June 27, 2022

Study Assesses Sex Disparities in Contemporary Transcatheter Hemodynamics and Outcomes in TAVI

June 27, 2022—A recent study published in The American Journal of Cardiology by Medranda and Waksman et al found that between 2015 and 2020, most females who underwent transcatheter aortic valve implantation (TAVI) with contemporary transcatheter heart valves (THVs) had significantly higher Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) as compared with males.

KEY FINDINGS

Patients with small aortic annuli (< 430 mm²) were predominately female (82.5%).
Moderate patient-prosthesis mismatch rates were significantly higher in females compared with males (38.3% vs 15.2%; P < .001).
Short-term mortality at 30 days and 1 year was slightly higher in females than males and in patients with smaller versus larger aortic annuli.

Of the 869 patients included in this retrospective analysis of patients with symptomatic severe aortic stenosis (AS) who underwent TAVI using contemporary THVs at a single institution between 2015 and 2020, those with a small aortic annular area (defined as < 430 mm²) were overwhelmingly female (82.5%), while most patients with a larger aortic annular area (≥ 430 mm²) were mostly male (76.8%).

Investigators reported that females were found to have statistically similar but numerically higher all-cause mortality at 30 days (1.5% vs 0.6%; P = .313) and 1 year (4.1% vs 2.7%; P = .265). However, at 30 days, females had significantly higher rates of moderate patient-prosthesis mismatch (PPM; 38.8% vs 15.2%; P < .001). Rates of severe PPM did not significantly differ (13.9% vs 11.3%; P = .242).

In a subset analysis of the 262 females who had a small aortic annulus, those who received a self-expanding valve (SEV) had a lower STS-PROM than those who received a balloon-expandable valve (BEV; 5.2% vs 6.2%; P = .039). At 30 days, those with an SEV also had lower mean gradients (8.0 vs 13.8 mm Hg; P < .001) and rates of moderate PPM (21.2% vs 73.6%; P < .001) than those with BEVs.

Of note, rates of permanent pacemaker implantation were significantly higher in females with small annuli who received a SEV versus a BEV (14.4% vs 4.2%; P = .009).

Limitations of this study included its retrospective design, that it was underpowered to detect differences in clinical events such as mortality, and that it had limited follow-up of 1 year. Investigators noted that longer follow-up is needed to further evaluate the impact of THV hemodynamics on durability and long-term mortality.

CARDIAC INTERVENTIONS TODAY ASKS…

We asked study investigators Giorgio A. Medrandra, MD, and Ron Waksman, MD, both with MedStar Washington Hospital in Washington, DC, to expand on the study’s findings.

What are the clinical implications of these findings? How can physicians better address the treatment of patients with smaller aortic annuli who are undergoing TAVI?

The optimal treatment for patients with symptomatic severe AS and small aortic annuli remains controversial. Our real-world study of contemporary TAVI patients confirmed that most patients with small aortic annuli are female. As a result, female patients were more likely to develop PPM. Gradients were consistently lower in female patients receiving a SEV, with the most benefit seen in those with small annuli. This adds to findings from earlier TAVI studies, which suggested that leaflet positioning within the THV stent, and not necessarily valve deployment type, influences THV hemodynamics.

Our study also demonstrated a trend toward higher all-cause mortality among females with smaller annuli who received a BEV compared to those who received a SEV, but our study was underpowered for this outcome. Given the robust data demonstrating smaller anatomy in females and the association between PPM and mortality in surgical aortic valve replacement, it is possible that a similar association exists in females with small annuli undergoing TAVI. These are important considerations when selecting the optimal THV for female patients referred for TAVI

What size/anatomy considerations need to be addressed when developing newer valve technologies?

Despite females representing nearly half of all patients undergoing TAVI and the majority of patients with small annuli, currently available devices are not tailored to these patients. Future THVs should strive to offer a wide range of valve sizes suited to treat patients across the entire spectrum of aortic anatomies. If future prospective studies corroborate our findings suggesting a link between PPM and mortality in females undergoing TAVI, forthcoming THVs must emphasize optimizing hemodynamics while offering an acceptable risk of permanent pacemaker.

You noted in the discussion that, to your knowledge, this is the first study evaluating the possible mechanisms for sex disparities in TAVI using the interactions between sex and THV hemodynamics. What should future studies look like to further corroborate your findings?

The retrospective nature of our study limits our ability to establish any causal relationship between smaller aortic anatomy, PPM, and mortality. Longer follow-up and/or larger prospective cohorts are required to elucidate subtle differences between THV types and the impact PPM may have on clinical outcomes in females with small aortic annuli. The SMART (SMall Annuli Randomized To Evolut or SAPIEN) trial is actively and prospectively enrolling patients with small annuli (aortic annular area < 430 mm²), randomizing them to receive either the CoreValve Evolut Pro/Pro+ THV (Medtronic) or the Sapien 3/3 Ultra THV (Edwards Lifesciences). As we await the results of these ongoing trials, our retrospective observational study of contemporary TAVI patients suggests that females with small aortic annuli have higher rates of PPM.

Furthermore, our study also demonstrated that female patients receiving a contemporary SEV had higher rates of permanent pacemaker implantation. However, changes in SEV implantation using the cusp-overlap technique may mitigate the risk of requiring a permanent pacemaker. Finally, based on these results, female sex may be a consideration for THV type and size selection.

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