Biomimetic TAVR restores aortic flow towards native physiology

Abstract Backgroud While transcatheter aortic valve replacement (TAVR) reliably unloads transvalvular pressure, restoration of physiological ascending aortic haemodynamics is inconsistent with conventional designs. Flow displacement (FD) and flow reversal ratio (FRR) quantify aortic flow asymmetry and retrograde energy, respectively, and are linked to persistent afterload and suboptimal reverse remodelling 1. A biomimetic leaflet geometry engineered to reproduce native cusp kinematics and central systolic jet formation aims to normalise aortic flow 2. Purpose To test whether a biomimetic-leaflet TAVR normalises ascending aortic haemodynamics—quantified by FD and FRR—relative to native-valve controls. Methods We studied three prospectively enrolled cohorts: patients with severe aortic stenosis (AS, n = 50), recipients of a biomimetic-leaflet TAVR at 6-month follow-up (first-in-human cohort; n = 35), and non-AS age-comorbidity matched controls (n = 35), for a total sample of 120. All participants underwent echocardiography and 4D-flow CMR with pre-specified quantification of ascending aortic FD and FRR; left-ventricular (LV) indices and aortic geometry (including ascending aortic minimum area) were recorded. Controls were recruited from an institutional registry, age–sex matchund disease states. Control inclusion criteria were: available 4D-flow CMR; LVEF and RVEF ≥50%; aortic backward flow ≤5 ml/s and ≤10%; LGE ≤10%; BMI ≤30 kg/m² and native T1 950–1050 ms. Stepwise multivariable regression across the pooled dataset identified independent determinants of FD and FRR. Because recipients had larger ascending aortas, FD and FRR were indexed to the minimum area of the ascending aorta, the a priori principal geometric confounder. Results At 6 months post-implant, age/sex were comparable across cohorts (Fig 1). Clinical status and functional capacity improved versus severe AS (p=0.0001) with lower PCWP (p=0.002). CMR-derived LV mass regressed from 142.4 ± 47 g (severe AS) to 115.5 ± 31.4 g at 6 months post-implant (p=0.004), and was indistinguishable from native-valve controls (114.2 ± 43.7 g; p=0.88). After indexing to ascending aortic minimum area, aortic flow haemodynamics significantly improved from severe AS to the biomimetic-leaflet TAVR cohort, with reductions in both indexed FD (4.1 ± 1.3% vs 3.5 ± 0.9%, p=0.01) and FRR (4.0 ± 1.0% vs 2.4 ± 0.7%, p0.0001) (Fig 2). Furthermore, aortic flow haemodynamics in recipients were statistically indistinguishable from native-valve controls (FD 3.5 ± 0.9%, FRR 2.4 ± 0.7%; controls FD 3.5 ± 1.4%, FRR 2.1 ± 0.8%; both P = NS), indicating restoration of near-physiological flow rather than pressure unloading alone. Conclusions A biomimetic-leaflet TAVR normalises mean transvalvular gradients, resulting in LV reverse remodelling, and restores aortic flow (FD, FRR) to native-like values—establishing flow restoration, not merely gradient reduction, as a core multi-modal efficacy dimension for TAVR.For image description, please refer to the figure legend and surrounding text. For image description, please refer to the figure legend and surrounding text.