Ineffective Orifice Area: Practical Limitations of Accurate EOA Assessment for Low-Gradient Heart Valve Prostheses.

PURPOSE: The goal of this study was to demonstrate the range in effective orifice area (EOA) values that may be possible given the ISO 5840 definition of EOA and the practical limits in the accurate measurement of pressure differential across large diameter valves. METHODS: A 31 mm mechanical valve was tested on a commercially available pulse duplicator configured for mitral valve testing and tuned to nominal conditions. The experimental data was used as a basis for performing Monte Carlo analyses with published specifications for commonly used pressure sensors as well as measurement equipment accuracy requirements described in ISO 5840. The sources of error were modeled as normally distributed random variables and the simulation was iterated 1,000,000 times. RESULTS: Experimentally-derived EOAs ranged from 2.7 to 5.0 cm2, while the Monte Carlo simulation provided results ranging from approximately 0.4 to 6.7 cm2. Many of these results are clearly non-physical with EOAs larger than the valve's geometric orifice area and exceedingly short positive pressure differential periods, yet they align with other published results for the same valve model. CONCLUSIONS: The volatility of the standard EOA formulation at low mean gradients combined with the difficulty in accurately measuring such small differentials with industry-standard fluid pressure transducers results in a performance metric which is very sensitive to test execution, particularly for low-gradient prostheses.

Transcatheter aortic valve deployment influences neo-sinus thrombosis risk: An in vitro flow study.

OBJECTIVES: We investigated the impact of (transcatheter heart valve) THV expansion at the level of the native annulus and implant depth on valve performance and neo-sinus flow stasis. BACKGROUND: Flow stasis in the neo-sinus is one of the identified risk factors of THV thrombosis. METHODS: A 29 mm CoreValve and 26 mm SAPIEN 3 were deployed under different expansions (CoreValve, SAPIEN 3) and implant depths (CoreValve) within a patient-derived aortic root in a pulse duplicator. Fluorescent dye was injected during diastole into the neo-sinus and imaged over 20 cardiac cycles. Washout times were computed as a measure of flow stasis for each deployment. RESULTS: The 10% CoreValve under-expansion improved neo-sinus washout over full expansion by 8% (p < .001), and higher CoreValve implant depth improved neo-sinus washout (p < .001). The 10% SAPIEN 3 under-expansion improved neo-sinus washout by 23% (p < .001). Under-expansion of both valve types caused higher pressure gradients and smaller effective orifice areas than full expansion. CONCLUSIONS: Neo-sinus flow stasis is influenced by THV expansion and implant depth (CoreValve). The 10% valve under-deployment (oversizing) may facilitate reduced flow stasis in the neo-sinus with minimal increase in pressure gradients. This strategy may be helpful for patient anatomies, which are in-between transcatheter valve sizes.

A mechanistic investigation of the EDWARDS INTUITY Elite valve's hemodynamic performance.

OBJECTIVE: Rapid deployment surgical aortic valve replacement has emerged as an alternative to the contemporary sutured valve technique. A difference in transvalvular pressure has been observed clinically between RD-SAVR and contemporary SAVR. A mechanistic inquiry into the impact of the rapid deployment valve inflow frame design on the left ventricular outflow tract and valve hemodynamics is needed. METHODS: A 23 mm EDWARDS INTUITY Elite rapid deployment valve and a control contemporary, sutured valve, a 23 mm Magna Ease valve, were implanted in an explanted human heart by an experienced cardiac surgeon. Per convention, the rapid deployment valve was implanted with three non-pledgeted, simple guiding sutures, while fifteen pledgeted, mattress sutures were used to implant the contemporary surgical valve. In vitro flow models were created from micro-computed tomography scans of the implanted valves and surrounding cardiac anatomy. Particle image velocimetry and hydrodynamic characterization experiments were conducted in the vicinity of the valves in a validated pulsatile flow loop system. RESULTS: The rapid deployment and control valves were found to have mean transvalvular pressure gradients of 7.92 ± 0.37 and 10.13 ± 0.48 mmHg, respectively. The inflow frame of the rapid deployment valve formed a larger, more circular, left ventricular outflow tract compared to the control valve. Furthermore, it was found that the presence of the control valve's sub-annular pledgets compromised its velocity distribution and consequently its pressure gradient. CONCLUSIONS: The rapid deployment valve's intra-annular inflow frame provides for a larger, left ventricular outflow tract, thus reducing the transvalvular pressure gradient and improving overall hemodynamic performance.

An Evaluation of the Influence of Coronary Flow on Transcatheter Heart Valve Neo-Sinus Flow Stasis.

Transcatheter heart valve (THV) leaflet thrombosis in the neo-sinus and associated reduced leaflet motion is of clinical concern due to risks of embolism and worsened valve hemodynamics. Flow stasis in the neo-sinus (the space between the native and THV leaflets) is a known risk factor, but the role of proximal coronary flow is yet to be investigated. We tested two replicas of FDA approved commercial THVs-intra-annular and supra-annular (similar to the SAPIEN 3 and CoreValve families)-in a left heart simulator with coronary flow. Velocity fields in the left coronary cusp (LCC) and non (NCC) neo-sinus were quantified using high speed particle image velocimetry and particle residence times (PRT) were computed to evaluate flow stasis in the region. The supra-annular THV LCC neo-sinus had shorter PRT than its NCC neo-sinus (0.66 ± 0.00 vs. 0.76 ± 0.04, p = 0.038), while the intra-annular THV LCC neo-sinus had similar PRT to its NCC neo-sinus (1.93 ± 0.05 vs. 1.92 ± 0.03 cycles, p = 0.889). The supra-annular valve LCC and NCC neo-sinuses had shorter PRT than their intra-annular valve counterparts (p < 0.001). These results showed that coronary flow reduces flow stasis in the supra-annular THV neo-sinus and, ostensibly, thrombosis risk in the region. This effect was not significant in the intra-annular valve.

A Systematic Review of Cost-Effectiveness Analyses of Left Ventricular Assist Devices: Issues and Challenges.

BACKGROUND: Advanced heart failure (HF) can be treated conservatively or aggressively, with left ventricular assist devices (LVADs) and heart transplant (HT) being the most aggressive strategies. OBJECTIVE: The goal of this review was to identify, describe, critique and summarize published cost-effectiveness analyses on LVADs for adults with HF. METHODS: We conducted a literature search using PubMed and ProQuest DIALOG databases to identify English-language publications from 2006 to 2017 describing cost-effectiveness analyses of LVADs and reviewed them against inclusion criteria. Those that met criteria were obtained for full-text review and abstracted if they continued to meet study requirements. RESULTS: A total of 12 cost-effectiveness studies (13 articles) were identified, all of which described models; they were almost evenly split between those examining LVADs as destination therapy (DT) or as bridge to transplant (BTT). Studies were Markov or semi-Markov models with one- or three-month cycles that followed patients until death. Inputs came from a variety of sources, with the REMATCH trial and INTERMACS registry common clinical data sources, although some publications also used data from studies at their own institutions. Costs were derived from standard sources in many studies but from individual hospital data in some. Inputs for health utilities, which were used in 11 of 12 studies, were generally derived from two studies. None of the studies reported a societal perspective, that is, included non-medical costs such as caregiving. CONCLUSIONS: No study found LVADs to be cost effective for DT or BTT with base case assumptions, although incremental cost-effectiveness ratios met thresholds for cost effectiveness in some probabilistic analyses. With constant improvements in LVADs and expanding indications, understanding and re-evaluating the cost effectiveness of their use will be critical to making treatment decisions.

Characterization of aortic root geometry in transcatheter aortic valve replacement patients.

PURPOSE: The study aimed to characterize the geometry of the aortic root pre- and post-transcatheter aortic valve replacement (TAVR) and investigate differences in pre- and post-TAVR anatomy. BACKGROUND: A greater understanding of how aortic root geometry changes after TAVR is needed to facilitate further investigation into the hemodynamic profiles of the post-TAVR aortic root. METHODS: Anatomical measurements were conducted on de-identified, retrospective post-TAVR 4DCT scans of 109 patients with aortic stenosis obtained from the RESOLVE study. The diameter of the aortic root was measured at the level of the annulus, left ventricular outflow tract (LVOT), sinus of Valsalva, sinotubular junction (STJ) and ascending aorta. The heights of the STJ and coronary arteries were also measured. RESULTS: All aortic root dimensions were normally distributed across the cohort and changed significantly between pre- and post-TAVR conditions (P < 0.01). Post-TAVR dimensions changed significantly from peak systole to end diastole (P < 0.01). Regression models were obtained for all aortic root dimensions in terms of annulus diameter with excellent coefficient of determination (R2 > 0.95, P < 0.001). CONCLUSIONS: There are significant differences between pre- and post-TAVR as well as peak systolic and end diastolic aortic root anatomy. Appropriate anatomical dimensions should be selected for benchtop testing as the geometry varies greatly throughout the cardiac cycle.

The Fluid Mechanics of Transcatheter Heart Valve Leaflet Thrombosis in the Neosinus.

BACKGROUND: Transcatheter heart valve (THV) thrombosis has been increasingly reported. In these studies, thrombus quantification has been based on a 2-dimensional assessment of a 3-dimensional phenomenon. METHODS: Postprocedural, 4-dimensional, volume-rendered CT data of patients with CoreValve, Evolut R, and SAPIEN 3 transcatheter aortic valve replacement enrolled in the RESOLVE study (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Dysfunction With Multimodality Imaging and Its Treatment with Anticoagulation) were included in this analysis. Patients on anticoagulation were excluded. SAPIEN 3 and CoreValve/Evolut R patients with and without hypoattenuated leaflet thickening were included to study differences between groups. Patients were classified as having THV thrombosis if there was any evidence of hypoattenuated leaflet thickening. Anatomic and THV deployment geometries were analyzed, and thrombus volumes were computed through manual 3-dimensional reconstruction. We aimed to identify and evaluate risk factors that contribute to THV thrombosis through the combination of retrospective clinical data analysis and in vitro imaging in the space between the native and THV leaflets (neosinus). RESULTS: SAPIEN 3 valves with leaflet thrombosis were on average 10% further expanded (by diameter) than those without (95.5±5.2% versus 85.4±3.9%; P<0.001). However, this relationship was not evident with the CoreValve/Evolut R. In CoreValve/Evolut Rs with thrombosis, the thrombus volume increased linearly with implant depth (R2=0.7, P<0.001). This finding was not seen in the SAPIEN 3. The in vitro analysis showed that a supraannular THV deployment resulted in a nearly 7-fold decrease in stagnation zone size (velocities <0.1 m/s) when compared with an intraannular deployment. In addition, the in vitro model indicated that the size of the stagnation zone increased as cardiac output decreased. CONCLUSIONS: Although transcatheter aortic valve replacement thrombosis is a multifactorial process involving foreign materials, patient-specific blood chemistry, and complex flow patterns, our study indicates that deployed THV geometry may have implications on the occurrence of thrombosis. In addition, a supraannular neosinus may reduce thrombosis risk because of reduced flow stasis. Although additional prospective studies are needed to further develop strategies for minimizing thrombus burden, these results may help identify patients at higher thrombosis risk and aid in the development of next-generation devices with reduced thrombosis risk.

Aortic Regurgitation Generates a Kinematic Obstruction Which Hinders Left Ventricular Filling.

An incompetent aortic valve (AV) results in aortic regurgitation (AR), where retrograde flow of blood into the left ventricle (LV) is observed. In this work, we parametrically characterized the detailed changes in intra-ventricular flow during diastole as a result of AR in a physiological in vitro left-heart simulator (LHS). The loss of energy within the LV as the level of AR increased was also assessed. The validated LHS consisted of an optically-clear, flexible wall LV and a modular AV holder. Two-component, planar, digital particle image velocimetry was used to visualize and quantify intra-ventricular flow. A large coherent vortical structure which engulfed the whole LV was observed under control conditions. In the cases with AR, the regurgitant jet was observed to generate a "kinematic obstruction" between the mitral valve and the LV apex, preventing the trans-mitral jet from generating a coherent vortical structure. The regurgitant jet was also observed to impinge on the inferolateral wall of the LV. Energy dissipation rate (EDR) for no, trace, mild, and moderate AR were found to be 1.15, 2.26, 3.56, and 5.99 W/m3, respectively. This study has, for the first time, performed an in vitro characterization of intra-ventricular flow in the presence of AR. Mechanistically, the formation of a "kinematic obstruction" appears to be the cause of the increased EDR (a metric quantifiable in vivo) during AR. EDR increases non-linearly with AR fraction and could potentially be used as a metric to grade severity of AR and develop clinical interventional timing strategies for patients.

On the Mechanics of Transcatheter Aortic Valve Replacement.

Transcatheter aortic valves (TAVs) represent the latest advances in prosthetic heart valve technology. TAVs are truly transformational as they bring the benefit of heart valve replacement to patients that would otherwise not be operated on. Nevertheless, like any new device technology, the high expectations are dampened with growing concerns arising from frequent complications that develop in patients, indicating that the technology is far from being mature. Some of the most common complications that plague current TAV devices include malpositioning, crimp-induced leaflet damage, paravalvular leak, thrombosis, conduction abnormalities and prosthesis-patient mismatch. In this article, we provide an in-depth review of the current state-of-the-art pertaining the mechanics of TAVs while highlighting various studies guiding clinicians, regulatory agencies, and next-generation device designers.

The Effect of Valve-in-Valve Implantation Height on Sinus Flow.

Valve-in-valve transcatheter aortic valve replacement (VIV-TAVR) has proven to be a successful treatment for high risk patients with failing aortic surgical bioprostheses. However, thrombus formation on the leaflets of the valve has emerged as a major issue in such procedures, posing a risk of restenosis, thromboembolism, and reduced durability. In this work we attempted to understand the effect of deployment position of the transcatheter heart valve (THV) on the spatio-temporal flow field within the sinus in VIV-TAVR. Experiments were performed in an in vitro pulsatile left heart simulator using high-speed Particle Image Velocimetry (PIV) to measure the flow field in the sinus region. The time-resolved velocity data was used to understand the qualitative and quantitative flow patterns. In addition, a particle tracking technique was used to evaluate relative thrombosis risk via sinus washout. The velocity data demonstrate that implantation position directly affects sinus flow patterns, leading to increased flow stagnation with increasing deployment height. The particle tracking simulations showed that implantation position directly affected washout time, with the highest implantation resulting in the least washout. These results clearly demonstrate the flow pattern and flow stagnation in the sinus is sensitive to THV position. It is, therefore, important for the interventional cardiologist and cardiac surgeon to consider how deployment position could impact flow stagnation during VIV-TAVR.

Valve Type, Size, and Deployment Location Affect Hemodynamics in an In Vitro Valve-in-Valve Model.

OBJECTIVES: The purpose of this study was to optimize hemodynamic performance of valve-in-valve (VIV) according to transcatheter heart valve (THV) type (balloon vs. self-expandable), size, and deployment positions in an in vitro model. BACKGROUND: VIV transcatheter aortic valve replacement is increasingly used for the treatment of patients with a failing surgical bioprosthesis. However, there is a paucity in understanding the THV hemodynamic performance in this setting. METHODS: VIV transcatheter aortic valve replacement was simulated in a physiologic left heart simulator by deploying a 23-mm SAPIEN, 23-mm CoreValve, and 26-mm CoreValve within a 23-mm Edwards PERIMOUNT surgical bioprosthesis. Each THV was deployed into 5 different positions: normal (inflow of THV was juxtaposed with inflow of surgical bioprosthesis), -3 and -6 mm subannular, and +3 and +6 mm supra-annular. At a heart rate of 70 bpm and cardiac output of 5.0 l/min, mean transvalvular pressure gradients (TVPG), regurgitant fraction (RF), effective orifice area, pinwheeling index, and pullout forces were evaluated and compared between THVs. RESULTS: Although all THV deployments resulted in hemodynamics that would have been consistent with Valve Academic Research Consortium-2 procedure success, we found significant differences between THV type, size, and deployment position. For a SAPIEN valve, hemodynamic performance improved with a supra-annular deployment, with the best performance observed at +6 mm. Compared with a normal position, +6 mm resulted in lower TVPG (9.31 ± 0.22 mm Hg vs. 11.66 ± 0.22 mm Hg; p < 0.01), RF (0.95 ± 0.60% vs. 1.27 ± 0.66%; p < 0.01), and PI (1.23 ± 0.22% vs. 3.46 ± 0.18%; p < 0.01), and higher effective orifice area (1.51 ± 0.08 cm(2) vs. 1.35 ± 0.02 cm(2); p < 0.01) at the cost of lower pullout forces (5.54 ± 0.20 N vs. 7.09 ± 0.49 N; p < 0.01). For both CoreValve sizes, optimal deployment was observed at the normal position. The 26-mm CoreValve, when compared with the 23-mm CoreValve and 23-mm SAPIEN, had a lower TVPG (7.76 ± 0.14 mm Hg vs. 10.27 ± 0.18 mm Hg vs. 9.31 ± 0.22 mm Hg; p < 0.01) and higher effective orifice area (1.66 ± 0.05 cm(2) vs. 1.44 ± 0.05 cm(2) vs. 1.51 ± 0.08 cm(2); p < 0.01), RF (4.79 ± 0.67% vs. 1.98 ± 0.36% vs. 0.95 ± 1.68%; p < 0.01), PI (29.13 ± 0.22% vs. 6.57 ± 0.14% vs. 1.23 ± 0.22%; p < 0.01), and pullout forces (10.65 ± 0.66 N vs. 5.35 ± 0.18 N vs. 5.54 ± 0.20 N; p < 0.01). CONCLUSIONS: The optimal deployment location for VIV in a 23 PERIMOUNT surgical bioprosthesis was at a +6 mm supra-annular position for a 23-mm SAPIEN valve and at the normal position for both the 23-mm and 26-mm CoreValves. The 26-mm CoreValve had lower gradients, but higher RF and PI than the 23-mm CoreValve and the 23-mm SAPIEN. In their optimal positions, all valves resulted in hemodynamics consistent with the definitions of Valve Academic Research Consortium-2 procedural success. Long-term studies are needed to understand the clinical impact of these hemodynamic performance differences in patients who undergo VIV transcatheter aortic valve replacement.

How Can We Help a Patient With a Small Failing Bioprosthesis?: An In Vitro Case Study.

OBJECTIVES: The aim of this study was to investigate the hemodynamic performance of a transcatheter heart valve (THV) deployed at different valve-in-valve positions in an in vitro model using a small surgical bioprosthesis. BACKGROUND: Patients at high surgical risk with failing 19-mm surgical aortic bioprostheses are not candidates for valve-in-valve transcatheter aortic valve replacement, because of risk for high transvalvular pressure gradients (TVPGs) and patient-prosthesis mismatch. METHODS: A 19-mm stented aortic bioprosthesis was mounted into the aortic chamber of a pulse duplicator, and a 23-mm low-profile balloon-expandable THV was deployed (valve-in-valve) in 4 positions: normal (bottom of the THV stent aligned with the bottom of the surgical bioprosthesis sewing ring) and 3, 6, and 8 mm above the normal position. Under controlled hemodynamic status, the effect of these THV positions on valve performance (mean TVPG, geometric orifice area, and effective orifice area), thrombotic potential (sinus shear stress), and migration risk (pullout force and embolization flow rate) were assessed. RESULTS: Compared with normal implantation, a progressive reduction of mean TVPG was observed with each supra-annular THV position (normal: 33.10 mm Hg; 3 mm: 24.69 mm Hg; 6 mm: 19.16 mm Hg; and 8 mm: 12.98 mm Hg; p < 0.001). Simultaneously, we observed increases in geometric orifice area (normal: 0.83 cm(2); 8 mm: 1.60 cm(2); p < 0.001) and effective orifice area (normal: 0.80 cm(2); 8 mm: 1.28 cm(2); p < 0.001) and reductions in sinus shear stresses (normal: 153 dyne/cm(2); 8 mm: 40 dyne/cm(2); p < 0.001), pullout forces (normal: 1.55 N; 8 mm: 0.68 N; p < 0.05), and embolization flow rates (normal: 32.91 l/min; 8 mm: 26.06 l/min; p < 0.01). CONCLUSIONS: Supra-annular implantation of a THV in a small surgical bioprosthesis reduces mean TVPG but may increase the risk for leaflet thrombosis and valve migration. A 3- to 6-mm supra-annular deployment could be an optimal position in these cases.