Aortic Valve Trials

Study overview

Inclusion criteria

• Severe symptomatic AS
• ≥2 surgeons agreed surgical risk was prohibitive
• Suitable transfemoral access anatomy

Primary endpoint

All-cause mortality at 1 year.

Secondary endpoints

• Repeat hospitalization
• NYHA class
• 6-minute walk
• Cardiac symptoms / valve haemodynamics

Key results

• 1-yr death 30.7% vs 50.7% (HR 0.55, P<0.001)
• Large reduction in repeat hospitalization
• Survival benefit sustained to 5 years
• Higher early stroke and vascular complications with TAVR

Why this trial matters

First randomized proof that TAVR beats medical therapy — the trial that made TAVR a legitimate therapy rather than an experimental rescue.

Clinical pearls

• The comparator was genuinely 'no good option', which magnifies the effect size.
• Early-generation device: vascular/stroke rates are far higher than contemporary practice.

Limitations

• First-generation valve and large-bore sheaths
• High PVL and vascular complication rates by modern standards

Serial follow-ups & subanalyses 31

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Study overview

Inclusion criteria

• Severe symptomatic AS
• High but not prohibitive surgical risk
• Anatomically suitable for TAVR

Primary endpoint

All-cause mortality at 1 year (noninferiority).

Secondary endpoints

• Death or stroke
• NYHA class
• Valve haemodynamics
• Repeat hospitalization

Key results

• 1-yr death 24.2% (TAVR) vs 26.8% (SAVR); noninferiority met (P=0.001)
• More strokes / vascular complications early with TAVR
• More major bleeding and new AF with surgery
• 5-year outcomes similar between strategies

Why this trial matters

Opened the door to standard-of-care adoption of TAVR in high-risk patients.

Clinical pearls

• Included transapical access — no longer routine.
• Early stroke signal drove years of cerebral-protection research.

Limitations

• Early-generation valve
• Mixed access routes including transapical

Serial follow-ups & subanalyses 30

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Study overview

Inclusion criteria

• Severe symptomatic AS
• Predicted prohibitive surgical risk
• Iliofemoral access adequate

Primary endpoint

All-cause mortality or major stroke at 12 months vs an OPG of 43%.

Secondary endpoints

• All-cause mortality
• Major stroke
• Valve haemodynamics
• NYHA class

Key results

• Primary composite 26.0% vs 43.0% OPG (P<0.0001)
• All-cause mortality 24.3%; major stroke 4.3% at 1 year
• Marked functional and haemodynamic improvement

Why this trial matters

Gave prohibitive-risk patients a second device family and set up the pivotal high-risk randomized trial.

Clinical pearls

• Single-arm design — benchmarked against a goal, not surgery.
• Supra-annular design delivers large effective orifice area.

Limitations

• No randomized comparator
• Early-generation self-expanding valve

Serial follow-ups & subanalyses 22

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Study overview

Inclusion criteria

• Severe symptomatic AS
• High surgical risk
• Anatomy suitable for CoreValve

Primary endpoint

All-cause mortality at 1 year (noninferiority, then superiority tested).

Secondary endpoints

• Death or major stroke
• Valve haemodynamics
• Pacemaker implantation
• NYHA class

Key results

• 1-yr death 14.2% (TAVR) vs 19.1% (SAVR); superiority P=0.04
• Lower mortality maintained; large orifice areas
• Substantially higher permanent pacemaker rate with TAVR

Why this trial matters

Cemented device-platform diversity and put self-expanding TAVR alongside balloon-expandable in guidelines.

Clinical pearls

• Note the conduction trade-off: better survival but more pacemakers.
• Superiority — not just noninferiority — distinguishes this from PARTNER 1A.

Limitations

• Early-generation device
• Higher pacemaker burden than surgery

Serial follow-ups & subanalyses 23

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Study overview

Inclusion criteria

• Severe symptomatic AS
• Intermediate surgical risk
• Heart-team consensus

Primary endpoint

Death from any cause or disabling stroke at 2 years (noninferiority).

Secondary endpoints

• Transfemoral vs transthoracic subgroups
• Aortic regurgitation
• Rehospitalization
• Valve haemodynamics

Key results

• Primary composite 19.3% (TAVR) vs 21.1% (SAVR); noninferior (P=0.001)
• Transfemoral cohort favoured TAVR
• More vascular complications / PVL with TAVR; more bleeding & AKI with surgery

Why this trial matters

Extended the evidence base below high risk and reframed access route as a key determinant of benefit.

Clinical pearls

• The transfemoral signal, not the overall result, drove practice change.
• Second-generation valve — still pre-SAPIEN 3.

Limitations

• Included transthoracic access
• PVL higher than contemporary devices

Serial follow-ups & subanalyses 20

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Study overview

Inclusion criteria

• Severe symptomatic aortic stenosis
• Intermediate surgical risk
• Suitable anatomy for SAPIEN 3 TAVR

Primary endpoint

Death and disabling stroke, with comparison to a propensity-matched PARTNER 2A surgical cohort.

Secondary endpoints

• Valve haemodynamics
• Paravalvular regurgitation
• Quality of life
• Reintervention and structural valve outcomes

Key results

• Early clinical outcomes with SAPIEN 3 were favorable compared with propensity-matched surgery.
• At 5 years, death or disabling stroke was similar between SAPIEN 3 TAVR and surgery.
• At 10 years, mortality and reintervention were similar after propensity matching.

Why this trial matters

Supported expansion of contemporary balloon-expandable TAVR to intermediate-risk patients and should not be conflated with the randomized SAPIEN XT PARTNER 2A trial.

Clinical pearls

• The registry and PARTNER 2A shared a program but were different study designs and valve generations.
• Most patients underwent transfemoral access.

Limitations

• Nonrandomized registry comparison
• Propensity matching cannot eliminate unmeasured confounding

Serial follow-ups & subanalyses 12

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Study overview

Inclusion criteria

• Severe symptomatic AS
• Intermediate surgical risk
• Heart-team consensus

Primary endpoint

Death from any cause or disabling stroke at 24 months (noninferiority).

Secondary endpoints

• Pacemaker implantation
• PVL
• Valve haemodynamics
• AKI / bleeding

Key results

• Primary composite 12.6% (TAVR) vs 14.0% (SAVR); noninferior
• More pacemakers and moderate PVL with TAVR
• Better valve haemodynamics with the supra-annular valve

Why this trial matters

Gave intermediate-risk patients a validated self-expanding option and shaped heart-team decision-making.

Clinical pearls

• Conduction disturbance remains the main trade-off vs surgery.
• Supra-annular design gives lower gradients, useful in smaller annuli.

Limitations

• More pacemakers than surgery
• Moderate PVL more frequent than SAVR

Serial follow-ups & subanalyses 14

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Study overview

Inclusion criteria

• Severe symptomatic AS
• Age ≥70 with moderately increased risk
• Heart-team agreement either treatment reasonable

Primary endpoint

All-cause mortality at 1 year (noninferiority).

Secondary endpoints

• Stroke
• Rehospitalization
• PVL
• Quality of life

Key results

• 1-yr death 4.6% (TAVI) vs 6.6% (SAVR); noninferior
• Numerically lower mortality with TAVI
• Higher pacemaker and PVL with TAVI

Why this trial matters

Demonstrated generalizability beyond tightly controlled, industry-run pivotal trials.

Clinical pearls

• Operator device choice mirrors real-world practice.
• Open-label pragmatic design trades some rigor for external validity.

Limitations

• Open-label
• Heterogeneous devices
• 1-year primary follow-up only

Serial follow-ups & subanalyses 3

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Study overview

Inclusion criteria

• Severe symptomatic AS
• Low surgical risk
• Suitable transfemoral anatomy
• Tricuspid valve (bicuspid excluded)

Primary endpoint

Composite of death, stroke, or rehospitalization at 1 year.

Secondary endpoints

• Death or disabling stroke
• New AF
• Length of stay
• Valve haemodynamics
• KCCQ quality of life

Key results

• 1-yr composite 8.5% (TAVR) vs 15.1% (SAVR); superior (P=0.001)
• Shorter stay, less new AF with TAVR
• 7-year: 34.6% vs 37.2% — no significant difference (curves converge)

Why this trial matters

Triggered the low-risk paradigm shift and rapid regulatory expansion.

Clinical pearls

• Early superiority attenuates over time — critical when counselling younger patients.
• Bicuspid and complex anatomies were excluded — don't over-generalize.

Limitations

• Highly selected low-risk transfemoral population
• Excluded bicuspid / complex anatomy

Serial follow-ups & subanalyses 11

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Study overview

Inclusion criteria

• Severe symptomatic AS
• Low surgical risk
• Trileaflet valve

Primary endpoint

Death or disabling stroke at 24 months (noninferiority).

Secondary endpoints

• Pacemaker implantation
• PVL
• Prosthesis–patient mismatch
• Valve haemodynamics

Key results

• 24-mo death/disabling stroke 5.3% (TAVR) vs 6.7% (SAVR); noninferior
• Lower gradients and less prosthesis–patient mismatch with TAVR
• Higher permanent pacemaker rate with TAVR

Why this trial matters

Established durable, haemodynamically favourable low-risk self-expanding TAVR.

Clinical pearls

• Best haemodynamics in small annuli — foreshadowed the SMART trial.
• Conduction disturbance remains the key trade-off.

Limitations

• Excluded bicuspid / complex anatomy
• Pacemaker burden higher than surgery

Serial follow-ups & subanalyses 13

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Study overview

Inclusion criteria

• Severe symptomatic AS
• Age ≥70
• No prohibitive comorbidity

Primary endpoint

Composite of all-cause death, stroke, or MI at 1 year.

Secondary endpoints

• Structural valve deterioration
• Pacemaker
• Valve haemodynamics
• PVL

Key results

• No significant 1-year difference in the primary composite
• 5-year composite 38.0% (TAVI) vs 36.3% (SAVR), P=0.86
• Less structural valve deterioration but more pacemakers with TAVI

Why this trial matters

First randomized low-risk signal — conceptual groundwork for PARTNER 3 / Evolut Low Risk.

Clinical pearls

• Small trial; long follow-up is its real value.
• 10-year durability data are among the longest available for TAVI.

Limitations

• Small sample size
• Surgical outcomes worse than expected in some analyses

Serial follow-ups & subanalyses 10

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Study overview

Inclusion criteria

• Severe symptomatic AS
• Age ≤75
• Low surgical risk
• Tricuspid or bicuspid anatomy

Primary endpoint

Composite of death, stroke, or rehospitalization at 1 year.

Secondary endpoints

• Bicuspid vs tricuspid subgroups
• Valve haemodynamics
• PVL
• Pacemaker

Key results

• 1-yr composite 10.2% (TAVI) vs 7.1% (SAVR)
• Excess events concentrated in bicuspid anatomy
• Tricuspid subgroup more reassuring; 3-yr 16.1% vs 12.6%

Why this trial matters

Refines what 'low-risk' means once age and bicuspid anatomy enter the picture.

Clinical pearls

• Bicuspid signal drives the caution — anatomy matters more than risk score in the young.
• Underpowered for definitive subgroup conclusions.

Limitations

• Modest sample size
• Bicuspid signal not definitively powered

Serial follow-ups & subanalyses 2

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Study overview

Inclusion criteria

• Severe symptomatic AS
• Age 65–85
• Low-to-intermediate risk
• Bicuspid excluded

Primary endpoint

Composite of all-cause death or stroke at 1 year (noninferiority).

Secondary endpoints

• New AF
• Bleeding
• Aortic regurgitation
• Rehospitalization

Key results

• Primary composite noninferior; all-cause death 2.6% vs 6.2% (HR 0.43)
• Less AF and bleeding with TAVI
• More aortic regurgitation with TAVI

Why this trial matters

Independent confirmation of low-risk findings without industry funding.

Clinical pearls

• Operator-choice valves mirror real-world device selection.
• Short primary follow-up — durability still to be established.

Limitations

• Device heterogeneity
• Bicuspid excluded
• 1-year primary endpoint

Serial follow-ups & subanalyses 2

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Study overview

Inclusion criteria

• Severe symptomatic AS
• High surgical risk

Primary endpoint

Safety and device performance.

Secondary endpoints

• Valve haemodynamics
• PVL

Key results

• Favourable 5-year valve function in a small cohort
• Established repositionable deployment concept

Why this trial matters

Seeded the REPRISE program that produced REPRISE II and III.

Clinical pearls

• Tiny sample — hypothesis-generating only.

Limitations

• Very small n
• Single-arm
• Device later withdrawn

Serial follow-ups & subanalyses 4

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Study overview

Inclusion criteria

• Severe symptomatic AS
• High surgical risk
• Suitable for either valve

Primary endpoint

Device success (VARC).

Secondary endpoints

• Residual aortic regurgitation
• Pacemaker
• Valve haemodynamics
• Cardiovascular mortality

Key results

• Device success 95.9% (BE) vs 77.5% (SE); RR 1.24, P<0.001
• Less residual AR and fewer pacemakers with BE valve
• 5-year: no significant clinical difference; better forward flow with SE

Why this trial matters

First randomized platform comparison; still cited on device mechanics.

Clinical pearls

• First-generation devices — mechanics differ from current valves.
• Higher SE pacemaker rate reflects the older CoreValve.

Limitations

• Small, single-country
• First-generation devices
• Endpoint is acute device success

Serial follow-ups & subanalyses 4

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Study overview

Inclusion criteria

• Severe symptomatic AS
• High or extreme surgical risk

Primary endpoint

30-day mean aortic gradient; device performance.

Secondary endpoints

• Moderate/severe PVL
• Permanent pacemaker
• Valve haemodynamics

Key results

• Met the primary haemodynamic endpoint
• No moderate/severe PVL
• High permanent pacemaker rate (~28–35%)

Why this trial matters

Established the sealing advantage that carried into REPRISE III.

Clinical pearls

• Single-arm; benchmarked against goals not a comparator.
• Pacemaker burden foreshadowed REPRISE III.

Limitations

• Single-arm
• Device later withdrawn

Serial follow-ups & subanalyses 4

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Study overview

Inclusion criteria

• Severe symptomatic AS
• High or extreme surgical risk

Primary endpoint

30-day safety composite and 1-year effectiveness composite (noninferiority).

Secondary endpoints

• Moderate/severe PVL
• Permanent pacemaker
• Valve haemodynamics

Key results

• Safety noninferior (19.0% vs 16.2%); effectiveness superior (15.4% vs 25.5%)
• Much less moderate/severe PVL with Lotus
• Permanent pacemaker 35.5% vs 19.6% — a major trade-off

Why this trial matters

Proof that valve design changes shift the PVL/pacemaker balance.

Clinical pearls

• Lotus was withdrawn for commercial/technical reasons — limited current relevance.
• Illustrates the PVL-vs-pacemaker design tension cleanly.

Limitations

• Platform discontinued
• Results less relevant to marketed valves

Serial follow-ups & subanalyses 7

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Study overview

Inclusion criteria

• Severe symptomatic AS
• High or extreme surgical risk

Primary endpoint

30-day safety and 1-year death/stroke (noninferiority).

Secondary endpoints

• PVL
• Valve haemodynamics
• Pacemaker

Key results

• Both primary endpoints noninferior
• 30-day safety 13.8% vs 9.6%
• More early PVL with Portico

Why this trial matters

Supported development/approval of the Portico → Navitor platform lineage.

Clinical pearls

• Comparator era predates newest devices.
• Re-sheathing aids positioning but early sealing lagged.

Limitations

• Platform-evolution study
• Older comparator devices

Serial follow-ups & subanalyses 4

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Study overview

Inclusion criteria

• Severe symptomatic AS
• Transfemoral candidate
• Increased surgical risk

Primary endpoint

Two 30-day composites (valve arm; anaesthesia arm) — equivalence.

Secondary endpoints

• Stroke
• PVL
• Pacemaker
• Procedural outcomes

Key results

• Valves clinically equivalent at 30 days
• Conscious sedation equivalent to general anaesthesia
• 1-year: more stroke with SAPIEN 3 (6.9% vs 1.0%) in this small sample

Why this trial matters

Evidence base for valve equipoise and minimalist anaesthesia strategy.

Clinical pearls

• Underpowered for small clinical differences.
• Supports conscious-sedation transfemoral workflows.

Limitations

• Modest sample size
• Not powered for rare events

Serial follow-ups & subanalyses 5

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Study overview

Inclusion criteria

• Severe symptomatic AS
• Aortic annulus area ≤430 mm²
• TAVR candidate

Primary endpoint

Co-primary: clinical composite (noninferiority) + bioprosthetic valve dysfunction (superiority) at 12 months.

Secondary endpoints

• Mean gradient / effective orifice area
• Prosthesis–patient mismatch
• PVL

Key results

• Clinical composite 9.4% vs 10.6% — noninferior
• Bioprosthetic valve dysfunction 9.4% vs 41.6% — superior for self-expanding
• Lower gradients and less severe PPM with Evolut

Why this trial matters

Provides direct, randomized device guidance for small annuli — a major, under-studied population (frequently women).

Clinical pearls

• Practice-defining for small annuli / prosthesis–patient mismatch decisions.
• Follow-up still short for durability claims.

Limitations

• Annulus-specific population
• Short follow-up for durability

Serial follow-ups & subanalyses 2

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Study overview

Inclusion criteria

• Severe symptomatic native AS
• Indicated for TAVI

Primary endpoint

30-day VARC-3 early safety composite (noninferiority).

Secondary endpoints

• Device success
• PVL
• Pacemaker
• 1-year outcomes

Key results

• 30-day composite ~25% vs ~27% — noninferior
• Noninferiority sustained at 1 year
• Comparable PVL and pacemaker profiles

Why this trial matters

Expands the global competitive landscape of balloon-expandable devices.

Clinical pearls

• Availability is region-dependent.
• Broadens options beyond the two dominant device families.

Limitations

• Platform availability varies by region
• Not a U.S. registration trial

Serial follow-ups & subanalyses 6

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Study overview

Inclusion criteria

• Asymptomatic severe AS
• Negative exercise test
• Low operative risk

Primary endpoint

Composite of all-cause death, MI, stroke, or unplanned HF hospitalization.

Secondary endpoints

• All-cause mortality
• HF hospitalization

Key results

• Primary composite 15.2% (early surgery) vs 34.7% (conservative)
• Extended follow-up HR ~0.42 favouring early surgery
• Supports early intervention in asymptomatic severe AS

Why this trial matters

Alongside RECOVERY and EARLY TAVR, part of the broader shift toward earlier intervention in asymptomatic severe AS.

Clinical pearls

• This is SURGERY — do not cite as TAVR evidence.
• Complements EARLY TAVR's transcatheter timing data.

Limitations

• Small sample
• Surgical (not transcatheter) intervention

Serial follow-ups & subanalyses 3

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Study overview

Inclusion criteria

• Asymptomatic severe AS
• Midwall late gadolinium enhancement on CMR

Primary endpoint

Composite of all-cause death or unplanned AS-related hospitalization.

Secondary endpoints

• Unplanned AS hospitalization
• Symptom onset
• LV remodelling

Key results

• Primary composite not significantly different
• Fewer unplanned AS hospitalizations with early AVR (secondary)
• Neutral overall for the enrichment strategy

Why this trial matters

Tests whether imaging enrichment can justify pre-symptomatic intervention — it did not, on its own.

Clinical pearls

• Contrast with EARLY TAVR: enrichment biomarker vs pure timing.
• Event rates lower than anticipated.

Limitations

• Modest sample
• Lower-than-expected event rate
• Mixed AVR modality

Serial follow-ups & subanalyses 2

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Study overview

Inclusion criteria

• Severe AS by echo
• Truly asymptomatic (negative exercise test)
• Suitable transfemoral anatomy

Primary endpoint

Composite of death, stroke, or unplanned cardiovascular hospitalization.

Secondary endpoints

• Unplanned CV hospitalization
• Symptom development
• LV function
• QoL

Key results

• Primary composite favoured early TAVR (26.8% vs surveillance)
• Benefit driven largely by fewer unplanned CV hospitalizations
• Most surveillance patients ultimately required valve replacement

Why this trial matters

First large RCT to test intervention before symptoms in severe AS.

Clinical pearls

• Hospitalization-driven composite — parse the components when counselling.
• Crossover to treatment in surveillance arm was high.

Limitations

• Composite driven by softer endpoint
• High eventual crossover

Serial follow-ups & subanalyses 6

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Study overview

Inclusion criteria

• Moderate AS
• Reduced LV ejection fraction
• Heart failure on GDMT

Primary endpoint

Hierarchical composite (win ratio) of death, disabling stroke, HF events, and KCCQ change.

Secondary endpoints

• HF hospitalization
• Quality of life
• LV remodelling

Key results

• Win ratio 1.31 (95% CI 0.91–1.88, P=0.14) — not significant
• Early quality-of-life signal did not translate into clear clinical benefit

Why this trial matters

Tests whether treating moderate AS early helps failing ventricles — it did not, yet.

Clinical pearls

• Moderate AS remains a research space, not a routine TAVR indication.
• Ongoing PROGRESS/EXPAND-type trials continue to explore moderate AS.

Limitations

• Small sample
• Open-label
• Underpowered for hard endpoints

Serial follow-ups & subanalyses 1

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Study overview

Inclusion criteria

• Failed surgical aortic bioprosthesis
• ViV-TAVR performed

Primary endpoint

30-day and 1-year survival and clinical outcomes.

Secondary endpoints

• Residual stenosis vs regurgitation mode of failure
• Valve size effect

Key results

• 30-day mortality 7.6%; 1-year survival ~83.2%
• Worse outcomes with small valves and stenotic (vs regurgitant) failure
• Established ViV feasibility across device types

Why this trial matters

First large global evidence base for ViV — shaped device sizing and patient selection.

Clinical pearls

• Stenotic mode of failure + small valve = highest-risk ViV.
• Drove interest in bioprosthetic valve fracture.

Limitations

• Early-era registry
• Heterogeneous devices and techniques

Serial follow-ups & subanalyses 3

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Study overview

Inclusion criteria

• Failed surgical aortic bioprosthesis
• High surgical reoperation risk

Primary endpoint

Safety and effectiveness (VARC framework).

Secondary endpoints

• Survival
• Valve haemodynamics / residual gradient
• NYHA class

Key results

• Favourable survival through 5 years
• Sustained haemodynamic and symptom improvement
• Higher residual gradients in small surgical valves

Why this trial matters

Provided the durable outcome data that made ViV a routine alternative to reoperation.

Clinical pearls

• Watch residual gradients in small (≤21 mm) surgical valves.
• Bioprosthetic valve fracture can help in selected small valves.

Limitations

• Registry (non-randomized)
• Selected high-risk population

Serial follow-ups & subanalyses 3

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Study overview

Inclusion criteria

• Degenerated / failed index transcatheter valve
• Considered for redo-TAVR

Primary endpoint

Procedural success and clinical outcomes (VARC).

Secondary endpoints

• Coronary obstruction risk
• Residual gradient
• Survival

Key results

• Redo-TAVR remains rare (~0.3% of TAVR)
• Higher procedural success for TAV-in-TAV than TAV-in-SAV in matched analysis
• Coronary access / obstruction is a key planning concern

Why this trial matters

Central to lifetime-management planning as younger patients receive TAVR first.

Clinical pearls

• Index valve type dictates future redo and coronary-access feasibility.
• Commissural alignment at first TAVR matters for the future.

Limitations

• Observational registry
• Selection bias
• Limited long-term data

Serial follow-ups & subanalyses 1

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Study overview

Inclusion criteria

• Low-risk severe AS
• Bicuspid aortic valve

Primary endpoint

Feasibility / 30-day safety.

Secondary endpoints

• Hypoattenuated leaflet thickening (HALT)
• PVL
• Valve haemodynamics

Key results

• Favourable 30-day results in selected bicuspid patients
• Provided early CT/leaflet data in bicuspid anatomy

Why this trial matters

Among the first prospective U.S. low-risk bicuspid TAVR experiences.

Clinical pearls

• First-mover data — hypothesis-generating.
• Complements PARTNER 3 and Evolut bicuspid registries.

Limitations

• Small feasibility cohort
• No randomized comparator

Serial follow-ups & subanalyses 8

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Study overview

Inclusion criteria

• Low-risk severe AS
• Bicuspid aortic valve
• Suitable anatomy

Primary endpoint

30-day safety and efficacy (descriptive endpoints).

Secondary endpoints

• PVL
• Pacemaker
• Valve haemodynamics
• 3-year outcomes

Key results

• Favourable 30-day results in selected bicuspid anatomy
• Durable 3-year outcomes reported

Why this trial matters

Extends confidence in self-expanding bicuspid TAVR in selected patients.

Clinical pearls

• Supra-annular design manages small/asymmetric anatomy well.
• Sizing in bicuspid anatomy is challenging — use annular + supra-annular assessment.

Limitations

• Single-arm
• Selected anatomy
• Not randomized

Serial follow-ups & subanalyses 3

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Study overview

Inclusion criteria

• Low-risk severe AS
• Bicuspid aortic valve
• Suitable anatomy

Primary endpoint

1-year clinical outcomes vs matched tricuspid cohort.

Secondary endpoints

• Stroke
• PVL
• Valve haemodynamics

Key results

• Similar 1-year outcomes to matched tricuspid patients
• Acceptable PVL and haemodynamics in selected anatomy

Why this trial matters

Supports feasibility of bicuspid TAVR in carefully chosen patients.

Clinical pearls

• Selection is everything — calcification pattern and asymmetry matter.
• Not randomized; excludes the most complex bicuspid morphologies.

Limitations

• Registry
• Selected anatomy
• Not randomized

Serial follow-ups & subanalyses 8

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Study overview

Inclusion criteria

• Symptomatic moderate-to-severe or severe native AR
• High surgical risk
• Suitable anatomy for the dedicated device

Primary endpoint

30-day safety and 1-year all-cause mortality vs performance goals.

Secondary endpoints

• Residual AR
• Pacemaker implantation
• LV remodelling
• NYHA class

Key results

• Met the 30-day safety goal (26.7% event rate)
• Met the 1-year efficacy goal (all-cause mortality 7.8%)
• Permanent pacemaker ~24%

Why this trial matters

Native AR lacks a leaflet calcium anchor; a dedicated clipping device solves the fixation problem standard TAVR valves cannot.

Clinical pearls

• Standard balloon/self-expanding valves are unreliable in pure AR — device design matters.
• Pacemaker rate is a notable trade-off.

Limitations

• Single-arm (no randomized comparator)
• High-risk population only

Serial follow-ups & subanalyses 1

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Study overview

Inclusion criteria

• Symptomatic native AR
• Suitable transfemoral anatomy

Primary endpoint

VARC-3 30-day early-safety composite.

Secondary endpoints

—

Key results

• Pending — enrollment underway (started Oct 2024)

Why this trial matters

Broadens the dedicated-AR device pipeline beyond JenaValve.

Clinical pearls

• Transfemoral dedicated-AR access is the key differentiator.
• Watch for head-to-head positioning vs Trilogy.

Limitations

• Not yet reporting

Study overview

Inclusion criteria

• Symptomatic native AR
• Non-high-risk surgical profile

Primary endpoint

To be defined (safety/effectiveness vs surgery).

Secondary endpoints

—

Key results

• Pending — trial ongoing / in setup

Why this trial matters

A randomized comparison would move dedicated-AR TAVR beyond single-arm evidence.

Clinical pearls

• One to watch for the future of transcatheter AR therapy.

Limitations

• Not yet reporting

Study overview

Inclusion criteria

• Symptomatic native AR
• Suitable transfemoral anatomy

Primary endpoint

Feasibility / early safety.

Secondary endpoints

—

Key results

• Pending — feasibility ongoing

Why this trial matters

Feasibility precursor to the JOURNEY pivotal trial.

Clinical pearls

• Feasibility data shape the pivotal design.

Limitations

• Not yet reporting

Study overview

Inclusion criteria

• Symptomatic native AR
• Randomizable to device or surgery

Primary endpoint

To be defined (safety/effectiveness vs surgery).

Secondary endpoints

—

Key results

• Pending — trial ongoing

Why this trial matters

A positive randomized result would establish transcatheter AR therapy in the U.S.

Clinical pearls

• The AR analogue to the low-risk AS RCTs.

Limitations

• Not yet reporting

Study overview

Inclusion criteria

• Severe symptomatic AS
• High or extreme surgical risk

Primary endpoint

30-day all-cause mortality.

Secondary endpoints

• Effective orifice area / gradient
• PVL
• Pacemaker

Key results

• Favourable 30-day outcomes; large EOA and low gradients
• 1-year all-cause mortality ~14.6%

Why this trial matters

Adds a regional device option; limited penetration in major markets.

Clinical pearls

• Regionally relevant; sparse comparative data.
• Large orifice area is its main selling point.

Limitations

• Single-arm
• Limited comparative / long-term data

Serial follow-ups & subanalyses 2

Click a follow-up to reveal its paper links.

Study overview

Inclusion criteria

• Severe symptomatic AS
• Intermediate/low risk or failed bioprosthesis

Primary endpoint

Mortality / fatal stroke and PVL performance objectives.

Secondary endpoints

• Moderate-or-worse PVL
• Pacemaker
• Valve haemodynamics

Key results

• Favourable early outcomes reported
• Very low moderate-or-worse PVL at 30 days in reports
• Ongoing follow-up

Why this trial matters

Extends Navitor evidence toward lower-risk and ViV use OUS.

Clinical pearls

• Device is Abbott Navitor — a common point of confusion.
• Sealing performance is the headline metric.

Limitations

• Single-arm
• OUS population

Study overview

Inclusion criteria

• Severe symptomatic AS
• TAVI candidate

Primary endpoint

Safety / effectiveness and PVL performance (program-dependent).

Secondary endpoints

—

Key results

• Low reported moderate-or-worse PVL at 30 days / 1 year in early cohorts
• Ongoing global evaluation

Why this trial matters

Positions Abbott's platform on sealing performance in a competitive market.

Clinical pearls

• Active sealing skirt targets the PVL problem directly.
• Feeds the VANTAGE and ENVISION IDE programs.

Limitations

• Program-level (not a single RCT)
• Ongoing data

Study overview

Inclusion criteria

• Severe symptomatic AS
• Low or intermediate surgical risk

Primary endpoint

Safety and effectiveness vs commercial valves.

Secondary endpoints

—

Key results

• Pending — trial ongoing

Why this trial matters

Potential future U.S. regulatory expansion for the Navitor platform.

Clinical pearls

• Long horizon — completion projected years out.
• Head-to-head vs established valves raises the evidentiary bar.

Limitations

• Not yet reporting
• Long follow-up horizon

Study overview

Inclusion criteria

• Severe symptomatic AS
• TAVI candidate

Primary endpoint

Feasibility / safety (EFS); comparative endpoints (PARADIGM RCT).

Secondary endpoints

• Effective orifice area / laminar flow
• PVL
• Durability signals

Key results

• Pending — EFS ongoing; PARADIGM RCT planned

Why this trial matters

Tests whether biomimetic single-piece design can improve flow and durability.

Clinical pearls

• Single-piece biomimetic leaflet is the design bet.
• PARADIGM RCT will be the real test.

Limitations

• Very early stage
• No comparative outcome data yet