Evidence summary

Population and studies description

This interventional procedures overview is based on 45,629 people from 4 systematic review and meta-analyses, 1 prospective case series, 1 retrospective propensity score matched study and 2 retrospective analyses. Of these 45,629 people, 13,722 people had the procedure for AR. 27,851 patients had SAVR, and 4056 patients had TAVI for AS. This is a rapid review of the literature, and a flow chart of the complete selection process is shown in figure 1. This overview presents 8 studies as the key evidence in table 2 and table 3, and lists 77 other relevant studies in appendix B, table 5.

Table 2 presents study details.

A systematic review and meta-analysis of 19 studies on TAVI for native AR was conducted according to PRISMA guidelines. Pooled estimates were calculated using a random-effects model. NGDs were compared with EGDs. Subgroup analysis and meta-regression were performed to study the effects of study level covariates on outcomes. There was significant heterogeneity across the available studies in terms of device used, access site, and outcomes reported. Some studies varied in patient characteristics and some have incomplete data reporting. Most of the studies had small sample sizes, reported their outcomes peri procedurally and lack data on long-term outcomes (Rawasi 2019).

In a meta-analysis of 11 studies on TAVI for AR, pooled estimates were calculated a using random-effects model. Subgroup meta-analysis of studies using EGDs and NGDs was also performed. Studies were heterogenous with different sample sizes, inclusion criteria, patient characteristics, types of valves, and TAVI approaches. Most of the studies were multicentre studies and there might be an overlap of patients and that might have overestimated the effects of the intervention. Meta-regression were performed to study the effects of 12 covariates on 30-day all-cause mortality (Takagi 2020).

A systematic review and meta-analysis of 31 studies on NGDs was based on small retrospective observational studies with heterogenous populations. The study was conducted according to PRISMA guidelines. Most pooled studies had a low risk of bias. Authors state that there might be an overlap of study cohorts in pooled multicentre studies conducted in the same country. The study did not report results separately for SE and BE prostheses because it was not possible to differentiate in the articles (Liu 2024).

A large multicentre prospective case series of 180 patients (the JenaValve ALIGN-AR pivotal trial) in the USA assessed TAVI in patients with severe symptomatic AR and at high risk of surgery. Findings were compared with a pre-specified performance goal and analysis was on early outcomes (Vahl 2024).

The PANTHEON study was a retrospective international registry analysis that assessed both SE and BE NGDs in patients with severe pure native AR and considered high-risk or inoperable. TF approach was the most common approach used. Different types of valves were used and only 10% were JenaValve Trilogy THV, which is a dedicated device system for native AR. Echocardiographic outcomes were not reported so the rate of moderate to severe AR at follow-up are unknown (Polleti 2023).

One retrospective analysis with small sample and short follow-up period assessed TAVI with off-label NGDs in different risk groups. Patients were classified into different risk groups based on STS scores and not on EuroSCORE (Da-Wei 2024).

A systematic review and meta-analysis of 6 studies comparing TAVI with SAVR in patients with pure native AR followed the Cochrane Handbook for Systematic Reviews of Intervention, AMSTAR -2 guidelines and reported it according to the PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of included studies and all included studies posed a low risk of bias. The strength of evidence was assessed using the GRADE scale. Heterogeneity was assessed using inconsistent test. Meta-analysis was done using the random effect model and subgroup analysis was done depending on the approach of TAVI (TF and TA) and the country of origin. The efficacy of TAVI and SAVR in patients with different surgical risk was not analysed. (Elkasaby 2024).

A retrospective propensity score matched study comparing TAVI in AR with TAVI in AS used NRD codes for diagnosis of AR and these might be subject to misclassification and may not be accurate. Procedural and echocardiographic outcomes were not assessed in this study due to lack of data. Patients were either symptomatic or had a compelling indication for valvular replacement. They were of similar age in both groups and had similar comorbidities (the Elixhauser comorbidity index [to predict in-hospital mortality] was comparable) (Ullah 2024).

Figure 1 Flow chart of study selection

**Table 2 Study details**
Study no.	First author, date country	Characteristics of people in the study (as reported by the study)	Study design	Inclusion criteria	Intervention	Follow up
1	Rawasia WF 2019 USA	19 studies (n=998 patients with pure native AR) 13 full studies and 6 abstracts. Mean age: ranged from 68 to 84 years, mean logistic EUROSCORE ranged from 9.8 to 34.0.	Systematic review and meta-analysis Databases searched: MEDLINE, Scopus, and Cochrane CENTRAL	Studies in English with at least 5 patients undergoing TAVR for pure native AR, reporting at least one of the endpoints were included in the meta-analysis. Case reports and editorials were excluded. In case of serial publications, only the most recent one was included.	TAVI NGDs versus EGDs Valves used new generation (purpose-specific valves: JenaValve, ACCURATE TA; non-purpose-specific valves: CoreValve, Sapien XT, Direct Flow]) or (early generation [CoreValve and Sapien XT) Access route: TF or TA access. Valve size: not reported.	Varied across studies. 30 days to 1 year
2	Takagi H 2020 Japan	11 studies (n=911 patients undergoing TAVI for AR) Age: range 73 to 75 years.	Systematic review and meta-analysis of single arm studies. Databases searched: Medline and EMBASE, up to July 2018	Studies with more than 20 patients undergoing TAVI for AR were included.	TAVI NGDs versus EGDs Access route: TF or TA access. NGDs were used in 7 studies (SAPIEN 3, JenaValve, J-Valve, Accurate, Direct Flow, Engager, Evolut R, Lotus, Portico). EGDs were used in 5 studies (CoreValve, SAPIEN, SAPIEN XT). 2 studies (Yoon 2017, de Backer 2018) compared NGD and EGDs. 1 compared off label with on-label devices (Frerker 2015). 1 compared TAVI for AR with TAVI for AS or TAVI for AS + concomitant-grade of AR (Testa 2014). 5 studies (Silaschi 2018, Liu 2018, Seiffert 2014, Toggweiler 2018, Zhu 2016) used only NGDs and 3 studies (Testa 2014, Roy 2013, Frerker 2015) used only EGDs.	Varied across studies. 30 days to 1 year
3	Liu 2024 China	31 observational studies (n=1,851 patients with severe AR and not suitable for surgery)	Systematic review and meta-analysis Databases searched MEDLINE, Embase, Cochrane Library, and Scopus; until April 2023.	RCTs and observational studies including cohort studies, case-controlled studies, and case series with at least 10 cases were included. Studies not reporting the outcomes or from which summary data could not be extracted were excluded.	TAVI with NGDs Compared 'off-label' devices and 'on-label devices. On label devices (20 studies, n=1067): J valve, 15 studies, n=949 Jena valve, 5 studies, n=307 Off label devices (11 studies, n=784): Evolut, n=284 SAPIEN 3, n=61 Direct Flow, n=90 ACURATE, n=76 Lotus, n=34 Engager, n=26 Portico, n=9 Symetis, n=15 Valve size: 27mm valves mostly used. Access route: 70% TA access 30% TF access	Varied across studies. 30 days to 1 year
4	Poletti, 2023, 16 centres across Europe and USA	N= 201 patients with pure severe native AR. Median age: 79 years (IQR: 73-83 years) Gender: 55.2% male (47.7% in the SE group versus 69.6% in the BE group). Median STS risk score of 5.1% (SE 5.2, BE 4.8, p= 0.005). Rate of NYHA functional class III or IV was 76.2%.	Retrospective analysis (of procedures between2014-2022) NCT05319171 PANTHEON international registry	Patients who underwent TAVI for pure severe native valve AR and considered inoperable high risk surgical candidates were included. Those with concomitant moderate to severe AS, treated with older THVs no longer commercially available and those treated via transapical access were excluded.	TAVI with NGDs SE valves (n=132; Evolut R 76, Accurate Neo 25, Jena valve 21, Navitor Portico 10) and BE valves (n=69; Myval 40, Sapien S3 29). Access route: TF approach: n=192 Trans-subclavian approach n=8. SE valves were oversized and 80% patients needed rapid pacing. 10% SE valves were dedicated valves (Jena valve in 21).	30 days and 1 year. Median follow-up duration was 377 days (IQR: 138-915 days) in 181 patients.
5	Vahl TP 2024 USA	ALIGN-AR IDE trial (NCT 04415047) n=180 patients with pure AR. Mean age: 75.5 years Gender: 53% (95/180) male 73% (131/180) were white. mean STS-PROM score 4.1% (SD 3.4). 89% (161/180) patients were deemed to be at high risk on the basis of comorbidities; 34% (61/180) patients were assessed as frail. AR severity: moderate to severe in 32% (57/180); severe in 64% (116/180) patients. NYHA class III-IV 68% (122/180)	Prospective case series (at-20 centres in USA).	Inclusion criteria: Symptomatic patients with NYHA functional class II or higher, aged 18 years or older with moderate-to-severe or severe native AR (according to the ASE criteria), deemed at high risk for mortality and complications after SAVR by the heart team and independent screening committee assessments. Exclusion criteria: congenital unicuspid or bicuspid valve morphology, previous prosthetic aortic valve implant, straight ascending aorta length less than 55 mm, aortic annulus angulation less than 70°, and severely reduced LVEF (less than 25%).	TAVI with on-label NGD JenaValve Access route: TF Device size: 23 mm (40 [23%] patients), 25 mm (35 [20%]), and 27 mm (102 [58%]). Mean oversizing was 12.6% for the 27-mm valve, 15.4% for the 25-mm valve, and 17.7% for the 23-mm valve. General anaesthesia in 164 (91%) and monitored anaesthesia care in 16 (9%).	At 30 days, 6 months and 1 year.
6	Da-Wei, 2024, China	N= 75 patients with pure severe AR. Categorized into 2 groups: low-risk group: (STS score < 4), n=38; intermediate and high-risk group: (STS score ≥ 4), n=37. Age: low risk group 73.1 years, high risk group 76.4 years, p=0.028. Gender: n=46 male Patients in the lower risk group were younger, had a lower BMI, lower prevalence of hypertension, COPD, and previous percutaneous coronary intervention compared to high-risk group (p all <0.05). There was no significant difference between the 2 groups for prevalence of hyperlipidaemia, diabetes, and AF.	Retrospective analysis compared the outcomes of TAVI between low-risk and intermediate/high-risk patients with severe AR.	Patients with pure severe AR eligible for TAVI and had no contraindications for the procedure.	TAVI with off-label NGD (Venus-A and VitaFlow valves) in low-risk patients (STS<4) and intermediate and high-risk patients with severe AR (STS>4). Low risk, n=38 (Venus n=16, VitaFlow n=22) Intermediate and high risk, n=37 (Venus n=17, VitaFlow n=20) Access route: TF access Size of valve: no significant difference between low risk and high-risk groups (0.73)	30 days.
7	Elkasaby MH 2024	n=6 retrospective cohort studies 33,484 patients with pure/isolated AR. (5,633 patients in the TAVI group and 27,851 in SAVR group). 3 studies in USA, 1 in China, and 2 in Germany. Age: TAVI group ranged from 67 to 77 years, versus 60.0 to 75.6 years in the SAVR group. TAVI patients were older and had higher comorbidity scores.	Systematic review and meta-analysis Databases searched: PubMed, Embase, Web of Science (WOS), Scopus, and the Cochrane Library Central Register of Controlled Trials (CENTRAL) until June 2023.	Included RCTs or cohort studies including patients with pure AR, comparing TAVI with SAVR, reporting in-hospital mortality or stroke. Excluded single-arm studies, studies with more than one publication, studies including AS patients or patients with mixed AR and AS, case reports, reviews, abstracts, and animal studies.	TAVI versus SAVR in pure AR Various types of valves were included in studies.	Varied across studies (from in-hospital to 1 year).
8	Ullah W 2024 USA	Unmatched sample n=185,703 (AI 3873, AS 181,830) patients. Matched sample of 7,929 patients (AI 3,873, AS 4,056). Mean age: TAVI for AI (mean 76.8 years), TAVI for AS (76.9 years). Female patients in AI versus AS groups was 38% versus 37%. The Elixhauser comorbidity index (to predict in-hospital mortality) for TAVI in AI versus TAVI in AS (2.63 versus 2.78, p = 0.51).	Retrospective study Propensity-score matched (PSM) analysis NRD claims data from (2015-19) were used.	All US adult patients (over 18 years) who underwent TAVI for pure AS or AI were included, indicating that patients were either symptomatic or had a compelling indication for valvular replacement. Patients who underwent SAVR, had mixed AS and AI, or had the unspecified aortic valvular disease were excluded from the analysis.	TAVI for AI versus TAVI for AS Details of valves used were not available in the article	In-hospital, 30 days and 180 days.

**Table 3 Study outcomes**
First author, date	Efficacy outcomes	Safety outcomes
Rawasi 2019	NGDs versus EGDs Device success (14 studies, n=524/659 events) ES 0.862 (95% CI 0.788 to 0.922), I² 81.01%, p<0.001. Device success was higher with purpose-specific valves (96.3%, 95% CI 92.2 to 98.9%; I²=0%) compared with non-purpose specific valves (84.4% (95% CI 75 to 91.9%); I²=46%) (p=0.02). Device success did not differ significantly (p = 0.32) between the transfemoral [82.1% (68%–92.8%); I² = 78%] and transapical subgroups [90.3% (79.2%– 97.4%); I² = 87%].	NGDs versus EGDs Mortality 30-day (19 studies, n=122/998) ES 0.119 (95% CI 0.094 to 0.147), I²=27.99%, p=0.110 There was no statistically significant difference in the rate of 30-day mortality between those purpose-specific (8.2%; 95% CI 4.3 to 13.1%; I²=0%) and non-purpose specific valves (13.0%; 95% CI 8.2 to 18.6%; I²=25%); p=0.13). Also, there was no significant difference in 30-day mortality (p = 0.41) between the subgroup (n = 475) with primarily transapical access [10% (7.4%– 12.8%); I² = 0%], and the subgroup (n = 173) with primarily femoral access [12.6% (7.3%–19.0%); I² = 0%. 1 year (6 studies, n=155/618) ES 0.247 (95% CI 0.213 to 0.281), I²=0%, p=0.481. PPM implantation (14 studies, n=92/63) ES 0.131 (95% CI 0.093 to 0.175), I²=44.1%, p=0.034) There was no statistically significant difference in the rate of PPM implantation between purpose-specific (6.8% [3.2 to 11.7%; I²=0%] and non-purpose-specific valves (19.8% [95% CI 6.7 to 37.5%; I²=76%); (p=0.06). Also, there was no statistically significant difference in the rate of PPM implantation between studies using transfemoral access (13% [95% CI 5.4 to 23.3%; I²=58%), and those using transapical access (12%, 95% CI 8.9 to 15.6%]; I²=8%); (p=0.84). Major bleeding (11 studies, n=69/582) ES 0.124 (95% CI 0.061 to 0.204), I²=82.13%, p<0.001 Residual moderate to severe AR (18 studies, n=99/966) ES 0.092 (95% CI 0.055 to 0.137), I²=75%, p<0.001. moderate to severe AR was significantly lower (p = 0.002) with the use of purpose-specific valves [3.1% (0.9% –6.4%); I 2 = 0%] compared with non-purpose-specific valves [14.4% (7.6%, 22.9%); I 2 = 54%]. There was no significant difference (P = 0.18) in the risk of residual moderate to severe AR between studies using transapical access [5.2% (2.0%, 9.6%); I² = 57%], and studies using transfemoral access [12.9% (4.4%– 25%); I² = 75%]. Stroke (14 studies, n=20/648) ES 0.036% (95% CI 0.023 to 0.051), I²=0%, p=0.967 Myocardial infarction at 30 days (11 studies): no cases
Takagi H 2020	NGDs versus EGDs Device success Overall,80.4% (95% CI 72.2 to 88.6%, I²=92.36%, p=0.000) EGDs (5 studies) 67.2% (95% CI 54.4 to 79.9%, I²=81.95%, p=0.000); NGDs (7 studies) 90.2% (95% CI 84.0 to 96.3%, I²=81.63%, p=0.000); p<0.001 between groups.	NGDs versus EGDs Conversion to open surgery Overall, 3.0% (95% CI 1.5 to 4.4) EGDs 2.8% (95% CI 0.4 to 5.1); NGDs 3.1% (95% CI 1.3 to 4.9); p=0.840 between groups. Coronary obstruction Overall, 0.7% (95% CI 0.1 to 1.4) EGDs 0.4% (95% CI 0 to 1.3) NGDs 1.2% (95% CI 0.2 to 2.2); p=0.243 between groups. Valve in valve deployment Overall, 10.5% (95% CI 4.9 to 16.2, I²=86.21%, p=0.000) EGDs (3 studies) 22.1% (95% CI 16.2 to 28.0, I²=0, p=0.665) NGDs (5 studies) 4.7% (95% CI 0 to 9.7, I²=78.52%, p=0.001); p<0.001 between groups. Annulus rupture Overall, 1.5% (95% CI 0.3 to 2.6) EGDs 1.7% (95% CI 0 to 4.0) NGDs 1.4% (95% CI 0.1 to 2.7); p= 0.834 between groups. Reintervention Overall, 3.9% (95% CI 2.5 to 5.3) EGDs 4.3% (95% CI 1.7 to 6.9) NGDs 4.0% (95% CI 2.1 to 5.9), p=0.868 between groups. PPM implantation Overall, 11.6% (95% CI 6.8 to 16.4, I²=81.68, p=0.000) EGDs (4 studies) 15.6% (95% CI 9.4 to 21.8, I²=72.07%, p=0.013) NGDs (6 studies) 8.3% (95% CI 2.0 to 14.5, I²=75.78%, p=0.001), p=0.085 between groups. Moderate or higher paravalvular AR Overall, 7.4% (95% CI 4.0 to 10.9, I²=78.02%, p=0.000) EGDs (4 studies) 17.3% (95% CI 6.7 to 27.9, I²=83.17%, p=0.000) NGDs (7 studies) 3.4% (95% CI 1.8 to 5.0, I²=0, p=0.908); p<0.001 between groups. 30-day mortality All cause Overall, 9.5% (95% CI 6.4 to 12.6, I²=61.25%, p=0.003) EGDs (5 studies) 14.7% (95% CI 10.8 to 18.6, I²=0%, p=0.417) NGDs (7 studies) 6.1% (95% CI 3.2 to 8.9, I²=40.31%, p=0.122); p<0.001 between groups. Cardiovascular related Overall,6.6% (95% CI 4.4 to 8.8) EGDs 9.5% (95% CI 3.2 to 15.7) NGDs 5.8% (95% CI 3.7 to 7.9); p=0.193. Mid-term all-cause mortality (between 6 to 12 months) Overall, 18.8% (95% CI 10.9 to 26.7, I²=84.85%, p=0.000) EGDs (4 studies) 32.2% (95% CI 25.7 to 38.8, I²=0%, p=0.454) NGDs (6 studies) 11.8% (95% CI 4.5 to 19.0, I²=77.79%, p=0.000); p<0.001 between groups. Stroke Overall, 2.7% (95% CI 1.7 to 3.8) EGDs 2.3% (95% CI 0.6 to 3.9) NGDs 2.9% (95% CI 1.5 to 4.4); p=0.541 between groups. Life threatening or major bleeding complications Overall, 5.7% (95% CI 2.8 to 8.6, I²=0%, p=0.480) EGDs (5 studies) 12.4% (95% CI 4.9 to 19.9, I²=0%, p=0.950) NGDs (6 studies) 3.5% (95% CI 0.4 to 6.7, I²=0%, p=0.458); p=0.015 between groups. Acute kidney injury (stage 1 to 3): Overall, 10.5% (95% CI 2.6 to 18.3) EGDs 18.2% (95% CI 2.1 to 34.3) NGDs 9.1% (95% CI 0.9 to 17.33); p=0.309 between groups. Major vascular complications: Overall, 3.9 (95% CI 2.7 to 5.2) EGDs 6.2% (95% CI 3.5 to 8.8) NGDs 3.0% (95% CI 1.5 to 4.5); p=0.041 between groups. Stepwise random-effects meta-regression Meta-regression showed that none of the covariates/factors assessed were associated with 30-day all-cause mortality.
Liu 2024	Device success at 30 days (as per VARC-2 criteria) NGDs: ES 0.945 (95% CI 0.913 to 0.971), I²=76.8%, p=0.000. On label devices: ES 0.978 (95% CI 0.964 to 0.989), I²=8.2, p=0.358. Off label devices (6 studies, n=258): ES 0.899 (95% CI 0.848 to 0.941), I²=10.3, p=0.350; (p<0.001 between on and off label devices) Access route: TF (8 studies, n=340): ES 0.925 (95% CI 0.875 to 0.964), I²=35.6, p=0.144. TA (16 studies, n=873): ES 0.961 (95% CI 0.939 to 0.979), I²=50.4, p=0.003. (p=0.000 between routes).	NGDs; on label versus off label Mortality 30 days NGDs: ES 0.042 (95% CI 0.027 to 0.059), I²=43.8, p=0.008 On label devices: ES 0.026 (95% CI 0.013 to 0.043), I²=22.1, p=0.192 Off label devices: ES 0.051 (95% CI 0.016 to 0.102), I²=30.4, p=0.219 (p=0.006 between on and off label devices) Access route: TF: ES 0.040 (0.012 to 0.078), I²=28.9, p=0.208 TA: ES 0.029 (0.014 to 0.047), I²=30.7, p=0.117 (p=0.052 between routes) 1 year NGDs: ES 0.081 (95% CI 0.051 to 0.117), I²=67.3, P=0.001 On label devices: ES 0.059 (95% CI 0.035 to 0.087), I²=23.3, p=0.251 Off label devices: NA Permanent pacemaker implantation NGDs: ES 0.088 (95% CI 0.061 to 0.119), I²=57, p=0.000 On label devices: ES 0.069 (95% CI 0.046 to 0.095), I²=40, p=0.041 Off label devices: ES 0.184 (95% CI 0.132 to 0.242), I²=0, p=0.928 (p<0.001 between on and off label devices) Access route: TF: ES 0.194 (95% CI 0.148 to 0.244), I²=0, p=0.814 TA: ES 0.060 (0.043 to 0.078), I²=0, P=0.787 (p=0.000 between routes) Conversion to SAVR NGDs: ES 0.022 (95% CI 0.009 to 0.038), I²=0, p=0.981 On label devices: ES 0.025 (95% CI 0.012 to 0.042), I²=0, p=0.957 Off label devices: NA Annulus rupture NGDs: ES 0.002 (95% CI 0.000 to 0.017), I²=0, P=0.941 ON label devices: NA Off label devices: NA Reintervention NGDs: ES 0.023 (95% CI 0.007 to 0.045), I²=13.9, p=0.324 On label devices: NA Off label devices: ES 0.028 (95% CI 0.000 to 0.114), I²=54.6, p=0.111 Greater than mild PVL NGDs: ES 0.012 (95% CI 0.004 to 0.022), I²=0, p=0.713 On label devices: ES 0.009 (95% CI 0.002 to 0.019), I²=0, p=0.942 Off label devices: ES 0.038 (95% CI 0.012 to 0.074), I²=0, p=0.611 (p=0.003 between on and off label devices) Access route: TF ES 0.034 (95% CI 0.012 to 0.063), I²= 0.0, P= 0.791 TA ES 0.008 (95% CI 0.001 to 0.018), I²= 0.0, P= 0.960 (p=0.002 between routes) Mild PVL NGDs: ES 0.209 (95% CI 0.176 to 0.244), I²=12.8, p=0.304 On label devices: ES 0.203 (95% CI 0.165 to 0.243), I²=19, p=0.241 Off label: NA Access route: TF ES 0.184 (95% CI 0.115 to 0.263), I²= 29.5, P= 0.235 TA ES 0.216 (95% CI 0.117 to 0.259), I²= 13.1, P= 0.314 (p=0.314 between routes) None/trace PVL NGDs: ES 0.774 (95% CI 0.708–0.835), I²=71.3, p=0 On label devices: ES 0.780 (95% CI 0.705–0.847), I²=73.4, p=0 Off label: NA Access route: TF ES 0.781 (95% CI 0.685–0.866), I²= 42.9, P= 0.154 TA ES 0.769 (95% CI 0.683–0.846), I²= 76.2, P= 0.000 (p=0.897 between routes)
Poletti, 2023 NCT05319171 PANTHEON international registry	Technical success (according to the VARC-3 criteria included freedom from mortality, successful delivery of the device, retrieval of the delivery system, correct positioning of the valve and freedom from surgery or intervention related to the device, access or cardiac structural complication at the time of exit from the procedure room): Overall: 83.6% (168/201) SE: 80.3% (106/132) versus BE: 89.9% (62/69); p = 0.108. Device Success at 1 month (defined as technical success at 30 days along with satisfactory valve performance (mean gradient less than 20 mmHg, and less than moderate regurgitation): Overall: 76.1% (153/201) SE: 75.8% (100/132) versus BE: 76.8% (53/69); p = 0.868.	In-hospital events All-cause death Overall, 5% (10/201) SE group 5.3% (7/132) versus BE group 4.4% (3/69), p=0.767 Cardiovascular Death: Overall: 4.0% (8/201) SE group 3.8% (5/132) versus BE group 4.4% (3/69), p = 0.847 Stroke/TIA: Overall: 1.5% (3/201) SE group 2.3% (3/132) versus BE group 0 (0), p = 0.553 Transcatheter valve embolisation or migration (TVEM defined according to the VARC-3 definition and included valve migration, embolisation and ectopic valve deployment). The causes of TVEM were malpositioning [32%], oversizing [20%], valve failure to anchor [20%], manipulation [8%] and unknown causes [12%] Overall, 12.4% (25/201) SE group 13.6% (18/132) versus BE group 10.1% (7/69), p=0.476. Post-dilation was the single independent variable associated with TVEM on multivariate analysis. Residual moderate or greater AR (in-hospital echocardiography): Overall, 9.5% (19/201) SE group 9.2% (12/132) versus BE group 10.1% (7/69), p=0.835. New PPM implantation: Overall: 22.3% (36/201) SE group 22.6% (24/132) versus BE: 21.8% (12/69), p = 0.918 Major vascular complications: Overall: 7.5% (13/201) SE group 8.1% (9/201) versus BE group 6.5% (4/69), p = 0.532. Major bleeding: Overall: 10.6% (20/201) SE: 12.6% (16/132) versus BE group 6.5% (4/69), p = 0.197 Conversion to surgery: Overall: 2.0% (4/201) SE group 1.5% (2/132) versus BE group 2.9% (2/69), p = 0.612 AKI (network classification≥ 2): Overall: 10.5% (18/201) SE group 10.9% (12/201) versus BE group 9.8% (6/69), p = 0.827 Second valve needed: Overall: 10.5% (21/201) (THV implantation in 10, snaring in 5, repositioning in 2, procedure aborted in 4). SE group 11.4% (15/132) versus BE group 8.7% (6/69), p = 0.557 Postprocedural mean gradient (mm Hg): Overall: 6.7 (SD 3.9) SE group 6.3 (SD 2.7) versus BE: 7.5 (SD 5.3), p = 0.049 Final transvalvular gradient: BE group (7.5 SD 5.3 mm Hg) versus SE group (6.3 SD 2.7 mm Hg); p = 0.049. Composite endpoint at 1 year (composite of all-cause mortality and heart failure rehospitalisation), in 90% (181/201): Overall incidence 17.1% (95% CI: 10.4%-23.4%), SE group 18.1% (95% CI: 9.1%-26.2%) BE group15.1% (95% CI: 4.7%-24.4%) (log-rank p= 0.52). Incidence of composite endpoint in patients with TVEM: 25.7% (95% CI: 5.6%-41.5%) versus those without TVEM: 15.8% (95% CI: 10.4%-23.4%); p = 0.05. There was no significant difference in the incidence of TVEM between the SE and BE device groups (14.6% for SE and 16.1% for BE, p = 0.835). After adjusting for propensity score, there was no significant difference between the SE or BE valves in terms of technical failure (aOR: 0.48; 95% CI: 0.18-1.18; P = 0.127), device failure (aOR:1.04; 95% CI: 0.49-2.13; p = 0.923), TVEM (aOR: 0.71; 95% CI: 0.25-1.81; P = 0.486), or the rate of residual moderate or severe AR (aOR: 1.07; 95% CI: 0.36-2.98; P = 0.894). Even after propensity matching, TVEM led to higher 1-year incidence of the composite endpoint (HR: 2.45; 95% CI: 1.00–6.18; p=0.05) and all-cause mortality (HR: 4.06; 95% CI: 1.50–11.0; p=0.006).
Vahl 2024 NCT 04415047	NGD with on label (JenaValve) Technical success 95% (171/180). Mean total procedure time was 71.8 min (SD 24.9). All-cause mortality at 1-year (primary efficacy point): achieved, in 7.8% (14/180 [97.5% CI 3.3 to 12.3]) patients (p <0.0001) when compared for non-inferiority with a performance goal of 25%. In pre-specified group who received successful valve implantation: primary efficacy was achieved in 16.2% (11/177; [97.5% CI 2.2 to 10.3)]; p_{non-inferiority}<0.0001) patients at 1 year. Haemodynamic outcomes Data are mean (SD) Mean aortic gradient, mm Hg Baseline (n=180) 8.7 (6.6) 30 days (n=172) 3.9 (1.6) 6 months (n=154) 4.3 (2.0) 12 months (n=141) 4.3 (1.8). Effective orifice area, cm² 30 days (n=172) 2.9 (0.6) 6 months (n=154) 2.7 (0.6) 12 months (n=141) 2.8 (0.6). Effective orifice area index, cm²/m² 30 days (n=172) 1.7 (0.4) 6 months (n=154) 1.5 (0.4) 12 months (n=141) 1.6 (0.3). LVEF, % Baseline (n=180) 53.8 (11.4) 30 days (n=172) 49.7(12.6) 6 months (n=154) 51.9 (12.0) 12 months (n=141) 55.0 (11.6). LV remodelling/ dimensions (by echocardiography) Mean LV mass declined from 323.7 g (SD 123.4) at baseline to 219.5 g (SD 101.4; p<0.0001) at 1 year Mean LVESd decreased from 39.6 mm (SD 10.2) at baseline to 34.2 mm (SD 9.0; p<0.0001) at 1 year. Functional status (NYHA classification) Baseline Class II 32% Class III 63% Class IV 5% At 30 days Class I 51% (91/180) Class II 34% (62/180) Class III 9% (17/180). At 1 year Class I 50% (90/180) Class II 27% (48/180) NYHA functional class improved by at least one category in 125 (83%) patients. Quality of life (assessed using KCCQ scoring) From baseline to 1-year, the mean KCCQ overall score increased by 20.6 points (SD 24.3) from a mean of 55.3 (27.1) to 77.6 (22.7; p<0·0001; Large improvement (20-point or more increase) 41% (63/152) Moderate improvement (increase between 10 and <20 points 16% (24/152) Small improvement (increase between 5 and <10 points) 7% (11/152) No change (change between –5 and less than 5 points) 18% (27/152) Worse (more than 5-point decrease from baseline) 11% (16/152) Dead 7% (11/152). 6-minute walk test An increase in 6-min walk test distance was found and 48% (62/180) patients had an improvement of at least 15 m from baseline to 1 year.	NGD with on label (JenaValve) The 30-day composite primary safety endpoint* was achieved in 27% (48/180) [97.5% CI 19.2 to 34.0]) patients (p _{non-inferiority}<0.0001), when compared with the pre-specified safety performance goal of 40.5%. (a non-hierarchical composite consisting of all-cause mortality, any stroke, life-threatening or major bleeding, AKI stage 2 to 3 or dialysis [7-day endpoint], major vascular complications, surgery or intervention related to the device [including coronary intervention], new permanent pacemaker implantation, and moderate or severe total AR at 30-days after the procedure according to VARC-2 definitions). Total adverse events 27% (48/180)* Death 2% (4/180) Any stroke 2% (4/180) Disabling stroke 1% (1/180) Non-disabling stroke 1% (1/180) Major or life-threatening bleeding 4% (8/180) Major vascular complication 4% (7/180) AKI (stage 2 or 3) or dialysis (7 days) 1% (2/180) Surgery or intervention related to the device 3% (5/180) SAVR for valve embolisation 1 Commercial THV for valve embolisation 1 aortic endograft and commercial THV for catheter induced aortic dissection 1 second Trilogy THV for valve embolisation in 2 New PPM implantation in 24% (36/150) (30 people had a previous pacemaker) Paravalvular AR at 1 year Moderate or greater paravalvular AR 1 Mild or mild to moderate PAR reduced from 19% (n=31) at 30 days to 8% (n=11) none or trace in 92% (n=130)
Da-Wei, 2024	Echocardiography outcomes Low-risk group: LVEDd andLVESd significantly decreased at 1 month from baseline (LVEDd: 54.3 [SD 6.2] versus 50.4 [SD 6.4], p = 0.017; LVESd: 40.2 [8.4] versus 35.9 [SD 7.3], p = 0.037). There was no significant difference in LVEF 50.9 [10.2] versus 51.8 [SD 11.0], p = 0.73). There was no significant difference in LVEF, moderate-to-severe MR, and moderate-to-severe TR. Intermediate and high-risk group: LVEDd decreased significantly at 1 month from baseline (57.6 [SD 6.2] versus 53.3 [SD 8.1], p=0.035) The rate of moderate-to-severe MR was also significant (p=0.036) but the difference in LVESd, LVEF, and moderate-to-severe TR, was not significant. NYHA functional class Changes in NYHA functional class in low risk and intermediate and high-risk groups significantly improved from baseline at both 1 and 30 days after TAVI (both p <0.001).	All-cause mortality (postoperative and at 30 days): Low risk group 0% (0/38) versus intermediate and high-risk group: 0% (0/37) Cardiovascular mortality (postoperative and at 30 days): Low risk group 0% (0/38) versus intermediate and high-risk group: 0% (0/37) Bleeding Events (postoperative and at 30 days): Low risk group 2.6% (1/38) versus intermediate and high-risk group: 0% (0/37), p= 0.32 Major vascular complications: Postoperative Low risk group 2.6% (1/38) versus intermediate and high-risk group: 2.7% (1/37), p= 0.98 30 days Low risk group 0 versus intermediate and high-risk group 0 Acute renal failure (postoperative and at 30 days): Low risk group 0 versus intermediate and high-risk group 0 Stroke (postoperative and at 30 days): Low risk group 0 versus intermediate and high-risk group: 2.7% (1/37), p= 0.31 Myocardial infarction (postoperative and at 30 days): Low risk group 0 versus intermediate and high-risk group 0 Degree of AR Changes in AR degree in low risk and intermediate and high-risk groups significantly improved from baseline at both 1 and 30 days after TAVI (both p <0.001). none had severe AR after TAVI. New-onset AF: Postoperative Low risk group 13.2% (5/38) versus intermediate and high-risk group: 8.1% (3/37), p= 0.48. 30 days Low risk group 0 versus intermediate and high-risk group 0 New left bundle branch block (LBBB): Postoperative Low risk group 13.2% (5/38) versus intermediate and high-risk group: 21.6% (8/37), p= 0.33. 30 days Low risk group 0 versus intermediate and high-risk group: 2.7% (1/37), p= 0.31. New atrioventricular block (AVB): Postoperative Low risk group 18.4% (7/38) versus intermediate and high-risk group: 18.9% (7/37), p= 0.96. 30 days Low risk group 0 versus intermediate and high-risk group 0 New complete AVB (postoperative and at 30 days): Low risk group 0 versus intermediate and high-risk group 0 New PPM implantation: Postoperative Low risk group 18.4% (7/38) versus intermediate and high-risk group: 13.5% (5/37), p= 0.56. 30 days Low risk group 2.6% (1/38) versus intermediate and high-risk group: 5.4% (2/37), p= 0.54. Endocarditis (postoperative and at 30 days): Low risk group 0 versus intermediate and high-risk group 0 Readmission for heart failure (30 days) Low risk group 2.6% (1/38) versus intermediate and high-risk group: 2.7% (1/37), p= 0.98. Valve in valve Low-risk group 13.2% (5/38) versus intermediate and high-risk group 10.8% (4/37)
Elkasaby 2024	TAVI versus SAVR Length of hospital stay (4 studies) TAVI (n=4,718) versus SAVR (n=17,115); (MD=−4.76 days; 95% CI: −5.27 to −4.25, p<0.001) (I²=88%, p<0.001).	TAVI versus SAVR In-hospital mortality (5 studies) TAVI (174/5442) versus SAVR (1027/27643); (RR=0.89, 95% CI 0.56 to 1.42, p=0.63) (I²=86%, p<0.001). In-hospital mortality (4 studies, excluding Stachon 2020) (RR=0.72; 95% CI: 0.59 to 0.89, p=0.003). Subgroup analysis according to access route: TA TAVI versus SAVR (RR=1.53; 95% CI 1.02 to 2.31, p=0.04) (I² =0%, p=0.47). TF TAVI versus SAVR (RR=0.99; 95% CI 0.48 to 2.04, p=0.97) (I² =91%, p<0.001). Undefined TAVI approach versus SAVR: (RR=0.60; 95% CI 0.41 to 0.87, p=0.008) (I²=9%, p=0.30). Subgroup analysis according to country TAVI was favoured over SAVR in studies conducted in China (RR=0.67; CI: 0.45 to 0.1, p=0.05). There were no differences between TAVI and SAVR in the USA (p=0.29) and Germany (p=0.88) subgroups. 30-day mortality (1 study Mentias 2023) TAVI (25/1147) versus SAVR (267/9880); (RR=0.81, 95% CI 0.54 to 1.21, p=0.30). 1 year mortality (1 study Mentias 2023) TAVI (79/1147) versus SAVR (563/9880); (RR=1.21, 95% CI 0.96 to 1.52, p=0.10). In-hospital stroke (4 studies) TAVI (80/4295) versus SAVR (735/17763); (RR=0.50; 95% CI 0.39 to 0.66, p<0.001) (I²=11%, p=0.34). 30-day stroke (1 study Mentias 2023) TAVI (29/1147) versus SAVR (198/9880); (RR=1.26, 95% CI 0.86 to 1.85, p=0.24). Postoperative new onset AF (2 studies) TAVI (436/2062) versus SAVR (3681/11270); (RR=0.26, 95% CI 0.02 to 3.80, p=0.33), (I²=100%, p<0.0001). Post-operative AKI (4 studies) TAVI (630/3987) versus SAVR (2711/13140); (RR=0.56; 95% CI: 0.41 to 0.76, p=0.0002), (I²=91%, p<0.00001). Postoperative major bleeding (5 studies) TAVI (276/5442) versus SAVR (5597/27643); (RR=0.23; 95% CI: 0.17 to 0.32, p<0.001) (I²=85%, p<0.001). Pacemaker implantation (3 studies) TAVI (507/3882) versus SAVR (945/13090); (RR=1.68; 95% CI: 1.50 to 1.88, p<0.001) (I²=0% p=0.83). Delirium (2 studies) TAVI (100/1560) versus SAVR (1216/14553); (RR 0.68, 95% CI 0.25 to 1.88, p=0.46), (I²=96%, p<0.0001) Pneumonia (2 studies) TAVI (74/2735) versus SAVR (161/3210); (RR 0.53, 95% CI 0.40 to 0.70, p<0.0001), (I²=0%, p=0.54) Sepsis (2 studies) TAVI (42/2735) versus SAVR (127/3210), (RR 0.15, 95% CI 0.01 to 2.23, p=0.17), (I²=74%, p=0.05).
Ullah W 2024	The mean length of stay (days) TAVI in AI=6.18 (SD 7.5) TAVI in AS=5.18 (SD 6.3).	Pooled outcomes between TAVI for AI and TAVI for AS In-hospital outcomes NACE TAVI in AI (5.6%, n=217) versus TAVI in AS (2.9%, n=117); (aOR 2.0, 95% CI 1.59 to 2.51) All-cause mortality TAVI in AI (2.5%, n=98) versus TAVI in AS (0.7%, n=29); (aOR 3.1, 95% CI 2.4 to 5.5) Stroke TAVI in AI (0.8%, n=29) versus TAVI in AS (0.6%, n=24); (aOR 1.3, 95% CI 0.7 to 2.2) Major bleeding TAVI in AI (2.8%, n=107) versus TAVI in AS (1.8%, n=74); (aOR 1.53, 95% CI 1.1 to 2.1) Cardiac tamponade TAVI in AI (n=<11 events) versus TAVI in AS (0.4%, n=16); (aOR 1.9, 95% CI 1.0 to 3.5) Cardiogenic shock TAVI in AI (0.8%, n=29) versus TAVI in AS (n=16); (aOR 0.5, 95% CI 0.2 to 1.2) Valvular complications (aOR 9.48, 95% CI 6.73 to 13.38) Adjusted analysis 30 days NACE TAVI in AI (5.9%, n=25) versus TAVI in AS (6.1%, n=26); (aOR 0.9, 95% CI 0.5 to 1.7) Mortality TAVI in AI (3.2%, n=14) versus TAVI in AS (3.3%, n=14); (aOR 1.0, 95% CI 0.5 to 2.1) Major bleeding TAVI in AI (n<11 events) versus TAVI in AS (3.1%, n=13); (aOR 0.8, 95% CI 0.3 to 1.7) PPM implantation TAVI in AI (9.7%, n=42) versus TAVI in AS (13.8%, n=59); (aOR 0.7, 95% CI 0.4 to 1.0) 180 days NACE TAVI in AI (7.3%, n=30) versus TAVI in AS (7.7%, n=33); (aOR 0.9, 95% CI 0.6 to 1.6) Mortality TAVI in AI (4.9%, n=20) versus TAVI in AS (3.7%, n=16); (aOR 1.3, 95% CI 0.7 to 2.6) Stroke TAVI in AI (n=<11 events) versus TAVI in AS (n=<11 events); (aOR 0.5, 95% CI 0.1 to 1.7) Major bleeding TAVI in AI (n=<11 events) versus TAVI in AS (n=<11 events); (aOR 0.6, 95% CI 0.2 to 1.7) PPM implantation TAVI in AI (12.4%, n=51) versus TAVI in AS (10.5, n=45); (aOR 1.2, 95% CI 0.8 to 1.8) Impact of age and sex on outcomes of TAVI for AI compared to AS. A sensitivity analysis based on age (<80 years and ≥80 years) and sex (male and female) mirrored the findings of the pooled analysis. On unadjusted analysis, TAVI in AI was associated with significantly higher odds of NACE, mortality, major bleeding, and post-procedure complications.

Procedure technique

There were variations in the devices used across studies. Existing old and new generation TAVI valves have been used on an off-label basis in some studies. Purpose specific on-label devices have been used in some studies. Both TA and TF access routes have been primarily used in studies. In limited cases (n=8) trans subclavian approach was used.

Efficacy

Technical success

NGD with on-label

In a prospective study of 180 symptomatic patients with moderate to severe or severe AR who had TF TAVI with an on-label dedicated device (ALIGN AR trial), technical success (defined as absence of procedural mortality, successful access, delivery, and retrieval of transcatheter delivery system, deployment and correct positioning of a single THV, freedom from reintervention related to the device or access procedure) was achieved in 95% (171/180) patients (Vahl 2024).

NGDs off-label (SE versus BE valves)

In an international PANTHEON registry analysis of 201 patients who had TAVI with NGDs (including only 10% dedicated valves) for pure severe native AR, the overall technical success rate according to the VARC-3 criteria (defined as freedom from mortality, successful delivery of the device, retrieval of the delivery system, correct positioning of the valve and freedom from surgery or intervention related to the device, access or cardiac structural complication at the time of exit from the procedure room) was 84%, with no statistically significant difference in technical success rates between those treated with SE and BE valves (80% versus 90%, p=0.108) (Poletti, 2023).

Device success

NGDs: on-label versus off-label devices

A systematic review and meta-analysis of 31 studies on TAVI with NGDs for pure AR, compared on-label (two valve prosthesis systems) and off label devices. Pooled analysis reported that the total device success rate (defined by the VARC-3 criteria) at 30 days was 95% (95% CI 91.3 to 97.1%, I²=76.8%). Subgroup pooled analysis showed that the device success rate was higher for TAVI with on-label devices than TAVI with off-label devices (98% versus 90%; p<0.001). When TA and TF access routes were compared, the TA approach showed a significantly higher device success rate than the TF approach (96% versus 93%, p<0.001) (Liu 2024).

NGDs off-label (SE versus BE valves)

In the PANTHEON international registry analysis of 201 patients who had TAVI with NGDs (including only 10% dedicated valves) for pure severe native AR, the overall device success rate at one month (defined as technical success at 30 days along with satisfactory valve performance [mean gradient less than 20 mmHg, and less than moderate regurgitation]) was 76%, with no statistically significant difference in device success rates between those treated with SE and BE valves (76% versus 77%, p = 0.868) (Poletti, 2023).

NGDs versus EGDs

In a meta-analysis of 19 studies on TAVI for pure AR, pooled analysis of 14 studies reported that the rate of device success (as per VARC-2 criteria, defined as a composite of absence of procedural mortality, correct positioning of valve prosthesis, and intended performance of the prosthetic valve) was 86% (524/659, 95% CI 78.8 to 92.2%, I²= 81.01%, p<0.001). Subgroup analysis showed the use of NGDs was associated with higher device success compared with EGDs (p=0.009). Device success was higher with new generation purpose-specific valves (96%, 95% CI 92.2 to 98.9%; I²=0%) compared with non-purpose specific valves (85% (95% CI 75 to 91.9%); I²=46%) (p=0.02) (Rawasi 2019).

A meta-analysis of 11 studies (including 911 patients with pure AR who had TAVI), reported device success of 81%. Subgroup pooled analysis reported significantly higher device success rates after TAVI using NGDs than TAVI using EGDs (90% versus 67%; p<0.001) (Takagi 2020).

Left ventricular remodelling (echocardiography findings)

NGD with on-label

In the prospective study of 180 symptomatic patients with moderate to severe or severe AR who had TF TAVI with an on-label dedicated device (ALIGN AR trial), mean LV mass declined from 323.7 g at baseline to 219.5 g (p<0.001) at 1 year and mean LVESd significantly decreased from 39.6 cm at baseline to 34.2 cm (p<0.0001) at 1 year (Vahl 2024).

NGDs off-label (low risk [STS <4] versus intermediate and high-risk groups [STS>4])

A retrospective analysis of 75 patients who had TAVI with off-label devices for pure severe AR reported that patients in the low-risk group reported statistically significant decrease in mean LVEDd (p=0.017) and LVESd (p=0.037) from baseline at 1 month follow-up. Patients in the intermediate and high-risk group reported a statistically significant decrease in LVEDd (p=0.035) but not LVESd (p=0.23) (Da-Wei 2024).

Functional status (NYHA classification)

NGD with on-label

In the prospective study of 180 symptomatic patients with moderate to severe or severe AR who had TF TAVI with an on-label dedicated device (ALIGN AR trial), 68% (122/180) patients had NYHA functional class III–IV disease at baseline. At 30 days, NYHA functional class status was class I in 51% (91/180), class II in 34% (62/180) of patients, and class III in 9% (17/180) of patients. At 1 year, 50% (90/180) of patients were class I and 27% (48/180) were class II. NYHA functional class improved by at least one category in 83% (125/180) of patients (Vahl 2024).

NGDs off-label (low risk [STS <4] versus intermediate and high-risk groups [STS>4])

The retrospective analysis of 75 patients who had TAVI with off-label devices for pure severe AR reported that compared to patients in low-risk group (n=38), those in the intermediate and high risk (n=37) had a statistically significant improvement in NYHA functional class from baseline at both 1- and 30-days after TAVI (both p<0.001) (Da-Wei 2024).

Quality of life

NGD with on-label

In the prospective study of 180 symptomatic patients with moderate to severe or severe AR who had TF TAVI with an on-label dedicated device (ALIGN AR trial), the mean KCCQ overall score increased by 20.6 points at 1 year (from baseline mean 55.3 to 77.6; p<0.0001). Of 152 respondents, the number of patients with a KCCQ overall score of at least 75 was 63% (88/152) and those who felt worse (5 point or more decrease from baseline) was 11% (16/152) (Vahl 2024).

6-minute walk test

NGD with on-label

In the prospective study of 180 symptomatic patients with moderate to severe or severe AR who had TF TAVI with an on-label dedicated device (ALIGN AR trial), an increase in 6-min walk test distance (from baseline 262.7 to 312.5 meters at 1 year) was reported and 48% (62/180) patients had an improvement of at least 15 meters at 1 year (p values were not reported) (Vahl 2024).

Length of hospital stay (LOS)

TAVI versus SAVR

In a systematic review and meta-analysis of 6 studies comparing TAVI with SAVR, pooled analysis of 4 studies showed that the LOS was shorter with TAVI compared to SAVR (MD=−4.76 days; 95% CI −5.27 to −4.25, p<0.001). Subgroup pooled analysis showed that TF TAVI was associated with shorter LOS compared to SAVR (MD=−4.33 days, 95% CI −4.42 to −4.23, p<0.001) but TA TAVI was not associated with shorter LOS compared to SAVR (MD=−1.98 days, 95% CI −4.33 to 0.93, p=0.21). The undefined TAVI approach subgroup was also associated with shorter LOS compared to SAVR (MD=−4.66days, 95% CI −5.35 to −3.98, p<0.0001) (Elkasaby 2024).

Safety

Composite primary safety endpoint

NGD with on-label

In the prospective study of 180 symptomatic patients with moderate to severe or severe AR who had TF TAVI with an on-label dedicated device (ALIGN AR trial), the 30-day composite primary safety endpoint (all-cause mortality, major bleeding, stroke, acute kidney injury, new pacemaker implantation or valve dysfunction requiring surgical or percutaneous intervention) was achieved in 27% (48/180, 97.5% CI 19.2 to 34.0) patients (p _{non-inferiority}<0·0001), when compared with the pre-specified safety performance goal of 40.5% (Vahl 2024).

Composite endpoint (all-cause mortality and heart failure rehospitalisation at 1 year)

NGDs off-label (SE versus BE valves)

The PANTHEON international registry analysis of 201 patients who had TAVI with NGDs (including only 10% dedicated valves) for pure severe native AR reported that the overall incidence of the composite endpoint (all-cause mortality and heart failure rehospitalisation) at 1 year (in 181 patients) was 17% (95% CI: 10.4 to 23.4%). There was no statistically significant difference in the incidence in patients treated with SE and BE valves (18% [95% CI 9.1 to 26.2%] versus 15% [95% CI 4.7 to 24.4%]; p = 0.52). Patients who had TVEM had a higher incidence of the composite endpoint compared to those in the non-TVEM group (25.7% [95% CI: 5.6% to 41.5%] versus 15.8% [95% CI: 8.5% to 22.5%]. log-rank p = 0.05). After adjusting for propensity scores, TVEM was associated with a higher one-year incidence of the composite endpoint (HR: 2.45; 95% CI: 1.00 to 6.18; p = 0.05) and increased all-cause mortality (HR: 4.06; 95% CI: 1.50 to 11.0; p = 0.006) (Poletti, 2023).

NACE (a composite of all-cause in-hospital mortality, stroke, and major bleeding)

TAVI for AR versus TAVI for AS

In a retrospective propensity score matched analysis of NRD data (n=7,929) comparing patients who had TAVI for AI (n=3,873) with those who had TAVI for AS (n=4,056), in-hospital NACE was statistically significantly higher in the AI group compared with the AS group (TAVI in AI [5.6%, n=217] versus TAVI in AS [2.9%, n=117]; aOR 2.0, 95% CI 1.6 to 2.5). However, there was no statistically significant difference in NACE at 30 days (TAVI in AI [5.9%, n=25] versus TAVI in AS [6.1%, n=26]; aOR 0.9, 95% CI 0.5 to 1.7) and 180 days (TAVI in AI [7.3%, n=30] versus TAVI in AS [7.7%, n=33]; aOR 0.9, 95% CI 0.6 to 1.6), respectively (Ullah 2024).

In-hospital mortality

NGD off-label (SE versus BE valves)

The PANTHEON international registry analysis of 201 patients with pure severe native AR who had TAVI with NGDs (including only 10% dedicated valves) reported that the incidence of in-hospital all-cause mortality was 5.0% (10/201), with no statistically significant difference in rates between those treated with SE and BE valves (5.3% [7/132] versus 4.4% [3/69], p= 0.767) (Poletti, 2023).

TAVI for AR versus TAVI for AS

In the retrospective propensity score matched analysis of NRD data (n=7,929) comparing patients who had TAVI for AI (n=3,873) with those who had TAVI for AS (n=4,056), in-hospital mortality was statistically significantly higher in the AI group compared with the AS group (TAVI in AI [2.5%, n=98] versus TAVI in AS [0.7%, n=29]; aOR 3.01, 95% CI 2.4 to 5.5) (Ullah 2024).

TAVI versus SAVR

In the systematic review and meta-analysis of 6 studies comparing TAVI with SAVR, pooled analysis of 6 studies showed that in-hospital mortality rate was comparable between the two procedures (RR=0.89, 95% CI 0.56 to 1.42, p=0.63; I²=86%). Pooled analysis after excluding 1 study (Stachon 2020, the source of heterogeneity) suggests that TAVI may be associated with a decreased mortality rate than SAVR (RR=0.72; 95% CI 0.59 to 0.89, p=0.003).

Subgroup analysis on the approach of TAVI (TA and TF) showed that TA TAVI was associated with an increased in-hospital mortality rate compared to SAVR (RR=1.53; 95% CI 1.02 to 2.31, p=0.04; I²=0%). TF TAVI was associated with a similar in-hospital mortality rate compared to SAVR (RR=0.99; 95% CI 0.48 to 2.04, p=0.97; I²=91%). Pooled results of undefined TAVI approaches showed a lower rate of in-hospital mortality compared to SAVR (RR=0.60; 95% CI 0.41 to 0.87, p=0.008; I²=9%). Subgroup analysis according to the country of origin showed that TAVI was favoured over SAVR in studies conducted in China (RR=0.67; CI 0.45 to 0.1, p=0.05). There were no differences between TAVI and SAVR in the USA (p=0.29) and German (p=0.88) subgroups (Elkasaby 2024).

Mortality at 30 days

NGD with on label

In the prospective study of 180 symptomatic patients with moderate to severe or severe AR who had TF TAVI with an on-label dedicated device (ALIGN AR trial) mortality at 30 days was 2% (4/180) (Vahl 2024).

NGD off-label (low risk [STS <4] versus intermediate and high-risk groups [STS>4])

A retrospective analysis of 75 patients who had TAVI with off-label devices for pure severe AR reported that in both the low-risk and intermediate and high-risk groups, there were no recorded cases of all-cause mortality following the procedure and at 30 days follow-up (Da-Wei 2024).

NGDs: on-label versus off label devices

The systematic review and meta-analysis of 31 studies on new generation TAVI devices for pure AR reported that the 30-day all-cause mortality was 4% (95% CI 2.7 to 5.9%, I²=43.8%). Subgroup analysis comparing on-label (two valve prosthesis systems) and off label devices showed a statistically significantly lower 30-day mortality rate for TAVI using on-label devices than off-label devices (3% versus 5%; p=0.006). When comparing TA and TF access routes, 30-day mortality was lower for the TA group than the TF group (3% versus 4%, p=0.052) (Liu 2024).

NGDs versus EGDs

In the systematic review and meta-analysis of 19 studies, pooled analysis reported that the rate of 30-day mortality was 12% (122/998, 95% CI 9.4 to 14.7%, I²=28%, p=0.110). Sub-group analysis showed the use of NGDs was associated with lower 30-day mortality compared to EGDs (p=0.02). There was no statistically significant difference in the rate of 30-day mortality between new generation purpose-specific (8.2%; 95% CI 4.3 to 13.1%; I²=0%) and non-purpose specific valves (13.0%; 95% CI 8.2 to 18.6%; I²=25%); (p=0.13) (Rawasi 2019).

In the meta-analysis of 11 studies (n=911), pooled analysis reported a 30-day all-cause mortality rate of 9.5% and a 30-day cardiovascular mortality rate of 6.6%. Sub-group analysis reported a statistically significantly lower incidence of 30-day all-cause mortality in the NGD group compared to EGD group (6% versus 15%; p<0.001). There were no statistically significant differences in the incidence of 30-day cardiovascular mortality between the two groups (6% versus 10%; p=0.193) (Takagi 2020).

TAVI for AR versus TAVI for AS

In the retrospective propensity score matched analysis of NRD data (n=7,929) comparing patients who had TAVI for AI (n=3,873) with those who had TAVI for AS (n=4,056), there was no statistically significant difference in mortality at 30 days (TAVI in AI [3.2%, n=14] versus TAVI in AS [3.3%, n=14]; aOR 1.0, 95% CI 0.5 to 2.1) and 180 days (TAVI in AI [4.9%, n=20] versus TAVI in AS [3.7%, n=16]; aOR 1.3, 95% CI 0.7 to 2.6) between the groups (Ullah 2024).

TAVI versus SAVR

In the systematic review and meta-analysis of 6 studies comparing TAVI with SAVR, one included study (Mentias 2023) reported that the mortality rates were comparable between the two procedures at 30-day follow-up (RR=0.81; 95% CI 0.54 to 1.21, p=0.30) (Elkasaby 2024).

Mortality at 1 year

NGD with on-label

In the prospective study of 180 symptomatic patients with moderate to severe or severe AR who had TF TAVI with an on-label dedicated device (ALIGN AR trial) all-cause mortality at 1-year (primary efficacy endpoint) was achieved, in 8% (14/180 [97.5% CI 3.3 to 12.3]) of patients (p<0·0001) when compared for non-inferiority with a performance goal of 25%.In the pre-specified group who received successful valve implantation (n=177), primary efficacy was achieved in 16% (11/177; [97.5% CI 2.2 to 10.3)]; p_{non-inferiority}<0.0001) patients at 1 year (Vahl 2024).

NGDs versus EGDs

The systematic review and meta-analysis of 31 studies on new generation TAVI devices for pure AR reported that the estimated 1-year mortality was 8% (95% CI: 5.1 to 11.7%, I²=67.3%). Subgroup analysis reported that the estimated 1-year mortality was 6% for TAVI using NGDs with on-label (Liu 2024).

In the meta-analysis of 11 studies (n=911), pooled analysis reported all-cause mortality of 19% at mid-term (4 months to 1 year). Sub-group analysis reported a significantly lower incidence of mid-term all-cause mortality in the NGD group compared to EGD group (12% versus 32%; p<0.001) (Takagi 2020).

In the systematic review and meta-analysis of 19 studies, 6 studies reported that the incidence of one-year mortality ranged from 20 to 31%, with a pooled incidence of 25% (155/618, 95% CI 21.3 to 28.1%; I²=0%, p=0.481) (Rawasi 2019).

TAVI versus SAVR

In the systematic review and meta-analysis of 6 studies comparing TAVI with SAVR, only one included study (Mentias 2023) reported that the mortality rates were comparable between the two procedures at one-year follow-up (RR=1.21; 95% CI 0.98 to 1.52, p=0.1) (Elkasaby 2024).

PPM implantation

NGD with on-label

In the prospective study of 180 symptomatic patients with moderate to severe or severe AR who had TF TAVI with an on-label dedicated device (ALIGN AR trial), new PPM implantation was reported in 24% (36/150) of patients without a PPM before the procedure. A pre-existing PPM was present in 30 patients (Vahl 2024).

NGD off-label (SE versus BE valves)

In the retrospective PANTHEON registry analysis of 201 patients with pure severe native AR who had TAVI with NGDs (including only 10% dedicated valves), new PPM implantation was reported in 22% (36/201) patients, with no statistically significant difference in rates between those treated with SE and BE valves (23% [24/132) versus 22% [12/69], p = 0.918) (Poletti, 2023).

NGD off-label (low risk [STS <4] versus intermediate and high-risk groups [STS>4])

The retrospective analysis of 75 patients who had TAVI with off-label devices for pure severe AR reported no statistically significant difference in rates of PPM implantation in low-risk and intermediate and high-risk patient groups at 30-days after TAVI (2.6%, 1/38 versus 5.4% 2/37, p=0.54) (Da-Wei 2024).

NGDs: on-label versus off-label devices

The systematic review and meta-analysis of 31 studies on new generation TAVI devices for pure AR reported that the PPM implantation rate at 30 days was 9% (95% CI 6.1 to 11.9%, I²=57.0%). Subgroup analysis reported that PPM implantation using on-label device was statistically significantly lower in the TAVI group using on-label devices than in those using off-label devices (7% versus 19%; p<0.001). When comparing access routes, PPM implantation were lower for the TA group than the TF group (6% versus 20%, p<0.001) (Liu 2024).

NGDs versus EGDs

In the systematic review and meta-analysis of 19 studies, pooled analysis of 14 studies reported the rate of post-procedural PPM implantation ranged from 0 to 44%, with a pooled estimate of 13% (95% CI 9.3 to17.5%; I²=44%, p=0.034). Subgroup analysis reported that there was no statistically significant difference in the rate of PPM implantation between the studies using NGDs [10.4% (95% CI 6.6 to 15.0%); I²=15%], and those using EGDs [17.7% (95% CI 10.6 to 26.1%); I²=62%], (p=0.09). There was no statistically significant difference in the rate of PPM implantation between new generation purpose-specific (6.8% [3.2 to 11.7%; I²=0%] and non-purpose-specific valves (19.8% [95% CI 6.7 to 37.5%; I²=76%); (p=0.06). Also, there was no statistically significant difference in the rate of PPM implantation between studies using TF access (13% [95% CI 5.4 to 23.3%; I²=58%), and those using TA access (12%, 95% CI 8.9 to 15.6%]; I²=8%); (p=0.84). Meta-regression revealed a statistically significant positive association between average age and rate of PPM implantation after the procedure (p<0.001). Rate of PPM implantation was not associated with mean annulus size (p=0.55), proportion of patients with moderate to severe MR (p=0.89), or logistic EUROSCORE (p=0.72) (Rawasi 2019).

In the meta-analysis of 11 studies (n=911), PPM implantation rate was 12% (95% CI 6.8 to 16.4). Sub-group analysis revealed that there were no statistically significant difference in the incidence of PPM implantation between the NGD and EGD groups (8% versus 16%; p=0.085) (Takagi 2020).

TAVI for AR versus TAVI for AS

In the retrospective propensity score matched analysis of NRD data (n=7,929) comparing patients who had TAVI for AI (n=3,873) with those who had TAVI for AS (n=4,056), there was no statistically significant difference in PPM implantation post procedure between the 2 groups (TAVI in AI [8.5%, n=328] versus TAVI in AS [7.5%, n=306]; aOR 1.1, 95% CI 1.0 to 1.3). The need for PPM was similar between the groups at 30 days (TAVI in AI [9.7%, n=42] versus TAVI in AS [13.8%, n=59]; aOR 0.7, 95% CI 0.4 to 1.0) and 180 days (TAVI in AI [12.4%, n=51] versus TAVI in AS [10.5%, n=45]; aOR 1.2, 95% CI 0.8 to 1.8). respectively (Ullah 2024).

TAVI versus SAVR

In the systematic review and meta-analysis of 6 studies comparing TAVI versus SAVR, pooled analysis of 4 studies showed that TAVI was associated with a higher rate of PPM implantation than SAVR (RR=1.68; 95% CI 1.50 to 1.88, p<0.001) (Elkasaby 2024).

Residual/post procedure AR

NGD with on-label

In the prospective study of 180 symptomatic patients with moderate to severe or severe AR who had TF TAVI with an on-label dedicated device (ALIGN AR trial), moderate paravalvular AR was present in one patient at 30 days and it was mild at 1 year. Mild or mild-to-moderate paravalvular AR decreased from 19% (31/180) at 30 days to 8% (11/180) at 1 year. Paravalvular AR was none or trace in 92% (130/180) patients at 1 year (Vahl 2024).

NGD off-label (SE versus BE valves)

In the retrospective PANTHEON registry analysis of 201 patients with pure severe native AR who had TAVI with NGDs (including only 10% dedicated valves), residual moderate or severe AR was reported in 10% (19/201) patients, with no statistically significant difference in rates between those treated with SE and BE valves (9% [12/132) versus 10% [7/69], p = 0.835) (Poletti, 2023).

NGD off-label (low risk [STS <4] versus intermediate and high-risk groups [STS>4])

The retrospective analysis of 75 patients who had TAVI off-label devices for pure severe AR reported that AR degree in low risk and intermediate and high-risk groups significantly improved from baseline at both 1 and 30 days after TAVI (both p <0.001). None of the patients had severe AR after TAVI. Trivial AR was observed in 3 cases on the first day post-procedure. By 30 days 7 patients showed mild residual AR (Da-Wei 2024).

NGDs on label versus off label

The systematic review and meta-analysis of 31 studies on new generation TAVI devices for pure AR reported that the rate of greater than mild PVL at 30 days was 1.2% (95% CI: 0.4 to 2.2%, I²=0.0%). Subgroup analysis reported that the rate of greater than mild PVL was statistically significantly higher in the TAVI group using on-label devices than those using off-label devices (0.9% versus 3.8%; p = 0.003). When comparing access routes, procedures with TA route had slightly higher PVL than TF route (22% versus 19%, p = 0.314) but greater-than-mild PVL rates were higher in the TF group than TA group (0.8% versus 4%, (Liu 2024).

NGDs versus EGDs

In the systematic review and meta-analysis of 19 studies, pooled analysis of 18 studies reported that the occurrence of residual moderate to severe AR ranged from 0 to 29%, with a pooled estimate of 9% (95% CI 5.5 to 13.7%; I² = 75%). Subgroup analysis reported that the residual moderate to severe AR after the procedure was statistically significantly lower in studies with NGDs (3% [95% CI 1.8 to 4.8%; I² = 0%) when compared with EGDs (20% [95% CI 11.5 to 28.6%; I² = 73%); (p<0.001). Also, it was statistically significantly lower in those who had new generation purpose-specific valves (3% (95% CI 0.9 to 6.4%; I² = 0%) compared with those who had non-purpose-specific valves (15% [95% CI 7.6 to 22.9%; I² = 54%) (p=0.002). There was no statistically significant difference in the outcome between studies using TA access (5%, 95% CI 2.0 to 9.6%; I² = 57%), and studies using TF access (13%, 95% CI 4.4 to 25%; I² = 75%); (p=0.18). Meta-regression revealed that moderate to severe AR was not associated with average age (p=0.53), mean annulus size (p=0.28), proportion of patients with moderate to severe MR (p=0.76), or logistic EUROSCORE (p=0.97) (Rawasi 2019).

In the meta-analysis of 11 studies (including 911 patients who had TAVI for AR), moderate or higher paravalvular AR rate was 8%. Subgroup pooled analysis revealed a significantly lower incidence of moderate or higher paravalvular AR in the NGD group than in the EGD group (4% versus 17%; p < 0.001) (Takagi 2020).

Major bleeding

NGD off label (SE versus BE valves)

In the retrospective PANTHEON registry analysis of 201 patients with pure severe native AR who had TAVI with NGDs (including only 10% dedicated valves), the incidence of major bleeding was reported in 11% (20/201) patients, with no statistically significant difference in rates between those treated with SE and BE valves (13% [16/132) versus 7% [4/69], p = 0.197) (Poletti, 2023).

NGD off-label (low risk [STS <4] versus intermediate and high-risk groups [STS>4])

The retrospective analysis of 75 patients who had TAVI off-label devices for pure severe AR reported no statistically significant difference in rates of bleeding complications in low-risk and intermediate and high-risk patient groups postoperatively and at 30-days after TAVI (2.6%, 1/38 versus 0, p=0.32) (Da-Wei 2024).

NGDs versus EGDs

In the systematic review and meta-analysis of 19 studies, pooled analysis of 11 studies (n=69/582) reported the incidence of major bleeding after the procedure ranged from 0 to 15%, with a pooled estimate of 13% [95% CI 6.1 to 20.4%, I² = 82%, p<0.001) (Rawasi 2019).

In the meta-analysis of 11 studies (including 911 patients), life-threatening or major bleeding complications rate was 6% (95% CI 2.8 to 8.6%). Subgroup analysis reported a statistically significantly lower incidence of major bleeding complications in the NGD group than in the EGD group (4% versus 13%; p = 0.015) (Takagi 2020).

TAVI for AR versus TAVI for AS

In the retrospective propensity score matched analysis of NRD data (n=7929) comparing patients who had TAVI for AI (n=3873) with those undergoing TAVI for AS (n=4056), major bleeding after the procedure was statistically significantly higher in patients who had TAVI for AI compared with those who had TAVI for AS (TAVI in AI [2.8%, n=107] versus TAVI in AS [1.8%, n=74]; aOR 1.5, 95% CI 1.1 to 2.1). However, there was no statistically significant difference between the groups at 30 days (TAVI in AI n=<11] versus TAVI in AS [n=13]; aOR 0.8, 95% CI 0.3 to 1.7) and 180 days (TAVI in AI [n<11] versus TAVI in AS [n<11]; aOR 0.6, 95% CI 0.2 to 1.7) respectively (Ullah 2024).

TAVI versus SAVR

In the systematic review and meta-analysis of 6 studies comparing TAVI with SAVR, pooled analysis of 5 studies showed that TAVI was associated with a statistically significantly lower risk of major bleeding than SAVR (RR 0.23, 95% CI 0.17 to 0.32, p<0.001). Subgroup analysis according to TAVI approach (TF or TA) reported that TA TAVI, TF TAVI and undefined TAVI approaches were favoured over SAVR, (RR=0.41; 95% CI 0.28 to 0.59, p<0.001), (I²=0%); (RR=0.19; 95% CI 0.11 to 0.34, p<0.001), (I²=87%) and (RR=0.26; 95% CI 0.20 to 0.34, p<0.001) (I²=55%, p=0.14) (Elkasaby 2024).

Cardiovascular outcomes (including stroke and MI)

NGD with on label

In the prospective study of 180 symptomatic patients with moderate to severe or severe AR who had TF TAVI with an on-label dedicated device (ALIGN AR trial), two (1%) disabling and two (1%) non-disabling strokes were reported at 30 days (Vahl 2024).

NGD off label (SE versus BE valves)

In the retrospective PANTHEON registry analysis of 201 patients with pure severe native AR who had TAVI with NGDs (including only 10% dedicated valves), cardiovascular death was reported in 4% (8/201) patients, with no statistically significant difference in rates between those treated with SE and BE valves (3.8% [5/132) versus 4.4% [3/69], p = 0.847). The overall rate of stroke and TIAs was 1.5% (3/201), with no statistically significant difference in rates between those treated with SE and BE valves (2.3% [3/132) versus 0 [0/69], p = 0.553) (Poletti, 2023).

NGD off-label (low risk [STS <4] versus intermediate and high-risk groups [STS>4])

The retrospective analysis of 75 patients who had TAVI off-label devices for pure severe AR reported no significant difference in rates of strokes in patients in low-risk and intermediate and high-risk groups postoperatively and at 30-days after TAVI (0 versus 2.7%, 1/37 versus 5.4% 2/37, p=0.31). There were no cases of MI reported in both groups (Da-Wei 2024).

NGDs versus EGDs

In the systematic review and meta-analysis of 19 studies, 11 studies reported no cases of MI at 30 days. 13 studies reported that the incidence of stroke ranged from 0 to 6%, with a pooled estimate of 3.6% [20/648, 95% CI 2.3 to 5.1%; I² = 0%, p=0.967) (Rawasi 2019).

In the meta-analysis of 11 studies (including 911 patients), the rate of stroke was 2.7%. There were no statistically significant differences in the incidence of stroke between the NGD and EGD subgroups (2.9% versus 2.3%; p = 0.541) (Takagi 2020).

TAVI for AR versus TAVI for AS

In the retrospective propensity score matched analysis of NRD data (n=7929) comparing patients who had TAVI for AI (n=3873) with those undergoing TAVI for AS (n=4056), the incidence of stroke after the procedure was similar between the groups at 30 days (TAVI in AI [0.8%, n=29] versus TAVI in AS [0.6%, n=24]; aOR 1.3, 95% CI 0.7 to 2.2) and at 180 days (TAVI in AI [n<11] versus TAVI in AS [n<11]; aOR 0.5, 95% CI 0.1 to 1.7) respectively (Ullah 2024).

TAVI versus SAVR

In the systematic review and meta-analysis of 6 studies comparing TAVI with SAVR, pooled analysis of 4 studies showed that in-hospital stroke was lower in TAVI group than SAVR group (RR=0.50; 95% CI 0.39 to 0.66, p<0.001), (I²=11%, p=0.34). Subgroup analysis on the approach of TAVI (TA and TF) found that TA TAVI was not protective against stroke compared to SAVR (RR=0.64; 95% CI 0.31 to 1.35, p=0.24) (I²=1%, p=0.31), while TF TAVI approach was protective compared to SAVR (RR=0.39; 95% CI 0.26 to 0.59, p<0.001), (I²=0%, p=0.85). Also, the undefined TAVI approach was associated with a lower rate of in-hospital stroke (RR=0.60; CI 0.41 to 0.87, p=0.008) (I²=9%, p=0.30). Subgroup analysis according to the country of origin reported that there was no statistically significant difference between TAVI and SAVR in the USA (RR=0.84; CI 0.40 to 1.74, p=0.63), while TAVI was protective in Germany (RR=0.42; CI 0.30 to 0.60, p<0.001) (I²=0%) and China (RR=0.54; 95% CI 0.36 to 0.80, p=0.002). One included study (Mentias 2023) reported that 30-day stroke was similar in TAVI and SAVR groups (RR=1.26; 95% CI 0.86 to 1.85, p=0.24). (Elkasaby 2024).

In the systematic review and meta-analysis of 6 studies comparing TAVI with SAVR, MI was reported only in one included study (Alharbi 2020), which showed no difference between TAVI and SAVR groups (RR=0.79; 95% CI 0.59 to 1.05], p=0.11) (Elkasaby 2024)

In the systematic review and meta-analysis of 6 studies comparing TAVI with SAVR, MACCE was reported only in one included study (Rali 2022), which favoured TAVI over SAVR (RR=0.48; 95% CI 0.25 to 0.90, p=0.02).

Conversion to open surgery

NGD off label (SE versus BE valves)

NGDs on label versus off label

The systematic review and meta-analysis of 31 studies on new generation TAVI devices for pure AR reported that the rate of conversion to SAVR at 30 days was 2.2% (95% CI 0.9 to 3.8%, I²=0.0%); and in the on-label group it was 2.5% (95% CI 1.2 to 4.2%, I²=0.0%) (Liu 2024).

NGDs versus EGDs

In the meta-analysis of 11 studies (including 911 patients), a conversion to open surgery rate was 3.0%. There were no statistically significant differences in the incidence of conversion to open surgery between the NGD and the EGD subgroups (3.1% versus 2.8%; p=0.840) (Takagi 2020).

Major vascular complications

NGD with on label

In the prospective study of 180 symptomatic patients with moderate to severe or severe AR who had TF TAVI with an on-label dedicated device (ALIGN AR trial), four valve embolisations occurred. In two patients, the embolised valves were placed in the descending aorta and a second THV was implanted, one was treated with a commercial THV and another with SAVR (Vahl 2024).

NGD off label (SE versus BE valves)

In the retrospective PANTHEON registry analysis of 201 patients with pure severe native AR who had TAVI with NGDs (including only 10% dedicated valves), major vascular complications were reported in 7.5% (13/201) patients, with no statistically significant difference in rates between those treated with SE and BE valves (8.1% [9/132) versus 6.5% [4/69], p = 0.532). In the same study, TVEM (defined according to the VARC-3 and included valve migration and embolisation as well as ectopic valve deployment) was reported in 12.4% (25/201) patients, with no statistically significant difference in rates between those treated with SE and BE valves (13.6% [18/132) versus 10.1% [7/69], p = 0.476) (Poletti, 2023).

NGDs versus EGDs

In the meta-analysis of 11 studies (including 911 patients), major vascular complications rate was 3.9%. Subgroup pooled analysis revealed a significantly lower incidence of major vascular complications in the NGD subgroup than in the EGD subgroup (3.0% versus 6.2%; p=0.041) (Takagi 2020).

TAVI for AR versus TAVI for AS

In the retrospective propensity score matched analysis of NRD data (n=7929) comparing patients who had TAVI for AI (n=3873) with those undergoing TAVI for AS (N=4056), valvular complications (paravalvular leak, embolisation and thrombosis) were statistically significantly higher in patients who had TAVI for AI compared with those who had TAVI for AS (aOR 9.48, 95% CI 6.73 to 13.38) (Ullah 2024).

Re-intervention

NGD off-label (SE versus BE valve)

In the retrospective PANTHEON registry analysis of 201 patients with pure severe native AR who had TAVI with NGDs (only 10% dedicated valves), reintervention (second valve) was needed in 10.5% (21/201) patients, with no statistically significant difference in rates between those treated with SE and BE valves (11.4% [15/132) versus 8.7% [6/69], p = 0.557). All these were done for management of TVEM, in 10 cases a second valve was implanted, snaring of the embolised valve was done in 5, repositioning of the valve was done in 2, 4 needed surgical conversion (Poletti, 2023).

NGD on label versus off label

The systematic review and meta-analysis of 31 studies on new generation TAVI devices for pure AR reported that the rate of reintervention (repeat procedure for second prosthetic heart valve at 30 days) was 2.3% (95% CI: 0.7 to 4.5%, I²=13.9%) and in the on-label devices group the estimated rate was 2.8% (95% CI 0.0 to 11.4%, I²=54.6%) (Liu 2024).

NGDs versus EGDs

The meta-analysis of 11 studies (including 911 patients) reported reintervention rate of 3.9%. There were no statistically significant differences in the incidence of reintervention rates between the NGD and EGD subgroups (4.0% versus 4.3%; p=0.868) (Takagi 2020). Valve in valve deployment rate was around 10.5%. Subgroup pooled analysis revealed a statistically significantly lower incidence of valve in valve deployment (4.7% versus 22.1%; p<0.001) in the NGD subgroup than in the EGD subgroup (Takagi 2020).

Annulus rupture

NGD on label versus off label

The systematic review and meta-analysis of 31 studies on new generation TAVI devices for pure AR reported that the rate of annulus rupture in procedure was 0.2% (95% CI 0.0 to 1.7%, I²=0.0%) (Liu 2024).

NGDs versus EGDs

The meta-analysis of 11 studies (including 911 patients), reported annulus rupture rate of 1.5%. There were no statistically significant differences in the incidence of annulus rupture (1.4% versus 1.7%; p = 0.834), between the NGD and EGD subgroups (Takagi 2020).

Acute kidney injury

NGD off-label (SE versus BE valves)

In the retrospective PANTHEON registry analysis of 201 patients with pure severe native AR who had TAVI with NGDs (only 10% dedicated valves), AKI was reported in 10.5% (18/201) patients, with no statistically significant difference in rates between those treated with SE and BE valves (10.9% [12/132) versus 9.8% [6/69], p = 0.827) (Poletti, 2023).

NGDs versus EGDs

The meta-analysis of 11 studies (including 911 patients), reported AKI (stage 1 to 3) rate of 10.5%. There were no statistically significant differences in the incidence of any AKI (9.1% versus 18.2%; p = 0.309) between the NGD and EGD subgroups (Takagi 2020).

TAVI versus SAVR

In the meta-analysis of 6 studies comparing TAVI with SAVR, pooled analysis of 4 studies showed that in-hospital AKI was lower in TAVI than SAVR (RR=0.56; 95% CI: [0.41, 0.76], p <0.001). Subgroup pooled analysis according to the approach of TAVI showed that the result favoured TF TAVI over SAVR (RR=0.36; 95% CI: [0.29, 0.45], p<0.001), and the undefined approach over SAVR (RR=0.66; 95% CI: [0.56, 0.78], p<0.001) (Elkasaby 2024).

Coronary obstruction

NGDs versus EGDs

The meta-analysis of 11 studies (including 911 patients), reported coronary obstruction rate of 0.7%. There were no significant differences in the incidence of coronary obstruction (1.2% versus 0.4%; p = 0.243), between the NGD and EGD subgroups (Takagi 2020).

Cardiac tamponade

TAVI for AR versus TAVI for AS

In the retrospective propensity score matched analysis of NRD data (n=7929) comparing patients who had TAVI for AI (n=3873) with those undergoing TAVI for AS (N=4056), cardiac tamponade was significantly higher in patients undergoing TAVI for AI compared with those undergoing TAVI for AS (TAVI in AI [0.8%, n=29] versus TAVI in AS [0.4%, n=16]; (aOR 1.91, 95% CI 1.0 to 3.5) (Ullah 2024).

Other adverse events

TAVI versus SAVR

In the meta-analysis of 6 studies comparing TAVI with SAVR, pooled analysis showed that the overall effect estimates for delirium and sepsis did not favour either of the two procedures (RR=0.68; 95% CI 0.25, 1.88, p =0.46); and (RR=0.15; 95% CI 0.01, 2.23, p =0.17) but TAVI was associated with an decreased risk of pneumonia (RR=0.53; 95% CI 0.40, 0.70, p < 0.001) (Elkasaby 2024).

Anecdotal and theoretical adverse events

Expert advice was sought from consultants who have been nominated or ratified by their professional society or royal college. They were asked if they knew of any other adverse events for this procedure that they had heard about (anecdotal), which were not reported in the literature. They were also asked if they thought there were other adverse events that might possibly occur, even if they had never happened (theoretical).

They listed the following anecdotal or theoretical adverse events:

Left ventricular migration/embolisation leading to severe aortic incompetence.

Seven professional expert questionnaires and British Cardiovascular Society support statement were submitted for this procedure. Find full details of what the professional experts said about the procedure in the specialist advice questionnaires for this procedure.

Validity and generalisability

There are no RCTs assessing the outcomes of TAVI in pure native AR.
Studies included in the systematic reviews were mainly small observational or registry studies reporting short term outcomes in patients with surgical risks.
There is no data on long-term outcomes.
There was significant heterogeneity across the available studies in terms of devices used, access site, and outcomes reported.
There is very limited data on haemodynamic outcomes and valve durability.
New generation dedicated TAVI devices for AR are now available and performance in patients with severe AR and high surgical risk has been analysed in one prospective study (Vahl 2024).

Any ongoing trials

NCT04864145: Transcatheter self-expandable valve implantation for the treatment of severe native aortic regurgitation a prospective, multicentre, randomised study; RCT (SEASON-AR), n=210 patients with severe native AR and high surgical risk, intervention: transfemoral TAVI (with VitaFlow™ system) plus medical therapy versus medical therapy alone; follow-up at 1, 6, and 12 months and annually until 5 years; location: China; completion date May 20; status recruiting.

NCT05536310: Trilogy heart valve system for management of patients with aortic valve disease: patient registry and post-market clinical follow-up study (TAVIS Registry). n=600 patients with aortic valve disease (symptomatic severe AR or symptomatic, severe AS, who are at high risk for SAVR), intervention: TAVI with JenaValve; primary outcome: all-cause mortality at 30 days; location Germany, follow-up 5 years, completion date October 2027; status not yet recruiting.

NCT06381271: Transcatheter aortic valve replacement for pure severe aortic valve regurgitation (TRUST TAVR registry); prospective cohort study, n=500 patients with native AR undergoing TAVI, follow-up 10 years, location: China, completion date October 2034; status: recruiting.

NCT06379386: Long-term prognosis and valve durability of TAVR (TRACE TAVR registry); prospective single centre observational study; n=1000 patients with aortic valve disease (AR, AS); intervention: TAVI; primary outcome: all-cause mortality, valve related long-term efficacy; follow-up 5 years; location: China, completion date December 2030; status: recruiting.

NCT05737264: Safety and effectiveness of transcatheter treatment of severe native aortic regurgitation with self-expandable valve implantation: a multicentre, observational, prospective cohort study (SENSE-AR). N=76, primary outcome: all-cause mortality; follow-up 12 months; location: China, completion date December 2023; status recruiting.

NCT06034028:J-Valve TF Early Feasibility Study; prospective, single arm, multi-centre, interventional study, n=25 patients with symptomatic severe native AR treated with J-Valve, primary outcome: freedom from death or disabling stroke at 30 days, clinical efficacy 5 years after the procedure; location: USA, Canada, completion date June 2029; status active.

NCT05580952: Efficacy and safety of the J-Valve transcatheter aortic valve replacement system in patients with aortic regurgitation disease. Prospective multicentre study; n=120 patients with symptomatic severe native AR treated with J-Valve, primary outcome: all-cause mortality at 12 months; location: China, completion date May 2024; status unknown.

NCT02732704: THE ALIGN-AR TRIAL: Safety and effectiveness/performance of the transfemoral JenaValve pericardial TAVR system in the treatment of patients with symptomatic severe aortic regurgitation (AR). n=100, primary outcome: all-cause mortality at 30 days; location: USA, completion date September 2027; status active.

NCT04671758: Transcatheter aortic valve implantation with Sapien 3 transcatheter heart valve for pure aortic regurgitation. Cohort study, n=50, primary outcome: feasibility and 30-day safety; location: France, completion date March 2022; status unknown.

NCT05424653: To evaluate safety and effectiveness of transcatheter aortic valve system in patients with severe aortic insufficiency. Observational study, n=10, primary outcomes: device success rate, procedure success rate, rate of no residual AR, incidence of MACCE, rate of all-cause mortality at 30 days; Location: China; completion date: August 2023; status unknown.

Neo2 registry: European multicentre registry on the use of ACURATE neo2 in native AR (ongoing study).

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Interventional procedure overview of transcatheter aortic valve implantation for native aortic valve regurgitation