Background: This study assessed the long-term hemodynamic functional performance of the new Inspiris Resilia aortic valve after accelerated wear testing (AWT). Methods: Three 21-mm and 23-mm Inspiris valves were used for the AWT procedure. After 1 billion cycles (equivalent to 25 years), the valves' hemodynamic performance was compared with that of the corresponding zero-cycled condition. Next, 1 AWT cycled valve of each valve size was selected at random for particle image velocimetry (PIV) and leaflet kinematic tests, and the data were compared with data for an uncycled Inspiris Resilia aortic valve of the same size. PIV was used to quantitatively evaluate flow fields downstream of the valve. Valves were tested according to International Standards Organization 5840-2:2015 protocols. Results: The 21-mm and 23-mm valves met the International Organization for Standardization (ISO) durability performance requirements to 1 billion cycles. The mean effective orifice areas for the 21-mm and 23-mm zero-cycled and 1 billion–cycled valves were 1.89 ± 0.02 cm2 and 1.94 ± 0.01 cm2, respectively (P < .05) and 2.3 ± 0.13 cm2 and 2.40 ± 0.11 cm2, respectively (P < .05). Flow characterization of the control valves and the study valves demonstrated similar flow characteristics. The velocity and shear stress fields were also similar in the control and study valves. Conclusions: The Inspiris Resilia aortic valve demonstrated very good durability and hemodynamic performance after an equivalent of 25 years of simulated in vitro accelerated wear. The study valves exceeded 1 billion cycles of simulated wear, 5 times longer than the standard requirement for a tissue valve as stipulated in ISO 5840-2:2015.

The authors report a closed-chest, transcatheter large-vessel connection (hepatic conduit to azygous vein) to reverse pulmonary arteriovenous malformations in a 10-year-old patient after Fontan for heterotaxy/interrupted inferior vena cava, with an increase in oxygen saturation from 78% to 96%. Computational fluid dynamics estimated a 14-fold increase in hepatic blood flow to the left pulmonary artery (from 1.3% to 14%). (Level of Difficulty: Advanced.)

This study evaluates reliability of current technology for measurement of renal arterial blood flow by breath-held velocity-encoded MRI. Overall accuracy was determined by comparing MRI measurements with known flow in controlled flow loop phantom studies. Measurements using prospective and retrospective gating methods were compared in phantom studies with pulsatile flow, not revealing significant differences. Phantom study results showed good accuracy with deviations from true flow consistently below 13% for vessel diameters 3 mm and above. Reproducibility in human subjects was evaluated by repeat studies in six healthy control subjects, comparing immediate repetition of the scan, repetition of the scan plane scouting, and week-to-week variation in repeated studies. The standard deviation in the four-week protocol of repeated in-vivo measurements of single-kidney renal flow in normal subjects was 59.7 ml/min, corresponding with an average coefficient of variation of 10.55%. Comparison of RBF reproducibility with and without gadolinium contrast showed no significant differences in mean or standard deviation. A breakdown among error components showed corresponding marginal standard deviations (coefficients of variation) 23.8 ml/min (4.21%) for immediate repetition of the breath-held flow scan, 39.13 ml/min (6.90%) for repeated plane scouting, and 40.76 ml/min (7.20%) for weekly fluctuations in renal blood flow.

HIF1A is significantly upregulated in calcified human aortic valves (AVs). Furthermore, HIF1A inhibitor PX-478 was shown to inhibit AV calcification under static and disturbed flow conditions. Since elevated stretch is one of the major mechanical stimuli for AV calcification, we investigated the effect of PX-478 on AV calcification and collagen turnover under a pathophysiological cyclic stretch (15%) condition. Porcine aortic valve (PAV) leaflets were cyclically (1 Hz) stretched at 15% for 24 days in osteogenic medium with or without PX-478. In addition, PAV leaflets were cyclically stretched at a physiological (10%) and 15% for 3 days in regular medium to assess its effect of on HIF1A mRNA expression. It was found that 100 μM (high concentration) PX-478 could significantly inhibit PAV calcification under 15% stretch, whereas 50 μM (moderate concentration) PX-478 showed a modest inhibitory effect on PAV calcification. Nonetheless, 50 μM PX-478 significantly reduced PAV collagen turnover under 15% stretch. Surprisingly, it was observed that cyclic stretch (15% vs. 10%) did not have any significant effect on HIF1A mRNA expression in PAV leaflets. These results suggest that HIF1A inhibitor PX-478 may impart its anti-calcific and anti-matrix remodeling effect in a stretch-independent manner.

Background: A clinical study comparing the hemodynamic outcomes of transcatheter mitral valve replacement (TMVR) with vs. without Laceration of the Anterior Mitral leaflet to Prevent Outflow Obstruction (LAMPOON) has never been designed nor conducted. Aims: To quantify the hemodynamic impact of LAMPOON in TMVR using patient-specific computational (in silico) models. Materials: Eight subjects from the LAMPOON investigational device exemption trial were included who had acceptable computed tomography (CT) data for analysis. All subjects were anticipated to be at prohibitive risk of left ventricular outflow tract (LVOT) obstruction from TMVR, and underwent successful LAMPOON immediately followed by TMVR. Using post-procedure CT scans, two 3D anatomical models were created for each subject: (1) TMVR with LAMPOON (performed procedure), and (2) TMVR without LAMPOON (virtual control). A validated computational fluid dynamics (CFD) paradigm was then used to simulate the hemodynamic outcomes for each condition. Results: LAMPOON exposed on average 2 ± 0.6 transcatheter valve cells (70 ± 20 mm2 total increase in outflow area) which provided an additional pathway for flow into the LVOT. As compared to TMVR without LAMPOON, TMVR with LAMPOON resulted in lower peak LVOT velocity, lower peak LVOT gradient, and higher peak LVOT effective orifice area by 0.4 ± 0.3 m/s (14 ± 7% improvement, p = 0.006), 7.6 ± 10.9 mmHg (31 ± 17% improvement, p = 0.01), and 0.2 ± 0.1 cm2 (17 ± 9% improvement, p = 0.002), respectively. Conclusion: This was the first study to permit a quantitative, patient-specific comparison of LVOT hemodynamics following TMVR with and without LAMPOON. The LAMPOON procedure achieved a critical increment in outflow area which was effective for improving LVOT hemodynamics, particularly for subjects with a small neo-left ventricular outflow tract (neo-LVOT).

Objective: The study objective was to develop a novel annuloplasty ring with regional flexibility and assess its suture force dynamics in healthy ovine subjects, as compared to fully-rigid or fully-flexible rings. Methods: Materially heterogeneous rings were created with rigid anterior and posterior, and flexible commissural segments. These rings were created to match the geometry of the Medtronic Profile 3D ring. Each ring was instrumented with ten force transducers to measure cyclic suture forces (FC) and undersized annuloplasty was performed in six healthy ovine subjects. FC were recorded and examined for cardiac cycles reaching a maximum left ventricular pressure of 100, 125, and 150mmHg. FC was compared to previously reported values from fully-rigid Profile 3D and fully-flexible prototype rings. Results: Relative to the fully-rigid, the heterogeneous ring exhibited 48% reduction in Fc at its commissural (rigid vs heterogeneous: 1.80 ± 0.94N vs 0.95 ± 0.52N, p<0.001) and 32% reduction in posterior (1.90 ± 0.92N vs 1.29 ± 0.91N, p <0.001) regions, but not in its anterior region (2.45 ± 1.21N vs 2.23 ± 1.22N, p = 0.279). Relative to the fully-flexible ring, the heterogeneous ring exhibited no significant differences in FC in any region. Conclusions: The reduced FC of the heterogeneous ring relative to the fully-rigid ring, suggest a promising approach to reduce suture loading, while preserving the annular remodeling capability of fully-rigid rings. Future studies in diseased subjects are necessary to explore repair effectiveness of this ring.

Patients with aortic heart valve disease are limited to valve replacements that lack the ability to grow and remodel. This presents a major challenge for pediatric patients who require a valve capable of somatic growth and at a smaller size. A patient-specific heart valve capable of growth and remodeling while maintaining proper valve function would address this major issue. Here, we recreate the native valve leaflet structure composed of poly-ε-caprolactone (PCL) and cell-laden gelatin-methacrylate/poly (ethylene glycol) diacrylate (GelMA/PEGDA) hydrogels using 3D printing and molding, and then evaluate the ability of the multilayered scaffold to produce collagen matrix under physiological shear stress conditions. We also characterized the valve hemodynamics under aortic physiological flow conditions. The valve's fibrosa layer was replicated by 3D printing PCL in a circumferential direction similar to collagen alignment in the native leaflet, and GelMA/PEGDA sustained and promoted cell viability in the spongiosa/ventricularis layers. We found that collagen type I production can be increased in the multilayered scaffold when it is exposed to pulsatile shear stress conditions over static conditions. When the PCL component was mounted onto a valve ring and tested under physiological aortic valve conditions, the hemodynamics were comparable to commercially available valves. Our results demonstrate that a structurally representative valve leaflet can be generated using 3D printing and that the PCL layer of the leaflet can sustain proper valve function under physiological aortic valve conditions.

Background Annuloplasty ring dehiscence is a well described mode of mitral valve repair failure. Defining the mechanisms underlying dehiscence may facilitate its prevention. Methods: Factors that govern suture dehiscence were examined with an ovine model. After undersized ring annuloplasty in live animals (n = 5), cyclic force (F C ) that acts on sutures during cardiac contraction was measured with custom transducers. F C was measured at ten suture positions, throughout cardiac cycles with peak left ventricular pressure (LVP max ) of 100, 125, and 150 mm Hg. Suture pullout testing was conducted on explanted mitral annuli (n = 12) to determine suture holding strength at each position. Finally, relative collagen density differences at suture sites around the annulus were assessed by two-photon excitation fluoroscopy. Results: Anterior F C exceeded posterior F C at each LVP max (eg, 2.8 ± 1.3 N versus 1.8 ± 1.2 N at LVP max = 125 mm Hg, p < 0.01). Anterior holding strength exceeded posterior holding strength (6.4 ± 3.6 N versus 3.9 ± 1.6 N, p < 0.0001). On the basis of F C at LVP max of 150 mm Hg, margin of safety before suture pullout was vastly higher between the trigones (exclusive) versus elsewhere (4.8 ± 0.9 N versus 1.9 ± 0.5 N, p < 0.001). Margin of safety exhibited strong correlation to collagen density (R 2 = 0.947). Conclusions: Despite lower cyclic loading on posterior sutures, the weaker posterior mitral annular tissue creates higher risk of dehiscence, apparently because of reduced collagen content. Sutures placed atop the trigones are less secure than predicted, because of a combination of reduced collagen and higher overall rigidity in this region. These findings highlight the inter-trigonal tissue as the superior anchor and have implications on the design and implantation techniques for next-generation mitral prostheses.

Background: Using a bifurcated Y-graft as the Fontan baffle is hypothesized to streamline and improve flow dynamics through the total cavopulmonary connection (TCPC). This study conducted numerical simulations to evaluate this hypothesis using postoperative data from 5 patients. Methods: Patients were imaged with cardiac magnetic resonance or computed tomography after receiving a bifurcated aorto-iliac Y-graft as their Fontan conduit. Numerical simulations were performed using in vivo flow rates, as well as 2 levels of simulated exercise. Two TCPC models were virtually created for each patient to serve as the basis for hemodynamic comparison. Comparative metrics included connection flow resistance and inferior vena caval flow distribution. Results: Results demonstrate good hemodynamic outcomes for the Y-graft options. The consistency of inferior vena caval flow distribution was improved over TCPC controls, whereas the connection resistances were generally no different from the TCPC values, except for 1 case in which there was a marked improvement under both resting and exercise conditions. Examination of the connection hemodynamics as they relate to surgical Y-graft implementation identified critical strategies and modifications that are needed to potentially realize the theoretical efficiency of such bifurcated connection designs. Conclusions: Five consecutive patients received a Y-graft connection to complete their Fontan procedure with positive hemodynamic results. Refining the surgical technique for implementation should result in further energetic improvements that may help improve long-term outcomes.

Background: Aortic arch reconstruction in neonates is commonly performed using deep hypothermic circulatory arrest. However, concerns have arisen regarding potential adverse neurologic outcomes from this complex procedure, raising questions about the best arterial cannulation approach for cerebral perfusion and effective systemic hypothermia. In this study, we use computational fluid dynamics to investigate the effect of different cannulation strategies in neonates. Methods: We used a realistic template of a hypoplastic neonatal aorta as the base geometry to investigate four cannulation options: (1) right innominate artery, (2) innominate root, (3) patent ductus arteriosus (PDA), or (4) innominate root and PDA. Performance was evaluated according to the numerically predicted cerebral and systemic flow distributions compared with physiologic perfusion under neonatal conditions. Results: The four cannulation strategies were associated with different local hemodynamics; however, this did not translate into any significant effect on the measured flow distributions. The largest difference only represented 0.8% of the cardiac output and was measured in the innominate artery, which received 23.2% of the cardiac output in option 3 vs 24% in option 4. Pulmonary artery snaring benefited all systemic vessels uniformly. Conclusions: Because of the very high vascular resistances in neonates, downstream vascular resistances dictated flow distribution to the different vascular beds rather than the cannulation strategy, allowing the surgical team to choose their method of preference. However, patients with aortic coarctation warrant further investigation and will most likely benefit from a 2-cannulae approach (option 4).