Transvalvular Pressure Research Articles

Transcatheter aortic valve implantation in patients with significant septal hypertrophy.

Previous reports suggest septal hypertrophy with an interventricular septum depth (IVSD) ≥ 14mm may adversely affect outcomes after transcatheter aortic valve implantation (TAVI) due to suboptimal valve placement, valve migration, or residual increasedLVOTpressure gradients. This analysis investigates the impact of interventricular septal hypertrophy on acute outcomes after TAVI. Between 2009 and 2021, 1033 consecutive patients (55.8% male, 80.5 ± 6.7years, EuroSCORE II 6.3 ± 6.5%) with documented IVSD underwent TAVI at our center and were included for analysis. Baseline, periprocedural, and 30-day outcome parameters of patients with normal IVSD (< 14mm; group 1) and increased IVSD (≥ 14mm; group 2) were compared. Data were retrospectively analyzed according to updated Valve Academic Research Consortium-3 (VARC-3) definitions. Comparison of outcome parameters was adjusted for baseline differences between groups using logistic and linear regression analyses. Of 1033 patients, 585 and 448 patients were allocated to groups 1 and 2, respectively. There was no significant difference between groups regarding transfemoral access rate (82.6% (n = 478) vs. 86.0% (n = 381), p = 0.157). Postprocedural mean transvalvular pressure gradient was significantly increased in group 2 (group 1, 7.8 ± 4.1mmHg, vs. group 2, 8.9 ± 4.9mmHg, p = 0.046). Despite this finding, there was no significant difference between groups regarding the rates of VARC-3 adjudicated composite endpoint device success (90.0% (n = 522) vs. 87.6% (n = 388), p = 0.538) or technical success (92.6% (n = 542) vs. 92.6% (n = 415), p = 0.639). Moreover, the groups showed no significant differences regarding the rates of paravalvular leakage ≥ moderate (3.1% (n = 14) vs. 2.6% (n = 9), p = 0.993), postprocedural permanent pacemaker implantation (13.4% (n = 77) vs. 13.8% (n = 61), p = 0.778), or 30-day mortality (5.1% (n = 30) vs. 4.5% (n = 20), p = 0.758). Although transvalvular mean pressure gradients were significantly higher in patients with increased IVSD after TAVI, acute outcomes were comparable between groups suggesting no early impact of adverse hemodynamics due to elevated IVSD. However, how these differences in hemodynamic findings may affect mid- and long-term outcomes, especially in terms of valve durability, needs to be evaluated in further investigations.

Acute Effect in Mechanical Efficiency by Pressure-Volume Loop Analysis after Transcatheter Aortic Valve Implantation.

This study aimed to evaluate the immediate effect of transcatheter aortic valve implantation (TAVI) on mechanical efficiency. A total of 46 patients (25 females) with an average age of 83 ± 6.4 years underwent TAVI using the CoreValve system. During the same hospitalization, we conducted a comprehensive comparison of the patients before and after TAVI without inotropic support using echocardiography. The parameters encompassed left ventricular (LV) geometry, valvular load, global LV afterload and ventricular hemodynamics. The analysis using pressure-volume loops enabled the determination of load-independent contractility (Ees) and afterload, in addition to assessing potential energy, stroke work, and mechanical efficiency. The immediate effect was an augmented aortic valve area accompanied by a reduction in the transvalvular pressure gradient. We observed reductions in left ventricular end-systolic volume and end-diastolic volume, and also reductions in global afterload and end-systolic meridional wall stress. The Ea index decreased, while the Ees index remained relatively stable. We noted increases in stroke volume and systemic arterial compliance, indicating more efficient blood transfer from the ventricle to aorta. These changes contributed to the normalization of ventricular-arterial coupling. In terms of mechanical work of the chamber, we observed significant decreases in potential energy, stroke work, and pressure-volume area. There was an increase in the mechanical efficiency of the chamber. The TAVI procedure immediately reduced global afterload and improved diastolic compliance of the chamber, resulting in enhanced ventricular function and mechanical efficiency.

Innovations in Aortic Valve Replacement: A Comprehensive Overview of the Intuity Rapid Deployment Valve

Rapid deployment/sutureless (RDS) valves have recently emerged as an innovative surgical solution, providing an alternative to traditional methods of surgical aortic valve replacement (SAVR) by eliminating the need for suture placement and tying. This innovation leads to a reduction in aortic crossclamp and cardiopulmonary bypass times, enhancing the efficiency of the procedure. Among the 2 available RDS valves, the Edwards Intuity valve in particular has been demonstrated to be a particularly promising substitute in the field of SAVR. The Intuity valve distinguishes itself from other RDS and conventional valves by yielding superior outcomes, such as a significant reduction in mortality, increase in the longevity of the valve, and a marked decrease in both mean and peak transvalvular pressure gradients. These benefits collectively contribute to its appeal as a favorable new solution. However, further investigation is needed to conclusively determine the long-term outcomes and safety of RDS valves. Nevertheless, the utilization of the Intuity valve presents an exciting solution to the existing limitations of conventional and minimally invasive SAVR, especially for patients afflicted with severe aortic stenosis.

AVCAPIR: A Novel Procalcific PIWI-Interacting RNA in Calcific Aortic Valve Disease.

Calcification of the aortic valve leads to increased leaflet stiffness and consequently results in the development of calcific aortic valve disease (CAVD). However, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified a novel aortic valve calcification-associated PIWI-interacting RNA (piRNA; AVCAPIR) that increases valvular calcification and promotes CAVD progression. Using piRNA sequencing, we identified piRNAs contributing to the pathogenesis of CAVD that we termed AVCAPIRs. High-cholesterol diet-fed ApoE-/- mice with AVCAPIR knockout were used to examine the role of AVCAPIR in aortic valve calcification (AVC). Gain- and loss-of-function assays were conducted to determine the role of AVCAPIR in the induced osteogenic differentiation of human valvular interstitial cells. To dissect the mechanisms underlying AVCAPIR-elicited procalcific effects, we performed various analyses, including an RNA pulldown assay followed by liquid chromatography-tandem mass spectrometry, methylated RNA immunoprecipitation sequencing, and RNA sequencing. RNA pulldown and RNA immunoprecipitation assays were used to study piRNA interactions with proteins. We found that AVCAPIR was significantly upregulated during AVC and exhibited potential diagnostic value for CAVD. AVCAPIR deletion markedly ameliorated AVC in high-cholesterol diet-fed ApoE-/- mice, as shown by reduced thickness and calcium deposition in the aortic valve leaflets, improved echocardiographic parameters (decreased peak transvalvular jet velocity and mean transvalvular pressure gradient, as well as increased aortic valve area), and diminished levels of osteogenic markers (Runx2 and Osterix) in aortic valves. These results were confirmed in osteogenic medium-induced human valvular interstitial cells. Using unbiased protein-RNA screening and molecular validation, we found that AVCAPIR directly interacts with FTO (fat mass and obesity-associated protein), subsequently blocking its N6-methyladenosine demethylase activity. Further transcriptomic and N6-methyladenosine modification epitranscriptomic screening followed by molecular validation confirmed that AVCAPIR hindered FTO-mediated demethylation of CD36 mRNA transcripts, thus enhancing CD36 mRNA stability through the N6-methyladenosine reader IGF2BP1 (insulin-like growth factor 2 mRNA binding protein 1). In turn, the AVCAPIR-dependent increase in CD36 stabilizes its binding partner PCSK9 (proprotein convertase subtilisin/kexin type 9), a procalcific gene, at the protein level, which accelerates the progression of AVC. We identified a novel piRNA that induced AVC through an RNA epigenetic mechanism and provide novel insights into piRNA-directed theranostics in CAVD.

Use of Sutureless Valve in Aortic Root Enlargement

The small aortic annulus is a surgical challenge in patients undergoing aortic valve replacement which may lead to patient prosthesis mismatch. Management options include aortic root enlargement, aortic root replacement, and the use of sutureless valves. In this case series, we report our results with aortic root enlargement, sutureless valve implantation, and benchtop modelling of the radial forces exerted. Five patients underwent aortic root enlargement and insertion of the Perceval valve as part of the management strategy to enlarge their effective orifice area. We further investigate this strategy with a benchtop model to quantify the radial forces exerted by the Perceval valve on the aortic annulus. Radial and hoop forces on the aortic annulus and inner ring of the Perceval valve were recorded using a Mylar force tester. Five female patients with native annulus between 18mm-20mm underwent root enlargement and insertion of a Perceval S valve. The postoperative course was uncomplicated for all patients except for one who required a permanent pacemaker insertion. Transvalvular pressure gradients remained low at up to 4 years of follow-up (12 mmHg-21 mmHg), with no evidence of paravalvular leak. Benchtop testing demonstrated radial forces exerted at the annulus in all-size Perceval S valves to be within physiological variables, whereas compressive forces required to deform the valves were supraphysiological. The deployment of a sutureless valve within a surgical enlarged aortic root is a feasible solution in patients with a small aortic root.

Effect of Sinotubular Junction Size on TAVR Leaflet Thrombosis: A Fluid-Structure Interaction Analysis.

TAVR has emerged as a standard approach for treating severe aortic stenosis patients. However, it is associated with several clinical complications, including subclinical leaflet thrombosis characterized by Hypoattenuated Leaflet Thickening (HALT). A rigorous analysis of TAVR device thrombogenicity considering anatomical variations is essential for estimating this risk. Clinicians use the Sinotubular Junction (STJ) diameter for TAVR sizing, but there is a paucity of research on its influence on TAVR devices thrombogenicity. A Medtronic Evolut® TAVR device was deployed in three patient models with varying STJ diameters (26, 30, and 34mm) to evaluate its impact on post-deployment hemodynamics and thrombogenicity, employing a novel computational framework combining prosthesis deployment and fluid-structure interaction analysis. The 30mm STJ patient case exhibited the best hemodynamic performance: 5.94mmHg mean transvalvular pressure gradient (TPG), 2.64 cm2 mean geometric orifice area (GOA), and the lowest mean residence time (TR)-indicating a reduced thrombogenic risk; 26mm STJ exhibited a 10 % reduction in GOA and a 35% increase in mean TPG compared to the 30mm STJ; 34mm STJ depicted hemodynamics comparable to the 30mm STJ, but with a 6% increase in TR and elevated platelet stress accumulation. A smaller STJ size impairs adequate expansion of the TAVR stent, which may lead to suboptimal hemodynamic performance. Conversely, a larger STJ size marginally enhances the hemodynamic performance but increases the risk of TAVR leaflet thrombosis. Such analysis can aid pre-procedural planning and minimize the risk of TAVR leaflet thrombosis.

Balloon-expandable transcatheter heart valves for treatment of aortic valve stenosis in patients with large aortic annuli: Evaluation of deployment balloon overfilling strategies.

Transcatheter aortic valve implantation (TAVI) using balloon-expandable (BE) transcatheter heart valves (THV) in aortic annuli above 29 mm includes particular procedural steps, mainly involving overfilling of the deployment balloon. Data on overfilling strategies in clinical daily practice is scarce. We herein aimed for a retrospective description of utilized overfilling strategies in those patients. Between January 2016 and December 2022, 45 patients (100% male, 76.9 ± 6.1 years) received TAVI in aortic annuli above 29 mm using a BE THV. Overfilling volumina of the deployment balloon were left to operators' discretion. Clinical and multislice computed tomography data were retrospectively collected. Clinical endpoints were adjudicated in accordance with the updated standardized VARC-3 definitions. Profound overfilling (+4/5 mL) was used in patients with a mild calcium burden (˂750 mm³) even in aortic annuli of 29.0-30.0 mm. Nominal/slight overfilling (+1 mL) was used in aortic annuli up to 32.5 mm but an intermediate to severe calcific burden (>750-3200 mm³). Accordingly, a low calcification group (˂750 mm³, n = 17) compared to a significant calcification group (≥750 mm³, n = 28), presented with higher overfilling volumina (2.1 ± 1.4 vs. 0.8 ± 1.0; p ˂ 0.001), although aortic annulus diameter was not different (29.8 ± 0.8 vs. 29.9 ± 0.9 mm; p = 0.7). All-cause 30-day mortality was 0%. Device success was 97.8%. Transvalvular mean pressure gradient at discharge was 9.5 ± 3.6 mmHg. No case of PVL >mild was documented. Extent of overfilling of the deployment balloon largely depends on calcification burden in addition to aortic annulus diameter with significant and profound overfilling particularly in patients with a calcification burden of the aortic valve complex ˂750 mm³.

Predicting pressure gradient using artificial intelligence for transcatheter aortic valve replacement

ObjectiveAfter transcatheter aortic valve replacement, the mean transvalvular pressure gradient indicates the effectiveness of the therapy. The objective is to develop artificial intelligence to predict the post–transcatheter aortic valve replacement aortic valve pressure gradient and aortic valve area from preprocedural echocardiography and computed tomography data. MethodsA retrospective study was conducted on patients who underwent transcatheter aortic valve replacement due to aortic valve stenosis. A total of 1091 patients were analyzed for pressure gradient predictions (mean age 76.8 ± 9.2 years, 57.8% male), and 1063 patients were analyzed for aortic valve area predictions (mean age 76.7 ± 9.3 years, 57.2% male). An artificial intelligence learning model was trained (training: n = 663 patients, validation: n = 206 patients) and tested (testing: n = 222 patients) to predict pressure gradient, and a separate artificial intelligence learning model was trained (training: n = 640 patients, validation: n = 218 patients) and tested (testing: n = 205 patients) for predicting aortic valve area. ResultsThe mean absolute error for pressure gradient and aortic valve area predictions was 3.0 mm Hg and 0.45 cm2, respectively. Valve sheath size, body surface area, and age were determined to be the top 3 predictors for pressure gradient, and valve sheath size, left ventricular ejection fraction, and aortic annulus mean diameter were identified to be the top 3 predictors of post–transcatheter aortic valve replacement aortic valve area. A training dataset size of more than 500 patients demonstrated good robustness of the artificial intelligence models for pressure gradient and aortic valve area. ConclusionsThe artificial intelligence–based algorithm has demonstrated potential in predicting post–transcatheter aortic valve replacement transvalvular pressure gradient predictions for patients with aortic valve stenosis. Further studies are necessary to differentiate pressure gradient between valve types.

Valvular and ascending aortic hemodynamics of the On-X aortic valved conduit by same-day echocardiography and 4D flow MRI.

This study aims to assess whether the On-X aortic valved conduit better restores normal valvular and ascending aortic hemodynamics than other commonly used bileaflet mechanical valved conduit prostheses from St. Jude Medical and Carbomedics by using same-day transthoracic echocardiography (TTE) and 4D flow magnetic resonance imaging (MRI) examinations. TTE and 4D flow MRI were performed back-to-back in 10 patients with On-X, six patients with St. Jude (two) and Carbomedics (four) prostheses, and 36 healthy volunteers. TTE evaluated valvular hemodynamic parameters: transvalvular peak velocity (TPV), mean and peak transvalvular pressure gradient (TPG), and effective orifice area (EOA). 4D flow MRI evaluated the peak systolic 3D viscous energy loss rate (VELR) density and mean vorticity magnitude in the ascending aorta (AAo). While higher TPV and mean and peak TPG were recorded in all patients compared to healthy subjects, the values in On-X patients were closer to those in healthy subjects (TPV 1.9 ± 0.3 vs. 2.2 ± 0.3 vs. 1.2 ± 0.2 m/s, mean TPG 7.4 ± 1.9 vs. 9.2 ± 2.3 vs. 3.1 ± 0.9 mmHg, peak TPG 15.3 ± 5.2 vs. 18.9 ± 5.2 vs. 6.1 ± 1.8 mmHg, p < 0.001). Likewise, while higher VELR density and mean vorticity magnitude were recorded in all patients than in healthy subjects, the values in On-X patients were closer to those in healthy subjects (VELR: 50.6 ± 20.1 vs. 89.8 ± 35.2 vs. 21.4 ± 9.2 W/m3, p < 0.001) and vorticity (147.6 ± 30.0 vs. 191.2 ± 26.0 vs. 84.6 ± 20.5 s-1, p < 0.001). This study demonstrates that the On-X aortic valved conduit may produce less aberrant hemodynamics in the AAo while maintaining similar valvular hemodynamics to St. Jude Medical and Carbomedics alternatives.

Determinants of trans-prosthetic gradients after isolated surgical aortic valve replacement and effect on survival

Abstract Background Surgical aortic valve replacement (sAVR) remains the primary therapeutic approach for severe symptomatic aortic stenosis. Patient-prosthetic mismatch (PPM) occurs when the implanted valve is too small for the patient and is characterized by a small orifice area and elevated trans-valvular pressure gradient identified on post-operative transthoracic echocardiography (TTE). PPM is thought to be associated with adverse clinical outcomes, especially when severe, however data is conflicting. Purpose We sought to determine the impact of patient- and prosthesis-related parameters on post-operative trans-valvular pressure gradient, as a surrogate of PPM, and identify its influence on survival in a large single centre study. Methods This was a retrospective study of patients who underwent isolated sAVR between June 2003 and February 2017 at our tertiary cardiothoracic centre. Patients were excluded if their clinical and surgical records were incomplete, they hadn’t attended post-operative follow up or they had undergone valve replacement with anything other than a conventional stented tissue or mechanical prosthesis. All patients underwent postoperative follow up at eight weeks, six months and annually thereafter in keeping with local guidelines. TTE was performed between six and 12 months after surgery. Peak trans-valvular gradient was calculated using the continuity equation based upon continuous wave doppler assessment through the aortic valve. The highest value obtained from multiple views was recorded. Independent predictors of post-operative gradient were determined using a cox-proportional hazards model. Survival analysis was evaluated by Kaplein-Meier curves and log-rank test. Results One thousand seven hundred and ninety patients underwent isolated SAVR during the study period, of which 604 patients satisfied the inclusion and exclusion criteria. Mean age was 69.5 (±11.4) years and 346 (59%) were male. Mean peak pressure gradient was 29.96 (±12.4) mmHg. Independent predictors of increased post-operative gradients were: smaller valve size, postoperative diuretic use, age, gender and operating surgeon (p&amp;lt;0.001) (Table 1). Seventy-two patients (12%) died during follow-up. Mean survival was 12.1 years. After adjusting for confounders, post-operative pressure gradient was identified as a significant predictor of mortality (HR 1.02, p=0.001), alongside age (HR 1.06, p=0.001) and diabetes mellitus (HR 2.18, p=0.007) (Figure 1). Conclusion In a large cohort of patients undergoing sAVR at a single centre in the UK, valve size was the biggest determinant of postoperative pressure gradient alongside sex, diabetes, diuretic use and operating surgeon. Postoperative pressure gradient was a significant predictor of all-cause mortality. Accordingly, implanting the largest possible valve size should be considered the single most effective way of reducing the post-operative gradient and long-term mortality in patients undergoing sAVR.Table 1:Multivariate linear regressionFigure 1:K-M curve

Valvular presence of coagulation factor XI correlates with the severity of aortic stenosis

Abstract Background The role of coagulation system as a factor involved in the progression of aortic stenosis (AS) has been proven. Considering recent studies about oral factor XIa (FXIa) inhibitor – asundexian with antithrombotic efficacy, our aim was to investigate whether FXI is present within stenotic leaflets in patients with severe AS and whether its expression correlates with valvular calcification. Methods We recruited 20 patients aged 66 ±9 years with severe AS defined as mean transvalvular pressure gradient (PGmean) ≥ 40mmHg, peak transvalvular velocity (Vmax) of ≥4.0 m/s and aortic valve area (AVA) &amp;lt;1 cm2. Stenotic aortic valves were obtained during valve replacement surgery. Aortic leaflets obtained from AS patients and from age-matched apparently healthy autopsy donors (n=3) were used to evaluate valvular expression of FXI, FIX, tissue factor (TF) and bone morphogenetic protein 2 (BMP2) by single and double-labeled immunostaining. The immunopositive valve area was computed as the ratio (%) of positively and negatively stained areas. The Ethical Committee approved the study and all participants provided written informed consent. Results AS patients with median PGmean of 54 [46-67] mmHg, Vmax of 4.5 [4.4-5.0] m/s and AVA of 0.8 [0.7-0.9] cm2 were treated with angiotensin converting enzyme inhibitors (80%), beta-blockers (90%), statins (70%) and acetylsalicylic acid (80%). In loco analysis revealed valvular expression of FXI within all studied stenotic valves, but not within control ones (Figure 1 A and B). The FXI-immunopositive valve area constituted 21.4±4.5% of the total leaflet area, while these for FIX and TF were 17.2 ±3.8% and 26.5±5.1%, respectively. The mean BMP2-positive area was 22.9±4.1%. The expression of studied proteins was observed at the aortic side of the stenotic leaflets and presented a condensed pattern of fluorescence. Moreover, the expression of FXI co-expressed with FIX in 76% and TF in 71%, suggesting local activation of FXI (Figure 1 D and E). Moreover, FXI co-expressed with BMP2 in 83% (Figure C), which may indicate that FXI activation occurs at the site of leaflet calcification. Interestingly, valvular amounts of FXI correlated with AS severity measured as PGmean (r=0.49, p=0.03), PGmax (r=0.53, p=0.02), Vmax (r=0.54, p=0.01) and AVA (r=-0.53, p=0.02). Conclusions We are the first to show the valvular presence of FXI, co-expressing with FIX and TF, which indicates FXI in loco activation. A strong co-expression of FXI with BMP2 and associations with disease severity highlight the impact of coagulation on valve calcification. It is tempting to speculate that FXIa inhibition could attenuate not only coagulation activation but also valvular calcification and thus retard AS progression. Clinical relevance of these findings requires further studies. This work was supported by the Polish National Science Centre (UMO-2021/41/N/NZ5/03323).Figure 1_ESC_2023

A Novel Transcatheter Device for the Edge-to-Edge Treatment of Tricuspid Regurgitation: A Preliminary Evaluation

Tricuspid regurgitation (TR) is the most common pathology of the tricuspid valve (TV), with significant mortality in severe cases. A well-established strategy to treat TR is represented by the clover surgical technique, which consists of stitching together the free edges of TV leaflets, producing a clover-shaped valvular orifice. Transcatheter treatments for TR constitute a valuable alternative for high-risk patients. In this work we investigated haemodynamic performances and safety of a novel device (StarTric device (STD)) aiming to perform the clover technique via percutaneous access. To assess haemodynamic performances, STD and clover were applied on porcine pathological TVs and tested. Fluid dynamic indexes of both strategies were compared to the pathological model. To evaluate device safety, forces exchanged between device and leaflets were compared to the extraction force (EF) required to STD to completely pass through the leaflet. Clover technique and STD induced a comparable TV backflow reduction (48% and 47%, respectively), with associated increase of TV flow in all tested conditions. Diastolic transvalvular pressure similarly increased indicating a reduction, though not significant, of the valvular orifice. Forces ranged from 1N to 1.71N, compared to an EF of 22.16 ± 8.6N. Force varied significantly amongst different working conditions (normotensive, mild, and severe hypertensive) for each leaflet, whilst no significative variation was found on different leaflets in the same working condition. In the adopted experimental scenario, STD demonstrated comparable efficacy to the surgical strategy in restoring TV haemodynamic. The forces acting on the leaflets following STD implantation were far lower when compared to EFs.

Development of Novel Sutureless Balloon Expandable Fetal Heart Valve Device Using Absorbable Polycaprolactone Leaflets.

Congenital heart disease (CHD) accounts for nearly one-third of all congenital defects, and patients often require repeated heart valve replacements throughout their lives, due to failed surgical repairs and lack of durability of bioprosthetic valve implants. This objective of this study is to develop and in vitro test a fetal transcatheter pulmonary valve replacement (FTPVR) using sutureless techniques to attach leaflets, as an option to correct congenital defects such as pulmonary atresia with intact ventricular septum (PA/IVS), in utero. A balloon expandable design was analyzed using computational simulations to identify areas of failure. Five manufactured valves were assembled using the unique sutureless approach and tested in the fetal right heart simulator (FRHS) to evaluate hemodynamic characteristics. Computational simulations showed that the commissural loads on the leaflet material were significantly reduced by changing the attachment techniques. Hemodynamic analysis showed an effective orifice area of 0.08 cm2, a mean transvalvular pressure gradient of 7.52mmHg, and a regurgitation fraction of 8.42%, calculated over 100 consecutive cardiac cycles. In conclusion, the FTPVR exhibited good hemodynamic characteristics, and studies with biodegradable stent materials are underway.

Transcatheter Aortic Valve Replacement in Degenerated Perceval Bioprosthesis: Clinical and Technical Aspects in 32 Cases.

Sutureless aortic bioprostheses are increasingly being used to provide shorter cross-clamp time and facilitate minimally invasive aortic valve replacement. As the use of sutureless valves has increased over the past decade, we begin to encounter their degeneration. We describe clinical outcomes and technical aspects in patients with degenerated sutureless Perceval (CorCym, Italy) aortic bioprosthesis treated with valve-in-valve transcatheter aortic valve replacement (VIV-TAVR). Between March 2011 and March 2023, 1310 patients underwent aortic valve replacement (AVR) with Perceval bioprosthesis implantation. Severe bioprosthesis degeneration treated with VIV-TAVR occurred in 32 patients with a mean of 6.4 ± 1.9 years (range: 2-10 years) after first implantation. Mean EuroSCORE II was 9.5 ± 6.4% (range: 1.9-35.1%). Thirty of thirty-two (94%) VIV-TAVR were performed via transfemoral and two (6%) via transapical approach. Vascular complications occurred in two patients (6%), and mean hospital stay was 4.6 ± 2.4 days. At mean follow-up of 16.7 ± 15.2 months (range: 1-50 months), survival was 100%, and mean transvalvular pressure gradient was 18.7 ± 5.3 mmHg. VIV-TAVR is a useful option for degenerated Perceval and appears safe and effective. This procedure is associated with good clinical results and excellent hemodynamic performance in our largest single-center experience.

Effect of TAVR commissural alignment on coronary flow: A fluid-structure interaction analysis

Background and ObjectivesCoronary obstruction is a complication that may affect patients receiving Transcatheter Aortic Valve Replacement (TAVR), with catastrophic consequences and long-term negative effects. To enable healthy coronary perfusion, it is fundamental to appropriately position the device with respect to the coronary ostia. Nonetheless, most TAVR delivery systems do not control commissural alignment to do so. Moreover, no in silico study has directly assessed the effect of commissural alignment on coronary perfusion. This work aims to evaluate the effect of TAVR commissural alignment on coronary perfusion and device performance. MethodsA two-way computational fluid-structure interaction model is used to predict coronary perfusion at different commissural alignments. Moreover, in each scenario, hemodynamic biomarkers are evaluated to assess device performance. ResultsCommissural misalignment is shown to reduce the total coronary perfusion by −3.2% and the flow rate to a single coronary branch by −6.8%. It is also observed to impair valvular function by reducing the systolic geometric orifice area by −2.5% and increasing the systolic transvalvular pressure gradients by +5.3% and the diastolic leaflet stresses by +16.0%. ConclusionsThe present TAVR patient model indicates that coronary perfusion, hemodynamic and structural performance are minimized when the prosthesis commissures are fully misaligned with the native ones. These results support the importance of enabling axial control in new TAVR delivery catheter systems and defining recommended values of commissural alignment in upcoming clinical treatment guidelines.

Self-Expanding Transcatheter Aortic Valves Optimize Transvalvular Hemodynamics Independent of Intra- Versus Supra-Annular Design

This study sought to characterize transvalvular hemodynamics during the first 30days after transcatheter aortic valve implantation (TAVI) across various transcatheter heart valves (THVs), while adjusting for annular dimensions. This was an observational study of TAVIs from September 2021 to October 2022. The primary outcome was mean transvalvular pressure gradient (TVPG), measured using transthoracic echocardiography at day 0, day 1, and day 30 post-TAVI, and were compared across 3 THV, including the self-expandable intra-annular Portico (Abbott Vascular, Santa Clara, California) valve, the balloon-expandable SAPIEN 3 Ultra (Edwards Lifesciences, Irvine, California), and the self-expandable supra-annular Evolut Pro+ (Medtronic, Minneapolis, Minnesota). A total of 560 patients who underwent TAVI were identified, of which 106 (18.9%) received a Portico THV, 176 (31.4%) received a SAPIEN THV, and 278 (49.6%) received an Evolut THV. For Portico THV, the TVPG on day 0 increased from 6.0 (4.7 to 9.0) to 7.0 (6.0 to 10.0) by day 30 (p=0.009). For SAPIEN THV, the TVPG on day 0 increased from 6.5 (5.0 to 8.0) to 12.0 (9.0 to 15.0) by day 30 (p <0.001). For Evolut THV, the TVPG on day 0 increased from 6.0 (5.0 to 9.0) to 7.2 (5.0 to 10.0) by day 30 (p=0.001). Adjusting for time and annular diameter in a multivariable mixed effects model, the SAPIEN group had a significantly greater increase in TVPG over time than the Evolut reference group (p <0.001), while there was no difference in the change of TVPG over time for the Portico group vs. the Evolut group (p=0.874). In conclusion, compared with balloon-expandable valves, self-expanding THV may optimize transvalvular hemodynamics across all annular diameters, independent of their supra-annular and intra-annular design.

Bio-Inspired Fiber Reinforcement for Aortic Valves: Scaffold Production Process and Characterization.

The application of tissue-engineered heart valves in the high-pressure circulatory system is still challenging. One possible solution is the development of biohybrid scaffolds with textile reinforcement to achieve improved mechanical properties. In this article, we present a manufacturing process of bio-inspired fiber reinforcement for an aortic valve scaffold. The reinforcement structure consists of polyvinylidene difluoride monofilament fibers that are biomimetically arranged by a novel winding process. The fibers were embedded and fixated into electrospun polycarbonate urethane on a cylindrical collector. The scaffold was characterized by biaxial tensile strength, bending stiffness, burst pressure and hemodynamically in a mock circulation system. The produced fiber-reinforced scaffold showed adequate acute mechanical and hemodynamic properties. The transvalvular pressure gradient was 3.02 ± 0.26 mmHg with an effective orifice area of 2.12 ± 0.22 cm2. The valves sustained aortic conditions, fulfilling the ISO-5840 standards. The fiber-reinforced scaffold failed in a circumferential direction at a stress of 461.64 ± 58.87 N/m and a strain of 49.43 ± 7.53%. These values were above the levels of tested native heart valve tissue. Overall, we demonstrated a novel manufacturing approach to develop a fiber-reinforced biomimetic scaffold for aortic heart valve tissue engineering. The characterization showed that this approach is promising for an in situ valve replacement.

Balloon-Expandable Versus Self-Expanding Transcatheter Aortic Valve Implantation in Patients With Small Aortic Annulus: A Meta-Analysis

Although transcatheter aortic valve implantation (TAVI) is considered a superior option to surgery in patients with small aortic annulus (SAA), it is not clear which type of transcatheter heart valve (THV) has better results in terms of echocardiographic hemodynamics and clinical outcomes. A random-effects meta-analysis was performed comparing balloon-expandable valves (BEVs) and self-expanding valves (SEVs) in patients with SAA who underwent TAVI regarding their impact on hemodynamic and clinical outcomes at short- and midterm follow-up. Relative risk (RR) and mean difference (MD) with 95% confidence interval (95% CI) were measured for the outcomes, as appropriate. Subgroup analyses were performed based on the generation type of devices and study designs. A total of 16 articles comprising 1 randomized trial, 3 propensity-matched studies, and 12 observational studies including 4,341 patients (1,967 in BEV and 2,374 in the SEV group) with SAA were included. The implantation of BEVs correlated with a lower indexed effective orifice area (MD -0.19 [-0.25 to -0.13]) and higher transvalvular mean pressure gradient (MD 3.91, 95% CI 2.96 to 4.87). Compared with SEVs, BEVs had increased risk of prosthesis-patient mismatch (PPM; RR 2.09, 95% CI 1.79 to 2.45) and severe PPM (RR 2.16, 95% CI 1.48 to 3.15). However, BEV had lower moderate and severe paravalvular leak (RR 0.45, 95% CI 0.29 to 0.69), risk of stroke (RR 0.57, 95% CI 0.42 to 0.76), and permanent pacemaker implantation (RR 0.63, 95% CI 0.44 to 0.91). The 1-year all-cause mortality (RR 1.13, 95% CI 0.86 to 1.49) and cardiac-related mortality (RR 1.53, 95% CI 0.24 to 9.81) were not different between the 2 groups. In conclusion, SEVs were associated with larger indexed effective orifice area and lower PPM but higher paravalvular leak. In contrast, patients with SEVs were more likely to develop stroke and required permanent pacemaker implantation. Both THVs did not show difference in terms of early and midterm all-cause and cardiac mortality. Because both types of THVs show similar results regarding mortality data, hemodynamics should be among the factors considered in decision making for patients with SAA who underwent TAVI.

Functional mechanical behavior of the murine pulmonary heart valve

Genetically modified mouse models provide a versatile and efficient platform to extend our understanding of the underlying disease processes and evaluate potential treatments for congenital heart valve diseases. However, applications have been limited to the gene and molecular levels due to the small size of murine heart valves, which prohibits the use of standard mechanical evaluation and in vivo imaging methods. We have developed an integrated imaging/computational mechanics approach to evaluate, for the first time, the functional mechanical behavior of the murine pulmonary heart valve (mPV). We utilized extant mPV high resolution µCT images of 1-year-old healthy C57BL/6J mice, with mPVs loaded to 0, 10, 20 or 30 mmHg then chemically fixed to preserve their shape. Individual mPV leaflets and annular boundaries were segmented and key geometric quantities of interest defined and quantified. The resulting observed inter-valve variations were small and consistent at each TVP level. This allowed us to develop a high fidelity NURBS-based geometric model. From the resultant individual mPV geometries, we developed a mPV shape-evolving geometric model (SEGM) that accurately represented mPV shape changes as a continuous function of transvalvular pressure. The SEGM was then integrated into an isogeometric finite element based inverse model that estimated the individual leaflet and regional mPV mechanical behaviors. We demonstrated that the mPV leaflet mechanical behaviors were highly anisotropic and nonlinear, with substantial leaflet and regional variations. We also observed the presence of strong axial mechanical coupling, suggesting the important role of the underlying collagen fiber architecture in the mPV. When compared to larger mammalian species, the mPV exhibited substantially different mechanical behaviors. Thus, while qualitatively similar, the mPV exhibited important functional differences that will need to accounted for in murine heart valve studies. The results of this novel study will allow detailed murine tissue and organ level investigations of semi-lunar heart valve diseases.

An FSEI approach for the assessment of stenotic aortic valve effects on the left heart hemodynamics

Fluid–structure-electrophysiology interaction (FSEI) deals with (i) the active contraction of the myocardium, (ii) the complex blood motion and (iii) the related deformation of the cardiac tissues. This three-way coupled approach is key for obtaining predictive cardiac information as the tissue kinematics comes as a part of the solution, rather than being imposed as a boundary condition. FSEI is here applied to study the effects induced by aortic valve stenosis on the hemodynamics. This pathology, typically occurring in elderly individuals, is caused by the stiffening of the valve leaflets, thus impairing the valve functioning and reducing the pumping efficiency of the heart. The disease severity is gradually increased within a high-fidelity model for the left heart, while keeping the same geometrical, elastic and electrophysiological properties of the cardiac system, which would be impossible with in-vivo experiments. We observe an increase of the transvalvular pressure drop and of the peak velocity of the systolic jet velocity along with a reduction of the cardiac ejection fraction. Furthermore, a stenotic aortic valve significantly alters the wall shear stresses and their spatial distribution over the aortic arch and valve leaflets, which may induce a remodeling process of the ventricular myocardium. The numerical results from the multi-physics model are fully consistent with the clinical experience, thus further opening the way for computational engineering aided medical diagnostic.