New-generation device, better sizing eliminates TAVR survival disparity between sexes

A larger valve option and more appropriate valve sizing using preprocedural imaging may eliminate the previously reported survival disparity between men and women undergoing transcatheter aortic valve replacement (TAVR), a new study in JACC: Cardiovascular Interventions suggests.

Men disproportionately benefited from these changes, researchers wrote, helping level the field with women, who had been previously found to experience less mortality in the wake of TAVR.

Lead researcher Molly Szerlip, MD, and colleagues studied the new-generation, balloon-expandable Sapien 3 valve manufactured by Edwards Lifesciences, which funded the study.

A total of 1,661 patients (40 percent women) with severe symptomatic aortic stenosis were enrolled in the trial from October 2013 through December 2014. The study included 583 patients deemed at high surgical risk—greater than 8 percent cardiac surgery mortality risk according to the Society of Thoracic Surgeons (STS) calculator—and 1,078 at intermediate risk (STS score between 4 and 8 percent).

Overall, there were no significant differences in mortality for women compared with men at 30 days (2 vs. 1.2 percent, respectively) or one year (9.3 vs. 10.2 percent). There wasn’t a substantial difference in disabling stroke or any stroke over those time periods, either, but women showed an increased risk of minor stroke at 30 days (2.1 percent vs. 0.7 percent).

Previous studies, including of earlier iterations of the Sapien valves, showed a “distinct survival advantage” in women versus men despite an increased short-term risk of vascular complications and bleeding events in women, Szerlip et al. pointed out.

But they offered three explanations for why the mortality risk may have been leveled in this study. First, patients were, on average, at lower risk than previous studies. Second, “procedural techniques including precise positioning, smaller vascular sheaths, and high transfemoral access rates resulting in low rates of vascular injury make the procedure safer compared with earlier studies.”

And finally, the authors said more appropriate valve sizing reduced paravalvular leak (PVL)—which has been linked to mortality—to low levels in both sexes. They credited the more accurate sizing to the mandatory use of preprocedural multidetector CT (MDCT) imaging and the addition of a 29-millimeter valve to the lineup. More than 35 percent of men in the study received this largest valve size, compared to just 1.4 percent of the women.

“The availability of 29-mm S3 valve and MDCT imaging for valve sizing in this study appears to have disproportionately benefited men more than women,” Szerlip et al. wrote. “Thus, proper valve sizing might have been achieved with relatively equivalent frequency in men and women in this analysis, whereas women were more likely to receive the optimal valve size in prior studies. With improved valve sizing benefitting predominantly men as compared with women, a decreased incidence of PVL in men should be reasonably expected.”

The authors suggested future studies should look at all newer-generation TAVR devices to determine whether sex-specific survival differences are truly eliminated.

In a related editorial, Brian R. Lindman, MD, MS, and Robert N. Piana, MD—both with Vanderbilt University Medical Center—analyzed this paper and another publication in JACC: Cardiovascular Interventions of an all-woman cohort undergoing TAVR. They pointed out these studies add important findings about sex-specific outcomes of TAVR, but do little to answer the question of whether sex should play a role in physicians’ recommendations of TAVR versus surgical aortic valve replacement (SAVR).

“The inclination of patients and providers will be to treat patients with (aortic stenosis) at extreme, high, or intermediate risk for surgery with TAVR,” Lindman and Piana wrote. “Beyond the tendency to prefer a less invasive approach, should female sex be a factor that more definitively favors TAVR over SAVR? Not quite.

“However, as multiple factors (for example, comorbidities, anatomy, concomitant valve lesions) are considered when weighing whether to recommend a transcatheter versus surgical therapy, along with the feasibility of a transfemoral approach, female sex would provide another firm ‘nudge’ toward TAVR.”