Decellularization Following Fixation of Explanted Aortic Valves as a Strategy for Preserving Native Mechanical Properties and Function

Mechanical or biological aortic valves are incorporated in physical cardiac simulators for surgical training, educational purposes, and device testing. They suffer from limitations including either a lack of anatomical and biomechanical accuracy or a short lifespan, hence limiting the authentic hands-on learning experience. Medical schools utilize hearts from human cadavers for teaching and research, but these formaldehyde-fixed aortic valves contort and stiffen relative to native valves. Here, we compare a panel of different chemical treatment methods on explanted porcine aortic valves and evaluate the microscopic and macroscopic features of each treatment with a primary focus on mechanical function. A surfactant-based decellularization method after formaldehyde fixation is shown to have mechanical properties close to those of the native aortic valve. Valves treated in this method were integrated into a custom-built left heart cardiac simulator to test their hemodynamic performance. This decellularization, post-fixation technique produced aortic valves which have ultimate stress and elastic modulus in the range of the native leaflets. Decellularization of fixed valves reduced the valvular regurgitation by 60% compared to formaldehyde-fixed valves. This fixation method has implications for scenarios where the dynamic function of preserved valves is required, such as in surgical trainers or device test rigs.

Two-Year Clinical Follow-Up Assessment of the Novel Cingular Surgical Bovine Pericardial Valve

Objectives: To evaluate the 2-year clinical safety and hemodynamic outcomes of the Cingular bovine pericardial bioprosthesis.Methods: A prospective, multicenter, single-arm trial was conducted in patients who required aortic or mitral valve replacement. From March 2016 to October 2017, 197 patients were implanted with the Cingular bovine pericardial valve at five sites in China. The clinical outcomes and hemodynamic performance were assessed through a 2-year follow-up. Clinical safety events were reviewed by an independent clinical events committee, and echocardiographic data were assessed by an independent core laboratory.Results: The mean age was 66.9 ± 4.9 years. The 2-year survival rate was 96.4%. A complete 2-year clinical follow-up was achieved in 189 of 190 survivors. No case of structural valve deterioration, major perivalvular leak, prosthetic valve endocarditis, or valve-related reoperation was seen. For the aortic valve, the mean pressure gradient observed was 12.5 ± 4.0 mm Hg, and the effective orifice area (EOA) was 2.0 ± 0.3 cm2. For the smaller size aortic valves, 19 mm and 21 mm, respective mean EOA values of 1.7 ± 0.2 cm2 and 1.8 ± 0.2 cm2 were found. The values for mean pressure gradient and mean EOA for mitral bioprostheses were 4.0 ± 1.4 mm Hg and 2.2 ± 0.3 cm2, respectively. There was no significant change between 1-year and 2-year hemodynamic performance.Conclusions: The Cingular bovine pericardial valve showed favorable clinical safety and hemodynamic outcomes over a 2-year follow-up. Further follow-up is required to validate the long-term durability.

CorFix: Virtual Reality Cardiac Surgical Planning Software for Designing Patient-Specific Vascular Grafts: Development and Pilot Usability Study (Preprint)

BACKGROUND Patients with single ventricle heart defects receives three stages of surgeries culminating in the Fontan surgery. During the Fontan surgery, a vascular graft is sutured between the inferior vena cava and pulmonary artery to divert deoxygenated blood flow to the lungs via passive flow. Customizing the graft configuration can maximize the long-term benefits of Fontan surgery. However, planning patient-specific surgery has several challenges including the ability for physicians to customize grafts and evaluate its hemodynamic performance. OBJECTIVE The aim of this study was to develop a virtual reality (VR) Fontan graft modeling and evaluation software for physicians. User study was performed to achieve three additional goals: 1) evaluate the software when used by medical doctors and engineers, 2) identify if doctors have a baseline intuition about hemodynamic performance of Fontan grafts in a VR setting, and 3) explore the impact of viewing hemodynamic simulation results in numerical and graphical formats. METHODS A total of 5 medical professionals including 4 physicians (1 fourth-year resident, 1 third-year cardiac fellow, 1 pediatric intensivist, and 1 pediatric cardiac surgeon) and 1 biomedical engineer voluntarily participated in the study. The study was pre-scripted to minimize the variability of the interactions between the experimenter and the participants. Unless a participant was familiar with the Fontan surgery, a quick information session was provided at the start. Then, all participants were trained to use the VR gear and our software, CorFix. Each participant designed one bifurcated and one tube-shaped Fontan graft for a single patient. Then a hemodynamic performance evaluation was completed, allowing the participants to further modify their tube-shaped design. The design time and hemodynamic performance for each graft design were recorded. At the end of the study, all participants were provided surveys to evaluate the usability and learnability of the software and rate the intensity of VR sickness. RESULTS The average time for creating one bifurcated and one tube-shaped grafts after a single 10-minute training were 13.40 and 5.49 minutes, accordingly. Three out of 5 bifurcated and 1 out of 5 tube-shaped graft designs were in the benchmark range of hepatic flow distribution. Reviewing hemodynamic performance results and modifying the tube-shaped design took an average time of 2.92 minutes. Participants who modified their tube-shaped graft designs were able to improve the non-physiologic wall shear stress percentage by 7.02%. All tube-shaped graft designs improved wall shear stress compared the native surgical case of the patient. None of the designs met the benchmark indexed power loss. CONCLUSIONS VR graft design software can quickly be taught to physicians without any engineering background and VR experience. Improving the system of CorFix could improve performance of the users in customizing and optimizing grafts for patients. With graphical visualization, physicians were able to improve wall shear stress of a tube-shaped graft, lowering the chance of thrombosis. Bifurcated graft designs showed potential strength in better flow split to the lungs, reducing the risk for pulmonary arteriovenous malformations.

One-Year Hemodynamic Performance of Three Cardiac Aortic Bioprostheses: A Randomized Comparative Clinical Trial

Background: We aimed to compare 1 year the hemodynamic in-vivo performance of three biological aortic prostheses (Carpentier Perimount Magna EaseTM, Crown PRTTM, and TrifectaTM). Methods: The sample used in this study comes from the “BEST-VALVE” clinical trial, which is a phase IV single-blinded randomized clinical trial with the three above-mentioned prostheses. Results: 154 patients were included. Carpentier Perimount Magna EaseTM (n = 48, 31.2%), Crown PRTTM (n = 51, 32.1%) and TrifectaTM (n = 55, 35.7%). One year after the surgery, the mean aortic gradient and the peak aortic velocity was 17.5 (IQR 11.3–26) and 227.1 (IQR 202.0–268.8) for Carpentier Perimount Magna EaseTM, 21.4 (IQR 14.5–26.7) and 237.8 (IQR 195.9–261.9) for Crown PRTTM, and 13 (IQR 9.6–17.8) and 209.7 (IQR 176.5–241.4) for TrifectaTM, respectively. Pairwise comparisons demonstrated improved mean gradients and maximum velocity of TrifectaTM as compared to Crown PRTTM. Among patients with nominal prosthesis sizes ≤21, the mean and peak aortic gradient was higher for Crown PRTTM compared with TrifectaTM, and in patients with an aortic annulus measured with metric Hegar dilators less than or equal to 22 mm. Conclusions: One year after surgery, the three prostheses presented a different hemodynamic performance, being TrifectaTM superior to Crown PRTTM.

Sutureless aortic valve replacement: a meta-analysis

Background and objectives Sutureless aortic valves aim to achieve better outcomes and to aid and facilitate the minimally invasive aortic valve replacement procedure by tackling the issue of cross clamp time, which is an independent predictor of post-operative outcomes especially in patients with serious comorbidities. (2, 3) By reducing the number of sutures, the time for sutures placement is reduced. (1) Our Meta-analysis tries to assess the safety and hemodynamic performance of the sutureless aortic valve prosthesis’s in an attempt to ascertain their benefits as a viable alternative to current established measures. Methodology From their beginnings to February 2017, electronic searches were conducted using six databases. Relevant studies using commercially accessible suture-free valves to replace the aortic valve have been recognized. Based on the predefined endpoints, data were collected and analyzed. Results FC For incorporation in qualitative and quantitative analyses, twenty-four studies were recognized, with a total number of 5073 patients undergoing sutureless aortic valve replacement (SU-AVR). Mortality incidence at 30 days and 12 months follow-ups were 2.5% and 2.7%, respectively, while the incidence of thromboembolic events (1.6%) and paravalvular leak (PVL) (0.5%) were acceptable. Conclusion Current available evidence indicates that sutureless aortic valve replacement is a safe operation showing low mortality and complication rates, with satisfactory hemodynamic performance.

Rate, correlates, and outcomes of hemodynamic valve deterioration after transcatheter aortic valve replacement

Objectives Treatment expenditure of transcatheter aortic valve replacement (TAVR) to younger individuals may potentially be limited by valve durability. Long-term hemodynamic performance of transcatheter aortic valves is not well documented. This study sought to determine the incidence, predisposing factors and outcomes of hemodynamic valve deterioration (HVD) after TAVR. Methods Consecutive patients undergoing TAVR between May 2007 and December 2018 (67.0% Sapien, 14.6% Evolut, 6.8% Acurate, 6.8% Portico, 4.8% other) were prospectively studied. Baseline assessment included echocardiography, laboratory, and clinical assessment. Echocardiographic and laboratory follow-up after TAVR was performed prior to discharge, at 3 and 12 months, and yearly thereafter. HVD was defined by Doppler assessment according to Valve Academic Research Consortium 3 criteria as a ≥10 mm Hg increase in mean gradient to ≥20 mm Hg OR worsening of (para-)prosthetic regurgitation ≥1/3 class to ≥moderate. The primary endpoint was the incidence of HVD. All-cause mortality served as secondary endpoint. Multivariate cox regression was used for outcome analysis. Results 649 patients (82.2±6.7 y/o, 55.5% female, EuroSCORE II 4.4±1.0) were analyzed. Among survivors with available echo data from ≥2 follow-ups (n=382), the incidence of HVD was 6.8% (n=26; 4.1% per valve-year), with no difference between valve types. Modes of HVD were stenosis (n=8), regurgitation (n=14), and both (n=4). Median time to HVD was 14.2 months (interquartile range, 9.4 to 35.0 months), and was significantly shorter in patients in the highest age quartile (Q4 vs. Q1–3: log-rank, p<0.01, Figure). Also, increased age was the only factor that independently predisposed for HVD (Q4 vs. Q1–3: adjusted hazard ratio [adj HR]: 2.86, 95% confidence interval [CI]: 1.30–6.30, p<0.01). Following TAVR, 355 patients (54.7%) had died after 64.2±31.9 months. Independent predictors of mortality were (para-)prosthetic regurgitation >mild at discharge (HR: 1.58, 95% CI: 1.21–2.06, p<0.001), male sex (HR: 1.57, 95% CI: 1.24–2.00, p<0.001), baseline NT-proBNP serum levels (graded into quartiles, HR: 1.31, 95% CI: 1.17–1.46, p<0.001), and diabetes (HR: 1.38, 95% CI: 1.08–1.76, p=0.011), but not time-dependent HVD (p>0.05, Figure). Conclusion This study reports good hemodynamic performance of transcatheter aortic valves up to 8 years following intervention. The incidence of HVD, which may develop over time – especially in the elderly –, is low and does not impact survival. Conversely, (para-)prosthetic regurgitation early after TAVR conveys detrimental prognostic implications and needs to be avoided – particularly in younger patients. FUNDunding Acknowledgement Type of funding sources: None. Hemodynamic valve deterioration in TAVR

Effects of a Short-Term Left Ventricular Assist Device on Hemodynamics in a Heart Failure Patient-Specific Aorta Model: A CFD Study

Patients with heart failure (HF) or undergoing cardiogenic shock and percutaneous coronary intervention require short-term cardiac support. Short-term cardiac support using a left ventricular assist device (LVAD) alters the pressure and flows of the vasculature by enhancing perfusion and improving the hemodynamic performance for the HF patients. However, due to the position of the inflow and outflow of the LVAD, the local hemodynamics within the aorta is altered with the LVAD support. Specifically, blood velocity, wall shear stress, and pressure difference are altered within the aorta. In this study, computational fluid dynamics (CFD) was used to elucidate the effects of a short-term LVAD for hemodynamic performance in a patient-specific aorta model. The three-dimensional (3D) geometric models of a patient-specific aorta and a short-term LVAD, Impella CP, were created. Velocity, wall shear stress, and pressure difference in the patient-specific aorta model with the Impella CP assistance were calculated and compared with the baseline values of the aorta without Impella CP support. Impella CP support augmented cardiac output, blood velocity, wall shear stress, and pressure difference in the aorta. The proposed CFD study could analyze the quantitative changes in the important hemodynamic parameters while considering the effects of Impella CP, and provide a scientific basis for further predicting and assessing the effects of these hemodynamic signals on the aorta.

Clinical results and 30-day outcomes of self-expanding transcatheter aortic valves: comparative case-matched analysis of CoreValve® versus ACURATE neo™

Background: Transcatheter aortic valve replacement (TAVR) is associated with excellent results in patients with severe aortic stenosis. In highly calcified aortic anuli with increased risk of annulus rupture and in favor of the supra-annular design, self-expandable prostheses are frequently used. In this regard, we aimed to perform a comparative analysis of clinical and 30-day outcomes after TAVR using the self-expanding CoreValve® Evolut R or ACURATE neo™ prosthesis. Methods: Out of 343 consecutive patients treated with either CoreValve® Evolut R or ACURATE neo™ from January 2014 to December 2017, 76 patients were assigned each per group after 1:1 propensity score matching in regard of preoperative characteristics. Pre- and periprocedural outcomes were retrospectively collected and assessed. Outcomes at 30 days are reported according to the established Valve Academic Research Consortium (VARC-2) criteria. Results: Device success and 30-day survival accounted for 93.4% ( n = 71), respectively 97.4% ( n = 74) in both groups (p = 1.00). No statistically significant differences regarding clinical parameters were observed. The combined safety endpoint at 30 days was comparable (84.2% ( n = 64) CoreValve® vs 85.5% ( n = 65) ACURATE neo™; p = 0.848). Except a trend toward higher stroke (p = 0.08) and pacemaker (p = 0.07) rate in the CoreValve® group, major vascular complications, incidence of life-threatening or disabling bleeding, and incidence of postoperative acute kidney injury were comparable. Postoperative hemodynamic parameters showed no significant differences between the implanted valves. Conclusion: Both self-expandable prostheses showed good postoperative hemodynamic performance with a low incidence of severe paravalvular leakage, all- cause mortality, and comparable clinical outcomes.