QUEBEC CITY — Although women appear to benefit as much as men do from left atrial appendage occlusion (LAAO) during surgery for atrial fibrillation (AF), they have far worse 30-day outcomes following mitral valve surgery, according to two studies presented at the Canadian Cardiovascular Congress (CCC) 2025.

“In cardiology and cardiovascular disease in general, [sex differences] is a hot topic,” Emmanuel Moss, MDCM, a cardiac surgeon at McGill University in Montreal, told Medscape News Canada. Moss chaired the session but was not involved in the trial.

Men and women have physiologic and biological differences and sometimes present with cardiovascular disease differently, said Moss. “We need to be able to recognize those differences in women and treat them [appropriately].”

Kevin John Um, MD, an adult cardiology resident and PhD student at McMaster University in Hamilton, Ontario, presented the results of a substudy of the LAAOS III trial. The original trial demonstrated that LAAO during cardiac surgery reduces the risk for stroke by about one third among patients with AF. No differences were observed between the sexes, but most (67%) participants were men, and patients were not stratified by sex before randomization.

“There is an increasing body of evidence [demonstrating] that outcomes after cardiac procedures, whether it’s valve replacement or revascularization, may differ by sex,” said Um. “We also know that across all risk categories, female sex tends to modify and increase the risk for stroke in AF. Furthermore, women still tend to be underrepresented in cardiac studies.”

The substudy used multivariable logistic regression to examine whether cardiac surgery outcomes differed by sex. Baseline characteristics were not balanced between men and women: Women had significantly higher rates of heart failure (62.5% vs 54.4%) and lower rates of hypertension (76.4% vs 84.4%), diabetes (28.4% vs 34.0%), and vascular disease (27.2% vs 41.7%).

Female sex did not significantly interact with the primary outcome of ischemic stroke or systemic thromboembolism, nor did it interact with the secondary outcomes of myocardial infarction, death, or major cardiac adverse events.

Conversely, a second study found a difference in outcomes by sex. Presented by Kenza Rahmouni, MDCM, a cardiac surgery resident at the University of Ottawa Heart Institute in Ottawa, the study assessed all-cause 30-day and long-term mortality in men and women following mitral valve surgery for chronic ischemic mitral valve disease.

The researchers retrospectively examined 1086 consecutive patients with chronic ischemic mitral valve disease who underwent mitral valve repair between 2000 and 2022 at the University of Ottawa or the University of Laval. The population included 330 women (30.4%) and 756 men (69.6%). The researchers used inverse probability of treatment weighting (IPTW) to balance baseline differences between the two groups.

One month after surgery, the mortality rate among women was almost double that of men (10.9% vs 5.6%; odds ratio [OR], 2.76). Female sex was also associated with higher odds of longer cardiopulmonary bypass time (OR, 1.017) and urgent or emergency surgery (OR, 10.09).

Sex differences were largely attenuated with long-term follow-up, however. Median survival was 9.7 years for women and 10.7 years for men. The IPTW-adjusted hazard ratio for mortality comparing women with men did not reach significance.

“The findings of this study need to be interpreted in light of some limitations,” Rahmouni acknowledged. “First, this was a retrospective study, which would have introduced some bias. Second, while IPTW allowed us to have a more balanced population between males and females, it did not address unknown confounders. Third, echocardiographic variables were not indexed to body size, which can vary between males and females. And last, because a high proportion of our patients did not have a cause of death on file, we could not assess cardiovascular-specific mortality.”

While recognizing the study’s limitations, Moss said that the findings could be relevant to discussions with patients and their families about the pros and cons of cardiac surgery. “If we feel that there’s a mortality risk in a given patient population, [such as females], then we will weigh the risks and benefits of going through that surgery differently.”

LAAOS III was funded by the Canadian Institutes of Health Research. Moss, Um, and Rahmouni reported having no relevant financial relationships.