Biomechanical Reappraisal of Planning for Thoracic Endovascular Aortic Repair

Aortic Dissection Clinical Trial

— MALAN  

Official title:

Mapping of Aortic Arch Hemodynamics by Biomechanical Analysis and Modeling for Planning Thoracic Endovascular Aortic Repair

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03824626
• Other study ID #: 160/int/2017
• Status: Recruiting
• Start date: May 23, 2019
• Est. completion date: January 30, 2022

Study information

• Verified date: October 2020
• Source: Ospedale San Donato
• Contact: Massimiliano M Marrocco-Trischitta, MD,PhD
• Phone: +393332084440
• Email: massimiliano.marroccotrischitta[@]grupposandonato.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Thoracic endovascular aortic repair (TEVAR) for disease involving the aortic arch remains complex and challenging due the angulation and tortuosity of the arch and its peculiar biomechanical environment. Currently, TEVAR planning is based on the analysis of anatomical features by means of static imaging protocols. Such an approach, however, disregards the impact of pulsatile forces that are transmitted as migration forces on the terminal fixation sites of the endograft, and may jeopardize the long-term clinical success of the procedure. Hence,the investigators aim to assess the migration forces acting on different proximal landing zones of the aortic arch by computational modeling, and develop in silico patient-specific simulations that can provide a quantitative evaluation of the stent-graft performance. Study's results are expected to provide valuable insights for proper proximal landing zone and stent-graft selection during TEVAR planning, and ultimately improve postoperative outcome.

Description:

Hypothesis and Significance: Specific and consistent fluid dynamic patterns and drag forces magnitude and distribution can be identified in the PLZs of the aortic arch providing valuable insights for proper PLZ and stent-graft selection during TEVAR planning.

Specific Aim: 1) To assess the drag forces acting on different PLZs of the aortic arch by means of Computed Fluid Dynamic (CFD) analysis of preoperative phase contrast-Magnetic Resonance (pc-MRI) and Computed Tomography Angiography (CTA) images. The specific goal is to identify the correlation between different magnitude and direction of migration forces and geometrical patterns of the arch to identify suboptimal landing zones for stent-graft deployment. 2) To develop and perform in-silico simulations of the deployment of different commercially available endografts with patient specific boundary conditions. The exact goal is to assess the impact of the mechanical characteristics of a specific device on the vessel wall by structural finite element analysis (FEA), and on the drag forces in different landing zones by CFD, to identify the more suitable endograft. 3) To assess the drag forces exerted postoperatively on the endograft by means of CFD analysis based on follow-up images (i.e., pc-MRI and CTA). The specific goal is to evaluate the predictive value of the drag forces measured preoperatively in the PLZs, and validate the results from in-silico simulations.

Experimental Design Aim 1: Preoperative medical images acquisition: CTA will be performed using a 16-slice unit (150 mAs, 110 kVp; acquisition thickness 5 mm, pitch 1.5; reconstruction thickness 1.2 mm), before and after intravenous administration of 100 mL of iodinated contrast material. MRI will be performed using a 1.5-T unit with 40-mT/m gradient power (Magneton Sonata Maestro Class, Siemens, Erlangen, Germany) and a four-channel cardio-thoracic coil. ECG-triggered, free-breathing through plane, and in-plane pc-MRI sequences will be performed for phase-velocity mapping of aortic and branches flow with the following technical parameters: TR/TE = 4/3.2 ms, thickness 5 mm, velocity encoding from 150 to 350 ms, and temporal resolution 41 ms.

Medical images processing: Ad hoc processing of preoperative CTAs, based on 3D multiplanar reconstruction, will be performed with 3Mensio Vascular software 8.0® (3Mensio Medical Imaging B.V.), which provides specific functions for automatic measurements. Patients will be stratified according to Aortic Arches Classification (AAC). Radius of curvature, PLZs angulation (tangent angle function) and tortuosity (tortuosity angle function) will be calculated. 3D segmentation of CTA, aimed for in-silico simulation purposes, will be performed by the software Mimics v18.0 (Materialise, Belgium). The 3D model of the aortic lumen in stl format will be used to create CFD suitable computational domain, called mesh by vmtk toolkit (www.vmtk.org). In-silico simulations: State-of-the-art CFD simulations for aortic hemodynamics will be performed by the CFD solver developed by the project EmPaTHIC (Emory Pavia Testing Hemodynamics) that updates LifeV Application Blood Flow through the collaboration among Emory University, Atlanta,Georgia,USA (Prof. A. Veneziani) and University of Pavia (UniPV) (Prof. F. Auricchio). The analysis will run on the cluster available at UniPV Nume-Lab. The project foresees to increase the computational power by adding another node to the available UniPV cluster and also the set-up of a server at Policlinico San Donato (PSD) dedicated to data storage and visualization of the results. Computation of drag forces: The post-processing of the simulations will be performed by python-scripts based on Visualization Toolkit (VTK) libraries and ParaView software (Kitware® Inc., France). Such an analysis aims at computing semi-automatically the aortic centerline, splitting the aortic arch in four regions (i.e., landing zones), and calculating the magnitude and direction of the drag forces in each zone, through the whole cardiac cycle. Preliminary analysis will be performed to assess if the systolic peak is the most relevant time instant for our purposes, in order to possibly reduce the post-processing efforts.

Experimental Design Aim 2: Medical images acquisition: The pre-operative images acquired for Aim 1 will be used. Medical images processing: The 3D models of the aortic lumen derived from the processing performed for Aim 1 will be used. In-silico simulations, Two types of analysis will be performed: 1) Simulation of TEVAR by FEA to predict endograft apposition; 2) CFD analysis to compute post-TEVAR hemodynamics. These simulations will be performed in a serial manner defining a computational framework, which is already developed and tested. FEA of TEVAR: As previously reported by our Group, the geometrical models of the implanted endografts resemble the main features of real endografts samples; mechanical properties are derived from available literature. ABAQUSv16 (Simulia, Dassault Systèmes®, FR) is used as FEA solver. CFD for post- TEVAR hemodynamics: Starting from the configuration of the endograft predicted by the FEA, the computational domain, resembling the aorta with the endovascular implant, is build using image-distance technique. The analysis is then run as described in Aim 1. Computation of drag forces: As described in Aim 1, the developed post-processing tool will be used to compute the magnitude and direction of the drag forces along the arch, and also on the inner surface of the deployed endograft.

Experimental Design Aim 3: Postoperative medical images acquisition: CTA and MRI studies and ad-hoc analysis of the images will be performed at 6-month follow-up in recruited patients as described in Aim 1. In-silico simulations: CFD analyses will be performed as described in Aim

1. Medical images processing: The same approach and the same tools proposed in Aim 1 will be used. Segmentation of post-operative CTA will be performed to reconstruct a 3D model of the aortic lumen and of the struts of the deployed endografts. Computation of drag forces and validation: As in Aim 1, 3D segmentation of post-operative CTA combined with flow data from pc-MRI will be used to run CFD analysis in order to: 1) Assess the predictive value of the drag forces measured preoperatively (Aim 1); 2) Validate the results from in-silico simulations (Aim 2).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: January 30, 2022
• Est. primary completion date: January 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age over 18 years old

• Must be able to give Informed Consent

• Must to be enrolled at the Surgery Unit of one of the recruitment centres with chronic thoracic aortic pathologies (including atherosclerotic and post-dissection aneurysms, and penetrating ulcer/intramural hematoma)

• Must to be scheduled for elective TEVAR with surgical supra-aortic vessel (SAV) debranching (established and performed according to Guidelines)

Exclusion Criteria:

• Patients with previous aortic surgical or endovascular procedures

• General contraindications to MRI or CT studies

• Suspected or manifested pregnancy

• Systemic diseases judged non-compatible with the procedures

• Any incapability to give informed consent

Related Conditions & MeSH terms

• Aneurysm
• Aneurysm, Dissecting
• Aortic Aneurysm
• Aortic Aneurysm, Thoracic
• Aortic Diseases
• Aortic Dissection
• Thoracic Aortic Aneurysm

Intervention

Diagnostic Test:
• TEVAR patients
Computed Tomography Angiography (CTA) will be performed using a 16-slice unit before and after intravenous administration of 100 mL of iodinated contrast material. Phase contrast-Magnetic Resonance (pc-MRI) will be performed using a 1.5-T unit with 40-mT/m gradient power and a four-channel cardio-thoracic coil. ECG-triggered, free-breathing through plane, and in-plane pc-MRI sequences will be performed for phase-velocity mapping of aortic and branches flow. Ad hoc processing of preoperative CTAs, based on 3D multiplanar reconstruction, will be performed with 3Mensio Vascular software 8.0® (3Mensio Medical Imaging B.V.), which provides specific functions for automatic measurements.

Locations

Country	Name	City	State
Italy	IRCCS Policlinico San Donato	San Donato Milanese	Milan

Sponsors (2)

Lead Sponsor	Collaborator
Ospedale San Donato	University of Pavia

Country where clinical trial is conducted

Italy, 

References & Publications (15)

Auricchio F, Conti M, Marconi S, Reali A, Tolenaar JL, Trimarchi S. Patient-specific aortic endografting simulation: from diagnosis to prediction. Comput Biol Med. 2013 May;43(4):386-94. doi: 10.1016/j.compbiomed.2013.01.006. Epub 2013 Feb 8. — View Citation

Auricchio, F., Conti, M., Lefieux, A. et al. Comput Mech (2014) 54: 943. https://doi.org/10.1007/s00466-014-0976-6

Böckler D, Brunkwall J, Taylor PR, Mangialardi N, Hüsing J, Larzon T; CTAG registry investigators. Thoracic Endovascular Aortic Repair of Aortic Arch Pathologies with the Conformable Thoracic Aortic Graft: Early and 2 year Results from a European Multicentre Registry. Eur J Vasc Endovasc Surg. 2016 Jun;51(6):791-800. doi: 10.1016/j.ejvs.2016.02.006. Epub 2016 Apr 20. — View Citation

Corbett TJ, Callanan A, O'Donnell MR, McGloughlin TM. An improved methodology for investigating the parameters influencing migration resistance of abdominal aortic stent-grafts. J Endovasc Ther. 2010 Feb;17(1):95-107. doi: 10.1583/09-2920.1. — View Citation

Elena Faggiano, Tommaso Lorenzi & Alfio Quarteroni (2016) Metal artefact reduction in computed tomography images by a fourth-order total variation flow, Computer Methods in Biomechanics and Biomedical Engineering: Imaging & Visualization, 4:3-4, 202-213, DOI: 10.1080/21681163.2014.940629

Erbel R, Aboyans V, Boileau C, Bossone E, Bartolomeo RD, Eggebrecht H, Evangelista A, Falk V, Frank H, Gaemperli O, Grabenwöger M, Haverich A, Iung B, Manolis AJ, Meijboom F, Nienaber CA, Roffi M, Rousseau H, Sechtem U, Sirnes PA, Allmen RS, Vrints CJ; ESC Committee for Practice Guidelines. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J. 2014 Nov 1;35(41):2873-926. doi: 10.1093/eurheartj/ehu281. Epub 2014 Aug 29. Erratum in: Eur Heart J. 2015 Nov 1;36(41):2779. — View Citation

Gillen JR, Schaheen BW, Yount KW, Cherry KJ, Kern JA, Kron IL, Upchurch GR Jr, Lau CL. Cost analysis of endovascular versus open repair in the treatment of thoracic aortic aneurysms. J Vasc Surg. 2015 Mar;61(3):596-603. doi: 10.1016/j.jvs.2014.09.009. Epub 2014 Oct 27. Review. — View Citation

Grabenwöger M, Alfonso F, Bachet J, Bonser R, Czerny M, Eggebrecht H, Evangelista A, Fattori R, Jakob H, Lönn L, Nienaber CA, Rocchi G, Rousseau H, Thompson M, Weigang E, Erbel R. Thoracic Endovascular Aortic Repair (TEVAR) for the treatment of aortic diseases: a position statement from the European Association for Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2012 Jul;33(13):1558-63. doi: 10.1093/eurheartj/ehs074. Epub 2012 May 4. — View Citation

Ishimaru S. Endografting of the aortic arch. J Endovasc Ther. 2004 Dec;11 Suppl 2:II62-71. Review. — View Citation

Madhwal S, Rajagopal V, Bhatt DL, Bajzer CT, Whitlow P, Kapadia SR. Predictors of difficult carotid stenting as determined by aortic arch angiography. J Invasive Cardiol. 2008 May;20(5):200-4. — View Citation

Marrocco-Trischitta MM, de Beaufort HW, Secchi F, van Bakel TM, Ranucci M, van Herwaarden JA, Moll FL, Trimarchi S. A geometric reappraisal of proximal landing zones for thoracic endovascular aortic repair according to aortic arch types. J Vasc Surg. 2017 Jun;65(6):1584-1590. doi: 10.1016/j.jvs.2016.10.113. Epub 2017 Feb 20. — View Citation

Marrocco-Trischitta MM, Melissano G, Kahlberg A, Calori G, Setacci F, Chiesa R. Chronic kidney disease classification stratifies mortality risk after elective stent graft repair of the thoracic aorta. J Vasc Surg. 2009 Feb;49(2):296-301. doi: 10.1016/j.jvs.2008.09.041. Epub 2008 Nov 22. — View Citation

Migliavacca F, Balossino R, Pennati G, Dubini G, Hsia TY, de Leval MR, Bove EL. Multiscale modelling in biofluidynamics: application to reconstructive paediatric cardiac surgery. J Biomech. 2006;39(6):1010-20. Epub 2005 Apr 25. — View Citation

Molony DS, Kavanagh EG, Madhavan P, Walsh MT, McGloughlin TM. A computational study of the magnitude and direction of migration forces in patient-specific abdominal aortic aneurysm stent-grafts. Eur J Vasc Endovasc Surg. 2010 Sep;40(3):332-9. doi: 10.1016/j.ejvs.2010.06.001. Epub 2010 Jun 22. — View Citation

van Bogerijen GH, Tolenaar JL, Conti M, Auricchio F, Secchi F, Sardanelli F, Moll FL, van Herwaarden JA, Rampoldi V, Trimarchi S. Contemporary Role of Computational Analysis in Endovascular Treatment for Thoracic Aortic Disease. Aorta (Stamford). 2013 Aug 1;1(3):171-81. doi: 10.12945/j.aorta.2013.13-003. eCollection 2013 Aug. Review. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Displacement Force [magnitude (N)]	Comparison among the Type of Arch (TOA); Comparison among pre- and post-Thoracic Endovascular Aortic Repair (TEVAR)	18 months
Primary	Displacement Force [Vector (-)]	Comparison among the Type of Arch (TOA); Comparison among pre- and post-Thoracic Endovascular Aortic Repair (TEVAR)	18 months
Secondary	Area of proximal landing zones (PLZs) (mm2)	Comparison among the TOA and PLZs; Comparison among pre- and post-TEVAR	18 months
Secondary	Equivalent Surface Traction (EST) (N/ mm2)	Comparison among the TOA and PLZs; Comparison among pre- and post-TEVAR	18 months
Secondary	Radius of curvature (1/mm)	Comparison among the TOA and PLZs; Comparison among pre- and post-TEVAR	18 months
Secondary	Angulation (tangent angle function)	Comparison among the TOA and PLZs; Comparison among pre- and post-TEVAR	18 months
Secondary	Tortuosity (tortuosity angle function)	Comparison among the TOA and PLZs; Comparison among pre- and post-TEVAR	18 months
Secondary	Mean and maximum flow velocity magnitude (cm/sec) in aortic along the cardiac cycle	Comparison among the TOA and PLZs; Comparison among pre- and post-TEVAR	18 months
Secondary	Systolic wall shear stress (dyn/cm2)	Comparison among the TOA and PLZs	18 months
Secondary	Time-averaged wall shear stress (TAWSS) (dyn/cm2)	Comparison among the TOA and PLZs; Comparison among pre- and post-TEVAR	18 months
Secondary	Oscillatory index (OSI) (%)	Comparison among the TOA and PLZs; Comparison among pre- and post-TEVAR	18 months
Secondary	Flow helicity	Comparison among the TOA and PLZs; Comparison among pre- and post-TEVAR	18 months
Secondary	Aortic inflow (L/min)	Comparison among the TOA; Comparison among pre- and post-TEVAR	18 months
Secondary	Aortic flow split (%)	Comparison among the TOA; Comparison among pre- and post-TEVAR	18 months
Secondary	Brachial arterial pressure (mmHg)	Comparison among the TOA; Comparison among pre- and post-TEVAR	18 months
Secondary	Mean and maximum arterial pressure (mmHg)	Comparison among the TOA; Comparison among pre- and post-TEVAR	18 months