Women with aortic stenosis often undergo surgery with a higher estimated operative risk, smaller body surface area, and smaller aortic annuli. These characteristics may influence treatment strategy, prosthesis size, and the risk of patient-prosthesis mismatch.
Santarpino et al. analyzed the prospective MANTRA registry, which included 535 patients (274 men and 261 women) undergoing aortic valve replacement with Perceval Plus at 35 centers between 2019 and 2024.
Although the median age was 73 years in both groups, women had a lower body surface area (1.8 vs 2.0 m²), higher estimated risk according to EuroSCORE II and STS, and a greater prevalence of pulmonary hypertension. Men more frequently had coronary artery disease, a history of smoking, and concomitant procedures, particularly CABG.
These differences were also reflected in the surgical strategy. A minimally invasive approach was used in 44.8% of women compared with 35% of men, whereas concomitant procedures were more frequent among men (49% vs 38.2%). Size S prostheses were implanted in 34.9% of women but in only 2.9% of men.
Cross-clamp and cardiopulmonary bypass times were shorter in women (49 vs 56.5 minutes and 76 vs 85 minutes, respectively). In-hospital mortality was 1.9% in women and 1.1% in men, without a significant difference. No differences were observed in stroke, acute kidney injury, length of hospital stay, or pacemaker implantation, although the latter was numerically less frequent in women (2.3% vs 5.1%; p=.11).
During follow-up, both groups showed improvements in functional class and quality of life. Mortality after hospital discharge was 1.9% in women and 3.3% in men. As an additional analysis, the authors performed a meta-regression of 48 studies including 20816 patients and found no association between the proportion of women enrolled in each study and overall mortality.
COMMENTARY:
This study provides relevant information through the analysis of a prospective, international registry with an almost equal representation of men and women. Its findings confirm that Perceval Plus® can be implanted with low early mortality and morbidity in both sexes.
However, lack of statistical significance should not be interpreted as evidence of equivalence. Only eight in-hospital deaths and fourteen deaths during follow-up occurred. With such a small number of events, the study has limited power to exclude clinically meaningful differences and was not designed as an equivalence analysis.
Moreover, the two groups represent different surgical scenarios. Men underwent more combined procedures, more CABG, and more full sternotomies. Consequently, the shorter operative times observed in women probably reflect lower procedural complexity rather than a direct effect of sex.
The meta-regression should also be interpreted cautiously. This analysis relates the proportion of women within each study to overall study-level mortality, rather than directly comparing outcomes between men and women within each cohort. It is therefore an ecological analysis and cannot establish that sex has no effect at the individual patient level.
The hemodynamic findings raise another important issue. At 1 year, women continued to have a higher MPG (12.2 vs 9.9 mmHg; p<.001) and a smaller EOA (1.4 vs 1.9 cm²; p<.001). The apparent disappearance of these differences thereafter is based on very small samples: gradient data were available for only 11 patients at 2 years, 22 at 3 years, and 12 at 4 years.
Indexed EOA was also not calculated, and the incidence of patient-prosthesis mismatch was not formally reported. Therefore, attributing the initially higher gradients to a mild and transient mismatch remains speculative. A contemporary series of 139 patients receiving Perceval®, using VARC-3 criteria, reported a higher incidence of patient-prosthesis mismatch in women (74.6% vs 22.1%), predominantly moderate. Although retrospective and limited in size, this study confirms that the issue remains unresolved.
Our experience provides a complementary perspective. In our consecutive series of 1742 Perceval® implantations, the largest single-center series worldwide, 780 patients were women and 962 were men. Isolated aortic valve replacement accounted for 73.6% of procedures, with mini-sternotomy being the predominant approach in this group. The overall pacemaker implantation rate was 5.5%, but annual rates subsequently decreased to 2.8–4% after implementation of a systematic strategy involving less oversizing and higher prosthesis deployment. This suggests that implantation technique, prosthesis sizing, and surgical era may influence outcomes as much as, or even more than, sex itself.
The major difference from MANTRA lies in the depth of follow-up. Our echocardiographic cohort includes 948 patients, with a median follow-up of 74.2 months. Using competing-risk analysis, the cumulative incidence of moderate hemodynamic valve deterioration was 0.6% at 5 years and 2.9% at 7 years. For severe deterioration, the corresponding incidences were 1.3% and 4.2%, respectively.
These results demonstrate a low incidence of valve deterioration during the first years after implantation. In the MANTRA registry, only one patient had reached 5 years of follow-up. Accordingly, MANTRA provides valuable information on early safety according to sex, but cannot yet address long-term durability or hemodynamic evolution.
In conclusion, Perceval Plus® provides favorable early outcomes in both men and women and represents a particularly attractive option for minimally invasive surgery and patients with small aortic annuli. Nevertheless, this study demonstrates an absence of detectable differences rather than equivalence. The potential interaction among sex, prosthesis size, implantation technique, patient-prosthesis mismatch, and durability should be assessed through adjusted patient-level analyses with sufficiently long follow-up. Given its size and longitudinal depth, our series provides an ideal opportunity to address this question.
REFERENCE:
Santarpino G, Lorusso R, Di Mauro M, D’Anna V, Prencipe CM, Voisine P, et al. Sex-Related Outcome After Sutureless Aortic Valve Replacement With Perceval Plus: Results From a Global Registry and Meta-Regression. Interdiscip Cardiovasc Thorac Surg. 2026 Jun 9;41(6):ivag170. doi: 10.1093/icvts/ivag170.
