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Prevalence, predictors, and outcomes of patient prosthesis mismatch in women undergoing TAVI for severe aortic stenosis: Insights from the WIN‐TAVI registry

To evaluate the incidence, predictors and outcomes of female patients with patient‐prosthesis mismatch (PPM) following transcatheter aortic valve intervention (TAVI) for severe aortic stenosis (AS).


| INTRODUCTION
The concept of patient prosthesis mismatch (PPM) was first described by Rahimtoola in 1978: "Mismatch can be considered to be present when the effective prosthetic valve area, after insertion into the patient, is less than that of a normal human valve." 1  However, for obese patients (body mass index [BMI] ≥30 kg/m 2 ) lower criteria may be more appropriate, given the hyperdynamic cardiac T A B L E 1 Baseline demographics, comorbidities, echocardiographic, and CT parameters in the two groups are associated with a larger EOA and iEOA, and lower peak as well as mean transprosthetic gradients. [7][8][9][10][11][12][13][14][15][16][17] Large surgical registries and a recent meta-analysis have demonstrated an association between PPM and decreased long-term survival. [18][19][20] Female gender was found to be a predictor of PPM in a recent literature review. 21

| Echocardiographic data
Baseline echocardiographic data pre-TAVI were similar in the two groups ( 54.6 ± 11.3 and 56.4 ± 10.5 in the PPM and no PPM groups, respectively (p = .220). Peak and mean gradients alongside aortic valve area were all similar in the two groups.
No significant differences were seen in terms of coronary artery disease severity.

| Female specific characteristics
With regards to female specific characteristics, there was a small trend for increase in history of pregnancy amongst patients with PPM post TAVI (Table 2). Gestational diabetes and hypertension, age at menopause, history of HRT use, history of gynecological or breast Ca and osteoporosis did not differ between the two groups.

| Procedural parameters
PPM was associated with significantly higher rates of balloon expand-  Figure 1 and Supplementary Table). There were no significant differences in rates of new pacemaker, moderate paravalvular leak, major vascular or bleeding complications.

| Follow-up
At 1-year echocardiographic follow-up there were significantly increased peak and mean gradients across the aortic valve in the PPM group (Table 5).
No significant differences were seen in VARC-2 early safety endpoint at 30-days (25.6% PPM group vs. 25.6% no PPM group, p = .888) or in any of the clinical outcomes at 1 year (Table 6).

| DISCUSSION
In the current study, prevalence of PPM in this all-female TAVI cohort was 32.8%. Independent predictors of PPM included larger BMI and valve size ≤23 mm, whereas there was no interaction between valve size and valve type. There does not appear to be any significant difference in 1-year clinical outcomes in the two groups; however, these results should be interpreted cautiously given the small sample size of our study and relatively short-term follow-up.
Despite several studies demonstrating that PPM incidence is reduced when patients are treated with TAVI compared to SAVR, 6,9 in the current cohort nearly one third of females treated with TAVI appear to have at least moderate PPM. This finding is important as PPM has the potential implication of reduced LV hypertrophy regression and persistence of residual LV afterload 11,27,28 which impacts on coronary flow reserve. 9 PPM post-TAVI has been associated with less regression of LV hypertrophy, LV diastolic dysfunction, LV filling pressure (measured by E/e'), less improvement in LV systolic function (LVEF and myocardial strain), and less reduction of left atrial volume. 11,28,29 Interestingly, however, there may be a differential impact of PPM on mortality in patients treated with TAVI and those with SAVR. 6,9,13,27,29 In the study by Pibarot et al 9 an increased mortality was seen in surgical patients with PPM but not in TAVI patients. In that particular study, as in the current study, TAVI PPM patients had significantly higher BMI, a previous shown independent predictor of PPM. 6 Body surface area greater than 1.88 m 2 independently predicted severe PPM with satisfactory sensitivity (0.71) and specificity (0.70). 30 A higher BMI has been shown to be a powerful independent predictor of improved 2-year survival post TAVI in the PARTNER-A TRIAL. 31 Such a higher BMI was not seen in PPM patients post surgery. 9 Furthermore, indexing the EOA to the patient's BSA may overestimate PPM severity in obese individuals. 32 The higher than expected valve gradient can be due, at least in part, to patient's supranormal cardiac output and high flow state due to morbid obesity. 33 In the current study we did not identify any survival benefit in females with no PPM, concurring with the study from Pibarot et al 9 ; however, the small patient numbers and reduced power limit our ability to answer this question with certainty.
Smaller valve size (≤23 mm) was associated with PPM in our cohort. Given that the CT annulus perimeter was not significantly different in the two groups, and assuming optimal sizing, this can be explained by valve choice (balloon expandable vs. self expanding).
This highlights the importance of optimal valve sizing based on CT parameters 34 and raises the question of a potential benefit in implantation of supra-annular self-expanding valves in female patients with small aortic annuli. In the randomized CHOICE study, 35  Previous studies have shown a hemodynamic benefit of TAVR over SAVR in the subset of patients with small aortic annulus. 9 In high-risk patients with severe AS and a small aortic annulus (diameter < 20 mm), TAVI compares favorably with currently available surgical options, and may provide a reasonable alternative to conventional AVR in elderly patients with a small aortic annulus. 37 In a recent meta-analysis, 23 female AS patients treated with TAVI had improved survival to those treated with SAVR and one of the potential explanations was the presence of a larger iEOA post procedure. Therefore, TAVI valve size and type selection becomes more important in females who are known to have smaller size aortic annuli than their male counterparts. 38,39 In the current study no differences were observed in new pace-

DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.