The primary endpoints were the incidence of post-TAVR PPM and its association with 3-year mortality.

Secondary endpoints included mean transvalvular gradient and paravalvular regurgitation at and 1 year after discharge. VARC-3-defined combined endpoints were reported: 30 days device success [technical success, freedom from mortality, freedom from reintervention related to the device, hemodynamic device performance (mean gradient <20 mmHg, peak velocity <3 m/s)] and modified 1-year clinical efficacy (freedom from all-cause mortality, freedom from stroke, freedom from procedure-related rehospitalization, and kansas city cardiomyopathy questionaire (KCCQ) score was not recorded) (9).

Major vascular complications were reported according to VARC-3 criteria at hospital discharge. Need for permanent pacemaker implantation and stroke (VARC-3 all stroke) were reported at 30 days (9).

Demographics, procedural details, intra-hospital course, and adverse events were prospectively recorded and reported according to the VARC-3 recommendations (9).

Echocardiography examination at discharge and at 1-year follow-up was performed with two-dimensional and Doppler TTE in accordance with the imaging recommendations of prosthetic heart valves (10). The EOA was measured at discharge by TTE using the continuity equation. The measurement was indexed for body surface area (BSA) to categorize PPM.

The Institutional Review Board of the Technical University of Munich approved the study (approved number of 540/20S).

All statistical analyses were performed using R-statistical software (version 3.6.1, R Foundation for Statistical Computing, Vienna, Austria).

Categorical variables were presented as absolute numbers and percentages. A χ² test (Fisher correction test) was used for categorical data, except for binomial variables with sufficiently low sample size, for which Fisher exact test was used. Continuous variables are expressed as mean ± SD or median with interquartile range (IQR), as appropriate.

An independent sample t-test was used to compare groups with normally distributed variables, and Mann–Whitney test was used for variables that were not normally distributed. Kaplan–Meier (KM) survival curve was computed to present all-cause mortality in patients with and without PPM, and in BEV and SEV groups, each endpoint was analyzed with KM. Differences in the endpoints were evaluated using the long-rank test. Propensity score matching was performed using non-parsimonious multivariate logistic regression. Because most variables were already balanced before matching, only the annulus perimeter, annulus area, and body surface area were entered into the logistic model to calculate the propensity score. The C-statistics of the logistic model was 0.60 and McFadden's pseudo R was 0.03 before matching. After matching, a corresponding model had a C-statistics of 0.51 and McFadden's pseudo R was 0.0004. The absolute standardized difference of means of the propensity score between the groups (Rubin's B) was 0.41 before and 0.02 after matching. The ratio of the variances of the propensity score between the groups (Rubin's R) was 0.67 before and 1.02 after matching.

Logistic regression was used to determine the risk factors for the development of an at least moderate PPM, and Cox regression was used to determine risk factors for death.

A total of 507 patients met the inclusion criteria with 310 patients undergoing TAVR with SEV [247 Evolut R/PRO (Medtronic, Minneapolis), 3 Portico (Boston Scientific, Marlborough), 60 Acurate Neo 2 (Abbott, Chicago)] and 197 individuals with BEV. Mean age was 81 ± 7 years, and the majority of patients were female (78%). Mean EuroScore II was 6% ± 7% and Society of Thoracic Surgeons predicted risk of mortality (STS-PROM) was 4.9% ± 4.8%. Baseline characteristics of the BEV and SEV groups are shown in Table 1.

Differences among the BEV and SEV groups were found in CT-derived aortic annulus perimeter (69 ± 3 vs. 67 ± 4 mm, p < 0.0001) and CT-derived aortic annulus area (358 ± 27 vs. 344 ± 43 mm², p < 0.0001).

Propensity score matching for imbalanced baseline CT-derived aortic annulus perimeter and area resulted in 192 patient pairs (Table 1). Within the SEV group, 148 were Evolut R/PRO, 42 Acurate neo 2, and 2 Portico THV.

About 151 (39%) patients showed PPM, 99 (26%) moderate PPM and 52 (14%) severe PPM. Rate of moderate (31% vs. 20%, p < 0.001) and severe PPM (18% vs. 9%, p < 0.001) was higher in BEV compared to SEV (Figure 1).

Independent risk factors associated with moderate and severe PPM were BSA (odds ratio (OR): 1.35, p < 0.001) implantation of a BEV (OR: 3.32, p < 0.001), and the absence of postdilatation (OR: 2.16, p < 0.013) (Figure 2). Patients without PPM had a higher 3-year survival (76%, CI: 0.66–0.79) compared to patients with ≥moderate pre-discharge PPM (67%, CI: 0.60–0.76, p = 0.03) (Figure 3).

Mean transvalvular gradient was reduced from 40 ± 16 to 10 ± 8 mmHg (p < 0.0001). At discharge, mean transvalvular gradient was 12 ± 9 mmHg in the BEV group and 7 ± 4 mmHg in the SEV group (p = 0.003). At 1-year follow-up, mean transvalvular gradient was 13 ± 3 mmHg in the BEV group and 7 ± 5 mmHg in the SEV group (p < 0.001) (Figure 4).

Echocardiographic findings of paravalvular leak (PVL) at and at 1 year after discharge are displayed in Table 2. VARC-3 device success [technical success, freedom from mortality, freedom from reintervention related to the device, and hemodynamic device performance (mean gradient <20 mmHg, peak velocity <3 m/s)] at 30 days was 86% in SEV and 84% in BEV (p = 0.8). VARC-3 clinical efficacy (freedom from all-cause mortality, freedom from stroke, freedom from procedure-related rehospitalization, KCCQ score was not recorded) at 1 year was 79% in BEV and 80% in SEV (p = 0.3).

Estimated survival after SEV was 85% (95% confidence interval (CI): 80%–90%) at 1 year, 80% (95% CI: 75%–86%) at 2 years, and 71% (95% CI: 65%–78%) at 3 years; estimated survival after BEV was 87% (95% CI: 82%–92%) at 1 year, 81% (95% CI: 75%–86%) at 2 years, and 72% (95% CI: 66%–79%) at 3 years, with no significant difference among the groups (p = 0.9) (Figure 5).

Male gender (OR: 2.25, p = 0.045) and increasing STS-PROM (OR: 1.08, p < 0.001) were associated with all-cause mortality after BEV and SEV (Figure 6).

At discharge, VARC-3 major vascular complications occurred in 13% of patients after BEV and in 9% of patients after SEV (p = 0.3). At 30 days, permanent pacemaker implantation was required in 5% with BEV and 6% with SEV (p = 0.6) (Table 3).

At 30 days, rate of stroke was 7% with BEV and in 5% with SEV (p = 0.7) Table 3.

In the present study, single digit mean transvalvular gradients were achieved in patients with small aortic annulus after SEV using predominantly the Medtronic Evolut R and PRO prostheses. The TAVI-SMALL registry analyzed 859 SEV patients with small aortic annulus applying the same sizing criteria as in our study. Comparable low transvalvular gradients were reported using SEVs, i.e., Medtronic’s Evolut R and PRO prostheses, Boston Scientific’s Acurate Neo, and Abbott St. Jude’s Portico (11). Compared to SEV, we found higher transvalvular gradients after BEV at and 1 year after discharge (p < 0.001). Mauri compared the Acurate Neo and the Sapien 3 in 92 propensity matched patient pairs with small annulus applying equal annulus size criteria as in our study and the TAVI-SMALL registry (6). SEV likewise resulted in lower transvalvular gradients at 30 days and 1 year compared to SEV (6). The TAVI-SMALL 2 registry analyzed 1,378 patients with small annulus. In line with our findings, higher transvalvular gradients were reported after BEV compared to SEV (12).

In our study, the lower transvalvular gradients after SEV translated into lower incidence of severe PPM compared to BEV (9% vs. 18%, p < 0.001). In the TAVI-SMALL registry, for SEV, a similar rate of 9.4% severe PPM is reported (11). Comparing SEV to BEV, Mauri reported a sevenfold higher incidence of severe PPM after BEV (3% vs. 22%, p = 0.004) in a propensity matched cohort (6). TAVI-SMALL 2 with imbalanced aortic annulus dimensions reports a more than twofold higher incidence of severe PPM with BEV (5.6% vs. 14.2%, p < 0.001) (12).

PPM in patients with small aortic annulus becomes clinically significant beyond 2 years after TAVR. At 1-year follow-up, we found no association of severe PPM to mortality neither after SEV or BEV. Similarly, (6) reported no difference in 1-year mortality after SEV and BEV (SEV 8.3% vs. BEV 13.3%, p = 0.233). Longer surveillance reveals an association of post-TAVR PPM with mortality. We found higher 3-year mortality rates in patients with any pre-discharge PPM. Likewise, the TAVI-SMALL registry reported severe PPM to be independently associated with 2-year mortality (12). In a study of 1,309 all-comer TAVR patients, severe PPM was an independent risk factor for 3-year mortality for a subgroup of patients with an ejection fraction <40% (13). Leon del Pino reported 6% severe PPM in a single-center study including 185 patients (14). Severe PPM was associated with a lower event-free survival (death, stroke, or hospitalization for heart failure) at 34 months (52% vs. 84%) (14). A meta-analysis including almost 82,000 patients showed an association between severe PPM and mortality after TAVR (15).

We found BSA, TAVR without postdilatation, and implantation of a BEV as risk factors for post-TAVR PPM. Likewise, the OCEAN registry including Japanese patients only identified implantation of a BEV, younger age, and small aortic annulus as risk factors for post-TAVR PPM (7). In the TAVI-SMALL registry, use of an intra-annular SEV was identified as a risk factor for post-TAVR PPM, while THV-oversizing and intraprocedural postdilatation reduced the incidence of severe PPM (11).

With growing evidence of the association of PMM with impaired midterm survival after TAVR in small aortaic annulus, prospective data are required. The prospective and randomized SMART trial (ClinicalTrials.gov Identifier: NCT04722250) completed enrollment in September 2022 and compares TAVR patients with small aortic annulus receiving either the Medtronic Evolut PRO or Pro+ or the Edwards Sapien 3/3 ultra. With a 5-year follow-up, the SMART trial will analyze clinical outcomes (mortality, stroke, and heart failure rehospitalization) and valve function (PPM and PVL among other endpoints).

In this study, we used the data from a single-center registry. The study is limited by its retrospective and non-randomized design. Selection and confounding bias cannot be excluded. Follow-up transthoracic echocardiography was performed by multiple echocardiographers. No core lab evaluation was performed for baseline computerized tomography and baseline and follow-up echocardiography.