DOI QR코드

DOI QR Code

Correct Closure of the Left Atrial Appendage Reduces Stagnant Blood Flow and the Risk of Thrombus Formation: A Proof-of-Concept Experimental Study Using 4D Flow Magnetic Resonance Imaging

  • Min Jae Cha (Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine) ;
  • Don-Gwan An (Department of Mechanical Convergence Engineering, Hanyang University) ;
  • Minsoo Kang (Department of Mechanical Convergence Engineering, Hanyang University) ;
  • Hyue Mee Kim (Division of Cardiology, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine) ;
  • Sang-Wook Kim (Division of Cardiology, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine) ;
  • Iksung Cho (Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System) ;
  • Joonhwa Hong (Department of Thoracic and Cardiovascular Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine) ;
  • Hyewon Choi (Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine) ;
  • Jee-Hyun Cho (Bio-Chemical Analysis Team, Korea Basic Science Institute) ;
  • Seung Yong Shin (Center for Precision Medicine Platform Based-on Smart Hemo-Dynamic Index) ;
  • Simon Song (Department of Mechanical Convergence Engineering, Hanyang University)
  • Received : 2022.11.23
  • Accepted : 2023.04.17
  • Published : 2023.07.01

Abstract

Objective: The study was conducted to investigate the effect of correct occlusion of the left atrial appendage (LAA) on intracardiac blood flow and thrombus formation in patients with atrial fibrillation (AF) using four-dimensional (4D) flow magnetic resonance imaging (MRI) and three-dimensional (3D)-printed phantoms. Materials and Methods: Three life-sized 3D-printed left atrium (LA) phantoms, including a pre-occlusion (i.e., before the occlusion procedure) model and correctly and incorrectly occluded post-procedural models, were constructed based on cardiac computed tomography images from an 86-year-old male with long-standing persistent AF. A custom-made closed-loop flow circuit was set up, and pulsatile simulated pulmonary venous flow was delivered by a pump. 4D flow MRI was performed using a 3T scanner, and the images were analyzed using MATLAB-based software (R2020b; Mathworks). Flow metrics associated with blood stasis and thrombogenicity, such as the volume of stasis defined by the velocity threshold ($\left|\vec{V}\right|$ < 3 cm/s), surface-and-time-averaged wall shear stress (WSS), and endothelial cell activation potential (ECAP), were analyzed and compared among the three LA phantom models. Results: Different spatial distributions, orientations, and magnitudes of LA flow were directly visualized within the three LA phantoms using 4D flow MRI. The time-averaged volume and its ratio to the corresponding entire volume of LA flow stasis were consistently reduced in the correctly occluded model (70.82 mL and 39.0%, respectively), followed by the incorrectly occluded (73.17 mL and 39.0%, respectively) and pre-occlusion (79.11 mL and 39.7%, respectively) models. The surfaceand-time-averaged WSS and ECAP were also lowest in the correctly occluded model (0.048 Pa and 4.004 Pa-1, respectively), followed by the incorrectly occluded (0.059 Pa and 4.792 Pa-1, respectively) and pre-occlusion (0.072 Pa and 5.861 Pa-1, respectively) models. Conclusion: These findings suggest that a correctly occluded LAA leads to the greatest reduction in LA flow stasis and thrombogenicity, presenting a tentative procedural goal to maximize clinical benefits in patients with AF.

Keywords

Acknowledgement

The authors appreciate the technical assistance of Mun Young Paek (from Siemens Healthcare), Bon Chul Ha, Hyeong Ho So and Min Gu Kim for helping with MRI scans.

References

  1. Pellman J, Sheikh F. Atrial fibrillation: mechanisms, therapeutics, and future directions. Compr Physiol 2015;5:649-665
  2. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370-2375
  3. Holmes DR Jr, Lakkireddy DR, Whitlock RP, Waksman R, Mack MJ. Left atrial appendage occlusion: opportunities and challenges. J Am Coll Cardiol 2014;63:291-298
  4. Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016;37:2893-2962
  5. Blackshear JL, Odell JA. Appendage obliteration to reduce stroke in cardiac surgical patients with atrial fibrillation. Ann Thorac Surg 1996;61:755-759
  6. Saw J, Lempereur M. Percutaneous left atrial appendage closure: procedural techniques and outcomes. JACC Cardiovasc Interv 2014;7:1205-1220
  7. Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, et al. Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet 2009;374:534-542
  8. Holmes DR Jr, Kar S, Price MJ, Whisenant B, Sievert H, Doshi SK, et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol 2014;64:1-12
  9. Osmancik P, Herman D, Neuzil P, Hala P, Taborsky M, Kala P, et al. Left atrial appendage closure versus direct oral anticoagulants in high-risk patients with atrial fibrillation. J Am Coll Cardiol 2020;75:3122-3135
  10. Staubach S, Schlatterbeck L, Mortl M, Strohm H, Hoppmann P, Laugwitz KL, et al. Long-term transesophageal echocardiography follow-up after percutaneous left atrial appendage closure. Heart Rhythm 2020;17(5 Pt A):728-733
  11. Mohanty S, Gianni C, Trivedi C, Gadiyaram V, Della Rocca DG, MacDonald B, et al. Risk of thromboembolic events after percutaneous left atrial appendage ligation in patients with atrial fibrillation: long-term results of a multicenter study. Heart Rhythm 2020;17:175-181
  12. Asinger RW, Koehler J, Pearce LA, Zabalgoitia M, Blackshear JL, Fenster PE, et al. Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: II. Dense spontaneous echocardiographic contrast (The Stroke Prevention in Atrial Fibrillation [SPAF-III] study). J Am Soc Echocardiogr 1999;12:1088-1096
  13. Markl M, Lee DC, Ng J, Carr M, Carr J, Goldberger JJ. Left atrial 4-dimensional flow magnetic resonance imaging: stasis and velocity mapping in patients with atrial fibrillation. Invest Radiol 2016;51:147-154
  14. Markl M, Lee DC, Furiasse N, Carr M, Foucar C, Ng J, et al. Left atrial and left atrial appendage 4D blood flow dynamics in atrial fibrillation. Circ Cardiovasc Imaging 2016;9:e004984
  15. Markl M, Fluckiger J, Lee DC, Ng J, Goldberger JJ. Velocity quantification by electrocardiography-gated phase contrast magnetic resonance imaging in patients with cardiac arrhythmia: a simulation study based on real time transesophageal echocardiography data in atrial fibrillation. J Comput Assist Tomogr 2015;39:422-427
  16. Garcia J, Sheitt H, Bristow MS, Lydell C, Howarth AG, Heydari B, et al. Left atrial vortex size and velocity distributions by 4D flow MRI in patients with paroxysmal atrial fibrillation: associations with age and CHA(2) DS(2) -VASc risk score. J Magn Reson Imaging 2020;51:871-884
  17. Elkins C, Markl M, Iyengar A, Wicker R, Eaton JK. Full-field velocity and temperature measurements using magnetic resonance imaging in turbulent complex internal flows. Int J Heat Fluid Flow 2004;25:702-710
  18. Benson MJ, Banko AJ, Elkins CJ, An DG, Song S, Bruschewski M, et al. The 2019 MRV challenge: turbulent flow through a U-bend. Exp Fluids 2020;61:148
  19. Wang CY, Gao Q, Wang HP, Wei RJ, Li T, Wang JJ. Divergence-free smoothing for volumetric PIV data. Exp Fluids 2016;57:15
  20. Bluestein D, Niu L, Schoephoerster RT, Dewanjee MK. Steady flow in an aneurysm model: correlation between fluid dynamics and blood platelet deposition. J Biomech Eng 1996;118:280-286
  21. Rayz VL, Boussel L, Lawton MT, Acevedo-Bolton G, Ge L, Young WL, et al. Numerical modeling of the flow in intracranial aneurysms: prediction of regions prone to thrombus formation. Ann Biomed Eng 2008;36:1793-1804
  22. Ko S, Yang B, Cho JH, Lee J, Song S. Novel and facile criterion to assess the accuracy of WSS estimation by 4D flow MRI. Med Image Anal 2019;53:95-103
  23. Yang B, Cho JH, Lee J, Song S. Development of custom-made RF coil for magnetic resonance velocimeter with a high spatial resolution. J Mech Sci Technol 2019;33:1681-1688
  24. Di Achille P, Tellides G, Figueroa CA, Humphrey JD. A haemodynamic predictor of intraluminal thrombus formation in abdominal aortic aneurysms. Proc R Soc A 2014;470:20140163
  25. Markl M, Carr M, Ng J, Lee DC, Jarvis K, Carr J, et al. Assessment of left and right atrial 3D hemodynamics in patients with atrial fibrillation: a 4D flow MRI study. Int J Cardiovasc Imaging 2016;32:807-815
  26. Demirkiran A, Amier RP, Hofman MBM, van der Geest RJ, Robbers LFHJ, Hopman LHGA, et al. Altered left atrial 4D flow characteristics in patients with paroxysmal atrial fibrillation in the absence of apparent remodeling. Sci Rep 2021;11:5965
  27. Zambrano BA, Gharahi H, Lim C, Jaberi FA, Choi J, Lee W, et al. Association of intraluminal thrombus, hemodynamic forces, and abdominal aortic aneurysm expansion using longitudinal CT images. Ann Biomed Eng 2016;44:1502-1514
  28. Kelsey LJ, Powell JT, Norman PE, Miller K, Doyle BJ. A comparison of hemodynamic metrics and intraluminal thrombus burden in a common iliac artery aneurysm. Int J Numer Method Biomed Eng 2017;33:e2821
  29. Ong C, Xiong F, Kabinejadian F, Praveen Kumar G, Cui F, Chen G, et al. Hemodynamic analysis of a novel stent graft design with slit perforations in thoracic aortic aneurysm. J Biomech 2019;85:210-217
  30. Kandail H, Hamady M, Xu XY. Effect of a flared renal stent on the performance of fenestrated stent-grafts at rest and exercise conditions. J Endovasc Ther 2016;23:809-820
  31. Ku DN, Giddens DP, Zarins CK, Glagov S. Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis 1985;5:293-302
  32. Markl M, Frydrychowicz A, Kozerke S, Hope M, Wieben O. 4D flow MRI. J Magn Reson Imaging 2012;36:1015-1036
  33. Fukumoto Y, Hiro T, Fujii T, Hashimoto G, Fujimura T, Yamada J, et al. Localized elevation of shear stress is related to coronary plaque rupture: a 3-dimensional intravascular ultrasound study with in-vivo color mapping of shear stress distribution. J Am Coll Cardiol 2008;51:645-650
  34. Chatzizisis YS, Jonas M, Coskun AU, Beigel R, Stone BV, Maynard C, et al. Prediction of the localization of high-risk coronary atherosclerotic plaques on the basis of low endothelial shear stress: an intravascular ultrasound and histopathology natural history study. Circulation 2008;117:993-1002
  35. Hwang J, Saha A, Boo YC, Sorescu GP, McNally JS, Holland SM, et al. Oscillatory shear stress stimulates endothelial production of O2- from p47phox-dependent NAD(P)H oxidases, leading to monocyte adhesion. J Biol Chem 2003;278:47291-47298
  36. Briceno DF, Villablanca P, Cyrille N, Massera D, Bader E, Manheimer E, et al. Left atrial appendage occlusion device and novel oral anticoagulants versus warfarin for stroke prevention in nonvalvular atrial fibrillation: systematic review and meta-analysis of randomized controlled trials. Circ Arrhythm Electrophysiol 2015;8:1057-1064
  37. Holmes DR Jr, Alkhouli M, Reddy V. Left atrial appendage occlusion for the unmet clinical needs of stroke prevention in nonvalvular atrial fibrillation. Mayo Clin Proc 2019;94:864-874
  38. Whitlock RP, Belley-Cote EP, Paparella D, Healey JS, Brady K, Sharma M, et al. Left atrial appendage occlusion during cardiac surgery to prevent stroke. N Engl J Med 2021;384:2081-2091
  39. Ha H, Huh HK, Park KJ, Dyverfeldt P, Ebbers T, Kim DH, et al. In-vitro and In-vivo assessment of 4D flow MRI reynolds stress mapping for pulsatile blood flow. Front Bioeng Biotechnol 2021;9:774954
  40. Biglino G, Cosentino D, Steeden JA, De Nova L, Castelli M, Ntsinjana H, et al. Using 4D cardiovascular magnetic resonance imaging to validate computational fluid dynamics: a case study. Front Pediatr 2015;3:107
  41. Toger J, Bidhult S, Revstedt J, Carlsson M, Arheden H, Heiberg E. Independent validation of four-dimensional flow MR velocities and vortex ring volume using particle imaging velocimetry and planar laser-Induced fluorescence. Magn Reson Med 2016;75:1064-1075
  42. Habigt MA, Gesenhues J, Stemmler M, Hein M, Rossaint R, Mechelinck M, et al. In vivo validation of a cardiovascular simulation model in pigs. Math Comput Appl 2022;27:28