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Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-in-valve with and without coronary flow
CARREV-01632; No of Pages 6 Cardiovascular Revascularization Medicine xxx (xxxx) xxx
Contents lists available at ScienceDirect
Cardiovascular Revascularization Medicine
Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-invalve with and without coronary flow Hoda Hatoum a, Pablo Maureira b, Scott Lilly c, Lakshmi Prasad Dasi a,⁎ a b c
Department of Biomedical Engineering, The Ohio State University, Columbus, OH, USA Department of Cardiovascular Surgery, CHU de Nancy, Nancy, France Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
a r t i c l e
i n f o
Article history: Received 7 April 2019 Received in revised form 21 June 2019 Accepted 25 June 2019 Available online xxxx Keywords: TAVR Valve-in-valve BASILICA Leaflet thrombosis Washout Laceration
a b s t r a c t Background/purpose: This study aims at evaluating the impact of BASILICA on neo-sinus and sinus hemodynamics with and without coronary flow. Leaflet thrombosis after valve-in-valve (ViV) may compromise not only leaflet mobility but also affect valve durability and performance. Methods/materials: In a 23 mm transparent surgical aortic valve model, a 23 mm Edwards SAPIEN 3 and a 26 mm Medtronic Evolut were deployed before and after leaflet laceration, in models with and without coronary flow. Neo-sinus and sinus hemodynamics were evaluated in the aortic position of a pulse duplicator and particle image velocimetry was performed in order to quantify sinus flow hemodynamics along with sinus and neosinus washout. Results: BASILICA-type leaflet laceration procedure led to (a) an increase in the velocities in the sinus and the neosinus by 50% for Evolut ViV with and without coronary flow, 70% for non-coronary SAPIEN 3 ViV and 10% for coronary SAPIEN 3 ViV, and (b) an improvement in overall washout up to 2 cycles in the neo-sinus and 0.5 cycles in the sinus. Conclusions: A BASILICA-type leaflet laceration approach may improve sinus and neo-sinus hemodynamics through decreasing flow stasis and enabling less confined blood flow. BASILICA confers coronary sinus flow patterns to the non-coronary sinus. © 2019 Elsevier Inc. All rights reserved.
1. Introduction Transcatheter aortic valve (TAV) in valve (ViV) is a less invasive alternative to repeat sternotomy and surgical aortic valve replacement (SAVR) [1]. Although TAV replacement (TAVR) and ViV are effective and less invasive than SAVR and redo-SAVR respectively, leaflet thrombus formation has been identified as a potential consequence of TAVR and ViV [2]. Leaflet thrombosis compromises leaflet mobility and may lead to increased pressure gradients jeopardizing the functionality, durability and performance of the valve [3–5]. Neo-sinus thrombus after VIV TAVR is an indicator of early valve structural deterioration, increasing gradients, stroke and transient ischemic attacks [6]. Different studies have demonstrated a relationship between valve hemodynamics and thrombus formation [5,7,8], in particular, flow
Abbreviations: BASILICA, bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction; PIV, particle image velocimetry; TAVR, transcatheter aortic valve replacement; ViV, valve-in-valve. ⁎ Corresponding author at: Department of Biomedical Engineering, The Ohio State University, 473 W 12th Ave., Columbus, OH 43210, USA. E-mail address: [email protected] (L.P. Dasi).
stasis and long residence times were associated with clotting processes. Residence time is the time that a particle spends inside a region, in this case, the sinus and the neo-sinus. Ideally, short residence times are desired. Several factors can help mitigate flow stasis, especially in the sinus. Among these are valve type and valve position [9,10]. More importantly, the presence of coronary flow may have a drastic effect on flow improvement and stasis alleviation [10–12]. Recently, the bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction, also recognized as BASILICA, was introduced as a method to mitigate coronary obstruction [13]. BASILICA consists of inducing a laceration in the (initial) surgical valve leaflet to create a communication between the sinus and neosinus. This communication may constitute the means to enhance sinus and neo-sinus washout [14,15]. Our group performed a study that examined the effect of BASILICA using a SAPIEN 3 TAV showed that BASILICA may enhance washout and probably decreases the risk of leaflet thrombosis in ViV procedures [14]. Additionally, we studied the effect that BASILICA has on improving overall hemodynamics in the sinus and neo-sinus with different TAVs [15]. It is necessary, however, to examine the effect that coronary flow may have on hemodynamics with and without BASILICA for a
https://doi.org/10.1016/j.carrev.2019.06.015 1553-8389/© 2019 Elsevier Inc. All rights reserved.
Please cite this article as: H. Hatoum, P. Maureira, S. Lilly, et al., Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-in-valve with and without coronar..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.06.015
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Fig. 1. Benchtop depictions of valve-in-valve with (a) Evolut 26 mm and (b) SAPIEN 3 23 mm and (c) Evolut and (d) SAPIEN 3 post-laceration.
comprehensive investigation. The objective of this study is to evaluate the impact of BASILICA on neo-sinus and sinus hemodynamics with and without coronary flow. 2. Methods 2.1. Valve selection and hemodynamic assessment In a 23 mm transparent surgical aortic valve (SAV) model that was designed and assembled in-house, two transcatheter aortic valves were deployed before and after performing BASILICA as shown in Fig. 1: Medtronic Evolut of (26 mm) and Edwards SAPIEN 3 (23 mm). The surgical valve chosen is made (designed and assembled) in-house using a laser-cut stent and polymeric leaflets made of Linear lowdensity polyethylene (LLDPE). The usage of a polymeric in-house made surgical aortic valve instead of a regular bioprosthetic valve is because neo-sinus dynamics will be obscured by the opaque bioprosthetic leaflet. The transparent leaflets on the other hand will not block the neosinus view. Hemodynamics in the sinus and the neo-sinus were evaluated in a pulse duplicator yielding physiological flow and pressure curves and including a left coronary loop [10,11,16–18] as shown in Fig. 2. Briefly, the left coronary flow is controlled by a Starling resistor that was collapsed or expanded during specific intervals to match the changes in coronary flow during myocardial contraction or relaxation respectively. Hemodynamic conditions for all conditions were maintained with a systolic to diastolic pressure of 120/80 mm Hg, a 60 beats per minute heart rate, a systolic duration of 33%, a cardiac output of 5 L/min and an average coronary flow rate of 250 mL with 70% going
into the left coronary (175 mL). The working fluid in this study is a mixture of water-glycerin producing a density of 1060 kg/m3 and a kinematic viscosity of 3.5 cSt similar to blood. The pressure, pressure gradient and flow measurements were taken over a hundred cycles. Particle Image Velocimetry (PIV) consistently with previous studies [9–11,16,19,20] was performed to evaluate the velocity fields and washout rate. More details can be found in the supplementary methods. The sinus and neo-sinus washout calculations were performed over six cardiac cycles until all particles exited the sinus. 3. Results The sinus and neo-sinus stasis was evaluated based on (1) washout and (2) the overall vector field in both regions (velocity and vorticity). Sinus and neo-sinus hemodynamics are important as there is a strong relationship between hemodynamics and development of leaflet thrombosis [21]. Poor washout and low velocity are factors that if combined, encourage flow stasis [9,10,16], and provide a favorable environment for thrombus formation [3,4,22]. The latter is one substrate for valve degeneration, and has been associated with cerebroembolic events [6]. These two indices of flow stasis, modeled with and without coronary flow, will be presented in sequence. 3.1. Neo-sinus washout Neo-sinus washout was improved after BASILICA independently of valve type or coronary flow presence. Fig. 3 depicts the washout in the neo-sinus of 8 different combinations of ViV (2 valve types, with and
Please cite this article as: H. Hatoum, P. Maureira, S. Lilly, et al., Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-in-valve with and without coronar..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.06.015
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Fig. 2. Schematic figure showing the pulse duplicator with the coronary circuit. The model has been described in detail elsewhere [10,16]. Briefly, the pulse duplicator mimics the dynamics of the left ventricle through a pumping mechanism controlled by a program, a resistance valve to control the flow (cardiac output) and a compliance chamber to simulate arterial compliance.
without coronary flow). The washout curve is presented as the ratio of particles remaining in the neo-sinus at a given number of cardiac cycles. Cardiac cycle length was 1 s in these models. In models without coronary flow, total neo-washout (0% particles remaining in the neosinus) with Evolut TAV was achieved after 2 s and after 3.5 s with SAPIEN 3, both N1 cardiac cycle. After BASILICA, total washout was reduced to 1 s and 0.7 s, respectively. In models with coronary flow, total washout with Evolut TAVR was achieved after 2.8 s and with SAPIEN 3 after 3.5 s. After BASILICA, total washout was achieved at 0.54 s and 1.3 s, respectively.
differed. Fig. 4 shows the washout in the sinus of the 8 different ViV combinations (2 valve types, with and without coronary flow). In models without coronary flow, total washout was achieved with Evolut ViV after 1.4 s and with SAPIEN 3 after 2.1 s. After leaflet laceration, total washout was achieved in 0.8 s and 2 s, respectively. When coronary flow was included in the model, total washout occurred with Evolut ViV after 0.8 s and with SAPIEN 3 after 1 s. Leaflet laceration reduced this time to 0.3 s with Evolut and kept it almost the same with SAPIEN with 1 s to washout.
3.2. Sinus washout
3.3. Neo-sinus and sinus flow velocity fields
Sinus washout was slightly improved after BASILICA irrespective of valve type or modeled coronary flow, although the magnitude of change
Video 1 shows the particle streak generated from the PIV data for the 8 different ViV combinations. The higher the velocity, and broader the
Fig. 3. Washout in the neo-sinus of the 8 different combinations of ViV with and without coronary flow with an Evolut TAV and a SAPIEN 3 TAV. The y-axis represents the ratio of particles remaining in the sinus. The x-axis represents a time interval, expressed as the number of cardiac cycles. In our models, we used a pump rate of 60 beats per minute. BASILICA (interrupted lines) reduces the amount of time particles remain in the neo-sinus (i.e. improves sinus washout) in all cases evaluated.
Please cite this article as: H. Hatoum, P. Maureira, S. Lilly, et al., Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-in-valve with and without coronar..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.06.015
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Fig. 4. Washout in the sinus of the 8 different ViV combinations with and without coronary flow with Evolut and SAPIEN 3 TAVs. BASILICA (interrupted lines) slightly improves sinus washout in all cases evaluated although the magnitude of difference varies by valve type and the presence or absence of modeled coronary flow.
vorticity contour, the less likely that stasis may occur. Values at peak systole were compared. The velocity field and vorticity (showing local rotation) contours in an Evolut ViV model are depicted in Fig. 5. In models without coronary flow, having leaflet laceration leads to increasing the velocity at the intersection between sinus and neo-sinus from 0.01 ± 0.004 m/s during acceleration to 0.054 ± 0.002 m/s. During peak, velocity increases from 0.046 ± 0.002 m/s to 0.073 ± 0.001 m/s and during deceleration, 0.04 ± 0.003 to 0.08 ± 0.003 m/s. During diastole, velocity was 0.032 ± 0.005 m/s pre-laceration compared with 0.039 ± 0.003 m/s postlaceration. With coronary flow, the velocity at the intersection between sinus and neo-sinus varies from 0.05 ± 0.005 m/s pre-laceration to 0.098 ± 0.001 m/s post-laceration during acceleration, from 0.08 ± 0.003 m/s
to 0.12 ± 0.006 m/s during peak, from 0.04 ± 0.002 m/s to 0.09 ± 0.006 m/s during deceleration and from 0.04 ± 0.01 m/s to 0.05 ± 0.005 m/s during diastole. Fig. 6 shows the flow velocity field along with vorticity contours for the SAPIEN 3 ViV with and without coronary flow pre and postlaceration. Without coronary flow, velocity at the intersection of the neo-sinus and sinus increased from 0.014 ± 0.005 m/s, 0.017 ± 0.002 m/s, 0.019 ± 0.004 m/s and 0.016 ± 0.002 m/s pre-laceration to 0.022 ± 0.01 m/s, 0.029 ± 0.006 m/s, 0.032 ± 0.004 m/s and 0.019 ± 0.003 m/s post-laceration during acceleration, peak systole, deceleration and diastole respectively. With coronary flow, the velocity at the intersection between sinus and neo-sinus varies from 0.04 ± 0.015 m/s to 0.042 ± 0.004 m/s during acceleration, from 0.066 ± 0.005 m/s to 0.07 ± 0.002 m/s during
Fig. 5. Flow velocity field (velocity at each point in the measurement zone) along with vorticity (showing the local rotation) contours for the Evolut ViV with and without coronary flow pre and post-laceration. Vorticity is represented with the red contours (counterclockwise rotation) and the blue contours (clockwise rotation). Higher velocities are present at the intersection of sinus and neo-sinus after BASILICA. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Please cite this article as: H. Hatoum, P. Maureira, S. Lilly, et al., Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-in-valve with and without coronar..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.06.015
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Fig. 6. Flow velocity field (velocity at each point in the measurement zone) along with vorticity (showing the local rotation) contours for the SAPIEN3 ViV with and without coronary flow pre and post-laceration. Vorticity is represented with the red contours (counterclockwise rotation) and the blue contours (clockwise rotation). Higher velocities are present at the intersection of sinus and neo-sinus after BASILICA. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
peak, from 0.044 ± 0.01 m/s to 0.055 ± 0.005 m/s during deceleration and from 0.06 ± 0.005 m/s to 0.09 ± 0.003 m/s during diastole.
4. Discussion Improving the hemodynamics of the sinus and the neo-sinus in attempt to decrease the likelihood of thrombus development is important given the relationship between flow stasis and thrombosis. Leaflet thrombosis has been identified after TAVR and ViV [23]. A number of procedural factors have been implicated, including valve axial location [10], angular orientation [10], axial tilt with respect to the axis of the aorta [9], the presence of coronary flow [10,12]. Thrombosis is most likely to occur in low-flow or stasis regions with reduced velocities and shear stresses [20,24]. Shear-dependent mass transport is responsible for atheroma growth and may lead to higher risk of thrombus formation [25]. Although BASILICA was initially employed to mitigate coronary obstruction, the possibility that it enhances sinus and neosinus flow has theoretical implications for valve durability. BASILICA results in a laceration of the in situ (or native) valve creating a communication between the neo-sinus and sinus, rather than blood being trapped in the compressed neo-sinus [26]. This exit likely improves flow rate in the neo-sinus. The results presented herein support this. First, velocities after BASILICA were higher than preBASILICA and then washout after BASILICA whether in the sinus or the neo-sinus was improved. These observations were uniform, and occurred whether or not coronary flow was included in the model. In the presence of coronary flow, the influx from the neo-sinus is almost directly and fully absorbed by the coronary ostium. BASILICA cut enhances the flow in the sinus (with the addition of the incoming flow from the neo-sinus) particularly in the area towards the annulus (leftmost side of the sinus as shown in Figs. 5 and 6) where stagnation is most likely to occur [9–11,16]. The impact of coronary flow on sinus hemodynamics in ViV [10,11,16] has been highlighted in several publications. It was shown that coronary flow leads to enhanced fluid motion
and velocity in the sinus [10,11,16]. A BASILICA-induced-laceration provides the non-coronary sinus the flow advantage that the coronary sinus has in terms of improved velocities and washouts. The results of this study can probably be extrapolated to regular TAVR (TAV implantation in a native annulus), should a laceration be performed. Adopting the same concepts, the laceration between the native leaflet and the bioprosthetic leaflet allows an overall enhancement in sinus and neo-sinus velocities and washout. 4.1. Limitations In this study, only two TAV sizes were tested (26 mm Evolut and 23 mm SAPIEN 3). Although not anticipated, valve-to-valve variability (for the same size) is not addressed in this study. 5. Conclusion In this benchtop model of aortic root flow after ViV TAVR, BASILICA significantly improved sinus and neo-sinus washout and velocities irrespective of the presence or absence of coronary flow. Despite being currently employed to prevent coronary obstruction, BASILICA could potentially mitigate neo-sinus and sinus flow stasis during ViV, prevent thrombus formation, and perhaps help improve long-term valve durability. BASILICA has the potential to confer coronary sinus flow advantages to the non-coronary sinus. Supplementary data to this article can be found online at https://doi. org/10.1016/j.carrev.2019.06.015. Sources of funding The research done was partly supported by National Institutes of Health (NIH) under Award Number R01HL119824 and the American Heart Association (AHA) under Award Number 19POST34380804.
Please cite this article as: H. Hatoum, P. Maureira, S. Lilly, et al., Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-in-valve with and without coronar..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.06.015
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Declaration of Competing Interest Dr. Dasi reports having patent applications filed on novel polymeric valves, vortex generators and superhydrophobic/omniphobic surfaces. No other conflicts were reported. References [1] Simonato M, Dvir D. Transcatheter aortic valve replacement in failed surgical valves. Heart 2019;105:s38–43. [2] Chakravarty T, Søndergaard L, Friedman J, De Backer O, Berman D, Kofoed KF, et al. Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study. The Lancet 2017;389:2383–92. [3] Mangione FM, Jatene T, Gonçalves A, Fishbein GA, Mitchell RN, Pelletier MP, et al. Leaflet thrombosis in surgically explanted or post-mortem TAVR valves. JACC Cardiovasc Imaging 2017;10:82–5. [4] Toggweiler S, Schmidt K, Paul M, Cuculi F, Kobza R, Jamshidi P. Valve thrombosis 3 years after transcatheter aortic valve implantation. Int J Cardiol 2016;207:122–4. [5] Trantalis G, Toutouzas K, Latsios G, Synetos A, Brili S, Logitsi D, et al. TAVR and thrombosis. JACC Cardiovasc Imaging 2017;10:86–7. [6] Makki N, Shreenivas S, Kereiakes D, Lilly S. A meta-analysis of reduced leaflet motion for surgical and transcatheter aortic valves: relationship to cerebrovascular events and valve degeneration. Cardiovasc Revasc Med 2018;19:868–73. [7] Herbig BA, Diamond SL. Thrombi produced in stagnation point flows have a core– shell structure. Cell Mol Bioeng 2017;10:515–21. [8] Jahren SE, Heinisch PP, Hasler D, Winkler BM, Stortecky S, Pilgrim T, et al. Can bioprosthetic valve thrombosis be promoted by aortic root morphology? An in vitro study. Interact Cardiovasc Thorac Surg 2018;27:108–15. [9] Hatoum H, Dollery J, Lilly SM, Crestanello J, Dasi LP. Impact of patient-specific morphologies on sinus flow stasis in transcatheter aortic valve replacement: an in vitro study. J Thorac Cardiovasc Surg 2019;157(2):540–9. [10] Hatoum H, Dollery J, Lilly SM, Crestanello JA, Dasi LP. Implantation depth and rotational orientation effect on valve-in-valve hemodynamics and sinus flow. The annals of thoracic surgery; 2018. [11] Moore BL, Dasi LP. Coronary flow impacts aortic leaflet mechanics and aortic sinus hemodynamics. Ann Biomed Eng 2015;43:2231–41. [12] Hatoum H, Dasi L, Crestanello J. Possible subclinical leaflet thrombosis in bioprosthetic aortic valves. N Engl J Med 2016;374:1590–2.
[13] Khan JM, Dvir D, Greenbaum AB, Babaliaros VC, Rogers T, Aldea G, et al. Transcatheter laceration of aortic leaflets to prevent coronary obstruction during transcatheter aortic valve replacement: concept to first-in-human. J Am Coll Cardiol Intv 2018;11:677–89. [14] Hatoum H, Maureira P, Lilly S, Dasi LP. Leaflet laceration to improve neosinus and sinus flow after valve-in-valve. Circ Cardiovasc Interv 2019;12:e007739. [15] Hatoum H, Maureira P, Lilly S, Dasi LP. Impact of leaflet laceration on transcatheter aortic valve-in-valve washout. JACC: Cardiovasc Interv 2019;12(13):1229–37. https://doi.org/10.1016/j.jcin.2019.04.013. [16] Hatoum H, Moore BL, Maureira P, Dollery J, Crestanello JA, Dasi LP. Aortic sinus flow stasis likely in valve-in-valve transcatheter aortic valve implantation. J Thorac Cardiovasc Surg 2017;154:32–43 [e1]. [17] Hatoum H, Heim F, Dasi LP. Stented valve dynamic behavior induced by polyester fiber leaflet material in transcatheter aortic valve devices. J Mech Behav Biomed Mater 2018;86:232–9. [18] Hatoum H, Moore BL, Dasi LP. On the significance of systolic flow waveform on aortic valve energy loss. Ann Biomed Eng 2018;46:2102–11. [19] Hatoum H, Yousefi A, Lilly S, Maureira P, Crestanello J, Dasi LP. An in vitro evaluation of turbulence after transcatheter aortic valve implantation. J Thorac Cardiovasc Surg 2018;156:1837–48. [20] Dasi LP, Hatoum H, Kheradvar A, Zareian R, Alavi SH, Sun W, et al. On the mechanics of transcatheter aortic valve replacement. Ann Biomed Eng 2017;45:310–31. [21] Del Trigo M, Muñoz-Garcia AJ, Wijeysundera HC, Nombela-Franco L, Cheema AN, Gutierrez E, et al. Incidence, timing, and predictors of valve hemodynamic deterioration after transcatheter aortic valve replacement: multicenter registry. J Am Coll Cardiol 2016;67:644–55. [22] Yanagisawa R, Hayashida K, Yamada Y, Tanaka M, Yashima F, Inohara T, et al. Incidence, predictors, and mid-term outcomes of possible leaflet thrombosis after TAVR. JACC Cardiovasc Imaging 2017;10:1–11. [23] Nijenhuis VJ, Brouwer J, Søndergaard L, Collet JP, Grove EL, Ten Berg JM. Antithrombotic therapy in patients undergoing transcatheter aortic valve implantation. Heart 2019;105(10):742–8. [24] Chandra S, Rajamannan NM, Sucosky P. Computational assessment of bicuspid aortic valve wall-shear stress: implications for calcific aortic valve disease. Biomech Model Mechanobiol 2012;11:1085–96. [25] Traub O, Berk BC. Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force. Arteriosclerosis, thrombosis, and vascular biology, 18. ; 1998. p. 677–85. [26] Kapadia S, Tuzcu EM, Svensson LG. Anatomy and flow characteristics of neosinus: important consideration for thrombosis of transcatheter aortic valves; 2017.
Please cite this article as: H. Hatoum, P. Maureira, S. Lilly, et al., Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-in-valve with and without coronar..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.06.015
Contents lists available at ScienceDirect
Cardiovascular Revascularization Medicine
Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-invalve with and without coronary flow Hoda Hatoum a, Pablo Maureira b, Scott Lilly c, Lakshmi Prasad Dasi a,⁎ a b c
Department of Biomedical Engineering, The Ohio State University, Columbus, OH, USA Department of Cardiovascular Surgery, CHU de Nancy, Nancy, France Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA
a r t i c l e
i n f o
Article history: Received 7 April 2019 Received in revised form 21 June 2019 Accepted 25 June 2019 Available online xxxx Keywords: TAVR Valve-in-valve BASILICA Leaflet thrombosis Washout Laceration
a b s t r a c t Background/purpose: This study aims at evaluating the impact of BASILICA on neo-sinus and sinus hemodynamics with and without coronary flow. Leaflet thrombosis after valve-in-valve (ViV) may compromise not only leaflet mobility but also affect valve durability and performance. Methods/materials: In a 23 mm transparent surgical aortic valve model, a 23 mm Edwards SAPIEN 3 and a 26 mm Medtronic Evolut were deployed before and after leaflet laceration, in models with and without coronary flow. Neo-sinus and sinus hemodynamics were evaluated in the aortic position of a pulse duplicator and particle image velocimetry was performed in order to quantify sinus flow hemodynamics along with sinus and neosinus washout. Results: BASILICA-type leaflet laceration procedure led to (a) an increase in the velocities in the sinus and the neosinus by 50% for Evolut ViV with and without coronary flow, 70% for non-coronary SAPIEN 3 ViV and 10% for coronary SAPIEN 3 ViV, and (b) an improvement in overall washout up to 2 cycles in the neo-sinus and 0.5 cycles in the sinus. Conclusions: A BASILICA-type leaflet laceration approach may improve sinus and neo-sinus hemodynamics through decreasing flow stasis and enabling less confined blood flow. BASILICA confers coronary sinus flow patterns to the non-coronary sinus. © 2019 Elsevier Inc. All rights reserved.
1. Introduction Transcatheter aortic valve (TAV) in valve (ViV) is a less invasive alternative to repeat sternotomy and surgical aortic valve replacement (SAVR) [1]. Although TAV replacement (TAVR) and ViV are effective and less invasive than SAVR and redo-SAVR respectively, leaflet thrombus formation has been identified as a potential consequence of TAVR and ViV [2]. Leaflet thrombosis compromises leaflet mobility and may lead to increased pressure gradients jeopardizing the functionality, durability and performance of the valve [3–5]. Neo-sinus thrombus after VIV TAVR is an indicator of early valve structural deterioration, increasing gradients, stroke and transient ischemic attacks [6]. Different studies have demonstrated a relationship between valve hemodynamics and thrombus formation [5,7,8], in particular, flow
Abbreviations: BASILICA, bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction; PIV, particle image velocimetry; TAVR, transcatheter aortic valve replacement; ViV, valve-in-valve. ⁎ Corresponding author at: Department of Biomedical Engineering, The Ohio State University, 473 W 12th Ave., Columbus, OH 43210, USA. E-mail address: [email protected] (L.P. Dasi).
stasis and long residence times were associated with clotting processes. Residence time is the time that a particle spends inside a region, in this case, the sinus and the neo-sinus. Ideally, short residence times are desired. Several factors can help mitigate flow stasis, especially in the sinus. Among these are valve type and valve position [9,10]. More importantly, the presence of coronary flow may have a drastic effect on flow improvement and stasis alleviation [10–12]. Recently, the bioprosthetic or native aortic scallop intentional laceration to prevent iatrogenic coronary artery obstruction, also recognized as BASILICA, was introduced as a method to mitigate coronary obstruction [13]. BASILICA consists of inducing a laceration in the (initial) surgical valve leaflet to create a communication between the sinus and neosinus. This communication may constitute the means to enhance sinus and neo-sinus washout [14,15]. Our group performed a study that examined the effect of BASILICA using a SAPIEN 3 TAV showed that BASILICA may enhance washout and probably decreases the risk of leaflet thrombosis in ViV procedures [14]. Additionally, we studied the effect that BASILICA has on improving overall hemodynamics in the sinus and neo-sinus with different TAVs [15]. It is necessary, however, to examine the effect that coronary flow may have on hemodynamics with and without BASILICA for a
https://doi.org/10.1016/j.carrev.2019.06.015 1553-8389/© 2019 Elsevier Inc. All rights reserved.
Please cite this article as: H. Hatoum, P. Maureira, S. Lilly, et al., Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-in-valve with and without coronar..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.06.015
2
H. Hatoum et al. / Cardiovascular Revascularization Medicine xxx (xxxx) xxx
Fig. 1. Benchtop depictions of valve-in-valve with (a) Evolut 26 mm and (b) SAPIEN 3 23 mm and (c) Evolut and (d) SAPIEN 3 post-laceration.
comprehensive investigation. The objective of this study is to evaluate the impact of BASILICA on neo-sinus and sinus hemodynamics with and without coronary flow. 2. Methods 2.1. Valve selection and hemodynamic assessment In a 23 mm transparent surgical aortic valve (SAV) model that was designed and assembled in-house, two transcatheter aortic valves were deployed before and after performing BASILICA as shown in Fig. 1: Medtronic Evolut of (26 mm) and Edwards SAPIEN 3 (23 mm). The surgical valve chosen is made (designed and assembled) in-house using a laser-cut stent and polymeric leaflets made of Linear lowdensity polyethylene (LLDPE). The usage of a polymeric in-house made surgical aortic valve instead of a regular bioprosthetic valve is because neo-sinus dynamics will be obscured by the opaque bioprosthetic leaflet. The transparent leaflets on the other hand will not block the neosinus view. Hemodynamics in the sinus and the neo-sinus were evaluated in a pulse duplicator yielding physiological flow and pressure curves and including a left coronary loop [10,11,16–18] as shown in Fig. 2. Briefly, the left coronary flow is controlled by a Starling resistor that was collapsed or expanded during specific intervals to match the changes in coronary flow during myocardial contraction or relaxation respectively. Hemodynamic conditions for all conditions were maintained with a systolic to diastolic pressure of 120/80 mm Hg, a 60 beats per minute heart rate, a systolic duration of 33%, a cardiac output of 5 L/min and an average coronary flow rate of 250 mL with 70% going
into the left coronary (175 mL). The working fluid in this study is a mixture of water-glycerin producing a density of 1060 kg/m3 and a kinematic viscosity of 3.5 cSt similar to blood. The pressure, pressure gradient and flow measurements were taken over a hundred cycles. Particle Image Velocimetry (PIV) consistently with previous studies [9–11,16,19,20] was performed to evaluate the velocity fields and washout rate. More details can be found in the supplementary methods. The sinus and neo-sinus washout calculations were performed over six cardiac cycles until all particles exited the sinus. 3. Results The sinus and neo-sinus stasis was evaluated based on (1) washout and (2) the overall vector field in both regions (velocity and vorticity). Sinus and neo-sinus hemodynamics are important as there is a strong relationship between hemodynamics and development of leaflet thrombosis [21]. Poor washout and low velocity are factors that if combined, encourage flow stasis [9,10,16], and provide a favorable environment for thrombus formation [3,4,22]. The latter is one substrate for valve degeneration, and has been associated with cerebroembolic events [6]. These two indices of flow stasis, modeled with and without coronary flow, will be presented in sequence. 3.1. Neo-sinus washout Neo-sinus washout was improved after BASILICA independently of valve type or coronary flow presence. Fig. 3 depicts the washout in the neo-sinus of 8 different combinations of ViV (2 valve types, with and
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Fig. 2. Schematic figure showing the pulse duplicator with the coronary circuit. The model has been described in detail elsewhere [10,16]. Briefly, the pulse duplicator mimics the dynamics of the left ventricle through a pumping mechanism controlled by a program, a resistance valve to control the flow (cardiac output) and a compliance chamber to simulate arterial compliance.
without coronary flow). The washout curve is presented as the ratio of particles remaining in the neo-sinus at a given number of cardiac cycles. Cardiac cycle length was 1 s in these models. In models without coronary flow, total neo-washout (0% particles remaining in the neosinus) with Evolut TAV was achieved after 2 s and after 3.5 s with SAPIEN 3, both N1 cardiac cycle. After BASILICA, total washout was reduced to 1 s and 0.7 s, respectively. In models with coronary flow, total washout with Evolut TAVR was achieved after 2.8 s and with SAPIEN 3 after 3.5 s. After BASILICA, total washout was achieved at 0.54 s and 1.3 s, respectively.
differed. Fig. 4 shows the washout in the sinus of the 8 different ViV combinations (2 valve types, with and without coronary flow). In models without coronary flow, total washout was achieved with Evolut ViV after 1.4 s and with SAPIEN 3 after 2.1 s. After leaflet laceration, total washout was achieved in 0.8 s and 2 s, respectively. When coronary flow was included in the model, total washout occurred with Evolut ViV after 0.8 s and with SAPIEN 3 after 1 s. Leaflet laceration reduced this time to 0.3 s with Evolut and kept it almost the same with SAPIEN with 1 s to washout.
3.2. Sinus washout
3.3. Neo-sinus and sinus flow velocity fields
Sinus washout was slightly improved after BASILICA irrespective of valve type or modeled coronary flow, although the magnitude of change
Video 1 shows the particle streak generated from the PIV data for the 8 different ViV combinations. The higher the velocity, and broader the
Fig. 3. Washout in the neo-sinus of the 8 different combinations of ViV with and without coronary flow with an Evolut TAV and a SAPIEN 3 TAV. The y-axis represents the ratio of particles remaining in the sinus. The x-axis represents a time interval, expressed as the number of cardiac cycles. In our models, we used a pump rate of 60 beats per minute. BASILICA (interrupted lines) reduces the amount of time particles remain in the neo-sinus (i.e. improves sinus washout) in all cases evaluated.
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Fig. 4. Washout in the sinus of the 8 different ViV combinations with and without coronary flow with Evolut and SAPIEN 3 TAVs. BASILICA (interrupted lines) slightly improves sinus washout in all cases evaluated although the magnitude of difference varies by valve type and the presence or absence of modeled coronary flow.
vorticity contour, the less likely that stasis may occur. Values at peak systole were compared. The velocity field and vorticity (showing local rotation) contours in an Evolut ViV model are depicted in Fig. 5. In models without coronary flow, having leaflet laceration leads to increasing the velocity at the intersection between sinus and neo-sinus from 0.01 ± 0.004 m/s during acceleration to 0.054 ± 0.002 m/s. During peak, velocity increases from 0.046 ± 0.002 m/s to 0.073 ± 0.001 m/s and during deceleration, 0.04 ± 0.003 to 0.08 ± 0.003 m/s. During diastole, velocity was 0.032 ± 0.005 m/s pre-laceration compared with 0.039 ± 0.003 m/s postlaceration. With coronary flow, the velocity at the intersection between sinus and neo-sinus varies from 0.05 ± 0.005 m/s pre-laceration to 0.098 ± 0.001 m/s post-laceration during acceleration, from 0.08 ± 0.003 m/s
to 0.12 ± 0.006 m/s during peak, from 0.04 ± 0.002 m/s to 0.09 ± 0.006 m/s during deceleration and from 0.04 ± 0.01 m/s to 0.05 ± 0.005 m/s during diastole. Fig. 6 shows the flow velocity field along with vorticity contours for the SAPIEN 3 ViV with and without coronary flow pre and postlaceration. Without coronary flow, velocity at the intersection of the neo-sinus and sinus increased from 0.014 ± 0.005 m/s, 0.017 ± 0.002 m/s, 0.019 ± 0.004 m/s and 0.016 ± 0.002 m/s pre-laceration to 0.022 ± 0.01 m/s, 0.029 ± 0.006 m/s, 0.032 ± 0.004 m/s and 0.019 ± 0.003 m/s post-laceration during acceleration, peak systole, deceleration and diastole respectively. With coronary flow, the velocity at the intersection between sinus and neo-sinus varies from 0.04 ± 0.015 m/s to 0.042 ± 0.004 m/s during acceleration, from 0.066 ± 0.005 m/s to 0.07 ± 0.002 m/s during
Fig. 5. Flow velocity field (velocity at each point in the measurement zone) along with vorticity (showing the local rotation) contours for the Evolut ViV with and without coronary flow pre and post-laceration. Vorticity is represented with the red contours (counterclockwise rotation) and the blue contours (clockwise rotation). Higher velocities are present at the intersection of sinus and neo-sinus after BASILICA. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
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Fig. 6. Flow velocity field (velocity at each point in the measurement zone) along with vorticity (showing the local rotation) contours for the SAPIEN3 ViV with and without coronary flow pre and post-laceration. Vorticity is represented with the red contours (counterclockwise rotation) and the blue contours (clockwise rotation). Higher velocities are present at the intersection of sinus and neo-sinus after BASILICA. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
peak, from 0.044 ± 0.01 m/s to 0.055 ± 0.005 m/s during deceleration and from 0.06 ± 0.005 m/s to 0.09 ± 0.003 m/s during diastole.
4. Discussion Improving the hemodynamics of the sinus and the neo-sinus in attempt to decrease the likelihood of thrombus development is important given the relationship between flow stasis and thrombosis. Leaflet thrombosis has been identified after TAVR and ViV [23]. A number of procedural factors have been implicated, including valve axial location [10], angular orientation [10], axial tilt with respect to the axis of the aorta [9], the presence of coronary flow [10,12]. Thrombosis is most likely to occur in low-flow or stasis regions with reduced velocities and shear stresses [20,24]. Shear-dependent mass transport is responsible for atheroma growth and may lead to higher risk of thrombus formation [25]. Although BASILICA was initially employed to mitigate coronary obstruction, the possibility that it enhances sinus and neosinus flow has theoretical implications for valve durability. BASILICA results in a laceration of the in situ (or native) valve creating a communication between the neo-sinus and sinus, rather than blood being trapped in the compressed neo-sinus [26]. This exit likely improves flow rate in the neo-sinus. The results presented herein support this. First, velocities after BASILICA were higher than preBASILICA and then washout after BASILICA whether in the sinus or the neo-sinus was improved. These observations were uniform, and occurred whether or not coronary flow was included in the model. In the presence of coronary flow, the influx from the neo-sinus is almost directly and fully absorbed by the coronary ostium. BASILICA cut enhances the flow in the sinus (with the addition of the incoming flow from the neo-sinus) particularly in the area towards the annulus (leftmost side of the sinus as shown in Figs. 5 and 6) where stagnation is most likely to occur [9–11,16]. The impact of coronary flow on sinus hemodynamics in ViV [10,11,16] has been highlighted in several publications. It was shown that coronary flow leads to enhanced fluid motion
and velocity in the sinus [10,11,16]. A BASILICA-induced-laceration provides the non-coronary sinus the flow advantage that the coronary sinus has in terms of improved velocities and washouts. The results of this study can probably be extrapolated to regular TAVR (TAV implantation in a native annulus), should a laceration be performed. Adopting the same concepts, the laceration between the native leaflet and the bioprosthetic leaflet allows an overall enhancement in sinus and neo-sinus velocities and washout. 4.1. Limitations In this study, only two TAV sizes were tested (26 mm Evolut and 23 mm SAPIEN 3). Although not anticipated, valve-to-valve variability (for the same size) is not addressed in this study. 5. Conclusion In this benchtop model of aortic root flow after ViV TAVR, BASILICA significantly improved sinus and neo-sinus washout and velocities irrespective of the presence or absence of coronary flow. Despite being currently employed to prevent coronary obstruction, BASILICA could potentially mitigate neo-sinus and sinus flow stasis during ViV, prevent thrombus formation, and perhaps help improve long-term valve durability. BASILICA has the potential to confer coronary sinus flow advantages to the non-coronary sinus. Supplementary data to this article can be found online at https://doi. org/10.1016/j.carrev.2019.06.015. Sources of funding The research done was partly supported by National Institutes of Health (NIH) under Award Number R01HL119824 and the American Heart Association (AHA) under Award Number 19POST34380804.
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Please cite this article as: H. Hatoum, P. Maureira, S. Lilly, et al., Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-in-valve with and without coronar..., Cardiovascular Revascularization Medicine, https://doi.org/10.1016/j.carrev.2019.06.015