Ali N. Azadani

Transcatheter aortic valves inadequately relieve stenosis in small degenerated bioprostheses

OBJECTIVES Transcatheter aortic valves (TAVs) are a promising treatment for high risk surgical patients suffering from degeneration of previously implanted bioprostheses (valve-in-valve therapy). However, unlike native stenosed aortic valves which have accommodated Edwards SAPIEN transcatheter valves after valvuloplasty, rigid bioprostheses may prevent full TAV stent expansion and disrupt leaflet function. We hypothesized that current 23 mm TAVs would not completely relieve severe stenosis in small bioprosthetic valves. The objective of this study was to study the hemodynamics of TAVs in degenerated bioprostheses. METHODS Twelve TAVs designed to mimic the 23 mm SAPIEN valve were created. Using a pulse duplicator, hemodynamics of valve-in-valve implantation were measured within 19, 21, and 23 mm Carpentier-Edwards PERIMOUNT degenerated bioprostheses (n=6 each). Bioprosthetic degeneration was simulated using BioGlue to achieve a mean pressure gradient of 50 mmHg. RESULTS TAVs significantly reduced the mean pressure gradient (50.9+/-4.7-9.1+/-4.1 mmHg, P<0.001) and total energy loss (870.3+/-157.4-307.8+/-87.3 mJ, P<0.001) in 23 mm degenerated bioprostheses. In 21 mm bioprostheses, the pressure gradient (52.3+/-7.0-19.5+/-5.0 mmHg, P<0.001) and energy loss (785.5+/-128.1-477.8+/-123.2 mJ, P=0.007) were reduced significantly. However, no significant changes in the pressure gradient (57.1+/-4.3-46.5+/-9.3 mmHg, P=0.086) or energy loss (839.3+/-49.3-960.5+/-158.1 mJ, P=0.144) were obtained after TAVI implantation in 19 mm bioprostheses. Incomplete stent expansion resulted in leaflet distortion and central regurgitation when implanted in 19 and 21 mm bioprostheses. CONCLUSIONS The bioprosthetic annulus and stent posts offered a suitable landing zone for TAVs. However, oversized transcatheter valves were constrained by the rigid bioprostheses resulting in inadequate resolution of bioprosthetic stenosis. Hemodynamics of valve-in-valve intervention was worse than comparable size surgical valve replacements, particularly in 19 and 21 mm valves. Small degenerated bioprostheses require modification of current TAV design to yield acceptable hemodynamics.

Valve-in-Valve Implantation Using a Novel Supravalvular Transcatheter Aortic Valve: Proof of Concept

BACKGROUND Transcatheter valve implantation within degenerated bioprostheses is a potentially promising treatment for high-risk surgical patients. Clinical experience is limited; however, we have shown in vitro that currently available transcatheter aortic valve sizes did not provide acceptable hemodynamics in small bioprostheses. The objective of this study was to develop a new transcatheter valve that would provide good hemodynamics within degenerated bioprostheses. METHODS Supravalvular transcatheter valves were created using a Dacron covered stainless steel stent at the base and trileaflet pericardial leaflets in an open stent above the bioprosthesis. The transcatheter valves were implanted within 19-, 21-, and 23-mm Carpentier-Edwards Perimount bioprostheses with simulated degeneration using BioGlue to achieve a mean pressure gradient of 50 mm Hg. Hemodynamics of valve-in-valve implantation were studied in a pulse duplicator. RESULTS Supravalvular transcatheter valves successfully relieved bioprosthetic stenosis. Acceptable hemodynamics were achieved with a significant reduction in mean pressure gradient of 54.0 +/- 3.5 to 9.2 +/- 6.3 mm Hg in 23-mm bioprostheses (p < 0.001), from 49.3 +/- 3.1 to 14.4 +/- 4.7 mmHg (p < 0.001) in 21 mm, and from 53.9 +/- 3.8 to 28.3 +/- 9.8 mm Hg (p = 0.013) in 19-mm bioprostheses. Effective orifice area after valve-in-valve implantation increased significantly and was comparable to rereplacement with the same size bioprosthesis. CONCLUSIONS Valve-in-valve implantation was performed using a novel supravalvular transcatheter valve, which successfully relieved bioprosthetic stenosis. The hemodynamics were comparable with standard surgical valve replacement. Further studies are required to assess device safety and efficacy in patients.

Mechanical Properties of Surgical Glues Used in Aortic Root Replacement

BACKGROUND Surgical glues are used in mechanical, stentless bioprosthetic, and homograft aortic root replacements to seal and reinforce anastomotic suture lines. The aortic root normally undergoes substantial physiologic dilation and may be affected by the stiffness of applied sealants. We determined the material properties of four common commercial glues, comparing them with known properties of aortic root replacements. METHODS Samples of BioGlue (CryoLife, Inc, Kennesaw, GA), CoSeal (Baxter Healthcare International, Palo Alto, CA), Tisseel (Baxter Healthcare Corp, Glendale, CA), and Crosseal (OMRIX Biopharmaceuticals, Inc, New York, NY) sealants underwent biaxial tensile testing. A Hookean strain energy function was fit to the stress-strain response of each sample, and the Youngs modulus was obtained for comparison of material stiffness. RESULTS Sealants demonstrate a relatively linear response to loading; mean elastic moduli for BioGlue (3,122.04 +/- 1,639.68 kPa), CoSeal (100.02 +/- 67.60 kPa), Tisseel (102.59 +/- 41.13 kPa), and Crosseal (53.56 +/- 32.59 kPa) varied greatly. CoSeal and Tisseel have no significant difference in stiffness (p = 0.897) while Crosseal is more compliant than Tisseel (p = 0.004) and CoSeal (p = 0.055). BioGlue is stiffer than CoSeal, Tisseel, and Crosseal (p < 0.001). Furthermore, BioGlue is much stiffer than cited properties of Dacron grafts, glutaraldehyde-fixed porcine roots, and human aortic tissue. However, CoSeal and Tisseel are much more compliant than the aortic root conduits. CONCLUSIONS BioGlue is much less compliant than the other sealants studied and materials available for aortic root replacement. A surgeons choice of glue should be determined by stiffness as well as sealant efficacy. Sealants with greater stiffness than aortic root replacement material may restrict normal physiologic dilation and cause anastomotic strictures.

Migration forces of transcatheter aortic valves in patients with noncalcific aortic insufficiency

OBJECTIVE Transcatheter aortic valves have been successfully implanted into the calcified leaflets of patients with severe aortic stenosis. However, their stability in patients with noncalcified aortic insufficiency is unknown. Similar to thoracic and abdominal aortic stent grafts, transcatheter aortic valves are subjected to antegrade ejection forces during systole. However, retrograde migration forces into the left ventricle are also generated by the diastolic pressure gradient across the closed valve. It has been suggested that leaflet calcification anchors the prosthesis, and measurements of migration forces should be considered before clinical trials in noncalcified aortic insufficiency. The objective of this study was to use computational fluid dynamics simulations to quantify forces that could potentially dislodge the prosthesis. METHODS A computational fluid dynamics model was developed to simulate systolic flow through a geometric mesh of the aortic root and transcatheter aortic valves. Hemodynamic measurements were made at discrete moments during ejection. Unsteady control volume analysis was used for calculations of force on the mesh. RESULTS Results of the simulation indicate that a total force of 0.602 N acts on the transcatheter aortic valves during systole, 99% of which is in the direction of axial flow. The largest contributor to force was the dynamic pressure gradient through the transcatheter aortic valves. This antegrade force is approximately 10 times smaller than the retrograde force (6.01 N) on the closed valve during diastole. CONCLUSION Our model simulated systolic flow through a transcatheter aortic valve and demonstrated migration into the left ventricle to be of greater concern than antegrade ejection.

Comparison of Mechanical Properties of Human Ascending Aorta and Aortic Sinuses

BACKGROUND Computational finite element models of the aortic root have previously used material properties of the ascending aorta to describe both aortic sinuses and ascending aorta. We have previously demonstrated significant material property differences between ascending aorta and sinuses in pigs. However, it is unknown whether these regional material property differences exist in humans. The main objective of this study was to investigate biomechanics of fresh human ascending aorta and aortic sinuses and compare nonlinear material properties of these regions. METHODS Fresh human aortic root specimens obtained from the California Transplant Donor Network (Oakland, CA) were subjected to displacement-controlled equibiaxial stretch testing within 24 hours of harvest. Stress-strain data recorded were used to derive strain energy functions for each region. Tissue behavior was quantified by tissue stiffness and a direct comparison was made between different regions of aortic root at physiologic stress levels. RESULTS All regions demonstrated a nonlinear response to strain during stretch testing in both circumferential and longitudinal directions. No significant difference in tissue stiffness was found between anterior and posterior regions of the ascending aorta or among the three sinuses in both directions. However, our results demonstrated that human ascending aorta is significantly more compliant than aortic sinuses in both circumferential and longitudinal directions within the physiologic stress range. CONCLUSIONS Significant material and structural differences were observed between human ascending aorta and aortic sinuses. Regionally specific material properties should be employed in computational models used to assess treatments of structural aortic root disease.

Computational fluid dynamics simulation of transcatheter aortic valve degeneration.

OBJECTIVES Studied under clinical trials, transcatheter aortic valves (TAV) have demonstrated good short-term feasibility and results in high-risk surgical patients with severe aortic stenosis. However, their long-term safety and durability are unknown. The objective of this study is to evaluate hemodynamic changes within TAV created by bioprosthetic leaflet degeneration. METHODS Computational fluid dynamics (CFD) simulations were performed to evaluate the hemodynamics through TAV sclerosis (35% orifice reduction) and stenosis (78% orifice reduction). A three-dimensional surface mesh of the TAV within the aortic root was generated for each simulation. Leaflets were contained within an open, cylindrical body without attachment to the sinus commissures representing the stent. A continuous surface between the annulus and TAV excluded the geometry of the native calcified leaflets and prevented paravalvular leak. Unsteady control volume analysis throughout systole was used to calculate leaflet shear stress and total force on the TAV. RESULTS Sclerosis increased total force on the TAV by 63% (0.602-0.98 N). Advancement of degeneration from sclerosis to stenosis was accompanied by an 86% increase in total force (1.82 N) but only a 32% increase in peak wall shear stress on the leaflets. Of the total force exerted on the TAV, 99% was in the direction of axial flow. Shear stresses on the TAV were greatest during peak systolic flow with stress concentrations on the tips of the leaflets. In the normal TAV, the aortic root geometry and physiologic flow dominate location and magnitude of shear stress. Following leaflet degeneration, the specific geometry of the stenosis dictates the profile of axial velocity leaving the TAV and shear stress on the leaflets. A dramatic increase in peak leaflet shear stress was observed (115 Pa stenosis vs. 87 Pa sclerosis and 29 Pa normal). CONCLUSIONS CFD simulations in this study provide the first of its kind data quantifying hemodynamics within stenosed TAV. Stenosis leads to significant forces of TAV during systole; however, diastolic forces predominate even with significant stenosis. Substantial changes in peak shear stress occur with TAV degeneration. As the first implanted TAV begin to stenose, the authors recommend watchful examination for device failure.

Biomechanical Properties of Human Ascending Thoracic Aortic Aneurysms

BACKGROUND Surgical management of ascending thoracic aortic aneurysms (aTAAs) relies on maximum diameter, growth rate, and presence of connective tissue disorders. However, dissection and rupture do occur in patients who do not meet criteria for surgical repair. This study investigated the mechanical properties of aTAAs compared with normal human ascending aortas for eventual development of biomechanical aTAA risk models. METHODS aTAA specimens (n = 18) were obtained from patients undergoing surgical aneurysm repair, and fresh, healthy ascending aortas (n = 19) as controls were obtained from the transplant donor network. Biaxial stretch testing was performed to obtain tissue mechanical properties. Patient-specific aTAA physiologic stress was calculated based on preoperative computed tomography diameter. aTAA and ascending aorta tissue stiffness at respective physiologic stress were determined. RESULTS Physiologic stress of aTAA was significantly greater (241.6 ± 59.4 kPa) than the 74 kPa for normal controls. Tissue stiffness of aTAAs was significantly greater than that of the ascending aortas at their respective physiologic stresses in the circumferential (3041.4 ± 1673.7 vs 905.1 ± 358.9 kPa, respectively; p < 0.001) and longitudinal (3498.2 ± 2456.8 vs 915.3 ± 368.9 kPa, respectively; p < 0.001) directions. Tissue stiffness of aTAAs positively correlated with aTAA diameter but did not correlate with patient age. No correlation was found between aTAA physiologic stress level and maximum aTAA diameter. CONCLUSIONS aTAAs are much stiffer than normal ascending aortas at their respective physiologic stress, which was also significantly greater in ATAAs than ascending aortas. Patient-specific physiologic stress did not correlate with maximum aTAA diameter, and patient-specific aTAA wall stress may be a useful variable to predict adverse aTAA events.

Energy Loss Due to Paravalvular Leak With Transcatheter Aortic Valve Implantation

BACKGROUND Mild to moderate paravalvular leaks commonly occur after transcatheter aortic valve (TAV) implantation. Current TAVs match and may exceed hemodynamic performance of surgically implanted bioprostheses based on pressure gradient and effective orifice area. However, these hemodynamic criteria do not account for paravalvular leaks. We recently demonstrated that TAV implantation within 23 mm Perimount bioprostheses (Edwards Lifesciences, Irvine, CA) yields similar hemodynamics to the 23 mm Perimount valve. However, mild paravalvular leakage was seen after TAV implantation. The present study quantifies energy loss during the entire cardiac cycle to assess the impact of TAV paravalvular leaks on the ventricle. METHODS Four TAVs designed to mimic the 23 mm SAPIEN valve (Edwards Lifesciences) were created. Transvalvular energy loss of 19, 21, and 23 mm Carpentier-Edwards bioprostheses were obtained in vitro within a pulse duplicator as a hemodynamic baseline (n = 4). The 23 mm TAVs were subsequently implanted within the 23 mm bioprostheses to assess energy loss due to paravalvular leak. RESULTS The 23 mm bioprosthesis demonstrated the least energy loss (213.25 +/- 31.35 mJ) compared with the 19 mm (330.00 +/- 36.97 mJ, p = 0.003) and 21 mm bioprostheses (298.00 +/- 37.25 mJ, p = 0.008). The TAV controls had similar energy loss (241.00 +/- 30.55 mJ, p = 0.17) as the 23 mm bioprostheses. However, after TAV implantation, total energy loss increased to 365.33 +/- 8.02 mJ significantly exceeding the energy loss of the 23 mm bioprosthesis (p < 0.001). Due to mild TAV paravalvular leakage, 39% of energy loss occurred during diastole. CONCLUSIONS Substantial energy loss during diastole occurs due to TAV paravalvular leakage. In the presence of mild paravalvular leakage, TAV implantation imposes a significantly higher workload on the left ventricle than an equivalently sized surgically implanted bioprosthesis.

Transcatheter Heart Valves for Failing Bioprostheses State-of-the-Art Review of Valve-in-Valve Implantation

Transcatheter aortic valve implantation (TAVI) is emerging as an alternative to conventional surgical aortic valve replacement (AVR) in high-risk patients with severe symptomatic aortic stenosis (AS).1,2 Since the first-in-man procedure in 2002,3 TAVI has been rapidly adopted in Europe and Canada, and, to date, more than 30 000 procedures have been performed worldwide. TAVI early and medium-term results have been promising.3–5 In the first prospective, multicenter, randomized, controlled clinical trial in the United States (PARTNER), safety and effectiveness of TAVI was evaluated in a stratified population of inoperable and high-risk patients with severe symptomatic AS.6,7 Superiority of TAVI over medical therapy, including balloon aortic valvuloplasty, has been proven in inoperable patients in whom TAVI significantly improved survival and reduced cardiac symptoms.6 Furthermore, in high-risk surgical cohorts, TAVI demonstrated noninferiority to gold-standard surgical AVR in which all-cause mortality was similar at 1 year.7 However, in both inoperable and high-risk cohorts, TAVI was associated with higher incidence of major stroke and major vascular events.6,7 While TAVI experience within native AS rapidly progresses, TAVI offers an attractive option for patients with failing bioprostheses (valve-in-valve concept). Over time, bioprostheses have been preferentially used over mechanical valves for valve replacement because of favorable clinical results, patient age, and preference—outperforming mechanical valves in market share.8 As life expectancy increases, degeneration of previously implanted bioprostheses will inevitably become more common, requiring reoperative valve replacement. Reoperation in patients with degenerated bioprostheses carries an operative mortality risk ranging from 1.5% to 23%, depending on patient age, sex, preoperative New York Heart Association (NYHA) class, left ventricular dysfunction, number of previous operations, urgency of operation, and technical difficulties caused by adhesions.9 In high-risk surgical patients who are candidates for reoperative valve replacement, TAVI …

Comparison of Porcine Pulmonary and Aortic Root Material Properties

BACKGROUND The pulmonary autograft remodels when subjected to systemic pressure and subsequent dilation can lead to reoperation. Inherent material property differences between pulmonary and aortic roots may influence remodeling but are currently unknown. The objective of this study was to determine stiffness across a wide range of strain and compare nonlinear material properties of corresponding regions of native aortic and pulmonary roots. METHODS Tissue samples from porcine aortic and pulmonary roots-sinuses and supravalvular artery distal to the sinotubular junction-were subjected to displacement-controlled equibiaxial stretch testing. Stress-strain data recorded were used to derive strain energy functions for each region. Stiffness from low to high strains at 0.15, 0.3, and 0.5 strain were determined for comparisons. RESULTS Aortic and pulmonary roots exhibited qualitatively similar material properties; both had greater nonlinearity in the sinus than supravalvular artery. The pulmonary artery was significantly more compliant than the ascending aorta both circumferentially and longitudinally throughout the strain range (p < 0.03), except at high strain circumferentially (p = 0.06). However, no differences in stiffness were seen circumferentially or longitudinally between pulmonary and aortic sinuses (p > or = 0.3) until high strain, when the pulmonary sinuses were significantly stiffer (p < 0.05) in both directions. CONCLUSIONS Differences in stiffness between porcine aortic and pulmonary roots are regionally specific, supravalvular artery versus sinus. These regional differences may impact the mode of remodeling to influence late autograft dilation.