Sex-Related Differences in Clinical Presentation and Outcome of Transcatheter Aortic Valve Implantation for Severe Aortic Stenosis

Study population and design

Between October 2006 and December 2010, consecutive high-risk patients with severe AS treated with TAVI at our institution were prospectively included in our database. Patients with symptomatic severe AS were considered candidates for TAVI if they had a logistic EuroSCORE >20%, or if surgery was deemed high risk, as previously described (8). The decision to proceed with TAVI was discussed by a dedicated heart team including experienced clinical and interventional cardiologists, cardiovascular surgeons, and anesthesiologists.

Valve and approach site selection strategy

Patients were selected to undergo TAVI by the transfemoral approach or alternative approaches depending on iliofemoral access (8). The valve prosthesis was selected according to the annulus size; the Edwards valve (Edwards Lifesciences, Irvine, California) was used in patients with an 18 to 24.5 mm annulus size, and the CoreValve (Medtronic, Santa Rosa, California) was used for 20 to 26.5 mm size (Fig. 1). The Edwards valve was predominantly used in patients with a 20 to 24.5 mm annulus amenable to treatment with either type of valve. The transapical and transsubclavian approaches were used as alternatives to unsuitable iliofemoral approach routes for the Edwards valve and CoreValve, respectively.

• Download figure
• Open in new tab
• Download powerpoint

Figure 1

Valve Bioprosthesis Selection Strategy

Patients were selected to undergo transcatheter aortic valve implantation (TAVI) by the transfemoral (TF) approach or alternative approaches depending on the iliofemoral access. The valve prosthesis was selected according to the annulus size; the Edwards valve was used in patients with an 18 mm to 24.5 mm annulus size and the CoreValve for 20 mm to 26.5 mm. CT = computed tomography; FA = femoral artery; SFAR = sheath outer diameter/femoral artery ratio; TA = transapical; TEE = transesophageal echocardiography; TS = transsubclavian.

Procedures

The technical aspects of the TAVI procedures have been previously described (9,10). The majority of patients were pre-treated with aspirin 75 to 160 mg and clopidogrel 75 mg daily. Intravenous heparin was administered to keep a target activated clotting time (ACT) of 250 to 300 s. General anesthesia was used for all transapical and transsubclavian cases and for initial transfemoral procedures. Local anesthesia with mild sedation was introduced later for the transfemoral cases.

Post-procedural care

All patients were monitored in the intensive care unit for at least 24 h. Dual-antiplatelet therapy (aspirin 160 mg, clopidogrel 75 mg) was administered for 3 to 6 months, and thereafter aspirin was continued indefinitely.

Follow-up

After TAVI, all patients were assessed by a physician at 1, 3, 6, and 12 months post-operatively and thereafter annually. Additional follow-up data were collected through telephone interviews and contact with patients' family physicians, except for 1 case lost during follow-up.

Endpoint definitions

The primary endpoints of this study were device success, all-cause mortality (30-day and midterm) and combined 30-day safety endpoints as defined by the VARC (7). Device success was defined as successful vascular access, delivery, and deployment of 1 prosthesis, and correct position and performance of the prosthetic valve.

Statistical analysis

Quantitative variables are expressed as mean ± SD, and qualitative variables using numbers and percentages. Comparison of quantitative variables was performed with an unpaired Student t test or Wilcoxon rank-sum test. The chi-square test or Fisher's exact test was used to compare qualitative variables. A Cox regression analysis was performed to determine the predictors for midterm mortality. Statistical significance was defined as p < 0.05. The data were analyzed with PASW statistics version 17.0 (SPSS, Chicago, Illinois).

Patient and procedural characteristics

Of 260 patients, 131 were women (Table 1). Female patients tended to be older than male patients (83.8 ± 5.9 years vs. 82.4 ± 6.5 years, p = 0.080), with less coronary artery disease (48.9% vs. 79.1%, p < 0.001), less previous cardiac surgery (13.7% vs. 26.4%, p = 0.011), and less peripheral artery disease (26.7% vs. 40.3%, p = 0.020), whereas left ventricular ejection fraction (LVEF) was higher in women compared to men (53.5 ± 12.9% vs. 47.1 ± 14.6%, p < 0.001). Finally, logistic EuroSCORE was lower in women than in men (22.3 ± 9.1% vs. 26.2 ± 13.0%, p = 0.005).

Echocardiography showed a similar aortic valve area (0.59 ± 0.17 cm² vs. 0.61 ± 0.13 cm², p = 0.248) but a larger valve area index (0.35 ± 0.10 cm²/m² vs. 0.33 ± 0.07 cm²/m², p = 0.037) in women who had a smaller body surface area (BSA [1.65 ± 0.17 vs. 1.85 ± 0.16 m², p < 0.001]) compared to women with a larger BSA. The annulus size was also smaller (20.9 ± 1.4 mm vs. 22.9 ± 1.7 mm, p < 0.001) as was the bioprosthesis size (23.9 ± 1.6 mm vs. 26.3 ± 1.5 mm, p < 0.001).

The Edwards valve was used in the majority (85.4%) of the whole cohort, and more frequently in women compared to men (91.6% vs. 79.1%, p = 0.005) (Table 2). The minimal femoral artery diameter (7.74 ± 1.03 mm vs. 8.55 ± 1.34 mm, p < 0.001) and femoral calcification score (0.37 ± 0.57 vs. 0.77 ± 0.75, p < 0.001) were smaller in women compared to men.

Device success, periprocedural complications, and outcome

Device success was achieved in 89.6% of the whole cohort, without significant sex-related differences (90.8% vs. 88.4%, p = 0.516). Although there was no significant difference in the rate of major vascular complications between sexes (11.5% vs. 9.3%, p = 0.570), iliac complications were more frequent in women compared to men (9.0% vs. 2.5%, p = 0.030) (Table 3). Conversion to open-heart surgery was required in 7 cases, 4 in female patients (2 valve migration, 1 annulus rupture, and 1 failed subclavian access) and 3 in male patients (1 valve migration, 1 annulus rupture, and 1 post-procedural severe AR [3.1% vs. 2.3%, p = 0.718]).

At discharge, the mean aortic pressure gradient was similar in both groups (11.6 ± 4.9 vs. 10.9 ± 4.9, p = 0.279) whereas post-procedural LVEF was higher in women than in men (56.8 ± 12.1 vs. 51.0 ± 12.7, p < 0.001), as it was before TAVI. No significant difference was observed in post-procedural aortic regurgitation ≥2 (34.4% vs. 27.1%, p = 0.228). The 30-day mortality was comparable between women and men (12.2% vs. 17.8%, p = 0.207) as was as the 30-day combined safety point (14.5% vs. 20.2%, p = 0.231).

Sex differences and predictors of midterm mortality

The median follow-up of this cohort was 217 days (interquartile range: 54 to 401 days). In total, 79 patients (32 female and 47 male) died during the follow-up period.

Although no significant sex differences were observed with respect to the 30-day mortality rate, women had a better midterm survival (Fig. 2). Male sex was also identified as a predictor of midterm mortality by Cox regression analysis (hazard ratio: 1.62, 95% confidence interval: 1.03 to 2.53, p = 0.037) (Table 4).

• Download figure
• Open in new tab
• Download powerpoint

Figure 2

Impact of Sex on Midterm Survival

Although no significant sex differences were observed with respect to the 30-day mortality rate, female patients (solid line) had a better midterm survival compared to male patients (broken line) (p = 0.037).

Study limitations

Our study reports results achieved in a single-center TAVI cohort consisting of a limited number of patients recruited in the initial phase of our experience with this new technology. Multivariate analysis was not performed because of the low endpoint count. Further studies of larger patient populations are required to confirm our results.