Medical Device Daily Executive Editor

ORLANDO — The past five years has seen increasing and much-needed focus on heart disease as a greater threat to women than breast cancer, but the results of this greater focus have been mixed.

Medical conferences are beginning to show more focus on the differences between men and women in terms of their responses to therapeutic strategies, but this is coming in the face of a continuing large obstacle: an ongoing lack of an accurate representative female presence in clinical trials.

This mix of improvement/not-so-improved has been clear at this year’s scientific sessions of the American Heart Association (Dallas), just wrapped up at the Orange County Convention Center. The improvement was seen in more studies on the specific impact of therapies in women, often focused on mechanical therapies, and study data broken out by gender, but one of the reports indicated that there has been no general improvement in the number of women enrolled in trials.

That report was presented by Soo Hyun Kim, MD, of the Cleveland Clinic, indicating that despite a clearly pointed directive by the National Institutes of Health 10 years ago, women do not have equal representation in trials.

One of the areas where this differential is most clearly seen is in the use of heart pump devices, mechanical systems often too large for placement in the female anatomy.

Abiomed (Danvers, Massachusetts) received some criticism about five years ago, when one woman’s group noted no implantations of its AbioCor artificial heart in women. But the company could rightly claim that the heart, about grapefruit-sized, is simply too large for most women’s anatomies, thus not reflecting any gender bias. And it hopes for implants in women with its smaller AbioCor II.

Thus, Thoratec (Pleasanton, California) received a good bit of publicity this week, including in Medical Device Daily, with its report that its next-generation ventricular assist device (VAD), the HeartMate II, had received implantation in 23% of the population in its recent trial — 52 of 231 patients total (MDD, Nov. 7, 2007).

Roberta Bogaev, MD, director of heart failure and cardiac transplantation at the Texas Heart Institute (Houston), lead study author and presenter, told MDD that the 23% inclusion of women is the largest female representation in “a trial of mechanical support.” And the study noted that the 11 smallest patients receiving the HeartMate II were women and all were alive at six-month follow-up.

The HeartMate II is generally described as being about the size of as a D battery, driven by a battery pack carried outside the body. Besides being seen primarily as offering a “bridge” to transplant, it has been explanted in some patients after their hearts had remodeled sufficiently to allow removal (six reported in the trial).

Long-term, the device is being touted as offering the possibility of “bridging” more women to heart transplant, hopefully up to twice as many.

One of the gender differences reported from the trial was that 3.3% of women and 2.2% of men in the trial had strokes within two days after implantation, and 12 patients — 13.6% of women, 5% of men — suffered strokes more than two days after the trial.

Bogaev told MDD that this result was not particularly surprising, since women “are more prone to have complications” than men across a range of cardiovascular and surgical procedures and that there are “more late strokes in women than men.”

This data, she said, “highlights the differences in vascular biology,” including “arterial function” and “hormonal differences.”

Overall, however, she said that the HeartMate II had benefited the women in the trial the same as men.

Asked if she felt the potential availability of the HeartMate II to a large female population would help to support its approval by the FDA — the company goes before the agency’s circulatory systems expert panel Nov. 30 — Bogaev was circumspect. “The FDA is very anxious to get data on a broad spectrum of patients,” she said. “This data could be helpful and reassuring.”

She said that with the HeartMate II, her institution had increased the percentage of women benefiting from LVADS from 7% to 37%.

In other studies highlighting gender differences:

• While women may benefit as much as men with VAD implantation, they do not fare as well as men when they received Implantable cardioverter defibrillators (ICDs).

Andrea Russo, MD, of the University of Pennsylvania (Philadelphia), reported that in a study of 1,530 individuals with ICDs, 293 (19%) of them women, the women were 22% more likely to die than men (6.8% vs. 4.1%) at about 11-month follow-up. Additionally, hospitalizations of the women were more frequent (7.9% vs. 5.7%).

The women in the study also were less likely to be treated with beta blockers and ACE inhibitors, and the researchers suggested that this under-treatment was a possible reason for the worse results for ICD use in women.

• A study highlighted the increasing prevalence of peripheral artery disease (PAD) among people who are still asymptomatic for heart disease.

Andrew Sumner, MD, told MDD that early PAD may come to be increasingly used as a “mechanical marker” for later cardiovascular disease, PAD determined in the study by use of the ankle-brachial index.

One of the interesting data points was that while overweight women have an increasing rate of PAD, overweight men showed a decrease, while the overall report indicated a link between obesity and increased PAD.

Sumner told MDD he wasn’t able to explain this and that more evidence of this difference might be determined in follow-on studies.

• Two other studies pointing to determining key cardiovascular risk factors were female-focused.

Nisha Parikh, MD, a cardiovascular fellow at BethIsrael Deaconess Medical Center (Boston), reported on a study indicating that breast-fed babies are less likely to have “certain” cardiovascular risk factors for cardiovascular disease, such as lower body mass index and more HDL, the “good” cholesterol.

Another report, delivered by Sadia Malik, MPH, of the University of Arkansas Medical School (Little Rock), indicated that a urinary tract infection (UTI) by pregnant women shortly before delivery was related to a greater chance of their babies having under-developed left side of the heart (hypoplastic left heart syndrome).

Malik’s conclusion: Detecting and treating UTI in women at conception “may decrease the risk of having an infant with a left-sided obstructive cardiac defect.”