Abstract 14689: Regional Aortic Wall Shear Stress Mapping Implicates Hemodynamics in Human Bicuspid Aortopathy
Introduction: A suspected genetic cause for bicuspid aortic valve (BAV) aortopathy has led to aggressive resection strategies. Using 4D flow MRI, we documented increased regional wall shear stress (WSS) in BAV patients. Local hemodynamics may exacerbate extracellular matrix (ECM) degradation leading to disease progression. If validated, preoperative regional hemodynamic assessment could be used to guide more targeted patient-specific aortic resection. For the first time, we correlated regional WSS with aortic tissue remodeling in BAV patients.
Methods & Results: BAV patients (N=11) undergoing ascending aortic resection received preoperative 4D flow MRI with regional WSS differences mapped. Paired aortic wall samples (from same-patient with elevated WSS paired to normal WSS regions) were collected during surgery and compared using histology (pentachrome), biomechanics (biaxial mechanical testing), and ECM regulation (protein expression). Patient mean age: 49±18 years; mean aortic diameter: 4.6±0.7cm (range: 3.6 - 6.3cm); 55% had R+L fusion pattern; 36% had severe aortic stenosis. All patients had heterogeneous WSS patterns with regions of elevated WSS adjacent to those of normal WSS. By histology, regions of increased WSS showed greater medial elastin fragmentation, fibrosis, and cystic medial necrosis compared to adjacent areas of normal WSS. Regions of increased WSS showed increased elastic modulus (fold change±SD: 1.53±0.68; P=0.06, N=5) and collagen stiffness (1.37±0.49; P=0.07, N=5) compared to normal WSS regions suggesting altered distensibility. Multiplex protein analyses of ECM regulatory molecules revealed an increase in transforming growth factor β-1 (1.49±0.71, P=0.02), MMP-1 (1.62±0.84; P=0.01), MMP-2 (1.49±1.00; P=0.06), MMP-3 (1.23±0.36; P=0.02), MMP-7 (1.57±0.75; P=0.02), and TIMP-2 (1.26±0.33; P=0.01) in elevated WSS regions suggesting ECM dysregulation consistent with aortic remodeling.
Conclusions: In BAV aorta, regional WSS corresponds with local histologic abnormalities, altered biomechanics, and ECM dysregulation. These novel data strongly implicate local hemodynamics as a mediator of BAV aortopathy. With further validation, 4D flow MRI could be used to guide personalized resection strategies.
Author Disclosures: D.G. Guzzardi: None. P. van Ooij: None. A.J. Barker: None. G. Martufi: None. K.E. Olsen: None. E.S. Di Martino: None. Y. Chen: None. M. Markl: None. P.M. McCarthy: Consultant/Advisory Board; Modest; Edwards Lifesciences, LLC. Other; Modest; Cleveland Clinic Health System (Cleveland Clinic Health System Physician Organization), Kapp Surgical Instrument, Inc. S.C. Malaisrie: Consultant/Advisory Board; Modest; ABIOMED, Inc., Edwards Lifesciences, LLC. Other; Modest; VIVA Physicians, Inc. J.J. Puthumana: Other; Modest; Kaiser Permanente San Francisco Medical Center and Medical Offices. D.D. Belke: None. E.R. O’Brien: None. H.E. Mewhort: None. D.A. Svystonyuk: None. J. Carr: Consultant/Advisory Board; Modest; Bayer HealthCare Pharmaceuticals, Inc., Lantheus Medical Imaging, Inc. R.O. Bonow: Consultant/Advisory Board; Modest; Gilead Sciences, Inc.. Other; Modest; American Heart Association, Inc.. P.W. Fedak: None.
- © 2014 by American Heart Association, Inc.