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Masiero et al. Mini-invasive Surg 2022;6:4 https://dx.doi.org/10.20517/2574-1225.2021.104 Page 7 of 19

Impact of sex on clinical outcomes
Overall, the impact of sex on clinical outcomes after SAVR or TAVI is not clearly defined. Higher rates of
mortality and peri-procedural complications have been reported among women than men receiving SAVR.
In the Italian Observational Multicenter Registry (OBSERVANT), female sex was an independent predictor
for risk-adjusted 30-day mortality [odds ratio (OR) = 2.34; P = 0.043] and transfusions (OR = 1.47; P =
[41]
0.003) after SAVR . In a propensity-matched analysis from the Nationwide Inpatient Sample, in-hospital
mortality was significantly higher in women compared with men following SAVR (3.3% vs. 2.9%, P < 0.001);
[42]
they also had higher rates of vascular complications and blood transfusions . Other studies did not find
sex-related differences in short- and long-term mortality after SAVR or reported better outcomes in
women [43-46] . In the Women’s INternational Transcatheter Aortic Valve Implantation (WIN TAVI) registry,
the first study that specifically assessed the performance of TAVI in a population of solely women (n =
1019), the primary Valve Academic Research Consortium (VARC)-2 early safety endpoint at 30 days
(composite of mortality, stroke, major vascular complications, life-threatening bleeding, stage 2 or 3 acute
kidney injury, coronary artery obstruction, or repeat procedure for valve-related dysfunction) was 14% with
[47]
a low incidence of early mortality (3.4%) and stroke (1.3%) . In addition, the VARC-2 efficacy endpoint
(composite of mortality, stroke, myocardial infarction, hospitalization for valve-related symptoms or heart
failure, or valve-related dysfunction) occurred in 10.9% and 16.5% of patients at 30 days and 1 year,
respectively, and 1-year survival was better than in men . The results of other observational studies and
[48]
subgroups analysis of randomized trials that evaluated the impact of sex on clinical outcomes after TAVI
are summarized in Table 1. Overall, in these studies, compared with men, women were older and with fewer
comorbidities; they had higher rates of procedure-related vascular complications and bleeding, and they had
comparable or even better survival at early and long term. Similarly, a patient-level data meta-analysis of
11,310 patients reported higher rates of major vascular complications, major bleeding events, and stroke in
women (48.6% of overall population) compared with men. However, female sex was found to be an
independent predictor of late survival after TAVI [adjusted hazard ratio = 0.79; 95% confidence interval
[39]
(CI): 0.73-0.86; P = 0.001] . In a meta-analysis including 47,188 patients (49.4% women), female sex
conveyed a lower risk of all-cause mortality at one year [risk ratio (RR) = 0.85; 95%CI: 0.79-0.91; P < 0.001],
[49]
despite a greater peri-procedural complications rate . Several factors might explain the sex-related
differences of clinical outcomes after TAVI and their peculiar time course. Advanced age, low body surface
area, and small vessels make women at higher risk for bleeding and vascular complications in the early
period after the procedure. Over a longer term, fewer comorbidities, lower occurrence of paravalvular
regurgitation and patient-prosthesis mismatch, and a more favorable left ventricular remodeling could drive
the survival advantage of women over men. In perspective, changing demographics of patients (younger
and at lower risk), device, and procedural amelioration could mitigate the impact of sex on TAVI outcomes.
In this regard, an analysis of the nonrandomized PARTNER II S3 trial showed equivalent mortality rates at
one year for women and men . Similarly, in a study of 298 patients receiving a new generation
[50]
transcatheter heart valve [Sapien 3 (Edwards Lifesciences, Irvine, California) or Corevalve Evolut R or
Evolut Pro (Medtronic, Minneapolis, Minnesota)], no significant differences were found in postprocedural
outcomes including all-cause mortality between women and men .
[51]

TECHNICAL SEX-SPECIFIC CONSIDERATION IN TAVI
Access management
Vascular complications still represent a relevant concern in TAVI procedures. In intermediate risk patients,
major vascular complications (MVC) with third-generation transcatheter heart valves (THV) have an
incidence ranging from 6% to 7.9% and are associated with worse clinical outcomes with a prolonged
[52]
[53]
hospital stay, an increased risk of wound infection, and a higher in-hospital mortality . A recent sub-
analysis from the WIN TAVI registry has outlined that women experiencing MVC after TAVR are at
significantly higher early risk of life-threatening or major bleeding and death and late risk of stroke,