Optimization of Enzymatic and Chemical Decellularization of Native Porcine Heart Valves for the Generation of Decellularized Xenografts.

One of the most important medical interventions for individuals with heart valvular disease is heart valve replacement, which is not without substantial challenges, particularly for pediatric patients. Due to their biological properties and biocompatibility, natural tissue-originated scaffolds derived from human or animal sources are one type of scaffold that is widely used in tissue engineering. However, they are known for their high potential for immunogenicity. Being free of cells and genetic material, decellularized xenografts, consequently, have low immunogenicity and, thus, are expected to be tolerated by the recipient's immune system. The scaffold ultrastructure and ECM composition can be affected by cell removal agents. Therefore, applying an appropriate method that preserves intact the structure of the ECM plays a critical role in the final result. So far, there has not been an effective decellularization technique that preserves the integrity of the heart valve's ultrastructure while securing the least amount of genetic material left. This study demonstrates a new protocol with untraceable cells and residual DNA, thereby maximally reducing any chance of immunogenicity. The mechanical and biochemical properties of the ECM resemble those of native heart valves. Results from this study strongly indicate that different critical factors, such as ionic detergent omission, the substitution of Triton X-100 with Tergitol, and using a lower concentration of trypsin and a higher concentration of DNase and RNase, play a significant role in maintaining intact the ultrastructure and function of the ECM.

Tricuspid Regurgitation and TAVR: Outcomes, Risk Factors and Biomarkers.

Background. The significance of concomitant tricuspid regurgitation (TR) in the context of transcatheter aortic valve replacement (TAVR) remains unclear. This study aimed to analyze the severity of TR before and after TAVR with regard to short- and long-term survival and to analyze the influencing factors. Methods. In our retrospective analysis, TR before and after TAVR was examined and patients were classified into groups accordingly. Special attention was paid to patients with post-interventional changes in TR. Mortality after TAVR was considered the primary endpoint of the analysis and major complications according to the Valve Academic Research Consortium 3 (VARC3) were compared. Moreover, biomarkers and risk factors for worsening or improvement of TR through TAVR were analyzed. Results. Among 775 patients who underwent TAVR in our center between January 2009 and December 2019, 686 patients (89%) featured low- and 89 patients (11%) high-grade TR. High-grade pre-TAVR TR was associated with worse short- (30-day), mid- (2-year) and long-term survival up to 8 years. Even though in nearly half of the patients with high-grade TR the regurgitation improved within seven days after TAVR (n = 42/89), this did not result in a survival benefit for this subgroup. On the other hand, a worsening of low-grade TR was seen in more than 10% of the patients (n = 73/686), which was also associated with a worse prognosis. Predictors of worsening of TR after TAVR were adipositas, impaired right ventricular function and the presence of mild TR. Age, atrial fibrillation, COPD, impaired renal function and elevated cardiac biomarkers were risk factors for mortality after TAVR independent from the grade of TR. Conclusions. Not only pre-interventional, but also post-TAVR high-grade TR is associated with a worse prognosis after TAVR. TAVR can change concomitant tricuspid regurgitation, but improvement does not have any impact on short- and long-term survival. Worsening of TR after TAVR is possible and impairs the prognosis.

Redo-TAVI with the ACURATE neo2 and Prime XL for balloon-expandable transcatheter heart valve failure.

BACKGROUND: There are limited data regarding treatment for failed balloon-expandable transcatheter heart valves (THVs) in redo-transcatheter aortic valve implantation (TAVI). AIMS: We aimed to assess THV performance, neoskirt height and expansion when performing redo-TAVI with the ACURATE platform inside a SAPIEN 3 (S3) compared to redo-TAVI with an S3 in an S3. METHODS: Redo-TAVI was performed on the bench using each available size of the S3, the ACURATE neo2 (ACn2) and the next-generation ACURATE Prime XL (AC XL) implanted at 2 different depths within 20 mm/23 mm/26 mm/29 mm S3s serving as the "failed" index THV. Hydrodynamic testing was performed to assess THV function. Multimodality assessment was performed using photography, X-ray, microcomputed tomography (micro-CT), and high-speed videos. RESULTS: The ACURATE in S3 combinations had favourable hydrodynamic performance compared to the S3 in S3 for all size combinations. In the 20 mm S3, redo-TAVI with the ACn2 had lower gradients compared to the S3 (mean gradient 16.3 mmHg for the ACn2 vs 24.7 mmHg for the 20 mm S3 in 20 mm S3). Pinwheeling was less marked for the ACURATE THVs than for the S3s. On micro-CT, the S3s used for redo-TAVI were underexpanded across all sizes. This was also observed for the ACURATE platform, but to a lesser extent. CONCLUSIONS: Redo-TAVI with an ACn2/AC XL within an S3 has favourable hydrodynamic performance and less pinwheeling compared to an S3 in S3. This comes at the price of a taller neoskirt.

Sensor-guided transcatheter aortic valve replacement.

OBJECTIVES: The SavvyWire(OpSens Medical) is a support wire for transcatheter aortic valve replacement (TAVR) procedures that, in addition to its dedicated left ventricle (LV) pacing capabilities, has a distal pressure sensor that measures live transvalvular hemodynamics during the procedure. We aimed to determine the safety, efficacy, and functionality of the SavvyWire during TAVR procedures in an all-comer population. METHODS: We performed a multicentric, prospective, observational, single-arm, all-comers registry of patients with symptomatic, severe aortic stenosis undergoing TAVR in 3 Canadian centers. Data were collected in a dedicated database, and pre-specified questionnaires were fulfilled by the heart team implanters after each procedure. RESULTS: A total of 60 patients were included (mean age: 78.6 ± 7.2 years; 51% women; mean Society of Thoracic Surgeons score: 2.2 ± 1.6%). TAVR was performed through a transfemoral approach in 90% of cases, and balloon- and self-expandable valves were used in 73% and 27% of patients, respectively. There were no cases of LV perforation, guidewire deformation, significant loss of capture, or major software malfunction. The rate of successful delivery of the TAVR system was 100%, and effective LV pacing was achieved in 98% of patients. The pre-TAVR mean gradient was 39 ± 14 mm Hg while the final post-TAVR gradient was 8 ± 5 mm Hg; the mean aortic systolic pressure during rapid pacing was 54 ± 12 mm Hg. In 97% of the TAVR procedures, SavvyWire's functionality was reported to be better or similar to other TAVR workhorse support wires. CONCLUSIONS: SavvyWire was safe, effective, and functional for live transvalvular hemodynamic evaluation and rapid pacing during TAVR procedures. More studies with larger sample sizes and comparison against different wires and gradient measurement methods are warranted.

Lifetime Management of Patients With Severe Aortic Stenosis in the Era of Transcatheter Aortic Valve Replacement.

Aortic stenosis is the most common valvular disease. Surgical aortic valve replacement (SAVR) using mechanical valves has been the preferred treatment for younger patients, but bioprosthetic valves are gaining favour to avoid anticoagulation with warfarin. Transcatheter aortic valve replacement (TAVR) was approved in recent years for the treatment of severe aortic stenosis in intermediate- and low-risk patients as an alternative to SAVR. The longer life expectancy of these groups of patients might exceed the durability of the TAVR or SAVR bioprosthetic valves. Therefore, many patients need 2 or even 3 interventions during their lifetime. Because it has important implications on the feasibility of subsequent procedures, the decision between opting for SAVR or TAVR as the primary procedure requires thorough consideration by the heart team, incorporating patient preferences, clinical indicators, and anatomic aspects. If TAVR is favoured initially, selecting the valve type and determining the implantation level should be conducted, aiming for positive outcomes in the index intervention and keeping in mind the potential for subsequent TAVR-in-TAVR procedures. When SAVR is selected as the primary procedure, the operator must make choices regarding the valve type and the potential need for aortic root enlargement, with the intention of facilitating future valve-in-valve interventions. This narrative review examines the existing evidence concerning the lifelong management of severe aortic stenosis, delving into available treatment strategies, particularly emphasising the initial procedure's selection and its impact on subsequent interventions.

Age- and Sex-Specific Nomographic CT Quantitative Plaque Data From a Large International Cohort.

BACKGROUND: With growing adoption of coronary computed tomographic angiography (CTA), there is increasing evidence for and interest in the prognostic importance of atherosclerotic plaque volume. Manual tools for plaque segmentation are cumbersome, and their routine implementation in clinical practice is limited. OBJECTIVES: The aim of this study was to develop nomographic quantitative plaque values from a large consecutive multicenter cohort using coronary CTA. METHODS: Quantitative assessment of total atherosclerotic plaque and plaque subtype volumes was performed in patients undergoing clinically indicated coronary CTA, using an Artificial Intelligence-Enabled Quantitative Coronary Plaque Analysis tool. RESULTS: A total of 11,808 patients were included in the analysis; their mean age was 62.7 ± 12.2 years, and 5,423 (45.9%) were women. The median total plaque volume was 223 mm3 (IQR: 29-614 mm3) and was significantly higher in male participants (360 mm3; IQR: 78-805 mm3) compared with female participants (108 mm3; IQR: 10-388 mm3) (P < 0.0001). Total plaque increased with age in both male and female patients. Younger patients exhibited a higher prevalence of noncalcified plaque. The distribution of total plaque volume and its components was reported in every decile by age group and sex. CONCLUSIONS: The authors developed pragmatic age- and sex-stratified percentile nomograms for atherosclerotic plaque measures using findings from coronary CTA. The impact of age and sex on total plaque and its components should be considered in the risk-benefit analysis when treating patients. Artificial Intelligence-Enabled Quantitative Coronary Plaque Analysis work flows could provide context to better interpret coronary computed tomographic angiographic measures and could be integrated into clinical decision making.

Producing and Testing Prototype Tissue-Engineered 3D Tri-Leaflet Valved Stents on Biodegradable Poly-ε-Caprolactone Scaffolds.

Transcatheter pulmonary valve replacement is a minimally-invasive alternative treatment for right ventricular outflow tract dysfunction and has been rapidly evolving over the past years. Heart valve prostheses currently available still have major limitations. Therefore, one of the significant challenges for the future is the roll out of transcatheter tissue engineered pulmonary valve replacement to more patients. In the present study, biodegradable poly-ε-caprolactone (PCL) nanofiber scaffolds in the form of a 3D leaflet matrix were successfully seeded with human endothelial colony-forming cells (ECFCs), human induced pluripotent stem cell-derived MSCs (hMSCs), and porcine MSCs (pMSCs) for three weeks for the generation of 3D tissue-engineered tri-leaflet valved stent grafts. The cell adhesion, proliferation, and distribution of these 3D heart leaflets was analyzed using fluorescence microscopy and scanning electron microscopy (SEM). All cell lineages were able to increase the overgrown leaflet area within the three-week timeframe. While hMSCs showed a consistent growth rate over the course of three weeks, ECFSs showed almost no increase between days 7 and 14 until a growth spurt appeared between days 14 and 21. More than 90% of heart valve leaflets were covered with cells after the full three-week culturing cycle in nearly all leaflet areas, regardless of which cell type was used. This study shows that seeded biodegradable PCL nanofiber scaffolds incorporated in nitinol or biodegradable stents will offer a new therapeutic option in the future.

Case Report: Stretching the limits-late valvuloplasty for THV dysfunction following redo mitral valve-in-valve implantation.

Late balloon valvuloplasty can be used to treat under-expansion-related transcatheter heart valve (THV) dysfunction. Whether this can be performed following redo-THV implantation is unknown. Herein, we report a case of a 72-year-old male presenting with symptomatic gradient elevation following redo mitral valve-in-valve implantation. The patient was successfully treated with late balloon valvuloplasty with gradient improvement. In conclusion, late valvuloplasty is effective even with several layers of valves. However, larger studies are required to clarify the role of this approach further.

Redo Transcatheter Aortic Valve Implantation in the Lotus Mechanically Expanded Transcatheter Heart Valve: Bench-Top Analysis, Clinical Experience, and Procedural Guidance.

BACKGROUND: Redo transcatheter aortic valve implantation (TAVI) is increasing as patients outlive their transcatheter heart valves (THVs) and present with bioprosthetic valve failure. The Lotus mechanically expanded THV has unique design characteristics, which have specific implications for Redo TAVI. METHODS: The design features of the Lotus valve and their relevance to Redo TAVI were reviewed. Bench-top analysis of Redo TAVI was performed using different contemporary THVs. Procedural and outcome data were obtained from 10 patients who had undergone Redo TAVI for Lotus bioprosthetic valve failure in 5 centers. Recommendations for performing Redo TAVI in Lotus are made, based on these findings. RESULTS: The Lotus leaflets extend from the frame inflow, with a Neoskirt of only 13 mm, hence a low risk of coronary obstruction during Redo TAVI. The Lotus frame posts prevent full apposition of the Redo prosthesis in the upper part of the frame, while implantation of the Redo THV above the Lotus inflow leads to inadequate apposition of the Lotus leaflets. Inflow-to-inflow positioning is therefore recommended for effective sealing and leaflet pinning. The Lotus locking mechanism prevents overexpansion of the frame, limiting Redo THV oversizing. Redo TAVI was favorable with SAPIEN 3, Evolut, and Navitor THVs on bench-top analysis but not with ACURATE Neo 2 due to the upper crowns and short stent preventing inflow-to-inflow deployment. Case review demonstrated satisfactory outcomes in 10 patients treated with Evolut (n=6), SAPIEN 3 (n=3), and Portico (n=1) valves, with no mortality, major morbidity, or coronary obstruction. Three patients had residual mean gradient ≥20 mm Hg, including 2 of 3 SAPIEN cases. Guidance on procedural planning, valve choice, sizing, and positioning is provided. CONCLUSIONS: Redo TAVI in Lotus requires an understanding of unique design characteristics, and adherence to key procedural recommendations, but can be safely and effectively performed with most contemporary valve types.

Challenges and Future Directions in Redo Aortic Valve Reintervention After Transcatheter Aortic Valve Replacement Failure.

Transcatheter aortic valve replacement (TAVR) is increasingly being performed in younger and lower surgical risk patients. Reintervention for failed transcatheter heart valves will likely increase in the future as younger patients are expected to outlive the initial bioprosthesis. While redo-TAVR has emerged as an attractive and less invasive alternative to surgical explantation (TAVR-explant) to treat transcatheter heart valve failure, it may not be feasible in all patients due to the risk of coronary obstruction and impaired coronary access. Conversely, TAVR-explant can be offered to most patients who are surgical candidates, but the reported outcomes have shown high mortality and morbidity. This review provides the latest evidence, current challenges, and future directions on redo-TAVR and TAVR-explant for transcatheter heart valve failure, to guide aortic valve reintervention and facilitate patients' lifetime management of aortic stenosis.

Feasibility of Coronary Access Following Redo-TAVR for Evolut Failure: A Computed Tomography Simulation Study.

BACKGROUND: Coronary accessibility following redo-transcatheter aortic valve replacement (redo-TAVR) is increasingly important, particularly in younger low-risk patients. This study aimed to predict coronary accessibility after simulated Sapien-3 balloon-expandable valve implantation within an Evolut supra-annular, self-expanding valve using pre-TAVR computed tomography (CT) imaging. METHODS: A total of 219 pre-TAVR CT scans from the Evolut Low-Risk CT substudy were analyzed. Virtual Evolut and Sapien-3 valves were sized using CT-based diameters. Two initial Evolut implant depths were analyzed, 3 and 5 mm. Coronary accessibility was evaluated for 2 Sapien-3 in Evolut implant positions: Sapien-3 outflow at Evolut node 4 and Evolut node 5. RESULTS: With a 3-mm initial Evolut implant depth, suitable coronary access was predicted in 84% of patients with the Sapien-3 outflow at Evolut node 4, and in 31% of cases with the Sapien-3 outflow at Evolut node 5 (P<0.001). Coronary accessibility improved with a 5-mm Evolut implant depth: 97% at node 4 and 65% at node 5 (P<0.001). When comparing 3- to 5-mm Evolut implant depth, sinus sequestration was the lowest with Sapien-3 outflow at Evolut node 4 (13% versus 2%; P<0.001), and the highest at Evolut node 5 (61% versus 32%; P<0.001). CONCLUSIONS: Coronary accessibility after Sapien-3 in Evolut redo-TAVR relates to the initial Evolut implant depth, the Sapien-3 outflow position within the Evolut, and the native annular anatomy. This CT-based quantitative analysis may provide useful information to inform and refine individualized preprocedural CT planning of the initial TAVR and guide lifetime management for future coronary access after redo-TAVR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02701283.

Restoration of flow in the aorta: a novel therapeutic target in aortic valve intervention.

Aortic blood flow patterns are closely linked to the morphology and function of the left ventricle, aortic valve and aorta. These flow patterns demonstrate the exceptional adaptability of the cardiovascular system to maintain blood circulation under a broad range of haemodynamic workloads and can be altered in various pathophysiological states. For instance, normal ascending aortic systolic flow is predominantly laminar, whereas abnormal aortic systolic flow is associated with increased eccentricity, vorticity and flow reversal. These flow abnormalities result in reduced aortic conduit function and increased energy loss in the cardiovascular system. Emerging evidence details the association of these flow patterns with loss of aortic compliance, which leads to adverse left ventricular remodelling, poor tissue perfusion, and an increased risk of morbidity and death. In this Perspective article, we review the evidence for the link between aortic flow-related abnormalities and cardiovascular disease and how these changes in aortic flow patterns are emerging as a therapeutic target for aortic valve intervention in first-in-human studies.

TAVR in TAVR: Where Are We in 2023 for Management of Failed TAVR Valves?

PURPOSE OF REVIEW: As TAVR is increasingly performed on younger patients with a longer life expectancy, the number of redo-TAVR procedures is likely to increase in the coming years. Limited data is currently available on this sometimes challenging procedure. We provide a summary of currently published literature on management of patients with a failed transcatheter aortic valve. RECENT FINDINGS: Recent registry data have increased the clinical knowledge on redo-TAVR. Additionally, numerous bench studies have provided valuable insights into the technical aspects of redo-TAVR with various combinations of valve types. Redo-TAVR can be performed safely in selected cases with a high procedural success and good short-term outcomes. However, at present, the procedure remains relatively infrequent and many patients are not eligible. Bench testing can be useful to understand important concepts such as valve expansion, neoskirt, leaflet overhang, and leaflet deflection as well as their potential clinical implications.

Update on Transcatheter Treatment of Mitral and Tricuspid Valve Regurgitation.

PURPOSE OF REVIEW: Mitral and tricuspid regurgitation represents a clinical challenge. They are associated with a poor prognosis, and many patients are not eligible for conventional surgery. Transcatheter therapies have been the focus of numerous studies and devices over the past decade. Here, we provide a summary of current options for transcatheter treatment of these 2 entities. RECENT FINDINGS: Recent studies have demonstrated the benefits of edge-to-edge repair for increasing numbers of patients. Encouraging early results with transcatheter valve replacement are also becoming available. To date, transcatheter edge-to-edge repair is currently the first-line transcatheter treatment for both mitral and tricuspid regurgitation for many patients who are not candidates for surgery. A number of transcatheter replacement devices are under development and clinical investigation but, for the most part, their current use is limited to compassionate cases or clinical trials.