Introduction: Data on patients with small aortic annuli (SAA) undergoing transcatheter aortic valve implantation (TAVI) are limited. We aim to describe the impact of aortic annular size, particularly SAA and TAVI valve type on valve haemodynamics, durability and clinical outcomes.
Method: All patients in National Heart Centre Singapore who underwent transfemoral TAVI for severe symptomatic native aortic stenosis from July 2012 to December 2019 were included. Outcome measures include valve haemodynamics, prosthesis-patient mismatch (PPM), structural valve degeneration (SVD) and mortality.
Results: A total of 244 patients were included. The mean Society of Thoracic Surgeons score was 6.22±6.08, with 52.5% patients with small aortic annulus (<23mm), 33.2% patients with medium aortic annulus (23–26mm) and 14.3% patients with large aortic annulus (>26mm). There were more patients with self-expanding valve (SEV) (65.2%) versus balloon-expandable valve (BEV) (34.8%). There were no significant differences in indexed aortic valve area (iAVA), mean pressure gradient (MPG), PPM, SVD or mortality across all aortic annular sizes. However, specific to the SAA group, patients with SEV had larger iAVA (SEV 1.19±0.35cm2/m2 vs BEV 0.88±0.15cm2/m2, P<0.01) and lower MPG (SEV 9.25±4.88 mmHg vs BEV 14.17±4.75 mmHg, P<0.01) at 1 year, without differences in PPM or mortality. Aortic annular size, TAVI valve type and PPM did not predict overall mortality up to 7 years. There was no significant difference in SVD between aortic annular sizes up to 5 years.
Conclusion: Valve haemodynamics and durability were similar across the different aortic annular sizes. In the SAA group, SEV had better haemodynamics than BEV at 1 year, but no differences in PPM or mortality. There were no significant differences in mortality between aortic annular sizes, TAVI valve types or PPM.
The management of severe aortic stenosis (AS) in patients with small aortic annulus (SAA) represents a therapeutic challenge due to the increased mortality and major adverse cardiac events (MACE) seen in this group of patients even after surgical aortic valve replacement (SAVR).1,2
In recent times, the role of transcatheter aortic valve implantation (TAVI) has expanded significantly to include even those with low surgical risk.3 With the increased life expectancy in this low-risk group, it has become imperative to understand the impact of aortic annular size and TAVI valve type on prosthesis-patient mismatch (PPM), structural valve degeneration (SVD) and other clinical outcomes. While the negative impact of PPM has been well elucidated in SAVR, the data within TAVI cohorts have been controversial.4-6 Several studies have evaluated the medium-to-long-term valve durability of TAVI,7-11 but there is limited data on patients with SAA especially in Western cohorts where patients with larger annular areas predominate; this information gap would be particularly useful in an Asian population, where a significant proportion have SAA.
This study aims to describe the impact of aortic annular sizing and TAVI valve type on valve haemodynamics and durability, as well as clinical outcomes in patients undergoing TAVI, with a particular focus on patients with SAA.
All consecutive patients with severe symptomatic AS treated with TAVI at National Heart Centre Singapore from July 2012 to December 2019 were prospectively recruited into the registry (Centralised Institutional Review Board Reference 2014/2165). Details of the registry have been previously published.12,13 In summary, a heart team was involved in the selection of patients, type of transcatheter aortic valve used, and approach. Registry participation did not impact on clinical management. Written informed consent was obtained from all patients and ethical approval for the study was procured from the institutional review board. The TAVI procedure was carried out as per previously published standard protocols.14,15 All patients underwent echocardiographic evaluation at baseline prior to intervention, before discharge, at 3 months’ follow-up and yearly thereafter.
All patients who had transfemoral TAVI performed for severe native aortic valve stenosis, and those with a computed tomography (CT) performed for valve sizing were included. Patients with severe aortic regurgitation, non-transfemoral TAVI, valve-in-valve TAVI, and use of other modalities for valve sizing (e.g. transoesophageal echocardiogram) were excluded.
All patients underwent pre-operative evaluation of the aortic valve and aortic root, as well as the aorto-ilio-femoral vasculature anatomy, with either a 64-detector or 320-detector row CT scanner (Canon Medical Systems Corp, Otawara, Japan). Acquisition protocols of multidetector computed tomography (MDCT) data were acquired as per recommended.16-18 In brief, contrast-enhanced ECG-gated acquisition of the aortic root was performed after the injection of iodinated contrast, with the region of interest placed in the ascending aorta and axial slice of <1mm. All the MDCT data sets were recorded and stored for post-processing using 3mensio (3mensio Medical Imaging BV, Bilthoven, The Netherlands).19 From the 3 multiplanar reformation planes and the 3-dimensional reconstruction, automatic segmentation of the aortic root and a centre line crossing the aortic lumen is provided. After validation of the lowest insertion points of all the aortic cusp and the perpendicular plane, the maximum, minimum and mean diameters, area and perimeter of the aortic valve annulus are measured using the systolic images, at 30–40% of the RR interval of the contrast-enhanced MDCT scans, for sizing of the device. This is based on either the annular area (for balloon-expandable valves [BEV]) or the perimeter (for self-expanding valves [SEV)) of the annular dimension. In addition, the coronary heights and the respective sinus of Valsalva, sinotubular junction and ascending aorta dimensions were obtained, as recommended.16-18 Patients were stratified based on the aortic annular diameter derived on MDCT, either by area-derived (for BEVs) or perimeter-derived (for SEVs) method, with small annulus defined as <23mm, medium as 23–26mm, and large as ≥26mm, respectively.
Patients included in the registry were followed up based on a fixed schedule, with all patients completing in-hospital follow-ups, although not all patients completed 1-year follow-up. Outcome measures were based on Valve Academic Research Consortium 3-defined endpoints.20 The primary outcome of this study was 1-year all-cause mortality. Secondary outcomes included in-hospital mortality, post-procedure complications, PPM and SVD. PPM was defined as an indexed aortic valve area (iAVA) of <0.85cm2/m2 based on the post-TAVI echocardiogram performed prior to patient discharged on index admission for TAVI, with those between 0.65 and 0.85cm2/m2 classified as moderate, and <0.65cm2/m2 classified as severe. SVD was defined by change in mean pressure gradient (MPG) and aortic valve area (AVA) and/or new occurrence of aortic regurgitation (AR) compared with serial echocardiographic assessments performed post-procedure. Moderate SVD was defined as an increase in MPG≥10mmHg resulting in mean gradient ≥20mmHg with a concomitant decrease in AVA ≥0.3cm2 or ≥25%, and/or a new occurrence or increase of ≥1 grade of intraprosthetic AR resulting in ≥moderate AR. Severe SVD was defined as an increase in MPG≥20mmHg resulting in mean gradient ≥30mmHg with concomitant decrease in AVA≥0.6cm2, and/or new occurrence, or increase of ≥2 grades of intraprosthetic AR, resulting in severe AR.
Continuous variables were expressed as mean±standard deviation (SD) and categorical data was expressed as proportions and percentages. Echocardiographic outcomes were limited in some patients and the percentages calculated for echocardiographic outcomes were based on the denominator of those with such parameters measured. Comparison between continuous data was performed using the independent t-test or one-way analysis of variance, while categorical data were compared using chi-square test or Fisher’s Exact test. Short-term outcomes between the different aortic annular sizes were compared using logistic regression, and longer-term outcomes were compared using cox regression with the corresponding hazard ratios (HRs) and 95% confidence intervals calculated. Subgroup analyses based on TAVI valve type and PPM were also performed. Univariate analysis was performed for clinically significant variables with P<0.10, and multivariate analyses was subsequently done to adjust for confounders. Statistical analyses were conducted using Stata version 16 (StataCorp, College Station, Texas).
A total of 244 patients with mean Society of Thoracic Surgeons (STS) score of 6.22±6.08 were included. The mean duration of follow-up was 1,147±798 days.
The majority of patients had a SAA, with 128 (52.5%) small (<23mm), 81 (33.2%) medium (23–26mm) and 35 (14.3%) large (≥26mm). There were more patients with SEV (65.2%) versus BEV (34.8%). Compared with other groups, patients with SAA weighed less (small 58.82±12.15kg vs medium 62.83±14.13kg vs large 64.73±12.45kg, P<0.001), were shorter (small 154.02±8.24cm vs medium 159.77±8.39cm vs large165.26±8.66cm, P<0.001), had lower body surface area (BSA) (small 1.55±0.18m2 vs medium 1.66±0.2m2 vs large 1.71±0.19m2, P<0.001) and were predominantly female (small 64.84% vs medium 37.16% vs large 14.39%, P<0.001). There was also a lower proportion of patients with bicuspid valves (small 5.08% vs medium 18.75% vs large 29.41%, P<0.001). Mean left ventricular ejection fraction was higher for patients with SAA (small 57.16±11.24 % vs medium 49.80±14.49 % vs large 48.31±17.26%, P<0.001), as seen in Table 1.
The CT parameters for the different aortic valve annuli are also reflected in Table 1. Of note, aortic calcium score was significantly lower for patients with smaller aortic valve annulus (small 2,179.78±1,281.58 vs medium 27,86.05±22,076.32 vs large 3,221.67±1,740.49, P<0.007). There was, however, no significant difference for presence of porcelain aorta.
In terms of pertinent periprocedural complications, there was no significant difference with regards to permanent pacemaker implantation (small 8.59% vs medium 7.41% vs large 8.57%, P>0.05) across the 3 groups.
Comparing haemodynamic outcomes, there was no significant difference in terms of PPM across different aortic annular sizes. While patients with SAA have a smaller AVA post-procedure (small 1.66±0.43cm2 vs medium 1.75±0.45cm2 vs large 1.93±0.52cm2, P=0.0016) after correcting for BSA, iAVA did not show any significant difference (small 1.08±0.29 vs medium 1.09±0.32 vs large 1.12±0.25, P=0.821). This is also corroborated by no significant differences for MPG between the different aortic annuli. At 1 year, however, there were significantly more patients with larger annulus with at least moderate paravalvular AR (small 10% vs medium 15.38% vs large 33.33%, small vs medium P=0.358, small vs large P=0.036).
In terms of mortality, there were no significant differences with regards to in-hospital or 1-year mortality (Table 2), or throughout the entire follow-up period as demonstrated in the Kaplan-Meier survival curve (Fig. 1) (P>0.05).
Fig. 1. Kaplan-Meier survival curve based on aortic annular size.
From a valve durability standpoint, there were no patients who developed severe SVD up to 5 years of follow-up. Comparing the 3 groups, there was no significant difference in terms of SVD (Table 3). There were also no marked changes in AVA and MPG up to 5 years (Fig. 2).
Fig. 2. Comparison of aortic valve area and mean pressure gradient over time based on aortic annular size.
AvMPG: aortic valve mean pressure gradient; AVA: aortic valve area
Among those with SAA, patients who underwent SEV had a larger AVA (SEV 1.76±0.49cm2 vs BEV 1.39±0.25cm2, P=0.001), larger iAVA (SEV 1.19±0.35cm2/m2 vs BEV 0.88±0.15cm2/m2, P<0.001) and lower MPG (SEV 9.25±4.88mmHg vs BEV 14.17±4.75mmHg, P<0.001), at 1 year as illustrated in Fig. 3. However, there was no significant difference in terms of PPM. There were also no significant differences with regard to the presence of AR or pacemaker implantation. Both inpatient and 1-year mortality was not significantly different between the groups (P>0.05) (Table 4).
Fig. 3. Comparison of aortic valve area and mean pressure gradient over time based on aortic annular size and stratified by TAVI valve type.
AvMPG: aortic valve mean pressure gradient; AVA: aortic valve area; BEV: balloon-expandable valve; SEV: self-expanding valve
Among patients with large aortic annuli, while there was a significant difference in iAVA during the index hospitalisation in those who underwent SEV compared to BEV (1.22±0.24 vs 1.02±0.24, P=0.042), there were no differences in AV MPG. In addition, these differences were not seen at 1-year follow-up.
As seen in Table 5, for both medium and large aortic annuli, there were no significant differences in inpatient or 1-year mortality (P>0.05). Additionally, regardless of annular size, having at least moderate PPM did not have any significant differences in inpatient and 1-year clinical outcomes (P>0.05).
In the overall cohort, multivariate analyses (Table 6) demonstrated that aortic annular size (reference group small, medium HR 1.03, 95% confidence interval [CI] 0.54–1.98, P=0.929, large HR 1.85, 95% CI 0.83–4.09, P=0.133), TAVI valve type (reference group BEV, SEV HR 1.45, 95% CI 0.78–2.68, P=0.240) and moderate to severe PPM (HR 1.72, 95% CI 0.86–3.44, P=0.113) were not significant predictors of mortality. Independent predictors of mortality include obstructive lung disease (HR 2.21, 95% CI 1.05–4.64, P=0.036) and a lower estimated glomerular filtration rate (eGFR) (HR 1.02 95% CI 1.01–1.03, P=0.001).
Table 6. Multivariate analysis for independent predictors of overall mortality
|Hazard ratio||95% Confidence interval||P value|
|Aortic annular size|
|Obstructive lung disease||2.21||1.05–4.64||0.036|
|Moderate or severe prosthesis patient mismatch||1.75||0.88–3.50||0.113|
BEV: balloon-expandable valve; eGFR: estimated glomerular filtration rate; NYHA: New York Heart Association; SEV: self-expanding valve
In this study, we evaluated the impact of aortic annular sizing and TAVI valve type on valve haemodynamics and durability, as well as clinical outcomes in patients undergoing TAVI. In particular, there were substantial data on patients with SAA. We observed several significant findings: (1) annular size had no impact on valve haemodynamics, PPM or mortality; (2) in patients with small annular size, SEV had better valve haemodynamics than BEV but no differences in mortality; (3) moderate or severe PPM did not impact on mortality, at least at 1 year; and (4) annular size did not impact on longer-term SVD.
In terms of anatomic features, aortic annular size appears to be one of the most relevant factors that could theoretically play a major role in influencing valve haemodynamic performance and clinical outcomes.21-23 In our cohort, however, we found that this theoretical risk with the SAA group was not apparent; the SAA group had similar valve haemodynamics, especially after correcting for BSA, and clinical outcomes as the other groups. These findings are corroborated by other similar studies, especially in other Asian populations where there are significant groups of patients with SAA.22,24,25 Additionally, the SAA group in our cohort also had lower rates of paravalvular regurgitation post-intervention when compared to patients with larger aortic annulus. This is consistent with other studies with the postulation that the presence of an SAA minimises prosthesis-annulus incongruity, and allows for better apposition of the prosthesis to the native valve.26 This might be clinically relevant in the long term as AR is known to be a determining factor of long-term mortality after TAVI.27,28 On balance, longer observation and larger patient numbers may be required to validate a potential impact on long-term survival.
Studies have shown that SEV have better valve haemodynamics and lower PPM rates than BEV.29,30 Anatomically, the result of better haemodynamics may be driven by the supra-annular location in SEV compared with intra-annular location in BEV.21 These findings were also seen in our study but primarily in the SAA group. Importantly, there was no impact on mortality at 1 year regardless of valve type.
In terms of PPM, subgroup analyses of our cohort showed that moderate or severe PPM had no significant impact on mortality, at least at 1 year. The presence of severe PPM had been associated with negative outcomes, especially for patients post-SAVR.31 However, the impact of PPM appears mixed for patients post-TAVI, with some reporting an increased risk of mortality,4 while more recent studies showing no difference in clinical outcomes.5,6, 32 The theoretical negative impact of PPM can be explained by poorer haemodynamics resulting in a delay of regression of post-operative left ventricular hypertrophy, which may result in increased morbidity (through limitations in physical activity) and mortality in the long run. With improvements and advances in the bioprosthetic valve hemodynamic performance in the past decades, the negative effects of PPM may be attenuated.32 Our study adds to the growing evidence that PPM may not necessarily be related to increased mortality at least at 1 year, although this warrants longer follow-up to evaluate its effects on medium-to-long-term mortality.
In terms of valve durability, our study showed that annular size did not have an impact on SVD. While the medium-to-long-term valve durability of TAVI has been evaluated.7-11 these have been mainly in Western cohorts of patients with predominantly larger annular areas. In summary, these studies have shown that valve haemodynamics remained consistent for up to 7 years, with similar freedom from severe SVD for TAVI when compared to SAVR. Given that severe PPM and small prosthesis size have been postulated to be potential factors leading to accelerated bioprosthetic degeneration,33 data from patients with SAA is valuable. This study adds further knowledge in this burgeoning field, demonstrating the stability of valve haemodynamics especially in the SAA cohort up to 5 years. We acknowledge that longer-term studies are warranted—especially among younger patients with smaller bioprostheses who are at risk of requiring future interventions through valve-in-valve TAVI or redoing SAVR in the longer term.
Intrinsic limitations in our non-randomised prospective observational single-centre study are the possibility of bias that may not be fully accounted for even with the adjustment of confounders. Furthermore, the smaller patient numbers may not have been enough to detect smaller differences. However, the data do provide valuable insights, especially in a cohort with a significant proportion of patients with SAA. Lastly, there were fewer patients with long-term follow-up data; such information may be needed, especially for studying the outcome of SVD and the impact of PPM. Nevertheless, interesting hypotheses have been raised, which will be the work for future research.
Valve haemodynamics and durability were similar across the different aortic annular sizes. In the SAA group, SEV had better haemodynamics than BEV at 1 year, but no differences in PPM or mortality. There were no significant differences in mortality between aortic annular sizes, TAVI valve types or PPM.
- Wilbring M, Alexiou K, Schumann E, et al. Isolated aortic valve replacement in patients with small aortic annulus-a high-risk group on long-term follow-up. Thorac Cardiovasc Surg 2013;61:379-85.
- Bahlmann E, Cramariuc D, Minners J, et al. Small aortic root in aortic valve stenosis: Clinical characteristics and prognostic implications. Eur Heart J Cardiovasc Imaging 2017;18:404-12.
- Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med 2019;380:1695-705.
- Herrmann HC, Daneshvar SA, Fonarow GC, et al. Prosthesis-patient mismatch in patients undergoing transcatheter aortic valve replacement: From the STS/ACC TVT Registry. J Am Coll Cardiol 2018;72:2701-11.
- Ternacle J, Pibarot P, Herrmann HC, et al. Prosthesis-patient mismatch after aortic valve replacement in the partner 2 trial and registry. JACC Cardiovasc Interv 2021;14:1466-77.
- Tang GHL, Sengupta A, Alexis SL, et al. Outcomes of prosthesis-patient mismatch following supra-annular transcatheter aortic valve replacement: From the STS/ACC TVT Registry. JACC Cardiovasc Interv 2021;14:964-76.
- Deutsch MA, Erlebach M, Burri M, et al. Beyond the 5-year horizon – long-term outcome of high-risk and inoperable patients undergoing TAVR with first-generation devices. EuroIntervention 2018:14:41-9.
- Gerckens U, Tamburino C, Bleiziffer S, et al. Final 5-year clinical and echocardiographic results for treatment of severe aortic stenosis with a self-expanding bioprosthesis from the advance study. Eur Heart J 2017;38:2729-38.
- Gleason TG, Reardon MJ, Popma JJ, et al. 5-year outcomes of self-expanding transcatheter versus surgical aortic valve replacement in high-risk patients. J Am Coll Cardiol 2018;72:2687-96.
- Mack MJ, Leon MB, Smith CR, et al. 5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (Partner 1): A randomised controlled trial. Lancet 2015;385:2477-84.
- Kapadia SR, Leon MB, Makkar RR, et al. 5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (Partner 1): A randomised controlled trial. Lancet 2015;385:2485-91.
- Yap JJ, Tay JC, Ewe SH, et al. Impact of chronic kidney disease on outcomes in transcatheter aortic valve implantation. Ann Acad Med Singap 2020;49:273-84.
- Koh JQS, Mohamed Rahim NB, Sng EL, et al. Five-meter walk test as a predictor of prolonged index hospitalization after transcatheter aortic valve implantation. Am J Cardiol 2020;132:100-5.
- Adams DH, Popma JJ, MJ R. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med 2014;371:967-8.
- Webb JG, Altwegg L, Masson JB, et al. A new transcatheter aortic valve and percutaneous valve delivery system. J Am Coll Cardiol 2009;53:1855-8.
- Blanke P, Weir-McCall JR, Achenbach S, et al. Computed tomography imaging in the context of transcatheter aortic valve implantation (TAVI)/transcatheter aortic valve replacement (TAVR): An expert consensus document of the society of cardiovascular computed tomography. JACC Cardiovasc Imaging 2019;12:1-24.
- Blanke P, Schoepf UJ, Liepsic JA. CT in transcatheter aortic valve replacement. Radiology 2013;269:650-69.
- Francone M, Budde RPJ, Bremerich J, et al. CT and MR imaging prior to transcatheter aortic valve implantation: Standardisation of scanning protocols, measurements and reporting-a consensus document by the european society of cardiovascular radiology (ESCR). Eur Radiol 2020;30:2627-50.
- Ewe SH, Ng AC, Schuijf JD, et al. Location and severity of aortic valve calcium and implications for aortic regurgitation after transcatheter aortic valve implantation. Am J Cardiol 2011;108:1470-7.
- VARC-3 Writing Committee, Généreux P, Piazza N, et al. Valve academic research consortium 3: Updated endpoint definitions for aortic valve clinical research. Eur Heart J 2021;42:1825-57.
- Freitas-Ferraz AB, Tirado-Conte G, Dagenais F, et al. Aortic stenosis and small aortic annulus. Circulation 2019;139:2685-702.
- Regazzoli D, Chiarito M, Cannata F, et al. Transcatheter self-expandable valve implantation for aortic stenosis in small aortic annuli: The TAVI-SMALL registry. JACC Cardiovasc Interv 2020;13:196-206.
- Pibarot P, Weissman NJ, Stewart WJ, et al. Incidence and sequelae of prosthesis-patient mismatch in transcatheter versus surgical valve replacement in high-risk patients with severe aortic stenosis: A partner trial cohort–a analysis. J Am Coll Cardiol 2014;64:1323-34.
- Hase H, Yoshijima N, Yanagisawa R, et al. Transcatheter aortic valve replacement with Evolut R versus Sapien 3 in japanese patients with a small aortic annulus: The OCEAN-TAVI registry. Catheter Cardiovasc Inter. 2021;97:E875-86.
- Kamioka N, Arita T, Hanyu M, et al. Valve hemodynamics and clinical outcomes after transcatheter aortic valve replacement for a small aortic annulus. Int Heart J 2019;60:86-92.
- Kalavrouziotis D, Rodés-Cabau J, Bagur R DD, et al. Transcatheter aortic valve implantation in patients with severe aortic stenosis and small aortic annulus. J Am Coll Cardiol 2011;58:1016-24.
- Athappan G, Patvardhan E, Tuzcu EM, et al. Incidence, predictors, and outcomes of aortic regurgitation after transcatheter aortic valve replacement: Meta-analysis and systematic review of literature. J Am Coll Cardiol 2013;61:1585-95.
- Dworakowski R, Wendler O, Halliday B, et al. Device-dependent association between paravalvar aortic regurgitation and outcome after TAVI. Heart 2014;100:1939-45.
- Mauri V, Kim WK, Abumayyaleh M, et al. Short-term outcome and hemodynamic performance of next-generation self-expanding versus balloon-expandable transcatheter aortic valves in patients with small aortic annulus: A multicenter propensity-matched comparison. Circ Cardiovasc Interv 2017;10:e005013.
- Voigtländer L, Kim WK, Mauri V, et al. Transcatheter aortic valve implantation in patients with a small aortic annulus: Performance of supra-, intra- and infra-annular transcatheter heart valves. Clin Res Cardiol 2021.
- Head SJ, Mokhles MM, Osnabrugge RL, et al. The impact of prosthesis-patient mismatch on long-term survival after aortic valve replacement: A systematic review and meta-analysis of 34 observational studies comprising 27 186 patients with 133 141 patient-years. Eur Heart J 2012;33:1518-29.
- Ternacle J, Abbas AE, Pibarot P. Prosthesis-patient mismatch after transcatheter aortic valve replacement: Has it become obsolete? JACC Cardiovasc Interv 2021;14:977-80.
- Costa G, Criscione E, Todaro D, et al. Long-term transcatheter aortic valve durability. Interv Cardiol 2019;14:62-9.