at this year's HRS meeting stated that the leads would be assessed only in animals and laboratory tests. And in commenting on the NEJM article, the society released a statement noting that in 2006 it issued recommendations concerning the surveillance and performance reporting of pacemakers and ICDs, with the purpose of creating "greater transparency" concerning the reliability of such devices.

It said that this year it created a task force that includes its members, "collaborating with regulatory agencies, industry and patients" to develop recommendations concerning lead performance.

Dr. N.A. (Mark) Estes, president of the society, told Cardiovascular Devices & Drugs that the society will address the task force report will issue of the appropriate type of testing for leads, but he did not want to say what its conclusions are likely to be. And he declined to give a personal opinion on the controversy until the task force report is issued.

He said that a draft report of the task force's work will be presented to the board of the society during 1Q09 and that the final recommendations are to be released at the society's annual scientific sessions in Boston next May.

STEMI deaths in women twice that of men

Men and women have about the same in-hospital death rate for heart attack – but women are twice as likely to die if hospitalized for a more severe type of heart attack, according to a report in Circulation: Journal of the American Heart Association.

Among patients with ST elevation myocardial infarction (STEMI) in a recent study, the death rate was 10.2 for women compared to 5.5 for men. Researchers said the women were older and had higher overall baseline risk profiles than men. The study also found that some recommended treatments are delayed and under-used in women.

Researchers analyzed data from the Get With The Guidelines (GWTG) program of the American Heart Association (Dallas) to determine if recent efforts to improve heart attack care at hospitals had closed the gender disparity gap. They reviewed the characteristics, treatments and outcomes of more than 78,000 patients diagnosed with myocardial infarction at 420 hospitals between 2001 and 2006.

"The finding that bears the most emphasis is that among both men and women presenting to Get With The Guidelines participating hospitals, there were no clinically meaningful differences in in-hospital survival after heart attack, once we factored in differences, such as age and other existing illnesses," said Hani Jneid, MD, lead author of the study and assistant professor of cardiovascular medicine at Baylor College of Medicine (Houston).

"However, the finding of persistently higher death rates among women experiencing [STEMI] and the persistent gender gap in certain aspects of care underscore the existing opportunities to enhance post-heart attack care among women."

Jneid and colleagues found that, compared to men, women were:

• 14% less likely to receive early aspirin.
• 10% less likely to receive beta blockers.
• 25% less likely to receive reperfusion therapy (to restore blood flow);
• 22% less likely to receive reperfusion therapy within 30 minutes of hospital arrival.
• 13% less likely to receive angioplasty within 90 minutes of hospital arrival.

"We could not determine in this study to which extent these differences were due to physicians' failures to administer optimal therapies to women vs. appropriate decision-making based on biological and other differences between men and women," Jneid said.

Furthermore, researchers found that women admitted with a STEMI were about twice as likely to die in the first 24 hours of hospitalization as men.

"Although STEMI is not as common among women as it is among men, it is a concern that there is still this gap in mortality between men and women after the more severe heart attack," said Laura Wexler, MD, study co-author and senior associate dean at the University of Cincinnati College of Medicine.

The findings were, as might be expected, disturbing to WomenHeart: The National Coalition for Women with Heart Disease (Washington), founded a decade ago, based on the misdiagnosis and under-treatment of women with cardiovascular disease.

Lisa Tate, CEO of WomenHeart, said, "It is a sad day when we can say that not only is the needle not moving to correct disparities in care for women with heart disease, but that it might be moving in the wrong direction. This study is a giant shout out for increased education about prevention, care and treatment for women with heart disease to both the public and physicians … [U]ntil healthcare professionals follow the specified treatment guidelines, thousands of women will continue to die needlessly."

Sharonne Hayes, MD, director of the Women's Heart Clinic at Mayo Clinic (Rochester, Minnesota) and a member of the WomenHeart board, said, "The fact that nothing has changed through the years and that disparities in care persist should outrage all of us. This study is only a single example of what we see in every population and database that's been looked at. And not just for heart attacks. We fall short in treating women for high cholesterol, heart failure, implanting life saving medical devices and participation in cardiac rehabilitation to name a few.

"We in the medical profession set our own benchmarks and guidelines for care, and then are unable to follow our own rules and advice. These hospitals knew they were having these care parameters measured, and still they fell short in caring for women."

Advanced OCT tech gives 4-D look at plaque

As we get older, our arteries develop plaque, which can be removed from the body and examined microscopically, but that provides little information concerning the source of the problem, or plaque growth and physiological characteristics within the body. And current scanning procedures provide only flat, 2-D views of obstructed arteries.

Now, researchers at the Wellman Center for Photomedicine of Massachusetts General Hospital's (MGH-Wellman; Boston) say they can get a highly detailed look at the interior of the coronary arteries using an advanced form of optical coherence tomography (OCT), called optical frequency-domain imaging (OFDI).

The researchers say that OFDI can provide microscopic 3-D views of inflammation and plaque in these arteries, providing significant information that would be highly helpful in both research and clinical applications. In terms of research, the study indicates that this technique could assist in tracking the "natural history" of plaque development.

This would allow an earlier look, providing guidance for interventional treatment of plaque build-up.

OCT can examine tissues "one point at a time," according to the MGH-Wellman researchers, but OFDI can look at more than 1,000 points simultaneously using an imaging device that they have developed. Inside a fiber-optic probe, a constantly rotating laser tip emits a light beam with an ever-changing wavelength. As the probe moves through the structure to be imaged, the measurement of how each wavelength is reflected back allows rapid acquisition of the data to create the more detailed microscopic observation.

The technique can provide these 3-D images of an artery's microstructure in seconds - though final processing takes awhile – and this increased speed reduces signal interference from blood, which had plagued the first-generation technology.

The technique has been used to create detailed retinal images, and in 2006 members of the MGH-Wellman team reported the successful use of OFDI to image the esophagus and the coronary arteries of pigs.

The current research enrolled three patients receiving coronary stents at the Lahey Clinic (Burlington, Massachusetts). After stent placement, OFDI was used to image 3 cm- to 7 cm-long segments of the patients' coronary arteries, including the stented areas.

"This is the first human demonstration of a technique that has the potential to change how cardiologists look at coronary arteries," said Gary Tearney, MD, PhD, of the MGH pathology department and MGH-Wellman, the study's lead author. "The wealth of information that we can now obtain will undoubtedly improve our ability to understand coronary artery disease …"